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Seo A, Chang AY. A systematic review of the social impact of diseases in Nordic countries. Scand J Public Health 2024; 52:997-1012. [PMID: 38166481 DOI: 10.1177/14034948231217365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
BACKGROUND We review the literature on the social impacts of diseases, defined as the social consequences of having a disease on the people around the patient, such as spouses, caregivers and offspring. The two objectives of this study are to summarise the social outcomes commonly associated with diseases and to compare the social impact across a range of diseases. METHODS A systematic review of the social impact of disease in Nordic countries was conducted using PubMed, PsycINFO and Google Scholar (PROSPERO registration number CRD42022291796). All articles that met the inclusion criteria were reviewed. We tabulated all outcomes and diseases studied, and synthesised the evidence based on the perspectives of patients, spouse/caregiver and offspring. RESULTS A total of 135 studies met the eligibility criteria, covering 76 diseases and 39 outcomes. From the patient's perspective, diseases impact divorce and marriage rates, social functioning, likelihood of committing a crime and being a victim of crime. From the caregiver's perspective, diseases affect their health-related quality of life and physical and psychological health. From the offspring's perspective, diseases impact their development, health and social adversities in later life. Diseases generally had negative social impacts, but there were some diseases associated with positive impacts. CONCLUSIONS The review provides a useful summary and gross comparison of the social impact of different diseases. The social impact of diseases can be large and significant. Thus, it should be considered when policymakers are setting priorities across disease areas.
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Affiliation(s)
- Ahreum Seo
- Department of Public Health, University of Southern Denmark, Denmark
| | - Angela Y Chang
- Danish Institute for Advanced Study, University of Southern Denmark, Denmark
- Department of Clinical Research, University of Southern Denmark, Denmark
- Interdisciplinary Centre on Population Dynamics (CPop), University of Southern Denmark, Denmark
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2
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Byrne BE, Siaw-Acheampong K, Evans O, Taylor J, Huddy F, Nilsson M, Griffiths EA, Low D, Gossage J, Dunn J, Zeki S, Markar S, Avery K, Blazeby JM, Cockbain A, Moss C, van Hemelrijck M, Andreyev J, Davies AR. REsolution of Symptoms afTer Oesophago-gastric cancer REsection delphi (RESTOREd)-standardizing the definition, investigation and management of gastrointestinal symptoms and conditions after surgery. Br J Surg 2024; 111:znae286. [PMID: 39657739 DOI: 10.1093/bjs/znae286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 09/03/2024] [Accepted: 10/07/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Oesophago-gastric cancer surgery negatively affects quality of life with a high postoperative symptom burden. Several conditions that may be diagnosed and treated after surgery are recognised. However, consensus regarding their definition and management is lacking. This study aimed to develop consensus regarding the definition, investigation and management of the common symptoms and conditions, and triggers to consider disease recurrence, as a foundation for improving management and quality of life in these patients. METHOD Modified two-round Delphi consensus study of a multidisciplinary expert panel. RESULTS Eighty-six of 127 (67.7%) and 77 of 93 (82.8%) responses were received in rounds 1 and 2. Consensus was achieved in defining 26 symptoms. For 10 conditions (anastomotic stricture, acid reflux, non-acid reflux, biliary gastritis, delayed gastric emptying, dumping syndrome, exocrine pancreatic insufficiency, bile acid diarrhoea, small intestinal bacterial overgrowth and carbohydrate malabsorption), definitions, diagnostic criteria, first- and second-line investigation and first-line treatments were agreed. Consensus was not reached for third-line investigation of some conditions, or for second-, third- or fourth-line treatments for others. Twelve of 14 (85.7%) symptoms were agreed as triggers to consider cancer recurrence, during the early (<1 year) and late (>1 year) postoperative periods. CONCLUSION Expert consensus regarding symptoms, conditions and triggers to consider investigation for recurrence after oesophago-gastric cancer surgery was achieved. This may allow standardization and timely diagnosis and treatment of postoperative conditions, reducing variation in care and optimizing patients' quality of life.
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Affiliation(s)
- Ben E Byrne
- Department of Oeosphago-Gastric Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- Centre for Surgical Research, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Kwabena Siaw-Acheampong
- Department of Upper GI Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Orla Evans
- Department of Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Joanna Taylor
- Department of Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Fiona Huddy
- Department of Nutrition and Dietetics, Royal Surrey NHS Foundation Trust, Guildford, UK
| | - Magnus Nilsson
- Division of Surgery and Oncology, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
- Nuffield Department of Surgery, University of Oxford, Oxford, UK
| | - Ewen A Griffiths
- Department of Upper GI Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Donald Low
- Department of Thoracic Surgery, Virginia Mason Medical Centre, Seattle, Washington, USA
| | - James Gossage
- Department of Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Jason Dunn
- Department of Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Sebastian Zeki
- Department of Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Sheraz Markar
- Nuffield Department of Surgery, University of Oxford, Oxford, UK
| | - Kerry Avery
- Centre for Surgical Research, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Jane M Blazeby
- Centre for Surgical Research, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Andrew Cockbain
- Department of Upper GI Surgery, St James's University Hospital, Leeds, UK
| | - Charlotte Moss
- Faculty of Life Sciences and Medicine, King's College London, London, UK
| | | | - Jervoise Andreyev
- Department of Gastroenterology, United Lincolnshire Hospitals NHS Trust, Lincoln, UK
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van der Zijden CJ, Olthof PB, van der Sluis PC, Wijnhoven BPL, Erodotou M, Hartgrink HH, van Etten B, van Esser S, Lagarde SM, Dekker JWT. N3 Disease in Esophageal Cancer: Results from a Nationwide Registry. Dig Surg 2024; 41:133-140. [PMID: 39097966 PMCID: PMC11382634 DOI: 10.1159/000540468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 07/17/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Patients with extensive lymph node metastases have a poor prognosis. Clinical staging of lymph node metastases poses significant challenges given the limited sensitivity and specificity of imaging techniques. The aim of this study was to investigate the overall survival (OS) of patients with N3 disease in a real-world Dutch population and the added value of surgery in these patients. METHODS Patients with cN3M0 esophageal or gastroesophageal cancer were identified from the Netherlands Cancer Registry (2012-2019). Treatment consisted of neoadjuvant chemo(radio)therapy followed by resection or chemo(radio)therapy, radiotherapy, or esophagectomy alone. OS was calculated using the Kaplan-Meier method. RESULTS Some 21,566 patients were diagnosed with esophageal cancer of whom 359 (1.7%) had cN3M0 disease. Median OS of these patients was 12.5 months (95% CI: 10.7-14.3). Median OS following chemoradiotherapy alone and neoadjuvant therapy plus surgery was 13.3 months (95% CI: 10.7-15.9) and 23.7 months (95% CI: 18.3-29.2), respectively. Of all patients who underwent esophagectomy, 391 (2.8%) had (y)pN3 disease, and median OS was 16.1 months (95% CI: 14.8-17.4). Twenty-one patients (5.4%) were correctly classified as cN3, and 3-year OS was 21%. CONCLUSION(S) Clinical staging appears to be difficult, apparently in patients with N3 esophageal cancer. Surgery seems to be of benefit to these patients. More research is required to address the ongoing challenges in clinical staging and the best neoadjuvant therapy.
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Affiliation(s)
| | - Pim B Olthof
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
- Department of Surgery, Reinier de Graaf Group, Delft, The Netherlands
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Bas P L Wijnhoven
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Maria Erodotou
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Henk H Hartgrink
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Boudewijn van Etten
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Stijn van Esser
- Department of Surgery, Reinier de Graaf Group, Delft, The Netherlands
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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4
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Merritt RE. Conduit Selection for Reconstruction After Esophagectomy for Esophageal Cancer. Surg Oncol Clin N Am 2024; 33:549-556. [PMID: 38789197 DOI: 10.1016/j.soc.2024.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2024]
Abstract
The reconstruction of the esophagus after esophagectomy presents many technical and management challenges to surgeons. An effective gastrointestinal conduit that replaces the resected esophagus must have adequate length to reach the upper thoracic space or the neck, have robust vascular perfusion, and provide sufficient function for an adequate swallowing mechanism. The stomach is currently the preferred conduit for esophageal reconstruction after esophagectomy. However, there are circumstances, where the stomach cannot be utilized as a conduit. In these cases, an alternative conduit must be considered. The current alternative conduits include colon, jejunum, and tubed skin flaps.
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Affiliation(s)
- Robert E Merritt
- Division of Thoracic Surgery, The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, N847 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210, USA.
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Miao Y, Nie X, He WW, Luo CY, Xia Y, Zhou AR, Wei SR, Wang CH, Fang Q, Peng L, Leng XF, Han YT, Luo L, Xie Q. Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma. Support Care Cancer 2024; 32:237. [PMID: 38509239 PMCID: PMC10954946 DOI: 10.1007/s00520-024-08428-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 03/08/2024] [Indexed: 03/22/2024]
Abstract
PURPOSE Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.
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Affiliation(s)
- Yan Miao
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Xin Nie
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Wen-Wu He
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Chun-Yan Luo
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Yan Xia
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Ao-Ru Zhou
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Si-Rui Wei
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Cheng-Hao Wang
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Qiang Fang
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Lin Peng
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Xue-Feng Leng
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Yong-Tao Han
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China
| | - Lei Luo
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China.
| | - Qin Xie
- Department of Thoracic Surgery, Sichuan Cancer Research Center for Cancer, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People's Republic of China.
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6
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Miller ED, Wu T, McKinley G, Slivnick J, Guha A, Mo X, Prasad R, Yildiz V, Diaz D, Merritt RE, Perry KA, Jin N, Hodge D, Poliner M, Chen S, Gambril J, Stock J, Wilbur J, Pierre-Charles J, Ghazi SM, Williams TM, Bazan JG, Addison D. Incident Atrial Fibrillation and Survival Outcomes in Esophageal Cancer following Radiotherapy. Int J Radiat Oncol Biol Phys 2024; 118:124-136. [PMID: 37574171 DOI: 10.1016/j.ijrobp.2023.08.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 06/29/2023] [Accepted: 08/05/2023] [Indexed: 08/15/2023]
Abstract
PURPOSE Radiation therapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown. METHODS AND MATERIALS Leveraging a large cohort of consecutive patients with esophageal cancer treated with thoracic RT from 2007 to 2019, we assessed incidence and outcomes of incident AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular arrhythmias, and sudden death, by cardiac RT dose. We also assessed the relationship between AF development and progression-free and overall survival. Observed incident AF rates were compared with Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relationship between clinical and RT measures, and outcomes. Differences in outcomes, by AF status, were also evaluated via 30-day landmark analysis. Furthermore, we assessed the effect of cardiac substructure RT dose (eg, left atrium, LA) on the risk of post RT-related outcomes. RESULTS Overall, from 238 RT treated patients with esophageal cancer, 21.4% developed incident AF, and 33% developed MACE with the majority (84%) of events occurring ≤2 years of RT initiation (median time to AF, 4.1 months). Cumulative incidence of AF and MACE at 1 year was 19.5%, and 25.7%, respectively; translating into an observed incident AF rate of 824 per 10,000 person-years, compared with the Framingham predicted rate of 92 (relative risk, 8.96; P < .001, absolute excess risk 732). Increasing LA dose strongly associated with incident AF (P = .001); and those with AF saw worse disease progression (hazard ratio, 1.54; P = .03). In multivariate models, outside of traditional cancer-related factors, increasing RT dose to the LA remained associated with worse overall survival. CONCLUSIONS Among patients with esophageal cancer, radiation therapy increases AF risk, and associates with worse long-term outcomes.
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Affiliation(s)
- Eric D Miller
- Department of Radiation Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
| | - Trudy Wu
- Department of Radiation Oncology, University of California, Los Angeles, California
| | - Grant McKinley
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - Jeremy Slivnick
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - Avirup Guha
- Department of Medicine, Cardiology, Medical College of Georgia, Augusta, Georgia
| | - Xiaokui Mo
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio
| | - Rahul Prasad
- Department of Radiation Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Vedat Yildiz
- Center for Biostatistics, Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio
| | - Dayssy Diaz
- Department of Radiation Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Robert E Merritt
- Division of Thoracic Surgery at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Kyle A Perry
- Department of General Surgery at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Ning Jin
- Department of Internal Medicine, Division of Medical Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Dinah Hodge
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - Michael Poliner
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - Sunnia Chen
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - John Gambril
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - James Stock
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - Jameson Wilbur
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - Jovan Pierre-Charles
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | - Sanam M Ghazi
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio
| | | | - Jose G Bazan
- Department of Radiation Oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
| | - Daniel Addison
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, Ohio; Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio.
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van der Wilk BJ, Eyck BM, Noordman BJ, Kranenburg LW, Oppe M, Lagarde SM, Wijnhoven BPL, Busschbach JJ, van Lanschot JJB. Characteristics Predicting Short-Term and Long-Term Health-Related Quality of Life in Patients with Esophageal Cancer After Neoadjuvant Chemoradiotherapy and Esophagectomy. Ann Surg Oncol 2023; 30:8192-8202. [PMID: 37587357 PMCID: PMC10625935 DOI: 10.1245/s10434-023-14028-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 06/05/2023] [Indexed: 08/18/2023]
Abstract
BACKGROUND Esophagectomy is associated with lasting effect on health-related quality of life (HRQOL). Patients desire detailed information on the expected impact of treatment on their postoperative HRQOL. The aim of the present study is to identify clinicopathological characteristics predictive for changes in short-term and long-term HRQOL after neoadjuvant chemoradiotherapy (nCRT) and surgery. METHODS HRQOL was measured using EORTC-QLQ-C30 and QLQ-OES24 questionnaires prior to nCRT, three, six, nine and twelve months postoperatively and at a minimum of six years postoperatively. Based on previous experience and available literature, several subgroups were predefined for different clinicopathological characteristics: baseline global HRQOL, WHO performance status, histology, tumor stage and tumor location. The primary endpoints of the present study were the change compared to baseline in the HRQOL dimensions physical functioning and eating problems. Secondary endpoints were global HRQOL, fatigue and emotional problems. RESULTS In total, 134 (76%) of 177 patients who received HRQOL questionnaires, responded at baseline. Patients who reported a high baseline global HRQOL had a more severe deterioration in eating problems (+14.5 to + 18.0), global HRQOL (-16.0 to -28.0) and fatigue (+10.5 to +14.9) up to six years postoperatively compared to patients who reported a low baseline global HRQOL. Patients who had stage 2 tumor (UICC 6th edition) had a more severe deterioration in eating problems (+14.6 to +19.0) and global HRQOL (-10.1 to -17.1) than patients who had stage 3 tumor. CONCLUSIONS The results suggest that patients with locally advanced esophageal cancer in favorable condition at baseline decline more in terms of various HRQOL outcomes.
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Affiliation(s)
- Berend J van der Wilk
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands.
| | - Ben M Eyck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands
| | - Bo J Noordman
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands
| | - Leonieke W Kranenburg
- Department of Psychiatry, Section of Medical Psychology and Psychotherapy, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - Mark Oppe
- Maths in Health, Rotterdam, The Netherlands
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands
| | - Jan J Busschbach
- Department of Psychiatry, Section of Medical Psychology and Psychotherapy, Erasmus MC-University Medical Center, Rotterdam, The Netherlands
| | - J Jan B van Lanschot
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Center, Rotterdam, The Netherlands
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Okamura A, Watanabe M, Okui J, Matsuda S, Takemura R, Kawakubo H, Takeuchi H, Muto M, Kakeji Y, Kitagawa Y, Doki Y. Neoadjuvant Chemotherapy or Neoadjuvant Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Real-World Data Comparison from A Japanese Nationwide Study. Ann Surg Oncol 2023; 30:5885-5894. [PMID: 37264286 DOI: 10.1245/s10434-023-13686-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/11/2023] [Indexed: 06/03/2023]
Abstract
BACKGROUND Although neoadjuvant treatment has become the standard of care for patients with locally advanced esophageal cancer, previous studies comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) have demonstrated inconclusive results. METHODS Our study cohort included 3978 patients from 85 institutions. Those who underwent NAC or NACRT followed by surgery for esophageal squamous cell carcinoma (ESCC) were eligible for inclusion. We used the inverse probability of treatment weighting (IPTW) method to compare the outcomes between NAC and NACRT. RESULTS Among the 3978 patients, 3777 (94.9%) received NAC and 201 (5.1%) received NACRT. After IPTW adjustment, the NACRT group had more patients with pathologically downstaged diseases and significantly better pathological response compared with the NAC group (p < 0.001); however, 5-year overall survival (OS), recurrence-free survival (RFS), and regional recurrence-specific survival (RRSS) were comparable between the groups. Subgroup analysis stratifying patients according to cT category showed that among cT1-2 patients, those in the NACRT group had significantly longer 5-year OS, RFS, and RRSS than those in the NAC group (P = 0.024, < 0.001, and 0.020, respectively). In contrast, no significant differences were observed among cT3-4a patients. The competing risks regression model showed comparable subdistribution hazard ratios for 10-year cancerous and noncancerous deaths between the NAC and NACRT groups. CONCLUSIONS Compared with NAC, NACRT for ESCC did not promote better survival despite better therapeutic effects and did not increase noncancerous deaths.
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Affiliation(s)
- Akihiko Okamura
- Department of Esophageal Surgery, Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Masayuki Watanabe
- Department of Esophageal Surgery, Gastroenterology Center, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
- Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Jun Okui
- Department of Preventive Medicine and Public Health, School of Medicine, Keio University, Tokyo, Japan
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Satoru Matsuda
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Ryo Takemura
- Biostatistics Unit, Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Manabu Muto
- Department of Therapeutic Oncology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yoshihiro Kakeji
- Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan
| | - Yuko Kitagawa
- Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
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9
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van der Zijden CJ, Lagarde SM, Hermus M, Kranenburg LW, van Lanschot JJB, Mostert B, Nuyttens JJME, Oudijk L, van der Sluis PC, Spaander MCW, Valkema MJ, Valkema R, Wijnhoven BPL. A prospective cohort study on active surveillance after neoadjuvant chemoradiotherapy for esophageal cancer: protocol of Surgery As Needed for Oesophageal cancer-2. BMC Cancer 2023; 23:327. [PMID: 37038138 PMCID: PMC10084614 DOI: 10.1186/s12885-023-10747-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Accepted: 03/15/2023] [Indexed: 04/12/2023] Open
Abstract
BACKGROUND Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for potentially curable esophageal cancer. Active surveillance in patients with a clinically complete response (cCR) 12 weeks after nCRT is regarded as possible alternative to standard surgery. The aim of this study is to monitor the safety, adherence and effectiveness of active surveillance in patients outside a randomized trial. METHODS This nationwide prospective cohort study aims to accrue operable patients with non-metastatic histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus or esophagogastric junction. Patients receive nCRT and response evaluation consists of upper endoscopy with bite-on-bite biopsies, endoscopic ultrasonography plus fine-needle aspiration of suspicious lymph nodes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. When residue or regrowth of tumor in the absence of distant metastases is detected, surgical resection is advised. Patients with cCR after nCRT are suitable to undergo active surveillance. Patients can consult an independent physician or psychologist to support decision-making. Primary endpoint is the number and severity of adverse events in patients with cCR undergoing active surveillance, defined as complications from response evaluations, delayed surgery and the development of distant metastases. Secondary endpoints include timing and quality of diagnostic modalities, overall survival, progression-free survival, fear of cancer recurrence and decisional regret. DISCUSSION Active surveillance after nCRT may be an alternative to standard surgery in patients with esophageal cancer. Similar to organ-sparing approaches applied in other cancer types, the safety and efficacy of active surveillance needs monitoring before data from randomized trials are available. TRIAL REGISTRATION The SANO-2 study has been registered at ClinicalTrials.gov as NCT04886635 (May 14, 2021) - Retrospectively registered.
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Affiliation(s)
- Charlène J van der Zijden
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, the Netherlands.
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, the Netherlands
| | - Merel Hermus
- Department of Medical Psychology and Psychotherapy, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Leonieke W Kranenburg
- Department of Medical Psychology and Psychotherapy, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - J Jan B van Lanschot
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, the Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Joost J M E Nuyttens
- Department of Radiation Oncology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Lindsey Oudijk
- Department of Pathology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Pieter C van der Sluis
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, the Netherlands
| | - Manon C W Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Maria J Valkema
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, the Netherlands
| | - Roelf Valkema
- Department of Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015GD, Rotterdam, the Netherlands
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10
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Katz A, Nevo Y, Ramírez García Luna JL, Anchouche S, Tankel J, Caminsky N, Mueller C, Spicer J, Cools-Lartigue J, Ferri L. Long-Term Quality of Life After Esophagectomy for Esophageal Cancer. Ann Thorac Surg 2023; 115:200-208. [PMID: 35926638 DOI: 10.1016/j.athoracsur.2022.07.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 06/21/2022] [Accepted: 07/19/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Surgery, as part of a multimodal approach, offers the greatest chance of cure for esophageal cancer. However, esophagectomy is often perceived as having a lasting impact on quality of life (QOL), biasing some physicians and patients toward nonoperative management. A comprehensive understanding of the dynamic changes in patient-centered outcomes is therefore important for decision making. Our objective was to determine the long-term QOL after esophagectomy. METHODS Data were obtained from a prospectively collected (2006-2015) esophagectomy database at a high-volume center, and patients surviving 3 or more years were identified. Health-related QOL was evaluated using the Functional Assessment of Cancer Therapy-Esophageal Module (FACT-E) at diagnosis and every 3 to 6 months, and was stratified according to operative approach, stage, and complications. In addition, QOL scores were compared with normative population values. RESULTS Of 480 patients, 47% (n = 226) survived 3 or more years and 70% (158 of 226) completed the health-related QOL assessments. Time of follow-up was 5.1 ± 2.8 years. After a reduction at 1 to 3 months, FACT-E increased from a baseline of 126 (95% CI, 121-131) to 133 (95% CI, 127-139) at 12 months, and to 147 (95% CI, 142-153) by 5 years. There was no difference in long-term FACT-E with respect to the surgical approach, clinical and pathologic stage, or postoperative complications. At long-term follow-up (more than 3 years), QOL did not differ significantly from the normative population reference values. CONCLUSIONS The long-term QOL of esophagectomy patients surviving at least 3 years is improved when compared with the time of diagnosis and does not differ from the general population.
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Affiliation(s)
- Amit Katz
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Yehonatan Nevo
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | | | - Sonia Anchouche
- Faculty of Medicine, McGill University, Montreal, Quebec, Canada
| | - James Tankel
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Natasha Caminsky
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Carmen Mueller
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Jonathan Spicer
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Jonathan Cools-Lartigue
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada
| | - Lorenzo Ferri
- Division of Thoracic and Upper Gastrointestinal Surgery, Department of Surgery, McGill University Health Center, Montreal, Quebec, Canada.
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11
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King E, Algeo N, Connolly D. Feasibility of OptiMaL, a Self-Management Programme for Oesophageal Cancer Survivors. Cancer Control 2023; 30:10732748231185002. [PMID: 37615435 PMCID: PMC10467166 DOI: 10.1177/10732748231185002] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/25/2023] Open
Abstract
INTRODUCTION There is limited availability of self-management interventions for oesophageal cancer survivors at present. This study examined the feasibility of OptiMal, a six-week, self-management programme to improve fatigue, mood and health-related quality of life for oesophageal cancer survivors. METHODS A mixed methods design was used to evaluate the feasibility of OptiMal. The quantitative arm of the study examined changes in the Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale, and the EQ-5D-3L, administered prior to OptiMal (T1), immediately following completion of OptiMal (T2), and three months following completion (T3). Qualitative inquiry in the study was guided by a qualitative descriptive approach through focus groups investigating the experiences of group participants, and individual semi-structured interviews at T3. Qualitative data were analysed using thematic analysis. RESULTS Two OptiMal programmes were delivered over a six-month period with a total of fourteen individuals who had finished treatment for oesophageal cancer. The attendance rate was 89.3%. Statistically significant reductions were observed in fatigue, difficulty performing usual activities, anxiety and depression at three-month follow-up. Qualitative findings identified acceptability of the content and delivery format of OptiMal. Participants reported applying self-management strategies acquired through OptiMal to increase participation in daily activities and improve their health and well-being. CONCLUSIONS This feasibility study yielded promising results in terms of self-management outcomes for oesophageal cancer survivors following attendance of OptiMal. Larger scale research studies with control groups are warranted to examine the outcomes in a robust manner.
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Affiliation(s)
- Eilish King
- Discipline of Occupational Therapy, School of Medicine, Trinity College, Dublin, Ireland
| | - Naomi Algeo
- Discipline of Occupational Therapy, School of Medicine, Trinity College, Dublin, Ireland
| | - Deirdre Connolly
- Discipline of Occupational Therapy, School of Medicine, Trinity College, Dublin, Ireland
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12
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Eyck BM, Jansen MP, Noordman BJ, Atmodimedjo PN, van der Wilk BJ, Martens JW, Helmijr JA, Beaufort CM, Mostert B, Doukas M, Wijnhoven BP, Lagarde SM, van Lanschot JJB, Dinjens WN. Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer. J Pathol 2023; 259:35-45. [PMID: 36196486 PMCID: PMC10092085 DOI: 10.1002/path.6016] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 09/05/2022] [Accepted: 09/30/2022] [Indexed: 11/05/2022]
Abstract
Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24-71) (8/17), specificity of 85% (95% CI 42-99) (6/7), positive predictive value (PPV) of 89% (95% CI 51-99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17-67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6-51) (3/14), specificity of 100% (95% CI 56-100) (7/7), PPV of 100% (95% CI 31-100) (3/3), and NPV of 39% (95% CI 18-64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Ben M Eyck
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Maurice Phm Jansen
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Bo Jan Noordman
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Peggy N Atmodimedjo
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Berend J van der Wilk
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - John Wm Martens
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Jean A Helmijr
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Corine M Beaufort
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Michail Doukas
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Bas Pl Wijnhoven
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - J Jan B van Lanschot
- Department of Surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - Winand Nm Dinjens
- Department of Pathology, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands
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13
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Schuring N, Markar SR, Hagens ERC, Jezerskyte E, Sprangers MAG, Lagergren P, Johar A, Gisbertz SS, van Berge Henegouwen MI. Health-related quality of life following neoadjuvant chemoradiotherapy versus perioperative chemotherapy and esophagectomy for esophageal cancer: a European multicenter study. Dis Esophagus 2022; 36:6761045. [PMID: 36241253 DOI: 10.1093/dote/doac069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 09/08/2022] [Indexed: 12/11/2022]
Abstract
Curative treatment for locally advanced esophageal cancer consists of (neo)adjuvant treatment followed by esophagectomy. Both neoadjuvant chemoradiotherapy and perioperative chemotherapy improve the 5-year overall survival rate compared with surgery alone. However, it is unknown whether these treatment strategies are associated with differences in long-term health-related quality of life (HRQL). The aim of this study is to compare long-term HRQL in patients after esophagectomy treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy. Disease-free cancer patients having undergone esophagectomy and (neo)adjuvant treatment in one of the participating lasting symptoms after esophageal resection (LASER) study centers between 2010 and 2016, were identified from the LASER study dataset. Included patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), EORTC QLQ-OG25, and LASER questionnaires at least 1 year after the completion of treatment. Long-term HRQL was compared between patients treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy, using univariable and multivariable regression and presented as differences in mean score. Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) perioperative chemotherapy. Patients treated with perioperative chemotherapy reported more symptomatology for diarrhea (difference in means 5.93), reflux (difference in means 7.40), and odynophagia (difference in means 4.66). The differences did not exceed the 10 points to be of clinical relevance. No significant differences for the LASER key symptoms were observed. The observed differences in long-term HRQL are in favor of patients treated with neoadjuvant chemoradiotherapy compared with patients treated with perioperative chemotherapy; however, the differences were small. Patients need to be informed about long-term HRQL when considering allocation of (neo)adjuvant treatment.
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Affiliation(s)
- N Schuring
- Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
| | - S R Markar
- Nuffield Department of Surgery, University of Oxford, Oxford, UK.,Department of Molecular Medicine & Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - E R C Hagens
- Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
| | - E Jezerskyte
- Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
| | - M A G Sprangers
- Department of Medical Psychology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands
| | - P Lagergren
- Department of Molecular Medicine & Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,Department of Surgery and Cancer, Imperial College London, London, UK
| | - A Johar
- Department of Molecular Medicine & Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - S S Gisbertz
- Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
| | - M I van Berge Henegouwen
- Department of Surgery, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.,Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
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14
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Hirahara N, Matsubara T, Kaji S, Hayashi H, Kawakami K, Sasaki Y, Takao S, Takao N, Hyakudomi R, Yamamoto T, Tajima Y. Feasibility study of adjuvant chemotherapy with S-1 after curative esophagectomy following neoadjuvant chemotherapy for esophageal cancer. BMC Cancer 2022; 22:718. [PMID: 35768866 PMCID: PMC9245214 DOI: 10.1186/s12885-022-09827-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 06/24/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Despite advances in surgical techniques, long-term survival after esophagectomy for esophageal cancer remains unacceptably low, and more effective perioperative chemotherapy is expected. However, an important concern regarding the application of postoperative adjuvant chemotherapy is treatment toxicity. We aimed to evaluate the feasibility of adjuvant chemotherapy with S-1 in patients after esophagectomy. METHODS We investigated the tolerability of a 2-week administration followed by 1-week rest regimen of S1 as postoperative adjuvant therapy in 20 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (NAC) and 22 patients who did not receive NAC during 2011-2020. RESULTS In the non-NAC group, the mean and median relative dose intensity (RDI) were 78.7% and 99.4%, respectively, and 11 patients (50%) had altered treatment schedules. The corresponding rates in the NAC group were 77.9% and 100%, respectively, and nine patients (45%) had altered treatment schedules, with no significant difference among the groups. Moreover, 17 patients (77.2%) in the non-NAC group and 16 patients (80.0%) in the NAC group continued S-1 treatment as planned for one year postoperatively, with no significant difference in the S-1 continuation rate (p = 0.500). Seventeen of 22 patients (77.3%) and 15 of 20 patients (75.0%) experienced several adverse events in the non-NAC and NAC groups, respectively. The frequency, severity, and type of adverse events were consistent among patients with and without NAC. CONCLUSIONS S-1 could be safely and continuously administered as adjuvant chemotherapy for patients with esophageal cancer regardless of NAC. Long-term prognosis should be evaluated for S-1 to become the standard treatment after esophagectomy.
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Affiliation(s)
- Noriyuki Hirahara
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan.
| | - Takeshi Matsubara
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Shunsuke Kaji
- Department of Surgery, Matsue Red Cross Hospital, Horo-machi, Matsue, Shimane, 690-8506, Japan
| | - Hikota Hayashi
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Koki Kawakami
- Department of Surgery, Matsue Red Cross Hospital, Horo-machi, Matsue, Shimane, 690-8506, Japan
| | - Yohei Sasaki
- Department of Surgery, Masuda Red Cross Hospital, Otoyoshi-cho, Masuda, Shimane, 698-8501, Japan
| | - Satoshi Takao
- Department of Surgery, Unnan City Hospital, Daito-cho, Unnan, Shimane, 699-1221, Japan
| | - Natsuko Takao
- Department of Surgery, Izumo City General Medical Center, Nadabun-cho, Shimane, 691-0003, Japan
| | - Ryoji Hyakudomi
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Tetsu Yamamoto
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
| | - Yoshitsugu Tajima
- Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan
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15
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Dalhammar K, Kristensson J, Falkenback D, Rasmussen BH, Malmström M. Symptoms, problems and quality of life in patients newly diagnosed with oesophageal and gastric cancer - a comparative study of treatment strategy. BMC Cancer 2022; 22:434. [PMID: 35448961 PMCID: PMC9022327 DOI: 10.1186/s12885-022-09536-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 04/11/2022] [Indexed: 12/24/2022] Open
Abstract
Background Patients with oesophageal and gastric cancer have a low likelihood of being cured and suffer from a broad spectrum of symptoms and problems that negatively affect their quality-of-life (QOL). Although the majority (67–75%) of patients at the time of diagnosis suffer from an incurable disease, research has primarily focused on the pre- and postoperative phase among patients treated with curative intent, with little attention to symptoms and problems in the diagnostic phase, especially in those who cannot be offered a cure. Methods In this cross-sectional study 158 patients newly diagnosed with oesophageal and gastric cancer visiting the surgical outpatient department for a preplanned care visit were included consecutively during 2018–2020. The validated instruments QLQ-C30 and QLQ-OG25, developed by the European Organization for Research and Treatment of Cancer (EORTC), and selected items from the Integrated Patient Outcome Scale (IPOS) were used to assess QOL, symptoms and problems. Differences between patients with a curative and a palliative treatment strategy were analysed using t-test and Mann–Whitney U test. The QLQ-C30 and QLQ-OG25 scores were compared to published reference data on the general Swedish population. Results Among all, the QOL was markedly lower, compared with general Swedish population (mean ± SD, 55.9 ± 24.7 vs 76.4 ± 22.8, p < 0.001). Compared to general population, the patients had significant impairment in all QOL aspects, particularly for role and emotional functioning and for symptoms such as eating-related problems, fatigue, insomnia and dyspnea. Majority of patients also reported severe anxiety among family and friends. Among patients with oesophageal cancer those with a palliative treatment strategy, compared with curative strategy, reported significantly lower QOL (mean ± SD, 50.8 ± 28.6 vs 62.0 ± 22.9 p = 0.030), physical (65.5 ± 22.6 vs 83.9 ± 16.5, p < 0.001) and role functioning (55.7 ± 36.6 vs 73.9 ± 33.3, p = 0.012), and a higher burden of several symptoms and problems. No significant differences between treatment groups were shown among patients with gastric cancer. Conclusions Patients newly diagnosed with oesophageal and gastric cancer, and especially those with incurable oesophageal cancer, have a severely affected QOL and several burdensome symptoms and problems. To better address patients’ needs, it seems important to integrate a palliative approach into oesophageal and gastric cancer care.
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Affiliation(s)
- Karin Dalhammar
- Institute for Palliative Care, Lund University and Region Skåne, Lund, Sweden. .,Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
| | - Jimmie Kristensson
- Institute for Palliative Care, Lund University and Region Skåne, Lund, Sweden.,Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden
| | - Dan Falkenback
- Department of Surgery, Skåne University Hospital, Lund, Sweden.,Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden
| | - Birgit H Rasmussen
- Institute for Palliative Care, Lund University and Region Skåne, Lund, Sweden.,Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden
| | - Marlene Malmström
- Institute for Palliative Care, Lund University and Region Skåne, Lund, Sweden.,Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden
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16
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van der Wilk BJ, Eyck BM, Hofstetter WL, Ajani JA, Piessen G, Castoro C, Alfieri R, Kim JH, Kim SB, Furlong H, Walsh TN, Nieboer D, Wijnhoven BPL, Lagarde SM, Lanschot JJBV. Chemoradiotherapy Followed by Active Surveillance Versus Standard Esophagectomy for Esophageal Cancer: A Systematic Review and Individual Patient Data Meta-analysis. Ann Surg 2022; 275:467-476. [PMID: 34191461 DOI: 10.1097/sla.0000000000004930] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To compare overall survival of patients with a cCR undergoing active surveillance versus standard esophagectomy. SUMMARY OF BACKGROUND DATA One-third of patients with esophageal cancer have a pathologically complete response in the resection specimen after neoadjuvant chemoradiotherapy. Active surveillance may be of benefit in patients with cCR, determined with diagnostics during response evaluations after chemoradiotherapy. METHODS A systematic review and meta-analysis was performed comparing overall survival between patients with cCR after chemoradiotherapy undergoing active surveillance versus standard esophagectomy. Authors were contacted to supply individual patient data. Overall and progression-free survival were compared using random effects meta-analysis of randomized or propensity score matched data. Locoregional recurrence rate was assessed. The study-protocol was registered (PROSPERO: CRD42020167070). RESULTS Seven studies were identified comprising 788 patients, of which after randomization or propensity score matching yielded 196 active surveillance and 257 standard esophagectomy patients. All authors provided individual patient data. The risk of all-cause mortality for active surveillance was 1.08 [95% confidence interval (CI): 0.62-1.87, P = 0.75] after intention-to-treat analysis and 0.93 (95% CI: 0.56-1.54, P = 0.75) after per-protocol analysis. The risk of progression or all-cause mortality for active surveillance was 1.14 (95% CI: 0.83-1.58, P = 0.36). Five-year locoregional recurrence rate during active surveillance was 40% (95% CI: 26%-59%). 95% of active surveillance patients undergoing postponed esophagectomy for locoregional recurrence had radical resection. CONCLUSIONS Overall survival was comparable in patients with cCR after chemoradiotherapy undergoing active surveillance or standard esophagectomy. Diagnostic follow-up is mandatory in active surveillance and postponed esophagectomy should be offered to operable patients in case of locoregional recurrence.
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Affiliation(s)
- Berend J van der Wilk
- Department of Surgery, Erasmus MC - University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Ben M Eyck
- Department of Surgery, Erasmus MC - University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Wayne L Hofstetter
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Guillaume Piessen
- University of Lille, Department of Digestive and Oncological Surgery, Claude Huriez University Hospital, Lille, France
| | - Carlo Castoro
- Division of Upper Gastro-Intestinal Surgery, Department of Surgery, Humanitas University, Humanitas Clinical and Research Center-IRCCS, Milan, Italy
- Department of Oncological Surgery, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy
| | - Rita Alfieri
- Department of Oncological Surgery, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy
| | - Jong H Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Bae Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heidi Furlong
- Department of Surgery, Connolly Hospital, Dublin, Ireland
| | - Thomas N Walsh
- Department of Surgery, Connolly Hospital, Dublin, Ireland
| | - Daan Nieboer
- Department of Public Health, Erasmus MC - University Medical Center, Rotterdam, The Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus MC - University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus MC - University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - J Jan B van Lanschot
- Department of Surgery, Erasmus MC - University Medical Center, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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17
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Yu Y, Li M, Kang R, Liu X, Wang N, Zhu Q, Cao J, Cong M. The effectiveness of telephone and Internet-based supportive care for patients with esophageal cancer on enhanced recovery after surgery in China: A randomized controlled trial. Asia Pac J Oncol Nurs 2022; 9:217-228. [PMID: 35571631 PMCID: PMC9096733 DOI: 10.1016/j.apjon.2022.02.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/23/2022] [Indexed: 12/24/2022] Open
Abstract
Objective The aim of this study was to establish a nurse-led supportive care program based on telephone and Internet support and evaluate its efficacy in comparison with conventional care on enhanced recovery after surgery. Methods The study was designed as an open-label, randomized controlled trial to value the efficacy of a nurse-led supportive care program in comparison with conventional care. A convenience sampling method was employed to recruit patients with esophageal cancer in a tertiary Grade A cancer center in Beijing from November 2018 to January 2019. Patients were assigned randomly (1:1) to one of the two groups (intervention group vs control group) via a web randomization system. The control group received conventional care. Patients from the intervention group received conventional care and one-on-one phone calls from nurses following their discharge assessments and education about nutrition and symptoms. Nurses also set up a WeChat group, which they invited patients to join in before discharge for better communication during follow-up. Statistical testing, including nutritional status, quality of life, the helpfulness of the follow-up service, and the patients’ satisfaction with their care, was conducted 6 months after discharge to assess for differences between the two groups. The independent sample t, chi-squared, and Mann–Whitney tests were used to compare between the experiences of the intervention and control groups. The Spearman correlation analysis was used for the analysis of correlation of the nutritional index and quality of life. Results Finally, 168 patients were included in the study, with 86 patients in the intervention group and 82 in the control group. Significant differences between the intervention and control groups were found in the nutrition risk screening 2002 and simple diet self-assessment tool scores. The changes in blood albumin, prealbumin, and transferrin were also statistically significant. All (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) QLQ-C30 results of the intervention group were better than those of the control group. A significant positive correlation of the simple diet self-assessment tool (the higher, the better) and the scores for total health/quality of life were detected (r = 0.214, P = 0.005). A significant negative correlation of the nutrition risk screening 2002 (the lower, the better) and the scores of total health/quality of life was detected (r = −0.446, P = 0.000). The patients’ scores on the helpfulness of the follow-up service and their satisfaction with it were both significantly higher in the intervention group than in the control group. Conclusions This study highlighted the important role of nurse-led supportive care based on telephone and Internet-based support for patients after enhanced recovery after surgery. The supportive care improved patients’ nutritional status, elevated their quality of life, and improved their satisfaction with the care provided to them.
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Affiliation(s)
- Yuan Yu
- Thoracic Surgery Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Corresponding author.
| | - Min Li
- Thoracic Surgery Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ran Kang
- Thoracic Surgery Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinzhe Liu
- Thoracic Surgery Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nuoxiaoxuan Wang
- Thoracic Surgery Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qingmiao Zhu
- Thoracic Surgery Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Cao
- Thoracic Surgery Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Minghua Cong
- Comprehensive Oncology Department of National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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18
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Weis J, Kiemen A, Schmoor C, Hipp J, Czornik M, Reeh M, Grimminger PP, Bruns C, Hoeppner J. Study Protocol of a Prospective Multicenter Study on Patient Participation for the Clinical Trial: Surgery as Needed Versus Surgery on Principle in Post-Neoadjuvant Complete Tumor Response of Esophageal Cancer (ESORES). Front Oncol 2022; 11:789155. [PMID: 35117993 PMCID: PMC8803636 DOI: 10.3389/fonc.2021.789155] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 12/24/2021] [Indexed: 11/23/2022] Open
Abstract
Ideally, patient-centered trial information material encourages the discussion with the treating physician, and helps patients making trade-offs regarding treatment decisions In a situation of possible equivalent treatment options in terms of overall survival (OS), it can make it easier to weigh up advantages and disadvantages. Preferences for choice of treatment in esophageal cancer (EC) are complex, and no standardized assessment tools are available. We will explore patient’s factors for treatment choice and develop a comprehensive patient information leaflet for the inclusion into randomized controlled trials (RCT) on EC. We conduct a cross-sectional, observational study based on a mixed-methods design with patients suffering from non-metastatic EC with post-neoadjuvant complete response after neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiation (nCRT), to develop patient-centered trial information material. This pilot study is performed in a concept development phase and a subsequent pilot phase. We start with patient interviews (n = 10–15) in the concept development phase to evaluate patients’ needs, and develop a Preference and Decision Aid Questionnaire (PDAQ). We pre-test the PDAQ with another n = 10 patients with EC after nCT or nCRT, former patients from a self-help organization, and n = 10 medical experts for their comments on the questionnaire. In the pilot phase, a multicenter trial using the PDAQ and additional measures is carried out (n = 120). Based on evidence of a possible equivalence in terms of OS of the treatment options “surgery as needed” and “surgery on principle” in patients with post-neoadjuvant complete response of EC, this pilot study on patient participation is conducted to assess patient’s needs and preferences, and optimize patients’ inclusion in a planned RCT. The aim is to develop patient-centered trial information material for the RCT to increase patients’ consent and compliance with the randomized treatment. The trial is registered at the German Clinical Trials Register (DRKS00022050, October 15, 2020).
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Affiliation(s)
- Joachim Weis
- Endowed Professorship Self-Help Research, Comprehensive Cancer Center, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
- *Correspondence: Joachim Weis,
| | - Andrea Kiemen
- Endowed Professorship Self-Help Research, Comprehensive Cancer Center, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Claudia Schmoor
- Clinical Trials Unit, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Julian Hipp
- Department of General Surgery, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Manuel Czornik
- Endowed Professorship Self-Help Research, Comprehensive Cancer Center, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Peter P. Grimminger
- Department of General, Visceral and Transplantation Surgery, University Medical Center Mainz, Mainz, Germany
| | - Christiane Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, Cologne, Germany
| | - Jens Hoeppner
- Clinic for Surgery, University Medical Center Schleswig-Holstein, Lübeck, Germany
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19
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Sheng WG, Assogba E, Billa O, Meunier B, Gagnière J, Collet D, D'Journo XB, Brigand C, Piessen G, Dabakuyo-Yonli TS. Does baseline quality of life predict the occurrence of complications in resectable esophageal cancer? Surg Oncol 2021; 40:101707. [PMID: 35030410 DOI: 10.1016/j.suronc.2021.101707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 12/21/2021] [Accepted: 12/28/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND The aim of this study was to assess the impact of baseline health related quality of life (HRQOL) on the occurrence of postoperative complications and death in patients with resectable esophageal cancer. METHODS Existing data from a prospective, multicenter, open label, randomized, controlled phase III trial comparing hybrid versus open esophagectomy in patients with resectable esophageal cancer from 2009 to 2012 in France were used. A Cox regression model was used to assess the prognostic value of the baseline HRQOL score on the occurrence of major complications (MC), and major pulmonary complications (MPC) at 30 days post-surgery, as well as on 1-year postoperative overall survival (OS). RESULTS Every 10-point increase in the baseline role functioning score was associated with a 14% reduction in the risk of MC, while every 10-point increase in fatigue or pain score was associated with an 18% increase in the risk of MC. Similarly, higher scores on fatigue and pain were associated with a higher risk of MPC. Compared with the hybrid procedure, patients undergoing open esophagectomy had a significantly higher risk of MC and MPC. Patients diagnosed with esophageal adenocarcinoma were at significantly lower risk of MC or MPC compared to patients with esophageal squamous cell carcinoma. Higher pain (HR = 1.23, p = 0.035) and insomnia (HR = 1.16, P = 0.031) scores were associated with increased 1-year OS. CONCLUSION Fatigue, pain, insomnia, and squamous cell pathology were indicators of poor prognosis, and that the presence of these findings might possibly change the management plan towards other forms of treatment and warrant close attention.
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Affiliation(s)
- Wei Gilis Sheng
- Epidemiology and Quality of Life Unit, Georges-François Leclerc Cancer Centre-UNICANCER, Dijon, France
| | - Emerline Assogba
- Epidemiology and Quality of Life Unit, Georges-François Leclerc Cancer Centre-UNICANCER, Dijon, France
| | - Oumar Billa
- Epidemiology and Quality of Life Unit, Georges-François Leclerc Cancer Centre-UNICANCER, Dijon, France
| | - Bernard Meunier
- Department of Hepatobiliary and Digestive Surgery, CHU Rennes, University of Rennes 1, Rennes, France
| | - Johan Gagnière
- Department of Digestive Surgery, INSERM, CHU Clermont-Ferrand, University of Clermont Auvergne, Clermont-Ferrand, France
| | - Denis Collet
- Department of Digestive Surgery, Haut Lévèque University Hospital, Bordeaux, France
| | - Xavier Benoît D'Journo
- Department of Thoracic Surgery, Nord Hospital, University of Aix-Marseille, Public Assistance-Marseille Hospitals, Marseille, France
| | - Cécile Brigand
- Department of Digestive Surgery, Strasbourg University, Strasbourg, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, Claude Huriez Hospital, CHU Lille. Place de Verdun, 59037, Lille, Cedex, France
| | - Tienhan Sandrine Dabakuyo-Yonli
- Epidemiology and Quality of Life Unit, Georges-François Leclerc Cancer Centre-UNICANCER, Dijon, France; National Quality of Life and Cancer Clinical Research Platform, Dijon, France.
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20
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Tukanova KH, Chidambaram S, Guidozzi N, Hanna GB, McGregor AH, Markar SR. Physiotherapy Regimens in Esophagectomy and Gastrectomy: a Systematic Review and Meta-Analysis. Ann Surg Oncol 2021; 29:3148-3167. [PMID: 34961901 PMCID: PMC8990957 DOI: 10.1245/s10434-021-11122-7] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 11/11/2021] [Indexed: 12/30/2022]
Abstract
Background Esophageal and gastric cancer surgery are associated with considerable morbidity, specifically postoperative pulmonary complications (PPCs), potentially accentuated by underlying challenges with malnutrition and cachexia affecting respiratory muscle mass. Physiotherapy regimens aim to increase the respiratory muscle strength and may prevent postoperative morbidity. Objective The aim of this study was to assess the impact of physiotherapy regimens in patients treated with esophagectomy or gastrectomy. Methods An electronic database search was performed in the MEDLINE, EMBASE, CENTRAL, CINAHL and Pedro databases. A meta-analysis was performed to assess the impact of physiotherapy on the functional capacity, incidence of PPCs and postoperative morbidity, in-hospital mortality rate, length of hospital stay (LOS) and health-related quality of life (HRQoL). Results Seven randomized controlled trials (RCTs) and seven cohort studies assessing prehabilitation totaling 960 patients, and five RCTs and five cohort studies assessing peri- or postoperative physiotherapy with 703 total patients, were included. Prehabilitation resulted in a lower incidence of postoperative pneumonia and morbidity (Clavien–Dindo score ≥ II). No difference was observed in functional exercise capacity and in-hospital mortality following prehabilitation. Meanwhile, peri- or postoperative rehabilitation resulted in a lower incidence of pneumonia, shorter LOS, and better HRQoL scores for dyspnea and physical functioning, while no differences were found for the QoL summary score, global health status, fatigue, and pain scores. Conclusion This meta-analysis suggests that implementing an exercise intervention may be beneficial in both the preoperative and peri- or postoperative periods. Further investigation is needed to understand the mechanism through which exercise interventions improve clinical outcomes and which patient subgroup will gain the maximal benefit. Supplementary Information The online version contains supplementary material available at 10.1245/s10434-021-11122-7.
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Affiliation(s)
- Karina H Tukanova
- Department of Surgery and Cancer, Imperial College London, London, UK
| | | | - Nadia Guidozzi
- Department of Surgery, University of the Witwatersrand, Johannesburg, South Africa
| | - George B Hanna
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Alison H McGregor
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Sheraz R Markar
- Department of Surgery and Cancer, Imperial College London, London, UK. .,Nuffield Department of Surgery, University of Oxford, Oxford, UK. .,Department of Molecular Medicine and Surgery, Karolinska Institutet, Solna, Sweden. .,Division of Surgery, Department of Surgery and Cancer, St Mary's Hospital, London, UK.
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21
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Sunde B, Lindblad M, Malmström M, Hedberg J, Lagergren P, Nilsson M. Health-related quality of life one year after the diagnosis of oesophageal cancer: a population-based study from the Swedish National Registry for Oesophageal and Gastric Cancer. BMC Cancer 2021; 21:1277. [PMID: 34836512 PMCID: PMC8620917 DOI: 10.1186/s12885-021-09007-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 11/11/2021] [Indexed: 12/09/2022] Open
Abstract
BACKGROUND Population-based patient reported outcome data in oesophageal cancer are rare. The main purpose of this study was to describe health-related quality of life (HRQOL) 1 year after the diagnosis of oesophageal cancer, comparing subgroups of curatively and palliatively managed patients. METHODS This is a nationwide population-based cohort study, based on the Swedish National Registry for Oesophageal and Gastric Cancer (NREV) with prospectively registered data, including HRQOL instruments from the European Organisation for Research and Treatment of Cancer including the core and disease specific questionnaires (EORTC QLQ-C30 and QLQ-OG25). Patients diagnosed with oesophageal cancer between 2009 and 2016 and with complete HRQOL data at 1 year follow-up were included. HRQOL of included patients was compared to a reference population matched by age and gender to to a previous cohort of unselected Swedish oesophageal cancer patients. Linear regression was performed to calculate mean scores with 95% confidence intervals (CI) and adjusted linear regression analysis was used to calculate mean score differences (MD) with 95% CI. RESULTS A total of 1156 patients were included. Functions and global health/quality of life were lower in both the curative and palliative cohorts compared to the reference population. Both curatively and palliatively managed patients reported a severe symptom burden compared to the reference population. Patients who underwent surgery reported more problems with diarrhoea compared to those treated with definitive chemoradiotherapy (dCRT) (MD -14; 95% CI - 20 to - 8). Dysphagia was more common in patiens treated with dCRT compared to surgically treated patients (MD 11; 95% CI 4 to 18). Those with palliative intent due to advanced tumour stage reported more problems with dysphagia compared to those with palliative intent due to frailty (MD -18; 95% CI - 33 to - 3). CONCLUSIONS One year after diagnosis both curative and palliative intent patients reported low function scores and severe symptoms. Dysphagia, choking, and other eating related problems were more pronounced in palliatively managed patients and in the curative intent patients treated with dCRT.
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Affiliation(s)
- Berit Sunde
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet and Department of Upper Abdominal Diseases, Karolinska University Hospital, SE-14186, Stockholm, Sweden.
| | - Mats Lindblad
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet and Department of Upper Abdominal Diseases, Karolinska University Hospital, SE-14186, Stockholm, Sweden
| | - Marlene Malmström
- Lund University, Department of Health Sciences and Department of surgery, Skane University Hospital, 221 85, Lund, Sweden
| | - Jakob Hedberg
- Department of Surgical Sciences, Uppsala University, 751 85, Uppsala, Sweden
| | - Pernilla Lagergren
- Surgical Care Science, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden.,Department of Surgery and Cancer, Imperial College London, London, SW7 2AZ, UK
| | - Magnus Nilsson
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet and Department of Upper Abdominal Diseases, Karolinska University Hospital, SE-14186, Stockholm, Sweden
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22
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Ukegjini K, Vetter D, Fehr R, Dirr V, Gubler C, Gutschow CA. Functional syndromes and symptom-orientated aftercare after esophagectomy. Langenbecks Arch Surg 2021; 406:2249-2261. [PMID: 34036407 PMCID: PMC8578083 DOI: 10.1007/s00423-021-02203-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 05/16/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND Surgery is the cornerstone of esophageal cancer treatment but remains burdened with significant postoperative changes of gastrointestinal function and quality of life. PURPOSE The aim of this narrative review is to assess and summarize the current knowledge on postoperative functional syndromes and quality of life after esophagectomy for cancer, and to provide orientation for the reader in the challenging field of functional aftercare. CONCLUSIONS Post-esophagectomy syndromes include various conditions such as dysphagia, reflux, delayed gastric emptying, dumping syndrome, weight loss, and chronic diarrhea. Clinical pictures and individual expressions are highly variable and may be extremely distressing for those affected. Therefore, in addition to a mostly well-coordinated oncological follow-up, we strongly emphasize the need for regular monitoring of physical well-being and gastrointestinal function. The prerequisite for an effective functional aftercare covering the whole spectrum of postoperative syndromes is a comprehensive knowledge of the pathophysiological background. As functional conditions often require a complex diagnostic workup and long-term therapy, close interdisciplinary cooperation with radiologists, gastroenterologists, oncologists, and specialized nutritional counseling is imperative for successful management.
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Affiliation(s)
- Kristjan Ukegjini
- Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland
- Department of General, Visceral, Endocrine and Transplant Surgery, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Diana Vetter
- Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Rebecca Fehr
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland
| | - Valerian Dirr
- Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Christoph Gubler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Christian A Gutschow
- Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland.
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23
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Squires MH, Gower N, Benbow JH, Donahue EE, Bohl CE, Prabhu RS, Hill JS, Salo JC. PET Imaging and Rate of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 2021; 29:1327-1333. [PMID: 34625880 DOI: 10.1245/s10434-021-10644-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 07/30/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35-50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a 'watch and wait' strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. METHODS ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. RESULTS Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. CONCLUSION Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a 'watch and wait' strategy for ESCC treated with ChemoRT.
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Affiliation(s)
- M Hart Squires
- Division of Surgical Oncology, Department of Surgery, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Nicole Gower
- LCI Research Support, Clinical Trials Office, Levine Cancer Institute, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Jennifer H Benbow
- LCI Research Support, Clinical Trials Office, Levine Cancer Institute, Carolinas Medical Center, Atrium Health, Charlotte, NC, USA
| | - Erin E Donahue
- Department of Biostatistics, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Casey E Bohl
- Charlotte Radiology, Atrium Health, Charlotte, NC, USA
| | - Roshan S Prabhu
- Southeast Radiation Oncology Group, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Joshua S Hill
- Division of Surgical Oncology, Department of Surgery, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
| | - Jonathan C Salo
- Division of Surgical Oncology, Department of Surgery, Carolinas Medical Center, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA.
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24
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Joshy G, Thandrayen J, Koczwara B, Butow P, Laidsaar-Powell R, Rankin N, Canfell K, Stubbs J, Grogan P, Bailey L, Yazidjoglou A, Banks E. Disability, psychological distress and quality of life in relation to cancer diagnosis and cancer type: population-based Australian study of 22,505 cancer survivors and 244,000 people without cancer. BMC Med 2020; 18:372. [PMID: 33256726 PMCID: PMC7708114 DOI: 10.1186/s12916-020-01830-4] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 10/27/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Improved survival means that cancer is increasingly becoming a chronic disease. Understanding and improving functional outcomes are critical to optimising survivorship. We quantified physical and mental health-related outcomes in people with versus without cancer, according to cancer type. METHODS Questionnaire data from an Australian population-based cohort study (45 and Up Study (n = 267,153)) were linked to cancer registration data to ascertain cancer diagnoses up to enrolment. Modified Poisson regression estimated age- and sex-adjusted prevalence ratios (PRs) for adverse person-centred outcomes-severe physical functional limitations (disability), moderate/high psychological distress and fair/poor quality of life (QoL)-in participants with versus without cancer, for 13 cancer types. RESULTS Compared to participants without cancer (n = 244,000), cancer survivors (n = 22,505) had greater disability (20.6% versus 12.6%, respectively, PR = 1.28, 95%CI = (1.25-1.32)), psychological (22.2% versus 23.5%, 1.05 (1.02-1.08)) and poor/fair QoL (15.2% versus 10.2%; 1.28 (1.24-1.32)). The outcomes varied by cancer type, being worse for multiple myeloma (PRs versus participants without cancer for disability 3.10, 2.56-3.77; distress 1.53, 1.20-1.96; poor/fair QoL 2.40, 1.87-3.07), lung cancer (disability 2.81, 2.50-3.15; distress 1.67, 1.46-1.92; poor/fair QoL 2.53, 2.21-2.91) and non-Hodgkin's lymphoma (disability 1.56, 1.37-1.78; distress 1.20, 1.05-1.36; poor/fair QoL 1.66, 1.44-1.92) and closer to those in people without cancer for breast cancer (disability 1.23, 1.16-1.32; distress 0.95, 0.90-1.01; poor/fair QoL 1.15, 1.05-1.25), prostate cancer (disability 1.11, 1.04-1.19; distress 1.09, 1.02-1.15; poor/fair QoL 1.15, 1.08-1.23) and melanoma (disability 1.02, 0.94-1.10; distress 0.96, 0.89-1.03; poor/fair QoL 0.92, 0.83-1.01). Outcomes were worse with recent diagnosis and treatment and advanced stage. Physical disability in cancer survivors was greater in all population subgroups examined and was a major contributor to adverse distress and QoL outcomes. CONCLUSIONS Physical disability, distress and reduced QoL are common after cancer and vary according to cancer type suggesting priority areas for research, and care and support.
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Affiliation(s)
- Grace Joshy
- National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Mills Road, Acton, Canberra, ACT, 2601, Australia.
| | - Joanne Thandrayen
- National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Mills Road, Acton, Canberra, ACT, 2601, Australia
| | - Bogda Koczwara
- Flinders University and Flinders Medical Centre, Adelaide, SA, Australia
| | - Phyllis Butow
- Centre for Medical Psychology and Evidence-based Medicine, School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
| | - Rebekah Laidsaar-Powell
- Centre for Medical Psychology and Evidence-based Medicine, School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
| | - Nicole Rankin
- Centre for Medical Psychology and Evidence-based Medicine, School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia
| | - Karen Canfell
- Centre for Medical Psychology and Evidence-based Medicine, School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW, Australia.,Cancer Research Division, Cancer Council New South Wales, Kings Cross, NSW, Australia.,Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia
| | | | - Paul Grogan
- Cancer Research Division, Cancer Council New South Wales, Kings Cross, NSW, Australia
| | - Louise Bailey
- Primary Care Collaborative Cancer Clinical Trials Group Community Advisory Group, Melbourne, VIC, Australia.,Psycho-oncology Cooperative Research Group Community Advisory Group, Camperdown, NSW, Australia
| | - Amelia Yazidjoglou
- National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Mills Road, Acton, Canberra, ACT, 2601, Australia
| | - Emily Banks
- National Centre for Epidemiology and Population Health, Research School of Population Health, Australian National University, Mills Road, Acton, Canberra, ACT, 2601, Australia.,Sax Institute, Haymarket, NSW, Australia
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25
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Kim L, Loccoh EC, Sanchez R, Ruz P, Anaba U, Williams TM, Slivnick J, Vallakati A, Baliga R, Ayan A, Miller ED, Addison D. Contemporary Understandings of Cardiovascular Disease After Cancer Radiotherapy: a Focus on Ischemic Heart Disease. Curr Cardiol Rep 2020; 22:151. [PMID: 32964267 DOI: 10.1007/s11886-020-01380-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Radiation-induced cardiovascular disease, including coronary artery disease, is a well-known sequela of radiation therapy and represents a significant source of morbidity and mortality for cancer survivors. This review examines current literature and guidelines to care for this growing population of cancer survivors. RECENT FINDINGS The development of radiation-induced ischemic heart disease following radiation can lead even to early cardiotoxicities, inclusive of coronary artery disease, which limit cancer treatment outcomes. These coronary lesions tend to be diffuse, complex, and proximal. Early detection with multimodality imaging and targeted intervention is required to minimize these risks. Early awareness, detection, and management of radiation-induced cardiovascular disease are paramount as cancer survivorship continues to grow.
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Affiliation(s)
- Lisa Kim
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Emefah C Loccoh
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Reynaldo Sanchez
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Patrick Ruz
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Uzoma Anaba
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Terence M Williams
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Jeremy Slivnick
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Ajay Vallakati
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Ragavendra Baliga
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA
| | - Ahmet Ayan
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
| | - Daniel Addison
- Cardio-Oncology Program, Division of Cardiology, The Ohio State University Medical Center, Columbus, OH, USA.
- Division of Cancer Control and Prevention, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, OH, USA.
- Division of Cardiology, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, 473 W. 12th Ave., Columbus, OH, 43210, USA.
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26
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Yang L, Shen C, Pettit CJ, Li T, Hu AJ, Miller ED, Zhang J, Lin SH, Williams TM. Wee1 Kinase Inhibitor AZD1775 Effectively Sensitizes Esophageal Cancer to Radiotherapy. Clin Cancer Res 2020; 26:3740-3750. [PMID: 32220892 PMCID: PMC7367716 DOI: 10.1158/1078-0432.ccr-19-3373] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 02/20/2020] [Accepted: 03/24/2020] [Indexed: 12/31/2022]
Abstract
PURPOSE Esophageal cancer is a deadly malignancy with a 5-year survival rate of only 5% to 20%, which has remained unchanged for decades. Esophageal cancer possesses a high frequency of TP53 mutations leading to dysfunctional G1 cell-cycle checkpoint, which likely makes esophageal cancer cells highly reliant upon G2-M checkpoint for adaptation to DNA replication stress and DNA damage after radiation. We aim to explore whether targeting Wee1 kinase to abolish G2-M checkpoint sensitizes esophageal cancer cells to radiotherapy. EXPERIMENTAL DESIGN Cell viability was assessed by cytotoxicity and colony-forming assays, cell-cycle distribution was analyzed by flow cytometry, and mitotic catastrophe was assessed by immunofluorescence staining. Human esophageal cancer xenografts were generated to explore the radiosensitizing effect of AZD1775 in vivo. RESULTS The IC50 concentrations of AZD1775 on esophageal cancer cell lines were between 300 and 600 nmol/L. AZD1775 (100 nmol/L) as monotherapy did not alter the viability of esophageal cancer cells, but significantly radiosensitized esophageal cancer cells. AZD1775 significantly abrogated radiation-induced G2-M phase arrest and attenuation of p-CDK1-Y15. Moreover, AZD1775 increased radiation-induced mitotic catastrophe, which was accompanied by increased γH2AX levels, and subsequently reduced survival after radiation. Importantly, AZD1775 in combination with radiotherapy resulted in marked tumor regression of esophageal cancer tumor xenografts. CONCLUSIONS Abrogation of G2-M checkpoint by targeting Wee1 kinase with AZD1775 sensitizes esophageal cancer cells to radiotherapy in vitro and in mouse xenografts. Our findings suggest that inhibition of Wee1 by AZD1775 is an effective strategy for radiosensitization in esophageal cancer and warrants clinical testing.
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Affiliation(s)
- Linlin Yang
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio
| | - Changxian Shen
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio
| | - Cory J Pettit
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio
| | - Tianyun Li
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio
| | - Andrew J Hu
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio
| | - Eric D Miller
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio
| | - Junran Zhang
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio
| | - Steven H Lin
- The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Terence M Williams
- The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, Ohio.
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27
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Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Systematic Review and Meta-analysis. Ann Surg 2020; 271:245-256. [PMID: 31188203 DOI: 10.1097/sla.0000000000003397] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The aim of this study was to perform a meta-analysis on the accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) for detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. SUMMARY OF BACKGROUND DATA After nCRT, one-third of patients have a pathologically complete response in the resection specimen. Before an active surveillance strategy could be offered to these patients, clinically complete responders should be accurately identified. METHODS Embase, Medline, Cochrane, and Web-of-Science were searched until February 2018 for studies on accuracy of endoscopic biopsies, EUS, or PET(-CT) for detecting locoregional residual disease after nCRT for squamous cell- or adenocarcinoma. Pooled sensitivities and specificities were calculated using random-effect meta-analyses. RESULTS Forty-four studies were included for meta-analyses. For detecting residual disease at the primary tumor site, 12 studies evaluated endoscopic biopsies, 11 qualitative EUS, 14 qualitative PET, 8 quantitative PET using maximum standardized uptake value (SUVmax), and 7 quantitative PET using percentage reduction of SUVmax (%ΔSUVmax). Pooled sensitivities and specificities were 33% and 95% for endoscopic biopsies, 96% and 8% for qualitative EUS, 74% and 52% for qualitative PET, 69% and 72% for PET-SUVmax, and 73% and 63% for PET-%ΔSUVmax. For detecting residual nodal disease, 11 studies evaluated qualitative EUS with a pooled sensitivity and specificity of 68% and 57%, respectively. In subgroup analyses, sensitivity of PET-%ΔSUVmax and EUS for nodal disease was higher in squamous cell carcinoma than adenocarcinoma. CONCLUSIONS Current literature suggests insufficient accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) as single modalities for detecting residual disease after nCRT for esophageal cancer.
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28
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Borggreve AS, Heethuis SE, Boekhoff MR, Goense L, van Rossum PSN, Brosens LAA, van Lier ALHMW, van Hillegersberg R, Lagendijk JJW, Mook S, Ruurda JP, Meijer GJ. Optimal timing for prediction of pathologic complete response to neoadjuvant chemoradiotherapy with diffusion-weighted MRI in patients with esophageal cancer. Eur Radiol 2020; 30:1896-1907. [PMID: 31822974 PMCID: PMC7062655 DOI: 10.1007/s00330-019-06513-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 09/18/2019] [Accepted: 10/14/2019] [Indexed: 12/14/2022]
Abstract
OBJECTIVE This study was conducted in order to determine the optimal timing of diffusion-weighted magnetic resonance imaging (DW-MRI) for prediction of pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS Patients with esophageal adenocarcinoma or squamous cell carcinoma who planned to undergo nCRT followed by surgery were enrolled in this prospective study. Patients underwent six DW-MRI scans: one baseline scan before the start of nCRT and weekly scans during 5 weeks of nCRT. Relative changes in mean apparent diffusion coefficient (ADC) values between the baseline scans and the scans during nCRT (ΔADC(%)) were compared between pathologic complete responders (pCR) and non-pCR (tumor regression grades 2-5). The discriminative ability of ΔADC(%) was determined based on the c-statistic. RESULTS A total of 24 patients with 142 DW-MRI scans were included. pCR was observed in seven patients (29%). ΔADC(%) from baseline to week 2 was significantly higher in patients with pCR versus non-pCR (median [IQR], 36% [30%, 41%] for pCR versus 16% [14%, 29%] for non-pCR, p = 0.004). The ΔADC(%) of the second week in combination with histology resulted in the highest c-statistic for the prediction of pCR versus non-pCR (0.87). The c-statistic of this model increased to 0.97 after additional exclusion of patients with a small tumor volume (< 7 mL, n = 3) and tumor histology of the resection specimen other than adenocarcinoma or squamous cell carcinoma (n = 1). CONCLUSION The relative change in tumor ADC (ΔADC(%)) during the first 2 weeks of nCRT is the most predictive for pathologic complete response to nCRT in esophageal cancer patients. KEY POINTS • DW-MRI during the second week of neoadjuvant chemoradiotherapy is most predictive for pathologic complete response in esophageal cancer. • A model including ΔADCweek 2was able to discriminate between pathologic complete responders and non-pathologic complete responders in 87%. • Improvements in future MRI studies for esophageal cancer may be obtained by incorporating motion management techniques.
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Affiliation(s)
- Alicia S Borggreve
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.
| | - Sophie E Heethuis
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Mick R Boekhoff
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Lucas Goense
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Peter S N van Rossum
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Astrid L H M W van Lier
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Richard van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Jan J W Lagendijk
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Stella Mook
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Jelle P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands
| | - Gert J Meijer
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584, CX, Utrecht, The Netherlands.
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29
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Janssen HJ, Fransen LF, Ponten JE, Nieuwenhuijzen GA, Luyer MD. Micronutrient Deficiencies Following Minimally Invasive Esophagectomy for Cancer. Nutrients 2020; 12:E778. [PMID: 32183492 PMCID: PMC7146612 DOI: 10.3390/nu12030778] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 03/05/2020] [Accepted: 03/13/2020] [Indexed: 12/15/2022] Open
Abstract
Over the past decades, survival rates for patients with resectable esophageal cancer have improved significantly. Consequently, the sequelae of having a gastric conduit, such as development of micronutrient deficiencies, become increasingly apparent. This study investigated postoperative micronutrient trends in the follow-up of patients following a minimally invasive esophagectomy (MIE) for cancer. Patients were included if they had at least one postoperative evaluation of iron, ferritin, vitamins B1, B6, B12, D, folate or methylmalonic acid. Data were available in 83 of 95 patients. Of these, 78.3% (65/83) had at least one and 37.3% (31/83) had more than one micronutrient deficiency at a median of 6.1 months (interquartile range (IQR) 5.4-7.5) of follow-up. Similar to the results found in previous studies, most common deficiencies identified were: iron, vitamin B12 and vitamin D. In addition, folate deficiency and anemia were detected in a substantial amount of patients in this cohort. At 24.8 months (IQR 19.4-33.1) of follow-up, micronutrient deficiencies were still common, however, most deficiencies normalized following supplementation on indication. In conclusion, patients undergoing a MIE are at risk of developing micronutrient deficiencies as early as 6 up to 24 months after surgery and should therefore be routinely checked and supplemented when needed.
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Affiliation(s)
| | | | | | | | - Misha D.P. Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, Michelangelolaan 2, 5623 EJ Eindhoven, The Netherlands
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30
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Backemar L, Johar A, Wikman A, Zylstra J, Gossage J, Davies A, Lagergren J, Lagergren P. The Influence of Comorbidity on Health-Related Quality of Life After Esophageal Cancer Surgery. Ann Surg Oncol 2020; 27:2637-2645. [PMID: 32162078 PMCID: PMC7334248 DOI: 10.1245/s10434-020-08303-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Esophageal cancer surgery reduces patients' health-related quality of life (HRQoL). This study examined whether comorbidities influence HRQoL in these patients. METHODS This prospective cohort study included esophageal cancer patients having undergone curatively intended esophagectomy at St Thomas' Hospital London in 2011-2015. Clinical data were collected from patient reports and medical records. Well-validated cancer-specific and esophageal cancer-specific questionnaires (EORTC QLQ-C30 and QLQ-OG25) were used to assess HRQoL before and 6 months after esophagectomy. Number of comorbidities, American Society of Anesthesiologists physical status classification (ASA), and specific comorbidities were analyzed in relation to HRQoL aspects using multivariable linear regression models. Mean score differences with 95% confidence intervals were adjusted for potential confounders. RESULTS Among 136 patients, those with three or more comorbidities at the time of surgery had poorer global quality of life and physical function and more fatigue compared with those with no comorbidity. Patients with ASA III-IV reported more problems with the above HRQoL aspects and worse social function and pain compared with those with ASA I-II. Cardiac comorbidity was associated with worse global quality of life and dyspnea, while pulmonary comorbidities were related to coughing. Patients assessed both before and 6 months after surgery (n = 80) deteriorated in most HRQoL aspects regardless of comorbidity status, but patients with several comorbidities had worse physical function and fatigue and more trouble with coughing compared with those with fewer comorbidities. CONCLUSION Comorbidity appears to negatively influence HRQoL before esophagectomy, but appears not to severely impact 6-month recovery of HRQoL.
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Affiliation(s)
- Lovisa Backemar
- Surgical Care Science, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Asif Johar
- Surgical Care Science, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Wikman
- Reproductive Health, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Janine Zylstra
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,School of Cancer and Pharmaceutical Sciences, Kings College, London, UK.,Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Trust, London, UK
| | - James Gossage
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,School of Cancer and Pharmaceutical Sciences, Kings College, London, UK.,Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Trust, London, UK
| | - Andrew Davies
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,School of Cancer and Pharmaceutical Sciences, Kings College, London, UK.,Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Trust, London, UK
| | - Jesper Lagergren
- Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,School of Cancer and Pharmaceutical Sciences, Kings College, London, UK.,Upper Gastrointestinal Surgery, Guy's and St Thomas' NHS Trust, London, UK
| | - Pernilla Lagergren
- Surgical Care Science, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
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31
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Zhang N, Gu M, Wang J, Wu S. Comparison of nodal irradiation dose using radiotherapy for patients with thoracic esophageal cancer. Oncol Lett 2020; 19:1042-1050. [PMID: 31897217 PMCID: PMC6924155 DOI: 10.3892/ol.2019.11178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 03/21/2019] [Indexed: 01/29/2023] Open
Abstract
The present study aimed to compare incidental nodal irradiation (INI) doses using volume-modulated arc therapy (VMAT), 5-field intensity-modulated radiotherapy (5F-IMRT) and 3D-conformal radiotherapy (3D-CRT) treatment plans for patients with thoracic esophageal cancer (EC). A total of 15 patients with thoracic EC were selected for participation between October 2016 and July 2017 at the Hangzhou Cancer Hospital. Regional lymph nodal stations were contoured according to 3D CT-based images of the Japan Esophageal Society Guidelines. All patients were treated with 60 Gy using VMAT, 5F-IMRT and 3D-CRT plans. Dose-volume histograms of planning target volume (PTV), lung, heart, spinal cord and incidental nodal irradiation were compared between the three plans. 5F-IMRT was superior in PTV_V95% (the volume of the PTV receiving 95% of the prescription dose, P=0.003) and the VMAT plan was best in terms of conformal index (P=0.005). V20 and V30 were reduced by 10.7-22.6% (P=0.002) and 12.8-21% (P=0.026), respectively, in normal lung tissue using the VMAT plan. 5F-IMRT demonstrated the lowest maximum dose (Dmax) for the spinal cord (P=0.037). For the INI, 3D-CRT exhibited the highest equivalent uniform dose (EUD) values for 106pre (P=0.014) and 106tb-L (P=0.03) in upper-thoracic EC. The mean EUD of all lymph nodal regions in middle-thoracic EC were >40 Gy in VMAT and 5F-IMRT plans; the VMAT plan had higher EUD values in lower-thoracic EC compared with 5F-IMRT, 3D-CRT plans for INI. VMAT were comparable to the 5F-IMRT plan with respect to dosimetric characteristics for planning and INI doses to thoracic nodal levels NO 105-112 are considerable for thoracic EC.
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Affiliation(s)
- Ni Zhang
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China
| | - Min Gu
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China
| | - Jiahao Wang
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China
| | - Shixiu Wu
- Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang 310002, P.R. China
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Noordman BJ, Verdam MGE, Onstenk B, Heisterkamp J, Jansen WJBM, Martijnse IS, Lagarde SM, Wijnhoven BPL, Acosta CMM, van der Gaast A, Sprangers MAG, van Lanschot JJB. Quality of Life During and After Completion of Neoadjuvant Chemoradiotherapy for Esophageal and Junctional Cancer. Ann Surg Oncol 2019; 26:4765-4772. [PMID: 31620943 PMCID: PMC6864114 DOI: 10.1245/s10434-019-07779-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Indexed: 12/28/2022]
Abstract
Background The course of health-related quality of life (HRQOL) during and after completion of neoadjuvant chemoradiotherapy (nCRT) for esophageal or junctional carcinoma is unknown. Methods This study was a multicenter prospective cohort investigation. Patients with esophageal or cancer to be treated with nCRT plus esophagectomy were eligible for inclusion in the study. The HRQOL of the patients was measured with European Organization for Research and Treatment of Cancer QLQ-C30, QLQ-OG25, and QLQ-CIPN20 questionnaires before and during nCRT, then 2, 4, 6, 8, 10, 12, 14, and 16 weeks after nCRT and before surgery. Predefined end points were based on the hypothesized impact of nCRT. The primary end points were physical functioning, odynophagia, and sensory symptoms. The secondary end points were global quality of life, fatigue, weight loss, and motor symptoms. Mixed modeling analysis was used to evaluate changes over time. Results Of 106 eligible patients, 96 (91%) were included in the study. The rate of questionnaires returned ranged from 94% to 99% until week 12, then dropped to 78% in week 16 after nCRT. A negative impact of nCRT on all HRQOL end points was observed during the last cycle of nCRT (all p < 0.001) and 2 weeks after nCRT (all p < 0.001). Physical functioning, odynophagia, and sensory symptoms were restored to pretreatment levels respectively 8, 4, and 6 weeks after nCRT. The secondary end points were restored to baseline levels 4–6 weeks after nCRT. Odynophagia, fatigue, and weight loss improved after nCRT compared with baseline levels at respectively 6 (p < 0.001), 16 (p = 0.001), and 12 weeks (p < 0.001). Conclusion After completion of nCRT for esophageal cancer, HRQOL decreases significantly, but all HRQOL end points are restored to baseline levels within 8 weeks. Odynophagia, fatigue, and weight loss improved 6–16 weeks after nCRT compared with baseline levels. Electronic supplementary material The online version of this article (10.1245/s10434-019-07779-w) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- B J Noordman
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands.
| | - M G E Verdam
- Department of Medical Psychology, Academic Medical Centre, Amsterdam, The Netherlands
| | - B Onstenk
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - J Heisterkamp
- Department of Surgery, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
| | - W J B M Jansen
- Department of Surgery, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
| | - I S Martijnse
- Department of Surgery, Elisabeth-Tweesteden Hospital, Tilburg, The Netherlands
| | - S M Lagarde
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - B P L Wijnhoven
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - C M M Acosta
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - A van der Gaast
- Department of Medical Oncology, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands
| | - M A G Sprangers
- Department of Medical Psychology, Academic Medical Centre, Amsterdam, The Netherlands
| | - J J B van Lanschot
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Rotterdam, The Netherlands
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33
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Hellstadius Y, Malmström M, Lagergren P, Sundbom M, Wikman A. Reflecting a crisis reaction: Narratives from patients with oesophageal cancer about the first 6 months after diagnosis and surgery. Nurs Open 2019; 6:1471-1480. [PMID: 31660175 PMCID: PMC6805708 DOI: 10.1002/nop2.348] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 07/04/2019] [Accepted: 07/05/2019] [Indexed: 12/16/2022] Open
Abstract
AIM The aim of the study was to describe patients' experiences of emotional adaption following treatment for oesophageal cancer from diagnosis to 6 months after surgery. DESIGN A qualitative interview study using an inductive approach was carried out. METHODS Participants were recruited from two university hospitals in Sweden. Ten patients who had been operated for oesophageal cancer with curative intent 6 months earlier and consented to participate in the study were included. Patients who had a disease recurrence were not eligible for inclusion. Participants were interviewed with a semi-structured interview approach. Data were analysed using qualitative content analysis. RESULTS One overarching theme was identified; Experiencing a crisis reaction, which comprised three key categories; (a) From emotionally numb to feeling quite alright; (b) From a focus on cure to reflections about a whole new life; and (c) From a severe treatment to suffering an emaciated, non-compliant body, derived from 14 distinct sub-categories. CONCLUSION This study highlights the process of emotional adaptation following oesophageal cancer surgery that patients describe when reflecting back on the first 6 months postoperatively pointing to a crisis reaction in this early postoperative period.
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Affiliation(s)
| | - Marlene Malmström
- Department of Clinical SciencesSkåne University Hospital, Lund UniversityLundSweden
| | - Pernilla Lagergren
- Department of Molecular Medicine and SurgeryKarolinska InstituteStockholmSweden
| | - Magnus Sundbom
- Department of Surgical SciencesUppsala UniversityUppsalaSweden
| | - Anna Wikman
- Department of Women's and Children's HealthUppsala UniversityUppsalaSweden
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34
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O'Neill L, Bennett AE, Guinan E, Reynolds JV, Hussey J. Physical recovery in the first six months following oesophago-gastric cancer surgery. Identifying rehabilitative needs: a qualitative interview study. Disabil Rehabil 2019; 43:1396-1403. [PMID: 31524528 DOI: 10.1080/09638288.2019.1663946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
PURPOSE To investigate patients' perspectives of their physical recovery in the first six months post oesophago-gastric cancer surgery. MATERIALS AND METHODS Semi-structured interviews were held at St James's Hospital, Dublin, with participants who were 4 weeks to 6 months post-oesophagectomy/gastrectomy. Interviews were an average of 14 min and included questions pertaining to physical recovery post-oesophagectomy/gastrectomy. Interviews were audio-taped, transcribed verbatim, and analyzed by thematic analysis. RESULTS Twenty participants (mean age 63.35(7.50) years) were recruited. Four themes were identified: i) challenges of recovery and impact on physical activity, ii) facilitators of, and barriers to, returning to physical activity, iii) physical challenges of returning to pre-operative societal roles, iv) recommendations for health services on measures which may enhance the return to physical activity. Post-operative barriers to physical activity included dietary issues, continuing treatments, pain, breathlessness, muscle weakness, fatigue, and anxiety. Participants identified that strategies such as a gradual return to activities, rest, and family support facilitated return to physical activity. Participants highlighted the need for i) greater physiotherapy input, ii) psycho-social support, and iii) fatigue management may aid physical recovery. CONCLUSIONS Following oesophago-gastric cancer surgery, patients experience physical and psychosocial difficulties which can hamper recovery, but many of which are amenable to rehabilitative intervention. Accordingly, rehabilitative measures throughout the early stages of recovery require investigation.Implications for RehabilitationCurative treatment for oesophageal and gastric cancer is associated with significant risk of post-operative morbidity, resulting in a myriad of physical and nutritional challenges which may impact on post-operative physical recovery.Greater provision of physiotherapy services to counteract physical impairments post oesophago-gastric cancer surgery is required.Physical recovery may also be aided through the enhanced provision of other supportive care services such as fatigue management and psychological support.
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Affiliation(s)
- Linda O'Neill
- Discipline of Physiotherapy, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | | | - Emer Guinan
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - John V Reynolds
- Trinity Translational Medicine Institute, Department of Surgery, Trinity College Dublin and St. James's Hospital, Dublin, Ireland
| | - Juliette Hussey
- Discipline of Physiotherapy, School of Medicine, Trinity College Dublin, Dublin, Ireland
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35
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Sunde B, Klevebro F, Johar A, Johnsen G, Jacobsen AB, Glenjen NI, Friesland S, Lindblad M, Ajengui A, Lundell L, Lagergren P, Nilsson M. Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial). Br J Surg 2019; 106:1452-1463. [PMID: 31436322 DOI: 10.1002/bjs.11246] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 04/02/2019] [Accepted: 05/02/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND There are few data comparing health-related quality of life (HRQoL) after neoadjuvant chemotherapy alone (nCT) compared with neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal cancer. METHODS In the NeoRes trial, patients were assigned randomly in a 1 : 1 ratio to receive either cisplatin 100 mg/m2 on day 1 and an infusion of 750 mg per m2 5-fluorouracil over 24 h on days 1-5 in three 21-day cycles (nCT) or the same chemotherapy regimen, but with the addition of 40 Gy radiotherapy (nCRT). HRQoL data were collected at baseline, after neoadjuvant therapy and at 1, 3 and 5 years after surgery. The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease-specific modules were used. RESULTS Of 181 patients randomized, 165 were included in the analysis of HRQoL. In a direct comparison between the allocated treatments, odynophagia after completion of neoadjuvant therapy but before surgery (P = 0·047) and troublesome coughing at 3 years' follow-up (P = 0·011) were more pronounced in the nCRT arm. In the longitudinal analyses within each treatment arm, a large deterioration in HRQoL was noted at 1 year. Some recovery was seen in both arms over time but, after 3 and 5 years, patients in the nCRT arm reported more symptoms compared with baseline than patients in the nCT arm. CONCLUSION HRQoL after multimodal treatment for cancer of the oesophagus or gastro-oesophageal junction was impaired and more pronounced in patients who underwent nCRT, with only partial recovery over time.
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Affiliation(s)
- B Sunde
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - F Klevebro
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - A Johar
- Department of Surgical Care Science, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - G Johnsen
- Department of Gastrointestinal Surgery, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
| | - A-B Jacobsen
- Department of Oncology, Oslo University Hospital, Oslo, Norway
| | - N I Glenjen
- Department of Oncology, Haukeland University Hospital, Bergen, Norway
| | - S Friesland
- Department of Oncology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - M Lindblad
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - A Ajengui
- Division of Surgery, Karolinska University Hospital, Stockholm, Sweden
| | - L Lundell
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - P Lagergren
- Department of Surgical Care Science, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.,Department of Surgery and Cancer, Imperial College London, London, UK
| | - M Nilsson
- Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.,Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
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Tramontano AC, Chen Y, Watson TR, Eckel A, Hur C, Kong CY. Esophageal cancer treatment costs by phase of care and treatment modality, 2000-2013. Cancer Med 2019; 8:5158-5172. [PMID: 31347306 PMCID: PMC6718574 DOI: 10.1002/cam4.2451] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 07/02/2019] [Accepted: 07/16/2019] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Detailed cost estimates are not widely available for esophageal cancer. Our study estimates phase-specific costs for esophageal cancer by age, year, histology, stage, and treatment for older patients in the United States and compares these costs within stage and treatment modalities. METHODS We identified 8061 esophageal cancer patients in the Surveillance, Epidemiology, and End Results-Medicare database for years 1998-2013. Total, cancer-attributable, and patient-liability costs were calculated based on separate phases of care-staging (or surgery), initial, continuing, and terminal. We estimated costs by treatment modality within stage and phase for esophageal adenocarcinoma and squamous cell carcinoma separately. We fit linear regression models using log transformation to determine cost by age and calendar year. All costs are reported in 2018 US dollars. RESULTS Overall, mean (95% CI) monthly total cost estimates were high during the staging ($8953 [$8385-$9485]) and initial phases ($7731 [$7492-$7970]), decreased over the continuing phase ($2984 [$2814-$3154]), and increased substantially during the 6-month terminal phase ($18 150 [$17 211-$19 089]). This pattern of high staging and initial phase costs, decreasing continuing phase costs, and increasing terminal phase costs was seen in all stages. The highest staging costs were in stages III ($9249, $8025-$10 474) and II ($9171, $7642-$10 699). The highest initial phase cost was in stage IV, $9263 ($8758-49 768), the lowest continuing phase cost was in stage I, $2338 ($2160-$2517), and the highest terminal phase costs were in stages II ($20 533, $17 772-$23 293) and III ($20 599, $18 268-$22 929). The linear regression models showed that cancer-attributable costs remained stable over the study period and were unaffected by age for most histology, stage, and treatment modality subgroups. CONCLUSIONS Our estimates demonstrate that esophageal cancer costs can vary widely by histology, stage, and treatment. These cost estimates can be used to guide future resource allocation for esophageal cancer care and research.
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Affiliation(s)
- Angela C. Tramontano
- Institute for Technology AssessmentMassachusetts General HospitalBostonMassachusetts
| | - Yufan Chen
- Institute for Technology AssessmentMassachusetts General HospitalBostonMassachusetts
| | - Tina R. Watson
- Institute for Technology AssessmentMassachusetts General HospitalBostonMassachusetts
| | - Andrew Eckel
- Institute for Technology AssessmentMassachusetts General HospitalBostonMassachusetts
| | - Chin Hur
- Columbia University Medical CenterNew York CityNew York
| | - Chung Yin Kong
- Institute for Technology AssessmentMassachusetts General HospitalBostonMassachusetts,Harvard Medical SchoolBostonMassachusetts
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Sugawara K, Yoshimura S, Yagi K, Nishida M, Aikou S, Yamagata Y, Mori K, Yamashita H, Seto Y. Long-term health-related quality of life following robot-assisted radical transmediastinal esophagectomy. Surg Endosc 2019; 34:1602-1611. [DOI: 10.1007/s00464-019-06923-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Accepted: 06/12/2019] [Indexed: 02/08/2023]
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Bull J, Oster C, Flight I, Wilson C, Koczwara B, Watson DI, Bright T. The role of rehabilitation in patients undergoing oesophagectomy for cancer and pre-malignant disease: A qualitative exploration of the views of patients, carers and healthcare providers. Eur J Cancer Care (Engl) 2019; 28:e12996. [PMID: 30675740 DOI: 10.1111/ecc.12996] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 10/23/2018] [Accepted: 12/12/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Oesophagectomy for cancer is associated with significant morbidity and mortality, and reduced quality of life. Structured rehabilitation potentially offers improved physical and psychological outcomes. We aimed to explore patient, carer and healthcare provider attitudes and preferences towards the role of rehabilitation. METHODS We interviewed 15 patients who had undergone an oesophagectomy, 10 carers and 13 healthcare providers about perceived impacts of treatment; preferred components of a rehabilitation program; barriers/enablers of support provision; and participation in rehabilitation programs. Data were analysed using framework analysis. RESULTS The overarching theme was "Getting back to normal." Diagnosis of disease signified a disruption to the normal trajectory of patients' lives and the post-treatment period was characterised as striving to return to normal. Patients and carers focused on rehabilitation needs post-treatment including dietary support, physiotherapy and healthcare provider support. Healthcare providers described rehabilitation as potentially beneficial from the pre-treatment phase and, along with carers, highlighted the importance of psychological support. Barriers included access to services, cost of service provision and appointment burden. CONCLUSION A need for rehabilitation services was identified by healthcare providers from the point of diagnosis, rather than only after surgery. Implications include improved service provision by healthcare institutions for patients undergoing oesophagectomy.
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Affiliation(s)
- Jeff Bull
- College of Medicine and Public Health, Flinders University Discipline of Surgery, Bedford Park, South Australia, Australia
| | - Candice Oster
- Flinders Human Behaviour and Health Research Unit, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
| | - Ingrid Flight
- Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
| | - Carlene Wilson
- Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.,La Trobe University/Olivia Newton John Cancer Wellness and Research Centre, Austin Hospital, Heidelberg, Victoria, Australia
| | - Bogda Koczwara
- Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia
| | - David I Watson
- College of Medicine and Public Health, Flinders University Discipline of Surgery, Bedford Park, South Australia, Australia
| | - Tim Bright
- College of Medicine and Public Health, Flinders University Discipline of Surgery, Bedford Park, South Australia, Australia
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Eyck BM, van der Wilk BJ, Lagarde SM, Wijnhoven BPL, Valkema R, Spaander MCW, Nuyttens JJME, van der Gaast A, van Lanschot JJB. Neoadjuvant chemoradiotherapy for resectable oesophageal cancer. Best Pract Res Clin Gastroenterol 2018; 36-37:37-44. [PMID: 30551855 DOI: 10.1016/j.bpg.2018.11.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 11/19/2018] [Indexed: 01/31/2023]
Abstract
At present, treatment of potentially curable oesophageal cancer includes neoadjuvant chemoradiotherapy followed by oesophagectomy. Alternatively, neoadjuvant chemotherapy is used. To date, strong evidence on the superiority of one modality over the other has not been provided. Currently, up to one-third of patients show a pathologically complete response after neoadjuvant chemoradiotherapy. To optimise the efficacy of neoadjuvant treatment for individual patients, prediction of response to neoadjuvant treatment is highly desired. Therefore, several clinical diagnostic modalities have been investigated for early response evaluation, of which positron emission tomography (PET) has been studied most extensively. To identify patients who might benefit from postponing or even omitting surgery, recent advances have been made in evaluating response after completion of neoadjuvant chemoradiotherapy. This review provides an overview of current evidence and recent advances in neoadjuvant chemoradiotherapy for oesophageal cancer and discusses the use of neoadjuvant chemotherapy compared to chemoradiotherapy. Moreover, clinical response evaluation to neoadjuvant chemoradiotherapy is reviewed.
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Affiliation(s)
- B M Eyck
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands.
| | - B J van der Wilk
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
| | - S M Lagarde
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
| | - B P L Wijnhoven
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
| | - R Valkema
- Department of Radiology and Nuclear Medicine, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
| | - M C W Spaander
- Department of Gastroenterology & Hepatology, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
| | - J J M E Nuyttens
- Department of Radiotherapy, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
| | - A van der Gaast
- Department of Medical Oncology, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
| | - J J B van Lanschot
- Department of Surgery, Erasmus MC - University Medical Centre Rotterdam, Dr. Molenwaterplein 40, 3000 CA, Rotterdam, the Netherlands
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40
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The role of definitive chemoradiation in patients with non-metastatic oesophageal cancer. Best Pract Res Clin Gastroenterol 2018; 36-37:53-59. [PMID: 30551857 DOI: 10.1016/j.bpg.2018.11.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 11/19/2018] [Indexed: 01/31/2023]
Abstract
Definitive chemoradiation (dCRT) is a curative treatment option for patients with oesophageal cancer. It is effective in both adenocarcinoma and squamous cell carcinoma. However, locoregional control is less after dCRT compared to preoperative CRT (pCRT) followed by surgery. Also, overall survival is lower compared to pCRT followed by surgery, which can only partly be explained by a negative selection of patients. The optimal dose of radiotherapy remains to be determined, but dose escalation above 50.4Gy might be beneficial. Cisplatinum/5-FU is the most applied concurrent chemotherapy, but carboplatin/paclitaxel seems equally effective with less toxicity. The addition of 5-FU to a taxane and platinum seems promising. Accelerated fractionation and addition of cetuximab did not improve results. dCRT is a successful treatment for regional lymph node recurrences, but less so for recurrences at the anastomotic site. Re-irradiation after prior curative radiotherapy yields poor results. dCRT can be safely used in carefully selected elderly.
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Borggreve AS, Mook S, Verheij M, Mul VEM, Bergman JJ, Bartels-Rutten A, Ter Beek LC, Beets-Tan RGH, Bennink RJ, van Berge Henegouwen MI, Brosens LAA, Defize IL, van Dieren JM, Dijkstra H, van Hillegersberg R, Hulshof MC, van Laarhoven HWM, Lam MGEH, van Lier ALHMW, Muijs CT, Nagengast WB, Nederveen AJ, Noordzij W, Plukker JTM, van Rossum PSN, Ruurda JP, van Sandick JW, Weusten BLAM, Voncken FEM, Yakar D, Meijer GJ. Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study. BMC Cancer 2018; 18:1006. [PMID: 30342494 PMCID: PMC6195948 DOI: 10.1186/s12885-018-4892-6] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 10/03/2018] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .
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Affiliation(s)
- A S Borggreve
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. .,Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
| | - S Mook
- Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - M Verheij
- Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - V E M Mul
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands
| | - J J Bergman
- Department of Gastroenterology, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - A Bartels-Rutten
- Department of Radiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - L C Ter Beek
- Department of Radiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - R G H Beets-Tan
- Department of Radiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - R J Bennink
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - M I van Berge Henegouwen
- Department of Surgical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - L A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - I L Defize
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.,Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - J M van Dieren
- Department of Gastroenterology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - H Dijkstra
- Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands
| | - R van Hillegersberg
- Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - M C Hulshof
- Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - H W M van Laarhoven
- Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - M G E H Lam
- Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - A L H M W van Lier
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - C T Muijs
- Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands
| | - W B Nagengast
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands
| | - A J Nederveen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - W Noordzij
- Department of Nuclear Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands
| | - J T M Plukker
- Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands
| | - P S N van Rossum
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - J P Ruurda
- Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - J W van Sandick
- Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - B L A M Weusten
- Department of Gastroenterology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - F E M Voncken
- Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
| | - D Yakar
- Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands
| | - G J Meijer
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
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Changes in health-related quality of life in oesophagogastric cancer patients participating in palliative and curative therapies. Med J Islam Repub Iran 2018; 32:31. [PMID: 30159282 PMCID: PMC6108255 DOI: 10.14196/mjiri.32.31] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2017] [Indexed: 02/08/2023] Open
Abstract
Background: Various treatments are used to prolong survival and improve quality of life (QOL). The purpose of this study was to assess the change in QOL scores in patients with Oesophagogastric (OG) cancer undergoing curative intent and palliative therapy.
Methods: This was a mix-designed cohort study with a consecutive sampling of patients with OG cancer who underwent curative or palliative treatment regimens. The QOL, as a determinant of efficacy and impact of cancer care, was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires. QOL data were collected from the eligible subjects at three points of time. The repeated measurement test was used to compare the significance of change in scores.
Results: Overall, 149 patients (54.4% male, 61.1% curative intent, 52.3% esophageal, 37.6 % gastric, 10.1% OG junction cancer; with mean age 62 year) with OG cancer were eligible for inclusion in the study. Compared to the palliative group, the curative group was more likely to have an esophageal tumor site, Squamous Cell Carcinoma, and stage 2 (versus stomach, Adenocarcinoma, and stage 4 in the palliative group). In comparing the patients' functional, global health status, and cancer symptom, considering time, group of treatment, and their mutual effect the result indicated significant difference between the intervention groups.
Conclusion: Most patients with Oesophagogastric cancer are diagnosed with an incurable form of the disease. Hence in absence of curative treatment, palliative therapy is the most effective therapy to maintain patient independency and relieve pain and symptom in order to improve their QOL. The present study has shown that palliative similar to curative intervention can improve the QOL in cancer patient especially in short term.
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Samson P, Puri V, Lockhart AC, Robinson C, Broderick S, Patterson GA, Meyers B, Crabtree T. Adjuvant chemotherapy for patients with pathologic node-positive esophageal cancer after induction chemotherapy is associated with improved survival. J Thorac Cardiovasc Surg 2018; 156:1725-1735. [PMID: 30054137 DOI: 10.1016/j.jtcvs.2018.05.100] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 03/13/2018] [Accepted: 05/07/2018] [Indexed: 01/09/2023]
Abstract
OBJECTIVES The study objectives were to identify variables associated with the use of adjuvant chemotherapy among patients with node-positive esophageal cancer who received induction therapy and to evaluate its relationship with overall survival. METHODS Treatment data for patients with esophageal cancer receiving induction chemotherapy ± radiotherapy and esophagectomy were abstracted from the National Cancer Data Base. Pathologic node-positive patients were dichotomized by whether they received 2 or more cycles of adjuvant chemotherapy or none. Kaplan-Meier survival curves were generated, and a Cox proportional hazards model was done to identify factors associated with overall survival. RESULTS From 2006 to 2012, 3100 patients had pathologic positive nodes after induction therapy and esophagectomy. A total of 2625 patients (84.7%) did not receive adjuvant chemotherapy, and 475 patients (15.3%) did. N3 nodal stage was associated with an increased likelihood of receiving adjuvant chemotherapy (reference: N1, odds ratio, 1.82, 95% confidence interval, 1.15-2.97, P = .01), whereas increasing age (by year, odds ratio, 0.97, confidence interval, 0.96-0.98, P < .001), induction chemoradiation therapy (reference: induction chemotherapy, odds ratio, 0.39, confidence interval, 0.30-0.52, P < .001), and increasing inpatient length of stay after esophagectomy (per day: odds ratio, 0.98, confidence interval, 0.97-0.99, P = .007) were associated with a decreased likelihood. Patients receiving adjuvant chemotherapy had improved overall survival at each pathologic nodal stage: 31.6 months versus 22.7 months for N1 disease (P < .001), 32.4 months versus 19.2 months for N2 disease (P = .035), and 19.5 months versus 10.4 months for N3 disease (P < .001). Adjuvant therapy was independently associated with decreased mortality hazard (hazard ratio, 0.69, 95% confidence interval, 0.57-0.83, P < .001). CONCLUSIONS Patients receiving adjuvant chemotherapy after induction therapy and esophagectomy show a survival benefit at all positive nodal stages. Prospective studies may help further delineate this benefit.
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Affiliation(s)
- Pamela Samson
- Division of Cardiothoracic Surgery, Washington University in St Louis, St Louis, Mo
| | - Varun Puri
- Division of Cardiothoracic Surgery, Washington University in St Louis, St Louis, Mo
| | | | - Clifford Robinson
- Department of Radiation Oncology, Washington University in St Louis, St Louis, Mo
| | - Stephen Broderick
- Division of Cardiothoracic Surgery, Johns Hopkins University, Baltimore, Md
| | | | - Bryan Meyers
- Division of Cardiothoracic Surgery, Washington University in St Louis, St Louis, Mo
| | - Traves Crabtree
- Division of Cardiothoracic Surgery, Southern Illinois University, Springfield, Ill.
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Zhang Y, Yang X, Geng D, Duan Y, Fu J. The change of health-related quality of life after minimally invasive esophagectomy for esophageal cancer: a meta-analysis. World J Surg Oncol 2018; 16:97. [PMID: 29793487 PMCID: PMC5968615 DOI: 10.1186/s12957-018-1330-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Accepted: 02/04/2018] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND Short- and long-term health-related quality of life (HRQL) was severely affected after surgery. This study aimed to assess the direction and duration of HRQL from 3- to 24-month follow-ups after minimally invasive esophagectomy (MIE) for esophageal cancer. METHODS A systematic literature search in MEDLINE, EMBASE, and the Cochrane database was performed for all potentially relevant studies published until February 2017. Studies were included if they addressed the question of HRQL with OERTC-QLQ-C30 and OES18. Primary outcomes were HRQL change at 3-month follow-up. Secondary outcomes were HRQL change from 3-, 6- (short-term) to 12- (mid-term), and/or 24-month (long-term) follow-ups. RESULTS Six articles were included to estimate the change in 24 HRQL outcomes after MIE. Most of the patients' HRQL outcomes deteriorated at short-term follow-up and some lasted to mid- or long-term after MIE. Patients' physical function and global QOL deteriorated from short- to long-term follow-ups, and emotional function had no change. The directions of dyspnea, pain, fatigue, insomnia, constipation, diarrhea, cough, and speech problems were increased. The deterioration in global function lasted 6 months, the increase in constipation and speech problems lasted 12 months, and insomnia increased more than 12 months after MIE. CONCLUSIONS The emotional function had no change after MIE. The global QOL become worse during early postoperative period; the symptoms of constipation, speech problems, and insomnia increased for a long time after MIE.
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Affiliation(s)
- Yong Zhang
- Department of Thoracic Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, 710061 China
| | - Xiaomei Yang
- Hospital 521 of China’s Ordnance Industry Group, Xi’an, 710065 China
| | - Donghong Geng
- School of Continuing Education of Xi’an Jiaotong University, Xi’an, 710061 China
| | - Yingfei Duan
- Department of Pathology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061 China
| | - Junke Fu
- Department of Thoracic Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, 710061 China
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Abstract
A postoperative complications rate of nearly 50% has compelled oesophago-gastric practice to adopt minimally invasive techniques such as robotic surgery
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Affiliation(s)
- Y A Qureshi
- Department of Oesophago-Gastric Surgery, University College London Hospital , London
| | - B Mohammadi
- Department of Oesophago-Gastric Surgery, University College London Hospital , London
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46
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Anandavadivelan P, Wikman A, Johar A, Lagergren P. Profiles of patient and tumour characteristics in relation to health-related quality of life after oesophageal cancer surgery. PLoS One 2018; 13:e0196187. [PMID: 29708994 PMCID: PMC5927451 DOI: 10.1371/journal.pone.0196187] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 03/18/2018] [Indexed: 12/17/2022] Open
Abstract
Strong deterioration in health-related quality of life (HRQOL) is a major concern in a sub-group of long-term oesophageal cancer survivors. This study aimed to identify potential clustering of patients and tumour variables that predicts such deterioration. Patient and tumour variables were collected in a prospective cohort of patients who underwent surgery for oesophageal cancer in Sweden 2001-2005. Latent cluster analysis identified statistically significant clustering of these variables. Multivariable logistic regression adjusted for age, BMI, tumour stage and marital status was used to determine odds ratios (ORs) with 95% confidence intervals (CIs) between patient profiles and HRQOL at 3 and 5 years from surgery. Among 155 included patients at 3 years, three patient profiles were identified: 1) 'reference profile' (males, younger age, employed, upper secondary education, co-habitating, urban dwellers, adenocarcinoma and advanced tumour stage) (n = 47;30%), 2) 'adenocarcinoma profile' (middle age, unemployed/retired, males, low education, co-habitating, adenocarcinoma, advanced tumour stage, tumour in lower oesophagus/cardia, and co-morbidities (n = 79;51%), and 3) 'squamous-cell carcinoma profile' (unemployed/retired, middle-age, males, low BMI, urban dwellers, squamous-cell carcinoma, tumour in upper/middle oesophagus (n = 29;19%). These profiles did not differ regarding most HRQOL measures. Exceptions were the squamous-cell carcinoma profile, reporting more constipation (OR = 5.69; 95%CI: 1.34-24.28) and trouble swallowing saliva (OR = 4.87; 95%CI: 1.04-22.78) and the adenocarcinoma profile reporting more dyspnoea (OR = 2.60; 95%CI: 1.00-6.77) and constipation (OR = 3.31; 95%CI: 1.00-10.97) compared to the reference profile. Three distinct patient profiles were identified but these could not explain the substantial deterioration in HRQOL observed in the sub-sample of survivors.
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Affiliation(s)
- Poorna Anandavadivelan
- Surgical Care Science, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Anna Wikman
- Reproductive Health, Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
| | - Asif Johar
- Surgical Care Science, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Pernilla Lagergren
- Surgical Care Science, Department of Molecular medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Chu JN, Choi J, Tramontano A, Morse C, Forcione D, Nishioka NS, Abrams JA, Rubenstein JH, Kong CY, Inadomi JM, Hur C. Surgical vs Endoscopic Management of T1 Esophageal Adenocarcinoma: A Modeling Decision Analysis. Clin Gastroenterol Hepatol 2018; 16:392-400.e7. [PMID: 29079222 PMCID: PMC5852380 DOI: 10.1016/j.cgh.2017.10.024] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Revised: 10/13/2017] [Accepted: 10/17/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Although treatment of T1a esophageal adenocarcinoma (EAC) is shifting from esophagectomy to endoscopic therapy, T1b EACs are considered too high risk to be treated endoscopically. We investigated the effectiveness and cost effectiveness of esophagectomy vs endoscopic therapy for T1a and T1b EACs, and the effects of age and comorbidities, using a decision analytic Markov model. METHODS We developed a model to simulate a hypothetical cohort of men 75 years old with Charlson comorbidity index scores of 0 and either T1aN0M0 or T1bN0M0 EAC, as a base case. We used the model to compare the effects of esophagectomy vs serial endoscopic therapy. We performed sensitivity analyses based on age at diagnosis of 60-85 years, comorbidity indices of 0-2, and utilities. Post-procedure cancer-specific mortality was derived from the Surveillance, Epidemiology, and End Results Medicare database. RESULTS In the T1a base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (6.97 vs 6.81), but fewer quality-adjusted life years (QALYs, 4.95 for esophagectomy vs 5.22 for endoscopic therapy). In the T1b base case, esophagectomy yielded more unadjusted life years than endoscopic therapy (5.73 vs 5.01) and QALYs (4.07 vs 3.85 for endoscopic therapy), but was not cost effective (incremental cost-effectiveness ratio $156,981). Sensitivity analyses showed endoscopic therapy optimized QALYs for patients more than 80 years old with a comorbidity index of 1 or 2, or if the ratio of post-esophagectomy to post-endoscopic therapy utilities was below 0.875. CONCLUSION In a Markov model, we showed that endoscopic therapy of T1a EAC yields more QALYs and is more cost effective than esophagectomy for patients of all ages and comorbidity indices tested. In contrast, selection of therapy for T1b EAC depends on age and comorbidities, due to surgical mortality and the competing risk of non-cancer death.
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Affiliation(s)
- Jacqueline N Chu
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Jin Choi
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts
| | - Angela Tramontano
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts
| | - Christopher Morse
- Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - David Forcione
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Norman S Nishioka
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
| | - Julian A Abrams
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, New York
| | - Joel H Rubenstein
- Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan; Barrett's Esophagus Program, Division of Gastroenterology, University of Michigan School of Medicine, Ann Arbor, Michigan
| | - Chung Yin Kong
- Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts
| | - John M Inadomi
- Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington
| | - Chin Hur
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Institute for Technology Assessment, Massachusetts General Hospital, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
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48
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Mantoan S, Cavallin F, Pinto E, Saadeh LM, Alfieri R, Cagol M, Bellissimo MC, Castoro C, Scarpa M. Long-term quality of life after esophagectomy with gastric pull-up. J Surg Oncol 2018; 117:970-976. [PMID: 29409116 DOI: 10.1002/jso.24995] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Accepted: 01/04/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND OBJECTIVES Data on long-term health-related quality of life (HRQL) after esophagectomy for cancer show contradictory results. The aim was to analyze long-term HRQL at 3 or more years after esophagectomy. METHODS Survivors were identified among patients who had undergone esophagectomy during 2007-2013 using the local clinic database. Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and OG25 questionnaires. Specific aspects were selected a priori and compared with published scores from European healthy subjects (mean difference, MD). RESULTS Sixty-five long-term survivors (median follow-up 4 years) were identified. All functional scales and most symptom scales were clinically similar between EC long-term survivors and European healthy subjects. Survivors reported more problems concerning eating (MD 13.1, 95% C.I. 10.6-15.6) and reflux (MD 19.7, 95% C.I. 15.9-23.5). HQRL variation from discharge to long term was available in 27 participants who reported improvements in role functioning (MD 40.1, 95%C.I. 24.3-56.0) and dysphagia (MD -41.9, 95% C.I. -51.7 to 32.0). CONCLUSIONS Long-term HRQL after esophagectomy is similar between EC survivors and European healthy subjects, despite persisting reflux and eating problems. Further research may focus on improvements of postoperative alimentary habits.
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Affiliation(s)
- Silvia Mantoan
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Francesco Cavallin
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Eleonora Pinto
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Luca M Saadeh
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Rita Alfieri
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Matteo Cagol
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Maria C Bellissimo
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Carlo Castoro
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
| | - Marco Scarpa
- Surgical Oncology Unit, Veneto Institute of Oncology IOV IRCCS, Padua, Italy
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49
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Noordman BJ, Wijnhoven BPL, Lagarde SM, Boonstra JJ, Coene PPLO, Dekker JWT, Doukas M, van der Gaast A, Heisterkamp J, Kouwenhoven EA, Nieuwenhuijzen GAP, Pierie JPEN, Rosman C, van Sandick JW, van der Sangen MJC, Sosef MN, Spaander MCW, Valkema R, van der Zaag ES, Steyerberg EW, van Lanschot JJB. Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial. BMC Cancer 2018; 18:142. [PMID: 29409469 PMCID: PMC5801846 DOI: 10.1186/s12885-018-4034-1] [Citation(s) in RCA: 166] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Accepted: 01/23/2018] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. METHODS This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. DISCUSSION If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care.
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Affiliation(s)
- Bo Jan Noordman
- Department of Surgery, Erasmus MC – University Medical Centre, Suite Z-839, P.O. Box 2040 3000, CA Rotterdam, The Netherlands
| | - Bas P. L. Wijnhoven
- Department of Surgery, Erasmus MC – University Medical Centre, Suite Z-839, P.O. Box 2040 3000, CA Rotterdam, The Netherlands
| | - Sjoerd M. Lagarde
- Department of Surgery, Erasmus MC – University Medical Centre, Suite Z-839, P.O. Box 2040 3000, CA Rotterdam, The Netherlands
| | - Jurjen J. Boonstra
- Department of Gastroenterology, Leiden University Medical Centre, Leiden, the Netherlands
| | | | | | - Michael Doukas
- Department of Pathology, Erasmus MC – University Medical Centre, Rotterdam, the Netherlands
| | - Ate van der Gaast
- Department of Medical Oncology, Erasmus MC – University Medical Centre, Rotterdam, the Netherlands
| | - Joos Heisterkamp
- Department of Surgery, Elisabeth Tweesteden Hospital, Tilburg, the Netherlands
| | | | | | | | - Camiel Rosman
- Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Johanna W. van Sandick
- Department of Surgery, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands
| | | | - Meindert N. Sosef
- Department of Surgery, Zuyderland Medical Centre, Heerlen, the Netherlands
| | - Manon C. W. Spaander
- Department of Gastroenterology, Erasmus MC – University Medical Centre, Rotterdam, the Netherlands
| | - Roelf Valkema
- Department of Radiology and Nuclear Medicine, Erasmus MC – University Medical Centre, Rotterdam, the Netherlands
| | | | - Ewout W. Steyerberg
- Department of Medical Statistics and Bioinformatics, Leiden University Medical Centre, formerly department of Public Health, Erasmus MC – University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - J. Jan B. van Lanschot
- Department of Surgery, Erasmus MC – University Medical Centre, Suite Z-839, P.O. Box 2040 3000, CA Rotterdam, The Netherlands
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50
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Noordman BJ, Verdam MG, Lagarde SM, Hulshof MC, van Hagen P, van Berge Henegouwen MI, Wijnhoven BP, van Laarhoven HW, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJM, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A, Sprangers MA, van Lanschot JJB. Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial. J Clin Oncol 2018; 36:268-275. [DOI: 10.1200/jco.2017.73.7718] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and –Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24). Results A total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen’s d: −0.93, P < .001; 0.47, P < .001; −0.84, P < .001; 1.45, P < .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen’s d: −1.00, 0.33, −0.47, −0.34, and 0.33, respectively; all P < .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen’s d: 0.52 and −0.53, respectively; both P < .001). Conclusion Although HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study–regimen can be regarded as a standard of care.
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Affiliation(s)
- Bo Jan Noordman
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Mathilde G.E. Verdam
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Sjoerd M. Lagarde
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Maarten C.C.M. Hulshof
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Pieter van Hagen
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Mark I. van Berge Henegouwen
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Bas P.L. Wijnhoven
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Hanneke W.M. van Laarhoven
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Grard A.P. Nieuwenhuijzen
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Geke A.P. Hospers
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Johannes J. Bonenkamp
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Miguel A. Cuesta
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Reinoud J.B. Blaisse
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Olivier R. Busch
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Fiebo J.W. ten Kate
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Geert-Jan M. Creemers
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Cornelis J.A. Punt
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - John Th.M. Plukker
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Henk M.W. Verheul
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Ernst J. Spillenaar Bilgen
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Herman van Dekken
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Maurice J.C. van der Sangen
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Tom Rozema
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Katharina Biermann
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Jannet C. Beukema
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Anna H.M. Piet
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Caroline M. van Rij
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Janny G. Reinders
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Hugo W. Tilanus
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Ewout W. Steyerberg
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Ate van der Gaast
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - Mirjam A.G. Sprangers
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
| | - J. Jan B. van Lanschot
- Bo Jan Noordman, Sjoerd M. Lagarde, Pieter van Hagen, Bas P.L. Wijnhoven, Fiebo J.W. ten Kate, Katharina Biermann, Caroline M. van Rij, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast, and J. Jan B. van Lanschot, Erasmus MC–University Medical Center Rotterdam; Mathilde G.E. Verdam, Maarten C.C.M. Hulshof, Mark I. van Berge Henegouwen, Hanneke W.M. van Laarhoven, Olivier R. Busch, Fiebo J.W. ten Kate, Cornelis J.A. Punt, and Mirjam A.G. Sprangers, Academic Medical Center; Miguel A. Cuesta, Henk M
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