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Tolonen A, Lehtomäki K, Kerminen H, Huhtala H, Bärlund M, Österlund P, Arponen O. Computed tomography-determined high visceral adipose tissue and sarcopenic obesity and their associations with survival in vulnerable or frail older adults with cancer considered for systemic anticancer treatment. J Geriatr Oncol 2025; 16:102171. [PMID: 39675314 DOI: 10.1016/j.jgo.2024.102171] [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] [Received: 03/03/2024] [Revised: 11/05/2024] [Accepted: 12/02/2024] [Indexed: 12/17/2024]
Abstract
INTRODUCTION Treatment decisions are challenging in older adults with solid tumors. Geriatric 8 (G8)-screening and comprehensive geriatric assessment (CGA) are important but additional methods are needed. We examined the association of computed tomography (CT)-derived high visceral adipose tissue index (VATI) with or without low skeletal muscle index (SMI) on three-month and overall survival (OS). MATERIALS AND METHODS Vulnerability was evaluated with G8 in patients ≥75 years referred for systemic anticancer treatment. Vulnerable/frail patients (G8 ≤ 14) received CGA and were included. VATI and SMI were retrospectively measured from CT scans. We examined associations between high VATI with or without low SMI and three-month and OS with Cox regression models and Kaplan-Meier estimation. RESULTS Seventy-nine patients with median age of 80 (range 75-91) years were evaluated. In the palliative-intent group (n = 58), three-month OS rates were 88 % and 58 % in the normal and high VATI groups, respectively (hazard ratio 4.3; 95 % confidence interval 1.3-14), and 88 % vs. 47 % in group without and with 'high VATI+low SMI', respectively (5.5; 1.9-17). The median OS was 12.7 vs. 9.5 months in normal VATI/SMI and 'high VATI+low SMI' (1.9; 1.1-3.2), respectively. In Cox multivariable models with established predictive factors (ECOG PS, Clinical Frailty Scale, and sex), only high VATI (4.9; 1.0-24) or 'high VATI+low SMI' (8.9; 1.7-46) remained significant predictors of three-month OS. DISCUSSION High VATI with or without low SMI were associated with impaired three-month OS in the palliative-intent group and with OS in the whole cohort independently of oncologic and geriatric functional status measures; thus, they may aid in treatment decision-making.
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Affiliation(s)
- Antti Tolonen
- Department of Radiology, Tampere University Hospital, Kuntokatu 2, 33520 Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520 Tampere, Finland; Department of Oncology, Tays Cancer Centre, Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland.
| | - Kaisa Lehtomäki
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520 Tampere, Finland; Department of Oncology, Tays Cancer Centre, Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland.
| | - Hanna Kerminen
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520 Tampere, Finland; Centre of Geriatrics, Tampere University Hospital, Kuntokatu 2, 33520 Tampere, Finland; Gerontology Research Center (GEREC), Tampere University, Arvo Ylpön Katu 34, 33520 Tampere, Finland.
| | - Heini Huhtala
- Faculty of Social Sciences, Tampere University, Kalevantie 5, 33014 Tampere, Finland.
| | - Maarit Bärlund
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520 Tampere, Finland; Department of Oncology, Tays Cancer Centre, Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland.
| | - Pia Österlund
- Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520 Tampere, Finland; Department of Oncology, Tays Cancer Centre, Tampere University Hospital, Teiskontie 35, 33520 Tampere, Finland; Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki, Finland; Department of Gastrointestinal Oncology, Tema Cancer, Karolinska Universitetssjukhuset, Eugeniavägen 3, 17176 Solna, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Solnavägen 1, 17177, Solna, Sweden.
| | - Otso Arponen
- Department of Radiology, Tampere University Hospital, Kuntokatu 2, 33520 Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön Katu 34, 33520 Tampere, Finland; Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
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Baltussen JC, van den Bos F, Slingerland M, Binda TRR, Liefers GJ, van den Hout WB, Fiocco M, Verschoor AJ, Cloos-van Balen M, Holterhues C, Houtsma D, Jochems A, Spierings LEAMM, van Bodegom-Vos L, Mooijaart SP, Gelderblom H, Speetjens FM, de Glas NA, Portielje JEA. DOSAGE study: protocol for a phase III non-inferiority randomised trial investigating dose-reduced chemotherapy for advanced colorectal cancer in older patients. BMJ Open 2024; 14:e089882. [PMID: 39142680 PMCID: PMC11331880 DOI: 10.1136/bmjopen-2024-089882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 07/03/2024] [Indexed: 08/16/2024] Open
Abstract
INTRODUCTION Treating older adults with chemotherapy remains a challenge, given their under-representation in clinical trials and the lack of robust treatment guidelines for this population. Moreover, older patients, especially those with frailty, have an increased risk of developing chemotherapy-related toxicity, resulting in a decreased quality of life (QoL), increased hospitalisations and high healthcare costs. Phase II trials have suggested that upfront dose reduction of chemotherapy can reduce toxicity rates while maintaining efficacy, leading to fewer treatment discontinuations and an improved QoL. The DOSAGE aims to show that upfront dose-reduced chemotherapy in older patients with metastatic colorectal cancer is non-inferior to full-dose treatment in terms of progression-free survival (PFS), with adaption of the treatment plan (monotherapy or doublet chemotherapy) based on expected risk of treatment toxicity. METHODS AND ANALYSIS The DOSAGE study is an investigator-initiated phase III, open-label, non-inferiority, randomised controlled trial in patients aged≥70 years with metastatic colorectal cancer eligible for palliative chemotherapy. Based on toxicity risk, assessed using the Geriatric 8 (G8) tool, patients will be stratified to either doublet chemotherapy (fluoropyrimidine with oxaliplatin) or fluoropyrimidine monotherapy. Patients classified as low risk will be randomised between a fluoropyrimidine plus oxaliplatin in either full-dose or with an upfront dose reduction of 25%. Patients classified as high risk will be randomised between fluoropyrimidine monotherapy in either full-dose or with an upfront dose reduction. In the dose-reduced arm, dose escalation after two cycles is allowed. The primary outcome is PFS. Secondary endpoints include grade≥3 toxicity, QoL, physical functioning, number of treatment cycles, dose reductions, hospital admissions, overall survival, cumulative received dosage and cost-effectiveness. Considering a median PFS of 8 months and non-inferiority margin of 8 weeks, we shall include 587 patients. The study will be enrolled in 36 Dutch Hospitals, with enrolment scheduled to start in July 2024. This study will provide new evidence regarding the effect of dose-reduced chemotherapy on survival and treatment outcomes, as well as the use of the G8 to choose between doublet chemotherapy or monotherapy. Results will contribute to a more individualised approach in older patients with metastatic colorectal cancer, potentially leading to improved QoL while maintaining survival benefits. ETHICS AND DISSEMINATION This trial has received ethical approval by the ethical committee Leiden Den Haag Delft (P24.018) and will be approved by the Institutional Ethical Committee of the participating institutions. The results will be disseminated in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER NCT06275958.
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Affiliation(s)
- Joosje C Baltussen
- Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Frederiek van den Bos
- Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
- LUMC Center for Medicine for Older People, Leiden University Medical Centre, Leiden, The Netherlands
| | - Marije Slingerland
- Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Trishika R R Binda
- Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Gerrit-Jan Liefers
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Wilbert B van den Hout
- Department of Biomedical Data Sciences, Section of Medical Decision Making, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Marta Fiocco
- Department of Biomedical Data Sciences, Section of Medical Statistics and Bioinformatics, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
- Mathematical Institute, Leiden University, Leiden, The Netherlands
| | - Arjan J Verschoor
- Department of Medical Oncology, Reinier de Graaf Hospital, Delft, The Netherlands
| | - Marissa Cloos-van Balen
- Department of Internal Medicine, Groene Hart Ziekenhuis, Gouda, Zuid-Holland, The Netherlands
| | - Cynthia Holterhues
- Department of Medical Oncology, Haga Hospital, Den Haag, The Netherlands
| | - Danny Houtsma
- Department of Medical Oncology, Haga Hospital, Den Haag, The Netherlands
| | - Anouk Jochems
- Department of Medical Oncology, Medisch Centrum Haaglanden Westeinde, Den Haag, Zuid-Holland, The Netherlands
| | | | - Leti van Bodegom-Vos
- Department of Biomedical Data Sciences, Section of Medical Decision Making, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Simon P Mooijaart
- Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
- LUMC Center for Medicine for Older People, Leiden University Medical Centre, Leiden, The Netherlands
| | - Hans Gelderblom
- Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Frank M Speetjens
- Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Nienke A de Glas
- Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
| | - Johanneke E A Portielje
- Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
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Murugappan MN, King-Kallimanis BL, Bhatnagar V, Kanapuru B, Farley JF, Seifert RD, Stenehjem DD, Chen TY, Horodniceanu EG, Kluetz PG. Measuring Frailty Using Patient-Reported Outcomes (PRO) Data: A Feasibility Study in Patients with Multiple Myeloma. Qual Life Res 2023; 32:2281-2292. [PMID: 36935467 PMCID: PMC10025057 DOI: 10.1007/s11136-023-03390-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/03/2023] [Indexed: 03/21/2023]
Abstract
PURPOSE The objective of this retrospective study was to determine the feasibility of measuring frailty using patient responses to relevant EORTC QLQ-C30 items as proxy criteria for the Fried Frailty Phenotype, in a cohort of patients with Relapsed/Refractory Multiple Myeloma (RRMM). METHODS Data were pooled from nine Phase III randomized clinical trials submitted to the FDA for regulatory review between 2010 and 2021, for the treatment of RRMM. Baseline EORTC QLQ-C30 responses were used to derive a patient-reported frailty phenotype (PRFP), based on the Fried definition of frailty. PRFP was assessed for internal consistency reliability, structural validity, and known groups validity. RESULTS This study demonstrated the feasibility of adapting patient responses to relevant EORTC QLQ-C30 items to serve as proxy Fried frailty criteria. Selected items were well correlated with one another and PRFP as a whole demonstrated adequate internal consistency reliability and structural validity. Known groups analysis demonstrated that PRFP could be used to detect distinct comorbidity levels and distinguish between different functional profiles, with frail patients reporting more difficulty in walking about, washing/dressing, and doing usual activities, as compared to their pre-frail and fit counterparts. Among the 4928 patients included in this study, PRFP classified 2729 (55.4%) patients as fit, 1209 (24.5%) as pre-frail, and 990 (20.1%) as frail. CONCLUSION Constructing a frailty scale from existing PRO items commonly collected in cancer trials may be a patient-centric and practical approach to measuring frailty. Additional psychometric evaluation and research is warranted to further explore the utility of such an approach.
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Affiliation(s)
- Meena N Murugappan
- Office of Oncologic Diseases, Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (U.S. FDA), Silver Spring, MD, USA.
- Department of Pharmaceutical Care and Health Systems, University of Minnesota - College of Pharmacy, Minneapolis, MN, USA.
- Oncology Center of Excellence, Food and Drug Administration, Building 22, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
| | | | - Vishal Bhatnagar
- Oncology Center for Excellence (U.S. FDA), Silver Spring, MD, USA
| | - Bindu Kanapuru
- Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (U.S. FDA), Silver Spring, MD, USA
| | - Joel F Farley
- Department of Pharmaceutical Care and Health Systems, University of Minnesota - College of Pharmacy, Minneapolis, MN, USA
| | - Randall D Seifert
- Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota - College of Pharmacy, Minneapolis, MN, USA
| | - David D Stenehjem
- Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota - College of Pharmacy, Minneapolis, MN, USA
| | - Ting-Yu Chen
- Office of Oncologic Diseases, Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (U.S. FDA), Silver Spring, MD, USA
| | | | - Paul G Kluetz
- Oncology Center for Excellence (U.S. FDA), Silver Spring, MD, USA
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Pramanik R, Agarwala S, Sreenivas V, Dhawan D, Bakhshi S. Quality of life in paediatric solid tumours: a randomised study of metronomic chemotherapy versus placebo. BMJ Support Palliat Care 2023; 13:234-237. [PMID: 33468507 DOI: 10.1136/bmjspcare-2020-002731] [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] [Received: 10/06/2020] [Revised: 12/13/2020] [Accepted: 01/03/2021] [Indexed: 11/04/2022]
Abstract
OBJECTIVE Health-related quality of life (HRQoL) is an important outcome for paediatric cancer studies. We compared the HRQoL between patients of progressive paediatric solid tumours randomised to metronomic chemotherapy versus placebo. METHODS In this double-blinded, placebo-controlled randomised study of 108 children with progressive malignancies, HRQoL was evaluated using the PedsQOL Cancer module V.3 at baseline (A1), A2 (9 weeks or earlier if progressed) or A3 (18 weeks or earlier if progressed). RESULTS There was no statistically significant difference in the change in quality of life produced by each arm from A1 to A2 in either mean total scores or individual domain scores, reported by children or their parents. On analysing the response according to the minimal clinically important difference, defined as an improvement by 4.5 points, we found no significant differences, be it among bone-sarcomas, other tumours, responders (those who received ≥9 weeks of treatment) or non-responders. CONCLUSIONS The present study concludes that there was no significant difference in HRQoL, between the patients in the two arms at second and later assessments. This is consistent with the other survival endpoints in the study. TRIAL REGISTRATION NUMBER Clinical trial registration: clinicaltrials.gov Identifier: NCT01858571.
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Affiliation(s)
- Raja Pramanik
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Sandeep Agarwala
- Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Vishnubhatla Sreenivas
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Deepa Dhawan
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Sameer Bakhshi
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, Delhi, India
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Lafaie L, Chanelière-Sauvant AF, Magné N, Bouleftour W, Tinquaut F, Célarier T, Bertoletti L. Impact of Medical Specialties on Diagnostic and Therapeutic Management of Elderly Cancer Patients. Geriatrics (Basel) 2023; 8:62. [PMID: 37367094 DOI: 10.3390/geriatrics8030062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 05/24/2023] [Accepted: 05/31/2023] [Indexed: 06/28/2023] Open
Abstract
The management (diagnostic and therapeutic) of cancer in the geriatric population involves a number of complex difficulties. The aim of this study was to assess the impact of a medical specialty on the diagnostic and therapeutic management of elderly cancer patients. Four clinical scenarios of cancer in the geriatric population, with a dedicated survey to gather information regarding each clinical case's diagnostic and therapeutic approaches, as well as the different criteria influencing physicians' therapeutic decisions, were exposed to geriatricians, oncologists, and radiotherapists in Saint-Etienne. The surveys were filled out by 13 geriatricians, 11 oncologists, and 7 radiotherapists. There was a homogeneity of responses regarding the confirmation of cancer diagnostics in the elderly. There were strong disparities (inter- and intra-specialties) for several clinical situations regarding the therapeutic management of cancer. There were significant disparities in terms of surgical management, the implementation of a chemotherapy protocol, and the adaptation of the chemotherapy dosage. Contrary to oncologists, who primarily consider the G8 and the Karnofsky score, geriatric autonomy scores and frailty with cognitive assessment were the key factors determining diagnostic/therapeutic therapy for geriatricians. These results raise important ethical questions, requiring specific studies in geriatric populations to provide the homogenous management of elderly patients with cancer.
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Affiliation(s)
- Ludovic Lafaie
- Département de Gérontologie Clinique, CHU de Saint-Étienne, F-42055 Saint-Etienne, France
- INSERM, UMR1059, Equipe Dysfonction Vasculaire et Hémostase, Université Jean-Monnet, F-42055 Saint-Etienne, France
| | | | - Nicolas Magné
- Département de Radiothérapie, Institut Bergonié, F-33076 Bordeaux, France
| | - Wafa Bouleftour
- Département d'Oncologie Médicale, CHU de Saint-Etienne, F-42055 Saint-Etienne, France
| | - Fabien Tinquaut
- Département de Santé Publique, CHU de Saint-Etienne, F-42055 Saint-Etienne, France
| | - Thomas Célarier
- Département de Gérontologie Clinique, CHU de Saint-Étienne, F-42055 Saint-Etienne, France
- Gérontopôle Auvergne Rhône-Alpes, F-42055 Saint-Etienne, France
- Chaire Santé des Ainés, Université Jean Monnet, F-42055 Saint-Etienne, France
| | - Laurent Bertoletti
- INSERM, UMR1059, Equipe Dysfonction Vasculaire et Hémostase, Université Jean-Monnet, F-42055 Saint-Etienne, France
- Service de Médecine Vasculaire et Thérapeutique, CHU de Saint-Etienne, F-42055 Saint-Etienne, France
- INSERM, CIC-1408, CHU de Saint-Etienne, F-42055 Saint-Etienne, France
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Chen TH, Chen MH, Hung YP, Chiang NJ, Huang KH, Lin YH, Lin RW, Chao Y, Li AFY, Yu HY, Hwang HE, Yeh YC, Wang YC, Fang WL. Elevated PD-L1 Expression and Microsatellite Instability in Elderly Patients With Gastric Cancer. J Immunother 2023; 46:111-119. [PMID: 36809276 DOI: 10.1097/cji.0000000000000458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 01/25/2023] [Indexed: 02/23/2023]
Abstract
Immunotherapy in combination with chemotherapy is the current treatment of choice for frontline programmed cell death ligand 1 (PD-L1)-positive gastric cancer. However, the best treatment strategy remains an unmet medical need for elderly or fragile patients with gastric cancer. Previous studies have revealed that PD-L1 expression, Epstein-Barr virus association, and microsatellite instability-high (MSI-H) are the potential predictive biomarkers for immunotherapy use in gastric cancer. In this study, we showed that PD-L1 expression, tumor mutation burden, and the proportion of MSI-H were significantly elevated in elderly patients with gastric cancer who were older than 70 years compared with patients younger than 70 years from analysis of The Cancer Genome Atlas gastric adenocarcinoma cohort [≥70/<70: MSI-H: 26.8%/15.0%, P =0.003; tumor mutation burden: 6.7/5.1 Mut/Mb, P =0.0004; PD-L1 mRNA: 5.6/3.9 counts per million mapped reads, P =0.005]. In our real-world study, 416 gastric cancer patients were analyzed and showed similar results (≥70/<70: MSI-H: 12.5%/6.6%, P =0.041; combined positive score ≥1: 38.1%/21.5%, P <0.001). We also evaluated 16 elderly patients with gastric cancer treated with immunotherapy and revealed an objective response of 43.8%, a median overall survival of 14.8 months, and a median progression-free survival of 7.0 months. Our research showed that a durable clinical response could be expected when treating elderly patients with gastric cancer with immunotherapy, and this approach is worth further study.
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Affiliation(s)
- Tien-Hua Chen
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Huang Chen
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Ping Hung
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Nai-Jung Chiang
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Kuo-Hung Huang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Lin
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ryan Weihsiang Lin
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yee Chao
- Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Center for Immuno-Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Anna Fen-Yau Li
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Pathology, and Laboratory Medicine Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hung-Yuan Yu
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Hospitalist ward, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsuen-En Hwang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Chen Yeh
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Pathology, and Laboratory Medicine Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Chao Wang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Liang Fang
- Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
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Büttelmann M, Hofheinz RD, Kröcher A, Ubbelohde U, Stintzing S, Reinacher-Schick A, Bornhäuser M, Folprecht G. Geriatric assessment and the variance of treatment recommendations in geriatric patients with gastrointestinal cancer-a study in AIO oncologists. ESMO Open 2023; 8:100761. [PMID: 36638708 PMCID: PMC10024156 DOI: 10.1016/j.esmoop.2022.100761] [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] [Received: 06/17/2022] [Revised: 11/27/2022] [Accepted: 11/30/2022] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Geriatric assessment (GA) is recommended to detect vulnerabilities for elderly cancer patients. To assess whether results of GA actually influence the treatment recommendations, we conducted a case vignette-based study in medical oncologists. MATERIALS AND METHODS Seventy oncologists gave their medical treatment recommendations for a maximum of 4 out of 10 gastrointestinal cancer patients in three steps: (i) based on tumor findings alone to simulate the guideline recommendation for a '50-year-old standard patient without comorbidities'; (ii) for the same situation in elderly patients (median age 77.5 years) according to the comorbidities, laboratory values and a short video simulating the clinical consultation; and (iii) after the results of a full GA including interpretation aid [Barthel Index, Cumulative Illness Rating Scale (CIRS), Geriatric 8 (G8), Geriatric Depression Scale (GDS), Mini Mental Status Examination (MMSE), Mini-Nutritional Assessment (MNA), Timed Get Up and Go (TGUG), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30), stair climb test]. RESULTS Data on 164 treatment recommendations were analyzed. The recommendations had a significantly higher variance for elderly patients than for 'standard' patients (944 versus 602, P < 0.0001) indicating a lower agreement between oncologists. Knowledge on GA had marginal influence on the treatment recommendation or its variance (944 versus 940, P = 0.92). There was no statistically significant influence of the working place or the years of experience in oncology on the variance of recommendations. The geriatric tools were rated approximately two times higher as being 'meaningful' (53%) and 'useful for the presented cases' (49%) than they were 'used in clinical practice' (19%). The most commonly used geriatric tool in patient care was the MNA (30%). CONCLUSIONS The higher variance of treatment recommendations indicates that it is less likely for elderly patients to get the optimal recommendation. Although the proposed therapeutic regimen varied higher in elderly patients and the oncologists rated the GA results as 'useful', the GA results did not influence the individual recommendations or its variance. Continuing education on GA and research on implementation into clinical practice are needed.
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Affiliation(s)
- M Büttelmann
- TU Dresden / University Hospital Carl Gustav Carus, National Center for Tumor Diseases (NCT/UCC), Medical Dept. I, Dresden, Germany
| | | | - A Kröcher
- TU Dresden / University Hospital Carl Gustav Carus, National Center for Tumor Diseases (NCT/UCC), Medical Dept. I, Dresden, Germany
| | - U Ubbelohde
- TU Dresden / University Hospital Carl Gustav Carus, National Center for Tumor Diseases (NCT/UCC), Medical Dept. I, Dresden, Germany
| | - S Stintzing
- Charité - Universitaetsmedizin Berlin, Department of Hematology, Oncology, and Cancer Immunology (CCM), Berlin, Germany
| | - A Reinacher-Schick
- Ruhr University Bochum, St. Josef Hospital, Department of Hematology, Oncology and Palliative Care, Bochum, Germany
| | - M Bornhäuser
- TU Dresden / University Hospital Carl Gustav Carus, National Center for Tumor Diseases (NCT/UCC), Medical Dept. I, Dresden, Germany
| | - G Folprecht
- TU Dresden / University Hospital Carl Gustav Carus, National Center for Tumor Diseases (NCT/UCC), Medical Dept. I, Dresden, Germany.
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Sun P, Antwi SO, Sartorius K, Zheng X, Li X. Tumor Microenvironment, Clinical Features, and Advances in Therapy for Bone Metastasis in Gastric Cancer. Cancers (Basel) 2022; 14:4888. [PMID: 36230816 PMCID: PMC9563035 DOI: 10.3390/cancers14194888] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 09/30/2022] [Accepted: 10/01/2022] [Indexed: 11/16/2022] Open
Abstract
Gastric cancer (GC) is one of the most malignant neoplasms worldwide, accounting for about 770,000 deaths in 2020. The incidence of gastric cancer bone metastasis (GC-BM) is low, about 0.9-13.4%, and GC patients develop GC-BM because of a suitable bone microenvironment. Osteoblasts, osteoclasts, and tumor cells interact with each other, secreting cytokines such as PTHrP, RANK-L, IL-6, and other growth factors that disrupt the normal bone balance and promote tumor growth. The functions and numbers of immune cells in the bone microenvironment are continuously inhibited, resulting in bone balance disorder due to the cytokines released from destroyed bone and growing tumor cells. Patients with GC-BM are generally younger than 65 years old and they often present with a later stage of the disease, as well as more aggressive tumors. They usually have shorter overall survival (OS) because of the occurrence of skeletal-related events (SREs) and undetected bone destruction due to the untimely bone inspection. Current treatments of GC-BM focus mainly on gastric cancer and SRE-related treatment. This article reviews the clinical features, possible molecular pathogeneses, and the most commonly used diagnostic methods and treatments of bone metastasis in gastric cancer.
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Affiliation(s)
- Pengcheng Sun
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
| | - Samuel O. Antwi
- Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, FL 32224, USA
- The Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL 32224, USA
| | - Kurt Sartorius
- The Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL 32224, USA
- School of Laboratory Medicine and Molecular Sciences, College of Health Sciences, University of Kwazulu-Natal, Durban 4041, South Africa
- UKZN Gastrointestinal Cancer Research Unit, University of Kwazulu-Natal, Durban 4041, South Africa
| | - Xiao Zheng
- Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
| | - Xiaodong Li
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213004, China
- The Africa Hepatopancreatobiliary Cancer Consortium (AHPBCC), Mayo Clinic, Jacksonville, FL 32224, USA
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Wildiers H, Meyskens T, Marréaud S, Lago LD, Vuylsteke P, Curigliano G, Waters S, Brouwers B, Meulemans B, Sousa B, Poncet C, Brain E. Long term outcome data from the EORTC 75111-10114 ETF/BCG randomized phase II study: Pertuzumab and trastuzumab with or without metronomic chemotherapy for older patients with HER2-positive metastatic breast cancer, followed by T-DM1 after progression. Breast 2022; 64:100-111. [PMID: 35636341 PMCID: PMC9157551 DOI: 10.1016/j.breast.2022.05.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 04/27/2022] [Accepted: 05/13/2022] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC). PATIENTS AND METHODS This phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression. RESULTS In total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2-32.4) and 28.7% (95% CI 15.8-43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7-58.5) and grade 3 or higher AE occurred in 18 pts (45%). CONCLUSIONS Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients.
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Affiliation(s)
- Hans Wildiers
- Department of General Medical Oncology, University Hospitals Leuven and Department of Oncology, KU Leuven, Leuven, Belgium.
| | - Thomas Meyskens
- European Organization for Research and Treatment of Cancer (EORTC) - Headquarters, Brussels, Belgium
| | - Sandrine Marréaud
- European Organization for Research and Treatment of Cancer (EORTC) - Headquarters, Brussels, Belgium
| | | | | | - Giuseppe Curigliano
- Division of Early Drug Development, Istituto Europeo di Oncologia, IRCCS, Italy; University of Milano, Milan, Italy
| | | | - Barbara Brouwers
- Department of Medical Oncology, AZ Sint-Jan Hospital, Brugge, Belgium
| | - Bart Meulemans
- European Organization for Research and Treatment of Cancer (EORTC) - Headquarters, Brussels, Belgium
| | - Berta Sousa
- Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation, Lisbon, Portugal
| | - Coralie Poncet
- European Organization for Research and Treatment of Cancer (EORTC) - Headquarters, Brussels, Belgium
| | - Etienne Brain
- Department of Medical Oncology, Institut Curie - Hôpital René Huguenin, Saint-Cloud, France
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10
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Kim JH, Ahn B, Hong SM, Jung HY, Kim DH, Choi KD, Ahn JY, Lee JH, Na HK, Kim JH, Kim YH, Kim HR, Lee HJ, Kim SB, Park SR. Real-World Efficacy Data and Predictive Clinical Parameters for Treatment Outcomes in Advanced Esophageal Squamous Cell Carcinoma Treated with Immune Checkpoint Inhibitors. Cancer Res Treat 2022; 54:505-516. [PMID: 34176250 PMCID: PMC9016310 DOI: 10.4143/crt.2020.1198] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 06/15/2021] [Indexed: 12/24/2022] Open
Abstract
PURPOSE This study aimed to evaluate the real-world efficacy of immune checkpoint inhibitors (ICIs), and to identify clinicolaboratory factors to predict treatment outcomes in patients with advanced esophageal squamous cell carcinoma (ESCC) receiving ICIs. MATERIALS AND METHODS Sixty patients with metastatic or unresectable ESCC treated with nivolumab (n=48) or pembrolizumab (n=12) as ≥ second-line treatment between 2016 and 2019 at Asan Medical Center were included. RESULTS The median age of the patients was 68 years (range, 52 to 76 years), and 93.3% were male. Most patients had metastatic disease (81.7%) and had been previously treated with fluoropyrimidines, platinum, and taxane. In 53 patients with measurable disease, the overall response rate and disease control rate were 15.1% and 35.8%, respectively. With a median follow-up duration of 16.0 months, the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval [CI], 1.54 to 2.19) and 6.4 months (95% CI, 4.77 to 8.11), respectively. After multivariate analysis, recent use of antibiotics, low prognostic nutrition index (< 35.93), high Glasgow Prognosis Score (≥ 1) at baseline, and ≥ 1.4-fold increase in neutrophil-to-lymphocyte ratio after one cycle from baseline were significantly unfavorable factors for both PFS and OS. Younger age (< 65 years) was a significant factor for unfavorable PFS and hyponatremia (< 135 mmol/L) for unfavorable OS. CONCLUSION The use of ICIs after the failure of chemotherapy showed comparable efficacy in patients with advanced ESCC in real practice; this may be associated with host immune-nutritional status, which could be predicted by clinical and routine laboratory factors.
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Affiliation(s)
- Jwa Hoon Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
- Division of Oncology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul,
Korea
| | - Bokyung Ahn
- Department of Pathology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Seung-Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Hwoon-Yong Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Do Hoon Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Kee Don Choi
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Jeong Hoon Lee
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Hee Kyoung Na
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Jong Hoon Kim
- Department of Radiation Oncology, University of Ulsan College of Medicine, Seoul,
Korea
| | - Yong-Hee Kim
- Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Seoul,
Korea
| | - Hyeong Ryul Kim
- Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Seoul,
Korea
| | - Hyun Joo Lee
- Department of Radiology, 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
| | - Sook Ryun Park
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul,
Korea
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11
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Considerations and Challenges in the Management of the Older Patients with Gastric Cancer. Cancers (Basel) 2022; 14:cancers14061587. [PMID: 35326739 PMCID: PMC8946244 DOI: 10.3390/cancers14061587] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 03/17/2022] [Accepted: 03/19/2022] [Indexed: 12/07/2022] Open
Abstract
Gastric cancer is one of the commonest malignancies with high rates of mortality worldwide. Older patients represent a substantial proportion of cases with this diagnosis. However, there are very few 'elderly-specific' trials in this setting. In addition, the inclusion rate of such patients in randomised clinical trials is poor, presumably due to concerns about increased toxicity, co-existing comorbidities and impaired performance status. Therapeutic strategies for this patient group are therefore mostly based on retrospective subgroup analysis of randomised clinical trials. Review of currently available evidence suggests that older gastric cancer patients who are fit for trial inclusion may benefit from surgical intervention and peri-operative systemic chemotherapy strategies. For patients with metastatic disease, management has been revolutionized by the use of anti-HER2 directed therapies as well as immune checkpoint inhibitors with or without chemotherapy. Early data suggest that fit older patients may also benefit from these therapeutic interventions. However, once again there may be limitations in extrapolating these data to everyday clinical practice with older patients being less likely to have a good performance status and an intact immune system. Therefore, determining the functional age and not just the chronological age of a patient prior to initiating therapy becomes very important. The functional decline including reduced organ function that may occur in older patients makes the integration of some form of geriatric assessment in routine clinical practice very relevant.
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12
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Ajani JA, D'Amico TA, Bentrem DJ, Chao J, Cooke D, Corvera C, Das P, Enzinger PC, Enzler T, Fanta P, Farjah F, Gerdes H, Gibson MK, Hochwald S, Hofstetter WL, Ilson DH, Keswani RN, Kim S, Kleinberg LR, Klempner SJ, Lacy J, Ly QP, Matkowskyj KA, McNamara M, Mulcahy MF, Outlaw D, Park H, Perry KA, Pimiento J, Poultsides GA, Reznik S, Roses RE, Strong VE, Su S, Wang HL, Wiesner G, Willett CG, Yakoub D, Yoon H, McMillian N, Pluchino LA. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022; 20:167-192. [PMID: 35130500 DOI: 10.6004/jnccn.2022.0008] [Citation(s) in RCA: 909] [Impact Index Per Article: 303.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.
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Affiliation(s)
| | | | - David J Bentrem
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Prajnan Das
- The University of Texas MD Anderson Cancer Center
| | - Peter C Enzinger
- Dana-Farber/Brigham and Women's Cancer Center
- Massachusetts General Hospital Cancer Center
| | | | | | - Farhood Farjah
- Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance
| | | | | | | | | | | | - Rajesh N Keswani
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | - Samuel J Klempner
- Dana-Farber/Brigham and Women's Cancer Center
- Massachusetts General Hospital Cancer Center
| | - Jill Lacy
- Yale Cancer Center/Smilow Cancer Hospital
| | | | | | - Michael McNamara
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | - Mary F Mulcahy
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | - Haeseong Park
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | - Kyle A Perry
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | - Scott Reznik
- UT Southwestern Simmons Comprehensive Cancer Center
| | - Robert E Roses
- Abramson Cancer Center at the University of Pennsylvania
| | | | | | | | | | | | - Danny Yakoub
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
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13
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Baxter MA, Marinho J, Soto-Perez-de-Celis E, Rodriquenz MG, Arora SP, Lok WCW, Shih YY, Liposits G, O'Hanlon S, Petty RD. Gastroesophageal adenocarcinoma in older adults: A comprehensive narrative review of management by the Young International Society of Geriatric Oncology. J Geriatr Oncol 2022; 13:7-19. [PMID: 34548259 DOI: 10.1016/j.jgo.2021.09.006] [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: 03/26/2021] [Revised: 08/26/2021] [Accepted: 09/07/2021] [Indexed: 12/24/2022]
Abstract
Gastroesophageal adenocarcinoma is a disease of older adults with very poor survival rates. Its incidence has risen dramatically across the world in recent decades. Current treatment approaches for older adults are based largely on extrapolated evidence from clinical trials conducted in younger and fitter participants than those more commonly encountered in clinical practice. Understanding how to apply available evidence to our patients in the clinic setting is essential given the high morbidity of both curative and palliative treatment. This review aims to use available data to inform the management of an older adult with gastroesophageal adenocarcinoma.
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Affiliation(s)
- Mark A Baxter
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK; Tayside Cancer Centre, Ninewells Hospital, Dundee, UK.
| | - Joana Marinho
- Department of Medical Oncology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal; Associação de Investigação de Cuidados de Suporte em Oncologia (AICSO), Espinho, Portugal
| | - Enrique Soto-Perez-de-Celis
- Department of Geriatrics, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
| | - Maria Grazia Rodriquenz
- Oncology Unit, Foundation IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Sukeshi Patel Arora
- Mays Cancer Center, University of Texas Health San Antonio, Leader in Gastrointestinal Malignancies, 7979 Wurzbach Rd, 78229 San Antonio, TX, USA
| | - Wendy Chan Wing Lok
- Department of Clinical Oncology, LKS Faculty of Medicine, University of Hong Kong, China
| | - Yung-Yu Shih
- Department of Hematology and Oncology, Kaiser Franz Josef Hospital-Clinic Favoriten, Vienna, Austria
| | - Gabor Liposits
- Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; Academy of Geriatric Cancer Research (AgeCare), Odense, Denmark
| | - Shane O'Hanlon
- Department of Geriatric Medicine, St Vincent's University Hospital, Dublin, Ireland; University College, Dublin, Ireland
| | - Russell D Petty
- Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK; Tayside Cancer Centre, Ninewells Hospital, Dundee, UK
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14
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Burgess J, Ferdousi M, Gosal D, Boon C, Matsumoto K, Marshall A, Mak T, Marshall A, Frank B, Malik RA, Alam U. Chemotherapy-Induced Peripheral Neuropathy: Epidemiology, Pathomechanisms and Treatment. Oncol Ther 2021; 9:385-450. [PMID: 34655433 PMCID: PMC8593126 DOI: 10.1007/s40487-021-00168-y] [Citation(s) in RCA: 139] [Impact Index Per Article: 34.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 08/12/2021] [Indexed: 12/14/2022] Open
Abstract
PURPOSE This review provides an update on the current clinical, epidemiological and pathophysiological evidence alongside the diagnostic, prevention and treatment approach to chemotherapy-induced peripheral neuropathy (CIPN). FINDINGS The incidence of cancer and long-term survival after treatment is increasing. CIPN affects sensory, motor and autonomic nerves and is one of the most common adverse events caused by chemotherapeutic agents, which in severe cases leads to dose reduction or treatment cessation, with increased mortality. The primary classes of chemotherapeutic agents associated with CIPN are platinum-based drugs, taxanes, vinca alkaloids, bortezomib and thalidomide. Platinum agents are the most neurotoxic, with oxaliplatin causing the highest prevalence of CIPN. CIPN can progress from acute to chronic, may deteriorate even after treatment cessation (a phenomenon known as coasting) or only partially attenuate. Different chemotherapeutic agents share both similarities and key differences in pathophysiology and clinical presentation. The diagnosis of CIPN relies heavily on identifying symptoms, with limited objective diagnostic approaches targeting the class of affected nerve fibres. Studies have consistently failed to identify at-risk cohorts, and there are no proven strategies or interventions to prevent or limit the development of CIPN. Furthermore, multiple treatments developed to relieve symptoms and to modify the underlying disease in CIPN have failed. IMPLICATIONS The increasing prevalence of CIPN demands an objective approach to identify at-risk patients in order to prevent or limit progression and effectively alleviate the symptoms associated with CIPN. An evidence base for novel targets and both pharmacological and non-pharmacological treatments is beginning to emerge and has been recognised recently in publications by the American Society of Clinical Oncology and analgesic trial design expert groups such as ACTTION.
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Affiliation(s)
- Jamie Burgess
- Department of Cardiovascular and Metabolic Medicine, The Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool University Hospital NHS Trust, Liverpool, UK.
- Clinical Sciences Centre, Aintree University Hospital, Longmoor Lane, Liverpool, L9 7AL, UK.
| | - Maryam Ferdousi
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, NIHR/Wellcome Trust Clinical Research Facility, Manchester, UK
| | - David Gosal
- Department of Neurology, Salford Royal NHS Foundation Trust, Salford, UK
| | - Cheng Boon
- Department of Clinical Oncology, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | - Kohei Matsumoto
- Department of Cardiovascular and Metabolic Medicine, The Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool University Hospital NHS Trust, Liverpool, UK
| | - Anne Marshall
- Department of Cardiovascular and Metabolic Medicine, The Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool University Hospital NHS Trust, Liverpool, UK
| | - Tony Mak
- Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Andrew Marshall
- Faculty of Health and Life Sciences, Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L7 8TX, UK
- Faculty of Health and Life Sciences, The Pain Research Institute, University of Liverpool, Liverpool, L9 7AL, UK
- Department of Pain Medicine, The Walton Centre, Liverpool, L9 7LJ, UK
| | - Bernhard Frank
- Department of Pain Medicine, The Walton Centre, Liverpool, L9 7LJ, UK
| | - Rayaz A Malik
- Research Division, Qatar Foundation, Weill Cornell Medicine-Qatar, Education City, Doha, Qatar
- Institute of Cardiovascular Sciences, University of Manchester, Manchester, M13 9PL, UK
| | - Uazman Alam
- Department of Cardiovascular and Metabolic Medicine, The Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool University Hospital NHS Trust, Liverpool, UK.
- Division of Endocrinology, Diabetes and Gastroenterology, University of Manchester, Manchester, M13 9PT, UK.
- Clinical Sciences Centre, Aintree University Hospital, Longmoor Lane, Liverpool, L9 7AL, UK.
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15
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Li D, Sun CL, Kim H, Soto-Perez-de-Celis E, Chung V, Koczywas M, Fakih M, Chao J, Cabrera Chien L, Charles K, Hughes SFDS, Katheria V, Trent M, Roberts E, Jayani R, Moreno J, Kelly C, Sedrak MS, Dale W. Geriatric Assessment-Driven Intervention (GAIN) on Chemotherapy-Related Toxic Effects in Older Adults With Cancer: A Randomized Clinical Trial. JAMA Oncol 2021; 7:e214158. [PMID: 34591080 DOI: 10.1001/jamaoncol.2021.4158] [Citation(s) in RCA: 273] [Impact Index Per Article: 68.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Importance Although geriatric assessment-driven intervention improves patient-centered outcomes, its influence on chemotherapy-related toxic effects remains unknown. Objective To assess whether specific geriatric assessment-driven intervention (GAIN) can reduce chemotherapy-related toxic effects in older adults with cancer. Design, Setting, and Participants A randomized clinical trial enrolled 613 participants from a National Cancer Institute-designated cancer center between 2015 and 2019. Patients were 65 years and older with a solid malignant neoplasm, were starting a new chemotherapy regimen, and completed a geriatric assessment. Patients were followed up until chemotherapy completion or 6 months after initiation, whichever occurred first. Data analysis was done by intention-to-treat principle. Interventions Patients were randomized (2:1) to either the GAIN (intervention) or standard of care (SOC) arm. In the GAIN arm, a geriatrics-trained multidisciplinary team composed of an oncologist, nurse practitioner, social worker, physical/occupation therapist, nutritionist, and pharmacist reviewed geriatric assessment results and implemented interventions based on prespecified thresholds built into the geriatric assessment's domains. In the SOC arm, geriatric assessment results were sent to treating oncologists for consideration. Main Outcomes and Measures The primary outcome was incidence of grade 3 or higher chemotherapy-related toxic effects (graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0). Secondary outcomes included advance directive completion, emergency department visits, unplanned hospitalizations, average length of stay, unplanned hospital readmissions, chemotherapy dose modifications, and early discontinuation. Overall survival analysis was performed up to 12 months after chemotherapy initiation. Results Among the 605 eligible participants for analysis, median (range) age was 71 (65-91) years, 357 (59.0%) were women, and 432 (71.4%) had stage IV disease. Cancer types included gastrointestinal (202 [33.4%]), breast (136 [22.5%]), lung (97 [16.0%]), genitourinary (91 [15.0%]), gynecologic (54 [8.9%]), and other (25 [4.1%]). Incidence of grade 3 or higher chemotherapy-related toxic effects was 50.5% (95% CI, 45.6% to 55.4%) in the GAIN arm and 60.6% (95% CI, 53.9% to 67.3%) in the SOC arm, resulting in a significant 10.1% reduction (95% CI, -1.5 to -18.2%; P = .02). A significant absolute increase in advance directive completion of 28.4% with GAIN vs 13.3% with SOC (P < .001) was observed. No significant differences were observed in emergency department visits, unplanned hospitalizations, average length of stay, unplanned readmissions, chemotherapy dose modifications or discontinuations, or overall survival. Conclusions and Relevance In this randomized clinical trial, integration of multidisciplinary GAIN significantly reduced grade 3 or higher chemotherapy-related toxic effects in older adults with cancer. Implementation of GAIN into oncology clinical practice should be considered among older adults receiving chemotherapy. Trial Registration ClinicalTrials.gov Identifier: NCT02517034.
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Affiliation(s)
- Daneng Li
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Can-Lan Sun
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Heeyoung Kim
- City of Hope Comprehensive Cancer Center, Duarte, California
| | | | - Vincent Chung
- City of Hope Comprehensive Cancer Center, Duarte, California
| | | | - Marwan Fakih
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Joseph Chao
- City of Hope Comprehensive Cancer Center, Duarte, California
| | | | | | | | - Vani Katheria
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Monica Trent
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Elsa Roberts
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Reena Jayani
- Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jeanine Moreno
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Cynthia Kelly
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - Mina S Sedrak
- City of Hope Comprehensive Cancer Center, Duarte, California
| | - William Dale
- City of Hope Comprehensive Cancer Center, Duarte, California
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16
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Wang F, Zhang X, Li Y, Tang L, Qu X, Ying J, Zhang J, Sun L, Lin R, Qiu H, Wang C, Qiu M, Cai M, Wu Q, Liu H, Guan W, Zhou A, Zhang Y, Liu T, Bi F, Yuan X, Rao S, Xin Y, Sheng W, Xu H, Li G, Ji J, Zhou Z, Liang H, Zhang Y, Jin J, Shen L, Li J, Xu R. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2021. Cancer Commun (Lond) 2021; 41:747-795. [PMID: 34197702 PMCID: PMC8360643 DOI: 10.1002/cac2.12193] [Citation(s) in RCA: 442] [Impact Index Per Article: 110.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 06/21/2021] [Accepted: 06/23/2021] [Indexed: 02/05/2023] Open
Abstract
There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow-up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non-metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third-line to the first-line of treatment for different patient groups with detailed notes are provided.
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Cavanagh KE, Baxter MA, Petty RD. Best supportive care and prognosis: advanced gastroesophageal adenocarcinoma. BMJ Support Palliat Care 2021:bmjspcare-2020-002637. [PMID: 34301644 DOI: 10.1136/bmjspcare-2020-002637] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 06/30/2021] [Indexed: 11/04/2022]
Abstract
OBJECTIVES Real-world data are lacking on survival in patients with advanced gastroesophageal adenocarcinoma (GOA) treated with best supportive care (BSC) alone. This knowledge is vital to personalise cancer treatment and obtain informed consent. This study aimed to define and compare survival in patients with advanced GOA treated with and without palliative chemotherapy (CTx), and to explore the factors that impact prognosis. METHODS Patients in NHS Tayside, Scotland, diagnosed with advanced GOA (defined as non-resectable) over a 2-year period were identified retrospectively. Clinical data were obtained from electronic records. Kaplan-Meier and Cox regression analysis were performed to determine median overall survival (mOS) and investigate contributing factors. RESULTS 127 eligible patients were identified. There was a significant difference in mOS between patients in the BSC and CTx groups (3.1 months vs 8.9 months, p=0.00089). This was maintained when those deemed not fit for CTx were removed. One-year survival was 16% versus 33%. Cox regression analysis in the BSC group identified stage (p<0.001) and Eastern Cooperative Oncology Group performance status (ECOG PS) (p=0.013) as having independent predictive value for survival. Age was not related to outcome. Palliative stents were inserted in 48 patients (37.8%). CONCLUSIONS To our knowledge, this is the largest reported study in Europe of outcomes in patients with advanced GOA treated with BSC only. The mOS with BSC is approximately 3 months. Cancer stage and ECOG PS have a role in prognostication at diagnosis. Our findings support the benefit of palliative chemotherapy in this population, and real-world survival corresponds to published trial data.
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Affiliation(s)
- Kirsty E Cavanagh
- School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Mark A Baxter
- Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
- Tayside Cancer Centre, Ninewells Hospital and Medical School, NHS Tayside, Dundee, UK
| | - Russell D Petty
- Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
- Tayside Cancer Centre, Ninewells Hospital and Medical School, NHS Tayside, Dundee, UK
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18
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Schütte K, Schulz C, Middelberg-Bisping K. Impact of gastric cancer treatment on quality of life of patients. Best Pract Res Clin Gastroenterol 2021; 50-51:101727. [PMID: 33975681 DOI: 10.1016/j.bpg.2021.101727] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 01/29/2021] [Accepted: 02/01/2021] [Indexed: 01/31/2023]
Abstract
Treatment of gastric cancer is stage specific and ranges from endoscopic resections in early gastric cancer to gastrectomy and multimodal treatment in locally advanced tumour situations. Palliative systemic treatment has the potential to prolong survival in advanced tumour stages. However, tumour-directed therapies and their side-effects potentially worsen the general condition of a patient. Treatment discussions and decisions, especially when trading-off the options with the patient, have widened their focus from 'technical' terms like overall survival, disease-free survival and progression-free survival to patient reported outcomes (PROs) including quality of life (QoL). The assessment of PROs has evolved as important endpoint in clinical studies. A precise definition of QoL seems impossible. Its multiple dimensions can be evaluated by various validated questionnaires like the QLQ-C30 and FACT-G focusing on different priorities. Special additional tools have been developed and validated to assess QoL in gastric cancer patients (QLQ-STO22, FACT-Ga). We herein give an overview on the options to evaluate QoL in patients with gastric cancer and on published data on the impact of tumour-targeted therapy on QoL in these patients.
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Affiliation(s)
- Kerstin Schütte
- Department of Internal Medicine and Gastroenterology, Niels-Stensen-Klinken Marienhospital Osnabrück, Germany.
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Germany
| | - Kristina Middelberg-Bisping
- Department of Internal Medicine and Gastroenterology, Niels-Stensen-Klinken Marienhospital Osnabrück, Germany
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19
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Attia H, Smyth E. Evolving therapies in advanced oesophago-gastric cancers and the increasing role of immunotherapy. Expert Rev Anticancer Ther 2021; 21:535-546. [PMID: 33349073 DOI: 10.1080/14737140.2021.1866548] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Esophagogastric cancers remain a considerable health burden and among the top causes of global cancer-related deaths. Chemotherapy remains the cornerstone of treatment for patients with advanced disease. Doublet platinum/fluoropyrimidine therapy is established as first-line treatment with the option of adding a taxane in selected patients. Irinotecan, taxanes, and ramucirumab are approved as second-line treatments. Results from the trials KEYNOTE-059, ATTRACTION-2, and TAGS have established the use of immune checkpoint inhibitors and trifluridine/tipiracil as a third-line treatment. High PD-L1 expression, microsatellite instability, tumor mutational burden, and Epstein-Barr virus status may also be used to enrich for responses to immunotherapy. AREAS COVERED In this review, we discuss the outcome of recent trials in the later lines of therapy for esophagogastric cancer and place these in the context of current treatment paradigms. We also discuss the biology of esophagogastric cancers and how this might inform the development of new treatments. Finally, we comment on promising new drugs in development. EXPERT OPINION Recent advances in the treatment of chemo-refractory esophagogastric cancer add to the improving survival of patients with this disease. Further research is needed to improve patient selection to therapies and the earlier incorporation of these agents in the treatment journey.
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Affiliation(s)
- Hossameldin Attia
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
| | - Elizabeth Smyth
- Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, UK
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20
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van Holstein Y, van Deudekom FJ, Trompet S, Postmus I, Uit den Boogaard A, van der Elst MJT, de Glas NA, van Heemst D, Labots G, Altena M, Slingerland M, Liefers GJ, van den Bos F, van der Bol JM, Blauw GJ, Portielje JEA, Mooijaart SP. Design and rationale of a routine clinical care pathway and prospective cohort study in older patients needing intensive treatment. BMC Geriatr 2021; 21:29. [PMID: 33413165 PMCID: PMC7791733 DOI: 10.1186/s12877-020-01975-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Treatment decisions concerning older patients can be very challenging and individualised treatment plans are often required in this very heterogeneous group. In 2015 we have implemented a routine clinical care pathway for older patients in need of intensive treatment, including a comprehensive geriatric assessment (CGA) that was used to support clinical decision making. An ongoing prospective cohort study, the Triaging Elderly Needing Treatment (TENT) study, has also been initiated in 2016 for participants in this clinical care pathway, to study associations between geriatric characteristics and outcomes of treatment that are relevant to older patients. The aim of this paper is to describe the implementation and rationale of the routine clinical care pathway and design of the TENT study. METHODS A routine clinical care pathway has been designed and implemented in multiple hospitals in the Netherlands. Patients aged ≥70 years who are candidates for intensive treatments, such as chemotherapy, (chemo-)radiation therapy or major surgery, undergo frailty screening based on the Geriatric 8 (G-8) questionnaire and the Six-Item Cognitive Impairment Test (6CIT). If screening reveals potential frailty, a CGA is performed. All patients are invited to participate in the TENT study. Clinical data and blood samples for biomarker studies are collected at baseline. During follow-up, information about treatment complications, hospitalisations, functional decline, quality of life and mortality is collected. The primary outcome is the composite endpoint of functional decline or mortality at 1 year. DISCUSSION Implementation of a routine clinical care pathway for older patients in need of intensive treatment provides the opportunity to study associations between determinants of frailty and outcomes of treatment. Results of the TENT study will support individualised treatment for future patients. TRIAL REGISTRATION The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107 . Date of registration: 22-10-2019.
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Affiliation(s)
- Yara van Holstein
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands.
| | - Floor J van Deudekom
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | - Stella Trompet
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | - Iris Postmus
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | - Anna Uit den Boogaard
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | - Marjan J T van der Elst
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | - Nienke A de Glas
- Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
| | - Diana van Heemst
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | - Geert Labots
- Department of Internal Medicine, Haga Hospital, The Hague, The Netherlands
| | - Mariëtte Altena
- Department of Internal Medicine, Haaglanden Medical Center, The Hague, The Netherlands
| | - Marije Slingerland
- Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
| | - Gerrit Jan Liefers
- Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Frederiek van den Bos
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | | | - Gerard J Blauw
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
| | | | - Simon P Mooijaart
- Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO box 9600, 2300 RC, Leiden, The Netherlands
- Institute for Evidence-based Medicine in Old Age (IEMO), Leiden, The Netherlands
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21
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Sedrak MS, Freedman RA, Cohen HJ, Muss HB, Jatoi A, Klepin HD, Wildes TM, Le-Rademacher JG, Kimmick GG, Tew WP, George K, Padam S, Liu J, Wong AR, Lynch A, Djulbegovic B, Mohile SG, Dale W. Older adult participation in cancer clinical trials: A systematic review of barriers and interventions. CA Cancer J Clin 2021; 71:78-92. [PMID: 33002206 PMCID: PMC7854940 DOI: 10.3322/caac.21638] [Citation(s) in RCA: 291] [Impact Index Per Article: 72.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 07/31/2020] [Accepted: 08/11/2020] [Indexed: 12/20/2022] Open
Abstract
Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.
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Affiliation(s)
| | | | | | - Hyman B. Muss
- UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA
| | | | | | - Tanya M. Wildes
- Washington University School of Medicine, St. Louis, MO, USA
| | | | | | - William P. Tew
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kevin George
- City of Hope National Medical Center, Duarte, CA, USA
| | - Simran Padam
- City of Hope National Medical Center, Duarte, CA, USA
| | - Jennifer Liu
- City of Hope National Medical Center, Duarte, CA, USA
| | | | - Andrea Lynch
- City of Hope National Medical Center, Duarte, CA, USA
| | | | | | - William Dale
- City of Hope National Medical Center, Duarte, CA, USA
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22
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Zhang Y, Zhang ZX, Lu ZX, Liu F, Hu GY, Tao F, Ye MF. Individualized treatment for gastric cancer with rib metastasis: A case report. World J Gastrointest Surg 2020; 12:555-563. [PMID: 33437406 PMCID: PMC7769748 DOI: 10.4240/wjgs.v12.i12.555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 11/03/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even less common. The clinical prognosis of GC with bone metastasis is poor given the lack of an effective treatment.
CASE SUMMARY A 70 year old man was referred to Shaoxing People’s Hospital with left chest pain and slight dyspnea. Chest computed tomography (CT) revealed a metastatic lesion in the left 3rd rib. Esophagogastroduodenoscopy revealed several ulcers in the angle and antrum of the stomach, and tumor biomarkers including CEA and CA-199 were clearly increased. In addition, lymph node metastasis in the lesser curvature of the stomach was identified by positron emission tomography/CT scanning. Further pathological examination confirmed metastatic adenocarcinoma in the rib and medium-low differentiated adenocarcinoma in the gastric space. The patient had GC with rib metastasis, and was clinically staged as T3NxM1 (IVB). Based on multidisciplinary team opinions, the patient received five courses of chemotherapy (CAPOX plus aptinib), and then underwent rib resection and laparoscopic radical distal gastrectomy. The patient started four courses of chemotherapy after surgery, and then capecitabine and aptinib were administered orally for 3 mo. Follow-up was performed on an outpatient basis using abdominal/chest CT and tumor biomarkers. The patient exhibited an overall survival greater than 2 years, and the disease-free survival was approximately 18 mo. His adverse events were tolerable.
CONCLUSION The incidence of GC with rib metastases is extremely low, and patients can obtain more benefits from individualized treatment formulated by multidisciplinary team. Chemotherapy plus surgery might represent an alternative option for GC with rib metastasis.
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Affiliation(s)
- Yu Zhang
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital; Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China
| | - Zhen-Xing Zhang
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital; Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China
| | - Zeng-Xin Lu
- Department of Radiology, Shaoxing People's Hospital; Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China
| | - Fang Liu
- Department of Pathology, Shaoxing People's Hospital; Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China
| | - Geng-Yuan Hu
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital; Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China
| | - Feng Tao
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital; Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China
| | - Min-Feng Ye
- Department of Gastrointestinal Surgery, Shaoxing People's Hospital; Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang Province, China
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23
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Fukuda N, Yunokawa M, Fujiwara Y, Wang X, Ohmoto A, Hayashi N, Urasaki T, Sato Y, Nakano K, Ono M, Tomomatsu J, Mitani H, Takahashi S. Comparison of the efficacy and safety of the EXTREME regimen for treating recurrent or metastatic head and neck squamous cell carcinoma in older and younger adult patients. Cancer Rep (Hoboken) 2020; 4:e1322. [PMID: 33295110 PMCID: PMC8451378 DOI: 10.1002/cnr2.1322] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/22/2020] [Accepted: 10/27/2020] [Indexed: 12/27/2022] Open
Abstract
Background Head and neck squamous cell carcinoma (HNSCC) is a geriatric cancer. However, older adult patients are frequently underrepresented in large clinical trials. Aims The aim of this study is to assess the efficacy and safety of the EXTREME regimen (platinum + fluorouracil + cetuximab) in older and younger adult patients with HNSCC. Methods and results Patients with recurrent or metastatic HNSCC treated with the EXTREME regimen were retrospectively analyzed. We compare the efficacy and safety in older (aged ≥70 years) younger (aged <70 years) adult patients. Of the 86 patients examined in this study, 21 (24.4%) were older adults. There was no difference in overall response rate (46.9% vs 38.5%, P = .76), median progression‐free survival [5.7 months vs 5.8 months, hazard ratio (HR) 0.88, 95% confidence interval (CI) = 0.52‐1.51, P = .66] and overall survival (OS) (14.6 months vs 15.2 months, HR 0.79, 95% CI 0.43‐1.43, P = .44) in younger vs older patients. There was also no difference in the incidence of grade 3/4 adverse events between groups. The exploratory analysis for geriatric nutritional risk index (GNRI) showed the association with lower GNRI (≤98) and poor OS in older adult patients (37.7 months vs 7.0 months, HR 0.53, 95% CI 0.31‐0.89, P = .002). Conclusions The EXTREME regimen with optimal dose modification is safe and effective for both older and younger adult patients with HNSCC. The GNRI can be an indicator to select the older adult patients who can get benefit from the EXTREME regimen.
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Affiliation(s)
- Naoki Fukuda
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Mayu Yunokawa
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yu Fujiwara
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Xiaofei Wang
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akihiro Ohmoto
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naomi Hayashi
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tetsuya Urasaki
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yasuyoshi Sato
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kenji Nakano
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Makiko Ono
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Junichi Tomomatsu
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiroki Mitani
- Department of Head and Neck Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shunji Takahashi
- Department of Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
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VanderWalde NA, Williams GR. Developing an electronic geriatric assessment to improve care of older adults with cancer receiving radiotherapy. Tech Innov Patient Support Radiat Oncol 2020; 16:24-29. [PMID: 33385071 PMCID: PMC7769846 DOI: 10.1016/j.tipsro.2020.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 09/04/2020] [Accepted: 09/09/2020] [Indexed: 01/02/2023] Open
Abstract
Older adults make up a substantial proportion of patients diagnosed with cancer. Gaps in evidence of care for older adults with cancer leads to treatment heterogeneity and poor outcomes. Medical and Surgical Oncology clinics throughout the world are increasingly using Geriatric Assessment (GA) based approaches to treatment that are beginning to improve care through treatment decision-making communication, health-related quality of life outcomes, and reducing chemotherapy toxicities. Yet, GA based approaches are not often used in radiation oncology clinics. This manuscript aims to describe the ongoing development of an electronic patient-reported GA with real-time data interpretation and recommendation delivery to help increase the use of a personalized GA based approach to the care of older adults within radiation oncology clinics. Future studies demonstrating the utility and benefit of GA based approaches to help older adults undergoing radiotherapy for their cancers are still sorely needed.
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Affiliation(s)
- Noam A. VanderWalde
- Department of Radiation Oncology, West Cancer Center and Research Institute, University of Tennessee Health Science Center, Memphis, TN, United States
| | - Grant R. Williams
- Division of Hematology and Oncology, Department of Medicine, University of Alabama Birmingham, Birmingham, AL, United States
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25
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Kadambi S, Loh KP, Dunne R, Magnuson A, Maggiore R, Zittel J, Flannery M, Inglis J, Gilmore N, Mohamed M, Ramsdale E, Mohile S. Older adults with cancer and their caregivers - current landscape and future directions for clinical care. Nat Rev Clin Oncol 2020; 17:742-755. [PMID: 32879429 PMCID: PMC7851836 DOI: 10.1038/s41571-020-0421-z] [Citation(s) in RCA: 88] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2020] [Indexed: 12/13/2022]
Abstract
Despite substantial improvements in the outcomes of patients with cancer over the past two decades, older adults (aged ≥65 years) with cancer are a rapidly increasing population and continue to have worse outcomes than their younger counterparts. Managing cancer in this population can be challenging because of competing health and ageing-related conditions that can influence treatment decision-making and affect outcomes. Geriatric screening tools and comprehensive geriatric assessment can help to identify patients who are most at risk of poor outcomes from cancer treatment and to better allocate treatment for these patients. The use of evidence-based management strategies to optimize geriatric conditions can improve communication and satisfaction between physicians, patients and caregivers as well as clinical outcomes in this population. Clinical trials are currently underway to further determine the effect of geriatric assessment combined with management interventions on cancer outcomes as well as the predictive value of geriatric assessment in the context of treatment with contemporary systemic therapies such as immunotherapies and targeted therapies. In this Review, we summarize the unique challenges of treating older adults with cancer and describe the current guidelines as well as investigational studies underway to improve the outcomes of these patients.
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Affiliation(s)
- Sindhuja Kadambi
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA.
| | - Kah Poh Loh
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Richard Dunne
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Allison Magnuson
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Ronald Maggiore
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Jason Zittel
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Marie Flannery
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Julia Inglis
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Nikesha Gilmore
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Mostafa Mohamed
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Erika Ramsdale
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA
| | - Supriya Mohile
- University of Rochester Medical Center, Wilmot Cancer Institute, Department of Haematology/Oncology, Rochester, NY, USA.
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Slagter AE, Vollebergh MA, Jansen EPM, van Sandick JW, Cats A, van Grieken NCT, Verheij M. Towards Personalization in the Curative Treatment of Gastric Cancer. Front Oncol 2020; 10:614907. [PMID: 33330111 PMCID: PMC7734340 DOI: 10.3389/fonc.2020.614907] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 11/02/2020] [Indexed: 12/12/2022] Open
Abstract
Gastric cancer is the fifth most common cancer worldwide and has a high mortality rate. In the last decades, treatment strategy has shifted from an exclusive surgical approach to a multidisciplinary strategy. Treatment options for patients with resectable gastric cancer as recommended by different worldwide guidelines, include perioperative chemotherapy, pre- or postoperative chemoradiotherapy and postoperative chemotherapy. Although gastric cancer is a heterogeneous disease with respect to patient-, tumor-, and molecular characteristics, the current standard of care is still according to a one-size-fits-all approach. In this review, we discuss the background of the different treatment strategies in resectable gastric cancer including the current standard, the specific role of radiotherapy, and describe the current areas of research and potential strategies for personalization of therapy.
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Affiliation(s)
- Astrid E Slagter
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Marieke A Vollebergh
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | - Edwin P M Jansen
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | | | - Annemieke Cats
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands
| | | | - Marcel Verheij
- Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands.,Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands
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27
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Ghebriou D, Prebet C, Bonnet G, Benderra MA. [New therapies in oncogeriatrics]. SOINS. GÉRONTOLOGIE 2020; 26:16-19. [PMID: 33549236 DOI: 10.1016/j.sger.2020.10.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Cancer management is changing rapidly. Changes in practices are not all transferable to the elderly population, which is heterogeneous. The description of the intrinsic toxicity of anti-cancer treatments is insufficient in the elderly. Recent studies dedicated to the elderly incorporate composite evaluation criteria combining efficacy and toxicity with a broad definition including, among other things, loss of functional autonomy. These new data acquired, as well as new organisations integrating the new profession of advanced practice nurse in oncogeriatrics will enable us to better respond to the challenge of caring for elderly patients in the future.
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Affiliation(s)
- Djamel Ghebriou
- Oncologie médicale, site Tenon, Institut universitaire de cancérologie, Assistance publique-Hôpitaux de Paris, Sorbonne université, unité de coordination et antennes d'oncogériatrie Île-de-France-Paris-Est, 20 rue de la Chine, 75020 Paris, France.
| | - Coralie Prebet
- Oncologie médicale, site Tenon, Institut universitaire de cancérologie, Assistance publique-Hôpitaux de Paris, Sorbonne université, unité de coordination et antennes d'oncogériatrie Île-de-France-Paris-Est, 20 rue de la Chine, 75020 Paris, France
| | - Guillaume Bonnet
- Unité de coordination en oncogériatrie de Picardie, centre hospitalier universitaire Amiens-Picardie, site Sud, entrée secondaire, 30 avenue de la Croix-Jourdain, 80054 Amiens cedex 1, France
| | - Marc Antoine Benderra
- Oncologie médicale, site Tenon, Institut universitaire de cancérologie, Assistance publique-Hôpitaux de Paris, Sorbonne université, unité de coordination et antennes d'oncogériatrie Île-de-France-Paris-Est, 20 rue de la Chine, 75020 Paris, France
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28
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Anticancer drugs are not well tolerated in all older patients with cancer. LANCET HEALTHY LONGEVITY 2020; 1:e43-e47. [DOI: 10.1016/s2666-7568(20)30001-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/04/2020] [Accepted: 08/12/2020] [Indexed: 10/23/2022]
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Athauda A, Nankivell M, Langley RE, Alderson D, Allum W, Grabsch HI, Starling N, Chau I, Cunningham D. Impact of sex and age on chemotherapy efficacy, toxicity and survival in localised oesophagogastric cancer: A pooled analysis of 3265 individual patient data from four large randomised trials (OE02, OE05, MAGIC and ST03). Eur J Cancer 2020; 137:45-56. [PMID: 32745964 DOI: 10.1016/j.ejca.2020.06.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/27/2020] [Accepted: 06/07/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND There is a lack of large-scale randomised data evaluating the impact of sex and age in patients undergoing chemotherapy followed by potentially curative surgery for oesophagogastric cancer. PATIENTS AND METHODS Individual patient data from four prospective randomised controlled trials were pooled using a two-stage meta-analysis. For survival analysis, hazard ratios (HRs) were calculated for patients aged <70 and ≥ 70 years, as well as between males and females. Mandard tumour regression grade (TRG) and, ≥grade III toxicities were compared using logistic regression models to calculate odds ratios. All analyses were adjusted for the type of chemotherapy received. RESULTS 3265 patients were included for survival analysis (2668 [82%] male, 597 [18%] female; 2627 (80%) <70 years, 638 (20%) ≥70 years). A significant improvement in overall survival (OS) (HR: 0.78; p < 0.001) and disease-specific survival (DSS) (HR: 0.78; p < 0.001) was observed in females compared with males. No significant differences in OS (HR: 1.11; p = 0.045) or DSS (HR: 1.01; p = 0.821) were observed in older patients compared with younger patients. For patients who underwent resection, older patients (15% vs 10%; p = 0.03) and female patients (14% vs 10%, p = 0.10) were more likely to achieve favourable Mandard TRG scores. Females experienced significantly more ≥grade III nausea (10% vs 5%; p≤0.001), vomiting (10% vs 4%; p≤0.001) and diarrhoea (9% vs 4%; p≤0.001) than males. CONCLUSIONS In this large pooled analysis using prospective randomised trial data, females had significantly improved survival while experiencing more gastrointestinal toxicities. Older patients achieved comparable survival to younger patients and thus, dependent on fitness, should be offered the same treatment paradigm.
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Affiliation(s)
- Avani Athauda
- Gastrointestinal and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, United Kingdom
| | - Matthew Nankivell
- Medical Research Council Clinical Trials Unit at University College London, 90 High Holborn, Second Floor, London, WC1V 6LJ, United Kingdom
| | - Ruth E Langley
- Medical Research Council Clinical Trials Unit at University College London, 90 High Holborn, Second Floor, London, WC1V 6LJ, United Kingdom
| | - Derek Alderson
- Department of Surgery, Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB, United Kingdom
| | - William Allum
- Gastrointestinal and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, United Kingdom
| | - Heike I Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, LS9 7TF, United Kingdom
| | - Naureen Starling
- Gastrointestinal and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, United Kingdom
| | - Ian Chau
- Gastrointestinal and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, United Kingdom
| | - David Cunningham
- Gastrointestinal and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, United Kingdom.
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30
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Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet 2020; 396:635-648. [PMID: 32861308 DOI: 10.1016/s0140-6736(20)31288-5] [Citation(s) in RCA: 2755] [Impact Index Per Article: 551.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/06/2020] [Accepted: 05/07/2020] [Indexed: 02/06/2023]
Abstract
Gastric cancer is the fifth most common cancer and the third most common cause of cancer death globally. Risk factors for the condition include Helicobacter pylori infection, age, high salt intake, and diets low in fruit and vegetables. Gastric cancer is diagnosed histologically after endoscopic biopsy and staged using CT, endoscopic ultrasound, PET, and laparoscopy. It is a molecularly and phenotypically highly heterogeneous disease. The main treatment for early gastric cancer is endoscopic resection. Non-early operable gastric cancer is treated with surgery, which should include D2 lymphadenectomy (including lymph node stations in the perigastric mesentery and along the celiac arterial branches). Perioperative or adjuvant chemotherapy improves survival in patients with stage 1B or higher cancers. Advanced gastric cancer is treated with sequential lines of chemotherapy, starting with a platinum and fluoropyrimidine doublet in the first line; median survival is less than 1 year. Targeted therapies licensed to treat gastric cancer include trastuzumab (HER2-positive patients first line), ramucirumab (anti-angiogenic second line), and nivolumab or pembrolizumab (anti-PD-1 third line).
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Affiliation(s)
- Elizabeth C Smyth
- Department of Oncology, Cambridge University Hospitals National Health Service Foundation Trust, Hill's Road, Cambridge, UK.
| | - Magnus Nilsson
- Division of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden; Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Heike I Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, Netherlands; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | - Nicole Ct van Grieken
- Department of Pathology, Amsterdam University Medical Centre, Cancer Center Amsterdam, VU University, Amsterdam, Netherlands
| | - Florian Lordick
- University Cancer Center Leipzig, Leipzig University Medical Center, Leipzig, Germany
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31
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Franck C, Müller C, Rosania R, Croner RS, Pech M, Venerito M. Advanced Pancreatic Ductal Adenocarcinoma: Moving Forward. Cancers (Basel) 2020; 12:E1955. [PMID: 32708493 PMCID: PMC7409054 DOI: 10.3390/cancers12071955] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 07/13/2020] [Accepted: 07/15/2020] [Indexed: 02/06/2023] Open
Abstract
Globally, the death rate of pancreatic ductal adenocarcinoma (PDAC) has doubled over 30 years and is likely to further increase, making PDAC a leading cause of cancer-related death in the coming years. PDAC is typically diagnosed at an advanced stage, and modified FOLFIRINOX or nab-paclitaxel and gemcitabine are the mainstay of systemic therapy. For elderly patients with good performance status, low-dose treatment can preserve quality of life without compromising cancer control or survival. Maintenance therapy should be considered in PDAC patients achieving disease control with systemic therapy. In particular, olaparib has demonstrated a progression-free survival benefit of 3.6 months in a subgroup of PDAC patients with germline BRCA1/2 mutations (ca. 10% of all PDAC). Pancreatic enzyme replacement therapy is often omitted in the treatment of patients with PDAC, with possibly deleterious consequences. Small intestinal bacterial overgrowth is highly prevalent in patients with PDAC and should be considered in the diagnostic algorithm of PDAC patients with bloating and diarrhea. Rivaroxaban has been associated with a reduced risk of thrombosis without an increase in major bleeding events, and its use should be considered in every patient with advanced PDAC undergoing systemic therapy.
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Affiliation(s)
- Caspar Franck
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany; (C.F.); (C.M.); (R.R.)
| | - Christian Müller
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany; (C.F.); (C.M.); (R.R.)
| | - Rosa Rosania
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany; (C.F.); (C.M.); (R.R.)
| | - Roland S. Croner
- Department of General-, Visceral-, Vascular- and Transplant Surgery, Otto-von-Guericke University Hospital Magdeburg, 39120 Magdeburg, Germany;
| | - Maciej Pech
- Department of Radiology and Nuclear Medicine, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany;
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, 39120 Magdeburg, Germany; (C.F.); (C.M.); (R.R.)
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32
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Adapting care for older cancer patients during the COVID-19 pandemic: Recommendations from the International Society of Geriatric Oncology (SIOG) COVID-19 Working Group. J Geriatr Oncol 2020; 11:1190-1198. [PMID: 32709495 PMCID: PMC7365054 DOI: 10.1016/j.jgo.2020.07.008] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 07/10/2020] [Indexed: 12/25/2022]
Abstract
The COVID-19 pandemic poses a barrier to equal and evidence-based management of cancer in older adults. The International Society of Geriatric Oncology (SIOG) formed a panel of experts to develop consensus recommendations on the implications of the pandemic on several aspects of cancer care in this age group including geriatric assessment (GA), surgery, radiotherapy, systemic treatment, palliative care and research. Age and cancer diagnosis are significant predictors of adverse outcomes of the COVID-19 infection. In this setting, GA is particularly valuable to drive decision-making. GA may aid estimating physiologic reserve and adaptive capability, assessing risk-benefits of either providing or temporarily withholding treatments, and determining patient preferences to help inform treatment decisions. In a resource-constrained setting, geriatric screening tools may be administered remotely to identify patients requiring comprehensive GA. Tele-health is also crucial to ensure adequate continuity of care and minimize the risk of infection exposure. In general, therapeutic decisions should favor the most effective and least invasive approach with the lowest risk of adverse outcomes. In selected cases, this might require deferring or omitting surgery, radiotherapy or systemic treatments especially where benefits are marginal and alternative safe therapeutic options are available. Ongoing research is necessary to expand knowledge of the management of cancer in older adults. However, the pandemic presents a significant barrier and efforts should be made to ensure equitable access to clinical trials and prospective data collection to elucidate the outcomes of COVID-19 in this population.
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Joharatnam-Hogan N, Shiu KK, Khan K. Challenges in the treatment of gastric cancer in the older patient. Cancer Treat Rev 2020; 85:101980. [PMID: 32065879 DOI: 10.1016/j.ctrv.2020.101980] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 02/04/2020] [Accepted: 02/05/2020] [Indexed: 12/24/2022]
Abstract
Gastric cancer is considered an age-related disease, with the majority of new cases in the UK diagnosed in individuals over the age of 75. At present most guidance related to the management of gastric cancer is based on trials undertaken in the fit, younger patient. Historically the elderly have been underrepresented in clinical trials, which frequently have a restricted inclusion to an upper age limit of 75. The European Society for Medical Oncology (ESMO) recommends use of a geriatric assessment to determine functional age when initiating treatment in elderly patients with gastric cancer, which has been shown to be a better predictor of treatment response than chronological age. The physiological changes that occur with age, including reduced organ function and pharmacokinetic and pharmacodynamic variability, together with impaired functional status, necessitate a more individualised approach to treatment decisions in the older patient to provide them with the same advantages from radical treatment and palliative chemotherapy as younger patients. This review summarises the current evidence extrapolated from trial data on how best to optimise treatment for elderly patients with gastric cancer.
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Affiliation(s)
- Nalinie Joharatnam-Hogan
- Gastrointestinal Oncology, Department of Medicine, University College London NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK
| | - Kai Keen Shiu
- Gastrointestinal Oncology, Department of Medicine, University College London NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK
| | - Khurum Khan
- Gastrointestinal Oncology, Department of Medicine, University College London NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.
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34
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Vora A. Next steps for geriatric oncology in India. CANCER RESEARCH, STATISTICS, AND TREATMENT 2020. [DOI: 10.4103/crst.crst_231_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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35
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Wagner AD, Lordick F, Grabsch HI, Terashima M, Terada M, Yoshikawa T, Boku N, Kataoka K, Smyth EC, Mauer M, Haustermans K, Moehler MH. Multidisciplinary management of stage II-III gastric and gastro-oesophageal junction cancer. Eur J Cancer 2019; 124:67-76. [PMID: 31759294 DOI: 10.1016/j.ejca.2019.09.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 08/20/2019] [Accepted: 09/17/2019] [Indexed: 12/19/2022]
Abstract
The aim of this manuscript is to discuss the viewpoint of the European Organisation for Research and Treatment of Cancer (EORTC) Gastric Cancer Taskforce and Japan Clinical Oncology Group (JCOG) Gastric Cancer Study Group on the current challenges in the multidisciplinary management of stage II-III gastric and gastro-oesophageal junction (GEJ) cancer. We seek to outline how these challenges are addressed in current trials of both groups. Key elements of future trials of EORTC and JCOG in this indication are described, and a joint vision on how multidisciplinary research of gastric and GEJ cancer patients should be organised is outlined.
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Affiliation(s)
- Anna D Wagner
- Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
| | - Florian Lordick
- University Cancer Center Leipzig, University Medicine Leipzig, Leipzig, Germany
| | - Heike I Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands; Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
| | | | - Mitsumi Terada
- Japan Clinical Oncology Group, Clinical Research Support Office and National Cancer Center Hospital, Tokyo, Japan
| | - Takaki Yoshikawa
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Narikazu Boku
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kozo Kataoka
- Department of Surgery, Division of Lower GI, Hyogo College of Medicine, Hyogo, Japan
| | - Elizabeth C Smyth
- Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | | | - Karin Haustermans
- Department of Radiotherapy and Oncology, University of Leuven, Leuven, Belgium
| | - Markus H Moehler
- University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany
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36
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Martin P, O'Leary E, Deady S, Horgan A. The Uptake and Efficacy of Neoadjuvant Therapy in Older Adults with Locally Advanced Esophogastric Cancer. J Gastrointest Cancer 2019; 51:893-900. [PMID: 31701400 DOI: 10.1007/s12029-019-00320-y] [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] [Indexed: 10/25/2022]
Abstract
BACKGROUND Data on Neo+/- adjuvant treatment in older patients with cancer is sparse. The management of locally advanced esophagogastric cancer (LAEC) in older patients was evaluated to determine treatment modalities and identify factors associated with survival. METHODS Patients diagnosed with LAEC (stage II or III) over 5 years were identified from the National Cancer Registry of Ireland. Treatment was classified as "best supportive care (BSC)," "surgery only," "neo/adjuvant treatment," and "chemo/radiation alone."Survival was assessed. Univariate and multivariate analysis (MVA) of clinicopathological factors and treatment was conducted. RESULTS Forty-six percent (n = 580) of the 1251 patients were ≥ 70 years, 11% (n = 134) received BSC, 23% (n = 288) surgery only, 31% (n = 390) had chemo/radiation alone, and 35% (n = 439) had neo/adjuvant treatment. Forty-six percent, 10%, and 0% of patients < 75, ≥ 75, and ≥ 80 years of age, respectively, received neoadjuvant treatment. Age was associated with treatment received (p < 0.001). Older patients were less likely to receive neo/adjuvant treatment, surgery, and any treatment. Median survival (OS) decreased with age (< 70 years: 23 months; 70-74: 19 months; 75-79: 13 months; ≥ 80 years: 10 months). In MVA, older age, smoking, later stage, and higher grade were significantly associated with a higher risk of death. Patients receiving neo/adjuvant treatment had lower risk of death than any other treatment group regardless of age. CONCLUSION Older patients were less likely to receive treatment for LAEC than younger patients. Patients aged ≥ 70 years benefit from neo/adjuvant treatment. Prospective clinical trials focusing on older patients and incorporating life expectancy, comorbidities, and geriatric assessment are needed to guide treatment.
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Affiliation(s)
- Petra Martin
- University Hospital Waterford, Waterford, Ireland. .,Midland Regional Hospital Tullamore, Tullamore, Ireland. .,St. James's Hospital, Dublin, Ireland.
| | | | - Sandra Deady
- National Cancer Registry Ireland (NCRI), Cork, Ireland
| | - Anne Horgan
- University Hospital Waterford, Waterford, Ireland
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Arora SP, Liposits G, Caird S, Dunne RF, Moffat GT, Okonji D, Rodriquenz MG, Dua D, Dotan E. Hepatocellular carcinoma in older adults: A comprehensive review by Young International Society of Geriatric Oncology. J Geriatr Oncol 2019; 11:557-565. [PMID: 31704038 DOI: 10.1016/j.jgo.2019.10.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 09/12/2019] [Accepted: 10/03/2019] [Indexed: 02/08/2023]
Abstract
Given the prevalence and the rising incidence of hepatocellular carcinoma (HCC) in older adults worldwide, there is an urgent need to improve our understanding of the implications of treatment modalities in this population. The care of older patients with HCC is challenging due to the lack of evidence-based recommendations in this population. The current treatment approach for older patients relies on extrapolation of data from clinical trials conducted mostly in younger patients or fit older adults. Further, in the last few years, the arsenal of systemic treatments has increased with currently seven FDA-approved therapies available for patients with advanced HCC. Therefore, understanding how to apply current data to this unique and diverse patient population is necessary. This review will aim to shed light on the approach to older adults with HCC through an assessment of available data in the literature.
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Affiliation(s)
- Sukeshi Patel Arora
- Mays Cancer Center, University of Texas Health San Antonio, Leader in Gastrointestinal Malignancies, 7979 Wurzbach Rd, 78229 San Antonio, TX, USA.
| | | | - Susan Caird
- Gold Coast University Hospital, Southport, Australia, Griffith University, School of Medicine, Australia
| | - Richard F Dunne
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA
| | | | - David Okonji
- Wellington Blood and Cancer Centre, Wellington Regional Hospital, Wellington, New Zealand
| | | | | | - Efrat Dotan
- Fox Chase Cancer Center, Philadelphia, PA, USA
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38
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Sheikh AR, Hsu T, Subbiah IM, Arora SP. Perspectives on Geriatric Oncology Research presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting. J Geriatr Oncol 2019; 10:998-1002. [PMID: 31326394 DOI: 10.1016/j.jgo.2019.07.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Accepted: 07/09/2019] [Indexed: 10/26/2022]
Affiliation(s)
- Ayesha R Sheikh
- Solomont Center for Hematology & Medical Oncology, Boston University Medical Center, FGH building, 1st floor, 820 Harrison Avenue, Boston, MA 02118, United States.
| | - Tina Hsu
- The Ottawa Hospital Cancer Center, University of Ottawa, ON, Canada
| | - Ishwaria M Subbiah
- The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Sukeshi Patel Arora
- Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, United States
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DuMontier C, Sedrak MS, Soo WK, Kenis C, Williams GR, Haase K, Harneshaug M, Mian H, Loh KP, Rostoft S, Dale W, Cohen HJ. Arti Hurria and the progress in integrating the geriatric assessment into oncology: Young International Society of Geriatric Oncology review paper. J Geriatr Oncol 2019; 11:203-211. [PMID: 31451439 DOI: 10.1016/j.jgo.2019.08.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 07/11/2019] [Accepted: 08/13/2019] [Indexed: 12/18/2022]
Abstract
Until recently, the progress in the diagnosis and management of cancer has not been matched by similar progress in the assessment of the increasing numbers of older and more complex patients with cancer. Dr. Arti Hurria identified this gap at the outset of her career, which she dedicated toward studying the geriatric assessment (GA) as an improvement over traditional methods used in oncology to assess vulnerability in older patients with cancer. This review documents the progress of the GA and its integration into oncology. First, we detail the GA's origins in the field of geriatrics. Next, we chronicle the early rise of geriatric oncology, highlighting the calls of early thought-leaders to meet the demands of the rapidly aging cancer population. We describe Dr. Hurria's early efforts toward meeting these calls though the implementation of the GA in oncology research. We then summarize some of the seminal studies constituting the evidence base supporting GA's implementation. Finally, we lay out the evolution of cancer-focused guidelines recommending the GA, concluding with future needs to advance the next steps toward more widespread implementation in routine cancer care. Throughout, we describe Dr. Hurria's vision and its execution in driving progress of the GA in oncology, from her fellowship training to her co-authored guidelines recommending GA for all older adults with cancer-published in the year of her untimely death.
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Affiliation(s)
- Clark DuMontier
- Brigham and Women's Hospital, Marcus Institute for Aging Research, Harvard Medical School, Boston, MA, United States of America.
| | - Mina S Sedrak
- City of Hope Comprehensive Cancer Center, Duarte, CA, United States of America
| | - Wee Kheng Soo
- Eastern Health Clinical School, Monash University, 5 Arnold St, Box Hill, VIC, Australia; Department of Aged Medicine, Eastern Health, 8 Arnold St, Box Hill, VIC, Australia; Department of Cancer Services, Eastern Health, 8 Arnold St, Box Hill, VIC, Australia
| | - Cindy Kenis
- Department of General Medical Oncology and Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Grant R Williams
- Division of Hematology/Oncology, Geriatrics, and Palliative Care, Institute of Cancer Outcomes and Survivorship, O'Neal Comprehensive Cancer Center at UAB, University of Alabama at Birmingham, UK
| | - Kristen Haase
- College of Nursing, University of Saskatchewan, 104 Clinic Place, Saskatoon, Canada
| | - Magnus Harneshaug
- The Research Centre for Age Related Functional Decline and Diseases, Innlandet Hospital Trust, P.O. box 68, 2313 Ottestad, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, P.O. box 4956, Nydalen, 0424 Oslo, Norway
| | - Hira Mian
- Juravinski Cancer Center, Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Kah Poh Loh
- James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA
| | - Siri Rostoft
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
| | - William Dale
- City of Hope Comprehensive Cancer Center, Duarte, CA, United States of America
| | - Harvey Jay Cohen
- Center for the Study of Aging and Human Development, Duke University, Durham, NC, United States of America
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Noronha V, Simha V, Patil V, Joshi A, Prabhash K. Role of palliative chemotherapy and targeted therapy in advanced esophageal and gastroesophageal junction cancers. CANCER RESEARCH, STATISTICS, AND TREATMENT 2019. [DOI: 10.4103/crst.crst_10_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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