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Wang W, Zhao R, Liang X, Liu M, Bai H, Ge J, Yao B, Zhi Z, He J. Efficacies of radiotherapy in rectal cancer patients treated with total mesorectal excision or other types of surgery: an updated meta-analysis. Oncol Rev 2025; 19:1567818. [PMID: 40376112 PMCID: PMC12078337 DOI: 10.3389/or.2025.1567818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 03/18/2025] [Indexed: 05/18/2025] Open
Abstract
Background An updated meta-analysis was conducted to evaluate the efficacy of radiotherapy in rectal cancer patients treated with total mesorectal excision (TME) or other types of surgery (non-TME-only). Methods The PubMed, Cochrane Library, and CNKI databases were searched. Data on overall survival (OS) were extracted. Results Hazard ratios (HRs) for OS associated with preoperative radiotherapy, preoperative long-course concurrent chemoradiotherapy (LCCRT), preoperative radiotherapy alone, and postoperative radiotherapy in patients treated with TME were 1.02 [95% CI: 0.92-1.14, P = 0.65], 1.04 [95% CI: 0.93-1.16, P = 0.47], 0.87 [95% CI: 0.61-1.25, P = 0.46], and 1.18 [95% CI: 0.91-1.52, P = 0.20], respectively. HRs for OS associated with preoperative radiotherapy, preoperative LCCRT, preoperative radiotherapy alone, preoperative long-course RT (LCRT), and preoperative short-course radiotherapy (SCRT) in patients treated with non-TME-only surgery were 0.85 [95% CI: 0.79-0.90, P < 0.00001], 0.77 [95% CI: 0.63-0.94, P = 0.009], 0.86 [95% CI: 0.80-0.92, P < 0.0001], 0.83 [95% CI: 0.73-0.95, P = 0.005], and 0.84 [95% CI: 0.77-0.91, P= <0.0001], respectively. The HR for postoperative radiotherapy in patients treated with non-TME-only surgery was 1.08 [95% CI: 0.84-1.39, P = 0.57]. Conclusion Preoperative radiotherapy, regardless of the regimen, improves the OS in patients treated with non-TME-only surgery, but not in those treated with TME. Postoperative radiotherapy does not improve OS. Advances in knowledge This meta-analysis will serve as a reference for decision-making in multidisciplinary approaches for rectal cancer patients.
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Affiliation(s)
- Wenshu Wang
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Runyuan Zhao
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xi Liang
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Manjun Liu
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Haiyan Bai
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Jianli Ge
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Binxi Yao
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Zheng Zhi
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
| | - Jianming He
- Department of Radiotherapy, Hebei Province Hospital of Chinese Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China
- Key Laboratory of Integrated Chinese and Western Medicine for Gastroenterology Research (Hebei), Shijiazhuang, China
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Valentini V, Alfieri S, Coco C, D'Ugo D, Crucitti A, Pacelli F, Persiani R, Sofo L, Picciocchi A, Doglietto GB, Barbaro B, Vecchio FM, Ricci R, Damiani A, Savino MC, Boldrini L, Cellini F, Meldolesi E, Romano A, Chiloiro G, Gambacorta MA. Four steps in the evolution of rectal cancer managements through 40 years of clinical practice: Pioneering, standardization, challenges and personalization. Radiother Oncol 2024; 194:110190. [PMID: 38438019 DOI: 10.1016/j.radonc.2024.110190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 02/26/2024] [Indexed: 03/06/2024]
Affiliation(s)
- Vincenzo Valentini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Sergio Alfieri
- Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Claudio Coco
- U.O.C. Chirurgia Generale 2, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Domenico D'Ugo
- Unità di chirurgia generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | | | - Fabio Pacelli
- Unità chirurgica del peritoneo e del retroperitoneo, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Roberto Persiani
- Unità di chirurgia generale, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Luigi Sofo
- Divisione di Chirurgia Addominale, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Aurelio Picciocchi
- Dipartimento di Chirurgia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giovanni Battista Doglietto
- Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Brunella Barbaro
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Fabio Maria Vecchio
- Dipartimento di Patologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Riccardo Ricci
- Dipartimento di Patologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Andrea Damiani
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maria Chiara Savino
- Gemelli Generator Real World Data Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Luca Boldrini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Cellini
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Elisa Meldolesi
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Angela Romano
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Giuditta Chiloiro
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
| | - Maria Antonietta Gambacorta
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Temmink SJD, Peeters KCMJ, Nilsson PJ, Martling A, van de Velde CJH. Surgical Outcomes after Radiotherapy in Rectal Cancer. Cancers (Basel) 2024; 16:1539. [PMID: 38672621 PMCID: PMC11048284 DOI: 10.3390/cancers16081539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/12/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.
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Affiliation(s)
- Sofieke J. D. Temmink
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
| | - Koen C. M. J. Peeters
- Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Per J. Nilsson
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
| | - Anna Martling
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
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Simillis C, Khatri A, Dai N, Afxentiou T, Jephcott C, Smith S, Jadon R, Papamichael D, Khan J, Powar MP, Fearnhead NS, Wheeler J, Davies J. A systematic review and network meta-analysis of randomised controlled trials comparing neoadjuvant treatment strategies for stage II and III rectal cancer. Crit Rev Oncol Hematol 2023; 183:103927. [PMID: 36706968 DOI: 10.1016/j.critrevonc.2023.103927] [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: 12/15/2022] [Revised: 01/08/2023] [Accepted: 01/23/2023] [Indexed: 01/27/2023] Open
Abstract
AIM Multiple neoadjuvant therapy strategies have been used and compared for rectal cancer and there has been no true consensus as to the optimal neoadjuvant therapy regimen. The aim is to identify and compare the neoadjuvant therapies available for stage II and III rectal cancer. DESIGN A systematic literature review was performed, from inception to August 2022, of the following databases: MEDLINE, EMBASE, Science Citation Index Expanded, Cochrane Library. Only randomized controlled trials comparing neoadjuvant therapies for stage II and III rectal cancer were considered. Stata was used to draw network plots, and a Bayesian network meta-analysis was conducted through models utilizing the Markov Chain Monte Carlo method in WinBUGS. RESULTS A total of 58 articles were included based on 41 randomised controlled trials, reporting on 12,404 participants that underwent 15 neoadjuvant treatment regimens. No significant difference was identified between treatments for major or total postoperative complications, anastomotic leak rates, or sphincter-saving surgery. Straight to surgery (STS) ranked as best treatment for preoperative toxicity but ranked worst treatment for positive resection margins and complete response. STS had significantly increased positive resection margins compared to long-course chemoradiotherapy with short-wait (LCCRT-SW) or long-wait (LCCRT-LW) to surgery, or short-course radiotherapy with short-wait (SCRT-SW) or immediate surgery (SCRT-IS). LCCRT-SW or LCCRT-LW resulted in significantly increased complete response rates compared to STS. LCCRT-LW significantly improved 2-year overall survival compared to STS, SCRT-IS, SCRT-SW. Total neoadjuvant therapy regimes with short-course radiotherapy followed by consolidation chemotherapy (SCRT-CT-SW), induction chemotherapy followed by long-course chemoradiotherapy (CT-LCCRT-S), long-course chemoradiotherapy followed by consolidation chemotherapy (LCCRT-CT-S), significantly improved positive resection margins, complete response, and disease-free survival compared to STS. Chemotherapy with monoclonal antibodies followed by long-course chemoradiotherapy (CT+MAB-LCCRT+MAB-S) significantly improved complete response and positive resection margins compared to STS, and 2-year disease-free survival compared to STS, SCRT-IS, SCRT-SW, SCRT-CT-SW, LCCRT-SW, LCCRT-LW. CT+MAB-LCCRT+MAB-S ranked as best treatment for disease-free survival and overall survival. CONCLUSIONS Conventional neoadjuvant therapies with short-course radiation or long-course chemoradiotherapy have oncological benefits compared to no neoadjuvant therapy without increasing perioperative complication rates. Prolonged wait to surgery may improve oncological outcomes. Total neoadjuvant therapies provide additional benefits in terms of complete response, positive resection margins, and disease-free survival. Monoclonal antibody therapy may further improve oncological outcomes but currently is only applicable to a small subgroup of patients and requires further validation.
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Affiliation(s)
- Constantinos Simillis
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK.
| | - Amulya Khatri
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nick Dai
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Thalia Afxentiou
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Catherine Jephcott
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Sarah Smith
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Rashmi Jadon
- Department of Oncology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | | | - Jim Khan
- Department of Colorectal Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Michael P Powar
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Nicola S Fearnhead
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - James Wheeler
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Justin Davies
- Cambridge Colorectal Unit, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Department of Surgery, University of Cambridge, Cambridge, UK
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Shulman RM, Meyer JE. Current Trends in the Treatment of Locally Advanced Rectal Cancer: Where We Are and How We Got Here. CURRENT COLORECTAL CANCER REPORTS 2021. [DOI: 10.1007/s11888-021-00471-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
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Pach R, Sierzega M, Szczepanik A, Popiela T, Richter P. Preoperative radiotherapy 5 × 5 Gy and short versus long interval between surgery for resectable rectal cancer: 10-Year follow-up of the randomised controlled trial. Radiother Oncol 2021; 164:268-274. [PMID: 34653526 DOI: 10.1016/j.radonc.2021.10.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 10/06/2021] [Accepted: 10/07/2021] [Indexed: 01/04/2023]
Abstract
BACKGROUND Studies on short-course preoperative radiotherapy in combination with total mesorectal excision for rectal cancer reported improved local control without clear survival benefits. The optimal fractionation and interval between radiotherapy and surgery are still under debate. We, therefore, aimed to report 10-year results of a randomized clinical trial (RCT, NCT01444495) comparing different time intervals between irradiation and surgery for rectal cancer. MATERIAL AND METHODS Data from the RCT conducted at a single academic centre were reviewed based on regular control visits with the median follow-up of 12 years. Patients with rectal cancer were randomly assigned to short-course preoperative radiotherapy (5 × 5 Gy) followed by surgery 7-10 days (short interval) or 4-5 weeks (long interval) after the end of irradiation. The primary endpoint was the local recurrence rate at 5 years. The secondary endpoints included overall survival, disease-free survival, systemic recurrence rate, and downstaging. RESULTS A total of 154 patients were randomly assigned to short (n = 77) or long interval (n = 77) surgery. The cumulative incidence of local recurrence at 10 years was 1.3% and 11.7% in the short and long-interval groups, respectively (p = 0.031). Accordingly, the incidence of systemic relapse was 14.3% versus 9.1% (p = 0.0319). There were no differences in the overall 10-year survival between patients subject to short and long-interval surgery (58% vs 61%, p = 0.754). However, patients with downstaging after radiotherapy had significantly better 10-year survival rates than non-responders. CONCLUSIONS Short-course preoperative radiotherapy with delayed surgery demonstrated an increased risk of local relapse over a 10-year follow-up.
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Affiliation(s)
- Radoslaw Pach
- First Department of Surgery, Jagiellonian University Medical College, Krakow, Poland.
| | - Marek Sierzega
- First Department of Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Antoni Szczepanik
- First Department of Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Tadeusz Popiela
- First Department of Surgery, Jagiellonian University Medical College, Krakow, Poland
| | - Piotr Richter
- First Department of Surgery, Jagiellonian University Medical College, Krakow, Poland
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Li WC, Zhao JK, Feng WQ, Miao YM, Xu ZF, Xu ZQ, Gao H, Sun J, Zheng MH, Zong YP, Lu AG. Retrospective research of neoadjuvant therapy on tumor-downstaging, post-operative complications, and prognosis in locally advanced rectal cancer. World J Gastrointest Surg 2021; 13:267-278. [PMID: 33796215 PMCID: PMC7992997 DOI: 10.4240/wjgs.v13.i3.267] [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: 10/09/2020] [Revised: 12/13/2020] [Accepted: 01/15/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neoadjuvant therapy (NAT) is becoming increasingly important in locally advanced rectal cancer. Hence, such research has become a problem. AIM To evaluate the downstaging effect of NAT, its impact on postoperative complications and its prognosis with different medical regimens. METHODS Seventy-seven cases from Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine were retrospectively collected and divided into the neoadjuvant radiochemotherapy (NRCT) group and the neoadjuvant chemotherapy (NCT) group. The differences between the two groups in tumor regression, postoperative complications, rectal function, disease-free survival, and overall survival were compared using the χ 2 test and Kaplan-Meier analysis. RESULTS Baseline data showed no statistical differences between the two groups, whereas the NRCT group had a higher rate of T4 (30/55 vs 5/22, P < 0.05) than the NCT groups. Twelve cases were evaluated as complete responders, and 15 cases were evaluated as tumor regression grade 0. Except for the reduction rate of T stage (NRCT 37/55 vs NCT 9/22, P < 0.05), there was no difference in effectiveness between the two groups. Preoperative radiation was not a risk factor for poor reaction or anastomotic leakage. No significant difference in postoperative complications and disease-free survival between the two groups was observed, although the NRCT group might have better long-term overall survival. CONCLUSION NAT can cause tumor downstaging preoperatively or even complete remission of the primary tumor. Radiochemotherapy could lead to better T downstaging and promising overall survival without more complications.
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Affiliation(s)
- Wen-Chang Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Jing-Kun Zhao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Wen-Qing Feng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Yi-Ming Miao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Zi-Feng Xu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Zhuo-Qing Xu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Han Gao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Jing Sun
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Min-Hua Zheng
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Ya-Ping Zong
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Ai-Guo Lu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
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Flanagan M, Clancy C, Sorensen J, Thompson L, Kranenbarg EMK, van de Velde CJH, Sebag-Montefiore D, Burke J. Neoadjuvant Short-Course Radiotherapy for Upper Third Rectal Tumors: Systematic Review and Individual Patient Data Metaanalysis of Randomized Controlled Trials. Ann Surg Oncol 2021; 28:5238-5249. [PMID: 33712984 DOI: 10.1245/s10434-021-09795-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 01/30/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND There is no consensus on the use of neoadjuvant radiotherapy for tumors of the upper third of the rectum. Due to conflicting findings in high-quality trials and significant long-term side effects associated with neoadjuvant radiotherapy, the benefit of neoadjuvant radiotherapy for upper third rectal tumors is less certain than for lower two third rectal tumors. This metaanalysis compares oncological outcomes with neoadjuvant radiotherapy and surgery versus surgery alone for upper third rectal tumors. PATIENTS AND METHODS PubMed, Embase, and the Cochrane library databases were searched. Randomized controlled trials (RCT) comparing neoadjuvant radiotherapy and surgery versus surgery alone for resectable rectal cancer were included. Individual patient data were sought from the principal investigator of each eligible trial for comparative data on patients with upper third rectal tumors. The main outcomes measured were survival outcomes, oncological outcomes, postoperative morbidity, and late toxicity. RESULTS Individual patient data from two RCTs examining outcomes in 758 patients were obtained. Published data from one further RCT containing comparable data on upper third rectal tumors were included in analysis of local recurrence. In patients with curative surgery, there was no significant reduction in local recurrence or significant improvement in overall survival or disease-free survival with neoadjuvant radiotherapy (LR RR: 0.38, 95% CI 0.14-1.04, p = 0.06) (OS RR: 1.10, 95% CI 0.98-1.24, p = 0.11) (DFS RR: 1.11, 95% CI 0.97-1.26, p = 0.13). CONCLUSIONS The benefit of neoadjuvant radiotherapy for upper third rectal tumors is not certain, and surgery alone for patients with potentially curative disease at preoperative staging may be sufficient.
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Affiliation(s)
- Michael Flanagan
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - Cillian Clancy
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland
| | - Jan Sorensen
- Healthcare Outcomes Research Centre, Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland
| | | | | | | | | | - John Burke
- Department of Colorectal Surgery, Beaumont Hospital, Dublin 9, Ireland.
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Glynne-Jones R, Hall M, Nagtegaal ID. The optimal timing for the interval to surgery after short course preoperative radiotherapy (5 ×5 Gy) in rectal cancer - are we too eager for surgery? Cancer Treat Rev 2020; 90:102104. [PMID: 33002819 DOI: 10.1016/j.ctrv.2020.102104] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 09/04/2020] [Accepted: 09/06/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND The improved overall survival (OS) after short course preoperative radiotherapy (SCPRT) using 5 × 5 Gy reported in the early rectal cancer trials could not be replicated in subsequent phase III trials. This original survival advantage is attributed to poor quality of surgery and the large differential in local recurrence rates, with and without SCPRT. Immuno-modulation during and after SCPRT and its clinical implications have been poorly investigated. We propose an alternative explanation for this survival benefit in terms of immunological mechanisms induced by SCPRT and the timing of surgery, which may validate the concept of consolidation chemotherapy. MATERIAL AND METHODS We reviewed randomized controlled trials (RCTs) and studies of SCPRT from 1985 to 2019. We aimed to examine the precise timing of surgery in days following SCPRT and identify evidence for immune modulation, neo-antigens and memory cell induction by radiation. RESULTS Considerable variability is reported in randomised trials for median overall treatment time (OTT) from start of SCPRT to surgery (8-14 days). Only three early trials showed a benefit in terms of OS from SCPRT, although the level of benefit in preventing local recurrence was consistent across all trials. Different patterns of immune effects are observed within days after SCPRT depending on the OTT, but human leukocyte antigen (HLA)-1 expression was not upregulated. CONCLUSIONS SCPRT has a substantial immune-stimulatory potential. The importance of the timing of surgery after SCPRT may have been underestimated. An optimal interval for surgery after 5 × 5 Gy may lead to better outcomes, which is possibly exploited in total neoadjuvant therapy schedules using consolidation chemotherapy. Individual patient meta-analyses from appropriate SCPRT trials examining outcomes for each day and prospective trials are needed to clarify the validity of this hypothesis. The interaction of SCPRT with tumour adaptive immunology, in particular the kinetics and timing, should be examined further.
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Affiliation(s)
- R Glynne-Jones
- Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood HA6 2RN, United Kingdom.
| | - M Hall
- Department of Medical Oncology, Mount Vernon Centre for Cancer Treatment, Mount Vernon Hospital, Northwood HA6 2RN, United Kingdom
| | - I D Nagtegaal
- Department of Pathology, Radboudumc, PO BOX 9101, 6500 HB Nijmegen, the Netherlands
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Zhong W, Xue X, Dai L, Li R, Nie K, Zhou S. Neoadjuvant treatments for resectable rectal cancer: A network meta-analysis. Exp Ther Med 2020; 19:2604-2614. [PMID: 32256740 PMCID: PMC7086160 DOI: 10.3892/etm.2020.8494] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 11/06/2019] [Indexed: 12/18/2022] Open
Abstract
Different neoadjuvant therapy regimens are available for rectal cancer, but the relative effects are controversial. The aim of the present network meta-analysis (NMA) was to estimate the relative efficacy and safety of neoadjuvant therapies for resectable rectal cancer. MEDLINE, EMBASE and Cochrane Central Registry of Controlled Trials were searched for publications dated from 1946 up to June 2018. The present study included randomized clinical trials that compared treatments for resected rectal cancer: Surgery alone, surgery preceded by neoadjuvant radiotherapy (RT), neoadjuvant chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT). Direct pairwise comparisons and NMA were conducted. A total of 23 randomized controlled trials were included in the present study. RT had an overall survival (OS) benefit when compared with surgery alone [HR (hazard ratio), 0.89; 95% confidence interval (CI), 0.82-0.97; quality of evidence, high]. All three neoadjuvant regimens were associated with lower local recurrence (LR) when compared with surgery alone [RT: odds ratio (OR), 0.44; 95% CI, 0.35-0.65; quality of evidence, high; CRT: OR, 0.34; 95% CI, 0.23-0.56; quality of evidence, low and CT: OR, 0.32; 95% CI, 0.11-1.00; quality of evidence, low]. There were no significant differences in OS and LR between CRT and RT (OS: OR, 1.10); 95% CI, 0.93-1.20; LR: OR, 0.81; 95% CI, 0.61-1.10). Ranking probabilities indicated that CRT was the best strategy for local control, with a surface under the cumulative ranking curve (SUCRA) of 78.78%. Patients treated with RT had improved disease-free survival compared with those treated with surgery alone (HR, 0.82; 95% CI, 0.64-1.00; quality of evidence, low). Neoadjuvant RT or CRT did not significantly improve distant metastases compared with surgery alone (RT: OR, 0.87; 95% CI, 0.69-1.10 and CRT: OR, 0.75; 95% CI, 0.47-1.10). CRT had an improved pathological complete response rate compared with RT (OR, 4.90; 95% CI, 21.80-17.00; quality of evidence, low). No significant difference for the risk of anastomotic leak between each treatment was observed in the NMA. In conclusion, RT decreased the LR and improved OS compared with surgery alone for resected rectal cancer. CRT was the best neoadjuvant therapy analyzed and CT was likely the second best for all outcomes based on SUCRA. However, these findings were limited by overall low quality of evidence.
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Affiliation(s)
- Wei Zhong
- Department of General Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China
| | - Xiaojun Xue
- Department of General Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China
| | - Lianzhi Dai
- Medical Affairs Department, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China
| | - Ranran Li
- Department of General Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China
| | - Kai Nie
- Department of General Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China
| | - Song Zhou
- Department of General Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, Fujian 363000, P.R. China
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12
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Abraha I, Aristei C, Palumbo I, Lupattelli M, Trastulli S, Cirocchi R, De Florio R, Valentini V, Cochrane Colorectal Cancer Group. Preoperative radiotherapy and curative surgery for the management of localised rectal carcinoma. Cochrane Database Syst Rev 2018; 10:CD002102. [PMID: 30284239 PMCID: PMC6517113 DOI: 10.1002/14651858.cd002102.pub3] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND This is an update of the original review published in 2007.Carcinoma of the rectum is a common malignancy, especially in high income countries. Local recurrence may occur after surgery alone. Preoperative radiotherapy (PRT) has the potential to reduce the risk of local recurrence and improve outcomes in rectal cancer. OBJECTIVES To determine the effect of preoperative radiotherapy for people with localised resectable rectal cancer compared to surgery alone. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library; Issue 5, 2018) (4 June 2018), MEDLINE (Ovid) (1950 to 4 June 2018), and Embase (Ovid) (1974 to 4 June 2018). We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant ongoing trials (4 June 2018). SELECTION CRITERIA We included randomised controlled trials comparing PRT and surgery with surgery alone for people with localised advanced rectal cancer planned for radical surgery. We excluded trials that did not use contemporary radiotherapy techniques (with more than two fields to the pelvis). DATA COLLECTION AND ANALYSIS Two review authors independently assessed the 'Risk of bias' domains for each included trial, and extracted data. For time-to-event data, we calculated the Peto odds ratio (Peto OR) and variances, and for dichotomous data we calculated risk ratios (RR) using the random-effects method. Potential sources of heterogeneity hypothesised a priori included study quality, staging, and the use of total mesorectal excision (TME) surgery. MAIN RESULTS We included four trials with a total of 4663 participants. All four trials reported short PRT courses, with three trials using 25 Gy in five fractions, and one trial using 20 Gy in four fractions. Only one study specifically required TME surgery for inclusion, whereas in another study 90% of participants received TME surgery.Preoperative radiotherapy probably reduces overall mortality at 4 to 12 years' follow-up (4 trials, 4663 participants; Peto OR 0.90, 95% CI 0.83 to 0.98; moderate-quality evidence). For every 1000 people who undergo surgery alone, 454 would die compared with 45 fewer (the true effect may lie between 77 fewer to 9 fewer) in the PRT group. There was some evidence from subgroup analyses that in trials using TME no or little effect of PRT on survival (P = 0.03 for the difference between subgroups).Preoperative radiotherapy may have little or no effect in reducing cause-specific mortality for rectal cancer (2 trials, 2145 participants; Peto OR 0.89, 95% CI 0.77 to 1.03; low-quality evidence).We found moderate-quality evidence that PRT reduces local recurrence (4 trials, 4663 participants; Peto OR 0.48, 95% CI 0.40 to 0.57). In absolute terms, 161 out of 1000 patients receiving surgery alone would experience local recurrence compared with 83 fewer with PRT. The results were consistent in TME and non-TME studies.There may be little or no difference in curative resection (4 trials, 4673 participants; RR 1.00, 95% CI 0.97 to 1.02; low-quality evidence) or in the need for sphincter-sparing surgery (3 trials, 4379 participants; RR 0.99, 95% CI 0.94 to 1.04; I2 = 0%; low-quality evidence) between PRT and surgery alone.Low-quality evidence suggests that PRT may increase the risk of sepsis from 13% to 16% (2 trials, 2698 participants; RR 1.25, 95% CI 1.04 to 1.52) and surgical complications from 25% to 30% (2 trials, 2698 participants; RR 1.20, 95% CI 1.01 to 1.42) compared to surgery alone.Two trials evaluated quality of life using different scales. Both studies concluded that sexual dysfunction occurred more in the PRT group. Mixed results were found for faecal incontinence, and irradiated participants tended to resume work later than non-irradiated participants between 6 and 12 months, but this effect had attenuated after 18 months (low-quality evidence). AUTHORS' CONCLUSIONS We found moderate-quality evidence that PRT reduces overall mortality. Subgroup analysis did not confirm this effect in people undergoing TME surgery. We found consistent evidence that PRT reduces local recurrence. Risk of sepsis and postsurgical complications may be higher with PRT.The main limitation of the findings of the present review concerns their applicability. The included trials only assessed short-course radiotherapy and did not use chemotherapy, which is widely used in the contemporary management of rectal cancer disease. The differences between the trials regarding the criteria used to define rectal cancer, staging, radiotherapy delivered, the time between radiotherapy and surgery, and the use of adjuvant or postoperative therapy did not appear to influence the size of effect across the studies.Future trials should focus on identifying participants that are most likely to benefit from PRT especially in terms of improving local control, sphincter preservation, and overall survival while reducing acute and late toxicities (especially rectal and sexual function), as well as determining the effect of radiotherapy when chemotherapy is used and the optimal timing of surgery following radiotherapy.
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Affiliation(s)
- Iosief Abraha
- Regional Health Authority of UmbriaHealth Planning ServicePerugiaItaly06124
| | - Cynthia Aristei
- University of Perugia and Perugia General HospitalRadiation Oncology Section, Department of Surgical and Biomedical SciencePerugiaItaly
| | - Isabella Palumbo
- University of Perugia and Perugia General HospitalRadiation Oncology Section, Department of Surgical and Biomedical SciencePerugiaItaly
| | | | | | | | - Rita De Florio
- Local Health Unit of PerugiaGeneral MedicineAzienda SanitariaLocale USL 1, Medicina GeneralePerugiaItaly
| | - Vincenzo Valentini
- Fondazione Policlinico Universitario A.Gemelli IRCCSRadiation Oncology DepartmentRomeItaly
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13
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Agas RAF, Co LBA, Jacinto JCKM, Yu KKL, Sogono PG, Bacorro WR, Sy Ortin TT. Neoadjuvant Radiotherapy Versus No Radiotherapy for Stage IV Rectal Cancer: a Systematic Review and Meta-analysis. J Gastrointest Cancer 2018; 49:389-401. [DOI: 10.1007/s12029-018-0141-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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14
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Abstract
Since the first reports in the late 1950's, a large amount of data have been collected. The analysis of the main evidence from the major randomized trials will be analyzed in this paper according to preoperative, postoperative and chemoradiation approaches. Fifteen randomized preoperative trials were reported; they have been grouped according to the fractionation schedule. In the hypofractionation group (5 Gy for fraction), all five studies that delivered 3-5 doses in one week had a significant improvement in local control and one of them also showed improvement in survival. Operative mortality was higher in the radiotherapy arm if inadequate techniques had been applied. In 3 out of 8 studies with conventional fractionation there was a significant improvement in local control, but no impact in survival was detected. No studies with total dose lower than 34 Gy had an improvement in local control. None of the six randomized postoperative studies showed an improvement in local control or survival. In all trials the local control rate was uniform; ranging from 76% to 84%. Toxicity was higher in the radiotherapy arm. One preoperative and five postoperative randomized studies that used chemoradiation were analyzed. One postoperative chemoradiation study showed a significant improvement in survival in comparison to the surgery arm, and another showed the same advantage compared to the postoperative arm. Protracted infusional administration of 5FU concomitant to radiotherapy showed better survival than bolus administration. No advantages were shown in using MeCCNU or Levamisole in two studies. Toxicity was high and related to the dose and the modality of administration of the drugs in order to adequately treat the different stages of rectal cancer, patients must be carefully selected in order to prescribe the most effective and the least toxic treatment for the individual stage; organ preservation should be an essential goal for its impact on quality of life, and the cost estimates should be taken into account.
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Affiliation(s)
- V Valentini
- Cattedra di Radioterapia, Università Cattolica S. Cuore, Rome, Italy.
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15
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Jacobs L, van der Vlies E, Ten Bokkel Huinink D, Bloemendal H, Intven M, Smits AB, Weusten BLAM, Siersema PD, van Lelyveld N, Los M. Tolerability, Safety, and Outcomes of Neoadjuvant Chemoradiotherapy With Capecitabine for Patients Aged ≥ 70 Years With Locally Advanced Rectal Cancer. Clin Colorectal Cancer 2018; 17:179-186. [PMID: 29661620 DOI: 10.1016/j.clcc.2018.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 02/17/2018] [Accepted: 03/05/2018] [Indexed: 12/12/2022]
Abstract
INTRODUCTION In studies of colorectal cancer, the elderly have been frequently underrepresented because comorbid conditions and functional status often lead to study exclusion. For elderly patients with an indication for neoadjuvant chemoradiotherapy (nCRT), physicians usually decide using clinical factors whether nCRT should be offered. The aim of the present retrospective study was to assess the tolerability of nCRT with capecitabine and the surgical outcomes in patients aged ≥ 70 years with locally advanced rectal cancer. PATIENTS AND METHODS Data from 1372 rectal cancer patients diagnosed from 2002 to 2012 at 4 Dutch hospitals were used. Patients aged ≥ 70 years were included if they had received nCRT, and their data were analyzed for treatment deviations, postoperative complications, mortality, disease-free survival (DFS), and overall survival (OS). The data were stratified into 3 age groups (ie, 70-74, 75-79, and ≥ 80 years). RESULTS We identified 447 patients aged ≥ 70 years. Of these patients, 42 had received nCRT, and 37 (88%) had completed nCRT. Radiation dermatitis, fatigue, and diarrhea were reported in 62%, 57%, and 43% of the 42 patients, respectively. Of the 42 patients, 40 (95%) underwent surgery, 1 patient refused resection, and 1 patient died during nCRT of severe mucositis due to dihydropyrimidine dehydrogenase deficiency. The postoperative complication rate was 30%, and the 30-day mortality rate was 0%. A pathologic complete response was found in 7.5%. The 2- and 5-year DFS and OS rates were 58.5% and 40.7% and 81.0% and 58.2%, respectively. CONCLUSION The results of the present multicenter study have shown that if selected on clinical factors, nCRT with capecitabine is safe and well tolerated in elderly patients. No negative effect on surgical outcome was measured, and the beneficial effect (pathologic complete response, DFS, and OS) seemed comparable to that for younger age groups. We believe that elderly patients should not be excluded from nCRT on the basis of age only.
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Affiliation(s)
- Lotte Jacobs
- Department of Gastroenterology and Hepatology, St Antonius Hospital Nieuwegein, Nieuwegein, Netherlands.
| | - Ellen van der Vlies
- Department of Internal Medicine/Oncology, St Antonius Hospital Nieuwegein, Nieuwegein, Netherlands
| | | | - Haiko Bloemendal
- Department of Internal Medicine/Oncology, Meander Medical Center Amersfoort, Amersfoort, Netherlands
| | - Martijn Intven
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, Netherlands
| | - Anke B Smits
- Department of Surgery, St Antonius Hospital Nieuwegein, Nieuwegein, Netherlands
| | - Bas L A M Weusten
- Department of Gastroenterology and Hepatology, St Antonius Hospital Nieuwegein, Nieuwegein, Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Nijmegen, Netherlands
| | - Niels van Lelyveld
- Department of Gastroenterology and Hepatology, St Antonius Hospital Nieuwegein, Nieuwegein, Netherlands
| | - Maartje Los
- Department of Internal Medicine/Oncology, St Antonius Hospital Nieuwegein, Nieuwegein, Netherlands
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16
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Gural Z, Saglam S, Yucel S, Kaytan-Saglam E, Asoglu O, Ordu C, Acun H, Sharifov R, Onder S, Kizir A, Oral EN. Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study. World J Gastrointest Oncol 2018; 10:40-47. [PMID: 29375747 PMCID: PMC5767792 DOI: 10.4251/wjgo.v10.i1.40] [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: 09/04/2017] [Revised: 11/26/2017] [Accepted: 12/04/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer. METHODS A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS In the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively. CONCLUSION Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.
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Affiliation(s)
- Zeynep Gural
- Department of Radiation Oncology, Acibadem University Medical Faculty, Istanbul 34303, Turkey
| | - Sezer Saglam
- Department of Medical Oncology, Istanbul Bilim University, Istanbul 34349, Turkey
| | - Serap Yucel
- Department of Radiation Oncology, Acibadem University Medical Faculty, Istanbul 34303, Turkey
| | - Esra Kaytan-Saglam
- Department of Radiation Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey
| | - Oktar Asoglu
- Department of General Surgery, Academia of Clinical Science of Bogazici, Istanbul 34357, Turkey
| | - Cetin Ordu
- Department of Medical Oncology, Istanbul Bilim University, Istanbul 34349, Turkey
| | - Hediye Acun
- Department of Medical Biophysics, Harran University Medical Faculty, Şanlıurfa 60300, Turkey
| | - Rasul Sharifov
- Department of Radiology, Bezm-i Alem University, Istanbul 34093, Turkey
| | - Semen Onder
- Department of Pathology, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey
| | - Ahmet Kizir
- Department of Radiation Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey
| | - Ethem N Oral
- Department of Radiation Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey
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17
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Plastiras A, Sideris M, Gaya A, Haji A, Nunoo-Mensah J, Haq A, Papagrigoriadis S. Waiting Time following Neoadjuvant Chemoradiotherapy for Rectal Cancer: Does It Really Matter. Gastrointest Tumors 2017; 4:96-103. [PMID: 29594111 DOI: 10.1159/000484982] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 11/02/2017] [Indexed: 01/04/2023] Open
Abstract
Background Neoadjuvant chemoradiotherapy (CRT) is considered the standard approach before any surgical intervention for locally advanced rectal tumors and has been proven to significantly improve the local recurrence rates of rectal cancer. However, the optimal timing of surgical resection after neoadjuvant CRT remains debatable. Objective and Methods We conducted a retrospective review of 65 consecutive patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection in order to evaluate the optimal time for surgical treatment. We used two alternative groups for analysis: patients who underwent surgery up to 6 weeks after CRT (n = 28) and those who underwent surgery 6 weeks or more after CRT (n = 27). Also, we compared patients who were operated on within 3 months (n = 39) with those who underwent surgical resection after more than 3 months (n = 16). Nonresponders to CRT were excluded from the analysis. Results There was no statistically significant association between waiting period post CRT and radiological downstaging for any group (p > 0.05 for any association). Also, there was no association between recurrence of disease, cancer-related deaths, perineural invasion, or positive lymph node ratio and any waiting period up to 3 months (p > 0.05 for all associations). Conclusion In this small exploratory study there was no evident difference in outcome according to timing of surgery, which suggests that further research in larger cohorts is warranted.
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Affiliation(s)
- Aris Plastiras
- King's College Hospital, NHS Foundation Trust, London, United Kingdom
| | - Michail Sideris
- King's College Hospital, NHS Foundation Trust, London, United Kingdom
| | - Andy Gaya
- Guy's and St. Thomas' Hospital, NHS Foundation Trust, London, United Kingdom
| | - Amyn Haji
- King's College Hospital, NHS Foundation Trust, London, United Kingdom
| | | | - Asif Haq
- King's College Hospital, NHS Foundation Trust, London, United Kingdom
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18
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Rana N, Chakravarthy AB, Kachnic LA. Neoadjuvant Treatment for Locally Advanced Rectal Cancer: New Concepts in Clinical Trial Design. Curr Treat Options Oncol 2017; 18:13. [PMID: 28281215 DOI: 10.1007/s11864-017-0454-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OPINION STATEMENT Treatment for locally advanced rectal cancer has evolved from surgery alone to surgery plus adjuvant therapy. Preoperative 5-fluorouracil- or capecitabine-based chemoradiation with standard fractionated radiation, surgery utilizing total mesorectal excision, and further chemotherapy has become the standard of care in the USA. Preoperative adjuvant chemoradiation treatment sequencing has allowed for decreased toxicity, more sphincter-sparing surgery, and improved local control rates as compared to delivering the chemoradiation postoperatively. Yet, given the heterogeneity of locally advanced disease, some patients may be over-treated with this approach, leading to unnecessary toxicity and costs, while others may have a propensity to develop distant metastases and may benefit from intensified therapy. Therefore, the trend in modern clinical trial design has been to individualize therapy. As such, current studies are examining shortening the duration of radiation, omitting preoperative chemoradiation in patients who have a robust response to induction chemotherapy alone, omitting or delaying surgery in patients who have a clinical complete response to preoperative chemoradiation, and completing all of the adjuvant treatment prior to surgery.
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Affiliation(s)
- Nitesh Rana
- Department of Radiation Oncology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, B1003 Preston Research Building, Nashville, TN, 37232, USA
| | - A Bapsi Chakravarthy
- Department of Radiation Oncology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, B1003 Preston Research Building, Nashville, TN, 37232, USA
| | - Lisa A Kachnic
- Department of Radiation Oncology, Vanderbilt University School of Medicine, 2220 Pierce Avenue, B1003 Preston Research Building, Nashville, TN, 37232, USA.
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19
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Optimal Sequencing of Neoadjuvant Therapies (NAT) in Rectal Cancer: Upfront Chemotherapy vs. Upfront Chemoradiation. CURRENT COLORECTAL CANCER REPORTS 2017. [DOI: 10.1007/s11888-017-0358-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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20
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Arias F, Eito C, Asín G, Mora I, Cambra K, Mañeru F, Ibáñez B, Arbea L, Viudez A, Hernández I, Arrarás JI, Errasti M, Barrado M, Campo M, Visus I, Flamarique S, Ciga MA. Fecal incontinence and radiation dose on anal sphincter in patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiotherapy: a retrospective, single-institutional study. Clin Transl Oncol 2017; 19:969-975. [DOI: 10.1007/s12094-017-1627-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 02/02/2017] [Indexed: 01/13/2023]
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21
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Gaertner WB, Kwaan MR, Madoff RD, Melton GB. Rectal cancer: An evidence-based update for primary care providers. World J Gastroenterol 2015; 21:7659-7671. [PMID: 26167068 PMCID: PMC4491955 DOI: 10.3748/wjg.v21.i25.7659] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 04/04/2015] [Accepted: 05/21/2015] [Indexed: 02/07/2023] Open
Abstract
Rectal adenocarcinoma is an important cause of cancer-related deaths worldwide, and key anatomic differences between the rectum and the colon have significant implications for management of rectal cancer. Many advances have been made in the diagnosis and management of rectal cancer. These include clinical staging with imaging studies such as endorectal ultrasound and pelvic magnetic resonance imaging, operative approaches such as transanal endoscopic microsurgery and laparoscopic and robotic assisted proctectomy, as well as refined neoadjuvant and adjuvant therapies. For stage II and III rectal cancers, combined chemoradiotherapy offers the lowest rates of local and distant relapse, and is delivered neoadjuvantly to improve tolerability and optimize surgical outcomes, particularly when sphincter-sparing surgery is an endpoint. The goal in rectal cancer treatment is to optimize disease-free and overall survival while minimizing the risk of local recurrence and toxicity from both radiation and systemic therapy. Optimal patient outcomes depend on multidisciplinary involvement for tailored therapy. The successful management of rectal cancer requires a multidisciplinary approach, with the involvement of enterostomal nurses, gastroenterologists, medical and radiation oncologists, radiologists, pathologists and surgeons. The identification of patients who are candidates for combined modality treatment is particularly useful to optimize outcomes. This article provides an overview of the diagnosis, staging and multimodal therapy of patients with rectal cancer for primary care providers.
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22
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Sterzing F, Hoehle F, Ulrich A, Jensen A, Debus J, Muenter M. Clinical results and toxicity for short-course preoperative radiotherapy and total mesorectal excision in rectal cancer patients. JOURNAL OF RADIATION RESEARCH 2015; 56:169-176. [PMID: 25341424 PMCID: PMC4572597 DOI: 10.1093/jrr/rru089] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2014] [Revised: 09/01/2014] [Accepted: 09/11/2014] [Indexed: 06/04/2023]
Abstract
Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009. Local control and survival were analyzed. Chronic adverse effects for 154 patients without local relapse were evaluated according to the NCI-CTCAE version 4.0 classification, with a median follow-up of 48 months. We found a 5-year disease-free survival (DFS) and overall survival (OS) of 71%. The 5-year estimated local control (LC) rate was 94%. A positive resection margin was found in 4% of the patients and was significantly correlated with decreased DFS, OS and LC. Chronic adverse effects were reported by 58% of the patients, of which 10% were Grade 3 toxicities. The most frequent Grade 2 toxicity was stool incontinence (13%). Sexual dysfunction was found in 36% of the patients (31% Grade 1 or 2, and only 5% Grade 3). SCPRT combined with TME produced excellent LC rates together with a low rate of high-grade chronic adverse effects.
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Affiliation(s)
- Florian Sterzing
- Department of Radiation Oncology, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Frieder Hoehle
- Department of Radiation Oncology, University Hospital Marburg, Germany
| | - Alexis Ulrich
- Department of Surgery, University Hospital Heidelberg, Germany
| | - Alexandra Jensen
- Department of Radiation Oncology, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany
| | - Jürgen Debus
- Department of Radiation Oncology, University Hospital Heidelberg, INF 400, 69120 Heidelberg, Germany Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Marc Muenter
- Department of Radiation Oncology, Katharinen Hospital, Stuttgart, Germany
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23
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Abstract
SUMMARY In the treatment of rectal cancer, neoadjuvant (chemo)radiotherapy is used to decrease the locoregional recurrence risk. The most common treatment consists of neoadjuvant radiotherapy to a dose of 45–50 Gy, combined with 5-fluorouracil or capecitabine-based chemotherapy. In parts of Europe, a short-course radiotherapy schedule of 5 × 5 Gy in 1 week is practiced for patients in whom no downstaging is required to achieve a radical resection. With the increased interest in organ preserving strategies, indications for chemoradiotherapy are changing and the focus has changed from achieving radical resections toward maximal downstaging. In this review, indications for and types of neoadjuvant treatment in rectal cancer are discussed, as well as new aspects related to organ preservation.
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Affiliation(s)
- Stefan AJ Hutschemaekers
- Department of Clinical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
| | - Corrie AM Marijnen
- Department of Clinical Oncology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
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Sclafani F, Cunningham D. Neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer. Future Oncol 2014; 10:2243-57. [DOI: 10.2217/fon.14.127] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
ABSTRACT Chemoradiotherapy or short-course radiotherapy followed by surgery is a standard treatment for locally advanced rectal cancer. This multimodality strategy has reduced the risk of local recurrence but failed to improve survival. Moreover, mid- and long-term side effects of radiotherapy have been reported. Alternative strategies have been investigated in an attempt to minimize treatment-related toxicities and improve outcome. Neoadjuvant chemotherapy without radiotherapy is an attractive therapeutic option that yields theoretical advantages. Moreover, if carefully selected, patients may be spared the effects of radiotherapy without compromising the oncology outcome. The authors review the available evidence on neoadjuvant chemotherapy without radiotherapy in locally advanced rectal cancer and try to anticipate potential algorithms of treatment selection to implement in clinical practice in the future.
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Affiliation(s)
- Francesco Sclafani
- Department of Medicine, The Royal Marsden NHS Foundation Trust, London & Surrey, UK
| | - David Cunningham
- Department of Medicine, The Royal Marsden NHS Foundation Trust, London & Surrey, UK
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Takasu M, Yamagami T, Nakamura Y, Komoto D, Kaichi Y, Tani C, Date S, Kiguchi M, Awai K. Multidetector computed tomography-based microstructural analysis reveals reduced bone mineral content and trabecular bone changes in the lumbar spine after transarterial chemoembolization therapy for hepatocellular carcinoma. PLoS One 2014; 9:e110106. [PMID: 25329933 PMCID: PMC4199685 DOI: 10.1371/journal.pone.0110106] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 09/16/2014] [Indexed: 11/19/2022] Open
Abstract
PURPOSE It is well recognized that therapeutic irradiation can result in bone damage. However, long-term bone toxicity associated with computed tomography (CT) performed during interventional angiography has received little attention. The purpose of this study was to determine the prevalence of osteoporosis and trabecular microstructural changes in patients after transarterial chemoembolization (TACE) for hepatocellular carcinoma therapy using an interventional-CT system. MATERIALS AND METHODS Spinal microarchitecture was examined by 64-detector CT in 81 patients who underwent TACE, 35 patients with chronic hepatitis, and 79 controls. For each patient, the volumetric CT dose index (CTDIv) during TACE (CTDIv (TACE)), the dose-length product (DLP) during TACE (DLP (TACE)), and CTDIv and DLP of routine dynamic CT scans (CTDIv (CT) and DLP (CT), respectively), were calculated as the sum since 2008. Using a three dimensional (3D) image analysis system, the tissue bone mineral density (tBMD) and trabecular parameters of the 12th thoracic vertebra were calculated. Using tBMD at a reported cutoff value of 68 mg/cm3, the prevalence of osteoporosis was assessed. RESULTS The prevalence of osteoporosis was significantly greater in the TACE vs. the control group (39.6% vs. 18.2% for males, P<0.05 and 60.6% vs. 34.8% for females, P<0.01). Multivariate regression analysis demonstrated that sex, age, and CTDIv (CT) significantly affected the risk of osteoporosis. Of these indices, CTDIv (CT) had the highest area under the curve (AUC) (0.735). Correlation analyses of tBMD with cumulative radiation dose revealed weak correlations between tBMD and CTDIv (CT) (r2 = 0.194, P<0.001). CONCLUSION The prevalence of osteoporosis was significantly higher in post TACE patients than in control subjects. The cumulative radiation dose related to routine dynamic CT studies was a significant contributor to the prevalence of osteoporosis.
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Affiliation(s)
- Miyuki Takasu
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Takuji Yamagami
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuko Nakamura
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Daisuke Komoto
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoko Kaichi
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Chihiro Tani
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Shuji Date
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Masao Kiguchi
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
| | - Kazuo Awai
- Department of Diagnostic Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
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Sirohi B, Barreto SG, Patkar S, Gupta A, DeSouza A, Talole S, Deodhar K, Shetty N, Engineer R, Goel M, Shrikhande SV. Down-staging following neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: Does timing of surgery really matter? Indian J Med Paediatr Oncol 2014; 35:263-266. [PMID: 25538402 PMCID: PMC4264271 DOI: 10.4103/0971-5851.144986] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Neoadjuvant chemoradiotherapy (NACTRT) improves local recurrence rate in locally advanced (LA) rectal cancer with no survival benefit. Pathological complete response (pCR) post-NACTRT is associated with improved outcome. Debate is ongoing as to when would be the opportune time to operate. AIM To determine if greater down-staging can be achieved by a longer time interval from NACTRT to surgery (tumor regression score [TRS]) and whether this would impact sphincter saving surgery rates and early relapse rates. MATERIALS AND METHODS A retrospective analysis of a prospectively maintained database of patients with LA rectal adenocarcinoma treated from January 2012 to August 2013 was carried out. One hundred and ten patients who completed NACTRT (50 Gy/25 fractions with capecitabine 825 mg/m(2) twice daily) followed by surgical resection were included. For response evaluation patients were divided into two groups, Group 1 (TRS ≤60 days, n = 42) and 2 (TRS >60 days, n = 68). Tumor down-staging, pCR rate, tumor regression grade (TRG) post-NACTRT and relapse rates were correlated with TRS. RESULTS Of 110 patients (median age: 49 years (21-73), 71% males; 18 (16.5%) with signet ring histology) 96% patients underwent an R0 resection. Post-NACTRT, CR was attained in 5 (4.5%), partial response in 98 (89%) and stable disease in 7 (6.4%) patients. Median time from completion of NACTRT to surgery was 64.5 days (6-474). Median lymph nodes harvested were 10 (1-50). Overall, 22 (20%) patients achieved pCR. 26 (62%) patients in Group 1 compared to 36 (53%) in Group 2 underwent sphincter sparing surgery (SSS) (P = 0.357). Six patients (14%) in Group 1 and 16 (24%) in Group 2 achieved pCR (P = 0.24). Median TRG in both groups was three. CONCLUSION Timing of surgery following NACTRT for LA rectal cancer does not influence pathological response, ability to perform SSS or disease-free survival. There is no incremental benefit of delaying the surgery though this needs to be confirmed in a prospective randomized trial.
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Affiliation(s)
- Bhawna Sirohi
- Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Savio George Barreto
- Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Shraddha Patkar
- Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Alok Gupta
- Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Ashwin DeSouza
- Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Sanjay Talole
- Department of Biostatistics, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Kedar Deodhar
- Department of Pathology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Nitin Shetty
- Department of Radiodiagnosis, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Reena Engineer
- Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Mahesh Goel
- Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
| | - Shailesh V. Shrikhande
- Department of Gastrointestinal and Hepato-Pancreato-Biliary Surgical Oncology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
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Abstract
The treatment of rectal cancer has evolved significantly in recent decades. Both modern radiotherapy treatment concepts and surgical techniques have been able to improve oncological as well as functional outcomes for rectal cancer patients. Large-scale, multicenter, randomized trials have been able to demonstrate the benefits of neoadjuvant treatment over adjuvant radiotherapy. In addition, local tumor control is improved by neoadjuvant irradiation. Conversely, patients receiving a total mesorectal excision showed no survival advantage following irradiation vs. only surgically resected patients. In addition, radiation therapy is associated with a certain morbidity and mortality. This paper summarizes the available evidence regarding postoperative morbidity, mortality, and long-term chronic effects of neoadjuvant radiotherapy.
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Chiang JM, Hsieh PS, Chen JS, Tang R, You JF, Yeh CY. Rectal cancer level significantly affects rates and patterns of distant metastases among rectal cancer patients post curative-intent surgery without neoadjuvant therapy. World J Surg Oncol 2014; 12:197. [PMID: 24980147 PMCID: PMC4108971 DOI: 10.1186/1477-7819-12-197] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2014] [Accepted: 06/12/2014] [Indexed: 11/21/2022] Open
Abstract
Background Rectal cancer patients have a higher incidence of pulmonary metastases than those with colon cancer. This study aimed to examine the effects of rectal cancer level on recurrence patterns in rectal cancer patients. Methods Patients with T3/T4 rectal cancers who underwent surgery between 2002 and 2006 were recruited in this study. All the patients were followed up on until death. Recurrence patterns and survival rates were calculated in relation to clinical variables. Results There were 884 patients were enrolled in this study. Patients with low-rectal cancer had significantly worse five-year overall survival (OS) and disease-free survival (DFS) rates (47.25% and 44.07%, respectively) than patients with mid-rectal (63.46% and 60.22%, respectively) and upper-rectal cancers (73.91% and 71.87%, respectively). The level of the tumor (P <0.001), nodal status (P <0.001), tumor invasion depth (P <0.001), and tumor differentiation (P = 0.047, P = 0.015) significantly affected the surgical outcomes related to OS and DFS in the univariate and multivariate analyses. Furthermore, the level of the rectal cancer was a significant risk factor (hazard ratio 1.114; 95% CI, 1.074 to 1.161; P <0.001) for local recurrence, lung metastases, bone metastases, and systemic lymph node metastases. Significantly higher incidence rates of bone (53.8%) and brain metastases (22.6%) after initial lung metastases rather than initial liver metastases (14.8% and 2.9%, respectively) were also observed. Conclusions For rectal cancer patients who underwent surgical resection, the rectal cancer level significantly affected surgical outcomes including rates and patterns of distant metastases.
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Affiliation(s)
- Jy Ming Chiang
- Division of colorectal surgery, Department of surgery, Chang Gung Memorial Hospital, Lin-Kou medical center, and College of Medicine, Chang Gung University, No,5, Fu-Hsing St, Kuei-Shan, Tao-Yuan 333, Taiwan.
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Wasserberg N. Interval to surgery after neoadjuvant treatment for colorectal cancer. World J Gastroenterol 2014; 20:4256-4262. [PMID: 24764663 PMCID: PMC3989961 DOI: 10.3748/wjg.v20.i15.4256] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/11/2013] [Accepted: 01/14/2014] [Indexed: 02/06/2023] Open
Abstract
The current standard treatment of low-lying locally advanced rectal cancer consists of chemoradiation followed by radical surgery. The interval between chemoradiation and surgery varied for many years until the 1999 Lyon R90-01 trial which compared the effects of a short (2-wk) and long (6-wk) interval. Results showed a better clinical tumor response (71.7% vs 53.1%) and higher rate of positive and pathologic tumor regression (26% vs 10.3%) after the longer interval. Accordingly, a 6-wk interval between chemoradiation and surgery was set to balance the oncological results with the surgical complexity. However, several recent retrospective studies reported that prolonging the interval beyond 8 or even 12 wk may lead to significantly higher rates of tumor downstaging and pathologic complete response. This in turn, according to some reports, may improve overall and disease-free survival, without increasing the surgical difficulty or complications. This work reviews the data on the effect of different intervals, derived mostly from retrospective analyses using a wide variation of treatment protocols. Prospective randomized trials are currently ongoing.
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Palta M, Willett CG, Czito BG. Long- Versus Short-Course Radiotherapy for Rectal Cancer. COLORECTAL CANCER 2014. [DOI: 10.1002/9781118337929.ch11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Palta M, Willett C, Czito B. Current options in chemoradiotherapy for rectal cancer. COLORECTAL CANCER 2013. [DOI: 10.2217/crc.13.50] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
SUMMARY The management of rectal adenocarcinoma and the role of radiation in the adjuvant and neoadjuvant setting is evolving. Randomized clinical trials established the role of neoadjuvant chemoradiation (CRT), primarily in patients with T3/T4 and/or node-positive tumor presentations. Clinical trials comparing short-course radiotherapy with long-course CRT have been undertaken, and data supporting treatment with definitive CRT-reserving surgery for salvage is emerging. Clinical research to enhance the efficacy of the 5-fluorouracil-based CRT platform is being investigated, incorporating a variety of chemotherapeutics and targeted agents.
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Affiliation(s)
- Manisha Palta
- Department of Radiation Oncology, Duke University, NC, USA
| | | | - Brian Czito
- Department of Radiation Oncology, Duke University, NC, USA
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Marks J, Nassif G, Schoonyoung H, DeNittis A, Zeger E, Mohiuddin M, Marks G. Sphincter-sparing surgery for adenocarcinoma of the distal 3 cm of the true rectum: results after neoadjuvant therapy and minimally invasive radical surgery or local excision. Surg Endosc 2013; 27:4469-77. [PMID: 24057070 DOI: 10.1007/s00464-013-3092-3] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2012] [Accepted: 07/01/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Ideal treatment of rectal cancer includes controlling the cancer; minimizing trauma, morbidity, and mortality; and avoiding a colostomy with preservation of adequate function. These goals become more challenging the further distal in the rectum the cancer is located. We sought to determine whether minimally invasive sphincter-preservation surgery (SPS) can accomplish good cancer control, maintaining sphincter function with minimal morbidity and mortality in rectal cancers of the distal 3 cm after receiving neoadjuvant chemoradiotherapy. METHODS We retrospectively reviewed a prospectively maintained rectal cancer database of a single colorectal surgeon to identify all patients with cancers of the distal 3 cm undergoing SPS via a laparoscopic total mesorectal excision or transanal endoscopic microsurgery (TEM). All patients received neoadjuvant chemoradiotherapy. Patient data, including demographics, initial tumor characteristics, staging, radiation dose, perioperative morbidity and mortality, and local recurrence (LR) and survival, were analyzed. RESULTS A total of 161 patients (108 men) underwent SPS via 3 techniques: transanal abdominal transanal proctosigmoidectomy (TATA, n = 106), TEM (n = 49), or ultralow anterior resection (LAR, n = 6). Average age was 62 years (range 22-90 years). The mean levels in rectum from the anorectal ring were as follows: TATA, 1.3 cm (range -1.0 to 3.0 cm), TEM, 1.5 cm (range -0.5 to -3.0 cm), and LAR, 2.9 cm (range 2.5-3.0 cm) (p > 0.05). Preoperative T stage was as follows: T3, n = 108 (TATA 83, TEM 20, LAR 5), T2, n = 48 (TATA 22, TEM 25, LAR 1), T1, n = 3 (TATA 1, TEM 2), and T4, n = 2 (both TEM). All patients received concomitant 5-fluorouracil-based chemotherapy and radiotherapy (mean, 5300 cGy; range 3,000-7,295 cGy). The mean estimated blood loss was 376 ml (range 10-3,600 ml). There were no mortalities. Morbidity rates were as follows: LAR, 0; TATA, 13.2%; and TEM, 32 % (wound disruption: major, 10%; minor, 16%). Pathologic staging was as follows: ypCR: uT2, 34%, and uT3, 19%. Overall LR was 3.7%. By procedure, the follow-up, LR, and KM5YAS, respectively, were: TATA, 37.9 months, 3 and 95%; TEM, 36.3 months, 6 and 88%; and LAR, 63.1 months, 0 and 75% (p > 0.05). CONCLUSIONS This study demonstrates positive oncologic outcomes, low LR rates, and high KM5YS after minimally invasive SPS. A colostomy-free lifestyle and cancer control make the minimally invasive surgical approach an excellent treatment option for complex distal rectal cancers.
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Affiliation(s)
- John Marks
- Section of Colorectal Surgery, Lankenau Medical Center, Wynnewood, PA, USA,
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Pettersson D, Glimelius B, Iversen H, Johansson H, Holm T, Martling A. Impaired postoperative leucocyte counts after preoperative radiotherapy for rectal cancer in the Stockholm III Trial. Br J Surg 2013; 100:969-75. [PMID: 23553796 DOI: 10.1002/bjs.9117] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/06/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND Radiotherapy (RT) in rectal cancer increases postoperative morbidity. A suggested reason is RT-induced bone marrow depression resulting in impaired leucocyte counts. The ongoing Stockholm III Trial randomizes patients with operable rectal cancers to short-course RT with immediate surgery (SRT), short-course RT with surgery delayed for 4-8 weeks (SRT-delay) and long-course RT with surgery delayed for 4-8 weeks (LRT-delay). This study examined differences between the randomization arms regarding leucocyte response and postoperative complications. METHODS Patients randomized in the Stockholm III Trial between October 1998 and November 2010 were included. Data were collected in a prospective register. Additional data were obtained by retrospective review of clinical records. RESULTS Of 657 randomized patients, 585 had data on leucocytes. The SRT arm had the highest proportion of postoperative complications (SRT, 52·5 per cent; SRT-delay, 39·4 per cent; LRT-delay, 41 per cent; P = 0·010). There was no association between low preoperative leucocyte count and postoperative complications (P = 0·238). Irrespective of randomization arm, patients with an impaired postoperative to preoperative leucocyte ratio had the highest rate of complications (low ratio, 56·6 per cent; intermediate ratio, 46·9 per cent; high ratio, 36·3 per cent; P = 0·010). The SRT arm had the highest proportion of low ratios (SRT, 48·9 per cent; SRT-delay, 22·8 per cent; LRT-delay, 22 per cent; P < 0·001). CONCLUSION An impaired postoperative leucocyte response is associated with postoperative complications. The highest risk is with immediate surgery following short-course radiotherapy. REGISTRATION NUMBER NCT 00904813 (http://www.clinicaltrials.gov).
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Affiliation(s)
- D Pettersson
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
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Lee JH, Jo IY, Lee JH, Yoon SC, Kim YS, Choi BO, Kim JG, Oh ST, Lee MA, Jang HS. The role of postoperative pelvic radiation in stage IV rectal cancer after resection of primary tumor. Radiat Oncol J 2012; 30:205-12. [PMID: 23346540 PMCID: PMC3546289 DOI: 10.3857/roj.2012.30.4.205] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Revised: 10/17/2012] [Accepted: 10/23/2012] [Indexed: 12/19/2022] Open
Abstract
Purpose To evaluate the effect of pelvic radiotherapy (RT) in patients with stage IV rectal cancer treated with resection of primary tumor with or without metastasectomy. Materials and Methods Medical records of 112 patients with stage IV rectal cancer treated with resection of primary tumor between 1990 and 2011 were retrospectively reviewed. Fifty-nine patients received synchronous or staged metastasectomy whereas fifty-three patients did not. Twenty-six patients received pelvic radiotherapy. Results Median overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS) of all patients was 27, 70, and 11 months, respectively. Pathologic T (pT), N (pN) classification and complete metastasectomy were statistically significant factors in OS (p = 0.040, 0.020, and 0.002, respectively). RT did not improve OS or LRFS. There were no significant factors in LRFS. pT and pN classification were also significant prognostic factors in PFS (p = 0.010 and p = 0.033, respectively). In the subgroup analysis, RT improved LRFS in patients with pT4 disease (p = 0.026). The locoregional failure rate of the RT group and the non-RT group were 23.1% and 33.7%, showing no difference in the failure pattern of both groups (p = 0.260). Conclusion Postoperative pelvic RT did not improve LRFS of all metastatic rectal cancer patients; however, it can be recommended to patients with pT4 disease. A complete resection of metastatic masses should be performed if possible.
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Affiliation(s)
- Joo Hwan Lee
- Department of Radiation Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea
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Salmenkylä S, Kouri M, Österlund P, Pukkala E, Luukkonen P, Hyöty M, Pääkkönen M, Mäkelä J, Mustonen H, Järvinen HJ. Does Preoperative Radiotherapy with Postoperative Chemotherapy Increase Acute Side-Effects and Postoperative Complications of Total Mesorectal Excision? Report of the Randomized Finnish Rectal Cancer Trial. Scand J Surg 2012; 101:275-82. [DOI: 10.1177/145749691210100410] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Background and Aims: In a randomized trial the effect of short-term preoperative radio therapy and postoperative chemotherapy was studied in patients undergoing total mesorectal excision (TME) for clinically resectable rectal cancer. The primary endpoint was overall survival. The secondary endpoints published herein were the incidence of postoperative complications and adverse events with perioperative adjuvant therapy. Material and Methods: In 1995–2002, 278 eligible patients with stage II and stage III rectal cancer were randomly assigned to TME alone (surgery group) or to preoperative 25Gy radiotherapy in 5 fractions and postoperative 5-fluorouracil and leucovorin chemotherapy in addition (RT+CTgroup). Results: Anastomotic leakage rate did not significantly differ between the surgery and the RT + CT group, 20.6% vs. 27.4%. Postoperative infections (15.5 vs. 26.2%, p = 0.037) and perineal wound dehiscence (15.9 vs. 38.5%, p = 0.045) were more common after radiotherapy. Grade 3–5 adverse events were uncommon with preoperative radiotherapy (one, 0.7% with reversible lumbar plexopathy) and postoperative chemotherapy (hematologic in 10.8%, with one septic death, and gastrointestinal in 4.8%). Conclusions: Perioperative adjuvant therapy was generally well tolerated and did not lead to an increase in serious surgical complications. Wound infections and perineal wound dehiscence were more common in irradiated patients.
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Affiliation(s)
- S. Salmenkylä
- Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
| | - M. Kouri
- Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
| | - P. Österlund
- Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
| | - E. Pukkala
- Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
| | - P. Luukkonen
- Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
| | - M. Hyöty
- Department of Surgery, Tampere University Hospital, Tampere, Finland
| | - M. Pääkkönen
- Department of Surgery, Kuopio University Hospital, Kuopio, Finland
| | - J. Mäkelä
- Department of Surgery, Oulu University Hospital, Oulu, Finland
| | - H. Mustonen
- Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
| | - H. J. Järvinen
- Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
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Bębenek M, Tupikowski W, Cisarż K, Balcerzak A, Wojciechowski L, Stankowska A, Tarkowski R. Preoperative treatment does not improve the therapeutic results of abdominosacral amputation of the rectum. World J Surg 2012; 36:1686-92. [PMID: 22411086 DOI: 10.1007/s00268-012-1527-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND This study reviewed the impact of preoperative chemoradiotherapy/short-term radiotherapy on abdominosacral amputations of the rectum (ASAR) for the treatment of low-rectum cancers in terms of postoperative morbidity, local recurrence rates, and survival. METHODS A total of 198 patients with stage II and III tumors located within 6 cm of the anorectal junction underwent ASAR between 1998 and 2008 and were selected for further analysis. Patients were compared according to the following groups: those who had surgery only (Group A) and those who had preoperative chemoradiotherapy/short-term radiotherapy (Group B). RESULTS There were 44 and 154 patients in Groups A and B, respectively, including 135 males. The median age of the subjects was 63 years (range = 35-88). The median follow-up period was 81 months (range = 23-138). Neither the local recurrence rates (6.8% in Group A vs. 4.6% in Group B, p = 0.544) nor the 5-year relative survival rates (72.4% in Group A vs. 69.3% in Group B, p = 0.127) differed significantly between the groups. CONCLUSION Preoperative therapy in low-rectum cancer does not improve the therapeutic results of ASAR.
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Affiliation(s)
- Marek Bębenek
- 1st Department of Surgical Oncology, Regional Comprehensive Cancer Center, pl. Hirszfelda 12, 53-413, Wroclaw, Poland.
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Chang CY, Kim HC, Park YS, Park JO, Choi DH, Park HC, Cho YB, Yun SH, Lee WY, Chun HK. The effect of postoperative pelvic irradiation after complete resection of metastatic rectal cancer. J Surg Oncol 2011; 105:244-8. [PMID: 21987401 DOI: 10.1002/jso.22109] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2011] [Accepted: 09/13/2011] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND OBJECTIVES The 2010 NCCN clinical practice guidelines recommend radiation as a part of the standard adjuvant or neoadjuvant treatment for stage IV rectal cancer patients. This study evaluated the oncologic efficacy of postoperative radiotherapy (RTx) in loco-regional control after complete removal of primary and metastatic lesions in stage IV rectal cancer. METHODS Sixty-eight patients with metastatic rectal cancer were enrolled and analyzed. Twenty-eight of the enrolled patients received concurrent postoperative RTx with chemotherapy (RTx group) and the remaining 40 received only postoperative systemic chemotherapy (CTx) without RTx (non-RTx group). The eligibility criteria were as follows: a primary rectal tumor located in the low or mid-rectum, no postoperative macroscopic and microscopic evidence of residual tumor in primary and metastatic sites, and no history of prior CTx or pelvic RTx. RESULTS The recurrence rates were 75.0% in the RTx group and 72.5% in the non-RTx group. Local recurrence rates were 7.1% (RTx group) and 22.5% (non-RTx group) (P = 0.108). There were no differences in overall survival (OS), local recurrence-free survival, and disease-free survival between the two groups. The 2-year OS rates were 78.9% (RTx group) and 74.1% (non-RTx group) (P = 0.395). CONCLUSIONS Survival benefit of postoperative RTx in stage IV rectal cancer after complete removal of tumors was not apparent. RTx could be recommended for selected patients at high risk of local recurrence or for palliation of symptoms.
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Affiliation(s)
- Chul Young Chang
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Use of primary radiotherapy for rectal cancer in the Netherlands between 1997 and 2008: a population-based study. Clin Oncol (R Coll Radiol) 2011; 24:e1-8. [PMID: 21968247 DOI: 10.1016/j.clon.2011.09.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2011] [Revised: 06/23/2011] [Accepted: 08/10/2011] [Indexed: 01/27/2023]
Abstract
AIMS To describe variation in the utilisation rates of primary radiotherapy for patients with rectal cancer in the Netherlands, focusing on time trends and age effects. MATERIALS AND METHODS Data on primary non-metastatic rectal cancer were derived from the population-based cancer registries of four comprehensive cancer centres (regions) in the Netherlands (1997-2008, n=13,055). RESULTS An increase in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66-76% in 2008, for both genders. This increase was found predominately for preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of receiving radiotherapy decreased with age: the odds of receiving preoperative radiotherapy was reduced in patients aged 65 years and older, as well as the odds of receiving postoperative radiotherapy in those aged 75 years and older, which remained significant after adjustment for stage, gender and region. Regional differences persisted in multivariable analyses, i.e. the odds of receiving preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95% confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving postoperative radiotherapy was significantly increased in these regions [odds ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another [odds ratio 0.8 (0.6-0.96)]. CONCLUSIONS The utilisation rate of radiotherapy for rectal cancer increased significantly over time, particularly for preoperative radiotherapy and was most pronounced for T2-3 patients. Due to national multidisciplinary treatment guidelines, regional differences became limited in recent years after adjustment for age and stage of the disease. A low utilisation rate of radiotherapy was seen in women and elderly patients.
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Elliott SP, Jarosek SL, Alanee SR, Konety BR, Dusenbery KE, Virnig BA. Three-dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture. Cancer 2011; 117:4557-65. [PMID: 21412999 PMCID: PMC3135749 DOI: 10.1002/cncr.25994] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2010] [Revised: 12/17/2010] [Accepted: 01/03/2011] [Indexed: 11/06/2022]
Abstract
BACKGROUND Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown. METHODS From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992-2004 were identified. By using Kaplan-Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall-related fracture outside the radiation field. RESULTS After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR], 1.76; 95% confidence interval [CI], 1.38-2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56-1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88-3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17-1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97-2.10). The number needed to treat to result in 1 hip fracture during a 10-year period was 51 patients (95% CI, 31-103). CONCLUSIONS In men with prostate cancer, pelvic 3-D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short-course AST to EBRT. This risk associated with EBRT must be site-specific as there was no increase in the risk of fall-related fractures in bones that were outside the radiation field.
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Affiliation(s)
- Sean P Elliott
- Department Urologic Surgery, School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
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Marks JH, Frenkel JL, D’Andrea AP, Greenleaf CE. Maximizing Rectal Cancer Results: TEM and TATA Techniques to Expand Sphincter Preservation. Surg Oncol Clin N Am 2011; 20:501-20, viii-ix. [DOI: 10.1016/j.soc.2011.01.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Topova L, Hellmich G, Puffer E, Schubert C, Christen N, Boldt T, Wiedemann B, Witzigmann H, Stelzner S. Prognostic value of tumor response to neoadjuvant therapy in rectal carcinoma. Dis Colon Rectum 2011; 54:401-11. [PMID: 21383559 DOI: 10.1007/dcr.0b013e3182070efb] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Neoadjuvant treatment in the multimodal therapy concept of rectal carcinoma has considerable effects on prognosis appraisal. OBJECTIVE This study aimed to evaluate the tumor response specified as an improvement by at least one stage defined in terms of the International Union Against Cancer stages as a prognostic factor. DESIGN This investigation was designed as a prospective cohort study. SETTING This study was performed at a community-based hospital with a specialized colorectal unit. PATIENTS One hundred seventy-four patients with locally advanced rectal carcinoma, treated in the Dresden-Friedrichstadt hospital from 1997 to 2009, who received long-term preoperative chemoradiotherapy and underwent curative resection, were included in this study. MAIN OUTCOME MEASURES The main outcome measures were cause-specific and disease-free survival with respect to T and N category, International Union Against Cancer stage, venous and lymphatic invasions, grading, CEA level, complete pathologic response, tumor regression grading, International Union Against Cancer stage shift, T, N, and CEA shift, types of neoadjuvant therapy, adjuvant therapy, interval between completion of neoadjuvant chemoradiotherapy and surgery, and number of extracted lymph nodes in resected specimens. Univariate and multivariate analyses were performed. RESULTS Median follow-up was 45 months. One hundred twenty-one patients (69.5%) showed a response to the treatment, whereas 53 (30.5%) did not. Five-year cause-specific and disease-free survival for responders (n = 121) vs nonresponders (n = 53) were 92.6% and 73.7% vs 84.9% and 47.9%. In the univariate analysis, ypN category, venous and lymphatic invasion, tumor regression grading, International Union Against Cancer stage shift, and T and N shift were significantly predictive for cause-specific and disease-free survival. Furthermore, ypUICC stage, ypT category, grading, and complete pathologic response had an impact on disease-free survival. In the multivariate analysis, only the International Union Against Cancer stage shift kept its independent explanatory power for cause-specific P = .012, HR 3.10 (95% CI 1.28-7.51) and disease-free survival P < .001, HR 3.85 (95% CI 1.98-7.51). LIMITATIONS The determination of International Union Against Cancer stage shift depends on the pretreatment staging modalities. CONCLUSION Our investigation demonstrates that the response of tumor to neoadjuvant therapy is an independent prognostic factor in patients with rectal carcinoma.
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Affiliation(s)
- Larysa Topova
- Department of General and Visceral Surgery, Dresden-Friedrichstadt General Hospital, Teaching Hospital of the Technical University of Dresden, Dresden, Germany.
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Kao PS, Chang SC, Wang LW, Lee RC, Liang WY, Lin TC, Chen WS, Jiang JK, Yang SH, Wang HS, Lin JK. The impact of preoperative chemoradiotherapy on advanced low rectal cancer. J Surg Oncol 2011; 102:771-7. [PMID: 20872811 DOI: 10.1002/jso.21711] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Preoperative chemoradiotherapy (CCRT) followed by radical resection is an option for advanced low rectal cancer. This study was aimed to clarify the impact of CCRT on patients' outcome. PATIENTS AND METHODS One hundred thirty-six patients with rectal cancer (<10 cm from anal verge) were enrolled prospectively between July 2000 and December 2004. The preoperative clinical stage was T3, T4, or node-positive disease. Sixty-nine and 67 patients underwent surgery with and without preoperative CCRT, respectively. The regimen of pre-op CCRT was a radiation dosage of 45 Gy in 20 fractions and oral tegafur-uracil (UFUR) and leucovorin. RESULTS There was no statistical difference in the preserved anorectal function between two groups after 5 years of follow-up (62.3% vs. 47.8%; P = 0.125). The 5-year overall survival and disease-free survival (DFS) percentage were 88.4% and 76.8% for patients with preoperative CCRT, and 65.7% and 58.2% for patients without CCRT, respectively. Patients with preoperative CCRT had a higher overall survival rate and DFS (P = 0.001 and 0.015). CONCLUSIONS In patients with advanced low rectal cancer, preoperative CCRT followed by radical surgery significantly improved overall survival and DFS compared with surgery alone. The effect of sphincter preservation with preoperative CCRT is questionable.
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Affiliation(s)
- Ping-Sheng Kao
- Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan
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Garlipp B, Ptok H, Schmidt U, Meyer F, Gastinger I, Lippert H. Neoadjuvant chemoradiotherapy for rectal carcinoma: effects on anastomotic leak rate and postoperative bladder dysfunction after non-emergency sphincter-preserving anterior rectal resection. Langenbecks Arch Surg 2010; 395:1031-8. [DOI: 10.1007/s00423-010-0708-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2010] [Accepted: 08/04/2010] [Indexed: 01/08/2023]
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Abstract
The role of surgery in the loco-regional control of adenocarcinoma of the rectum is being increasingly challenged by the good response rates of neoadjuvant oncological treatment. This review represents an opinion paper outlining well-established choices and new trends in surgical intervention, unresolved difficulties of local and regional staging of rectal malignancy and accurate assessment of tumour response to preoperative downstaging chemoradiation. The influence of preoperative chemoradiation on subsequent surgical strategy is discussed highlighting several controversial aspects of surgical management both when the tumour fails to respond and appears to be irresectable and when complete clinical response is observed.
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Affiliation(s)
- D Y Artioukh
- Department of Surgery, Southport & Ormskirk Hospital, Southport, Merseyside, UK.
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Viani GA, Stefano EJ, Soares FV, Afonso SL. Evaluation of biologic effective dose and schedule of fractionation for preoperative radiotherapy for rectal cancer: meta-analyses and meta-regression. Int J Radiat Oncol Biol Phys 2010; 80:985-91. [PMID: 20615619 DOI: 10.1016/j.ijrobp.2010.03.008] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2009] [Revised: 03/09/2010] [Accepted: 03/17/2010] [Indexed: 12/01/2022]
Abstract
PURPOSE To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. METHODS AND MATERIALS A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy(10) and a short RT schedule; Group 2, RCTs with BED >30 Gy(10) and a long RT schedule; Group 3, RCTs with BED ≤ 30 Gy(10) and a short RT schedule; and Group 4, RCTs with BED ≤ 30 Gy(10) and a long RT schedule. RESULTS Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy(10) of BED. CONCLUSION Our data have shown that RT with a BED of >30 Gy(10) is more efficient in reducing local recurrence and mortality rates than a BED of ≤ 30 Gy(10), independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy(10) should be recommended for sphincter preservation.
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Abstract
Anorectal procedures are associated with significant morbidity and include complications of the perineum, which can cause substantial difficulty for the patient. Prevention of perineal complications is key, but many anorectal procedures are performed in difficult situations such as large bulky tumors or inflammatory bowel diseases. In this review, the authors outline many of the complications encountered following both simple and complex anorectal procedures while highlighting best evidence for treatment.
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Affiliation(s)
- James W Ogilvie
- Department of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, USA
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Abstract
OBJECTIVE This systematic review was designed to determine postoperative complication rates of radical surgery for rectal cancer (abdominal perineal resection and anterior resection). SUMMARY OF BACKGROUND DATA Lack of accepted complication rates for rectal cancer surgery may hinder quality improvement efforts and may impede the conception of future studies because of uncertainty regarding the expected event rates. METHODS All prospective studies of rectal cancer receiving radical surgery published between 1990 and August 2008 were obtained by searching Ovid MEDLINE, EMBASE, as well as ASCO GI, CAGS, and ASCRS meeting abstracts between 2004 and 2008. There was no language restriction. The outcomes extracted were anastomotic leak, pelvic sepsis, postoperative death, wound infection, and fecal incontinence. Summary complication rates were obtained using a random effects model; the Z-test was used to test for study heterogeneity. RESULTS Fifty-three prospective cohort studies and 45 randomized controlled studies with 36,315 patients (24,845 patients had an anastomosis) were eligible for inclusion. Most of the studies found were based in continental Europe (58%), followed by Asia (25%), United Kingdom (10%), North America (5%), and Australia/New Zealand. The anastomotic leak rate, reported in 84 studies, was 11% (95% CI: 10, 12); the pelvic sepsis rate, in 29 studies, was 12% (9, 16); the postoperative death rate, in 75 studies, was 2% (2, 3); and the wound infection rate, in 50 studies, was 7% (5, 8). Fecal incontinence rates were reported in too few studies and so heterogeneously that numerical summarization was inappropriate. Year of publication, use of preoperative radiation, use of laparoscopy, and use of protecting stoma were not significant variables, but average age, median tumor height, and method of detection (clinical vs. radiologic) showed significance to explain heterogeneity in anastomotic leak rates. Year of publication, study origin, average age, and use of laparoscopy were significant, but median tumor height and preoperative radiation use were not significant in explaining heterogeneity among observed postoperative death rates. With multivariable analysis, only average age for anastomotic leak and year of publication for postoperative death remained significant. CONCLUSIONS Benchmark complication rates for radical rectal cancer surgery were obtained for use in sample size calculations in future studies and for quality control purposes. Postoperative death rates showed improvement in recent years.
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Marks J, Mizrahi B, Dalane S, Nweze I, Marks G. Laparoscopic transanal abdominal transanal resection with sphincter preservation for rectal cancer in the distal 3 cm of the rectum after neoadjuvant therapy. Surg Endosc 2010; 24:2700-7. [PMID: 20414681 DOI: 10.1007/s00464-010-1028-8] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2009] [Accepted: 02/18/2010] [Indexed: 01/03/2023]
Abstract
BACKGROUND This study reports the short- and long-term results for a prospective rectal cancer management program using laparoscopic radical transanal abdominal transanal proctosigmoidectomy with coloanal anastomosis (TATA) after neoadjuvant therapy. METHODS A prospective database included 102 rectal cancer patients treated with laparoscopic TATA from 1998 to 2008. Patients with distant metastasis at presentation, patients with a tumor more than 3 cm from the anorectal ring, and patients not undergoing neoadjuvant therapy were excluded, leaving 79 patients (54 men and 25 women) with a mean age of 59.2 years (range, 22-85 years) for this study. 13 patients completed neoadjuvant therapy before the original evaluation, and they are excluded from the report of initial clinical assessment. Before treatment, 50 patients were staged as T3 and 16 patients as T2. The mean level in the rectum superior to the anorectal ring was 1.2 cm (range, -0.5 to 3 cm). In terms of fixity, 31 of the tumors were mobile, 27 were tethered, and 8 showed early fixation. Ulceration was absent in 8 cases, minimal in 12 cases, superficial in 7 cases, moderate in 22 cases, and deep in 17 cases. The mean pretreatment tumor size tumor was 4.8 cm (range, 1.5-12 cm). The median external beam radiation was 5,400 cGy (range, 3,000-8,040 cGy), and 77 patients underwent chemotherapy. RESULTS The mean follow-up period was 34.2 months (range, 1.9-113.9 months). There were no perioperative mortalities. The conversion rate was 2.5%, and the mean largest incision length was 4.3 cm (range, 1.2-21 cm). For 84% of the patients, the incision was less than 6.0 cm, and 46% of the patients had no abdominal incision for delivery of the specimen. The mean estimated blood loss was 367 ml (range, 75-2,200 ml). All the patients had a temporary diverting stoma. The major morbidity rate was 11%, and the minor morbidity rate was 19%. The major complications included four full-thickness rectal prolapses with repair, one ischemic neorectum with successful reanastomosis, two bowel obstructions, and two failed anastomoses requiring stoma. The ypT stages included 22 complete responses, 12 cases of ypT1, 22 cases of ypT2, 23 cases of ypT3; 65 cases of ypN0, and 14 cases of ypN + (T3 = 7, T2 = 4, T1 = 3). The local recurrence rate was 2.5% (2/79), and the distant metastases rate was 10.1% (8/79). The KM5YAS rate was 97%. Overall, 90% of the patients lived without a stoma. Neorectal loss was due to positive margins or recurrence and was followed by abdominoperineal resection in three cases and ischemia in two cases. The condition of two patients was not reversed due to comorbidities, and one patient had a stoma secondary to bowel obstruction. CONCLUSION The study results indicate excellent local recurrence (2.7%) and 5-year survival rates without the need for permanent colostomy in patients with cancers in the distal one-third of the rectum. Laparoscopic total mesorectal excision (TME) with the TATA approach is safe and can be performed laparoscopically. Multi-institutional studies are required to establish the reproducibility of this promising approach.
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Affiliation(s)
- J Marks
- Section of Colorectal Surgery, Lankenau Hospital and Institute for Medical Research, Wynnewood, PA, USA.
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Beable R, Collins P, Burli P, Wheatley D. Entero-caval fistula, a complication following chemoradiotherapy for a rectal carcinoma. Clin Radiol 2010; 65:85-8. [DOI: 10.1016/j.crad.2009.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2009] [Revised: 10/03/2009] [Accepted: 10/08/2009] [Indexed: 11/16/2022]
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