Eleonor Rivin Del Campo1, Oscar Matzinger2, Karin Haustermans3, Didier Peiffert4, Robert Glynne-Jones5, Kathryn A Winter6, Andre A Konski7, Jaffer A Ajani8, Jean-François Bosset9, Jean-Michel Hannoun-Levi10, Marc Puyraveau11, A Bapsi Chakravarthy12, Helen Meadows13, John Northover14, Laurence Collette15, Melissa Christiaens3, Philippe Maingon16. 1. Department of Radiation Oncology, Tenon University Hospital, Sorbonne University, Paris, France. Electronic address: eleonor.rivindelcampo@aphp.fr. 2. Department of Radiation Oncology, Genolier Clinic, Genolier, Switzerland. 3. Department of Radiation Oncology, UZ Leuven University Hospital, Leuven, Belgium. 4. Department of Radiation Oncology, Institut de Cancérologie de Lorraine, Nancy, France. 5. Department of Radiation Oncology, Mount Vernon Cancer Centre, Northwood, United Kingdom. 6. NRG Oncology Statistics and Data Management Center, American College of Radiology, Philadelphia, PA, USA. 7. Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Leonard Davis Institute of Health Economics, West Chester, PA, USA; Department of Radiation Oncology, The Chester County Hospital, West Chester, PA, USA. 8. Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA. 9. Department of Radiation Oncology, Jean Minjoz University Hospital, Besançon, France. 10. Department of Radiation Oncology, Centre Antoine Lacassagne, Nice, France. 11. Department of Statistics, Jean Minjoz University Hospital, Besançon, France. 12. Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA. 13. Cancer Research UK & UCL Cancer Trials Centre, London, United Kingdom. 14. Department of Surgery, The London Clinic and St Marks Hospital, London, United Kingdom. 15. Department of Statistics, EORTC Headquarters, Brussels, Belgium. 16. Department of Radiation Oncology, La Pitié Salpêtrière - Charles Foix University Hospital, Sorbonne University, Paris, France.
Abstract
PURPOSE: Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer. MATERIALS AND METHODS: Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up). RESULTS: After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p < 0.001) and male gender (p = 0.045). Although significant differences were not observed, subset analyses for LRF (dose range: 50.4-59 Gy) seemed to favour lower doses (p = 0.412), and when comparing a 2-week gap versus 3 (dose: 59.4 Gy), results suggested 3 weeks might be detrimental (p = 0.245). For a 2-week gap versus none (dose range: 55-59.4 Gy), no difference was observed (p = 0.89). Five-year PFS was 65.7% (95% CI: 62.8-68.5%). Higher PFS rates were observed in women (p < 0.001), smaller tumour sizes (p < 0.001) and shorter OTT (p = 0.025). Five-year overall survival [76.7% (95% CI: 73.9%-79.3%)] correlated positively with female gender (p < 0.001), small tumour size (p = 0.027) and short OTT (p = 0.026). Descriptive toxicity data are presented. CONCLUSION: For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome. Further trials involving modern techniques may better define optimal OTT and total dose.
PURPOSE: Concomitant external-beam radiochemotherapy (5-fluorouracil-mitomycin C) has become the standard of care in anal cancer since the '90s. A pooled analysis of individual patient data from 7 major trials was performed quantifying the effect of radiation therapy (RT)-related parameters on the outcome of patients with anal cancer. MATERIALS AND METHODS: Pooling databases from combined modality trials, the impact of RT parameters (total dose, gap duration, OTT: overall treatment time) on outcome including locoregional failure (LRF), 5-year progression free survival (PFS) and toxicities were investigated. Individual patient data were received for 10/13 identified published studies conducted from 1987 to 2008 (n = 3031). A Cox regression model was used (landmark = 3 months after RT for first follow-up). RESULTS: After data inspection indicating severe heterogeneity between trials, only 1343 patients from 7/10 studies received were analysed (the most recent ones, since 1994; median follow-up = 4.1 years). A higher overall 5-year LRF rate [22.8% (95% confidence interval [CI] 22.3-27.3%)] significantly correlated with longer OTT (p = 0.03), larger tumour size (p < 0.001) and male gender (p = 0.045). Although significant differences were not observed, subset analyses for LRF (dose range: 50.4-59 Gy) seemed to favour lower doses (p = 0.412), and when comparing a 2-week gap versus 3 (dose: 59.4 Gy), results suggested 3 weeks might be detrimental (p = 0.245). For a 2-week gap versus none (dose range: 55-59.4 Gy), no difference was observed (p = 0.89). Five-year PFS was 65.7% (95% CI: 62.8-68.5%). Higher PFS rates were observed in women (p < 0.001), smaller tumour sizes (p < 0.001) and shorter OTT (p = 0.025). Five-year overall survival [76.7% (95% CI: 73.9%-79.3%)] correlated positively with female gender (p < 0.001), small tumour size (p = 0.027) and short OTT (p = 0.026). Descriptive toxicity data are presented. CONCLUSION: For patients receiving concurrent external-beam doublet chemoradiation, a longer OTT seems detrimental to outcome. Further trials involving modern techniques may better define optimal OTT and total dose.
Authors: Jeung Eun Lee; Seung Jae Huh; Won Park; Do Hoon Lim; Yong Chan Ahn; Chang Soo Park; Byoung Gie Kim; Duk Soo Bae; Je Ho Lee; Chong Taik Park; Tae Jin Kim; Kyung Taek Lim; Hwan Wook Chung; Ki Heon Lee; Jae Uk Shim Journal: Cancer Res Treat Date: 2004-08-31 Impact factor: 4.679
Authors: J H Hendry; S M Bentzen; R G Dale; J F Fowler; T E Wheldon; B Jones; A J Munro; N J Slevin; A G Robertson Journal: Clin Oncol (R Coll Radiol) Date: 1996 Impact factor: 4.126
Authors: Ali Hosni; Kathy Han; Lisa W Le; Jolie Ringash; James Brierley; Rebecca Wong; Robert Dinniwell; Anthony Brade; Laura A Dawson; Bernard J Cummings; Monika K Krzyzanowska; Eric X Chen; David Hedley; Jennifer Knox; Alexandra M Easson; Patricia Lindsay; Tim Craig; John Kim Journal: Oncotarget Date: 2018-04-17