George A Plataniotis1, Roger G Dale2. 1. Department of Oncology, Queens Hospital, London, United Kingdom. Electronic address: george.plataniotis@nhs.net. 2. Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London, United Kingdom.
Abstract
PURPOSE: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. METHODS AND MATERIALS: A standard logistic dose-response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. RESULTS: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. CONCLUSION: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.
PURPOSE: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. METHODS AND MATERIALS: A standard logistic dose-response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. RESULTS: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. CONCLUSION: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.
Authors: Shaista Hafeez; Fiona McDonald; Susan Lalondrelle; Helen McNair; Karole Warren-Oseni; Kelly Jones; Victoria Harris; Helen Taylor; Vincent Khoo; Karen Thomas; Vibeke Hansen; David Dearnaley; Alan Horwich; Robert Huddart Journal: Int J Radiat Oncol Biol Phys Date: 2017-02-09 Impact factor: 7.038