Maria Thor1, Andrew Jackson2, Michael J Zelefsky3, Gunnar Steineck4, Asa Karlsdòttir5, Morten Høyer6, Mitchell Liu7, Nicola J Nasser3, Stine E Petersen6, Vitali Moiseenko8, Joseph O Deasy2. 1. Dept of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA. Electronic address: thorm@mskcc.org. 2. Dept of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, USA. 3. Dept of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA. 4. Division of Clinical Cancer Epidemiology, Dept. of Oncology, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Sweden. 5. Dept of Oncology, Haukeland University Hospital, Bergen, Norway. 6. Dept of Oncology, Aarhus University Hospital, Denmark. 7. British Columbia Cancer Agency, Vancouver Cancer Center, Canada. 8. Dept of Radiation, Medicine and Applied Sciences, University of California San Diego, La Jolla, USA.
Abstract
PURPOSE: To investigate whether inter-institutional cohort analysis uncovers more reliable dose-response relationships exemplified for late rectal bleeding (LRB) following prostate radiotherapy. MATERIAL AND METHODS: Data from five institutions were used. Rectal dose-volume histograms (DVHs) for 989 patients treated with 3DCRT or IMRT to 70-86.4 Gy@1.8-2.0 Gy/fraction were obtained, and corrected for fractionation effects (α/β = 3 Gy). Cohorts with best-fit Lyman-Kutcher-Burman volume-effect parameter a were pooled after calibration adjustments of the available LRB definitions. In the pooled cohort, dose-response modeling (incorporating rectal dose and geometry, and patient characteristics) was conducted on a training cohort (70%) followed by final testing on the remaining 30%. Multivariate logistic regression was performed to build models with bootstrap stability. RESULTS: Two cohorts with low bleeding rates (2%) were judged to be inconsistent with the remaining data, and were excluded. In the remaining pooled cohorts (n = 690; LRB rate = 12%), an optimal model was generated for 3DCRT using the minimum rectal dose and the absolute rectal volume receiving less than 55 Gy (AUC = 0.67; p = 0.0002; Hosmer-Lemeshow p-value, pHL = 0.59). The model performed nearly as well in the hold-out testing data (AUC = 0.71; p < 0.0001; pHL = 0.63), indicating a logistically shaped dose-response. CONCLUSION: We have demonstrated the importance of integrating datasets from multiple institutions, thereby reducing the impact of intra-institutional dose-volume parameters explicitly correlated with prescription dose levels. This uncovered an unexpected emphasis on sparing of the low to intermediate rectal dose range in the etiology of late rectal bleeding following prostate radiotherapy.
PURPOSE: To investigate whether inter-institutional cohort analysis uncovers more reliable dose-response relationships exemplified for late rectal bleeding (LRB) following prostate radiotherapy. MATERIAL AND METHODS: Data from five institutions were used. Rectal dose-volume histograms (DVHs) for 989 patients treated with 3DCRT or IMRT to 70-86.4 Gy@1.8-2.0 Gy/fraction were obtained, and corrected for fractionation effects (α/β = 3 Gy). Cohorts with best-fit Lyman-Kutcher-Burman volume-effect parameter a were pooled after calibration adjustments of the available LRB definitions. In the pooled cohort, dose-response modeling (incorporating rectal dose and geometry, and patient characteristics) was conducted on a training cohort (70%) followed by final testing on the remaining 30%. Multivariate logistic regression was performed to build models with bootstrap stability. RESULTS: Two cohorts with low bleeding rates (2%) were judged to be inconsistent with the remaining data, and were excluded. In the remaining pooled cohorts (n = 690; LRB rate = 12%), an optimal model was generated for 3DCRT using the minimum rectal dose and the absolute rectal volume receiving less than 55 Gy (AUC = 0.67; p = 0.0002; Hosmer-Lemeshow p-value, pHL = 0.59). The model performed nearly as well in the hold-out testing data (AUC = 0.71; p < 0.0001; pHL = 0.63), indicating a logistically shaped dose-response. CONCLUSION: We have demonstrated the importance of integrating datasets from multiple institutions, thereby reducing the impact of intra-institutional dose-volume parameters explicitly correlated with prescription dose levels. This uncovered an unexpected emphasis on sparing of the low to intermediate rectal dose range in the etiology of late rectal bleeding following prostate radiotherapy.
Authors: Maria Thor; Joseph O Deasy; Rebecca Paulus; W Robert Lee; Mahul B Amin; Deborah W Bruner; Daniel A Low; Amit B Shah; Shawn C Malone; Jeff M Michalski; Ian S Dayes; Samantha A Seaward; Elizabeth M Gore; Michele Albert; Thomas M Pisansky; Sergio L Faria; Yuhchyau Chen; Bridget F Koontz; Gregory P Swanson; Stephanie L Pugh; Howard M Sandler Journal: Radiother Oncol Date: 2019-03-05 Impact factor: 6.280
Authors: Howard J Lee; Meghan W Macomber; Matthew B Spraker; Stephen R Bowen; Daniel Hippe; Angela Fung; Kenneth J Russell; George E Laramore; Ramesh Rengan; Jay Liao; Smith Apisarnthanarax; Jing Zeng Journal: Adv Radiat Oncol Date: 2018-08-13