Faculty Collaboration Database

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415. Radiother Oncol 2019 Jun;135:19-24

Date

04/25/2019

Pubmed ID

31015166

Pubmed Central ID

PMC6582638

DOI

10.1016/j.radonc.2019.02.014

Scopus ID

2-s2.0-85062352777 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

PURPOSE/OBJECTIVE: Hypofractionated radiotherapy (HRT) regimens for prostate cancer are emerging, but tolerance doses for late adverse events are scarce. The purpose of this study is to define dose-volume predictors for late gastrointestinal and genitourinary (GI and GU) toxicities after HRT in the multi-center NRG Oncology/RTOG 0415 low-risk prostate cancer trial (N = 521).

MATERIAL/METHODS: Treatment in the studied HRT arm was delivered as 70 Gy at 2.5 Gy/fraction with 3D-CRT/IMRT (N = 108/413). At a median follow-up of 5.9 years, the crude late ≥Grade 2 GI and GU toxicities were 19% and 29%, respectively. For modeling, the complete HRT cohort was randomly split into training and validation (70% and 30%; preserved toxicity rates). Within training, dose-response modeling was based on dose-volume cut-points (EQD2Gy; bladder/rectum: α/β = 6 Gy/3Gy), age, acute ≥Grade 2 toxicity, and treatment technique using univariate and multivariate logistic regression on bootstrapping (UVA and MVA). Candidate predictors were determined at p ≤ 0.05, and the selected MVA models were explored on validation where model generalizability was judged if the area under the receiver-operating curve in validation (AUC_validation) was within AUC_training ± SD with p ≤ 0.05, and with an Hosmer-Lemeshow p-value (p_HL) > 0.05.

RESULTS: Three candidate predictors were suggested for late GI toxicity: the minimum dose to the hottest 5% rectal volume (D5%[Gy]), the absolute rectal volume <35 Gy, and acute GI toxicity (AUC = 0.59-0.63; p = 0.02-0.04). The two generalizable MVA models, i.e., D5%[Gy] with or without acute GI toxicity (AUC_validation = 0.64, 0.65; p = 0.01, 0.03; p_HL = 0.45-0.56), suggest that reducing late GI toxicity from 20% to 10% would require reducing D5%[Gy] from ≤65 Gy to ≤62 Gy (logistic function argument: 17+(0.24D5%[Gy])). Acute GU toxicity showed only a trend to predict late GU toxicity (AUC_training = 0.57; p = 0.07).

CONCLUSION: Late GI toxicity, following moderate HRT for low-risk prostate cancer, increases with higher doses to small rectal volumes. This work provides quantitative evidence that limiting small rectal dose 'hotspots' in clinical practice of such HRT regimens is likely to further reduce the associated rates of GI toxicity.

Author List

Thor M, Deasy JO, Paulus R, Robert Lee W, Amin MB, Bruner DW, Low DA, Shah AB, Malone SC, Michalski JM, Dayes IS, Seaward SA, Gore EM, Albert M, Pisansky TM, Faria SL, Chen Y, Koontz BF, Swanson GP, Pugh SL, Sandler HM

Author

Elizabeth M. Gore MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Dose-Response Relationship, Radiation
Gastrointestinal Diseases
Humans
Logistic Models
Male
Models, Statistical
Predictive Value of Tests
Proctitis
Prostatic Neoplasms
Radiation Injuries
Radiotherapy Dosage
Radiotherapy, Conformal
Rectum
Urogenital System