Format

Send to

Choose Destination
Radiother Oncol. 2019 Jun;135:19-24. doi: 10.1016/j.radonc.2019.02.014. Epub 2019 Mar 5.

Tolerance doses for late adverse events after hypofractionated radiotherapy for prostate cancer on trial NRG Oncology/RTOG 0415.

Author information

1
Memorial Sloan Kettering Cancer Center, United States. Electronic address: thorm@mskcc.org.
2
Memorial Sloan Kettering Cancer Center, United States.
3
Duke University Medical Center, United States.
4
University of Tennessee Health Science Center, United States.
5
Emory University/Winship Cancer Institute, United States.
6
UCLA, United States.
7
WellSpan Health-York Cancer Center (current) -Thomas Jefferson University Hospital (accrual), United States.
8
University of Western Ontario, United States.
9
Washington University, United States.
10
McMaster University, Canada.
11
Kaiser Permanente Northern California (current) University of California San Francisco (accruals), United States.
12
Medical College of Wisconsin and Zablocki Veterans Administration Medical Center, United States.
13
Saint Anne's Hospital (current) Massachusetts General Hospital (accruals), United States.
14
Mayo Clinic, United States.
15
McGill University, United States.
16
University of Rochester, United States.
17
Scott and White Memorial, United States.
18
NRG Oncology Statistics and Data Management Center, United States.
19
Cedars-Sinai Medical Center, United States.

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 (AUCvalidation) was within AUCtraining ± SD with p ≤ 0.05, and with an Hosmer-Lemeshow p-value (pHL) > 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 (AUCvalidation = 0.64, 0.65; p = 0.01, 0.03; pHL = 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 (AUCtraining = 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.

KEYWORDS:

Gastrointestinal; Genitourinary; Hypofractionation; Prostate cancer; Radiotherapy; Toxicity

PMID:
31015166
PMCID:
PMC6582638
[Available on 2020-06-01]
DOI:
10.1016/j.radonc.2019.02.014

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center