Late toxicity rates following definitive radiotherapy for prostate cancer

Nitin Ohri, Adam P. Dicker, Timothy N. Showalter

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Introduction: Most patients survive many years following external beam radiotherapy (RT) for nonmetastatic prostate cancer and are therefore at risk for late treatment sequelae. The relationships between RT dose, treatment technique, and late toxicity rates are incompletely understood. Here we perform a meta-analysis and systematic review to characterize those effects. Materials and methods: We performed a review of published series that report late gastrointestinal (GI) and genitourinary (GU) toxicity rates following definitive RT for prostate cancer using the RTOG Late Radiation Morbidity Scoring Schema. Univariate analyses were performed to test RT technique, RT dose, pelvic irradiation, and androgen deprivation therapy (ADT) as predictors of moderate (grade ≥ 2) and severe (grade ≥ 3) GI and GU toxicity. To isolate the effect of radiotherapy dose on late toxicity, we also performed a meta-analysis restricted to randomized trials that tested RT dose escalation. Statistical analyses were repeated using the subset of studies that utilized escalated RT doses. Results: Twenty published reports detailing the treatment techniques and toxicity outcomes of 35 patient series including a total of 11,835 patients were included in this analysis. Median rates of moderate late toxicity were 15% (GI) and 17% (GU). For severe effects, these values were 2% (GI) and 3% (GU). Meta-analysis of five randomized trials revealed that an 8-10 Gy increase in RT dose increases the rate of both moderate (OR = 1.63, 95% CI: [1.44 to 1.82], p < 0.001) and severe (OR = 2.03, 95% CI: [1.64 to 2.42], p < 0.001) late GI toxicity. Among 17 series where doses of at least 74 Gy were utilized, use of intensity-modulated radiotherapy (IMRT) or proton beam radiotherapy (PBRT) was associated with a significant decrease in the reported rate of severe GI toxicity compared to 3-D RT. Conclusion: Meta-analysis of randomized dose escalation trials demonstrates that late toxicity rates increase with RT dose. Series where dose escalated RT is delivered using IMRT or PBRT have relatively short follow up but report lower late GI toxicity rates than those employing 3-D RT.

Original languageEnglish (US)
Pages (from-to)6373-6380
Number of pages8
JournalCanadian Journal of Urology
Volume19
Issue number4
StatePublished - Aug 2012
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Radiotherapy
Meta-Analysis
Intensity-Modulated Radiotherapy
Protons
Therapeutics
Androgens
Radiation
Morbidity

Keywords

  • Dose
  • IMRT
  • Late toxicity
  • Prostate cancer
  • Proton
  • Radiation therapy

ASJC Scopus subject areas

  • Urology

Cite this

Late toxicity rates following definitive radiotherapy for prostate cancer. / Ohri, Nitin; Dicker, Adam P.; Showalter, Timothy N.

In: Canadian Journal of Urology, Vol. 19, No. 4, 08.2012, p. 6373-6380.

Research output: Contribution to journalArticle

Ohri, Nitin ; Dicker, Adam P. ; Showalter, Timothy N. / Late toxicity rates following definitive radiotherapy for prostate cancer. In: Canadian Journal of Urology. 2012 ; Vol. 19, No. 4. pp. 6373-6380.
@article{b33506893e00448ebe753e3e725638a7,
title = "Late toxicity rates following definitive radiotherapy for prostate cancer",
abstract = "Introduction: Most patients survive many years following external beam radiotherapy (RT) for nonmetastatic prostate cancer and are therefore at risk for late treatment sequelae. The relationships between RT dose, treatment technique, and late toxicity rates are incompletely understood. Here we perform a meta-analysis and systematic review to characterize those effects. Materials and methods: We performed a review of published series that report late gastrointestinal (GI) and genitourinary (GU) toxicity rates following definitive RT for prostate cancer using the RTOG Late Radiation Morbidity Scoring Schema. Univariate analyses were performed to test RT technique, RT dose, pelvic irradiation, and androgen deprivation therapy (ADT) as predictors of moderate (grade ≥ 2) and severe (grade ≥ 3) GI and GU toxicity. To isolate the effect of radiotherapy dose on late toxicity, we also performed a meta-analysis restricted to randomized trials that tested RT dose escalation. Statistical analyses were repeated using the subset of studies that utilized escalated RT doses. Results: Twenty published reports detailing the treatment techniques and toxicity outcomes of 35 patient series including a total of 11,835 patients were included in this analysis. Median rates of moderate late toxicity were 15{\%} (GI) and 17{\%} (GU). For severe effects, these values were 2{\%} (GI) and 3{\%} (GU). Meta-analysis of five randomized trials revealed that an 8-10 Gy increase in RT dose increases the rate of both moderate (OR = 1.63, 95{\%} CI: [1.44 to 1.82], p < 0.001) and severe (OR = 2.03, 95{\%} CI: [1.64 to 2.42], p < 0.001) late GI toxicity. Among 17 series where doses of at least 74 Gy were utilized, use of intensity-modulated radiotherapy (IMRT) or proton beam radiotherapy (PBRT) was associated with a significant decrease in the reported rate of severe GI toxicity compared to 3-D RT. Conclusion: Meta-analysis of randomized dose escalation trials demonstrates that late toxicity rates increase with RT dose. Series where dose escalated RT is delivered using IMRT or PBRT have relatively short follow up but report lower late GI toxicity rates than those employing 3-D RT.",
keywords = "Dose, IMRT, Late toxicity, Prostate cancer, Proton, Radiation therapy",
author = "Nitin Ohri and Dicker, {Adam P.} and Showalter, {Timothy N.}",
year = "2012",
month = "8",
language = "English (US)",
volume = "19",
pages = "6373--6380",
journal = "Canadian Journal of Urology",
issn = "1195-9479",
publisher = "Canadian Journal of Urology",
number = "4",

}

TY - JOUR

T1 - Late toxicity rates following definitive radiotherapy for prostate cancer

AU - Ohri, Nitin

AU - Dicker, Adam P.

AU - Showalter, Timothy N.

PY - 2012/8

Y1 - 2012/8

N2 - Introduction: Most patients survive many years following external beam radiotherapy (RT) for nonmetastatic prostate cancer and are therefore at risk for late treatment sequelae. The relationships between RT dose, treatment technique, and late toxicity rates are incompletely understood. Here we perform a meta-analysis and systematic review to characterize those effects. Materials and methods: We performed a review of published series that report late gastrointestinal (GI) and genitourinary (GU) toxicity rates following definitive RT for prostate cancer using the RTOG Late Radiation Morbidity Scoring Schema. Univariate analyses were performed to test RT technique, RT dose, pelvic irradiation, and androgen deprivation therapy (ADT) as predictors of moderate (grade ≥ 2) and severe (grade ≥ 3) GI and GU toxicity. To isolate the effect of radiotherapy dose on late toxicity, we also performed a meta-analysis restricted to randomized trials that tested RT dose escalation. Statistical analyses were repeated using the subset of studies that utilized escalated RT doses. Results: Twenty published reports detailing the treatment techniques and toxicity outcomes of 35 patient series including a total of 11,835 patients were included in this analysis. Median rates of moderate late toxicity were 15% (GI) and 17% (GU). For severe effects, these values were 2% (GI) and 3% (GU). Meta-analysis of five randomized trials revealed that an 8-10 Gy increase in RT dose increases the rate of both moderate (OR = 1.63, 95% CI: [1.44 to 1.82], p < 0.001) and severe (OR = 2.03, 95% CI: [1.64 to 2.42], p < 0.001) late GI toxicity. Among 17 series where doses of at least 74 Gy were utilized, use of intensity-modulated radiotherapy (IMRT) or proton beam radiotherapy (PBRT) was associated with a significant decrease in the reported rate of severe GI toxicity compared to 3-D RT. Conclusion: Meta-analysis of randomized dose escalation trials demonstrates that late toxicity rates increase with RT dose. Series where dose escalated RT is delivered using IMRT or PBRT have relatively short follow up but report lower late GI toxicity rates than those employing 3-D RT.

AB - Introduction: Most patients survive many years following external beam radiotherapy (RT) for nonmetastatic prostate cancer and are therefore at risk for late treatment sequelae. The relationships between RT dose, treatment technique, and late toxicity rates are incompletely understood. Here we perform a meta-analysis and systematic review to characterize those effects. Materials and methods: We performed a review of published series that report late gastrointestinal (GI) and genitourinary (GU) toxicity rates following definitive RT for prostate cancer using the RTOG Late Radiation Morbidity Scoring Schema. Univariate analyses were performed to test RT technique, RT dose, pelvic irradiation, and androgen deprivation therapy (ADT) as predictors of moderate (grade ≥ 2) and severe (grade ≥ 3) GI and GU toxicity. To isolate the effect of radiotherapy dose on late toxicity, we also performed a meta-analysis restricted to randomized trials that tested RT dose escalation. Statistical analyses were repeated using the subset of studies that utilized escalated RT doses. Results: Twenty published reports detailing the treatment techniques and toxicity outcomes of 35 patient series including a total of 11,835 patients were included in this analysis. Median rates of moderate late toxicity were 15% (GI) and 17% (GU). For severe effects, these values were 2% (GI) and 3% (GU). Meta-analysis of five randomized trials revealed that an 8-10 Gy increase in RT dose increases the rate of both moderate (OR = 1.63, 95% CI: [1.44 to 1.82], p < 0.001) and severe (OR = 2.03, 95% CI: [1.64 to 2.42], p < 0.001) late GI toxicity. Among 17 series where doses of at least 74 Gy were utilized, use of intensity-modulated radiotherapy (IMRT) or proton beam radiotherapy (PBRT) was associated with a significant decrease in the reported rate of severe GI toxicity compared to 3-D RT. Conclusion: Meta-analysis of randomized dose escalation trials demonstrates that late toxicity rates increase with RT dose. Series where dose escalated RT is delivered using IMRT or PBRT have relatively short follow up but report lower late GI toxicity rates than those employing 3-D RT.

KW - Dose

KW - IMRT

KW - Late toxicity

KW - Prostate cancer

KW - Proton

KW - Radiation therapy

UR - http://www.scopus.com/inward/record.url?scp=84874403859&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84874403859&partnerID=8YFLogxK

M3 - Article

C2 - 22892261

AN - SCOPUS:84874403859

VL - 19

SP - 6373

EP - 6380

JO - Canadian Journal of Urology

JF - Canadian Journal of Urology

SN - 1195-9479

IS - 4

ER -