A systematic post-QUANTEC review of tolerance doses for late toxicity after prostate cancer radiation therapy Journal Article


Authors: Olsson, C. E.; Jackson, A.; Deasy, J. O.; Thor, M.
Article Title: A systematic post-QUANTEC review of tolerance doses for late toxicity after prostate cancer radiation therapy
Abstract: Purpose: The aims of this study were to systematically review tolerance doses for late distinct gastrointestinal (GI), genitourinary (GU), and sexual dysfunction (SD) symptoms after external beam radiation therapy (EBRT) alone and treatments involving brachytherapy (BT) for prostate cancer after Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) and ultimately to perform quantitative syntheses of identified dose/volume tolerances represented by dose-volume histogram (DVH) thresholds, that is, statistically significant (P ≤.05) cutoff points between symptomatic and asymptomatic patients in a certain study. Methods and Materials: PubMed was scrutinized for full-text articles in English after QUANTEC (January 1, 2010). The inclusion criteria were randomized controlled trials, case-control studies, or cohort studies with tolerance doses for late distinct symptoms ≥3 months after primary radiation therapy for prostate cancer (N > 30). All DVH thresholds were converted into equivalent doses in 2-Gy fractions (EQD2α/β) and were fitted with a linear or linear-quadratic function (goodness of fit, R2). The review was registered on PROSPERO (CRD42016042464). Results: From 33 identified studies, which included 36 to 746 patients per symptom domain, the majority of dose/volume tolerances were derived for GI toxicity after EBRT alone (GI, 97 thresholds; GU, 8 thresholds; SD, 1 threshold). For 5 symptoms (defecation urgency, diarrhea, fecal incontinence, proctitis, and rectal bleeding), relationships between dose/volume tolerances across studies (R2 = 0.93 [0.82-1.00]), and across symptoms, leading to a curve for overall GI toxicity (R2 = 0.98), could be determined. For these symptoms, mainly rectal thresholds were found throughout low and high doses (10 Gy ≤ equivalent dose in 2-Gy fractions using α/β = 3Gy (EQD23) ≤ 50 Gy and 55 Gy ≤ EQD23 ≤ 78 Gy, respectively). For BT with or without EBRT, dose/volume tolerances were also mainly identified for GI toxicity (GI, 14 thresholds; GU, 4 thresholds; SD, 2 thresholds) with the largest number of DVH thresholds concerning rectal bleeding (5 thresholds). Conclusions: Updated dose/volume tolerances after QUANTEC were found for 17 GI, GU, or SD symptoms. A DVH curve described the relationship between dose/volume tolerances across 5 GI symptoms after EBRT alone. Restricting treatments for EBRT alone using the lower boundaries of this curve is likely to limit overall GI toxicity, but this should be explored prospectively. Dose/volume tolerances for GU and SD toxicity after EBRT alone and after BT with or without EBRT were scarce and support further research including data-sharing initiatives to untangle the dose/volume relationships for these symptoms. © 2018 Elsevier Inc.
Keywords: randomized controlled trial; radiotherapy; sexual dysfunction; radiation effects; urology; toxicity; diseases; fecal incontinence; external beam radiation therapy; asymptomatic patients; dose-volume histograms; methods and materials; fits and tolerances; primary radiations
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 102
Issue: 5
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2018-12-01
Start Page: 1514
End Page: 1532
Language: English
DOI: 10.1016/j.ijrobp.2018.08.015
PROVIDER: scopus
PUBMED: 30125635
PMCID: PMC6652194
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
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  1. Andrew Jackson
    253 Jackson
  2. Joseph Owen Deasy
    524 Deasy
  3. Maria Elisabeth Thor
    149 Thor