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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 (EQD2?/?) 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 ?/? = 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.

SUBMITTER: Olsson CE

PROVIDER: S-EPMC6652194 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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A Systematic Post-QUANTEC Review of Tolerance Doses for Late Toxicity After Prostate Cancer Radiation Therapy.

Olsson Caroline E CE Jackson Andrew A Deasy Joseph O JO Thor Maria M

International journal of radiation oncology, biology, physics 20180817 5

<h4>Purpose</h4>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 (D ...[more]

PMID: 30125635

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Project description:Purpose:Dose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity. Methods and materials:164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6?Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4?Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2?+?(G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ?35, 55%, and bladder-CTV V65, 40 ?50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ?20, 40, 80% and bladder V70, 65, 40 ?30, 60, 80%, respectively) guidelines were evaluated. Results:With a median follow-up time of of 33 months, the 4-year freedom from G2?+?GI and GU toxicity were both 91%. G2?+?GI (n?=?12) and GU (n?=?15) toxicity included 4% diarrhea (n?=?6), 4% hemorrhage (n?=?6), 1% proctitis (n?=?1), and 4% urinary frequency (n?=?7), 1% obstructive (n?=?2), 2% cystitis (n?=?3), and 3% incontinence (n?=?5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P?>?.1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity. Conclusions:More than 90% of men were free from late G2?+?toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

Project description:PurposeTo report acute and late bowel, urinary, and sexual dysfunction patient-reported outcome measures, among patients with localized prostate cancer who underwent stereotactic magnetic resonance-guided daily adaptive radiation therapy (SMART).Methods and materialsAll patients who completed a baseline 12-item Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events questionnaire, before undergoing SMART with 36.25 Gy in 5 fractions, were subsequently followed up with the same graded questionnaire at set time points. Latest prostate-specific antigen levels were recorded. The percentage of patients who reported no change from their baseline adverse event (AE) or reported a new ≥ "frequent or almost constant" or "severe grade or higher" AE grade during follow-up was calculated. The maximum 12-item Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events grade for each item was recorded for each patient. The percentage of toxicity levels for each separate AE item at set time points was calculated.ResultsThe total number of patients was 69 with a median follow-up of 27 months. Median age of the cohort was 73 years (range, 54-85 years). The median pretreatment prostate-specific antigen level, T stage, and Gleason score were 7.5 mmol/L (range, 4.5-32 mmol/L), T2b (range, T2-T3b), and 7 (3 + 4; range, 6-9), respectively. No patient had biochemical failure during follow-up. Regarding bowel symptoms, >80% of men reported no change from baseline toxicity during follow-up. New ≥ frequent or almost constant diarrhea was reported in 9% of patients. "Almost constant" diarrhea peaked at 1 month but was absent at >33 months. Regarding urinary symptoms, increased urinary urgency was the most common complaint (39%). Twenty percent of men reported new ≥ frequent or almost constant urinary urgency incidence peaking at 1 month but absent at >33 months. New "severe" sexual dysfunction was seen in 26% of patients and was persistent at >33 months.ConclusionsOur study is one the largest patient-reported outcomes study after prostate SMART. It shows acceptable levels of toxicity even up to 2 years after treatment.

Dataset Information

A Systematic Post-QUANTEC Review of Tolerance Doses for Late Toxicity After Prostate Cancer Radiation Therapy.

Publications

A Systematic Post-QUANTEC Review of Tolerance Doses for Late Toxicity After Prostate Cancer Radiation Therapy.

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