Dataset Information

Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397).

ABSTRACT:

Purpose

In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects.

Methods and materials

The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires.

Results

In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade >or=2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade >or=2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade >or=2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively.

Conclusions

There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

SUBMITTER: Syndikus I

PROVIDER: S-EPMC2937212 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Publications

Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397).

Syndikus Isabel I Morgan Rachel C RC Sydes Matthew R MR Graham John D JD Dearnaley David P DP

International journal of radiation oncology, biology, physics 20091014 3

<h4>Purpose</h4>In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects.<h4>Methods and materials</h4>The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly ass ...[more]

PMID: 19836155

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Project description:Purpose: Late gastrointestinal (GI) toxicity after radiotherapy for prostate cancer may have significant impact on the cancer survivor's quality of life. To date, little is known about local dose-effects after modern radiotherapy including hypofractionation. In the current study we related the local spatial distribution of radiation dose in the rectum to late patient-reported gastrointestinal (GI) toxicities for conventionally fractionated (CF) and hypofractionated (HF) modern radiotherapy in the randomized HYPRO trial. Material and Methods: Patients treated to 78 Gy in 2 Gy fractions (n = 298) or 64.6 Gy in 3.4 Gy fractions (n = 295) with available late toxicity questionnaires (n ? 2 within 1-5 years post-treatment) and available 3D planning data were eligible for this study. The majority received intensity modulated radiotherapy (IMRT). We calculated two types of dose surface maps: (1) the total delineated rectum with its central axis scaled to unity, and (2) the delineated rectum with a length of 7 cm along its central axis aligned on the prostate's half-height point (prostate-half). For each patient-reported GI symptom, dose difference maps were constructed by subtracting average co-registered EQD2 (equivalent dose in 2 Gy) dose maps of patients with and without the symptom of interest, separately for HF and CF. P-values were derived from permutation tests. We evaluated patient-reported moderate to severe GI symptoms. Results: Observed incidences of rectal bleeding and increased stool frequency were significantly higher in the HF group. For rectal bleeding (p = 0.016), mucus discharge (p = 0.015), and fecal incontinence (p = 0.001), significant local dose-effects were observed in HF patients but not in CF patients. For rectal pain, similar local dose-effects (p < 0.05) were observed in both groups. No significant local dose-effects were observed for increased stool frequency. Total rectum mapping vs. prostate-half mapping showed similar results. Conclusion: We demonstrated significant local dose-effect relationships for patient-reported late GI toxicity in patients treated with modern RT. HF patients were at higher risk for increased stool frequency and rectal bleeding, and showed the most pronounced local dose-effects in intermediate-high dose regions. These findings suggest that improvement of current treatment optimization protocols could lead to clinical benefit, in particular for HF treatment.

Dataset Information

Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397).

Purpose

Methods and materials

Results

Conclusions

Publications

Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397).

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