Analysis of Gastrointestinal Toxicity in Patients Receiving Proton Beam Therapy for Prostate Cancer: A Single-Institution Experience

Abstract

Purpose: We characterized both physician- and patient-reported rates of gastrointestinal (GI) toxicity in patients treated with proton beam therapy (PBT) at our institution for prostate adenocarcinoma and identified factors associated with toxicity.

Methods and materials: We treated 192 patients with PBT between July 2013 and July 2016. Included patients had ≥1 year of follow-up. Potential preexisting clinical and treatment-related risk factors for GI toxicity were recorded. Common Terminology Criteria for Adverse Events version 4.0 was used to score toxicity. Expanded Prostate Cancer Index Composite (EPIC) bowel domain questionnaires assessed patient-reported quality of life. Associations between grade (GR) 2+ toxicity and clinical, treatment, and dosimetric factors were assessed using Cox models and corresponding hazard ratios.

Results: The median follow-up was 1.7 years. Most of the observed GI toxicity (>90%) was in the form of rectal bleeding (RB). GR2+ GI toxicity and RB actuarial rates specifically at 2 years were 21.3% and 20.4%, respectively. GR3 toxicity was rare, with only 1 observed RB event. No GR4/5 toxicity was seen. The EPIC bowel domain median score was 96 (range, 61-100) pretreatment, 93 (range, 41-100) at 1 year, 89 (range, 57-100) at 1.5 years, and 89 (range, 50-100) at 2 years. Anticoagulation use was the only factor selected during multivariate analysis for predicting GR2+ RB, with a resulting concordance index of 0.59 (95% confidence interval, 0.48-0.68; P = .088). Type of proton technology (pencil beam scanning vs uniform scanning) and number of fields treated per day (1 vs 2) showed no significant difference in toxicity rate.

Conclusions: PBT was associated with acceptable rates of GR2+ transient GI toxicity, mostly in the form of RB, which correlated with anticoagulation use. High EPIC bowel domain quality of life was maintained in the 2 years after treatment.

Figure 1

Rectal dose-volume histogram parameter distributions for 192 patients. (A) Rectum V50 Cobalt gray equivalents (CGE); (B) rectum V70 CGE; (C) rectal wall V50 CGE; and (D) rectal wall V70 CGE.

Figure 2

Cumulative toxicity rates for grades 1+ and 2+ rectal bleeding. Solid lines indicate the Kaplan-Meier estimate, and dashed lines indicate the 95% confidence intervals.

Figure 3

Box-whisker representation of the Expanded Prostate Cancer Index Composite bowel domain survey scores at pretreatment and 1, 1.5, and 2 years posttreatment. Score decrease from pretreatment to 1 year was statistically significantly different (P < .001). There was no significant further decrease in score. Solid bolded black lines indicate median scores. Upper and lower box edges indicate 75th and 25th percent quartile score, respectively. Whiskers indicate 1.5 times the interquartile range of the box. Circular data points indicate individual recorded scores falling outside the boxes and whiskers.