A Phase III Randomized Trial Comparing Patient-Reported Toxicity and Quality of Life (QOL) During Pelvic Intensity Modulated Radiation Therapy as Compared to Conventional Radiation Therapy

To determine if pelvic intensity modulated radiation therapy (IMRT) results in a significant reduction in patient reported acute toxicity, and better QOL as compared to standard radiation. Patients with cervical and endometrial cancer who received pelvic radiation postoperatively were stratified by dose (45 or 50.4 Gy), use of chemotherapy (none or 5 cycles of weekly cisplatin at 40 mg/m2), and disease site, and then randomly assigned to standard 4-field radiation or IMRT. The primary endpoint was change in acute gastrointestinal (GI) toxicity from baseline to 5 weeks measured by the bowel domain of Expanded Prostate Cancer Index Composite (EPIC). Change in EPIC score was calculated such that a negative change score indicated a decline in function. With an effect size of 0.4, a t test with 1 interim look and a 2-sided alpha = 0.05, 225 patients were needed for 85% power. Secondary endpoints included a comparison of adverse events, urinary toxicity using EPIC and QOL using the FACT-G with cervix subscale. A Wilcoxon signed rank test was used for non-normal data. There were 289 patients enrolled between November 2012 and August 2015; 11 patients were found to be ineligible, leaving 278 eligible patients. The conventional RT arm had a significantly larger mean decline in EPIC bowel summary score at 5 weeks as compared to the IMRT arm (-23.6 vs. -18.6, P = 0.048). The median change in bowel function subscale was -17.9 for the conventional RT arm, as compared to -14.3 for the IMRT arm (P = 0.03). For the bother subscale, the median change in score was -21.4 as compared to -21.4 (P = 0.18). The conventional arm experienced a significantly larger mean decline in EPIC urinary summary score at 5 weeks as compared to the IMRT arm (-10.4 vs. -5.6, P = 0.03). At 5 weeks from the start of RT, the conventional arm experienced more high-level adverse events measured by the Patient-Reported Outcomes version of the Common Terminology for Adverse Events(PRO-CTCAE) for diarrhea (frequency, P = 0.01), and fecal incontinence (frequency, P = 0.01; interference, P = 0.04). In addition, 20.4% of women on the standard RT arm took 4 or more antidiarrheal medications daily, as compared to 7.8% of women on the IMRT arm (P = 0.04). Quality of life measured with the FACT-Cx demonstrated a greater decline in the trial outcome index score in patients treated with conventional radiation as compared to patients receiving IMRT (-12.8 vs. -8.8, P = 0.03). Intensity modulated radiation therapy reduces acute patient reported GI and GU toxicity as compared to standard RT. Furthermore, patients treated with IMRT experienced better QOL during treatment. Longer follow-up will be needed to determine if differences in acute toxicity result in lower rates of chronic toxicity.