Long term follow up confirms no improvement in OS with dose escalation in this study population. However, there are significant improvements in ABF, PBF, DM, LP, and need for salvage therapy. Despite the use of more salvage therapy in the low dose arm, dose escalated RT resulted in lower rates of DM, a clinically relevant endpoint. Patients receiving dose escalation do experience a higher rate of grade 2+ GU and GI toxicity but no worse grade 3+ toxicities.

The results of this study strongly support that body composition is related to all-cause mortality in men with localized PCa, with most deaths due to causes other than PCa. The inclusion of psoas cross-sectional area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction. This study also confirms the feasibility of performing body composition analysis using archived CT scans using NRG Oncology clinical trial data sets. These methods can be applied to other NRG Oncology data sets to further explore how body composition is related to patient outcomes.

To determine if there is a reduction in patient-reported adverse events (AEs) or differences in disease outcome with intensity-modulated radiation therapy (IMRT) compared to conventional 4-field pelvic radiation (CRT).

RTOG 1203 compared 3-D conformal radiation therapy (3D CRT) to intensity-modulated radiation therapy (IMRT) in patients (pts) with endometrial or cervical cancer requiring post-operative radiation therapy (RT) after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments. RTOG 1203 randomized pts having undergone hysterectomy to either 3DCRT or IMRT. Stratification factors included RT dose, chemotherapy, and disease site. The EQ-5D, both index and visual analog scale (VAS) were obtained at baseline, 5 weeks after the start of RT, 4-6 weeks post RT and 1& 3-years post RT. Quality adjusted survival (QAS) was calculated as the summation of index score multiplied by the duration of days and restricted to patients completing the EQ-5D at baseline and at least one follow-up assessment. EQ-5D index and VAS scores along with QAS were compared between treatment arms using the t-test at a two-sided significance level of 0.05. RTOG 1203 enrolled 289 pts of which 236 consented to participating in the patient reported outcome (PRO) tools. Compliance for the index score and VAS was 93.6% vs 83.5%, 80.5% vs 72.0%, 81.4% vs 72.5% and 68.6% vs 63.6% at baseline, week 5 of RT, 4-6 weeks post RT and 1-year post RT, respectively. QAS was not statistically different in women treated with IMRT, 792.7 days vs 785.6 days (p=0.86) compared to pts treated with 3DCRT. Pts treated with IMRT had less of a decline in VAS score 5 weeks post RT, -4.90, compared to pts treated with 3DCRT, -7.48, although not statistically significant (p=0.36). There was no difference in QAS and VAS score between patients who received IMRT vs. 3DCRT. These were secondary endpoints and the trial was not powered to show statistical differences in these endpoints. This is the first RTOG/NRG study to report QAS as an endpoint. This work may help inform statistical power for future studies of IMRT in the treatment of pts after surgery for gynecologic malignancy.

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.

The NCI Common Terminology Criteria for Adverse Events (CTCAE) have been used as standard practice in oncology trials to report toxicity; however, RTOG studies have previously shown that physician reporting may not accurately reflect toxicity from the patient's perspective. This analysis of NRG Oncology's RTOG 1203 aimed to compare the reporting of symptoms and their severity by patients and clinicians during radiotherapy. RTOG 1203 was a randomized phase III trial of 3D conformal (3DCRT) versus intensity-modulated (IMRT) pelvic radiation for postoperative treatment of endometrial and cervical cancer. Patients completed a six-item PRO-CTCAE GI toxicity questionnaire which asked about frequency, severity, and resulting interference from abdominal pain, diarrhea, and fecal incontinence at multiple time points. Patients reported toxicity on 5-point scales with regard to severity ("none" to "very severe"), interference ("not at all" to "very much"), or frequency ("never" to "almost constantly"). Clinicians also recorded CTCAE GI toxicity as grade 1 through 5. Physician-reported severe toxicity (CTCAE grade 3 or higher) was compared to patient-reported toxicity with high scores for severity, frequency, and/or interference. Physician-reported toxicity (grade 1 or higher) was compared to patients reporting at least a little bit of interference, mild severity, and rarely occurring toxicity. GI toxicities were compared using McNemar's test when rates were >0%. Of the 278 eligible patients, 235 completed the PRO-CTCAE during treatment and in follow-up. For abdominal pain, the grade 3+ CTCAE toxicity rate was 0.9%, whereas 19.6% of women reported severe or very severe abdominal pain, and 19.6% reported that their abdominal pain interfered with their activities quite a bit or very much (P < 0.0001 for both). For diarrhea, the grade 3+ CTCAE toxicity rate was 4.3%. The rate of patient-reported severe and very severe diarrhea was 41.7% (P < 0.0001). The rate of grade 3+ CTCAE fecal incontinence was 0%, whereas 5.1% of women reported frequent or almost constant fecal incontinence, and 8.5% reported that their fecal incontinence interfered with their activities quite a bit or very much. Similar effects were seen between grade 1+ CTCAE toxicity and at least some patient-reported toxicity. Clinician-reported toxicity differs significantly from patient-reported toxicity, and underrepresents the adverse events as experienced by the patient. These results support using PROs as the primary toxicity outcome measure in future oncology trials. This project was supported by grants U10CA21661, U10CA37422, CA81647, U24CA180803, U10CA180868, U10CA180822, and UG1CA189867 from the National Cancer Institute (NCI).