Fewer GI, GU Toxicities With Postoperative Pelvic IMRT in Gynecologic Malignancies

Ann H. Klopp, MD, PhD

Patients with endometrial and cervical cancer reported significantly less acute gastrointestinal toxicity (GI) when treated with pelvic intensity-modulated radiation therapy (IMRT) as opposed to standard pelvic radiation therapy, according to findings from a randomized phase III trial.

As assessed by a validated questionnaire, patients had a significantly higher composite bowel score after a 5-week IMRT protocol. The overall score was driven by a significantly higher score on the bowel-function component of the questionnaire, although patients randomized to IMRT also reported numerically less bowel bother.

Genitourinary (GU) toxicity, a secondary outcome, also was reduced among patients treated with IMRT, as reported at the 2016 American Society for Radiation Oncology (ASTRO) Annual Meeting in Boston.

“Pelvic IMRT reduces acute patient-reported GI and GU toxicity compared to standard pelvic RT,” said Ann H. Klopp, MD, PhD, an associate professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center. “Pelvic IMRT improves quality of life with regard to physical functioning and other treatment effects during treatment. Longer-term follow-up will be needed to determine if these differences in acute toxicity result in lower rates of late toxicity.”

Retrospective studies have suggested that pelvic IMRT is associated with less acute and chronic GI toxicity as compared with conventional pelvic radiation therapy. The RTOG-(now NRG) 0418 trial demonstrated the feasibility of postoperative pelvic IMRT in an multi-institutional investigation, and the technique was associated with a favorable rate of acute grade 2+ GI toxicity as compared with historical data for conventional pelvic radiation therapy (25%).

Klopp reported findings from a multicenter randomized trial to compare the toxicity associated with postoperative IMRT and conventional four-field pelvic radiation in patients with endometrial and cervical cancer. Treating physicians had the discretion to treat patients with a total radiation dose of 45 or 50.4 Gy and to give no chemotherapy or administer cisplatin weekly with radiation therapy at a dose of 40 mg/m².

The primary endpoint was patient-reported acute GI toxicity after 5 weeks of treatment. Secondary endpoints consisted of patient-reported acute urinary toxicity, quality of life, local control, disease-free survival, overall survival, and a health utilities analysis. Klopp reported only the data for the primary endpoint and for acute urinary toxicity at this meeting.

Using a series of validated instruments, investigators assessed patients at baseline, 3 weeks after starting radiation therapy, end of radiation therapy, 4 to 5 weeks after completing radiation therapy (resolution of acute toxicity), 1 year later (chronic toxicity), and 3 years later (long-term toxicity).

To assess acute GI toxicity, investigators used the bowel domain of the expanded prostate cancer index composite (EPIC) questionnaire. That portion of the questionnaire evaluated patient bowel function and bowel bother. The bowel function questions addressed rectal urgency, uncontrolled leakage of stool, loose stools, bloody stools, painful bowl movements, frequency of bowel movements, and associated abdominal or pelvic pain. Bowel bother questions addressed how big of a problem each of the issues posed for the patient.

The primary analysis included 278 patients who had a median age of 62, and 70% to 80% of the patients had a Zubrod performance status of 0. A majority (55% to 60%) of the patients received a total radiation dose of 45 Gy, and about three-fourths of the patients did not receive chemotherapy. The endometrium was the disease site in 84% of the patients in both treatment groups.

Comparison of bowel summary mean scores showed a 5-point difference in favor of the IMRT arm, -18.6 versus -23.6 for patients randomized to conventional pelvic radiation therapy (P = 0.048). The bowel function mean score was -14.8 in the IMRT group and -21.0 in the conventionally treated group (P = 0.02). The mean bowel bother scores were -22.3 in the IMRT group and -26.1 in the conventional RT group (P = 0.19).

Investigators also assessed patients by means of Pro-CTCAE—common terminology criteria for adverse events—questions related to bowel function and bother. The results showed that conventionally treated patients had significantly more diarrhea and fecal incontinence and required significantly more anti-diarrheal medication (P <0.05).

The summary results for the EPIC urinary questions showed a mean score of -5.6 for the IMRT group and -10.4 for the conventionally treated patients (P = 0.03).

Quality-of-life assessment by the FACT-Cx showed that IMRT had a significantly less detrimental effect on physical well being (P = 0.03) and resulted in significantly fewer additional treatment-related concerns (P = 0.01).

Klopp A, Yeung A, Deshmukh S, et al. A randomized phase III study (NRG Oncology’s RTOG 1203) of standard vs. IMRT pelvic radiation for post-operative treatment of endometrial and cervical cancer (TIME-C). Presented at: 2016 ASTRO Annual Meeting; Boston, Massachusetts, September 25-28, 2016.