BOSTON (FRONTLINE MEDICAL NEWS) – For women with cervical or endometrial cancers, postoperative pelvic irradiation with intensity-modulated radiation therapy (IMRT) is associated with a reduction in acute gastrointestinal or genitourinary side effects, better physical functioning, and better quality of life than standard four-field pelvic radiation therapy, investigators contend.

Five weeks after the start of radiation therapy, women treated with pelvic IMRT in a phase III multicenter randomized trial had significantly better bowel and urinary function scores on the Expanded Prostate Index Composite ( EPIC ) scale, a patient reported–outcomes instrument, said co-principal investigator Ann H. Klopp, MD , from the University of Texas MD Anderson Cancer in Houston.

“IMRT reduced acute GI and toxicity and patients needed less medication for diarrhea. It improved quality of life with regard to physical functioning, and we’ll need to follow these patients for a longer period of time to find out how these changes persist, if they do,” she said at the annual scientific meeting of the American Society of Radiation Oncology.

The trial, nicknamed TIME-C , was specifically designed to determine whether IMRT could reduce acute GI toxicities relative to standard therapy in the 5th week of treatment, after 23 to 25 radiation fractions had been delivered, with urinary toxicities and quality of life measures as secondary endpoints.

Eligible patients were women with pathologically proven diagnoses of endometrial and/or cervical cancer who required postoperative radiation or chemoradiation and had good performance statuses.

Following stratification by dose level (45 or 50.4 Gy), chemotherapy (five cycles of weekly cisplatin 40 mg/m2) or no chemotherapy, and disease site, the patients were randomly assigned to undergo either IMRT (129 patients) or standard 4-field radiation (149) to the pelvis.

Patients were evaluated for symptoms at baseline, 3 and 5 weeks after the start of radiation, and 4-5 weeks after completion, and follow-up is planned for 1 and 3 years after the start of radiation therapy.

EPIC findings

For the primary endpoint of change in the composite of EPIC bowel function and bother score from baseline, patients in both arms had declines in scores, signaling increased symptoms, but the decline was significantly greater among patients treated with four-field radiation (mean 23.6 point decline) vs. IMRT (mean 18.6 point decline, P = .048). Viewed separately, bowel function but not bowel bother scores were significantly lower in the standard radiation group. By 4 to 6 weeks after therapy, however, scores in both groups had recovered to baseline levels, Dr. Klopp noted.

Similarly, bowel-related scores on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events measure ( PRO-CTCAE ), a secondary endpoint, were significantly worse among patients who underwent standard radiation for the domains of diarrhea, fecal frequency, and fecal interference. There were no significant differences between the groups in abdominal pain measures, however.

For the secondary endpoint of EPIC urinary scores, IMRT was also associated with lower toxicities, with a mean urinary summary score decline of 5.6 points, compared with a 10.4-point drop among patients treated with standard four-field radiation (P = .03)

Finally, patients on IMRT had a smaller comparative decline in the physical wellbeing scale of the Functional Assessment of Cancer Therapy cervical cancer scale (P = .03).

The results support what many radiation oncologists believe but have not been able to prove until now, commented Geraldine Jacobson, MD, MPH , professor and chair of radiation oncology at West Virginia University, Morgantown.

“Many of us who have used IMRT for pelvic irradiation have believed, based on our experiences, that it was a better way of treatment for patients, but what I think is important about Dr. Klopp’s study is that it’s a randomized trial, and it does demonstrate that IMRT in these pelvic cancers is associated with fewer side effects, and better quality of life for patients. So these results should encourage the use of IMRT for pelvic tumors,” she said at a briefing.

But Supriya Chopra, MD, a radiation oncologist at the Tata Memorial Centre in Mumbai, India, the invited discussant at the plenary, said that the evidence in favor of IMRT is not so clear.

At the 2015 ASTRO annual meeting, Dr. Chopra and colleagues presented interim results of the PARCER study , in which grade III or higher radiation-induced bowel toxicity was lower with IMRT than with 3D-conformal radiation therapy. However, the 14.6% absolute difference, while significant (P = .02) was an exploratory endpoint only, and the observed differences in grade II or greater toxicities was not significant.

Differences in results between PARCER and TIME-C may be explained by the fact that patients in the PARCER trial had a higher proportion of concurrent cisplatin-based chemotherapy (about 88%) than patients in TIME-C (about 75%), with the excess cisplatin in the former trial possibly contributing to a worse symptom burden, she suggested.

“Pooled data from both trials is needed to assess the impact of IMRT for at least physician-reported acute GI toxicity, which both trials have captured. Long-term data from TIME-C and the final analysis of PARCER is awaited to assess the impact of late GI toxicity, and in my opinion, postoperative IMRT for gynecological cancers continues to be investigational,” she said.


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