Expert Discusses Benefit of IMRT in Gynecologic Cancers

Ann H. Klopp, MD, PhD

Intensity-modulated radiation therapy (IMRT) has been associated with less acute and chronic gastrointestinal toxicity (GI) compared with standard pelvic radiation in the treatment of patients with cervical or endometrial cancer, according to results of a phase III study presented by lead author Ann H. Klopp, MD, PhD, at the 2016 American Society for Radiation Oncology (ASTRO) Annual Meeting.

“We've long known that IMRT can reduce the amount of bowel that is treated, but the actual impact of that hadn't been studied. So, the goal of this study was to measure the clinical impact,” Klopp, an associate professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center, said in an interview with OncLive at ASTRO.

The multicenter phase III RTOG 1203 trial compared the toxicity associated with postoperative IMRT versus conventional four-field pelvic radiation in patients with endometrial and cervical cancer. To assess acute GI toxicity, investigators used the bowel domain of the expanded prostate cancer index composite (EPIC) questionnaire.

Comparison of bowel summary mean scores showed a 5-point difference in favor of the IMRT arm at -18.6 versus -23.6 for patients randomized to conventional pelvic radiation therapy (P = .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 = .19).

In her interview with OncLive, Klopp expanded on the significance of the phase III RTOG 1203 results and discussed remaining challenges with radiation therapy in gynecologic cancers.

OncLive: Please provide an overview of the trial.

Klopp: The study was a randomized trial for women with cervix and endometrial cancer who have indications for postoperative radiation. The women were randomized to 2 different methods to give that radiation. One is the standard approach, which is four field treatment plan essentially, where there is a beam that comes from the front, back, and 2 sides. The other one is IMRT which is a more sophisticated way of giving radiation where the beam comes from multiple angles and converges on the target.

Patients filled out a series of surveys about their experience on treatment, about how much diarrhea they had, and how much those symptoms bothered them. We do something called the EPIC questionnaire which has been developed in prostate cancer, but is relevant to these patients as well. We also did quality-of-life surveys—their physical functioning, and how well they were able to cope with life, essentially.

What we found was that over the course of radiation for all patients, the bowel function scores declined, representing more diarrhea and more symptoms, and then they got better when treatment was over. But the decline was greater for the patients who had standard treatment as compared to IMRT treatment. That demonstrated that there was a significant reduction in the amount of diarrhea in the patients who had IMRT.

What were the significance of these results?

I think this study provides really useful information for clinicians in making decisions about who benefits from IMRT and I think it gives us really solid evidence that those technologic advances result in meaningful changes to a patient’s treatment. I would say that it really supports using IMRT as a standard for pelvic radiation because we know that it can make the patient’s diarrhea less, and we also found associations in the quality of life scores, too, particularly with regard to the physical functioning scores. It really seems to have an impact, at least on their quality of life during treatment. The results of this study did not look at long-term toxicity, so that will be an important question to learn more about. So far, at least, we can show that it impacts short-term toxicity.

Were there any findings that were particularly surprising?

I think that the more striking thing for me was looking at some of the severe symptoms. Among patients who had the standard radiation, there was almost 10% of them who had trouble controlling bowel movements, whereas that was only 2% in the patients who had IMRT, so I was surprised to see how severe the patient experience was and I was encouraged to see it reduced. I think we are learning a lot about patient-reported outcomes that it is really much more sensitive to many forms of toxicity than physician-reported toxicity. I think this study has been a good example of how you can get more information by asking patients systematic questions about their experience as opposed to using physician-reported toxicity, which sometimes can be more subjective and probably less meaningful than what the patient experiences.

What would you like other community oncologists to take away from this study?

I would like them to know that there is randomized data demonstrating that using IMRT reduces patient-reported bowel toxicity and impacts quality of life. I think that really supports the use of IMRT for patients that need post-op radiation. An important element of that is that it has to be done the same way it was done in the study, because IMRT is very dependent on…everybody on the team to make sure that it is done the right way. The other part of it is just being cognizant of the technical aspects of the way it should be done. It’s more complicated and more research intensive, but it pays off in terms of reduced toxicity.

Other than the standard of care, are there any other promising treatments or treatments that IMRT could go up against?

Well in this post-op setting, the question then becomes how can you make it better. One possibility is proton radiation, but we haven't tested that systematically yet. We don't have any evidence to prove that that’s the case, but I think the next question that we can ask is seeing if we can do even better.

What challenges remain with radiation in gynecologic cancers?

Radiation is a big part of treatment for most locally advanced cervix cancers, vaginal, and vulvar cancers, and it can have a lot of side effects. I think one of our goals is to reduce the side effects with advanced radiation techniques. There is also a lot of opportunity to optimize the supportive care during treatment. We know that treating these cancers in an appropriate timeframe has a real impact on survival. So, managing symptoms is not just important for the patient's experience, but it’s important to make sure the treatment is completed in a timely fashion because we know that it’s a big predictor of survival following treatment.

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.