Post-hysterectomy image-guided intensity-modulated radiation therapy (IMRT) was superior to three-dimensional conformal radiation therapy (3D-CRT) in reducing the side effects of pelvic radiation while achieving similar tumor control in women with high-risk cervical cancer, according to the final analysis of the randomized, phase III PARCER trial1 presented at the 2020 American Society for Radiation Oncology (ASTRO) Annual Meeting, which was held virtually. Experts said these results suggest image-guided IMRT for pelvic radiation may improve patients’ quality of life without compromising disease-free survival.

“This is the first study in gynecologic cancer to show the impact of advanced technology in reducing long-term morbidity and improving the survivorship experience of patients. Given these results, women undergoing postoperative radiation should receive image-guided IMRT,” stated lead author Supriya Chopra, MD, Professor of Radiation Oncology at Tata Memorial Centre, Mumbai, India.

“This is the first study in gynecologic cancer to show the impact of advanced technology in reducing long-term morbidity and improving the survivorship experience of patients.”

— Supriya Chopra, MD

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Postoperative radiation is indicated for high-risk cervical and endometrial cancers, but it is associated with increased long-term toxicity, particularly gastrointestinal problems such as diarrhea, abdominal bloating, and pain. Studies have suggested that image-guided IMRT, a technique that is more highly focused conforming to the shape of the tumor, may reduce side effects compared with conventional radiation therapy.

“There is a lack of clarity on the long-term impact of postoperative IMRT,” Dr. Chopra stated. “Adoption of IMRT has been relatively slow in gynecologic cancers,” she said.

Cervical cancer affects seven times more women in India than in the United States—96,000 per year vs 14,000 per year. Cancers with intermediate- and high-risk features are typically treated with radiation or chemoradiation.

Study Details

Starting in 2011, the study was conducted at three different clinical sites at Tata Memorial Centre. Patients (n = 283) with cervical cancer were included if they had type III hysterectomy with intermediate- or high-risk features or type I/II hysterectomy necessitating adjuvant conformal radiation therapy. All cases were subject to a central review of target delineation and stratified according to the type of hysterectomy and the use of concurrent chemotherapy. Patients were randomly assigned in a 1:1 ratio to receive image-guided IMRT (n = 142) vs 3D-CRT (n = 141).

Quality of life and Common Terminology Criteria for Adverse Events (version 3.0) were assessed at baseline (using 11 gastrointestinal subscales), while on treatment and at each follow-up. Concurrent chemotherapy was administeredto 117 patients in the image-guided IMRT arm and 114 in the 3D-CRT arm. Brachytherapy boost was administered after external-beam radiation treatments.

At a median follow-up of 49 months, the rate of grade 2 or higher toxicity-free survival was significantly higher for image-guided IMRT: 78% with image-guided IMRT vs 57% with 3D-CRT (P = .0009). The grade 3 toxicity-free survival rate was 97.6% for image-guided IMRT vs 81.6% for 3D-CRT (P = .001). After 4 years, the rate of serious gastrointestinal toxicity was 19% in the image-guided IMRT group vs 38% in the 3D-CRT group (P = .005).

“[Image-guided] IMRT represents a new standard of care for postoperative radiotherapy in women with gynecologic cancers.”

— Supriya Chopra, MD

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Regarding other gastrointestinal side effects, no significant differences were seen between the two treatment arms for nausea and vomiting. Fewer patients treated with image-guided IMRT reported moderate to severe acute diarrhea (17% vs 27% for 3D-CRT), late abdominal bloating (14% vs 28%, respectively), bowel obstruction (1% vs 7%, respectively), and anorexia/appetite loss (1% vs 7%, respectively).

There was no significant difference between groups in pelvic relapse–free survival at any time point up to 108 months from randomization.

“A planned subgroup analysis showed that the benefit of [image-guided] IMRT was more pronounced in patients who also got radiosensitizing chemotherapy. The overall cohort also got benefit from image-guided IMRT, regardless of receipt of chemotherapy and the type of surgery, making this technique widely applicable,” Dr. Chopra reported.

“With its superiority in reducing late gastrointestinal toxicity in women undergoing postoperative pelvic radiation therapy and no difference in tumor control rates in the pelvis, image-guided IMRT represents a new standard of care for postoperative radiotherapy in women with gynecologic cancers,” Dr. Chopra stated.

Dr. Chopra said that PARCER differed from standard phase III trials of interventions in that it was designed to compare side effects and not survival benefits. PARCER used physician-reported data as a primary endpoint, with patient-reported data as a secondary outcome. In the future, patient-reported outcomes from PARCER will be reported.

Comments on PARCER

Press conference moderator, Sue S. Yom, MD, PhD, of the University of California, San Francisco, commented on the PARCER trial: “The use of higher-precision image-guided therapy offers the possibility of improving tumor -control. In PARCER, the use of image-guided IMRT reduced the rates of toxicity at 4 years, including bowel problems and anorexia, and improved acute diarrhea, without compromising pelvic tumor control.”

Sue S. Yom, MD, PhD

“This is the first phase III study to show definite long-term advantages, and it is confirmatory of the use of image-guided IMRT in this setting. It is noteworthy that the patients who got concurrent chemotherapy along with radiotherapy may stand to benefit the most,” Dr. Yom said.

Other Points of View

ASTRO President-Elect Geraldine M. Jacobson, MD, MPH, MBA, Chair and Professor in the Department of Radiation Oncology, West Virginia University School of Medicine, Morgantown, stated that PARCER was a step forward. It showed that precise image-guided radiotherapy decreases early and late gastrointestinal treatment-related toxicity, with no adverse impact on disease-free survival.

Geraldine M. Jacobson, MD, MPH, MBA

“Cervical cancer is the fourth most common female cancer worldwide but the second most common in developing countries. Pelvic radiation, with or without chemotherapy, is an important treatment for this cancer. The benefit of decreased acute and late side effects and improved quality of life with [image-guided] IMRT pelvic radiation supports the wider implementation of this modality,” Dr. Jacobson said.

“The technology and resources needed for [image-guided] IMRT may limit its usefulness in resource-limited health-care systems,” she said. “But for health systems that provide longitudinal population-based care, the long-term decrease in late side effects with image-guided IMRT may have an overall positive impact on health-care costs.”

‘Huge Advance’ in Cervical Cancer

Junzo P. Chino, MD, of the Department of Radiation Oncology, Duke Cancer Center, Durham, North Carolina, stated: “This study represents a huge advance in the treatment of women with cervical cancer. Dr. Chopra and colleagues were able to show dramatic and meaningful improvements in moderate and severe long-term toxicities from postoperative radiation therapy, all while maintaining the same rates of cure.” Dr. Chino was Co-Chair of the 2020 ASTRO Guideline on Radiation Therapy for Cervical Cancer.

“The use of image guidance is key in this work, as IMRT results in very tightly conformal treatments. Modern imaging technology allowing for the routine confirmation that the patient is being treated appropriately is an integral part of maintaining high cure rates while sparing normal tissue and toxicity,” Dr. Chino continued.

“This work adds tremendously to prior work from the [Radiation Therapy Oncology Group] looking at women treated with IMRT, in that the PARCER trial is a larger study and is limited only to patients with cervical cancer, and was therefore able to show such a strong effect on eventual outcome. It is also highly relevant that this study was performed outside of the traditionally ‘developed’ high-income countries. Countries such as India have a much higher rate of cervical cancer incidence but have much more limited access to resource-intense treatments such as [image-guided] IMRT. This demonstration of a clear benefit should help prioritization of resources, so women affected with this disease, no matter where they live, have access to the best treatment,” he stated. 

DISCLOSURE: The PARCER trial was funded by the Department of Science and Technology, India; Department of Atomic Energy, Clinical Trials Centre, India. Dr. Chopra has received research funding from Varian Medical Systems. Dr. Yom has received institutional research funding from BioMimetix, Bristol Myers Squibb, -Genentech, and Merck and holds patents or other intellectual property in Springer and UpToDate. Dr. Jacobson reported no conflicts of interest. Dr. Chino has received research funding from Varian Medical Systems.

REFERENCE

1. Chopra S, Dora T, Gupta S, et al: Phase III randomized trial of postoperative adjuvant conventional radiation vs image guided intensity modulated radiotherapy in cervical cancer: Final analysis. 2020 ASTRO Annual Meeting. Abstract 2. Presented October 28, 2020.