IMRT New Standard of Care for High-Risk Cervical Cancer

For women who receive radiotherapy after undergoing hysterectomy for high-risk cervical cancer, image-guided intensity-modulated radiotherapy (IG-IMRT) is superior to three-dimensional conformal radiotherapy (3D-CRT) at reducing late gastrointestinal (GI) toxicity and is similarly efficacious, according to new findings.

“IG-IMRT should represent the new standard of care for postoperative pelvic radiation therapy in women with gynecological cancers,” said study lead author Supriya Chopra, MD, of the Tata Memorial Center in Mumbai, India.

She noted that the study, known as PARCER, is the first in gynecologic cancer to show the impact of advanced technology in reducing long-term morbidity and thus improving the experience of survivors.

At 4 years, rates of late GI toxicity of grade 2 or higher in the IG-IMRT and 3D-CRT arms were 19.2% and 36.2%, respectively (P = .005). Rates of toxicity of grade 3 or higher were 2.0% and 8.7%, respectively (P < .01).

Chopra presented the results at the American Society for Radiation Oncology (ASTRO) 2020 Annual Meeting, which was held online.

Postoperative radiotherapy is indicated for women with cervical and endometrial cancers who have high-risk features, but long-term follow-up has shown an increase in GI symptom burden and toxicity in long-term survivors after adjuvant radiotherapy.

“The uptake of IMRT has been relatively slow in gynecological cancers,” said Chopra. She explained that previous data suggested a benefit with the use of IMRT, but long-term postoperative effects were unclear.

The new data amount to a “practice-change use” of IMRT for this indication, said Sue Yom, MD, PhD, of the University of California, San Francisco, who was not involved with the study. “I see this as having potentially important future impacts on clinical practice.”

I see this as having potentially important future impacts on clinical practice.
Dr Sue Yom

Yom explained that although there have been studies in the United States on the use of postoperative IMRT for pelvic cancer, “this is the first phase 3 study that has shown definite long-term advantages with the use of IMRT, and I would consider it confirmatory.”

In 2015, the preliminary results of PARCER were presented at the plenary session at ASTRO. The results showed that patients treated with IG-IMRT had fewer late GI toxicities at a median follow-up of 20 months. However, the difference between groups was not statistically significant in this earlier analysis.

Now at 49 Months’ Follow-Up

The study was conducted in three clinical sites of Tata Memorial Center and included a total of 300 patients with cervical cancer. The patients had undergone type III hysterectomy and had intermediate- or high-risk features, or they had undergone type I/II hysterectomy necessitating adjuvant chemoradiotherapy. They were randomly assigned to IG-IMRT (n = 151) or 3D-CRT (n = 149). Most patients (117 in the IG-IMRT arm and 114 in the 3D-CRT arm) received concurrent chemotherapy.

The primary endpoint was late GI toxicity of grade 2 or higher. Follow-up included clinical and quality-of-life evaluations, which were conducted every 3 months for 2 years and then every 6 months for years 2 to

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New Adjuvant RT Standard for Cervical Cancer

Image-guided intensity-modulated radiation therapy (IG-IMRT) for cervical cancer achieved disease control similar to three-dimensional conformal radiation therapy (3D-CRT) but with substantially less gastrointestinal (GI) toxicity, a potentially practice-changing clinical trial showed.

Patients who received adjuvant IG-IMRT had a 4-year GI toxicity-free survival rate of 78% compared with 57% for the 3D-CRT arm. Grades 2 and 3 GI toxicity rates were significantly reduced with IG-IMRT. Pelvic relapse-free survival did not differ significantly between the two groups (73% with IG-IMRT and 68% with 3D-CRT).

“We observed that there was a clear benefit of image-guided IMRT in toxicity-free survival,” said Supriya Chopra, MD, of Tata Memorial Center in Mumbai, India, during the virtual American Society for Radiation Oncology (ASTRO) annual meeting. “This is one of the few studies in radiation oncology looking at late toxicity as a time-to-event factor, and you can see that at even extended follow-up the difference between IG-IMRT and 3D-CRT persists. This [toxicity benefit] is at no cost of extra relapses, as 3D-CRT and IMRT have similar pelvic relapse-free survival.”

“Image-guided IMRT should represent the new standard of care for postoperative pelvic RT in women with gynecological cancers,” she concluded.

Vishal Gupta, MD, of Mount Sinai Medical Center in New York City, agreed that “this very important study” should make IG-IMRT the standard of care for cervical cancer and possibly other gynecologic malignancies.

“A prior North American study showed that IMRT only improved short-term GI toxicity,” Gupta told MedPage Today via email. “The Indian study’s results show that long-term GI toxicity is also improved, which provides a much more convincing argument that IMRT should now be considered the standard of care for these patients.

“It will likely be interpreted that uterine cancers would also benefit from IMRT over 3D-CRT. Uterine cancers are much more common in the U.S. so this study will likely impact many patients.”

Postoperative irradiation is standard practice for both cervical and endometrial cancers. However, long-term survivors often have high GI symptom and toxicity burdens, Chopra noted. The phase III NRG Oncology-RTOG 1203 trial, which compared IMRT and conventional four-field pelvic irradiation in patients with cervical or endometrial cancer, showed an improvement in patient-reported outcomes at 5 weeks and 1 year with IMRT but no difference at 3 years.

“So there is a lack of clarity on the long-term impact of postoperative IMRT,” said Chopra.

In an attempt to resolve the uncertainty, investigators at three clinical sites within Tata Memorial Center enrolled patients with cervical cancer treated with either type III hysterectomy with intermediate- or high-risk features or type I/II hysterectomy necessitating adjuvant chemoradiation therapy. The trial design excluded patients with positive para-aortic lymph nodes or another indication for extended-field RT, a history of multiple prior abdominal surgeries or irradiation, or any medical condition that would predispose them to bowel toxicity.

Following surgery, patients were randomized to 3D-CRT or IG-IMRT. Follow-up occurred at 3-month intervals for 2 years, then every 6 months thereafter. The primary endpoint was freedom from grade ≥2 GI toxicity at 4 years,

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