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, and the trial had statistical power to demonstrate a 13% reduction in late GI toxicity with IG-IMRT.
Data analysis included 279 patients who received planned treatment after randomization, of whom 231 received concurrent chemoradiation. After a median follow-up of 49 months, the 21% absolute difference in GI toxicity represented a 53% reduction in the hazard ratio in favor of IG-IMRT (P=0.009).
Patients had significantly less late GI toxicity with IG-IMRT, whether defined as grade ≥2 (HR 0.53, 95% CI 0.33-0.83, P=0.005) or grade ≥3 (HR 0.23, 95% CI 0.06-0.81, P<0.01). Additionally, acute grade ≥2 diarrhea occurred in 17.2% of patients treated with IG-IMRT versus 27.2% with 3D-CRT (P=0.004). A prespecified subgroup analysis showed that IG-IMRT had a greater impact on late GI toxicity among patients treated with chemoradiation versus radiotherapy alone (P=0.01).
Last Updated October 28, 2020
The study was supported by the Department of Science and Technology of India, the Department of Atomic Energy Clinical Trials Center of India, Varian International, Terry Fox Foundation, and Terry Fox International.
Chopra and co-investigators reported having no relevant relationships with industry.