SAN ANTONIO—The use of intensity-modulated radiation therapy (IMRT) has increased dramatically over the past decade, and although the technique requires more time, effort, and technology compared with conventional 3-D conformal radiation therapy (3-D CRT), use of IMRT may decrease the risk of late bowel toxicity in some settings.
As reported here at the American Society for Radiation Oncology Annual Meeting in a plenary presentation, interim results from the Phase III PARCER trial in cervical cancer with 117 patients point to a trend in that direction: Postoperative image-guided IMRT was associated with a 14 percent reduction in moderate-to-severe bowel side effects when compared with 3-D CRT (Abstract 8).
‘Not Statistically Significant, but Clinically Relevant’
“The difference was not statistically significant but it is clinically relevant,” said Supriya Chopra, MD, Assistant Professor of Radiation Oncology in the Advanced Centre for Treatment Research and Education in Cancer at Tata Memorial Center in Mumbai, India.
3-D conformal radiation remains the standard of care, she said, but the final results of this trial could have an impact on many patients, because not only cervical but also prostate, endometrial, and rectal cancer patients receive postoperative radiation and are at risk for bowel toxicity.
There was no difference in acute GI toxicity between 3-D CRT and IMRT, but the rate of late grade 2 and higher toxicities—the primary study endpoint—was 25 percent for 3-D CRT versus 11 percent for IMRT.
There was also a difference in late grade 3 and higher toxicities: 18 percent associated with 3-D CRT versus three percent for IMRT, but again not statistically significant.
Significantly less of the bowel was irradiated with IMRT, but there was no correlation between dose and toxicity.
‘Continue to Evolve’
Chopra said the toxicity rates in PARCER continue to evolve, with the curves separating after 20 months as of the time of the report. Since the stopping rules have not been met, the study continues accrual, with 167 of the expected 240 patients randomized to date.
As reported at the meeting, the planned interim analysis of the study assessed 117 of the patients, who had completed an average of 20 months of follow-up (range of two to 46 months).
Patients had intermediate- or high-risk features or incidental finding of cancer after simple hysterectomy: 56 were randomly assigned to receive 3-D CRT, and 61 received IMRT.
Approximately 40 percent of the patients in each study arm had undergone radical hysterectomies; and about 92 percent (51 patients) of the 3-D CRT group had chemoradiation therapy, as did 85.5 percent (52 patients) of the image-guided IMRT group.
Patients randomly assigned to the 3-D CRT group received treatment on a linear accelerator, and those in the IMRT group received treatment using tomotherapy. Neither the surgery type nor the administration of 3-D CRT had an impact on bowel side effects, Chopra reported.
Funding support for the study was provided by the Department of Atomic Energy, Clinical Trials Centre and Department of Science and Technology in India.
Questions from Discussant
The Discussant for the study, Akila Viswanathan, MD, MPH, Director of Gynecologic Radiation Oncology and Senior Physician at Dana-Farber Cancer Institute, said there were several questions about the data:
- All patients were treated supine, and the bowel loops were contoured: “One would ask whether treatment with 3-D CRT prone might be equal to IMRT supine, with prone bringing the bowel potentially out of the field?”
- The acute GI toxicity in the trial was twice that seen in the RTOG 0418 study: “Was this due to the 2 Gy fraction size, or the use of concurrent chemotherapy?”
- “In planning target volume margins, how much margin is required to account for organ motion? In this trial they created an integrated target volume and used 7 mm margins around the vagina. Could one consider larger margins that would cover more normal tissue but would allow for more movement of the vaginal area during treatment?”
- The doses most commonly administered in chemoradiotherapy are 45 Gy or 50.4 Gy in 1.8 Gy fractions to the pelvis, and concurrent chemotherapy for high-risk only. “PARCER used 50 Gy in 2 Gy fractions plus two intracavitary treatments, and the majority received concurrent chemotherapy, leading to the question: Is a fraction size of 2 Gy too high?”
Hope that NRG/RTOG Will Provide Definitive Results
She noted that an ongoing study of postoperative radiotherapy for endometrial or cervical cancer, NRG/RTOG 1203, recently completed accrual, and the hope is that it will provide definitive results. This compares 3-D conformal radiotherapy 45 or 50.4 Gy with vaginal brachytherapy optional versus IMRT 45 or 50.4 Gy with brachytherapy optional.
“So, are we ready for IMRT?” Viswanathan asked, coming back to the PARCER study. “I would say no.
“This is an interim analysis done before completion of accrual; there was no statistically significant difference in the primary endpoint of grade 2 or higher toxicity; the reduced late grade 3 and higher toxicities were in an unplanned analysis; and the volume of bowel irradiated was not correlated with acute or late toxicity.
“We eagerly await final data.”