Intensity-modulated radiation therapy (IMRT) for cervical cancer has led to a double-digit decrease in late bowel toxicity compared with 3-D conformal radiation therapy without statistical significance.
Intensity-modulated radiation therapy (IMRT) for cervical cancer has led to a double-digit decrease in late bowel toxicity compared with 3-D conformal radiation therapy, yet the improvement has yet to achieve statistical significance, interim results from an ongoing trial showed.
After 70% patient accrual, the incidence of late bowel toxicity (grade 2+) was 11.4% with image-guided IMRT versus 25% with 3-D conformal radiation therapy. An exploratory analysis of grade 3+ late toxicity showed almost a six-fold difference in favor of IMRT, which also failed to meet prespecified parameters of statistical significance, as reported at the American Society for Radiation Oncology meeting in San Antonio, TX.
“At this interim analysis, despite a 14% absolute difference, image-guided IMRT is statistically not superior to 3-D conformal radiation therapy for reducing bowel toxicity,” said Supriya Chopra, MD, a radiation oncologist at Tata Memorial Center in Mumbai, India. “As stopping rules are not met, the study continues accrual.”
“Although this study evaluated patients with cervical cancer, a significant proportion of patients with other types of cancersuch as prostate cancer—undergo postoperative pelvic radiation,” she added. “As a result, the outcome of this trial could impact the choice of radiation delivery for multiple pelvic malignancies.”
Late-occurring gastrointestinal toxicityparticularly bowel toxicity—is a well-recognized consequence of standard irradiation techniques used to treat pelvic malignancies. Whether or not modern techniques of radiation delivery can reduce the frequency of late gastrointestinal toxicity has remained unclear, said Chopra.
To inform the unresolved issue, investigators performed a phase III randomized trial involving women scheduled to receive postoperative radiation therapy for cervical cancer. Because of image-guided IMRT’s ability to deliver higher doses of more precisely targeted radiation to target areas, Chopra et al hypothesized that IMRT would significantly reduce grade 2+ late bowel toxicity compared with 3-D conformal radiation therapy.
The trial has a target accrual of 240 patients, 160 of whom have been enrolled to date. The methodology included stratified randomization according to hysterectomy technique (Wertheim’s hysterectomy or simple hysterectomy) and concurrent cisplatin-based chemotherapy versus radiation therapy alone.
Patients were randomized to 3-D conformal radiation therapy or image-guided IMRT. For patients assigned to IMRT, the trial protocol specified that no more than 200 cc of the small bowel would receive 15 Gy of radiation, and no more than 100 cc would be exposed to 40 Gy.
Toxicity was assessed at each follow-up visit in accordance with Common Toxicity Criteria for Adverse Event methodology. The worst grade of bowel toxicity during follow-up was included in the statistical analysis.
Chopra reported data for 120 randomized patients who had completed at least 20 months of follow-up. Almost 60% of the patients underwent complete hysterectomy, and 85% to 90% had concurrent chemotherapy with irradiation.
The data showed that 58.9% of patients in the 3-D conformal radiation therapy arm and 54% of those assigned to image-guided IMRT had acute grade 2+ bowel toxicity. The difference in late-occurring grade 2+ bowel toxicity failed to meet requirements for statistical significance (P= .23).
An exploratory analysis showed that grade 3+ bowel toxicity occurred in 17.6% of patients in the 3-D conformal radiation therapy group versus 3.2% of those in the IMRT arm. The difference met conventional criteria for statistical significance (P= .03), but because of the exploratory nature of the analysis, the difference did not meet the necessary criteria for significance, said Chopra.
A final analysis of late grade 2+ bowel toxicity will occur after 3 years of follow-up in the entire study population.
Chopra S. Phase III RCT of postoperative adjuvant conventional radiation (3DCRT) versus IGIMRT for reducing late bowel toxicity in cervical cancer (PARCER) (NCT01279135/CTRI2012/120349): Results of Interim Analyses. Presented at the American Society for Radiation Oncology: October 19, 2015; Abstract LBA8.