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Image-guided IMRT for cervical cancer may reduce late bowel effects
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Image-guided intensity-modulated radiation therapy reduced moderate-to-severe side effects in the bowel compared with conventional 3D-conformal radio therapy among patients with cervical cancer, according to results of a phase 3 randomized trial presented at the ASTRO Annual Meeting.
The current standard of care for many patients with cervical cancer consists of post-operative pelvic radiation therapy, which could cause long-term gastrointestinal adverse events involving the organs and tissue surrounding the pelvic region. Image-guided intensity-modulated radiation therapy (IG-IMRT) limits the radiation field to the shape of the tumor, which reduces exposure to the surrounding areas of the pelvis.
Supriya Chopra, MD, associate professor of radiation oncology at the Advanced Centre for Treatment Research and Education in Cancer at Tata Memorial Centre in Mumbai, India, and colleagues sought to demonstrate a reduction of grade 2 or worse late bowel toxicities among women undergoing adjuvant chemoradiation therapy for cervical cancer.
The current interim analysis included data from 117 patients — 56 of whom were randomly assigned to receive 3D-conformal radiotherapy (3D-CRT) and 61 who were randomly assigned to receive IG-IMRT — who had a median follow-up of 20 months (range, 2-46 months).
In total, 41.3% of the 3D-CRT arm and 43.5% of the IG-IMRT arm had undergone radical hysterectomies. Further, 91.8% of the patients in the 3D-CRT cohort had chemoradiation therapy — consisting of 40 mg/m2 cisplatin followed by two Gy fractions of brachytherapy — compared with 85.5% of the IG-IMRT cohort.
Radiation therapy consisted of 50 Gy administered in 25 treatments over 5 weeks.
A comparable proportion of patients who underwent IG-IMRT vs. 3D-CRT experienced two or more acute bowel toxicities, including severe diarrhea, vomiting, nausea, lower abdominal distention or pain (54% vs. 58.9%). Rate of grade 2 or worse late bowel toxicity also was not statistically different (11.4% vs. 25%).
However, the rate of grade 3 or worse late bowel toxicities — or severe diarrhea, lower abdominal pain, subacute intestinal obstruction requiring intervention, bowel perforation or death — was significantly lower in the IG-IMRT cohort (3.2% vs. 14%; P = .02).
“These initial results of this interim analysis are encouraging and trend toward possibly a clinically important reduction in moderate-to-severe bowel side effects with the use of IG-IMRT,” Chopra said in a press release. “However, at interim analysis the results are statistically non-significant.
“While we evaluated patients with cervical cancer in this trial, a significant proportion of patients with other cancers undergo postoperative pelvic radiation worldwide,” Chopra added. “Therefore, the results of this trial could impact the choice of future radiation delivery technique for various pelvic malignancies.”
The final analyses from this study will be conducted following the completion of accrual and a median follow up of 3 years, Chopra said. – by Anthony SanFilippo
For more information: Chopra S, et al. Abstract 8. Presented at: ASTRO Annual Meeting; Oct. 18-21, 2015; San Antonio, Texas.
Disclosure: The study was supported by the Department of Atomic Energy, Clinical Trials Centre and Department of Science and Technology in India.
Perspective
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Andrea L. Russo, MD
Chopra and colleagues at the Tata Memorial Centre in India presented the interim analysis of the PARCER trial (Postoperative Adjuvant 3D-CRT vs IG-IMRT for reducing Late Bowel Toxicity in Cervical Cancer). These are the first results of a phase 3 randomized controlled trial comparing IMRT to 3D conformal radiation therapy (3D-CRT) for patients with cervical cancer receiving adjuvant radiation. Although several retrospective and single institutional studies have published their results using IMRT, this is the first randomized phase 3 trial to present data.
A prospective phase 2 trial (RTOG 0418) of IMRT for patients with uterine and cervical cancers in the post-hysterectomy setting, demonstrated feasibility and improved hematologic toxicity, however gastrointestinal toxicity has not yet been reported. Standard four-field pelvic radiation results in grade 2 or worse late toxicity in approximately 15% to 25% of patients.
In the PARCER trial, the primary endpoint was a reduction in grade 2 or worse late toxicity. This endpoint was not met at the interim analysis — at 50% patient accrual — with a grade 2 or worse late toxicity rate of 25% with 3D-CRT vs. 11% for IMRT. In an unplanned exploratory analysis there was a reduction in grade 3 or worse late toxicity from 18% to 3% (P = .02) with the use of IMRT. The radiation compliance was excellent at 97.5%. Of note, the toxicity curves did not separate until 20 months for grade 3 and 36 months for grade 2 toxicity; therefore, longer follow-up may be necessary to see significance.
The PARCER trial used Common Terminology Criteria for Adverse Events version 3.0 to assess toxicity; however, patient-reported outcomes may be a better reflection of the daily health status of the patient. Patient-reported outcomes were assessed as a secondary endpoint. The NRG/RTOG 1203 prospective randomized trial of IMRT vs. 3D-CRT for postoperative endometrial or cervical cancer has completed accrual and uses patient-reported measures of acute GI toxicity using the Expanded Prostate Cancer Index Composite instrument. Results from this trial should also provide guidance on the use of IMRT in this patient population.
In summary, although IMRT appears promising for reducing GI toxicity, we are still awaiting conclusive phase 3 results. If IMRT is used as the treatment modality for patients with gynecologic malignancies, careful treatment planning — that includes simulation using bladder full and empty scans to create an integrated target volume — is imperative. Daily imaging can assist to reduce setup uncertainty. Consensus guidelines have previously been published for the delineation of a clinical target volume. Other factors contributing to toxicity must be taken into account, including concurrent chemotherapy, patient comorbidities, total volume irradiated and extent of prior surgery. I thank Chopra and colleagues for their important contribution to the field; final results from the PARCER trial will be eagerly awaited.References:
Basch E, et al. J Natl Cancer Inst. 2009;doi:10.1093/jnci/djp386.
Chen MF, et al. Int J Radiat Oncol Biol Phys. 2007;doi:10.1016/j.ijrobp.2006.11.005.
Klopp AH, et al. Int J Radiat Oncol Biol Phys. 2013; doi:10.1016/j.ijrobp.2013.01.017.
Mundt AJ, et al. Int J Radiat Oncol Biol Phys. 2003;doi:10.1016/S0360-3016(03)00325-0.
Small W, Jr., et al. Int J Radiat Oncol Biol Phys. 2008;71:428-434.
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