Intensity-modulated radiation therapy is as efficacious as conventional radiation therapy when used to treat anal cancer, and it has less acute toxicity, investigators have reported.
A total of 325 patients given conventional radiation therapy (RT) plus chemotherapy in a previous trial and 52 patients who underwent intensity-modulated radiation therapy (IMRT) plus chemotherapy in a new phase II trial had statistically indistinguishable 2-year rates of disease-free survival (75% and 77%) and overall survival (91% and 86%).
Of note, the IMRT group had significantly lower rates of grade 3 or higher acute skin toxicity and acute gastrointestinal toxicity, according to data presented Jan. 18 in advance of a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology. The trial was conducted by the Radiation Therapy Oncology Group (RTOG).
"Dose-painted IMRT with 5-fluoruracil and mitomycin-C chemotherapy for anal canal cancer is associated with significant sparing of grade 3+ dermatologic and gastrointestinal acute toxicity without compromising 2-year outcomes," principal investigator Dr. Lisa Kachnic said. "It is feasible with very rigorous quality assurance [QA] and continued education."
"Dose-painted IMRT with real-time QA will be our platform in future RTOG anal canal studies incorporating novel agents and may allow for further radiation dose escalation for those with more advanced-stage disease," she added.
Given the cross-trial nature of the comparison, a formal phase III trial is a possibility, according to Dr. Kachnic, who is chair of radiation oncology at Boston University.
"The goal of this study was not to, in a randomized phase III fashion, compare the efficacy between the two types of radiation. It was really to test the feasibility [of IMRT] and see if we can reduce the acute toxicities," she explained. "So I’m not making a claim that it is becoming standard in the U.S. It’s just going to be the radiation platform for RTOG."
In the RTOG 0529 trial (pdf) investigators enrolled patients with stage II or III (T2-4,N0-3,M0) squamous cell or cloacogenic cancer of the anal canal, including those having HIV.
The patients were treated with dose-painted IMRT plus concurrent chemotherapy. The IMRT was tailored to tumor stage and delivered in 28 to 30 fractions over 5.5 to 6 weeks. The chemotherapy consisted of 5-fluorouracil (1,000 mg/m2 per day as a 96-hour infusion) and mitomycin-C (10 mg/m2 as a bolus) on days 1 and 29.
"Probably the most important note to make about this trial was that quality assurance of all the radiation plans were done by myself and several of the other coinvestigators prior to any patients being treated," Dr. Kachnic noted.
The trial’s primary end point was a 15% reduction in the combined rate of grade 2 or higher acute gastrointestinal and genitourinary toxicities from that seen in one arm of an earlier trial, RTOG 9811, in which 325 patients received the same chemotherapy but with conventional, nonconformal RT.
The 52 analyzable patients had a median age of 58 years, and 81% were female. Approximately 54% had stage II disease, 25% had stage IIIA disease, and 21% had stage IIIB disease. Their median duration of follow-up was 26.7 months.
The IMRT and conventional RT populations were well balanced with respect to most clinical and pathologic characteristics, according to Dr. Kachnic. The former were significantly more likely to have node-positive disease and to have advanced disease, however.
The quality assurance procedure led to a recontouring of the treatment plan in 81% of cases, in particular, to ensure coverage of the mesorectum, which is typically avoided in prostate cancer radiation therapy.
"I think that since it was sort of a shift from what [the radiation oncologists] were used to with prostate, they were having some difficulty with this," she commented. The investigators also published an atlas that helped improve contouring.
On final review of dosimetry for the treated patients, only three were found to have major violations in their IMRT. "We put very tight constraints on our normal tissues in hoping to see toxicity sparing," she explained. "In those three cases, the tumor and all the nodes were covered beautifully, but the constraints we put on the normal tissues were slightly over what we made as our ... recommendation for the study."
Overall, 98% of patients completed their IMRT as planned, and 84% completed both cycles of chemotherapy as planned.
The median duration of radiation therapy was shorter for the IMRT group than for the historical conventional radiation therapy group (43 vs. 49 days, P less than .0001). "That’s important because we have seen from other studies, the longer the duration, the more chance of having local recurrence," she noted.