New Radiotherapy Technique Less Toxic for Patients with Anal Cancer

Using dose-painted intensitymodulated radiation therapy (DP-IMRT) to treat cancer in the anal canal reduces the risk of serious adverse events associated with standard radiation therapy without compromising survival according to data presented by Lisa Kachnic, MD, chief of radiation oncology at Boston Medical Center and an associate professor with Boston University School of Medicine, Massachusetts. She reported results from the phase 2 Radiation Therapy Oncology Group (RTOG)-0529 trial at a press briefing.

Kachnic said although the study did not achieve its goal of a 15% reduction in the rate of gastrointestinal (GI) and genitourinary toxicities ≥grade 2 observed in RTOG-9811, which used standard external beam radiation, DP-IMRT demonstrated enough benefit to become the “standard radiation technique in future RTOG anal cancer trials assessing novel agents in combination with radiation.” With DP-IMRT, the radiation dose is “painted” to conform to the shape of the targeted tissue and spares nearby healthy tissue.

Investigators analyzed data for 52 patients with stage II and stage III anal cancer enrolled in RTOG-0529 who received standard 5-fluorouracil/mitomycin- C chemotherapy plus DPIMRT. Patients with T2 disease received a total radiation dose of 50.4 Gy targeted to the tumor and 42 Gy delivered to elective lymph nodes in 28 fractions over 5.5 weeks. Patients with T3 to T4 disease received 54 Gy to the tumor and 45 Gy to the nodes, delivered in 30 fractions over 6 weeks. Findings were compared with results for the patients in RTOG-9811 who had received the same chemotherapy regimen plus conventional radiotherapy (n = 325).

The RTOG-0529 patients had significantly lower rates of acute GI and dermatologic toxicities. Nearly 20% of patients given DP-IMRT developed GI toxicities ≥grade 3 versus 35% of the selected RTOG-9811 patients (P = .0082). Whereas skin toxicities ≥grade 3 were observed in ~50% of the RTOG-9811 patients, the rate dropped to ~20% for patients in the DP-IMRT group (P <.0001). Kachnic said investigators were surprised by the significant 10% reduction in hematologic toxicities ≥grade 2 seen with DP-IMRT (P = .032).

At median follow-up of 27 months, the trials demonstrated similar 2-year rates of locoregional and distant failure and survival outcomes, even though RTOG-0529 had a higher proportion of node-positive patients. The median duration of DP-IMRT was 43 days versus 49 days for the conventional arm, and patients in RTOG-0529 experienced fewer treatment breaks, which Kachnic said was an important benefit.

Kachnic acknowledged DP-IMRT involved a learning curve and that “real-time quality assurance” is essential for safety and efficacy. She said the RTOG-0529 researchers concluded that “DP-IMRT is feasible with rigorous quality assurance and continued education...and may allow for further radiation dose escalation in advancedstage disease.”