Background
Phase II single-arm trial (RTOG 0529). 52 eligible patients with T2–T4 squamous cell carcinoma of the anal canal. Evaluated dose-painted IMRT (DP-IMRT) for anal cancer with concurrent 5-FU and MMC, compared to historical control from RTOG 9811 (3D-CRT). DP-IMRT prescribed 50.4 Gy to gross tumor (primary + involved nodes) and 42 Gy to elective nodal regions simultaneously in 28 fractions (simultaneous integrated boost). Chemotherapy: 5-FU 1000 mg/m²/d × 4d + MMC 10 mg/m² days 1 and 29. Primary goal: reduce grade 2+ hematologic adverse events.
Interventions and follow up
Arm A: DP-IMRT 50.4 Gy (primary/nodes) + 42 Gy (elective) in 28 fractions + 5-FU + MMC
Primary endpoint: Reduction in grade ≥2 hematologic adverse events vs historical RTOG 9811 rate (85%)
mFollow up: 26.9 month
Primary endpoint: Reduction in grade ≥2 hematologic adverse events vs historical RTOG 9811 rate (85%)
mFollow up: 26.9 month
Results
Grade ≥2 hematologic toxicity: 73% (RTOG 0529) vs 85% (RTOG 9811 historical), P<.0001
Grade ≥3 GI toxicity: 21% vs 36% (historical), P=.008
Grade ≥3 dermatologic toxicity: 23% vs 49% (historical), P<.0001
2-year locoregional failure: 22.1% — comparable to historical RTOG 9811 MMC arm (25%)
Grade ≥3 GI toxicity: 21% vs 36% (historical), P=.008
Grade ≥3 dermatologic toxicity: 23% vs 49% (historical), P<.0001
2-year locoregional failure: 22.1% — comparable to historical RTOG 9811 MMC arm (25%)
Adverse events
Main adverse events: Significantly reduced acute hematologic, GI, and dermatologic toxicity vs historical 3D-CRT outcomes. Grade 3–4 dermatologic toxicity 23% with IMRT vs 49% historically. No unexpected late toxicity identified at median follow-up.
Conclusions
Dose-painted IMRT significantly reduced acute hematologic, GI, and dermatologic toxicities compared to historical 3D-CRT (RTOG 9811) while maintaining locoregional control rates, establishing IMRT as the preferred radiation technique for anal cancer CRT.
Key Limitations
Key Limitations: Single-arm phase II trial — comparison to RTOG 9811 historical controls, not a randomized comparison. Differences in patient selection, staging (CT vs PET-CT), and chemotherapy delivery between eras may confound comparisons. 2-year outcomes are immature for a definitive assessment of efficacy. Relatively small cohort (52 evaluable patients).
Clinical Context
RTOG 0529 established IMRT as the preferred radiation delivery technique for anal cancer CRT, reducing acute toxicity without compromising tumor control. This led to widespread adoption of IMRT in NCCN and ESMO guidelines. The dose-painted simultaneous integrated boost (SIB) approach is now standard, and the study also served as the basis for RTOG anal cancer contouring guidelines (Myerson IJROBP 2009).
References