Locally Advanced (T3-T4 or N+) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy

Abstract

Aim: To report on clinical outcomes of a consecutive series of locally advanced (T3-T4N0-N3) anal cancer patients treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial.

Patients and methods: A cohort of 45 patients underwent SIB-IMRT employing a schedule consisting of 54 Gy/30 fractions to the macroscopic anal planning target volume (PTV), while clinical nodes were prescribed 50.4 Gy/30 fractions if sized ≤3 cm or 54 Gy/30 fractions if >3 cm. Elective nodal PTV was prescribed 45 Gy/30 fractions. Chemotherapy was administered concurrently following the Nigro regimen. Primary end-point was colostomy-free survival (CFS). Secondary end-points were locoregional control (LRC), disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS).

Results: Median follow-up was 39.7 months. The actuarial 3-year CFS was 63.4 % (95% confidence interval (CI=44.8-77.1%). Actuarial 3-year OS and CSS were 67.7% (95%CI=48.7-80.9%) and 72.9% (95%CI=53.8-85.1%), while DFS was 55.8% (95%CI=37.5.4-70.7%). Actuarial 3-year LRC was 74.1% (95%CI=56.7-85.4%). On multivariate analysis, male sex (hazard ratio (HR)=10.9; p=0.004; 95%CI=2.2-55.5%) had a significant impact on CFS, while higher clinical stage (Stage IIIB vs. others) had borderline significance (HR=2.7; p=0.062; 95%CI=1.8-5.9%). A shorter package time (HR=0.94; p=0.007; 95%CI=0.91-0.98%) predicted for higher CFS. Maximum detected events included: skin (G3): 13%; gastrointestinal (GI) (G3): 13%; genitourinary (GU) (G2): 38%; genitalia (G2): 45%; anemia (G2): 4%; leukopenia (G3): 24%, (G4):7%; neutropenia (G3): 16%; (G4): 11%; thrombocytopenia (G3): 9%, (G4): 2%.

Conclusion: Our clinical results support the use of SIB-IMRT in the combined modality treatment of locally advanced anal cancer patients.

Keywords: Anal cancer; IMRT; VMAT; acute toxicity; concomitant radiochemotherapy; radiation; radiotherapy; volumetric modulated arc-therapy.