Risk-Adjusted Chemoradiation according to Human Papilloma Virus Status for Anal Cancer: A Pilot Registry Study

Abstract

<h3>Purpose/Objective(s)</h3> Radiation with concurrent chemotherapy (CRT) represents standard definitive therapy for anal cancer. CRT protocols result in good local control, but are associated with significant acute and late morbidity. Whether radiation dose escalation beyond 55-60 Gy improves local control remains unknown. Most anal cancers are associated with HPV infection. Patients with HPV positive (+) cancers have better outcomes compared to those with HPV negative (-) disease. HPV+ anal cancer patients may not benefit from standard CRT. <h3>Materials/Methods</h3> Since 2019, we have instituted a REB-approved prospective registry study that tailored CRT for anal cancer according to HPV status in addition to disease stages. Patients with HPV+ T1, T2 and T3/T4 disease received a total dose of 45, 50.4 and 55.8 Gy respectively. Elective nodal radiation dose was 30.6 Gy. For HPV- disease, total doses for T1, T2 and T3/T4 disease were 50.4, 55.8 and 63 Gy respectively, and 36 Gy was given for N0 disease. Concurrent chemotherapy consisted of a single dose of mitomycin C (12 mg/m²) and daily oral capecitabine (825 mg/m² bid) on days of radiation only. Patients were planned following CT, PET/CT and MR simulation. Treatment was delivered using volumetric modulated arc radiotherapy (VMAT) with daily cone beam CT. We report results of an interim analysis, which was planned after the first consecutive cohort of patients had a minimum 18 months of follow-up from CRT. <h3>Results</h3> There were 20 patients with HPV+ (HPV16, 15; HPV18, 1; other HPV types, 3) tumor and 4 were HPV-. All HPV+ tumors demonstrated p16 immunoreactivity. In the HPV+ cohort, there were one T1 (1.6 cm), eleven T2 (2.1-4.8 cm), five T3 (5.1-5.8 cm) and three T4 (4-8.5 cm) lesions. Eight patients (N1a, 4; N1b, 1; N1c, 3) presented with nodal metastases. All HPV+ patients completed protocol RT without RT interruption. Two refused chemotherapy. Grade 2 acute toxicities were observed in all 20 patients and five had grade 3 acute toxicities (skin reactions, pain and anemia). Restaging MRI was done at a median of 170 days (103-204 days) from date of RT. There were two local failures. Both (T4N1c and T2N0) had persistent local disease. Of four patients with HPV- cancer, one (T2N1b) had persistent local disease and one (T2N1c) failed in the iliac nodes; one (T4N0) developed a perforated ischemic sigmoid at 14 months requiring surgery. The local failure rate of 4/24 (16.7%) in this registry study was similar to our historic local failure rate of 28/180 (15.6%) in a retrospective cohort of patients managed by CRT from 2001-2009. These patients were managed using the current RT protocol for HPV- disease but with two cycles of mitomycin C and 5-Fluorouracil. <h3>Conclusion</h3> Treatment de-escalation for HPV+ anal cancer appears safe and may result in similar local control rates compared to standard CRT protocols.