Alternative chemoradiotherapy to treat locally advanced (LA) anal carcinoma (AC) in patients (pts) with mutations in thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) genes: A case series.

605Background: 5-FU and mitomycin-C (MMC) with radiotherapy (RT) remain an established treatment for pts with LA (T2-4, N0-1, M0 or T1-4, N2-3, M0) AC. Genetic mutations in 2 major metabolizing enzymes for 5-FU; DPYD and TYMS have been associated with clinical response and toxicity. However their place in treatment of AC remains undetermined. Methods: We retrospectively reviewed 21 pts with LA AC treated between 2012 - 2018. All pts were treated with 5-FU 1,000mg/m2/day continuous IV infusion 1–4 and 29–32, MMC 10mg/m2 IV bolus Days 1 and 29 plus RT. Acute toxicity was recorded and discussed during weekly multidisciplinary meetings. The worst grade was scored from start of treatment until 30 days after the last fraction of radiotherapy according to the NCI-CTCAE, v4.03. Tumor response was evaluated by DRE and palpation of inguinal nodes during treatment, at the end of treatment, and radiological imaging 4–6 weeks after completion of treatment. Pts who developed ≥3 toxicities were tested for DPYD and TYMS ...