Improved oncological treatment of anal cancer

Sammanfattning: AbstractBackground: Squamous cell cancer of the anus (SCCA) is a rare malignancy, but the incidence is increasing. It isassociated with humman papilloma virus infection. The standard treatment is radiotherapy (RT) combined withchemotherapy, usually 5-fluorouracil (5FU)/Mitomycin C (MMC). This treatment is relatively effective, butrecurrence still represents a problem especially in locally advanced SCCA.The overall aim of this thesis was to improve the treatment of SCCA by analysing a large Nordic population-basedcohort and to explore a new treatment strategy in a prospective phase I study, NOAC 8.Methods: Studies I-III were based on a retrospective cohort comprising 1266 patients with SCCA treatedaccording to Nordic guidelines between 2000 and 2007 (cohort 1), with definitive RT, alone or combined withchemotherapy (CRT), stratified by tumor stage.The second cohort included 13 patients with locally advancedSCCA enrolled in the NOAC 8 trial, investigating RT combined with cetuximab and 5FU/MMC, a combination thathad not been tested before. The primary aim was to determine the maximum tolerated dose (MTD) ofchemotherapy using a pre-defined dose escalation scheme.Results: High age, male gender, large primary tumor, lymph node metastases, distant metastases, poorperformance status and non-inclusion into a protocol were all independent factors associated with worseoutcome.The treatment results were good, well in accordance with published randomized trials. A high incidence(11%) of inguinal lymph nodes recurrence was observed in patients with small tumors where adjuvant lymphirradiation was omitted. Surgery alone of early SCCA was associated with a high locoregional recurrence rate andpoor survival, which were significantly improved with postoperative RT/CRT.The outcome in patients withmetastatic SCCA was poor, but it was significantly better in patients receiving active treatment. Male gender,metachronous disease and multiple metastatic sites were identified as prognostic factors associated with worseprognosis.The MTD of 5FU/MMC in combination with cetuximab and RT was determined.Dose limiting toxicity werediarrhoea, febrile neutropenia and thrombocytopenia.Conclusions: Good treatment results were obtained with widely implemented Nordic guidelines. We recommendprophylactic inguinal lymph node irradiation also for small tumors. Postoperative RT/CRT is effective after primarysurgery for early SCCA. The addition of cetuximab to 5FU/MMC in combination with RT was a rather toxicregimen but the side-effects were manageable.