ABSTRACT
BACKGROUND: The purpose of this study was to evaluate HPV-DNA and p16(INK4a) (p16) expression as prognostic markers for outcome in patients with anal cancer. METHODS: From January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry. RESULTS: Median follow-up was 48.6months (range 2.8-169.1months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p=0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p<0.001] and improved local control [81.0% vs. 55.9%, p=0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p=0.015] and PFS [p=0.002] for cHPPAC. CONCLUSION: The combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.
Subject(s)
Anus Neoplasms/diagnosis , Anus Neoplasms/therapy , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Cyclin-Dependent Kinase Inhibitor p16/analysis , Papillomaviridae/isolation & purification , Adult , Aged , Aged, 80 and over , Anus Neoplasms/mortality , Anus Neoplasms/pathology , Anus Neoplasms/virology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/virology , Chemoradiotherapy/methods , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multivariate Analysis , Polymerase Chain Reaction/methods , Prognosis , Survival Rate , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Concurrent chemotherapy and radiation therapy is the preferred standard of care for patients with anal cancer. Several studies have suggested a benefit of intensity-modulated radiation therapy (IMRT) compared with 3D-conformal radiation (3D-CRT) regarding acute toxicity. This study evaluates outcome and toxicity of patients undergoing IMRT/Tomotherapy or 3D-CRT at our institution. METHODS: A cohort of 105 anal cancer patients was treated with chemoradiation or radiation alone (16.2%) between January 2000 and December 2011. 37 patients received 3D-CRT while 68 patients were treated with IMRT. Follow-up exams were performed every 3 to 6 months for a minimum of 3 years and then annually. RESULTS: Median follow-up was 41.4 months (2.8 - 158.4). Overall survival (OS), Progression-free survival (PFS) and local control (LC) at 3 years was 70.3%, 66.5%, 78.3% in the 3D-CRT group and 82.9%, 66.5%, 75.3% in the IMRT group without statistically significant difference. 3-year Colostomy-free survival (CFS) was 85.7% in the IMRT/Tomotherapy group and 91.8% in the 3D-CRT group (p = 0.48). No grade 4 toxicity was found in both groups. Severe (G2/3) acute skin toxicity (94.6% vs. 63.2%; p < 0.001) and acute gastrointestinal toxicity rate (67.6% vs. 47.1%; p = 0.03) was significantly higher with 3D-CRT compared to IMRT/Tomotherapy. CONCLUSION: The use of IMRT can reduce acute severe side effects of the skin and gastrointestinal tract but did not demonstrate improved results regarding OS, PFS, LC and CFS.
