A Prospective Cohort Study of Biomarkers in Squamous Cell Carcinoma of the Anal Canal (SCCAC) and their Influence on Treatment Outcomes

Author(s):Show less -

Venchiarutti Moniz, Camila Motta ^{[1, 2]} ; Riechelmann, Rachel Pimenta ^[3] ; Ribeiro Oliveira, Suilane Coelho ^[4] ; Bariani, Giovanni Mendonca ^[1] ; Rivelli, Thomas Giollo ^[1] ; Ortega, Cintia ^[1] ; Lima Pereira, Allan Andresson ^[5] ; Meireles, Sibele Inacio ^[6] ; Franco, Rejane ^[7] ; Chen, Andre ^[1] ; Bonadio, Renata Colombo ^[1] ; Nahas, Caio ^[1] ; Sabbaga, Jorge ^[1] ; Coudry, Renata Almeida ^{[6, 8]} ; Braghiroli, Maria Ignez ^{[1, 2]} ; Hoff, Paulo Marcelo ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Hosp Clin HCFMUSP, Fac Med, Inst Canc Estado Sao Paulo ICESP, Sao Paulo, SP - Brazil

^[2] Inst Pesquisa & Ensino IDOR, Sao Paulo, SP - Brazil

^[3] AC Camargo Canc Ctr, Clin Oncol Dept, Sao Paulo - Brazil

^[4] Univ Estadual Piaui UESPI, Fac Ciencias Med, Piaui - Brazil

^[5] Hosp Sirio Libanes, Brasilia, DF - Brazil

^[6] Hosp Sirio Libanes, Sao Paulo - Brazil

^[7] Univ Fed Parana, Hosp Clin, Curitiba, Parana - Brazil

^[8] UnitedHlth Grp Brazil, Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF CANCER; v. 12, n. 23, p. 7018-7025, 2021.
• Web of Science Citations: 0

Abstract

Background: Although Chemoradiation (CRT) is the curative treatment for SCCAC, many patients present primary resistance. Since it is a rare tumor, response predictors remain unknown. Methods: We performed a prospective cohort study to evaluate biomarkers associated with CRT response, progression-free survival (PFS), and overall survival (OS). The primary endpoint was response at 6 months (m). Tumor DNA and HPV were analyzed by next-generation sequencing, while KI-67 and PD-L1 by immunohistochemistry in tumor tissue. Results: Seventy-eight patients were recruited between October/2011 and December/2015, and 75 were response evaluable. The median age was 57 years, 65% (n=49) were stage III and 12% (n=9) were HIV positive (HIV+). At 6m, 62.7% (n=47) presented CR. On multivariate analyses, stage II patients were 4.7 more likely to achieve response than stage III (OR, 4.70; 95%CI, 1.36-16.30; p=0.015). HIV+ was associated with a worse response (OR, 5.72; 95%CI, 2.5-13.0; p<0.001). 5-year PFS and OS rates were 63.3% and 76.4%, respectively, with a median follow up of 66m. On multivariate analyses, older age (HR 1.06, p=0.022, 95%IC 1.01-1.11) and absence of CR at 6m (HR 3.36, p=0.007, 95%IC 1.39-8.09) were associated with inferior OS. The 5-year OS rate was 62.5% in HIV+ group compared to 78% among HIVpts, although this difference was not statistically significant (p=0.4). PIK3CA, MET and TP53 mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: Clinical stage III and HIV+ were associated with worse response to CRT at 6m. The absence of CR was the main factor associated with poor 5-year OS. (AU)

• FAPESP's process: 13/03093-0 - Expression profile of biomarkers in anal canal carcinoma and correlation with failed treatment with chemo-radiotherapy
• Grantee: Renata de Almeida Coudry
• Support Opportunities: Regular Research Grants