J Cancer 2021; 12(23):7018-7025. doi:10.7150/jca.57678 This issue

Research Paper

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

Camila Motta Venchiarutti Moniz1,2✉, Rachel Pimenta Riechelmann3, Suilane Coelho Ribeiro Oliveira4, Giovanni Mendonça Bariani1, Thomas Giollo Rivelli1, Cintia Ortega1, Allan Andresson Lima Pereira5, Sibele Inácio Meireles6, Rejane Franco7, Andre Chen1, Renata Colombo Bonadio1, Caio Nahas1, Jorge Sabbaga1, Renata Almeida Coudry6,8, Maria Ignez Braghiroli1,2, Paulo Marcelo Hoff1,2

1. Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, BR.
2. Instituto D'Or de Pesquisa e Ensino - IDOR, Sao Paulo, SP, BR.
3. Clinical Oncology Department, AC Camargo Cancer Center, Sao Paulo, BR.
4. Faculdade de Ciencias Médicas da Universidade Estadual do Piaui (UESPI), Piaui, BR.
5. Hospital Sírio Libânes, Brasília, BR.
6. Hospital Sírio Libânes, Sao Paulo, BR.
7. Universidade Federal do Paraná - Hospital de Clínicas, Curitiba, PR, Brasil.
8. UnitedHealth Group Brazil.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Moniz CMV, Riechelmann RP, Oliveira SCR, Bariani GM, Rivelli TG, Ortega C, Pereira AAL, Meireles SI, Franco R, Chen A, Bonadio RC, Nahas C, Sabbaga J, Coudry RA, Braghiroli MI, Hoff PM. A Prospective Cohort Study of Biomarkers in Squamous Cell Carcinoma of the Anal Canal (SCCAC) and their Influence on Treatment Outcomes. J Cancer 2021; 12(23):7018-7025. doi:10.7150/jca.57678. Available from https://www.jcancer.org/v12p7018.htm

File import instruction

Abstract

Graphic 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 HIV- pts, 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.

Keywords: Anal Carcinoma, Biomarkers, Ki-67, PD-L1, HPV, HIV