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

Imagem de Miniatura
Arquivos
art_MONIZ_A_Prospective_Cohort_Study_of_Biomarkers_in_Squamous_2021.PDF (568.52 KB)
Citações na Scopus
0
Tipo de produção
article
Data de publicação
2021
DOI
Scopus
Título da Revista
ISSN da Revista
Título do Volume
Editora
AMERICAN SOCIETY FOR HORTICULTURAL SCIENCE
Autores
RIECHELMANN, R. P.
OLIVEIRA, S. C. R.
PEREIRA, A. A. L.
MEIRELES, S. I.
FRANCO, R.
Citação
HORTSCIENCE, v.12, n.23, p.7018-7025, 2021
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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. © The author(s).
Palavras-chave
Anal Carcinoma, Biomarkers, HIV, HPV, Ki-67, PD-L1
URI
https://observatorio.fm.usp.br/handle/OPI/49015
Referências
  1. Glynne-Jones, R, Sebag-Montefiore, D, Meadows, HM, Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial (2017) Lancet Oncol, 18 (3), pp. 347-356
  2. Zhang, L, Wu, J, Ling, MT, The role of the PI3K/Akt/mTOR signalling pathway in human cancers induced by infection with human papillomaviruses (2015) Mol cancer, 14, p. 87
  3. Bernardi, MP, Ngan, SY, Michael, M, Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention (2015) Lancet Oncol, 16 (e), pp. 611-621
  4. Mai, S, Welzel, G, Ottstadt, M, Prognostic relevance of HPV infection and p16 overexpression in squamous cell anal cancer (2015) Int J Radiat Oncol Biol Phys, 93 (4), pp. 819-827
  5. Parwaiz, I, MacCabe, TA, Thomas, MG, A systematic review and meta-analysis of prognostic biomarkers in anal squamous cell carcinoma treated with primary chemoradiotherapy (2019) Clin Oncol (R Coll Radiol), 31 (12), pp. e1-e13
  6. Cacheux, W, Rouleau, E, Briaux, A, Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection (2016) Br J Cancer, 114 (12), pp. 1387-1394
  7. James, RD, Glynne-Jones, R, Meadows, HM, Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 x 2 factorial trial (2013) Lancet Oncol, 14 (6), pp. 516-524
  8. Yanik, EL, Kaunitz, GJ, Cottrell, TR, Association of HIV status with local immune response to anal squamous cell carcinoma: implications for immunotherapy (2017) JAMA Oncol, 3 (7), pp. 974-978
  9. Dyck, L, Mills, KHG., Immune checkpoints and their inhibition in cancer and infectious diseases (2017) Eur J Immunol, 47 (5), pp. 765-779
  10. Martin, D, Rodel, F, Balermpas, P, The immune microenvironment and HPV in anal cancer: Rationale to complement chemoradiation with immunotherapy (2017) Biochim Biophys Acta Rev Cancer, 1868 (1), pp. 221-230
  11. Ott, PA, Piha-Paul, SA, Munster, P, Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal (2017) Ann Oncol, 28 (5), pp. 1036-1041
  12. Lampejo, T, Kavanagh, D, Clark, J, Prognostic biomarkers in squamous cell carcinoma of the anus: a systematic review (2010) Br J cancer, 103 (12), pp. 1858-1869
  13. Edge, SB, Byrd, DR, Compton, CC, (2010) AJCC Cancer Staging Manual 7th, , Chicago, USA: Springer
  14. Eisenhauer, EA, Therasse, P, Bogaerts, J, New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) (2009) Eur J Cancer, 45 (2), pp. 228-247
  15. Trotti, A, Colevas, AD, Setser, A, CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment (2003) Seminars in radiation oncology, 13 (3), pp. 176-181
  16. Fraunholz, IB, Haberl, A, Klauke, S, Long-term effects of chemoradiotherapy for anal cancer in patients with HIV infection: oncological outcomes, immunological status, and the clinical course of the HIV disease (2014) Dis Colon Rectum, 57 (4), pp. 423-431
  17. Grew, D, Bitterman, D, Leichman, CG, HIV infection is associated with poor outcomes for patients with anal cancer in the highly active antiretroviral therapy era (2015) Dis Colon Rectum, 58 (12), pp. 1130-1136
  18. Hoots, BE, Palefsky, JM, Pimenta, JM, Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions (2009) International journal of cancer, 124 (10), pp. 2375-2383
  19. Ajani, JA, Wang, X, Izzo, JG, Molecular biomarkers correlate with disease-free survival in patients with anal canal carcinoma treated with chemoradiation (2010) Digestive diseases and sciences, 55 (4), pp. 1098-1105
  20. Welters, MJ, de Jong, A, van den Eeden, SJ, Frequent display of human papillomavirus type 16 E6-specific memory T-helper cells in the healthy population as witness of previous viral encounter (2003) Cancer research, 63 (3), pp. 636-641
  21. de Jong, A, van Poelgeest, MI, van der Hulst, JM, Human papillomavirus type 16-positive cervical cancer is associated with impaired CD4+ T-cell immunity against early antigens E2 and E6 (2004) Cancer research, 64 (15), pp. 5449-5455
  22. Morris, VK, Salem, ME, Nimeiri, H, Nivolumab for previously treated unresectable metastatic anal cancer (NCI9673): a multicentre, single-arm, phase 2 study (2017) Lancet Oncol, 18 (4), pp. 446-453
  23. Govindarajan, R, Gujja, S, Siegel, ER, Programmed Cell Death-Ligand 1 (PD-L1) Expression in Anal Cancer (2018) Am J Clin Oncol, 41 (7), pp. 638-642
  24. Chung, JH, Sanford, E, Johnson, A, Comprehensive genomic profiling of anal squamous cell carcinoma reveals distinct genomically defined classes (2016) Ann Oncol, 27 (7), pp. 1336-1341
  25. Juric, D, Krop, I, Ramanathan, RK, Phase I Dose Escalation Study of Taselisib (GDC-0032), an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors (2017) Cancer discovery, 7 (7), pp. 704-715
  26. Smaglo, BG, Tesfaye, A, Halfdanarson, TR, Comprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas (2015) Oncotarget, 6 (41), pp. 43594-43604
  27. Reungwetwattana, T, Liang, Y, Zhu, V, The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The Why, the How, the Who, the Unknown, and the Inevitable (2017) Lung cancer, 103, pp. 27-37
  28. Tan, SC, Ankathil, R., Genetic susceptibility to cervical cancer: role of common polymorphisms in apoptosis-related genes (2015) Tumour Biol, 36 (9), pp. 6633-6644
  29. Beaudenon, S, Huibregtse, JM., HPV E6, E6AP and cervical cancer (2008) BMC biochemistry, 9, p. S4. , (Suppl 1)
  30. Brady, CS, Duggan-Keen, MF, Davidson, JA, Human papillomavirus type 16 E6 variants in cervical carcinoma: relationship to host genetic factors and clinical parameters (1999) The Journal of general virology, 80 (12), pp. 3233-3240
  31. Storey, A, Thomas, M, Kalita, A, Role of a p53 polymorphism in the development of human papillomavirus-associated cancer (1998) Nature, 393 (6682), pp. 229-234
  32. Martin, V, Zanellato, E, Franzetti-Pellanda, A, EGFR, KRAS, BRAF, and PIK3CA characterization in squamous cell anal cancer (2014) Histology and histopathology, 29 (4), pp. 513-521
  33. Paliga, A, Onerheim, R, Gologan, A, EGFR and K-ras gene mutation status in squamous cell anal carcinoma: a role for concurrent radiation and EGFR inhibitors? (2012) British Journal of Cancer, 107 (11), pp. 1864-1868

Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - HC/ICESP
Artigos e Materiais de Revistas Científicas - HC/InRad
Artigos e Materiais de Revistas Científicas - LIM/07
Artigos e Materiais de Revistas Científicas - LIM/24
Artigos e Materiais de Revistas Científicas - ODS/03