Treatment algorithm and prognostic factors for patients with stage I–III carcinoma of the anal canal: a 20-year multicenter study

Autor: Jean-Baptiste Delhorme, Franck Monnien, Michael Herfs, Laurent Martin, Lucine Vuitton, Laurence Dusserre, Celia Reynders, Jean-François Bosset, Pascale Hubert, Prudence Colpart, Anne-Sophie Woronoff, Agnès Leroux, Patrick Roncarati, Philippe Delvenne, Laurent Arnould, Elodie Hendrick, Christiane Mougin, Marie Ancion, Didier Peiffert, Alexis Lepinoy, Jean-Luc Prétet, Olivier Peulen, Alexandra Luquain, Thomas Lerho, Diane Bruyère, Séverine Valmary-Degano, Charlotte Pilard, Chloé Molimard, Marie-Christine Bone-Lepinoy, Philippe Maingon, Jean-Pierre Ghnassia
Přispěvatelé: GIGA [Université Liège], Université de Liège, Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA-Research), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Modern Pathology
Modern Pathology, Nature Publishing Group: Open Access Hybrid Model Option B, 2021, 34 (1), pp.116-130. ⟨10.1038/s41379-020-0637-6⟩
ISSN: 0893-3952
1530-0285
DOI: 10.1038/s41379-020-0637-6⟩
Popis: Despite a growing incidence in developed countries and a recent improved understanding of its pathogenesis, anal cancer management has not evolved over the past decades and drug combination used as first-line regimen still largely depends on clinician preferences. Aiming at paving the way for precision medicine, a large cohort of 372 HIV-negative patients diagnosed over a 20-year time period with locally advanced anal carcinoma was collected and carefully characterized at the clinical, demographic, histopathologic, immunologic, and virologic levels. Both the prognostic relevance of each clinicopathological parameter and the efficacy of different concurrent chemoradiation strategies were determined. Overall, the incidence of anal cancer peaked during the sixth decade (mean: 63.4) and females outnumbered males (ratio: 2.51). After completion of treatment, 95 (25.5%) patients experienced progression of persistent disease or local/distant recurrence and 102 (27.4%) died during the follow-up period (median: 53.8 months). Importantly, uni-multivariate analyses indicated that both negative HPV/p16ink4a status and aberrant p53 expression were far better predictors for reduced progression-free survival than traditional risk factors such as tumor size and nodal status. As for overall survival, the significant influences of age at diagnosis, p16ink4a status, cTNM classification as well as both CD3+ and CD4+ T-cell infiltrations within tumor microenvironment were highlighted. Cisplatin-based chemoradiotherapy was superior to both radiotherapy alone and other concurrent chemoradiation therapies in the treatment of HPV-positive tumors. Regarding their HPV-uninfected counterparts, frequent relapses were observed, whatever the treatment regimen administered. Taken together, our findings reveal that current anal cancer management and treatment have reached their limits. A dualistic classification according to HPV/p53 status should be considered with implications for therapy personalization and optimization.
Databáze: OpenAIRE
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