Indolent cancer and pattern of progression: Two missing parameters in trial design for hepatology.

Autor:	Iavarone M; Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico-Division of Gastroenterology and Hepatology, Milan, Italy., Nault JC; Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris Cité, team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France.; Service d'hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bobigny, France.; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris nord, Bobigny, France., Cabibbo G; Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy., Torres F; Biostatistics Unit, Medical School, Universitat Autònoma de Barcelona, Barcelona, Spain., Reig M; Liver Oncology Unit. Liver Unit, Hospital Clínic Barcelona, Barcelona, Spain.; BCLC group, FUNDACIO/IDIBAPS, Barcelona, Spain.; CIBEREHD, Madrid, Spain.; Universitat de Barcelona, Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2024 Jun 01; Vol. 79 (6), pp. 1452-1462. Date of Electronic Publication: 2023 Jul 03.
DOI:	10.1097/HEP.0000000000000527
Abstrakt:	The indolent and aggressive behaviors of HCC might have a role in clinical trial (CT) results; however, the indolent HCC is less analyzed compared to others cancer. Indolent profile could be characterized as follows: (1) patients with low risk of progression itself due to the HCC molecular profile and/or due to the interaction between cancer cell their microenvironment; (2) patients who achieve objective response or present spontaneous regression; and (3) patients who develop radiological progression with no consequence on either the liver function or general status, and without trigger a change in the tumor stage. Patients with "indolent HCC" generally never develop cancer-related symptoms neither die for HCC-related causes. Thus, we hypothesize that the imbalance in the proportion of "indolent" versus "aggressive HCC" between arms or the underestimation/overestimation of HCC behavior at baseline in single-arm CT could be associated with CT failure or under-overestimation of trial results. The "indolent progression" may also explain the discrepancy between radiological progression-based end points and survival. Moreover, we discuss the related causes that explain the indolent profile of HCC and propose (1) refining the progression-related end point by the pattern of progression to minimize the limitations of the current end points; (2) considering alternative statistical tools for survival analysis such as milestone survival, or restricted mean survival time to capture the value of indolent HCC. According to these considerations, we propose incorporating novel end points into the single arm of phase I/II CT as exploratory analysis or as a secondary end point in phase III CT. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu