HCC-neuroendocrine transition: Tumor plasticity under immunotherapy

Sanduzzi‐Zamparelli, Marco; Fuster-Anglada, Carla; Bruix, Jordi; Reig, María; Díaz, Alba

doi:10.1016/j.gastrohep.2022.01.008

Cited by 1 publication

(2 citation statements)

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“…[50] In the BCLC cohort of patients with advanced HCC treated with immunotherapy, 3 patients who, after achieving response to treatment and radiological stability, later developed disease recurrence in the form of tumors with different lineages, 2 of them showing markers associated with neuroendocrine tumor. [51] This leads us to hypothesize that there is a "lineage preference" in patients with indolent versus aggressive HCC.…”

Section: Prognostic Genomic Signaturesmentioning

confidence: 99%

“…A recent study analyzed paired tumor biopsies before and after atezolizumab plus bevacizumab and described a decreased level of T regulatory gene signature in responders but not in nonresponders 50 . In the BCLC cohort of patients with advanced HCC treated with immunotherapy, 3 patients who, after achieving response to treatment and radiological stability, later developed disease recurrence in the form of tumors with different lineages, 2 of them showing markers associated with neuroendocrine tumor 51 …”

Section: Understanding What Is An Indolent Hcc At the Molecular Levelmentioning

confidence: 99%

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

et al. 2023

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The indolent and aggressive behaviors of hepatocellular carcinoma (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 follow: (a) patients with low risk of progression itself due to the HCC molecular profile and/or due to the interaction between cancer cell their microenvironment; (b) patients who achieve objective response or present spontaneous regression and (c) 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 under-/over-estimation of HCC behavior at baseline in single arm CT could be associated to 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 (a) refining the progression-related end-point by the pattern of progression to minimize the limitations of the current end-points; (b) 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.

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Section: Prognostic Genomic Signaturesmentioning

confidence: 99%

Section: Understanding What Is An Indolent Hcc At the Molecular Levelmentioning

confidence: 99%