Publications by authors named "Khalil Hodroj"

2 Publications

  • Page 1 of 1

Mutation as a Prognostic and Predictive Marker in Sarcoma: Pooled Analysis of MOSCATO and ProfiLER Precision Medicine Trials.

Cancers (Basel) 2021 Jul 5;13(13). Epub 2021 Jul 5.

Centre Léon Bérard, Medical Oncology Department, 69008 Lyon, France.

(1) Background: locally resected high-grade sarcomas relapse in 40% of cases. There is no prognostic or predictive genomic marker for response to peri-operative chemotherapy. (2) Methods: MOSCATO and ProfiLER are pan-tumor prospective precision medicine trials for advanced tumors. Molecular analysis in both trials comprised targeted next-generation sequencing and comparative genomic hybridization array. We investigated if molecular alterations identified in these trials in sarcomas were associated with disease-free survival (DFS) and response to anthracyclines. (3) Results: this analysis included 215 sarcomas, amongst which 53 leiomyosarcomas, 27 rhabdomyosarcomas, 20 undifferentiated pleomorphic sarcomas, and 17 liposarcomas. The most frequently altered gene was (46 mutations and eight deletions). There were 149 surgically resected localized sarcomas. Median DFS in wild type (WT), deleted, and mutated sarcomas was 16, 10, and 10 months, respectively ( = 0.028; deletions: HR = 1.55; 95% CI = 0.75-3.19; mutations: HR = 1.70; 95%CI = 1.13-2.64). In multivariate analysis, mutations remained associated with shorter DFS ( = 0.027; HR = 2.30; 95%CI = 1.10-4.82). There were 161 localized and advanced sarcomas evaluable for response to anthracyclines. Objective response rates were 35% and 55% in WT and mutated sarcomas, respectively (OR = 2.24; 95%CI = 1.01-5.03; = 0.05). In multivariate analysis, mutations remained associated with increased response (OR = 3.24; 95%CI = 1.30-8.45; = 0.01). (4) Conclusions: mutations are associated with shorter DFS and increased response to anthracyclines. Post-validation, these findings could assist in decision-making for peri-operative treatments.
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July 2021

Molecular Characterization of Ovarian Yolk Sac Tumor (OYST).

Cancers (Basel) 2021 Jan 9;13(2). Epub 2021 Jan 9.

Centre Léon Berard (CLB), 69008 Lyon, France.

Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient's tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in , , . Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome.
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January 2021