title: Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report.
abstract: Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug.
  
  
  
  Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity.
  
  
  
  Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients.
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, 47014, Meldola, Italy. andrea.casadei@irst.emr.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Casadei Gardini
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Chiadini
authors.affiliation: Department of Medical Oncology, AO Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Faloppi
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Marisi
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, 47014, Meldola, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Delmonte
authors.affiliation: Department of Medical Oncology, University of Cagliari, Cagliari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Scartozzi
authors.affiliation: Department of Medical Oncology, AO Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Loretelli
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, 47014, Meldola, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lucchesi
authors.affiliation: Radiology Unit, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Devil
authors.initials: D
authors.lastname: Oboldi
authors.affiliation: Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dubini
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, 47014, Meldola, Italy.
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Frassineti
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Paola
authors.identifier: 0000-0002-4334-9662
authors.initials: P
authors.lastname: Ulivi
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000235:genetics; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Case report; HCC; NSCLC; Sorafenib