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Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma

Pancreatic acinar cell carcinoma (PAC) is a rare disease with a poor prognosis. Treatment options for metastatic PAC are limited and often follow chemotherapeutic regimens for pancreatic ductal adenocarcinoma. Although recurrent genomic alterations, such as BRAF fusions and defects in genes involved...

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Autores principales: Busch, Elena, Kreutzfeldt, Simon, Agaimy, Abbas, Mechtersheimer, Gunhild, Horak, Peter, Brors, Benedikt, Hutter, Barbara, Fröhlich, Martina, Uhrig, Sebastian, Mayer, Philipp, Schröck, Evelin, Stenzinger, Albrecht, Glimm, Hanno, Jäger, Dirk, Springfeld, Christoph, Fröhling, Stefan, Zschäbitz, Stefanie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476408/
https://www.ncbi.nlm.nih.gov/pubmed/32843432
http://dx.doi.org/10.1101/mcs.a005553
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author Busch, Elena
Kreutzfeldt, Simon
Agaimy, Abbas
Mechtersheimer, Gunhild
Horak, Peter
Brors, Benedikt
Hutter, Barbara
Fröhlich, Martina
Uhrig, Sebastian
Mayer, Philipp
Schröck, Evelin
Stenzinger, Albrecht
Glimm, Hanno
Jäger, Dirk
Springfeld, Christoph
Fröhling, Stefan
Zschäbitz, Stefanie
author_facet Busch, Elena
Kreutzfeldt, Simon
Agaimy, Abbas
Mechtersheimer, Gunhild
Horak, Peter
Brors, Benedikt
Hutter, Barbara
Fröhlich, Martina
Uhrig, Sebastian
Mayer, Philipp
Schröck, Evelin
Stenzinger, Albrecht
Glimm, Hanno
Jäger, Dirk
Springfeld, Christoph
Fröhling, Stefan
Zschäbitz, Stefanie
author_sort Busch, Elena
collection PubMed
description Pancreatic acinar cell carcinoma (PAC) is a rare disease with a poor prognosis. Treatment options for metastatic PAC are limited and often follow chemotherapeutic regimens for pancreatic ductal adenocarcinoma. Although recurrent genomic alterations, such as BRAF fusions and defects in genes involved in homologous recombination DNA repair, have been described in PAC, data on the clinical efficacy of molecularly guided, targeted treatment are scarce. Here we describe the case of a 27-yr-old patient with BRAF(V600E)-mutated PAC who was successfully treated with a combination of BRAF and MEK inhibitors. The patient presented to our clinic with abdominal pain and weight loss. Imaging showed extensive retroperitoneal disease as well as mediastinal lymphadenopathy. Because of elevated α-fetoprotein (AFP) levels and inconclusive histologic findings, a germ cell tumor was suspected; however, PEI chemotherapy was unsuccessful. A repeat biopsy yielded the diagnosis of PAC and treatment with FOLFIRINOX was initiated. Comprehensive molecular profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program revealed a somatic BRAF(V600E) mutation and a germline PALB2 stop-gain mutation. Therapy was therefore switched to BRAF/MEK inhibition, resulting in almost complete remission and disease control for 12 mo and a remarkable improvement in the patient's general condition. These results indicate that BRAF alterations are a valid therapeutic target in PAC that should be routinely assessed in this patient population.
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spelling pubmed-74764082020-09-18 Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma Busch, Elena Kreutzfeldt, Simon Agaimy, Abbas Mechtersheimer, Gunhild Horak, Peter Brors, Benedikt Hutter, Barbara Fröhlich, Martina Uhrig, Sebastian Mayer, Philipp Schröck, Evelin Stenzinger, Albrecht Glimm, Hanno Jäger, Dirk Springfeld, Christoph Fröhling, Stefan Zschäbitz, Stefanie Cold Spring Harb Mol Case Stud Research Report Pancreatic acinar cell carcinoma (PAC) is a rare disease with a poor prognosis. Treatment options for metastatic PAC are limited and often follow chemotherapeutic regimens for pancreatic ductal adenocarcinoma. Although recurrent genomic alterations, such as BRAF fusions and defects in genes involved in homologous recombination DNA repair, have been described in PAC, data on the clinical efficacy of molecularly guided, targeted treatment are scarce. Here we describe the case of a 27-yr-old patient with BRAF(V600E)-mutated PAC who was successfully treated with a combination of BRAF and MEK inhibitors. The patient presented to our clinic with abdominal pain and weight loss. Imaging showed extensive retroperitoneal disease as well as mediastinal lymphadenopathy. Because of elevated α-fetoprotein (AFP) levels and inconclusive histologic findings, a germ cell tumor was suspected; however, PEI chemotherapy was unsuccessful. A repeat biopsy yielded the diagnosis of PAC and treatment with FOLFIRINOX was initiated. Comprehensive molecular profiling within the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) precision oncology program revealed a somatic BRAF(V600E) mutation and a germline PALB2 stop-gain mutation. Therapy was therefore switched to BRAF/MEK inhibition, resulting in almost complete remission and disease control for 12 mo and a remarkable improvement in the patient's general condition. These results indicate that BRAF alterations are a valid therapeutic target in PAC that should be routinely assessed in this patient population. Cold Spring Harbor Laboratory Press 2020-08 /pmc/articles/PMC7476408/ /pubmed/32843432 http://dx.doi.org/10.1101/mcs.a005553 Text en © 2020 Busch et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
spellingShingle Research Report
Busch, Elena
Kreutzfeldt, Simon
Agaimy, Abbas
Mechtersheimer, Gunhild
Horak, Peter
Brors, Benedikt
Hutter, Barbara
Fröhlich, Martina
Uhrig, Sebastian
Mayer, Philipp
Schröck, Evelin
Stenzinger, Albrecht
Glimm, Hanno
Jäger, Dirk
Springfeld, Christoph
Fröhling, Stefan
Zschäbitz, Stefanie
Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma
title Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma
title_full Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma
title_fullStr Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma
title_full_unstemmed Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma
title_short Successful BRAF/MEK inhibition in a patient with BRAF(V600E)-mutated extrapancreatic acinar cell carcinoma
title_sort successful braf/mek inhibition in a patient with braf(v600e)-mutated extrapancreatic acinar cell carcinoma
topic Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7476408/
https://www.ncbi.nlm.nih.gov/pubmed/32843432
http://dx.doi.org/10.1101/mcs.a005553
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