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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2020
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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. |
format | Online Article Text |
id | pubmed-7476408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
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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