Increased Rate of Complete Pathologic Response After Neoadjuvant FOLFIRINOX for BRCA Mutation Carriers with Borderline Resectable Pancreatic Cancer.


Journal

Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840

Informations de publication

Date de publication:
Oct 2020
Historique:
received: 15 10 2019
pubmed: 22 4 2020
medline: 5 5 2021
entrez: 22 4 2020
Statut: ppublish

Résumé

Neoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX. A dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients. The 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free. The study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.

Sections du résumé

BACKGROUND BACKGROUND
Neoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX.
METHODS METHODS
A dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients.
RESULTS RESULTS
The 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free.
CONCLUSIONS CONCLUSIONS
The study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.

Identifiants

pubmed: 32314163
doi: 10.1245/s10434-020-08469-8
pii: 10.1245/s10434-020-08469-8
doi:

Substances chimiques

folfirinox 0
Oxaliplatin 04ZR38536J
Irinotecan 7673326042
Leucovorin Q573I9DVLP
Fluorouracil U3P01618RT

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3963-3970

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Auteurs

Talia Golan (T)

Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.

Alex Barenboim (A)

Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel.

Guy Lahat (G)

Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel.

Ido Nachmany (I)

Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel.

Yacov Goykhman (Y)

Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel.

Einat Shacham-Shmueli (E)

Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.

Naama Halpern (N)

Institute of Oncology, Sheba Medical Center, Tel Hashomer, Israel.

Eli Brazowski (E)

Institute of Pathology, Tel-Aviv Medical Center, Tel Aviv, Israel.

Ravit Geva (R)

Institute of Oncology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Ido Wolf (I)

Institute of Oncology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Yuri Goldes (Y)

Department of Surgery, Sheba Medical Center, The Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Menahem Ben-Haim (M)

Department of Surgery, Shaarey Zedek Medical Center, Jerusalem, Israel.

Joseph M Klausner (JM)

Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel.

Nir Lubezky (N)

Liver Surgery Unit, Department of Surgery, Tel-Aviv Medical Center, Tel Aviv, Israel. nirl@tlvmc.gov.il.

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