Brain metastases in pancreatic ductal adenocarcinoma: Assessment of molecular genotype - Phenotype features - An entity with an increasing incidence? Journal Article


Authors: Jordan, E. J.; Lowery, M. A.; Basturk, O.; Allen, P. J.; Yu, K. H.; Tabar, V.; Beal, K.; Reidy, D. L.; Yamada, Y.; Janjigian, Y.; Abou-Alfa, G. K.; O'Reilly, E. M.
Article Title: Brain metastases in pancreatic ductal adenocarcinoma: Assessment of molecular genotype - Phenotype features - An entity with an increasing incidence?
Abstract: Brain metastases (BM) from pancreatic ductal adenocarcinoma (PDAC) are an infrequent event. We identified 25 patients with a median age of 58 years from Memorial Sloan Kettering Cancer Center with BM and PDAC. Median time to the development of BM was 17 months (range, 0-79 months); median overall survival from the time of BM development was 1.5 months (range, 1-31 months). Six patients underwent germ-line testing, with BRCA1 (n = 1) or BRCA2 (n = 2) alterations detected, and 7 patients underwent molecular profiling, with KRAS, TP53, and MYC amplification the most frequent. Purpose: To assess clinical characteristics of patients with metastatic pancreas ductal adenocarcinoma (PDAC) and brain metastases (BM), and to assess somatic and germ-line molecular profiles where performed. Patients and Methods: Patients with PDAC and BM between January 1990 and January 2016 were identified. Molecular characteristics of somatic and germ-line testing where performed in the subset of patients who had provided informed consent. Somatic alterations were assessed by either MSK-IMPACT testing (>340 key cancer genes) or Sequenom testing (8-gene panel). Overall survival was calculated from date of diagnosis to either date of last follow-up or death. Survival after BM was calculated from date of diagnosis of BM by radiology or pathology to either date of last follow-up or death. Results: From a total of 5824 patients with PDAC identified from January 2000 to January 2016, twenty-five patients (0.4%) had BM. Median age at PDAC diagnosis was 58 years. Median time to the development of BM from initial PDAC diagnosis was 17 months (range, 0-79 months). Median overall survival after BM diagnosis was 1.5 months (range, 1-31 months). Overall survival for patients who had craniotomy (n = 4) was 11 months (range, 1-31 months), with 2 long-term survivors at 21 and 31 months, respectively. Four patients had leptomeningeal disease. Six of 25 patients had germ-line testing, and 3 had BRCA mutations (2 BRCA1 and 1 BRCA2). Somatic profiling identified KRAS mutations in 100% (4 G12D, 2 G12V, and 1 Q61K). Conclusion: BM from PDAC is a rare event. We identified a speculative association of germ-line BRCA1/2 alterations with BM in PDAC, which requires corroboration. Survival after BM development is poor; prolonged survival occurred in selected patients via a multidisciplinary approach. © 2018 Elsevier Inc.
Keywords: genetics; pancreatic cancer; brca
Journal Title: Clinical Colorectal Cancer
Volume: 17
Issue: 2
ISSN: 1533-0028
Publisher: Elsevier Inc.  
Date Published: 2018-06-01
Start Page: e315
End Page: e321
Language: English
DOI: 10.1016/j.clcc.2018.01.009
PROVIDER: scopus
PUBMED: 29496399
DOI/URL:
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Viviane S Tabar
    123 Tabar
  2. Yoshiya Yamada
    359 Yamada
  3. Olca Basturk
    203 Basturk
  4. Ghassan Abou-Alfa
    229 Abou-Alfa
  5. Kathryn Beal
    157 Beal
  6. Diane Lauren Reidy
    153 Reidy
  7. Yelena Yuriy Janjigian
    148 Janjigian
  8. Maeve Aine Lowery
    98 Lowery
  9. Peter Allen
    442 Allen
  10. Kenneth Ho-Ming Yu
    65 Yu
  11. Eileen O'Reilly
    324 O'Reilly
  12. Emmet John Jordan
    30 Jordan