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Pathologic complete response following FOLFIRINOX and olaparib treatment for hepatic metastasized pancreatic ductal adenocarcinoma with a germline BRCA mutation

Clinical Journal of Gastroenterology (2022)Cite this article

Abstract

A 47-year-old female who was previously treated for BRCA1 germline mutant breast cancer presented with increasing back pain. Radiological and pathological investigations led to the diagnosis of pancreatic ductal adenocarcinoma with multiple hepatic metastases. Serum carbohydrate antigen 19–9 levels were highly elevated at 14,784 U/mL (normal, < 37 U/mL). After nine cycles of FOLFIRINOX treatment, radiological findings revealed remarkable shrinkage of the primary pancreatic tumor, disappearance of hepatic metastases, and normalized levels of carbohydrate antigen 19–9 levels. Because of increased neuropathy following FOLFIRINOX treatment, the patient was switched to maintenance olaparib treatment. Ten months later, her radiological response and normalized carbohydrate antigen 19-9 levels were stable. After staging laparoscopy, the patient underwent laparoscopic distal pancreatectomy as a conversion surgery. Histopathological examination revealed no signs of residual adenocarcinoma in the resected pancreatic specimens, which was diagnosed as a pathological complete response. The patient recovered without complications. Adjuvant olaparib treatment was administered with no signs of recurrence at 7 months after surgery. In conclusion, a pathologic complete response after FOLFIRINOX and olaparib maintenance treatment in hepatic metastasized pancreatic ductal adenocarcinoma is extremely rare. These bridging treatments may contribute to increased surgical resection rates and improved survival rates.

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Data availability

Data will be made available by the corresponding author upon reasonable request.

Abbreviations

PDAC:

Pancreatic ductal adenocarcinoma

FOLFIRINOX:

Leucovorin, fluorouracil, irinotecan, and oxaliplatin

CT:

Computed tomography

References

  1. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.

    Article  CAS  Google Scholar 

  2. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.

    Article  Google Scholar 

  3. Pietrasz D, Marthey L, Wagner M, et al. Pathologic major response after FOLFIRINOX is prognostic for patients secondary resected for borderline or locally advanced pancreatic adenocarcinoma: an AGEO-FRENCH, prospective, multicentric cohort. Ann Surg Oncol. 2015;22:S1196–205.

    Article  Google Scholar 

  4. Schneitler S, Kröpil P, Riemer J, et al. Metastasized pancreatic carcinoma with neoadjuvant FOLFIRINOX therapy and R0 resection. World J Gastroenterol. 2015;21:6384–90.

    Article  Google Scholar 

  5. Luu AM, Herzog T, Hoehn P, et al. FOLFIRINOX treatment leading to pathologic complete response of a locally advanced pancreatic cancer. J Gastrointest Oncol. 2018;9:E9–12.

    Article  Google Scholar 

  6. Luu AM, Hoehn P, Vogel SR, et al. Pathologic complete response of pancreatic cancer following neoadjuvant FOLFIRINOX treatment in hepatic metastasized pancreatic cancer. Visc Med. 2019;35:387–91.

    Article  Google Scholar 

  7. Tsujie M, Fumita S, Wakasa T, et al. A case of pathological complete response following FOLFIRINOX therapy for pancreatic adenocarcinoma with synchronous distant lymph node metastases. Int J Surg Case Rep. 2020;72:471–6.

    Article  Google Scholar 

  8. Golan T, Kindler HL, Park JO, et al. Geographic and ethnic heterogeneity in the BRCA1/2 prescreening population for the randomized phase III POLO study of olaparib maintenance in metastatic pancreatic cancer (mPC). JCO. 2018;36:4115.

    Article  Google Scholar 

  9. Bolton KL, Chenevix-Trench G, Goh C, et al. Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. JAMA. 2012;307:382–90.

    Article  CAS  Google Scholar 

  10. Golan T, Barenboim A, Lahat G, et al. Increased rate of complete pathologic response after neoadjuvant FOLFIRINOX for BRCA mutation carriers with borderline resectable pancreatic cancer. Ann Surg Oncol. 2020;27:3963–70.

    Article  Google Scholar 

  11. Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381:317–27.

    Article  CAS  Google Scholar 

  12. Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.

    Article  Google Scholar 

  13. Boone BA, Steve J, Krasinskas AM, et al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol. 2013;108:236–41.

    Article  CAS  Google Scholar 

  14. Paniccia A, Edil BH, Schulick RD, et al. Neoadjuvant FOLFIRINOX application in borderline resectable pancreatic adenocarcinoma: a retrospective cohort study. Med (Baltim). 2014;93: e198.

    Article  CAS  Google Scholar 

  15. Uesaka K, Boku N, Fukutomi A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388:248–57.

    Article  CAS  Google Scholar 

  16. Neoptolemos JP, Palmer DH, Ghaneh P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389:1011–24.

    Article  CAS  Google Scholar 

  17. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379:2395–406.

    Article  CAS  Google Scholar 

  18. Kondo N, Uemura K, Sumiyoshi T, et al. Prognosis following an extended duration of adjuvant gemcitabine plus S-1 chemotherapy in patients with pancreatic ductal adenocarcinoma: analysis using inverse probability of treatment weighting. J Hepatobiliary Pancreat Sci. 2022;29:911–21.

    Article  Google Scholar 

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Acknowledgements

We thank our colleagues at the Department of Surgery, Clinical Oncology, Gastroenterology, and Anatomical Pathology of the Graduate School of Biomedical and Health Sciences, Hiroshima University.

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Authors and Affiliations

  1. Department of Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Kasumi 1-2-3, Minami-Ku, Hiroshima, 734-8551, Japan

    Kenjiro Okada, Kenichiro Uemura, Tatsuaki Sumiyoshi, Ryuta Shintakuya, Hiroyuki Otsuka & Shinya Takahashi

  2. Department of Clinical Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Wataru Okamoto

  3. Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Masahiro Serikawa & Yasutaka Ishii

  4. Department of Anatomical Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Koji Arihiro

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  1. Kenjiro Okada
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  2. Kenichiro Uemura
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  3. Wataru Okamoto
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Correspondence to Kenichiro Uemura.

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Okada, K., Uemura, K., Okamoto, W. et al. Pathologic complete response following FOLFIRINOX and olaparib treatment for hepatic metastasized pancreatic ductal adenocarcinoma with a germline BRCA mutation. Clin J Gastroenterol (2022). https://doi.org/10.1007/s12328-022-01741-2

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Keywords

  • Pancreatic ductal adenocarcinoma
  • BRCA
  • FOLFIRINOX
  • Olaparib
  • Pathologic complete response