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Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer

  • SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment.

Methods

Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response.

Results

We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014).

Conclusion

CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.

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References

  1. Yachida S, Jones S, Bozic I, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467(7319):1114-1117. https://doi.org/10.1038/nature09515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Groot VP, Rezaee N, Wu W, et al. Patterns, Timing, and Predictors of Recurrence Following Pancreatectomy for Pancreatic Ductal Adenocarcinoma. Ann Surg. 2018;267(5):936-945. https://doi.org/10.1097/SLA.0000000000002234

    Article  PubMed  Google Scholar 

  3. Surveillance , Epidemiology , and End Results Program. Cancer Stat Facts: Pancreatic Cancer.

  4. McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018;24(43):4846-4861. https://doi.org/10.3748/wjg.v24.i43.4846

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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. The Lancet. 2017;389(10073):1011-1024. https://doi.org/10.1016/S0140-6736(16)32409-6

    Article  CAS  Google Scholar 

  6. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. New England Journal of Medicine. 2018;379(25):2395-2406. https://doi.org/10.1056/nejmoa1809775

    Article  CAS  PubMed  Google Scholar 

  7. Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: The CONKO-001 randomized trial. JAMA - Journal of the American Medical Association. 2013;310(14):1473-1481. https://doi.org/10.1001/jama.2013.279201

    Article  CAS  PubMed  Google Scholar 

  8. Merkow RP, Bilimoria KY, Tomlinson JS, et al. Postoperative complications reduce adjuvant chemotherapy use in resectable pancreatic cancer. In: Annals of Surgery. Vol 260. Lippincott Williams and Wilkins; 2014:372–377. https://doi.org/10.1097/SLA.0000000000000378

  9. Tzeng CWD, Balachandran A, Ahmad M, et al. Serum carbohydrate antigen 19-9 represents a marker of response to neoadjuvant therapy in patients with borderline resectable pancreatic cancer. HPB. 2014;16(5):430-438. https://doi.org/10.1111/hpb.12154

    Article  PubMed  Google Scholar 

  10. Wu W, He J, Cameron JL, et al. The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma. Ann Surg Oncol. 2014;21(9):2873-2881. https://doi.org/10.1245/s10434-014-3722-6

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bauer TM, El-Rayes BF, Li X, et al. Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: A pooled analysis of 6 prospective trials. Cancer. 2013;119(2):285-292. https://doi.org/10.1002/cncr.27734

    Article  CAS  PubMed  Google Scholar 

  12. Katz MHG, Varadhachary GR, Fleming JB, et al. Serum CA 19-9 as a marker of resectability and survival in patients with potentially resectable pancreatic cancer treated with neoadjuvant chemoradiation. Ann Surg Oncol. 2010;17(7):1794-1801. https://doi.org/10.1245/s10434-010-0943-1

    Article  PubMed  PubMed Central  Google Scholar 

  13. Yang GY, Malik NK, Chandrasekhar R, et al. Change in CA 19-9 levels after chemoradiotherapy predicts survival in patients with locally advanced unresectable pancreatic cancer. J Gastrointest Oncol. 2013;4(4):361-369. https://doi.org/10.3978/j.issn.2078-6891.2013.045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Boone BA, Steve J, Zenati MS, et al. Serum CA 19-9 Response to Neoadjuvant Therapy is Associated with Outcome in Pancreatic Adenocarcinoma. Ann Surg Oncol. 2014;21(13):4351-4358. https://doi.org/10.1245/s10434-014-3842-z

    Article  PubMed  Google Scholar 

  15. Tsai S, George B, Wittmann D, et al. Importance of Normalization of CA19-9 Levels following Neoadjuvant Therapy in Patients with Localized Pancreatic Cancer. Ann Surg. 2020;271(4):740-747. https://doi.org/10.1097/SLA.0000000000003049

    Article  PubMed  Google Scholar 

  16. Liu H, Zenati MS, Rieser CJ, et al. CA19-9 Change During Neoadjuvant Therapy May Guide the Need for Additional Adjuvant Therapy Following Resected Pancreatic Cancer. Ann Surg Oncol. 2020;27(10):3950-3960. https://doi.org/10.1245/s10434-020-08468-9

    Article  PubMed  PubMed Central  Google Scholar 

  17. de Geus SWL, Kasumova GG, Eskander MF, et al. Is Neoadjuvant Therapy Sufficient in Resected Pancreatic Cancer Patients? A National Study. Journal of Gastrointestinal Surgery. 2018;22(2):214-225. https://doi.org/10.1007/s11605-017-3541-8

    Article  PubMed  Google Scholar 

  18. Vreeland TJ, McAllister F, Javadi S, et al. Benefit of Gemcitabine/Nab-Paclitaxel Rescue of Patients with Borderline Resectable or Locally Advanced Pancreatic Adenocarcinoma after Early Failure of FOLFIRINOX. Pancreas. 2019;48(6):837-843. https://doi.org/10.1097/MPA.0000000000001345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Alva-Ruiz R, Yohanathan L, Yonkus JA, et al. Neoadjuvant Chemotherapy Switch in Borderline Resectable/Locally Advanced Pancreatic Cancer. Ann Surg Oncol. 2022;29(3):1579-1591. https://doi.org/10.1245/s10434-021-10991-2

    Article  PubMed  Google Scholar 

  20. Ghaneh P, Palmer DH, Cicconi S, et al. ESPAC-5F: Four-arm, prospective, multicenter, international randomized phase II trial of immediate surgery compared with neoadjuvant gemcitabine plus capecitabine (GEMCAP) or FOLFIRINOX or chemoradiotherapy (CRT) in patients with borderline resectable pancreatic cancer. Journal of Clinical Oncology. 2020;38(15_suppl):4505. https://doi.org/10.1200/JCO.2020.38.15_suppl.4505

  21. Sohal D, Duong MT, Ahmad SA, et al. SWOG S1505: Results of perioperative chemotherapy (peri-op CTx) with mfolfirinox versus gemcitabine/nab-paclitaxel (Gem/nabP) for resectable pancreatic ductal adenocarcinoma (PDA). Journal of Clinical Oncology. 2020;38(15_suppl):4504. https://doi.org/10.1200/JCO.2020.38.15_suppl.4504

  22. Janssen B v., Tutucu F, van Roessel S, et al. Amsterdam International Consensus Meeting: tumor response scoring in the pathology assessment of resected pancreatic cancer after neoadjuvant therapy. Modern Pathology. 2021;34(1):4–12. https://doi.org/10.1038/s41379-020-00683-9

  23. Maeda S, Mederos MA, Chawla A, et al. Pathological treatment response has different prognostic implications for pancreatic cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy. Surgery (United States). Published online May 1, 2021. https://doi.org/10.1016/j.surg.2021.10.015

  24. Chatterjee D, Katz MH, Rashid A, et al. Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: A predictor for patient outcome. Cancer. 2012;118(12):3182-3190. https://doi.org/10.1002/cncr.26651

    Article  PubMed  Google Scholar 

  25. Khorana AA, Mangu PB, Berlin J, et al. JOURNAL OF CLINICAL ONCOLOGY. J Clin Oncol. 2017;35:2324-2328. https://doi.org/10.1200/JCO

    Article  CAS  PubMed  Google Scholar 

  26. Murphy JE, Ly L, Wo JYL, et al. Dose intensity of neoadjuvant FOLFIRINOX (FFX) in borderline and locally advanced pancreatic cancer (LAPC): A comparison to the adjuvant benchmark. Journal of Clinical Oncology. 2019;37(4_suppl):392. https://doi.org/10.1200/JCO.2019.37.4_suppl.392

  27. Katz MHG, Shi Q, Meyers JP, et al. Alliance A021501: Preoperative mFOLFIRINOX or mFOLFIRINOX plus hypofractionated radiation therapy (RT) for borderline resectable (BR) adenocarcinoma of the pancreas. Journal of Clinical Oncology. 2021;39(3_suppl):377. https://doi.org/10.1200/JCO.2021.39.3_suppl.377

  28. Versteijne E, van Dam JL, Suker ; Mustafa, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol. Published online 2022:0. https://doi.org/10.1200/JCO.21

  29. Oba A, Ho F, Bao QR, Al-Musawi MH, Schulick RD, Chiaro M del. Neoadjuvant Treatment in Pancreatic Cancer. Front Oncol. 2020;10. https://doi.org/10.3389/fonc.2020.00245

  30. Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. Journal of Clinical Oncology. 2008;26(21):3487-3495. https://doi.org/10.1200/JCO.2007.15.8642

    Article  CAS  PubMed  Google Scholar 

  31. Yin L, Pu N, Thompson E, Miao Y, Wolfgang C, Yu J. Improved assessment of response status in patients with pancreatic cancer treated with neoadjuvant therapy using somatic mutations and liquid biopsy analysis. Clinical Cancer Research. 2021;27(3):740-748. https://doi.org/10.1158/1078-0432.CCR-20-1746

    Article  CAS  PubMed  Google Scholar 

  32. Shoucair S, Habib JR, Pu N, et al. Comprehensive Analysis of Somatic Mutations in Driver Genes of Resected Pancreatic Ductal Adenocarcinoma Reveals KRAS G12D and Mutant TP53 Combination as an Independent Predictor of Clinical Outcome. Ann Surg Oncol. 2022;29(4):2720-2731. https://doi.org/10.1245/s10434-021-11081-z

    Article  PubMed  Google Scholar 

  33. Driehuis E, van Hoeck A, Moore K, et al. Pancreatic cancer organoids recapitulate disease and allow personalized drug screening. Proc Natl Acad Sci U S A. 2019;116(52):26580-26590. https://doi.org/10.1073/pnas.1911273116/-/DCSupplemental

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Tiriac H, Belleau P, Engle DD, et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 2018;8(9):1112-1129. https://doi.org/10.1158/2159-8290.CD-18-0349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA

    Elie M. Ghabi, Sami Shoucair, Ding Ding, John L. Cameron, Christopher R. Shubert, Kelly J. Lafaro, Richard A. Burkhart, William R. Burns & Jin He

  2. Department of Surgery, NYU Langone Health, New York, NY, USA

    Ammar A. Javed & Christopher L. Wolfgang

  3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Elizabeth D. Thompson

  4. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Lei Zheng

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  1. Elie M. Ghabi
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Ghabi, E.M., Shoucair, S., Ding, D. et al. Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer. J Gastrointest Surg 27, 691–700 (2023). https://doi.org/10.1007/s11605-022-05476-w

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