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Neoadjuvant Therapy for Duodenal and Ampullary Adenocarcinoma: A Systematic Review

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The role of systemic therapy in the management of ampullary (AA) and duodenal adenocarcinoma (DA) remains poorly understood. This study sought to synthesize current evidence supporting the use of neoadjuvant therapy (NAT) in AA and DA.

Methods

The study searched PubMed, Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCO), and ClinicalTrials.gov databases for observational or randomized studies published between 2002 and 2022 evaluating survival outcomes for patients with non-metastatic AA or DA who received systemic therapy and surgical resection. The data extracted included overall survival, progression-free survival, and pathologic response (PR) rate.

Results

From the 347 abstracts identified in this study, 29 reports were reviewed in full, and 15 were included in the final review. The selected studies published from 2007 to 2022 were retrospective. Eight were single-center studies; five used the National Cancer Database (NCDB); and two were European multicenter/national studies. Overall, no studies identified survival differences between NAT and upfront surgery (with or without adjuvant therapy). Two NCDB studies reported longer survival with NAT/AT than with surgery. Five single-center studies reported a significant portion of NAT patients who achieved PR, and one study identified major PR as an independent predictor of survival. Other outcomes associated with NAT included conversion from unresectable to resectable disease, reduced lymph node positivity, and decreased local recurrence rate.

Conclusion

Evidence supporting the use of NAT in AA and DA is weak. No randomized studies exist, and observational data show mixed results. For patients with DA and AA, NAT appears safe, but better evidence is needed to understand the preferred multidisciplinary management of DA and AA periampullary malignancies.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

References

  1. Sarmiento JM, Nagomey DM, Sarr MG, Farnell MB. Periampullary cancers: are there differences? Surg Clin North Am. 2001;81:543–55.

    Article  CAS  PubMed  Google Scholar 

  2. Bakkevold KE, Arnesjo B, Dahl O, Kambestad B. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater: results of a controlled, prospective, randomised multicentre study. Eur J Cancer. 1993;29A:698–703.

    Article  CAS  PubMed  Google Scholar 

  3. Klinkenbijl JH, Jeekel J, Sahmoud T, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999;230:776–82; discussion 782–4.

  4. Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA. 2012;308:147–56.

    Article  CAS  PubMed  Google Scholar 

  5. Jin Z, Hartgers ML, Sanhueza CT, et al. Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience. Eur J Surg Oncol. 2018;44:677–83.

    Article  PubMed  Google Scholar 

  6. Vo NP, Nguyen HS, Loh EW, Tam KW. Efficacy and safety of adjuvant therapy after curative surgery for ampullary carcinoma: a systematic review and meta-analysis. Surgery. 2021;170(4):1205–14.

    Article  PubMed  Google Scholar 

  7. Meijer LL, Alberga AJ, de Bakker JK, et al. Outcomes and treatment options for duodenal adenocarcinoma: a systematic review and meta-analysis. Ann Surg Oncol. 2018;25(9):2681–92.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Turpin A, El Amrani M, Zaanan A. Localized small bowel adenocarcinoma management: evidence summary. Cancers (Basel). Jun 11 2022;14(12).

  9. National Comprehensive Cancer Network. Small Bowel. 2022; https://www.nccn.org/professionals/physician_gls/pdf/small_bowel.pdf. Accessed 13 Dec 2022.

  10. National Comprehensive Cancer Network. Ampullary Adenocarcinoma. 2022; https://www.nccn.org/professionals/physician_gls/pdf/ampullary.pdf. Accessed 13 Dec 2022.

  11. Oba A, Ho F, Bao QR, Al-Musawi MH, Schulick RD, Del Chiaro M. Neoadjuvant treatment in pancreatic cancer. Front Oncol. 2020;10:245.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). http://www.prisma-statement.org/?AspxAutoDetectCookieSupport=1. Accessed 3 May 2023.

  13. Sterne JA, Hernan MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919.

  14. Bolm L, Ohrner K, Nappo G, et al. Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy: a multicenter cohort study. Pancreatology. 2020;20(3):433–41.

    Article  PubMed  Google Scholar 

  15. Hester CA, Dogeas E, Augustine MM, et al. Incidence and comparative outcomes of periampullary cancer: a population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012. J Surg Oncol. 2019;119(3):303–17.

    Article  PubMed  Google Scholar 

  16. de Jong EJM, van der Geest LG, Besselink MG, et al. Treatment and overall survival of four types of non-metastatic periampullary cancer: nationwide population-based cohort study. HPB : Off. J. Int. Hepato Pancreato Biliary Assoc. 2022.

  17. Manoukian G, Lal A, Wen S, et al. Neoadjuvant therapy for adenocarcinomas of the duodenum and ampulla of Vater. J. Clin. Oncol. 2011;29(4).

  18. Colina A, Hwang H, Wang H, et al. Natural history and prognostic factors for localised small bowel adenocarcinoma. ESMO Open. 2020;5(6):e000960-000960.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Abo-Ryia M, Abd-Allah H, El-Khadrawy O, Moussa GI, El-Shora A, Saber SA. Primary duodenal malignancies: 2 Year experience at a tertiary hospital. Surg Endosc Other Intervent Tech. 2017;31:S240.

    Google Scholar 

  20. Kelsey CR, Nelson JW, Willett CG, et al. Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2007;69(5):1436–41.

    Article  PubMed  Google Scholar 

  21. Onkendi EO, Boostrom SY, Sarr MG, et al. Neoadjuvant treatment of duodenal adenocarcinoma: a rescue strategy. J Gastrointest Surg. 2012;16(2):320–4.

    Article  PubMed  Google Scholar 

  22. Bourgouin S, Ewald J, Mancini J, Moutardier V, Delpero JR, Le Treut YP. Disease-free survival following resection in non-ductal periampullary cancers: a retrospective multicenter analysis. Int J Surg. 2017;42:103–9.

    Article  PubMed  Google Scholar 

  23. Yamashita S, Overman MJ, Wang H, et al. Pathologic response to preoperative therapy as a novel prognosticator for ampullary and duodenal adenocarcinoma. Ann Surg Oncol. 2017;24(13):3954–63.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Adam MA, Glencer A, AlMasri S, et al. Neoadjuvant therapy versus upfront resection for nonpancreatic periampullary adenocarcinoma. Ann. Surg. Oncol. 2022.

  25. Cecchini S, Correa-Gallego C, Desphande V, et al. Superior prognostic importance of perineural invasion vs. lymph node involvement after curative resection of duodenal adenocarcinoma. J. Gastrointest. Surg. 2012;16(1):113–120; discussion 120.

  26. Lee SY, Lee JH, Hwang DW, Kim SC, Park KM, Lee YJ. Long-term outcomes in patients with duodenal adenocarcinoma. ANZ J. Surg. 2014;84(12):970–975.

  27. Buchbjerg T, Fristrup C, Mortensen MB. The incidence and prognosis of true duodenal carcinomas. Surg Oncol. 2015;24(2):110–6.

    Article  CAS  PubMed  Google Scholar 

  28. Lee TC, Wima K, Morris MC, et al. Small bowel adenocarcinomas: impact of location on survival. J Surg Res. 2020;252:116–24.

    Article  PubMed  Google Scholar 

  29. Linden K, Melillo A, Gaughan J, et al. The role of neoadjuvant versus adjuvant therapy for duodenal adenocarcinoma: a national cancer database propensity score matched analysis. Am. Surg. 2021;87(7):1066–1073.

  30. Palta M, Patel P, Broadwater G, et al. Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy. Ann Surg Oncol. 2012;19(5):1535–40.

    Article  PubMed  Google Scholar 

  31. Cloyd JM, Wang H, Overman M, et al. Influence of preoperative therapy on short- and long-term outcomes of patients with adenocarcinoma of the ampulla of Vater. Ann Surg Oncol. 2017;24(7):2031–9.

    Article  PubMed  Google Scholar 

  32. Guo M, Beal EW, Miller ED, et al. Neoadjuvant therapy versus surgery first for ampullary carcinoma: a propensity score-matched analysis of the NCDB. J Surg Oncol. 2021;123(7):1558–67.

    Article  PubMed  Google Scholar 

  33. Patel D, Jankov A, Gravenor D, et al. Clinical, operative, and pathologic outcomes following neoadjuvant therapy versus upfront surgery for ampullary, duodenal and distal bile duct adenocarcinoma. HPB. 2021;23:S562–3.

    Article  Google Scholar 

  34. Kaslow SR, Prendergast K, Vitiello GA, et al. Systemic therapy for duodenal adenocarcinoma: an analysis of the National Cancer Database (NCDB). Surgery. 2022;172(1):358–64.

    Article  PubMed  Google Scholar 

  35. Kwon J, Kim BH, Kim K, Chie EK, Ha SW. Survival benefit of adjuvant chemoradiotherapy in patients with ampulla of Vater cancer: a systematic review and meta-analysis. Ann Surg. 2015;262(1):47–52.

    Article  PubMed  Google Scholar 

  36. Nassour I, Hynan LS, Christie A, et al. Association of adjuvant therapy with improved survival in ampullary cancer: a National Cohort Study. J Gastrointest Surg. 2018;22(4):695–702.

    Article  PubMed  Google Scholar 

  37. Kim YI, Park JW, Kim BH, et al. Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for advanced-stage unresectable intrahepatic cholangiocarcinoma. Radiat. Oncol. Dec 21 2013;8:292.

  38. Autorino R, Mattiucci GC, Ardito F, et al. Radiochemotherapy with gemcitabine in unresectable extrahepatic cholangiocarcinoma: long-term results of a phase II study. Anticancer Res. 2016;36(2):737–40.

    CAS  PubMed  Google Scholar 

  39. Versteijne E, van Dam JL, Suker M, 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. 2022;40(11):1220–30.

    Article  CAS  PubMed  Google Scholar 

  40. Blazer DG 3rd, Kishi Y, Maru DM, et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008;26(33):5344–51.

    Article  PubMed  Google Scholar 

  41. 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):3182–90.

    Article  PubMed  Google Scholar 

  42. Hank T, Strobel O. Conversion surgery for advanced pancreatic cancer. J Clin Med. 2019;8(11).

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Correspondence to Bradley N. Reames MD, MS, FACS.

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Zhang, C., Lizalek, J.M., Dougherty, C. et al. Neoadjuvant Therapy for Duodenal and Ampullary Adenocarcinoma: A Systematic Review. Ann Surg Oncol 31, 792–803 (2024). https://doi.org/10.1245/s10434-023-14531-y

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  • DOI: https://doi.org/10.1245/s10434-023-14531-y

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