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Neoadjuvant Chemotherapy is Associated with Increased Risk of Postoperative DVT After Distal Pancreatectomy for Pancreatic Adenocarcinoma: a NSQIP Analysis

  • Pancreatic Tumors
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Abstract

Background

Venous thromboembolism (VTE) remains a persistent source of postoperative morbidity despite prevention and mitigation efforts. Cancer, surgery, and chemotherapy are known risk factors for VTE. Existing literature suggests that neoadjuvant therapy (NAT) may contribute to increased VTE risk in the postoperative period, but few authors specifically examine this relationship in distal pancreatic adenocarcinoma (PDAC). In this study, we analyze the association of NAT and postoperative VTE in patients who underwent distal pancreatectomy (DP) for PDAC.

Patients and Methods

Using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database, we analyzed the Procedure Targeted files for pancreatectomy from 2014 to 2020. Adults with PDAC who underwent DP were grouped by receipt of NAT. The primary outcome was the rate of deep venous thrombosis (DVT) and the secondary outcome was the rate of pulmonary embolism (PE). We performed univariate and multivariate logistic regression analysis to determine risk factors associated with postoperative DVT.

Results

There were 4327 patients with PDAC who underwent DP. Of these, 1414 (32.7%) had NAT. Receipt of NAT was significantly associated with postoperative DVT requiring therapy (3.5% vs. 2.3%, p = 0.02), but was not associated with PE (p = 0.42). On MVA, NAT was associated with a 73% greater chance of developing postoperative DVT [odds ratio (OR) 1.73, 95% CI 1.18–2.55].

Conclusions

Patients who receive NAT prior to DP for PDAC are 73% more likely to develop postoperative DVT compared with upfront resection. As NAT becomes more commonplace, these high-risk patients should be prioritized for guideline-recommended extended duration prophylaxis.

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References

  1. Ruppert A, Lees M, Steinle T. Clinical burden of venous thromboembolism. Curr Med Res Opin. 2010;26(10):2465–73.

    Article  PubMed  Google Scholar 

  2. Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob GE. The economic burden of incident venous thromboembolism in the United States: a review of estimated attributable healthcare costs. Thromb Res. 2016;137:3–10.

    Article  CAS  PubMed  Google Scholar 

  3. Lau BD, Streiff MB, Pronovost PJ, Haut ER. Venous thromboembolism quality measures fail to accurately measure quality. Circulation. 2018;137(12):1278–84.

    Article  PubMed  Google Scholar 

  4. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e227S-e277S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fanikos J, Stevens LA, Labreche M, et al. Adherence to pharmacological thromboprophylaxis orders in hospitalized patients. Am J Med. 2010;123(6):536–41.

    Article  PubMed  Google Scholar 

  6. Shermock KM, Lau BD, Haut ER, et al. Patterns of non-administration of ordered doses of venous thromboembolism prophylaxis: implications for novel intervention strategies. PLoS ONE. 2013;8(6):e66311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wun T, White RH. Venous thromboembolism (VTE) in patients with cancer: epidemiology and risk factors. Cancer Invest. 2009;27(Suppl 1):63–74.

    Article  PubMed  Google Scholar 

  8. Negus JJ, Gardner JJ, Tann O, Lewis S, Cohen AT. Thromboprophylaxis in major abdominal surgery for cancer. Eur J Surg Oncol. 2006;32(9):911–6.

    Article  CAS  PubMed  Google Scholar 

  9. Heit JA. Epidemiology of venous thromboembolism. Nat Rev Cardiol. 2015;12(8):464–74.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Eurola A, Mustonen H, Mattila N, Lassila R, Haglund C, Seppanen H. Preoperative oncologic therapy and the prolonged risk of venous thromboembolism in resectable pancreatic cancer. Cancer Med. 2022;11(7):1605–16.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Adiamah A, Ban L, West J, Humes DJ. The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy: a population-based cohort study. Dis Esophagus. 2020;33(6):doz079.

    Article  PubMed  Google Scholar 

  12. Mulder FI, Horvath-Puho E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood. 2021;137(14):1959–69.

    Article  CAS  PubMed  Google Scholar 

  13. Epstein AS, Soff GA, Capanu M, et al. Analysis of incidence and clinical outcomes in patients with thromboembolic events and invasive exocrine pancreatic cancer. Cancer. 2012;118(12):3053–61.

    Article  PubMed  Google Scholar 

  14. Tzeng CWD, Katz MHG, Lee JE, et al. Predicting the risk of venous thromboembolism versus post-pancreatectomy haemorrhage: analysis of 13,771 NSQIP patients. HPB (Oxford). 2014;16(4):373–83.

    Article  PubMed  Google Scholar 

  15. Mukherjee D, Lidor AO, Chu KM, Gearhart SL, Haut ER, Chang DC. Postoperative venous thromboembolism rates vary significantly after different types of major abdominal operations. J Gastrointest Surg. 2008;12(11):2015–22.

    Article  PubMed  Google Scholar 

  16. Willobee BA, Dosch AR, Allen CJ, et al. Minimally invasive surgery is associated with an increased risk of postoperative venous thromboembolism after distal pancreatectomy. Ann Surg Oncol. 2020;27(7):2498–505.

    Article  PubMed  Google Scholar 

  17. Czosnyka NM, Borgert AJ, Smith TJ. Pancreatic adenocarcinoma: effects of neoadjuvant therapy on post-pancreatectomy outcomes—an American College of Surgeons National Surgical Quality Improvement Program targeted variable review. HPB (Oxford). 2017;19(10):927–32.

    Article  PubMed  Google Scholar 

  18. Hanna-Sawires RG, Groen JV, Klok FA, et al. Outcomes following pancreatic surgery using three different thromboprophylaxis regimens. Br J Surg. 2019;106(6):765–73.

    Article  CAS  PubMed  Google Scholar 

  19. Fong ZV, Sell NM, Fernandez-Del Castillo C, et al. Does preoperative pharmacologic prophylaxis reduce the rate of venous thromboembolism in pancreatectomy patients? HPB (Oxford). 2020;22(7):1020–4.

    Article  PubMed  Google Scholar 

  20. Schlick CJR, Merkow RP, Yang AD, Bentrem DJ. Post-discharge venous thromboembolism after pancreatectomy for malignancy: predicting risk based on preoperative, intraoperative, and postoperative factors. J Surg Oncol. 2020. https://doi.org/10.1002/jso.26046.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Krell RW, McNeil LR, Yanala UR, Are C, Reames BN. Neoadjuvant therapy for pancreatic ductal adenocarcinoma: propensity-matched analysis of postoperative complications using ACS-NSQIP. Ann Surg Oncol. 2021;28(7):3810–22.

    Article  PubMed  Google Scholar 

  22. Dahdaleh FS, Naffouje SA, Hanna MH, Salti GI. Impact of neoadjuvant systemic therapy on pancreatic fistula rates following pancreatectomy: a population-based propensity-matched analysis. J Gastrointest Surg. 2021;25(3):747–56.

    Article  PubMed  Google Scholar 

  23. Hue JJ, Elshami M, Beckman MJ, et al. A propensity-matched analysis of the postoperative venous thromboembolism rate after pancreatoduodenectomy based on operative approach. J Gastrointest Surg. 2022;26(3):623–34.

    Article  PubMed  Google Scholar 

  24. Stitzel HJ, Hue JJ, Elshami M, et al. Assessing the use of extended venous thromboembolism prophylaxis on the rates of venous thromboembolism and post-pancreatectomy hemorrhage following pancreatectomy for malignancy. Ann Surg. 2022;278(1):e80–6.

    Article  PubMed  Google Scholar 

  25. Clancy TE, Baker EH, Maegawa FA, Raoof M, Winslow E, House MG. AHPBA guidelines for managing VTE prophylaxis and anticoagulation for pancreatic surgery. HPB (Oxford). 2022;24(5):575–85.

    Article  PubMed  Google Scholar 

  26. Henderson WG, Daley J. Design and statistical methodology of the National Surgical Quality Improvement Program: why is it what it is? Am J Surg. 2009;198(5 Suppl):S19-27.

    Article  PubMed  Google Scholar 

  27. Shiloach M, Frencher SK Jr, Steeger JE, et al. Toward robust information: data quality and inter-rater reliability in the American College of Surgeons National Surgical Quality Improvement Program. J Am Coll Surg. 2010;210(1):6–16.

    Article  PubMed  Google Scholar 

  28. Cohen ME, Ko CY, Bilimoria KY, et al. Optimizing ACS NSQIP modeling for evaluation of surgical quality and risk: patient risk adjustment, procedure mix adjustment, shrinkage adjustment, and surgical focus. J Am Coll Surg. 2013;217(2):336-346.e1.

    Article  PubMed  Google Scholar 

  29. Brown LB, Streiff MB, Haut ER. Venous thromboembolism prevention and treatment in cancer surgery. Adv Surg. 2020;54:17–30.

    Article  PubMed  Google Scholar 

  30. Sweetland S, Green J, Liu B, et al. Duration and magnitude of the postoperative risk of venous thromboembolism in middle aged women: prospective cohort study. BMJ. 2009;3(339):b4583.

    Article  Google Scholar 

  31. Xu Y, Jia Y, Zhang Q, Du Y, He Y, Zheng A. Incidence and risk factors for postoperative venous thromboembolism in patients with ovarian cancer: systematic review and meta-analysis. Gynecol Oncol. 2021;160(2):610–8.

    Article  PubMed  Google Scholar 

  32. Walker AJ, West J, Card TR, Crooks C, Kirwan CC, Grainge MJ. When are breast cancer patients at highest risk of venous thromboembolism? A cohort study using English health care data. Blood. 2016;127(7):849–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Brennan K, Karim S, Doiron RC, Siemens DR, Booth CM. Venous thromboembolism and peri-operative chemotherapy for muscle-invasive bladder cancer: a population-based study. Bladder Cancer. 2018;4(4):419–28.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kimura Y, Oki E, Ando K, Saeki H, Kusumoto T, Maehara Y. Incidence of venous thromboembolism following laparoscopic surgery for gastrointestinal cancer: a single-center, prospective cohort study. World J Surg. 2016;40(2):309–14.

    Article  PubMed  Google Scholar 

  35. Yuk J, Lee B, Kim K, et al. Incidence and risk of venous thromboembolism according to primary treatment in women with ovarian cancer: a retrospective cohort study. PLoS ONE. 2021;16(4):e0250723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Boone BA, Zenati MS, Rieser C, et al. Risk of venous thromboembolism for patients with pancreatic ductal adenocarcinoma undergoing preoperative chemotherapy followed by surgical resection. Ann Surg Oncol. 2019;26(5):1503–11.

    Article  PubMed  Google Scholar 

  37. Brown ZJ, Cloyd JM. Trends in the utilization of neoadjuvant therapy for pancreatic ductal adenocarcinoma. J Surg Oncol. 2021;123(6):1432–40.

    Article  CAS  PubMed  Google Scholar 

  38. Janssen QP, O’Reilly EM, van Eijck CHJ, Koerkamp BG. Neoadjuvant treatment in patients with resectable and borderline resectable pancreatic cancer. Front Oncol. 2020;2020(10):41.

    Article  Google Scholar 

  39. 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 

  40. National Comprehensive Cancer Network. Pancreatic Adenocarcinoma (Version 2.2022). https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed 25 Jan 2023.

  41. Nassour I, Adam MA, Kowalsky S, et al. Neoadjuvant therapy versus upfront surgery for early-stage left-sided pancreatic adenocarcinoma: a propensity-matched analysis from a national cohort of distal pancreatectomies. J Surg Oncol. 2021;123(1):245–51.

    Article  CAS  PubMed  Google Scholar 

  42. Lof S, Korrel M, van Hilst J, et al. Impact of neoadjuvant therapy in resected pancreatic ductal adenocarcinoma of the pancreatic body or tail on surgical and oncological outcome: a propensity-score matched multicenter study. Ann Surg Oncol. 2020;27(6):1986–96.

    Article  PubMed  Google Scholar 

  43. Nelson DW, Chang SC, Grunkemeier G, et al. Resectable distal pancreas cancer: time to reconsider the role of upfront surgery. Ann Surg Oncol. 2018;25(13):4012–9.

    Article  PubMed  Google Scholar 

  44. Hyun JJ, Rose JR, Alseidi AA, et al. Significance of radiographic splenic vessel involvement in pancreatic ductal adenocarcinoma of the body and tail of the gland. J Surg Oncol. 2019;120(2):262–9.

    Article  PubMed  Google Scholar 

  45. Kawai M, Hirono S, Okada KI, et al. Radiographic splenic artery involvement is a poor prognostic factor in upfront surgery for patients with resectable pancreatic body and tail cancer. Ann Surg Oncol. 2021;28(3):1521–32.

    Article  PubMed  Google Scholar 

  46. Yin F, Saad M, Lin J, et al. Splenic vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer. Gastroenterol Rep. 2020;9(2):139–45.

    Article  Google Scholar 

  47. Gantois D, Guilbaud T, Scemama U, et al. Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study. Langenbecks Arch Surg. 2022;407(1):153–65.

    Article  PubMed  Google Scholar 

  48. Crippa S, Cirocchi R, Maisonneuve P, et al. Systematic review and meta-analysis of prognostic role of splenic vessels infiltration in resectable pancreatic cancer. Eur J Surg Oncol. 2018;44(1):24–30.

    Article  PubMed  Google Scholar 

  49. Mizumoto T, Toyama H, Asari S, et al. Pathological and radiological splenic vein involvement are predictors of poor prognosis and early liver metastasis after surgery in patients with pancreatic adenocarcinoma of the body and tail. Ann Surg Oncol. 2018;25(3):638–46.

    Article  PubMed  Google Scholar 

  50. Farrow NE, Aboagye JK, Lau BD, et al. The role of extended / outpatient venous thromboembolism prophylaxis after abdominal surgery for cancer or inflammatory bowel disease. J Pat Saf Risk Manag. 2018;23(1):19–26.

    Google Scholar 

  51. Verdovati MC, Becattini C, Rondelli F, et al. A randomized study on 1-week versus 4-week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer. Ann Surg. 2014;259(4):655–9.

    Google Scholar 

  52. Kakkar VV, Balibrea JL, Martinez-Gonzalez J, Prandoni P, CANBESURE Study Group. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvis surgery for cancer: the CANBESURE randomized study. J Thromb Haemost. 2010;8(6):1223–9.

    Article  CAS  PubMed  Google Scholar 

  53. Bergqvist D, Agnelli G, Cohen AT, et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002;346(13):975–80.

    Article  CAS  PubMed  Google Scholar 

  54. Felder S, Rasmussen MS, King R, et al. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev. 2019;8(8):004318.

    Google Scholar 

  55. Knoll W, Fergusson N, Ivankovic V, et al. Extended thromboprophylaxis following major abdominal/pelvic cancer-related surgery: a systematic review and meta-analysis of the literature. Thromb Res. 2021;204:114–22.

    Article  CAS  PubMed  Google Scholar 

  56. Lyman GH, Carrier M, Ay C, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv. 2021;5(4):927–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. National Comprehensive Cancer Network. Cancer-Associated Venous Thromboembolic Disease (Version 1.2022). https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf. Accessed 25 Jan 2023.

  58. Farge D, Frere C, Connors JM, et al. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol. 2022;23(7):e334–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496–520.

    Article  PubMed  Google Scholar 

  60. Ruff SM, Ayabe RI, Wach MM, et al. Practice patterns of VTE chemoprophylaxis after discharge following hepatic and pancreatic resections for cancer: a survey of hepatopancreatobiliary surgeons. J Thromb Thrombolysis. 2019;48(1):119–24.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Kroger K, Weiland D, Ose C, et al. Risk factors for venous thromboembolic events in cancer patients. Ann Oncol. 2006;17(2):297–303.

    Article  CAS  PubMed  Google Scholar 

  62. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.

    Article  CAS  PubMed  Google Scholar 

  63. Berger AK, Singh HM, Werft W, et al. High prevalence of incidental and symptomatic venous thromboembolic events in patients with advanced pancreatic cancer under palliative chemotherapy: a retrospective cohort study. Pancreatology. 2017;17(4):629–34.

    Article  CAS  PubMed  Google Scholar 

  64. Riedl JM, Schwarzenbacher E, Moik F, et al. Patterns of thromboembolism in patients with advanced pancreatic cancer undergoing first-line chemotherapy with FOLFIRINOX or gemcitabine/nab-paclitaxel. Thromb Haemost. 2022;122(4):633–45.

    Article  PubMed  Google Scholar 

  65. Pohl A, Spaulding AC, Brennan ER, et al. Risk adjusted venous thromboembolism prophylaxis following pancreatic surgery. J Thromb Thrombolysis. 2023;55:604–16.

    Article  PubMed  Google Scholar 

  66. Truty MJ, Kendrick ML, Nagorney DM, et al. Factors predicting response, perioperative outcomes, and survival following total neoadjuvant therapy for borderline / locally advanced pancreatic cancer. Ann Surg. 2021;273(2):341–9.

    Article  PubMed  Google Scholar 

  67. Barrak D, Villano AM, Villafane-Ferriol N, et al. Total neoadjuvant therapy for pancreatic adenocarcinoma increases probability for a complete pathologic response. Eur J Surg Oncol. 2022;48(6):1356–61.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Villano AM, O’Halloran E, Goel N, et al. Total neoadjuvant therapy is associated with improved overall survival and pathologic response in pancreatic adenocarcinoma. J Surg Oncol. 2022;126(3):502–12.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgement

Drs. Robbins and Newcomer are grateful for support from NCI T32 CA009621.

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Authors and Affiliations

  1. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Keenan J. Robbins MBBS, MPHS, Kenneth F. Newcomer Jr. MD, Jingxia Liu MD, PhD & William G. Hawkins MD, FACS

  2. Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Erica K. Barnell MD, PhD

  3. Touro College of Osteopathic Medicine, New York, NY, USA

    Michael A. Anzelmo BS

  4. Alvin J. Siteman Cancer Center, St. Louis, MO, USA

    William G. Hawkins MD, FACS

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  1. Keenan J. Robbins MBBS, MPHS
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Correspondence to William G. Hawkins MD, FACS.

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DISCLOSURES

K.J.R. and K.F.N. received funding from NIH NCI T32 CA009621. E.K.B. is a founder and employee of Geneoscopy, and has stock and intellectual property related to this entity. This disclosure is not directly relevant to the current paper. W.G.H. is a founder of Accuronix Therapeutics and has a financial interest in this entity. W.G.H. also receives clinical trial support from Celldex Corporation. Neither of these disclosures is directly relevant to the current paper.

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Robbins, K.J., Newcomer, K.F., Barnell, E.K. et al. Neoadjuvant Chemotherapy is Associated with Increased Risk of Postoperative DVT After Distal Pancreatectomy for Pancreatic Adenocarcinoma: a NSQIP Analysis. Ann Surg Oncol 31, 2873–2881 (2024). https://doi.org/10.1245/s10434-023-14763-y

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