Advertisement

Evolving management of early stage pancreatic adenocarcinoma in older patients

      Highlights

      • As the population ages, the number of older patients with PDAC is expected to rise.
      • While older patients are absent from clinical trials, results are extrapolated to this population.
      • Almost 50% of patients over the age of 80 do not receive AT following an UFS approach.
      • Receipt of NAT in older patients is associated with improved R0 resection rates.
      • NAT is also associated with a survival benefit when compared to patients that had UFS + AT.

      Abstract

      Background

      Due to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise.

      Study design

      Utilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death.

      Results

      Of 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT.

      Conclusion

      For older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics.
        CA A Cancer J Clin. 2021; 68 (2021 January): 7-30
        • Rawla P.
        • Sunkara T.
        • Gaduputi V.
        Epidemiology of pancreatic cancer: global trends, etiology and risk factors.
        World J Oncol. 2019 February; 10: 10-27
        • Oettle H.
        • Neuhaus P.
        • Hochhaus A.
        • Hartmann J.T.
        • Gellert K.
        • Ridwelski K.
        • et al.
        Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.
        JAMA. 2013 October; 310: 1473-1481
        • Neoptolemos J.P.
        • Stocken D.D.
        • Friess H.
        • Bassi C.
        • Dunn J.A.
        • Hickey H.
        • et al.
        A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer.
        N Engl J Med. 2004 March; 350: 1200-1210
        • Labori K.J.
        • Katz M.H.
        • Tzeng C.W.
        • Bjørnbeth B.A.
        • Cvancarova M.
        • Edwin B.
        • Kure E.H.
        • Eide T.J.
        • Dueland S.
        • Buanes T.
        • Gladhaug I.P.
        Impact of early disease progression and surgical complications on adjuvant chemotherapy completion rates and survival in patients undergoing the surgery first approach for resectable pancreatic ductal adenocarcinoma - a population-based cohort study.
        Acta Oncol. 2016 July; 55: 265-277
        • Tzeng C.W.
        • Tran Cao H.S.
        • Lee J.E.
        • Pisters P.W.
        • Varadhachary G.R.
        • Wolff R.A.
        • Abbruzzese J.L.
        • Crane C.H.
        • Evans D.B.
        • Wang H.
        • Abbott D.E.
        • Vauthey J.N.
        • Aloia T.A.
        • Fleming J.B.
        • Katz M.H.
        Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survival.
        J Gastrointest Surg. 2014 January; 18: 16-25
        • Jang J.Y.
        • Han Y.
        • Lee H.
        • Kim S.W.
        • Kwon W.
        • Lee K.H.
        • Oh D.Y.
        • Chie E.K.
        • Lee J.M.
        • Heo J.S.
        • Park J.O.
        • Lim D.H.
        • Kim S.H.
        • Park S.H.
        • Lee W.J.
        • Koh Y.H.
        • Park J.S.
        • Yoon D.S.
        • Lee I.J.
        • Choi S.H.
        Oncological benefits of neoadjuvant chemoradiation with gemcitabine versus upfront surgery in pts with borderline resectable pancreatic cancer: a prospective randomized, open label, multicenter phase 2/3 trial.
        Ann Surg. 2018 August; 268: 215-222
        • Boffa D.J.
        • Rosen J.E.
        • Mallin K.
        • Loomis A.
        • Gay G.
        • Palis B.
        • Thoburn K.
        • Gress D.
        • McKellar D.P.
        • Shulman L.N.
        • Facktor M.A.
        • Winchester D.P.
        Using the national cancer database for outcomes research: a review.
        JAMA Oncol. 2017 December; 3: 1722-1728
        • Austin P.C.
        • Stuart E.A.
        Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies.
        Stat Med. 2015; 34: 3661-3679
        • Ridgeway G.
        • McCaffrey D.
        • Morral A.
        • Cefalu M.
        • Burgette L.
        • Pane J.
        • Griffin B.A.
        Twang: toolkit for weighting and analysis of nonequivalent groups, R package version.
        2021 Oct: 1-33
        • McCaffrey D.F.
        • Griffin B.A.
        • Almirall D.
        • Slaughter M.E.
        • Ramchand R.
        • Burgette L.F.
        A tutorial on propensity score estimation for multiple treatments using generalized boosted models.
        Stat Med. 2013 Aug; 32: 3388-3414
        • Normand S.L.
        • Landrum M.B.
        • Guadagnoli E.
        • Ayanian J.Z.
        • Ryan T.J.
        • Cleary P.D.
        • McNeil B.J.
        Validating recommendations for coronary angiography following acute myocardial infarction in the elderly: a matched analysis using propensity scores.
        J Clin Epidemiol. 2001 Apr 1; 54: 387-398
        • Lai T.Y.
        • Hu Y.W.
        Neoadjuvant therapy in resectable pancreatic cancer: immortal time bias and its correction.
        J Clin Oncol. 2017 May; 35: 1623-1630
        • Mirkin K.A.
        • Hollenbeak C.S.
        • Wong J.
        Survival impact of neoadjuvant therapy in resected pancreatic cancer: a prospective cohort study involving 18,332 patients from the National Cancer Data Base.
        Int J Surg. 2016 August; 34: 96-102
        • Mirkin K.A.
        • Hollenbeak C.S.
        • Wong J.
        Survival impact of neoadjuvant therapy in resected pancreatic cancer: a prospective cohort study involving 18,332 patients from the National Cancer Data Base.
        Int J Surg. 2016 August; 34: 96-102
        • He J.
        • Blair A.B.
        • Groot V.P.
        • Javed A.A.
        • Burkhart R.A.
        • Gemenetzis G.
        • Hruban R.H.
        • Water K.M.
        • Poling J.
        • Zheng L.
        • Laheru D.
        • Herman J.M.
        • Makary M.A.
        • Weiss M.J.
        • Cameron J.L.
        • Wolfgang C.L.
        Is a pathological complete response following neoadjuvant chemoradiation associated with prolonged survival in patients with pancreatic cancer?.
        Ann Surg. 2018 July; 268: 1-8
        • Strobel O.
        • Hinz U.
        • Gluth A.
        • Hank T.
        • Hackert T.
        • Bergmann F.
        • Werner J.
        • Büchler M.W.
        Pancreatic adenocarcinoma: number of positive nodes allows to distinguish several N categories.
        Ann Surg. 2015 May; 261: 961-969
        • Murakami Y.
        • Uemura K.
        • Sudo T.
        • Hayashidani Y.
        • Hashimoto Y.
        • Nakashima A.
        • Yuasa Y.
        • Kondo N.
        • Ohge H.
        • Sueda T.
        Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma.
        J Am Coll Surg. 2010 August; 211: 196-204
        • Elshaer M.
        • Gravante G.
        • Kosmin M.
        • Riaz A.
        • Al-Bahrani A.
        A systematic review of the prognostic value of lymph node ratio, number of positive nodes and total nodes examined in pancreatic ductal adenocarcinoma.
        Ann R Coll Surg Engl. 2017 February; 99: 101-106
        • Raut C.P.
        • Tseng J.F.
        • Sun C.C.
        • Wang H.
        • Wolff R.A.
        • Crane C.H.
        • Hwang R.
        • Vauthey J.N.
        • Abdalla E.K.
        • Lee J.E.
        • Pisters P.W.
        • Evans D.B.
        Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma.
        Ann Surg. 2007 July; 246: 52-60
        • Davila J.A.
        • Chiao E.Y.
        • Hasche J.C.
        • Petersen N.J.
        • McGlyn K.A.
        • Shaib Y.H.
        Utilization and determinants of adjuvant therapy among older patients who receive curative surgery for pancreatic cancer.
        Pancreas. 2009 January; 38: 1-7
        • Mackay T.M.
        • Smits F.J.
        • Roos D.
        • Bonsing B.A.
        • Bosscha K.
        • Busch O.R.
        • Creemers G.J.
        • van Dam R.M.
        • van Eijck C.H.J.
        • Gerhards M.F.
        • de Groot J.W.
        • Koerkamp B.G.
        • Mohammad N.H.
        • van der Harst E.
        • de Hingh I.
        • Homs M.
        • Kazemier G.
        • Liem M.
        • de Meijer V.E.
        • Molenaar I.Q.
        • Nieuwnhuijs V.B.
        • van Santvoort H.C.
        • van der Schelling G.P.
        • Stommel M.
        • Tije A.
        • Vos-Geelen J.
        • Wit F.
        • Wilmink J.W.
        • van Laarhoven H.
        • Besserlink M.G.
        The risk of not receiving adjuvant chemotherapy after resection of pancreatic ductal adenocarcinoma: a nationwide analysis.
        HPB. 2020 February; 22: 233-240
        • De Geus S.W.
        • Eskander M.F.
        • Bliss L.A.
        • Kasumova G.G.
        • Ng S.C.
        • Callery M.P.
        • Tseng J.F.
        Neoadjuvant therapy versus upfront surgery for resected pancreatic adenocarcinoma: a nationwide propensity score matched analysis.
        Surgery. 2017 March; 161: 592-601
        • Khan S.
        • Sclabas G.
        • Lombardo K.R.
        • Sarr M.G.
        • Nagorney D.
        • Kendrick M.L.
        • Donohue J.H.
        • Que F.G.
        • Farnell M.B.
        Pancreatoduodenectomy for ductal adenocarcinoma in the very elderly; is it safe and justified?.
        J Gastrointest Surg. 2010 November; 14: 1826-1831
        • Swanson R.S.
        • Pezzi C.M.
        • Mallin K.
        • Loomis A.M.
        • Winchester D.P.
        The 90-day mortality after pancreatectomy for cancer is double the 30-day mortality: more than 20,000 resections from the NCDB.
        Ann Surg Oncol. 2014 December; 21: 4059-4067
        • Higuera O.
        • Ghanem I.
        • Nasimi R.
        • Prieto I.
        • Koren L.
        • Feliu J.
        Management of pancreatic cancer in the elderly.
        World J Gastroenterol. 2016 January; 22: 764-775