Optimal Management of Resectable Pancreatic Head Cancer in the Elderly Patient: Does Neoadjuvant Therapy Offer a Survival Benefit?
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
25
09
2020
accepted:
22
02
2021
pubmed:
23
3
2021
medline:
28
9
2021
entrez:
22
3
2021
Statut:
ppublish
Résumé
Neoadjuvant therapy (NAT) is a growing strategy for patients with resectable pancreatic ductal adenocarcinoma (PDAC). Elderly patients are at increased risk of treatment withdrawal due to functional decline, and the benefit of NAT in this cohort remains to be studied. The objective of this study was to compare outcomes of elderly patients with resectable head PDAC who underwent NAT or a surgery-first (SF) approach. All patients 75 years of age and older with radiographically resectable (National Comprehensive Cancer Network criteria) PDAC who underwent pancreaticoduodenectomy at a single institution from 2008 to 2017 were analyzed. Baseline characteristics and perioperative outcomes were compared between the SF and NAT cohorts. Recurrence-free survival and overall survival (OS) were analyzed by treatment strategy. Overall, 158 patients were identified: SF cohort = 90 (57%) and NAT cohort = 68 (43%). Patients in the SF cohort were older (80 vs. 78 years; p = 0.01) but there were no differences in preoperative comorbidities or frailty indices. SF patients had a trend toward higher rates of major complications (38% vs. 24%; p = 0.06) with higher Comprehensive Complication Index totals (20.9 vs. 20; p = 0.03). There were similar rates of adjuvant therapy. NAT was associated with significantly longer OS (24.6 vs. 17.6 months; p = 0.01) in both the intent-to-treat and resected cohorts. On multivariable analysis (MVA), NAT remained an independent predictor of OS (hazard ratio 0.60; p = 0.02). NAT is safe and effective for elderly patients with PDAC. This study suggests NAT is associated with fewer complications after surgery, equal rates of adjuvant therapy receipt, and increased OS over a surgery-first approach.
Identifiants
pubmed: 33748894
doi: 10.1245/s10434-021-09822-1
pii: 10.1245/s10434-021-09822-1
pmc: PMC8614241
mid: NIHMS1750871
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6264-6272Subventions
Organisme : NCI NIH HHS
ID : T32 CA113263
Pays : United States
Organisme : NCI NIH HHS
ID : T32CA113263
Pays : United States
Informations de copyright
© 2021. Society of Surgical Oncology.
Références
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA A Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590 .
doi: 10.3322/caac.21590
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–21. https://doi.org/10.1158/0008-5472.Can-14-0155 .
doi: 10.1158/0008-5472.Can-14-0155
pubmed: 24840647
Howlader N, Noone A, Krapcho M, Miller D, Brest A, Yu M, et al. (eds). SEER Cancer Statistics Review, 1975–2016. National Cancer Institute. https://seer.cancer.gov/csr/1975_2016/ . Accessed Jan 2021.
Groot VP, Gemenetzis G, Blair AB, et al. Defining and predicting early recurrence in 957 patients with resected pancreatic ductal adenocarcinoma. Ann Surg. 2019;269(6):1154–62. https://doi.org/10.1097/sla.0000000000002734 .
doi: 10.1097/sla.0000000000002734
pubmed: 31082915
Neuhaus P, Riess H, Post S, et al. CONKO-001: Final results of the randomized, prospective, multicenter phase III trial of adjuvant chemotherapy with gemcitabine versus observation in patients with resected pancreatic cancer (PC). J Clin Oncol. 2008;26(15 Suppl):LBA4504. https://doi.org/10.1200/jco.2008.26.15_suppl.lba4504 .
doi: 10.1200/jco.2008.26.15_suppl.lba4504
Neoptolemos JP, Stocken DD, Bassi C, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA. 2010;304(10):1073–81. https://doi.org/10.1001/jama.2010.1275 .
doi: 10.1001/jama.2010.1275
pubmed: 20823433
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. 2013;310(14):1473–81. https://doi.org/10.1001/jama.2013.279201 .
doi: 10.1001/jama.2013.279201
pubmed: 24104372
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 (London, England). 2017;389(10073):1011–24. https://doi.org/10.1016/s0140-6736(16)32409-6 .
doi: 10.1016/s0140-6736(16)32409-6
pubmed: 28129987
Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395–406. https://doi.org/10.1056/NEJMoa1809775 .
doi: 10.1056/NEJMoa1809775
pubmed: 30575490
Sugiura T, Okamura Y, Ito T, Yamamoto Y, Ashida R, Uesaka K. Impact of patient age on the postoperative survival in pancreatic head cancer. Ann Surg Oncol. 2017;24(11):3220–8. https://doi.org/10.1245/s10434-017-5994-0 .
doi: 10.1245/s10434-017-5994-0
pubmed: 28695390
Parmar AD, Vargas GM, Tamirisa NP, Sheffield KM, Riall TS. Trajectory of care and use of multimodality therapy in older patients with pancreatic adenocarcinoma. Surgery. 2014;156(2):280–9. https://doi.org/10.1016/j.surg.2014.03.001 .
doi: 10.1016/j.surg.2014.03.001
pubmed: 24851723
Bakens MJ, van der Geest LG, van Putten M, et al. The use of adjuvant chemotherapy for pancreatic cancer varies widely between hospitals: a nationwide population-based analysis. Cancer Med. 2016;5(10):2825–31. https://doi.org/10.1002/cam4.921 .
doi: 10.1002/cam4.921
pubmed: 27671746
pmcid: 5083735
Eubanks A, Pepe J, Veldhuis P, de la Fuente SG. Age as a prognostic indicator for adjuvant therapy in patients who underwent pancreatic resections for cancer. J Geriatr Oncol. 2018;9(4):362–6. https://doi.org/10.1016/j.jgo.2017.12.004 .
doi: 10.1016/j.jgo.2017.12.004
pubmed: 29330039
Cooper AB, Holmes HM, des Bordes JK, et al. Role of neoadjuvant therapy in the multimodality treatment of older patients with pancreatic cancer. J Am Coll Surg. 2014;219(1):111–20. https://doi.org/10.1016/j.jamcollsurg.2014.02.023 .
doi: 10.1016/j.jamcollsurg.2014.02.023
pubmed: 24856952
Nagrial AM, Chang DK, Nguyen NQ, et al. Adjuvant chemotherapy in elderly patients with pancreatic cancer. Br J Cancer. 2014;110(2):313–9. https://doi.org/10.1038/bjc.2013.722 .
doi: 10.1038/bjc.2013.722
pubmed: 24263063
Paniccia A, Gleisner AL, Zenati MS, et al. Predictors of disease progression or performance status decline in patients undergoing neoadjuvant therapy for localized pancreatic head adenocarcinoma. Ann Surg Oncol. 2020;27(8):2961–71.
doi: 10.1245/s10434-020-08257-4
National Comprehensive Cancer Network. NCCN practice guidelines for pancreatic cancer, version 1.2020. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf . Accessed Jan 2021.
Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51. https://doi.org/10.1016/0895-4356(94)90129-5 .
doi: 10.1016/0895-4356(94)90129-5
pubmed: 7722560
Subramaniam S, Aalberg JJ, Soriano RP, Divino CM. New 5-Factor Modified Frailty Index Using American College of Surgeons NSQIP Data. J Am Coll Surg. 2018;226(2):173–181.e8. https://doi.org/10.1016/j.jamcollsurg.2017.11.005 .
doi: 10.1016/j.jamcollsurg.2017.11.005
pubmed: 29155268
Konstantinidis IT, Lewis A, Lee B, et al. Minimally invasive distal pancreatectomy: greatest benefit for the frail. Surg Endosc. 2017;31(12):5234–40. https://doi.org/10.1007/s00464-017-5593-y .
doi: 10.1007/s00464-017-5593-y
pubmed: 28493165
pmcid: 5980234
Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien PA. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013;258(1):1–7. https://doi.org/10.1097/SLA.0b013e318296c732 .
doi: 10.1097/SLA.0b013e318296c732
pubmed: 23728278
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. https://doi.org/10.1097/01.sla.0000133083.54934.ae .
doi: 10.1097/01.sla.0000133083.54934.ae
pubmed: 15273542
pmcid: 15273542
Bassi C, Marchegiani G, Dervenis C, et al. The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery. 2017;161(3):584–91. https://doi.org/10.1016/j.surg.2016.11.014 .
doi: 10.1016/j.surg.2016.11.014
pubmed: 28040257
Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2007;142(5):761–8. https://doi.org/10.1016/j.surg.2007.05.005 .
doi: 10.1016/j.surg.2007.05.005
pubmed: 17981197
Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758–65. https://doi.org/10.1200/jco.2008.20.8983 .
doi: 10.1200/jco.2008.20.8983
pubmed: 19403886
Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061–7. https://doi.org/10.1056/nejm199912303412706 .
doi: 10.1056/nejm199912303412706
pubmed: 10615079
Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol. 2004;22(22):4626–31. https://doi.org/10.1200/jco.2004.02.175 .
doi: 10.1200/jco.2004.02.175
pubmed: 15542812
Miura JT, Krepline AN, George B, et al. Use of neoadjuvant therapy in patients 75 years of age and older with pancreatic cancer. Surgery. 2015;158(6):1545–55. https://doi.org/10.1016/j.surg.2015.06.017 .
doi: 10.1016/j.surg.2015.06.017
pubmed: 26243342
Cooper AB, Parmar AD, Riall TS, et al. Does the use of neoadjuvant therapy for pancreatic adenocarcinoma increase postoperative morbidity and mortality rates? J Gastrointestinal Surg. 2015;19(1):80–6. https://doi.org/10.1007/s11605-014-2620-3 (discussion 86-7).
doi: 10.1007/s11605-014-2620-3
Kamarajah SK, Bundred JR, Boyle C, Oo J, Pandanaboyana S, Loveday B. Impact of neoadjuvant therapy on post-operative pancreatic fistula: a systematic review and meta-analysis. ANZ J Surg. 2020;90(11):2201–10. https://doi.org/10.1111/ans.15885 .
doi: 10.1111/ans.15885
pubmed: 32418344
Epelboym I, Zenati MS, Hamad A, et al. Analysis of perioperative chemotherapy in resected pancreatic cancer: identifying the number and sequence of chemotherapy cycles needed to optimize survival. Ann Surg Oncol. 2017;24(9):2744–51. https://doi.org/10.1245/s10434-017-5975-3 .
doi: 10.1245/s10434-017-5975-3
pubmed: 28681155
Valle JW, Palmer D, Jackson R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol. 2014;32(6):504–12. https://doi.org/10.1200/jco.2013.50.7657 .
doi: 10.1200/jco.2013.50.7657
pubmed: 24419109