Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node-Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy.


Journal

World journal of surgery
ISSN: 1432-2323
Titre abrégé: World J Surg
Pays: United States
ID NLM: 7704052

Informations de publication

Date de publication:
11 2022
Historique:
accepted: 30 06 2022
pubmed: 22 7 2022
medline: 6 10 2022
entrez: 21 7 2022
Statut: ppublish

Résumé

Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear. Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015-2019) were identified. Patients who received less than 2 months of neoadjuvant chemotherapy or died within 90 days from surgery were excluded. A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1 months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4 months, P = 0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5 months, P < 0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9 months; P = 0.406). Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease.

Sections du résumé

BACKGROUND
Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear.
METHODS
Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015-2019) were identified. Patients who received less than 2 months of neoadjuvant chemotherapy or died within 90 days from surgery were excluded.
RESULTS
A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1 months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4 months, P = 0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5 months, P < 0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9 months; P = 0.406).
CONCLUSION
Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease.

Identifiants

pubmed: 35861852
doi: 10.1007/s00268-022-06667-x
pii: 10.1007/s00268-022-06667-x
pmc: PMC9532378
mid: NIHMS1836463
doi:

Substances chimiques

Uronic Acids 0
N-acetyltalosaminuronic acid 90319-06-5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2751-2759

Subventions

Organisme : NCI NIH HHS
ID : P01 CA247886
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA062924
Pays : United States

Informations de copyright

© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.

Références

Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA Cancer J Clin 72(1):7–33
doi: 10.3322/caac.21708
Rahib L, Wehner MR, Matrisian LM, Nead KT (2021) Estimated projection of US cancer incidence and death to 2040. JAMA Netw Open 4(4):e214708
doi: 10.1001/jamanetworkopen.2021.4708
Sohal DP, Walsh RM, Ramanathan RK, Khorana AA (2014) Pancreatic adenocarcinoma: treating a systemic disease with systemic therapy. J Natl Cancer Inst 106(3):dju011
doi: 10.1093/jnci/dju011
Picozzi VJ, Oh SY, Edwards A, Mandelson MT, Dorer R, Rocha FG et al (2017) Five-Year actual overall survival in resected pancreatic cancer: a contemporary single-institution experience from a multidisciplinary perspective. Ann Surg Oncol 24(6):1722–1730
doi: 10.1245/s10434-016-5716-z
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364(19):1817–1825
doi: 10.1056/NEJMoa1011923
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703
doi: 10.1056/NEJMoa1304369
Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K et al (2007) Adjuvant chemotherapy with gemcitabine versus observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297(3):267–277
doi: 10.1001/jama.297.3.267
Neoptolemos JP, Moore MJ, Cox TF, Valle JW, Palmer DH, McDonald AC et al (2012) Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine versus observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA 308(2):147–156
doi: 10.1001/jama.2012.7352
Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL et al (2018) FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379(25):2395–2406
doi: 10.1056/NEJMoa1809775
Mackay TM, Smits FJ, Roos D, Bonsing BA, Bosscha K, Busch OR et al (2020) The risk of not receiving adjuvant chemotherapy after resection of pancreatic ductal adenocarcinoma: a nationwide analysis. HPB (Oxford) 22(2):233–240
doi: 10.1016/j.hpb.2019.06.019
Ward EP, Evans DB, Tsai S (2021) Ten-year experience in optimizing neoadjuvant therapy for localized pancreatic cancer-Medical college of Wisconsin perspective. J Surg Oncol 123(6):1405–1413
doi: 10.1002/jso.26395
Versteijne E, Vogel JA, Besselink MG, Busch ORC, Wilmink JW, Daams JG et al (2018) Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg 105(8):946–958
doi: 10.1002/bjs.10870
Jang J-Y, Han Y, Lee H, Kim S-W, Kwon W, Lee K-H et al (2018) Oncological benefits of neoadjuvant chemoradiation with gemcitabine versus upfront surgery in patients with borderline resectable pancreatic cancer: a prospective, randomized, open-label, multicenter phase 2/3 trial. Ann Surg 268(2):215–222
doi: 10.1097/SLA.0000000000002705
Motoi F, Kosuge T, Ueno H, Yamaue H, Satoi S, Sho M et al (2019) Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn J Clin Oncol 49(2):190–194
doi: 10.1093/jjco/hyy190
Versteijne E, Suker M, Groothuis K, Akkermans-Vogelaar JM, Besselink MG, Bonsing BA et al (2020) Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the dutch randomized phase III PREOPANC trial. J Clin Oncol 38(16):1763–1773
doi: 10.1200/JCO.19.02274
Janssen QP, Buettner S, Suker M, Beumer BR, Addeo P, Bachellier P et al (2019) Neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer: a systematic review and patient-level meta-analysis. JNCI J Natl Cancer Instit 111(8):782–794
doi: 10.1093/jnci/djz073
Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA et al (2016) FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 17(6):801–810
doi: 10.1016/S1470-2045(16)00172-8
Christians KK, Heimler JW, George B, Ritch PS, Erickson BA, Johnston F et al (2016) Survival of patients with resectable pancreatic cancer who received neoadjuvant therapy. Surgery 159(3):893–900
doi: 10.1016/j.surg.2015.09.018
Unno M, Hata T, Motoi F (2019) Long-term outcome following neoadjuvant therapy for resectable and borderline resectable pancreatic cancer compared to upfront surgery: a meta-analysis of comparative studies by intention-to-treat analysis. Surg Today 49(4):295–299
doi: 10.1007/s00595-019-01786-w
Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI et al (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 261(1):12–17
doi: 10.1097/SLA.0000000000000867
Asare EA, Evans DB, Erickson BA, Aburajab M, Tolat P, Tsai S (2016) Neoadjuvant treatment sequencing adds value to the care of patients with operable pancreatic cancer. J Surg Oncol 114(3):291–295
doi: 10.1002/jso.24316
de Geus SWL, Kasumova GG, Sachs TE, Ng SC, Kent TS, Moser AJ et al (2018) Neoadjuvant therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma. HPB (Oxford) 20(6):573–581
doi: 10.1016/j.hpb.2017.12.004
Raufi AG, Manji GA, Chabot JA, Bates SE (2019) Neoadjuvant treatment for pancreatic cancer. Semin Oncol 46(1):19–27
doi: 10.1053/j.seminoncol.2018.12.002
Khorana AA, McKernin SE, Berlin J, Hong TS, Maitra A, Moravek C et al (2019) Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update. J Clin Oncol 37(23):2082–2088
doi: 10.1200/JCO.19.00946
Tempero MA, Malafa MP, Chiorean EG, Czito B, Scaife C, Narang AK et al (2019) Pancreatic adenocarcinoma. J Natl Compr Canc Netw 17(3):202–210
doi: 10.6004/jnccn.2019.0014
Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP (2017) The Eighth Edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging: the Eighth Edition AJCC Cancer Staging Manual. CA Cancer J Clin 67(2):93–99. https://doi.org/10.3322/caac.21388
doi: 10.3322/caac.21388 pubmed: 28094848
Wu W, He J, Cameron JL, Makary M, Soares K, Ahuja N et al (2014) The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma. Ann Surg Oncol 21(9):2873–2881
doi: 10.1245/s10434-014-3722-6
Mokdad AA, Minter RM, Zhu H, Augustine MM, Porembka MR, Wang SC et al (2017) Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis. J Clin Oncol 35(5):515–522
doi: 10.1200/JCO.2016.68.5081
de Geus SW, Eskander MF, Bliss LA, Kasumova GG, Ng SC, Callery MP et al (2017) Neoadjuvant therapy versus upfront surgery for resected pancreatic adenocarcinoma: a nationwide propensity score matched analysis. Surgery 161(3):592–601
doi: 10.1016/j.surg.2016.08.040
Shubert CR, Bergquist JR, Groeschl RT, Habermann EB, Wilson PM, Truty MJ et al (2016) Overall survival is increased among stage III pancreatic adenocarcinoma patients receiving neoadjuvant chemotherapy compared to surgery first and adjuvant chemotherapy: an intention to treat analysis of the National Cancer Database. Surgery 160(4):1080–1096
doi: 10.1016/j.surg.2016.06.010
Satoi S, Unno M, Motoi F, Matsuyama Y, Matsumoto I, Aosasa S et al (2019) The effect of neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic cancer (randomized phase II/III trial; Prep-02/JSAP-05). J Clin Oncol 37:4126
doi: 10.1200/JCO.2019.37.15_suppl.4126
Habib JR, Kinny-Köster B, Bou-Samra P, Alsaad R, Sereni E, Javed AA et al (2021) Surgical decision making in pancreatic ductal adenocarcinoma: modeling prognosis following pancreatectomy in the era of induction and neoadjuvant chemotherapy. Ann Surg. https://doi.org/10.1097/SLA.0000000000004915
doi: 10.1097/SLA.0000000000004915 pubmed: 33843794
van Roessel S, van Veldhuisen E, Klompmaker S, Janssen QP, Abu Hilal M, Alseidi A et al (2020) Evaluation of adjuvant chemotherapy in patients with resected pancreatic cancer after neoadjuvant FOLFIRINOX treatment. JAMA Oncol 6(11):1733–1740
doi: 10.1001/jamaoncol.2020.3537
Perri G, Prakash L, Qiao W, Varadhachary GR, Wolff R, Fogelman D et al (2020) Postoperative chemotherapy benefits patients who received preoperative therapy and pancreatectomy for pancreatic adenocarcinoma. Ann Surg 271(6):996–1002
doi: 10.1097/SLA.0000000000003763
Malleo G, Maggino L, Qadan M, Marchegiani G, Ferrone CR, Paiella S et al (2020) Reassessment of the optimal number of examined lymph nodes in pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Ann Surg. https://doi.org/10.1097/SLA.0000000000004552
doi: 10.1097/SLA.0000000000004552 pubmed: 33378303
Malleo G, Maggino L, Ferrone CR, Marchegiani G, Mino-Kenudson M, Capelli P et al (2019) Number of examined lymph nodes and nodal status assessment in distal pancreatectomy for body/tail ductal adenocarcinoma. Ann Surg 270(6):1138–1146
doi: 10.1097/SLA.0000000000002781
Arrington AK, O’Grady C, Schaefer K, Khreiss M, Riall TS (2020) Significance of lymph node resection after neoadjuvant therapy in pancreatic, gastric, and rectal cancers. Ann Surg 272(3):438–446
doi: 10.1097/SLA.0000000000004181
Javed AA, Ding D, Baig E, Wright MJ, Teinor JA, Mansoor D et al (2022) Accurate nodal staging in pancreatic cancer in the era of neoadjuvant therapy. World J Surg 46(3):667–677. https://doi.org/10.1007/s00268-021-06410-y
doi: 10.1007/s00268-021-06410-y pubmed: 34994834
Sirody JR, Kaji AH, Hari DM, Chen KT (2020) The effect of neoadjuvant therapy on lymph node yield in pancreatic cancer. J Am Coll Surg 231(4):S283–S284
doi: 10.1016/j.jamcollsurg.2020.07.618
Klaiber U, Schnaidt ES, Hinz U, Gaida MM, Heger U, Hank T et al (2021) Prognostic factors of survival after neoadjuvant treatment and resection for initially unresectable pancreatic cancer. Ann Surg 273(1):154–162
doi: 10.1097/SLA.0000000000003270
Groot VP, Mosier S, Javed AA, Teinor JA, Gemenetzis G, Ding D et al (2019) Circulating tumor DNA as a clinical test in resected pancreatic cancer. Clin Cancer Res 25(16):4973–4984
doi: 10.1158/1078-0432.CCR-19-0197

Auteurs

Gabriel D Ivey (GD)

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

Sami Shoucair (S)

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

Daniel J Delitto (DJ)

Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.

Joseph R Habib (JR)

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

Benedict Kinny-Köster (B)

Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA.

Christopher R Shubert (CR)

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

Kelly J Lafaro (KJ)

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

John L Cameron (JL)

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

William R Burns (WR)

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

Richard A Burkhart (RA)

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

Elizabeth L Thompson (EL)

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

Amol Narang (A)

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

Lei Zheng (L)

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

Christopher L Wolfgang (CL)

Department of Surgery, NYU Grossman School of Medicine, New York, NY, USA.

Jin He (J)

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jhe11@jhmi.edu.

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