Prediction of Isolated Local Recurrence After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Study.

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:
27 Jun 2024

Historique:

received: 26 01 2024

accepted: 10 06 2024

medline: 28 6 2024

pubmed: 28 6 2024

entrez: 27 6 2024

Statut: aheadofprint

Résumé

Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection. An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed. Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved. This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

Sections du résumé

BACKGROUND BACKGROUND

PATIENTS AND METHODS METHODS

An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed.

RESULTS RESULTS

Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved.

CONCLUSIONS CONCLUSIONS

This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication.

Identifiants

DOI: 10.1245/s10434-024-15664-4 PMID: 38937412

pubmed: 38937412

doi: 10.1245/s10434-024-15664-4

pii: 10.1245/s10434-024-15664-4

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : KWF Kankerbestrijding

ID : 12568

Informations de copyright

Références

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7–33. https://doi.org/10.3322/caac.21708 .

doi: 10.3322/caac.21708 pubmed: 35020204

Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer [published correction appears in N Engl J Med. 2004 Aug 12;351(7):726]. N Engl J Med. 2004;350(12):1200–10. https://doi.org/10.1056/NEJMoa032295 .

doi: 10.1056/NEJMoa032295 pubmed: 15028824

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

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

Groot VP, Rezaee N, Wu W, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2018;267(5):936–45. https://doi.org/10.1097/SLA.0000000000002234 .

doi: 10.1097/SLA.0000000000002234 pubmed: 28338509

Latenstein AEJ, van der Geest LGM, Bonsing BA, et al. Nationwide trends in incidence, treatment and survival of pancreatic ductal adenocarcinoma. Eur J Cancer. 2020;125:83–93. https://doi.org/10.1016/j.ejca.2019.11.002 .

doi: 10.1016/j.ejca.2019.11.002 pubmed: 31841792

Groot VP, Gemenetzis G, Blair AB, et al. Implications of the pattern of disease recurrence on survival following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2018;25(8):2475–83. https://doi.org/10.1245/s10434-018-6558-7 .

doi: 10.1245/s10434-018-6558-7 pubmed: 29948425 pmcid: 6220676

Balaj C, Ayav A, Oliver A, et al. CT imaging of early local recurrence of pancreatic adenocarcinoma following pancreaticoduodenectomy. Abdom Radiol (NY). 2016;41(2):273–82. https://doi.org/10.1007/s00261-015-0564-z .

doi: 10.1007/s00261-015-0564-z pubmed: 26867909

Jung W, Jang JY, Kang MJ, et al. The clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in follow-up of curatively resected pancreatic cancer patients. HPB (Oxford). 2016;18(1):57–64. https://doi.org/10.1016/j.hpb.2015.06.001 .

doi: 10.1016/j.hpb.2015.06.001 pubmed: 26776852

Jones RP, Psarelli EE, Jackson R, et al. Patterns of recurrence after resection of pancreatic ductal adenocarcinoma: a secondary analysis of the ESPAC-4 randomized adjuvant chemotherapy trial. JAMA Surg. 2019;154(11):1038–48. https://doi.org/10.1001/jamasurg.2019.3337 .

doi: 10.1001/jamasurg.2019.3337 pubmed: 31483448 pmcid: 6727687

Tanaka M, Mihaljevic AL, Probst P, et al. Meta-analysis of recurrence pattern after resection for pancreatic cancer. Br J Surg. 2019;106(12):1590–601. https://doi.org/10.1002/bjs.11295 .

doi: 10.1002/bjs.11295 pubmed: 31454073

Strijker M, Mackay TM, Bonsing BA, et al. Establishing and coordinating a nationwide multidisciplinary study group: lessons learned by the Dutch Pancreatic Cancer Group. Ann Surg. 2020;271(4):e102–4. https://doi.org/10.1097/SLA.0000000000003779 .

doi: 10.1097/SLA.0000000000003779 pubmed: 32084037

Dutch Institute for Clinical Auditing. Dutch Pancreatic Cancer Audit (DPCA). Accessed January 9, 2024. http://www.dica.nl/dpca

Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD Statement. BMC Med. 2015;13:1. https://doi.org/10.1186/s12916-014-0241-z .

doi: 10.1186/s12916-014-0241-z pubmed: 25563062 pmcid: 4284921

von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (strobe) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. https://doi.org/10.1016/S0140-6736(07)61602-X .

doi: 10.1016/S0140-6736(07)61602-X

Dutch Pancreatic Cancer Group. Defining resectability in pancreatic cancer. Accessed May 11, 2023. https://dpcg.nl/richtlijnen/#:~:text=DPCG%2Ddefinities%20resectabiliteit%20pancreascarcinoom%20(PREOPANC%20trial%2C%20DPCG%202012 )

Versteijne E, van Eijck CH, Punt CJ, et al. 2016 Preoperative radiochemotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC trial): study protocol for a multicentre randomized controlled trial. Trials. 2016;17(1):127. https://doi.org/10.1186/s13063-016-1262-z .

doi: 10.1186/s13063-016-1262-z pubmed: 26955809 pmcid: 4784417

Janssen QP, van Dam JL, Bonsing BA, et al. Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial. BMC Cancer. 2021;21(1):300. https://doi.org/10.1186/s12885-021-08031-z .

doi: 10.1186/s12885-021-08031-z pubmed: 33757440 pmcid: 7989075

Federatie Medische Specialisten. Richtlijn Pancreascarcinoom 2019. Accessed January 9, 2024. https://richtlijnendatabase.nl/richtlijn/pancreascarcinoom/startpagina.html

Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):9399. https://doi.org/10.3322/caac.21388 .

doi: 10.3322/caac.21388

Donders AR, van der Heijden GJ, Stijnen T, Moons KG. Review: a gentle introduction to imputation of missing values. J Clin Epidemiol. 2006;59(10):1087–91. https://doi.org/10.1016/j.jclinepi.2006.01.014 .

doi: 10.1016/j.jclinepi.2006.01.014 pubmed: 16980149

Dodge Y. The concise encyclopedia of statistics. Berlin: Springer; 2008.

Watanabe Y, Nishihara K, Niina Y, et al. Patients with lung recurrence after curative resection for pancreatic ductal adenocarcinoma have a better prognosis than those with recurrence at other sites. J Pancreas. 2017;18:54–61.

Labori KJ, Katz MH, Tzeng CW, et al. 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;55(3):265–77. https://doi.org/10.3109/0284186X.2015.1068445 .

doi: 10.3109/0284186X.2015.1068445 pubmed: 26213211

Van Laethem JL, Hammel P, Mornex F, et al. Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase II study. J Clin Oncol. 2010;28(29):4450–6. https://doi.org/10.1200/JCO.2010.30.3446 .

doi: 10.1200/JCO.2010.30.3446 pubmed: 20837948 pmcid: 2988636

Ueno H, Kosuge T, Matsuyama Y, et al. A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer. Br J Cancer. 2009;101(6):908–15. https://doi.org/10.1038/sj.bjc.6605256 .

doi: 10.1038/sj.bjc.6605256 pubmed: 19690548 pmcid: 2743365

Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297(3):267–77. https://doi.org/10.1001/jama.297.3.267 .

doi: 10.1001/jama.297.3.267 pubmed: 17227978

Conroy T, Castan F, Lopez A, et al. Five-year outcomes of FOLFIRINOX vs gemcitabine as adjuvant therapy for pancreatic cancer: a randomized clinical trial [published correction appears in JAMA Oncol. 2023 Jan 1;9(1):151]. JAMA Oncol. 2022;8(11):1571–8. https://doi.org/10.1001/jamaoncol.2022.3829 .

doi: 10.1001/jamaoncol.2022.3829 pubmed: 36048453 pmcid: 9437831

Ghaly M, Gogineni E, Saif MW. The evolving field of stereotactic body radiation therapy in pancreatic cancer. Pancreas (Fairfax). 2019;3(1):9–14. https://doi.org/10.17140/POJ-3-110 .

doi: 10.17140/POJ-3-110 pubmed: 31930185 pmcid: 6954104

Crane CH. Hypofractionated ablative radiotherapy for locally advanced pancreatic cancer. J Radiat Res. 2016;57(11):i53–7. https://doi.org/10.1093/jrr/rrw016 .

doi: 10.1093/jrr/rrw016 pubmed: 27029741 pmcid: 4990109

Zhong J, Patel K, Switchenko J, et al. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation. Cancer. 2017;123(18):3486–93. https://doi.org/10.1002/cncr.30706 .

doi: 10.1002/cncr.30706 pubmed: 28493288

Park JJ, Hajj C, Reyngold M, et al. Stereotactic body radiation vs. intensity-modulated radiation for unresectable pancreatic cancer. Acta Oncol. 2017;56(12):1746–53. https://doi.org/10.1080/0284186X.2017.1342863 .

doi: 10.1080/0284186X.2017.1342863 pubmed: 28661823

Reyngold M, Parikh P, Crane CH. Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results. Radiat Oncol. 2019;14(1):95. https://doi.org/10.1186/s13014-019-1309-x .

doi: 10.1186/s13014-019-1309-x pubmed: 31171025 pmcid: 6555709

Rudra S, Jiang N, Rosenberg SA, et al. Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer. Cancer Med. 2019;8(5):2123–32. https://doi.org/10.1002/cam4.2100 .

doi: 10.1002/cam4.2100 pubmed: 30932367 pmcid: 6536981

Hassanzadeh C, Rudra S, Bommireddy A, et al. Ablative five-fraction stereotactic body radiation therapy for inoperable pancreatic cancer using online MR-guided adaptation. Adv Radiat Oncol. 2020;6(1):100506. https://doi.org/10.1016/j.adro.2020.06.010 .

doi: 10.1016/j.adro.2020.06.010 pubmed: 33665480 pmcid: 7897757

Raaymakers BW, Lagendijk JJ, Overweg J, et al. Integrating a 1.5 T MRI scanner with a 6 MV accelerator: proof of concept. Phys Med Biol. 2009;54(12):N229–37. https://doi.org/10.1088/0031-9155/54/12/N01 .

doi: 10.1088/0031-9155/54/12/N01 pubmed: 19451689

Lagendijk JJ, Raaymakers BW, van Vulpen M. The magnetic resonance imaging-linac system. Semin Radiat Oncol. 2014;24(3):207–9. https://doi.org/10.1016/j.semradonc.2014.02.009 .

doi: 10.1016/j.semradonc.2014.02.009 pubmed: 24931095

Kontaxis C, Bol GH, Lagendijk JJ, Raaymakers BW. A new methodology for inter- and intrafraction plan adaptation for the MR-linac. Phys Med Biol. 2015;60(19):7485–97. https://doi.org/10.1088/0031-9155/60/19/7485 .

doi: 10.1088/0031-9155/60/19/7485 pubmed: 26371425

Henke L, Kashani R, Robinson C, et al. Phase I trial of stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen. Radiother Oncol. 2018;126(3):519–26. https://doi.org/10.1016/j.radonc.2017.11.032 .

doi: 10.1016/j.radonc.2017.11.032 pubmed: 29277446

van Goor IWJM, Daamen LA, Besselink MG, et al. A nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy (ARCADE) [published correction appears in Trials. 2023 Jan 24;24(1):55]. Trials. 2022;23(1):913. https://doi.org/10.1186/s13063-022-06829-1 .

doi: 10.1186/s13063-022-06829-1 pubmed: 36307892 pmcid: 9617359

Hörner-Rieber J, Klüter S, Debus J, Adema G, Ansems M, Verheij M. MR-guided radiotherapy: the perfect partner for immunotherapy? Front Oncol. 2021;10:615697. https://doi.org/10.3389/fonc.2020.615697 .

doi: 10.3389/fonc.2020.615697 pubmed: 33604296 pmcid: 7884826

Gajiwala S, Torgeson A, Garrido-Laguna I, Kinsey C, Lloyd S. Combination immunotherapy and radiation therapy strategies for pancreatic cancer-targeting multiple steps in the cancer immunity cycle. J Gastrointest Oncol. 2018;9(6):1014–26. https://doi.org/10.21037/jgo.2018.05.16 .

doi: 10.21037/jgo.2018.05.16 pubmed: 30603120 pmcid: 6286952

Zhu X, Cao Y, Liu W, et al. Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2021;22(8):1093–102. https://doi.org/10.1016/S1470-2045(21)00286-2 .

doi: 10.1016/S1470-2045(21)00286-2 pubmed: 34237249

Ducreux M, Cuhna AS, Caramella C, et al. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol. 2017 Jul 1;28(suppl_4):iv167-iv168]. Ann Oncol. 2015;26(Suppl 5):v56–68. https://doi.org/10.1093/annonc/mdv295 .

doi: 10.1093/annonc/mdv295 pubmed: 26314780

Takaori K, Bassi C, Biankin A, et al. International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer. Pancreatology. 2016;16(1):14–27. https://doi.org/10.1016/j.pan.2015.10.013 .

doi: 10.1016/j.pan.2015.10.013 pubmed: 26699808

Liu KL, Wu T, Chen PT, et al. Deep learning to distinguish pancreatic cancer tissue from non-cancerous pancreatic tissue: a retrospective study with cross-racial external validation. Lancet Digit Health. 2020;2(6):e303–13. https://doi.org/10.1016/S2589-7500(20)30078-9 .

doi: 10.1016/S2589-7500(20)30078-9 pubmed: 33328124

Impact consortium. Accessed January 9, 2024. Available via https://impact-consortium.github.io/IMPACT/