Pancreatectomy with Vascular Resection After Neoadjuvant FOLFIRINOX: Who Survives More Than a Year After Surgery?
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:
Aug 2021
Aug 2021
Historique:
received:
31
08
2020
accepted:
10
12
2020
pubmed:
20
1
2021
medline:
9
7
2021
entrez:
19
1
2021
Statut:
ppublish
Résumé
Experienced pancreatic surgeons, for whom complexity is not an issue, must decide at the end of neoadjuvant therapy whether to continue or discontinue surgery, when pancreatectomy with vascular resection is planned in patients with pancreatic ductal adenocarcinoma (PDAC). Our study aimed to determine preoperative factors that can predict short postoperative survival in such situations. Overall, 105 patients with borderline or locally advanced PDAC received neoadjuvant FOLFIRINOX (followed by chemoradiation in 22% of patients) and underwent pancreatectomy with segmental venous and/or arterial resection at two high-volume centers. The primary endpoint was overall survival (OS) of < 1 year after surgery for patients who did not die from the surgery. Tumors were classified as borderline in 78% of cases and locally advanced in 22% of cases. Mean CA19-9 at diagnosis was 934 U/mL, which significantly decreased to 213 U/mL (p < 0.01) after a median of six cycles of FOLFIRINOX. Pancreaticoduodenectomy was performed most often (76%). The vast majority of patients underwent venous resection (92%), and a simultaneous arterial resection was performed in 16 patients (15%). The severe morbidity rate and 30- and 90-day mortality rates were 21%, 8.5%, and 10.4%, respectively. The median OS after surgery was 23 months. In the multivariate analysis, preoperative CA19-9 ≥ 450 U/mL was the only preoperative factor independently associated with OS of < 1 year (p = 0.044). The preoperative CA19-9 value should be considered in the clinical decision-making process when complex vascular resection is required.
Sections du résumé
BACKGROUND
BACKGROUND
Experienced pancreatic surgeons, for whom complexity is not an issue, must decide at the end of neoadjuvant therapy whether to continue or discontinue surgery, when pancreatectomy with vascular resection is planned in patients with pancreatic ductal adenocarcinoma (PDAC).
OBJECTIVE
OBJECTIVE
Our study aimed to determine preoperative factors that can predict short postoperative survival in such situations.
METHODS
METHODS
Overall, 105 patients with borderline or locally advanced PDAC received neoadjuvant FOLFIRINOX (followed by chemoradiation in 22% of patients) and underwent pancreatectomy with segmental venous and/or arterial resection at two high-volume centers. The primary endpoint was overall survival (OS) of < 1 year after surgery for patients who did not die from the surgery.
RESULTS
RESULTS
Tumors were classified as borderline in 78% of cases and locally advanced in 22% of cases. Mean CA19-9 at diagnosis was 934 U/mL, which significantly decreased to 213 U/mL (p < 0.01) after a median of six cycles of FOLFIRINOX. Pancreaticoduodenectomy was performed most often (76%). The vast majority of patients underwent venous resection (92%), and a simultaneous arterial resection was performed in 16 patients (15%). The severe morbidity rate and 30- and 90-day mortality rates were 21%, 8.5%, and 10.4%, respectively. The median OS after surgery was 23 months. In the multivariate analysis, preoperative CA19-9 ≥ 450 U/mL was the only preoperative factor independently associated with OS of < 1 year (p = 0.044).
CONCLUSION
CONCLUSIONS
The preoperative CA19-9 value should be considered in the clinical decision-making process when complex vascular resection is required.
Identifiants
pubmed: 33462718
doi: 10.1245/s10434-020-09520-4
pii: 10.1245/s10434-020-09520-4
doi:
Substances chimiques
folfirinox
0
Oxaliplatin
04ZR38536J
Irinotecan
7673326042
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4625-4634Références
Rangelova E, Wefer A, Persson S, et al. Surgery improves survival after neoadjuvant therapy for borderline and locally advanced pancreatic cancer: a single institution experience. Ann Surg. 2019. https://doi.org/10.1097/SLA.0000000000003301 .
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–25.
pubmed: 21561347
Hackert T, Sachsenmaier M, Hinz U, et al. Locally advanced pancreatic cancer: neoadjuvant therapy with Folfirinox results in resectability in 60% of the patients. Ann Surg. 2016;264:457–63.
pubmed: 27355262
Xu X, Wu Q, Wang Z, Zheng S, Ge K, Jia C. Meta-analysis of FOLFIRINOX regimen as the first-line chemotherapy for locally advanced pancreatic cancer and borderline resectable pancreatic cancer. Clin Exp Med. 2019;19:149–57.
pubmed: 30498929
Macedo FI, Ryon E, Maithel SK, et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270:400–13.
pubmed: 31283563
Amano R, Kimura K, Nakata B, et al. Pancreatectomy with major arterial resection after neoadjuvant chemoradiotherapy gemcitabine and S-1 and concurrent radiotherapy for locally advanced unresectable pancreatic cancer. Surgery. 2015;158:191–200.
pubmed: 25900035
Pietrasz D, Turrini O, Vendrely V, et al. How does chemoradiotherapy following induction FOLFIRINOX improve the results in resected borderline or locally advanced pancreatic adenocarcinoma? An AGEO-FRENCH multicentric cohort. Ann Surg Oncol. 2019;26:109–17.
pubmed: 30362063
Versteijne E, Suker M, Groothuis K, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the Dutch randomized phase III PREOPANC trial. J Clin Oncol. 2020;38:1763–73.
pubmed: 32105518
van Veldhuisen E, Vogel JA, Klompmaker S, et al. Added value of CA19-9 response in predicting resectability of locally advanced pancreatic cancer following induction chemotherapy. HPB (Oxford). 2018;20:605–11.
pubmed: 29475787
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. 2019. https://doi.org/10.1097/SLA.0000000000003284 .
Ferrone CR, Marchegiani G, Hong TS, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261:12–7.
pubmed: 25599322
Bachellier P, Rosso E, Fuchshuber P, et al. Use of a temporary intraoperative mesentericoportal shunt for pancreatic resection for locally advanced pancreatic cancer with portal vein occlusion and portal hypertension. Surgery. 2014;155:449–56.
pubmed: 24462078
Al Faraï A, Garnier J, Ewald J, et al. International Study Group of Pancreatic Surgery type 3 and 4 venous resections in patients with pancreatic adenocarcinoma:the Paoli-Calmettes Institute experience. Eur J Surg Oncol. 2019;45:1912–18.
pubmed: 31186204
Jegatheeswaran S, Baltatzis M, Jamdar S, Siriwardena AK. Superior mesenteric artery (SMA) resection during pancreatectomy for malignant disease of the pancreas: a systematic review. HPB (Oxford). 2017;19:483–90.
pubmed: 28410913
Klompmaker S, van Hilst J, Gerritsen SL, et al. Outcomes after distal pancreatectomy with celiac axis resection for pancreatic cancer: a Pan-European retrospective cohort study. Ann Surg Oncol. 2018;25:1440–7.
pubmed: 29532342
pmcid: 5891548
Bachellier P, Addeo P, Faitot F, Nappo G, Dufour P. Pancreatectomy with arterial resection for pancreatic adenocarcinoma: how can it be done safely and with which outcomes? A single institution’s experience with 118 patients. Ann Surg. 2020;271:932–40.
pubmed: 30188399
Liu L, Jia C, Xu S, Shen M. Arterial reconstruction by anastomosis of left gastric artery and superior mesenteric artery for locally advanced pancreatic carcinoma. J Vasc Surg Cases Innov Technol. 2018;5:4–6.
pubmed: 30619981
pmcid: 6313831
Alfano M, Marchese U, Poizat F, Turrini O, Delpero JR. How to reconstruct a Michels type 9 hepatic artery using the inverted splenic artery technique. ANZ J Surg. 2020;90(7–8):1474–6. https://doi.org/10.1111/ans.16027 .
doi: 10.1111/ans.16027
pubmed: 32500622
Tee MC, Krajewski AC, Groeschl RT, et al. Indications and perioperative outcomes for pancreatectomy with arterial resection. J Am Coll Surg. 2018;227:255–69.
pubmed: 29752997
Huang L, Jansen L, Balavarca Y, et al. Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations. Gut. 2019;68:130–9.
pubmed: 29158237
Isaji S, Mizuno S, Windsor JA, et al. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology. 2018;18:2–11.
pubmed: 29191513
Garnier J, Ewald J, Marchese U, et al. Outcomes of patients with initially locally advanced pancreatic adenocarcinoma who did not benefit from resection: a prospective cohort study. BMC Cancer. 2020;20:203.
pubmed: 32164564
pmcid: 7068994
Bockhorn M, Uzunoglu FG, Adham M, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2014;155:977–88.
pubmed: 24856119
van Roessel S, Strijker M, Steyerberg EW, et al. International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer. Eur J Surg Oncol. 2020;46:796–803.
pubmed: 31924432
Latenstein AEJ, van Roessel S, van der Geest LGM, et al. Conditional survival after resection for pancreatic cancer: a population-based study and prediction model. Ann Surg Oncol. 2020;27:2516–24.
pubmed: 32052299
pmcid: 7311496
Klompmaker S, Peters NA, van Hilst J, et al. Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR): An international multicenter analysis. Ann Surg Oncol. 2019;26:772–81.
pubmed: 30610560
pmcid: 6373251
Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15:1028–61.
Delpero JR, Sauvanet A. Vascular resection for pancreatic cancer: 2019 French recommendations based on a literature review from 2008 to 6-2019. Front Oncol. 2020;10:40.
pubmed: 32117714
pmcid: 7010716
Tempero MA, Malafa MP, Al-Hawary M, et al. NCCN Guidelines: Pancreatic Adenocarcinoma, Version 1.2020. J Natl Compr Canc Netw.
Schwarz L, Lupinacci RM, Svrcek M, et al. Para-aortic lymph node sampling in pancreatic head adenocarcinoma. Br J Surg. 2014;101:530–8.
pubmed: 24633831
Turrini O, Marchese U, Ewald J, Delpero JR. How I do hanging manoeuvres to facilitate portal vein resection during pancreaticoduodenectomy for borderline tumours. ANZ J Surg. 2018;88:106.
pubmed: 29194886
Tanaka H, Nakao A, Oshima K, et al. Splenic vein reconstruction is unnecessary in pancreatoduodenectomy combined with resection of the superior mesenteric vein–portal vein confluence according to short-term outcomes. HPB (Oxford). 2017;19:785–92.
pubmed: 28629642
Delpero JR, Bachellier P, Regenet N, et al. Pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: a French multicentre prospective evaluation of resection margins in 150 evaluable specimens. HPB (Oxford). 2014;16:20–33.
pubmed: 23464850
Delpero JR, Jeune F, Bachellier P, et al. Prognostic value of resection margin involvement after pancreaticoduodenectomy for ductal adenocarcinoma: updates from a French prospective multicenter study. Ann Surg. 2017;266:787–96.
pubmed: 28953554
Amini A, Jones BL, Stumpf P, et al. Patterns of care for locally advanced pancreatic adenocarcinoma using the National Cancer Database. Pancreas. 2017;46:904–12.
pubmed: 28697131
pmcid: 6218950
Pietrasz D, Marthey L, Wagner M, et al. Pathologic major response after FOLFIRINOX is prognostic for patients secondary resected for borderline or locally advanced pancreatic adenocarcinoma: an AGEO-FRENCH, prospective, multicentric cohort. Ann Surg Oncol. 2015;22:S1196–205.
pubmed: 26271395
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;240:205–13.
pubmed: 15273542
pmcid: 1360123
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;161:584–91.
pubmed: 28040257
Wente MN, Veit JA, Bassi C, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery. 2007;142:20–5.
pubmed: 17629996
Hartwig W, Gluth A, Hinz U, et al. Outcomes after extended pancreatectomy in patients with borderline resectable and locally advanced pancreatic cancer. Br J Surg. 2016;103:1683–94.
pubmed: 27686238
Mungroop TH, Klompmaker S, Wellner UF, et al. Updated alternative Fistula Risk Score (ua-FRS) to include minimally invasive pancreatoduodenectomy: Pan-European validation. Ann Surg. 2019. https://doi.org/10.1097/SLA.0000000000003234
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
Barenboim A, Lahat G, Geva R, et al. Neoadjuvant FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer: an intention to treat analysis. Eur J Surg Oncol. 2018;44:1619–23.
pubmed: 30146251
Versteijne E, Vogel JA, Besselink MG, et al. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg. 2018;105:946–58.
pubmed: 29708592
pmcid: 6033157
Cloyd JM, Heh V, Pawlik TM, et al. Neoadjuvant therapy for resectable and borderline resectable pancreatic cancer: a meta-analysis of randomized controlled trials. J Clin Med. 2020;9:1129.
pmcid: 7231310
You MS, Lee SH, Choi YH, et al. Lymph node ratio as valuable predictor in pancreatic cancer treated with R0 resection and adjuvant treatment. BMC Cancer. 2019;19: 952.
pubmed: 31615457
pmcid: 6794802
He J, Blair AB, Groot VP, et al. is a pathological complete response following neoadjuvant chemoradiation associated with prolonged survival in patients with pancreatic cancer? Ann Surg. 2018;268:1–8.
pubmed: 29334562
Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379:2395–406.
pubmed: 30575490
Yamada S, Yokoyama Y, Sonohara F, et al. Tumor marker recovery rather than major pathological response is a preferable prognostic factor in patients with pancreatic ductal adenocarcinoma with preoperative therapy. J Hepatobiliary Pancreat Sci. 2020;27:487–95.
pubmed: 32359199
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.
Cassinotto C, Mouries A, Lafourcade JP, et al. Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy. Radiology. 2014;273:108–16.
pubmed: 24960211
Akita H, Takahashi H, Ohigashi H, et al. FDG-PET predicts treatment efficacy and surgical outcome of pre-operative chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Eur J Surg Oncol. 2017;43:1061–67.
pubmed: 28389044
Wang ZJ, Behr S, Consunji MV, et al. Early response assessment in pancreatic ductal adenocarcinoma through integrated PET/MRI. AJR Am J Roentgenol. 2018;211:1010–19.
pubmed: 30063366
Michelakos T, Pergolini I, Castillo CF, et al. Predictors of resectability and survival in patients with borderline and locally advanced pancreatic cancer who underwent neoadjuvant treatment with FOLFIRINOX. Ann Surg. 2019;269:733–40.
pubmed: 29227344
Murphy JE, Wo JY, Ryan DP, et al. Total neoadjuvant therapy with FOLFIRINOX followed by individualized chemoradiotherapy for borderline resectable pancreatic adenocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2018;4:963–9.
pubmed: 29800971
pmcid: 6145728
Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–48.
pubmed: 18471707
pmcid: 5901743
Kang MJ, Jang JY, Kwon W, Kim SW. Clinical significance of defining borderline resectable pancreatic cancer. Pancreatology. 2018;18:139–45.
pubmed: 29274720
Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol. 2012;3:105–19.
pubmed: 22811878
pmcid: 3397644
Lee J, Lee J, Gromski MA, et al. Clinical outcomes of FOLFIRINOX in locally advanced pancreatic cancer: a single center experience. Medicine (Baltimore). 2018;97:e13592.
pubmed: 30558029
pmcid: 6320053
Tsai S, George B, Wittmann D, et al. Importance of normalization of CA19-9 levels following neoadjuvant therapy in patients with localized pancreatic cancer. Ann Surg. 2020;271:740–7.
pubmed: 30312198
Aldakkak M, Christians KK, Krepline AN, et al. Pre-treatment carbohydrate antigen 19-9 does not predict the response to neoadjuvant therapy in patients with localized pancreatic cancer. HPB (Oxford). 2015;17:942–52.
pubmed: 26255895
pmcid: 4571763
Boone BA, Steve J, Zenati MS, et al. Serum CA 19-9 response to neoadjuvant therapy is associated with outcome in pancreatic adenocarcinoma. Ann Surg Oncol. 2014;21:4351–58.
pubmed: 25092157
Rose JB, Edwards AM, Rocha FG, et al. Sustained carbohydrate antigen 19‐9 response to neoadjuvant chemotherapy in borderline resectable pancreatic cancer predicts progression and survival. Oncologist. 2020;25:859–66.
pubmed: 32277842
pmcid: 7543354
Bergquist JR, Puig CA, Shubert CR, et al. Carbohydrate antigen 19-9 elevation in anatomically resectable, early stage pancreatic cancer is independently associated with decreased overall survival and an indication for neoadjuvant therapy: a National Cancer Database study. J Am Coll Surg. 2016;223:52–65.
pubmed: 27049786
Medrano J, Garnier J, Ewald J, et al. Patient outcome according to the 2017 international consensus on the definition of borderline resectable pancreatic ductal adenocarcinoma. Pancreatology. 2020;20:223–28.
pubmed: 31839458
Truty MJ, Colglazier JJ, Mendes BC, et al. En bloc celiac axis resection for pancreatic cancer: Classification of anatomical variants based on tumor extent. J Am Coll Surg. 2020;231:8–29.
pubmed: 32422348
Schneider M, Strobel O, Hackert T, Büchler MW. Pancreatic resection for cancer—the Heidelberg technique. Langenbecks Arch Surg. 2019;404:1017–22.
pubmed: 31728630
Oehme F, Distler M, Müssle B, Kahlert C, Weitz J, Welsch T. Results of portosystemic shunts during extended pancreatic resections. Langenbecks Arch Surg. 2019;404:959–66.
pubmed: 31446472
Kwon J, Shin SH, Yoo D, et al. Arterial resection during pancreatectomy for pancreatic ductal adenocarcinoma with arterial invasion: a single-center experience with 109 patients. Medicine (Baltimore). 2020;99:e22115.
pubmed: 32925757
pmcid: 7489745
Meng L, Gao P, Peng B. Laparoscopic pancreaticoduodenectomy with superior mesenteric vein resection and artificial vascular graft reconstruction for borderline resectable pancreatic cancer. J Gastrointest Surg. 2020;24(12):2906–7. https://doi.org/10.1007/s11605-020-04808-y
doi: 10.1007/s11605-020-04808-y
pubmed: 33037557
Shyr BU, Chen SC, Shyr YM, Wang SE. Surgical, survival, and oncological outcomes after vascular resection in robotic and open pancreaticoduodenectomy. Surg Endosc. 2020;34:377–83.
pubmed: 30963260
Datta J, Wilson GC, D’Angelica MI, et al. A call for caution in overinterpreting exceptional outcomes following radical surgery for pancreatic cancer: Let the data speak. Ann Surg. 2020. https://doi.org/10.1097/SLA.0000000000004471
Vreeland TJ, McAllister F, Javadi S, et al. Benefit of gemcitabine/nab-paclitaxel rescue of patients with borderline resectable or locally advanced pancreatic adenocarcinoma after early failure of FOLFIRINOX. Pancreas. 2019;48:837–43.
pubmed: 31210666
pmcid: 7309587
Gemenetzis G, Groot VP, Blair AB, et al. Survival in locally advanced pancreatic cancer after neoadjuvant therapy and surgical resection. Ann Surg. 2019;270:340–7.
pubmed: 29596120