Neoadjuvant Phase II Trial of Chemoradiotherapy in Patients With Resectable and Borderline Resectable Pancreatic Cancer.
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Carcinoma, Pancreatic Ductal
/ surgery
Chemoradiotherapy
Deoxycytidine
/ analogs & derivatives
Female
Fluorouracil
/ therapeutic use
Humans
Induction Chemotherapy
Leucovorin
/ therapeutic use
Male
Middle Aged
Neoadjuvant Therapy
Organoplatinum Compounds
/ therapeutic use
Pancreatic Neoplasms
/ surgery
Radiotherapy, Intensity-Modulated
Gemcitabine
Journal
American journal of clinical oncology
ISSN: 1537-453X
Titre abrégé: Am J Clin Oncol
Pays: United States
ID NLM: 8207754
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
pubmed:
7
4
2020
medline:
7
8
2020
entrez:
7
4
2020
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.
Sections du résumé
BACKGROUND
Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease.
AIM
To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer.
MATERIALS AND METHODS
Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT).
RESULTS
From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection.
CONCLUSION
Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.
Identifiants
pubmed: 32251119
doi: 10.1097/COC.0000000000000688
pii: 00000421-202006000-00009
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Organoplatinum Compounds
0
Deoxycytidine
0W860991D6
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Gemcitabine
0
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
435-441Références
Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74:2913–2921.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.
Network, N.C.C. Pancreatic Adenocarcinoma (Version 2.2019). 2019 [cited 2019 June 20]; Available from: https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.
Al-Hawary MM, Francis IR, Chari ST, et al. Pancreatic ductal adenocarcinoma radiology reporting template: consensus statement of the Society of Abdominal Radiology and the American Pancreatic Association. Radiology. 2014;270:248–260.
Gillen S, Schuster T, Meyer Zum Buschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.
Neoptolemos JP, Kleeff J, Michl P, et al. Therapeutic developments in pancreatic cancer: current and future perspectives. Nat Rev Gastroenterol Hepatol. 2018;15:333–348.
Strobel O, Buchler MW. Pancreatic cancer: clinical practice guidelines—what is the evidence? Nat Rev Clin Oncol. 2016;13:593–594.
Cress RD, Yin D, Clarke L, et al. Survival among patients with adenocarcinoma of the pancreas: a population-based study (United States). Cancer Causes Control. 2006;17:403–409.
Tesfaye AA, Kamgar M, Azmi A, et al. The evolution into personalized therapies in pancreatic ductal adenocarcinoma: challenges and opportunities. Expert Rev Anticancer Ther. 2018;18:131–148.
Tang K, Lu W, Qin W, et al. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. Pancreatology. 2016;16:28–37.
Zhu CP, Shi J, Chen YX, et al. Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: a meta-analysis. Radiother Oncol. 2011;99:108–113.
Hall WJ, Wellner JA. Confidence bands for a survival curve from censored data. Biometrika. 1980;67:133–143.
Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817–1825.
Ghosn M, Farhat F, Kattan J, et al. FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer. Am J Clin Oncol. 2007;30:15–20.
Lawrence TS, Eisbruch A, Shewach DS. Gemcitabine-mediated radiosensitization. Semin Oncol. 1997;24(2 suppl 7):S7-24–S7-28.
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;261:12–17.
Kim SS, Nakakura EK, Wang ZJ, et al. Preoperative FOLFIRINOX for borderline resectable pancreatic cancer: is radiation necessary in the modern era of chemotherapy? J Surg Oncol. 2016;114:587–596.
Katz MH, Shi Q, Ahmad SA, et al. Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer: Alliance for Clinical Trials in Oncology Trial A021101. JAMA Surg. 2016;151:e161137.
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;4:963–969.
Murphy JE, Wo JY, Ryan DP, et al. Total neoadjuvant therapy with FOLFIRINOX in combination with losartan followed by chemoradiotherapy for locally advanced pancreatic cancer: a phase 2 clinical trial. JAMA Oncol. 2019;5:1020–1027.
Geertjan Van Tienhoven EV, Suker M, Groothuis KBC, et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1): a randomized, controlled, multicenter phase III trial. J Clin Oncol. 2018;36(suppl 18):LBA4002.