The application status and progress in neoadjuvant chemotherapy for pancreatic cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XI Shihang ,  WANG Xiaoming

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241000, P. R. China;

Corresponding author：

WANG Xiaoming, Email: wxm6901@aliyun.com

Keywords：

pancreatic cancer; neoadjuvant chemotherapy; regimen selection; efficacy assessment; review

DOI：

10.7507/1007-9424.201906052

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the current treatment status and progress of neoadjuvant chemotherapy for pancreatic cancer in order to improve the understanding of neoadjuvant chemotherapy and to guide clinical work.Method The relevant literatures at home and abroad on neoadjuvant chemotherapy for pancreatic cancer were readed and reviewed.Results Neoadjuvant chemotherapy could reduce tumor lesions, increase R0 resection rate, decrease postoperative complication rate, and improve patients’ survival, however, there was currently no high quality evidence-based medicine proof. At present, there was no unified neoadjuvant chemotherapy regimens for pancreatic cancer in the world. FOLFIRINOX, gemcitabine plus S-1, and gencitabine plus Nab-paclitaxel were the three common regimens we used. In addition, the neoadjuvant chemotherapy of pancreatic cancer had no uniform standard, and there were insufficient methods for evaluating therapeutic effects.Conclusion Although there are still some core problems need to be solved in neoadjuvant chemotherapy for pancreatic cancer, however, it’s curative effect is gradually recognized and widely used by clinicians, which is beneficial to provide a better prognosis for pancreatic cancer patients.

Citation： XI Shihang, WANG Xiaoming. The application status and progress in neoadjuvant chemotherapy for pancreatic cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(2): 226-231. doi: 10.7507/1007-9424.201906052 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Hahn S, Ayav A, Lopez A. Resection of locally advanced pancreatic neoplasms after neoadjuvant chemotherapy with Nab-paclitaxel and gemcitabine following FOLFIRINOX failure. Case Rep Gastroenterol, 2017, 11(2): 422-427.
3.	Kurahara H, Shinchi H, Ohtsuka T, et al. Significance of neoadjuvant therapy for borderline resectable pancreatic cancer: a multicenter retrospective study. Langenbecks Arch Surg, 2019, 404(2): 167-174.
4.	Blair AB, Rosati LM, Rezaee N, et al. Postoperative complications after resection of borderline resectable and locally advanced pancreatic cancer: the impact of neoadjuvant chemotherapy with conventional radiation or stereotactic body radiation therapy. Surgery, 2018, 163(5): 1090-1096.
5.	中国抗癌协会胰腺癌专业委员会. 胰腺癌综合诊治指南 (2018 版). 临床肝胆病杂志, 2018, 34(10): 2109-2120.
6.	Kaufmann B, Hartmann D, D’Haese JG, et al. Neoadjuvant treatment for borderline resectable pancreatic ductal adenocarcinoma. Dig Surg, 2018, [Epub ahead of print].
7.	Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
8.	Li X, Guo C, Li Q, et al. Association of modified-FOLFIRINOX-regimen-based neoadjuvant therapy with outcomes of locally advanced pancreatic cancer in Chinese population. Oncologist, 2019, 24(3): 301-393.
9.	Nagakawa Y, Sahara Y, Hosokawa Y, et al. Clinical impact of neoadjuvant chemotherapy and chemoradiotherapy in borderline resectable pancreatic cancer: analysis of 884 patients at facilities specializing in pancreatic surgery. Ann Surg Oncol, 2019, 26(6): 1629-1636.
10.	Yoo C, Shin SH, Kim KP, et al. Clinical outcomes of conversion surgery after neoadjuvant chemotherapy in patients with borderline resectable and locally advanced unresectable pancreatic cancer: a single-center, retrospective analysis. Cancers (Basel), 2019, 11(3): E278.
11.	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(7): 963-969.
12.	Zhan HX, Xu JW, Wu D, et al. Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies. Cancer Med, 2017, 6(6): 1201-1219.
13.	Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg, 1992, 127(11): 1335-1339.
14.	杨尹默, 马永蔌. 胰腺癌新辅助治疗评价—有的放矢还是无奈之举. 中国实用外科杂志, 2018, 38(7): 722-725.
15.	杨永超, 李宜雄. 胰腺癌外科治疗的历史和现状. 中国普通外科杂志, 2018, 27(3): 269-283.
16.	Jang JY, Kang JS, Han Y, et al. Long-term outcomes and recurrence patterns of standard versus extended pancreatectomy for pancreatic head cancer: a multicenter prospective randomized controlled study. J Hepatobiliary Pancreat Sci, 2017, 24(7): 426-433.
17.	Javed AA, Wright MJ, Siddique A, et al. Outcome of patients with borderline resectable pancreatic cancer in the contemporary era of neoadjuvant chemotherapy. J Gastrointest Surg, 2019, 23(1): 112-121.
18.	Jang JY, Han Y, Lee H, et al. 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, 2018, 268(2): 215-222.
19.	Bradley A, Van Der Meer R. Upfront surgery versus neoadjuvant therapy for resectable pancreatic cancer: systematic review and bayesian network meta-analysis. Sci Rep, 2019, 9(1): 4354.
20.	Ren X, Wei X, Ding Y, et al. Comparison of neoadjuvant therapy and upfront surgery in resectable pancreatic cancer: a meta-analysis and systematic review. Onco Targets Ther, 2019, 12: 733-744.
21.	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(8): 946-958.
22.	Unno M, Motoi F, Matsuyama Y, et al. Randomized phase Ⅱ/Ⅲ trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05). Jpn J Clin Oncol, 2019, 49(2): 190-194.
23.	Motoi F, Satoi S, Honda G, et al. A single-arm, phase Ⅱ trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study. J Gastroenterol, 2019, 54(2): 194-203.
24.	Hashmi A, Kozick Z, Fluck M, et al. Neoadjuvant versus adjuvant chemotherapy for resectable pancreatic adenocarcinoma: a national cancer database analysis. Am Surg, 2018, 84(9): 1439-1445.
25.	Golcher H, Brunner TB, Witzigmann H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase Ⅱ trial. Strahlenther Onkol, 2015, 191(1): 7-16.
26.	Casadei R, Di Marco M, Ricci C, et al. Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg, 2015, 19(10): 1802-1812.
27.	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(8): 1028-1061.
28.	Takahashi S. How to treat borderline resectable pancreatic cancer: current challenges and future directions. Jpn J Clin Oncol, 2018, 48(3): 205-213.
29.	Saito K, Isayama H, Sakamoto Y, et al. A phase Ⅱ trial of gemcitabine, S-1 and LV combination (GSL) neoadjuvant chemotherapy for patients with borderline resectable and locally advanced pancreatic cancer. Med Oncol, 2018, 35(7): 100.
30.	Gao S, Zhu X, Shi X, et al. Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase Ⅱ trial (BRPCNCC-1). Radiat Oncol, 2019, 14(1): 52.
31.	Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med, 2011, 364(19): 1817-1825.
32.	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(10): 1619-1623.
33.	Choi JG, Nipp RD, Tramontano A, et al. Neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced pancreatic cancer: results of a decision analysis. Oncologist, 2019, 24(7): 945-954.
34.	Chung MJ, Kang H, Kim HG, et al. Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. World J Gastrointest Oncol, 2018, 10(12): 505-515.
35.	高松, 赵天锁, 高春涛, 等. 改良 FOLFIRINOX 新辅助化疗治疗可能切除胰腺癌的临床疗效. 中华消化外科杂志, 2017, 16(10): 1013-1017.
36.	Li X, Ma T, Zhang Q, et al. Modified-FOLFIRINOX in metastatic pancreatic cancer: a prospective study in Chinese population. Cancer Lett, 2017, 406: 22-26.
37.	He M, Sun J, Zhao D, et al. Modified-FOLFIRINOX combined with deep regional hyperthermia in pancreatic cancer: a retrospective study in Chinese patients. Int J Hyperthermia, 2019, 36(1): 394-402.
38.	Miyashita T, Tajima H, Makino I, et al. Neoadjuvant chemotherapy with gemcitabine plus Nab-paclitaxel reduces the number of cancer-associated fibroblasts through depletion of pancreatic stroma. Anticancer Res, 2018, 38(1): 337-343.
39.	Heinemann V, Reni M, Ychou M, et al. Tumour-stroma interactions in pancreatic ductal adenocarcinoma: rationale and current evidence for new therapeutic strategies. Cancer Treat Rev, 2014, 40(1): 118-128.
40.	Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med, 2013, 369(18): 1691-1703.
41.	Peterson SL, Husnain M, Pollack T, et al. Neoadjuvant nab-paclitaxel and gemcitabine in borderline resectable or locally advanced unresectable pancreatic adenocarcinoma in patients who are ineligible for FOLFIRINOX. Anticancer Res, 2018, 38(7): 4035-4039.
42.	Miyasaka Y, Ohtsuka T, Kimura R, et al. Neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel for borderline resectable pancreatic cancer potentially improves survival and facilitates surgery. Ann Surg Oncol, 2019, 26(5): 1528-1534.
43.	Okada KI, Hirono S, Kawai M, et al. Phase Ⅰ study of Nab-paclitaxel plus gemcitabine as neoadjuvant therapy for borderline resectable pancreatic cancer. Anticancer Res, 2017, 37(2): 853-858.
44.	Ueno H, Ioka T, Ikeda M, et al. Randomized phase Ⅲ study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol, 2013, 31(13): 1640-1648.
45.	Zhong S, Qie S, Yang L, et al. S-1 monotherapy versus S-1 combination therapy in gemcitabine-refractory advanced pancreatic cancer: a meta-analysis (PRISMA) of randomized control trials. Medicine (Baltimore), 2017, 96(30): e7611.
46.	Li D, Chen C, Zhou Y, et al. Gemcitabine compared with gemcitabine and S-1 combination therapy in advanced pancreatic cancer: a systematic review and meta-analysis. Medicine (Baltimore), 2015, 94(35): e1345.
47.	Luo G, Liu C, Guo M, et al. Potential biomarkers in Lewis negative patients with pancreatic cancer. Ann Surg, 2017, 265(4): 800-805.
48.	朱善军, 徐震, 沈昊, 等. 血清 miR-27a 评估胰腺癌患者化疗疗效和预后的临床应用价值. 中华胰腺病杂志, 2018, 18(3): 196-197.
49.	White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg, 2001, 5(6): 626-633.
50.	Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer, 2012, 118(23): 5749-5756.
51.	Cassinotto C, Sa-Cunha A, Trillaud H. Radiological evaluation of response to neoadjuvant treatment in pancreatic cancer. Diagn Interv Imaging, 2016, 97(12): 1225-1232.
52.	Marchegiani G, Todaro V, Boninsegna E, et al. Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection. Eur Radiol, 2018, 28(10): 4265-4273.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Hahn S, Ayav A, Lopez A. Resection of locally advanced pancreatic neoplasms after neoadjuvant chemotherapy with Nab-paclitaxel and gemcitabine following FOLFIRINOX failure. Case Rep Gastroenterol, 2017, 11(2): 422-427.
3. Kurahara H, Shinchi H, Ohtsuka T, et al. Significance of neoadjuvant therapy for borderline resectable pancreatic cancer: a multicenter retrospective study. Langenbecks Arch Surg, 2019, 404(2): 167-174.
4. Blair AB, Rosati LM, Rezaee N, et al. Postoperative complications after resection of borderline resectable and locally advanced pancreatic cancer: the impact of neoadjuvant chemotherapy with conventional radiation or stereotactic body radiation therapy. Surgery, 2018, 163(5): 1090-1096.
5. 中国抗癌协会胰腺癌专业委员会. 胰腺癌综合诊治指南 (2018 版). 临床肝胆病杂志, 2018, 34(10): 2109-2120.
6. Kaufmann B, Hartmann D, D’Haese JG, et al. Neoadjuvant treatment for borderline resectable pancreatic ductal adenocarcinoma. Dig Surg, 2018, [Epub ahead of print].
7. Kamisawa T, Wood LD, Itoi T, et al. Pancreatic cancer. Lancet, 2016, 388(10039): 73-85.
8. Li X, Guo C, Li Q, et al. Association of modified-FOLFIRINOX-regimen-based neoadjuvant therapy with outcomes of locally advanced pancreatic cancer in Chinese population. Oncologist, 2019, 24(3): 301-393.
9. Nagakawa Y, Sahara Y, Hosokawa Y, et al. Clinical impact of neoadjuvant chemotherapy and chemoradiotherapy in borderline resectable pancreatic cancer: analysis of 884 patients at facilities specializing in pancreatic surgery. Ann Surg Oncol, 2019, 26(6): 1629-1636.
10. Yoo C, Shin SH, Kim KP, et al. Clinical outcomes of conversion surgery after neoadjuvant chemotherapy in patients with borderline resectable and locally advanced unresectable pancreatic cancer: a single-center, retrospective analysis. Cancers (Basel), 2019, 11(3): E278.
11. 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(7): 963-969.
12. Zhan HX, Xu JW, Wu D, et al. Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies. Cancer Med, 2017, 6(6): 1201-1219.
13. Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg, 1992, 127(11): 1335-1339.
14. 杨尹默, 马永蔌. 胰腺癌新辅助治疗评价—有的放矢还是无奈之举. 中国实用外科杂志, 2018, 38(7): 722-725.
15. 杨永超, 李宜雄. 胰腺癌外科治疗的历史和现状. 中国普通外科杂志, 2018, 27(3): 269-283.
16. Jang JY, Kang JS, Han Y, et al. Long-term outcomes and recurrence patterns of standard versus extended pancreatectomy for pancreatic head cancer: a multicenter prospective randomized controlled study. J Hepatobiliary Pancreat Sci, 2017, 24(7): 426-433.
17. Javed AA, Wright MJ, Siddique A, et al. Outcome of patients with borderline resectable pancreatic cancer in the contemporary era of neoadjuvant chemotherapy. J Gastrointest Surg, 2019, 23(1): 112-121.
18. Jang JY, Han Y, Lee H, et al. 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, 2018, 268(2): 215-222.
19. Bradley A, Van Der Meer R. Upfront surgery versus neoadjuvant therapy for resectable pancreatic cancer: systematic review and bayesian network meta-analysis. Sci Rep, 2019, 9(1): 4354.
20. Ren X, Wei X, Ding Y, et al. Comparison of neoadjuvant therapy and upfront surgery in resectable pancreatic cancer: a meta-analysis and systematic review. Onco Targets Ther, 2019, 12: 733-744.
21. 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(8): 946-958.
22. Unno M, Motoi F, Matsuyama Y, et al. Randomized phase Ⅱ/Ⅲ trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP-05). Jpn J Clin Oncol, 2019, 49(2): 190-194.
23. Motoi F, Satoi S, Honda G, et al. A single-arm, phase Ⅱ trial of neoadjuvant gemcitabine and S1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: PREP-01 study. J Gastroenterol, 2019, 54(2): 194-203.
24. Hashmi A, Kozick Z, Fluck M, et al. Neoadjuvant versus adjuvant chemotherapy for resectable pancreatic adenocarcinoma: a national cancer database analysis. Am Surg, 2018, 84(9): 1439-1445.
25. Golcher H, Brunner TB, Witzigmann H, et al. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer: results of the first prospective randomized phase Ⅱ trial. Strahlenther Onkol, 2015, 191(1): 7-16.
26. Casadei R, Di Marco M, Ricci C, et al. Neoadjuvant chemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer: a single-center prospective, randomized, controlled trial which failed to achieve accrual targets. J Gastrointest Surg, 2015, 19(10): 1802-1812.
27. 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(8): 1028-1061.
28. Takahashi S. How to treat borderline resectable pancreatic cancer: current challenges and future directions. Jpn J Clin Oncol, 2018, 48(3): 205-213.
29. Saito K, Isayama H, Sakamoto Y, et al. A phase Ⅱ trial of gemcitabine, S-1 and LV combination (GSL) neoadjuvant chemotherapy for patients with borderline resectable and locally advanced pancreatic cancer. Med Oncol, 2018, 35(7): 100.
30. Gao S, Zhu X, Shi X, et al. Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase Ⅱ trial (BRPCNCC-1). Radiat Oncol, 2019, 14(1): 52.
31. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med, 2011, 364(19): 1817-1825.
32. 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(10): 1619-1623.
33. Choi JG, Nipp RD, Tramontano A, et al. Neoadjuvant FOLFIRINOX for patients with borderline resectable or locally advanced pancreatic cancer: results of a decision analysis. Oncologist, 2019, 24(7): 945-954.
34. Chung MJ, Kang H, Kim HG, et al. Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. World J Gastrointest Oncol, 2018, 10(12): 505-515.
35. 高松, 赵天锁, 高春涛, 等. 改良 FOLFIRINOX 新辅助化疗治疗可能切除胰腺癌的临床疗效. 中华消化外科杂志, 2017, 16(10): 1013-1017.
36. Li X, Ma T, Zhang Q, et al. Modified-FOLFIRINOX in metastatic pancreatic cancer: a prospective study in Chinese population. Cancer Lett, 2017, 406: 22-26.
37. He M, Sun J, Zhao D, et al. Modified-FOLFIRINOX combined with deep regional hyperthermia in pancreatic cancer: a retrospective study in Chinese patients. Int J Hyperthermia, 2019, 36(1): 394-402.
38. Miyashita T, Tajima H, Makino I, et al. Neoadjuvant chemotherapy with gemcitabine plus Nab-paclitaxel reduces the number of cancer-associated fibroblasts through depletion of pancreatic stroma. Anticancer Res, 2018, 38(1): 337-343.
39. Heinemann V, Reni M, Ychou M, et al. Tumour-stroma interactions in pancreatic ductal adenocarcinoma: rationale and current evidence for new therapeutic strategies. Cancer Treat Rev, 2014, 40(1): 118-128.
40. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med, 2013, 369(18): 1691-1703.
41. Peterson SL, Husnain M, Pollack T, et al. Neoadjuvant nab-paclitaxel and gemcitabine in borderline resectable or locally advanced unresectable pancreatic adenocarcinoma in patients who are ineligible for FOLFIRINOX. Anticancer Res, 2018, 38(7): 4035-4039.
42. Miyasaka Y, Ohtsuka T, Kimura R, et al. Neoadjuvant chemotherapy with gemcitabine plus nab-paclitaxel for borderline resectable pancreatic cancer potentially improves survival and facilitates surgery. Ann Surg Oncol, 2019, 26(5): 1528-1534.
43. Okada KI, Hirono S, Kawai M, et al. Phase Ⅰ study of Nab-paclitaxel plus gemcitabine as neoadjuvant therapy for borderline resectable pancreatic cancer. Anticancer Res, 2017, 37(2): 853-858.
44. Ueno H, Ioka T, Ikeda M, et al. Randomized phase Ⅲ study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol, 2013, 31(13): 1640-1648.
45. Zhong S, Qie S, Yang L, et al. S-1 monotherapy versus S-1 combination therapy in gemcitabine-refractory advanced pancreatic cancer: a meta-analysis (PRISMA) of randomized control trials. Medicine (Baltimore), 2017, 96(30): e7611.
46. Li D, Chen C, Zhou Y, et al. Gemcitabine compared with gemcitabine and S-1 combination therapy in advanced pancreatic cancer: a systematic review and meta-analysis. Medicine (Baltimore), 2015, 94(35): e1345.
47. Luo G, Liu C, Guo M, et al. Potential biomarkers in Lewis negative patients with pancreatic cancer. Ann Surg, 2017, 265(4): 800-805.
48. 朱善军, 徐震, 沈昊, 等. 血清 miR-27a 评估胰腺癌患者化疗疗效和预后的临床应用价值. 中华胰腺病杂志, 2018, 18(3): 196-197.
49. White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg, 2001, 5(6): 626-633.
50. Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer, 2012, 118(23): 5749-5756.
51. Cassinotto C, Sa-Cunha A, Trillaud H. Radiological evaluation of response to neoadjuvant treatment in pancreatic cancer. Diagn Interv Imaging, 2016, 97(12): 1225-1232.
52. Marchegiani G, Todaro V, Boninsegna E, et al. Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection. Eur Radiol, 2018, 28(10): 4265-4273.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The application status and progress in neoadjuvant chemotherapy for pancreatic cancer

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