胰腺癌新辅助治疗的现状与展望
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摘要
对于不伴远处转移的胰腺癌,以手术为核心的综合治疗渐成为共识。目前,多项大样本回顾性临床研究已凸显新辅助治疗的价值,各权威指南也越来越重视新辅助治疗在胰腺癌中的地位。多项大型前瞻性多中心临床研究正在进行,且多数研究的初步结果均提示新辅助治疗可提高肿瘤的根治性切除率并改善生存。但新辅助治疗在胰腺癌中,特别是在可切除胰腺癌中的应用价值仍存在争议。此外,有关胰腺癌新辅助治疗的方案选择、治疗周期及术后接续的辅助方案等问题目前也尚无共识。相信随着高等级循证医学证据的不断出现,新辅助治疗将在胰腺癌中得到更广泛的应用。
The multimodality therapy with surgery as the core has gradually become the standard therapy for pancreatic cancer without distant metastasis. At present,many large-sample retrospective clinical studies have shown the value of neoadjuvant therapy in pancreatic cancer,and many international guidelines have recognized neoadjuvant therapy as a fundamental part of pancreatic cancer treatment. There are many ongoing large-scale,prospective,multi-center clinical trials,and the primary results of several studies have shown that neoadjuvant therapy can increase the radical resection rate of tumor and improve overall survival. However,there are still controversies over the value of neoadjuvant therapy in pancreatic cancer,especially resectable pancreatic cancer. In addition,no consensus has been reached on the selection of neoadjuvant regimen,the duration of neoadjuvant therapy,and neoadjuvant regimen after surgery for pancreatic cancer. It is believed that with the appearance of high-level evidence,neoadjuvant therapy will be widely used in pancreatic cancer.
The multimodality therapy with surgery as the core has gradually become the standard therapy for pancreatic cancer without distant metastasis. At present,many large-sample retrospective clinical studies have shown the value of neoadjuvant therapy in pancreatic cancer,and many international guidelines have recognized neoadjuvant therapy as a fundamental part of pancreatic cancer treatment. There are many ongoing large-scale,prospective,multi-center clinical trials,and the primary results of several studies have shown that neoadjuvant therapy can increase the radical resection rate of tumor and improve overall survival. However,there are still controversies over the value of neoadjuvant therapy in pancreatic cancer,especially resectable pancreatic cancer. In addition,no consensus has been reached on the selection of neoadjuvant regimen,the duration of neoadjuvant therapy,and neoadjuvant regimen after surgery for pancreatic cancer. It is believed that with the appearance of high-level evidence,neoadjuvant therapy will be widely used in pancreatic cancer.
引文
[1] SIEGEL RL,MILLER KD,JEMAL A. Cancer statistics,2018[J]. CA Cancer J Clin,2018,68(1):7-30.
[2] LOOS M,KLEEFF J,FRIESS H,et al. Surgical treatment of pancreatic cancer[J]. Ann N Y Acad Sci,2008,1138(1):169-180.
[3] 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[J]. JAMA,2007,297(3):267-277.
[4] DU L,WANG-GILLAM A. Trends in neoadjuvant approaches in pancreatic cancer[J]. J Natl Compr Canc Netw,2017,15(8):1070-1077.
[5] KHORANA AA,MANGU PB,BERLIN J,et al. Potentially curable pancreatic cancer:American society of clinical oncology clinical practice guideline[J]. J Clin Oncol,34(21):2541-2556.
[6] CLOYD JM,KATZ MH,PRAKASH L,et al. Preoperative therapy and pancreatoduodenectomy for pancreatic ductal adenocarcinoma:A 25-year single-institution experience[J]. J Gastrointest Surg,2017,21(1):164-174.
[7] MOKDAD AA,MINTER RM,ZHU H,et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer:A propensity score matched analysis[J].J Clin Oncol,2017,35(5):515-522.
[8] 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[J]. Br J Surg,2018,105(8):946-958.
[9] HEINRICH S,PESTALOZZI BC,SCHFER M,et al. Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head[J]. J Clin Oncol,2008,26(15):2526-2531.
[10] O'REILLY EM,PERELSHTEY NA,JARNAGIN WR,et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma[J]. Ann Surg,2014,260(1):142-148.
[11] MOTOI F,ISHIDA K,FUJISHIMA F,et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma:Results from a prospective multi-institutional phase 2 trial[J]. Ann Surg Oncol,2013,20(12):3794-3801.
[12] EVANS DB,VARADHACHARY GR,CRANE CH,et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head[J]. J Clin Oncol,2008,26(21):3496-3502.
[13] VARADHACHARY GR,WOLFF RA,CRANE CH,et al. Preoperative gemcitabine and cisplatin followed by gemcitabinebased chemoradiation for resectable adenocarcinoma of the pancreatic head[J]. J Clin Oncol,2008,26(21):3487-3495.
[14] CASADEI R,di MARCO M,RICCI C,et al. Neoadjuvantchemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer:A single-center prospective,randomized,controlled trial which failed to achieve accrual targets[J]. J Gastrointest Surg,2015,19(10):1802-1812.
[15] CLOYD JM,CHEN HC,WANG X,et al. Chemotherapy versus chemoradiation as preoperative therapy for resectable pancreatic ductal adenocarcinoma:A propensity score adjusted analysis[J]. Pancreas,2019,48(2):216-222.
[16] van TIENHOVEN G,VERSTEIJNE E,SUKER M,et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer(PREOPANC-1):A randomized,controlled,multicenter phase III trial[J]. J Clin Oncol,2018,36(18_Suppl):LBA4002-LBA4002.
[17] MOTOI F,KOSUGE T,UENO H,et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer(Prep-02/JSAP05)[J]. Jpn J Clin Oncol,2019,49(2):190-194.
[18] SOHAL D,McDONOUGH S,AHMAD SA,et al. SWOG S1505:Initial findings on eligibility and neoadjuvant chemotherapy experience with m FOLFIRINOX versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma[J]. J Clin Oncol,2019,39(Suppl 4):abstr414.
[19] de GEUS SW,ESKANDER MF,BLISS LA,et al. Neoadjuvant therapy versus upfront surgery for resected pancreatic adenocarcinoma:A nationwide propensity score matched analysis[J]. Surgery,2017,161(3):592-601.
[20] DATTA SK,BELINI G,SINGH M,et al. Survival outcomes between surgery with adjuvant therapy compared to neoadjuvant therapy with surgery in stage I pancreatic adenocarcinoma:Results from a large national cancer database[R]. 2019 Gastrointestinal Cancers Symposium,2019.
[21] LEE AJ,SIMONEAU E,CHIANG YJ,et al. Is early-stage pancreatic adenocarcinoma truly early:Stage migration on final pathology with surgery-first versus neoadjuvant therapy sequencing[J]. HPB(Oxford),2019.[Epub ahead of print]
[22] BAUGH KA,TRAN CAO HS,van BUREN G 2nd,et al. Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy[J]. Surgery,2019,165(2):307-314.
[23] 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[J]. Ann Surg Oncol,2019.[Epub ahead of print]
[24] 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[J]. JAMA Oncol,2018,4(7):963-969.
[25] 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[J]. JAMA Surg,2016,151(8):e161137.
[26] SUKER M,BEUMER BR,SADOT E,et al. FOLFIRINOX for locally advanced pancreatic cancer[J]. Lancet Oncol,2016,17(6):801-810.
[27] NITSCHE U,WENZEL P,SIVEKE JT,et al. Resectability after first-line FOLFIRINOX in initially unresectable locally advanced pancreatic cancer:A single-center experience[J].Ann Surg Oncol,2015,22(Suppl 3):s1212-s1220.
[28] POLISTINAF,COSTANTIN G,CASAMASSIMA F,et al. Unresectable locally advanced pancreatic cancer:A multimodal treatment using neoadjuvantchemoradiotherapy(gemcitabine plus stereotactic radiosurgery)and subsequent surgical exploration[J]. Ann Surg Oncol,2010,17(8):2092-2101.
[29] 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[J].Oncologist,2019,24(3):301-e93.
[30] BAI XL,SU RK,MA T,et al. Modified FOLFIRINOX for advanced pancreatic cancer:A tertiary center experience from China[J]. Chin J Surg,2016,54(4):270-275.(in Chinese)白雪莉,苏日嘎,马涛,等.改良FOLFIRINOX方案治疗进展期胰腺癌单中心经验[J].中华外科杂志,2016,54(4):270-275.
[31] LI X,MA T,ZHANG Q,et al. Modified-FOLFIRINOX in metastatic pancreatic cancer:A prospective study in Chinese population[J]. Cancer Lett,2017,406:22-26.
[32] von HOFF DD,ERVIN T,ARENA FP,et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine[J]. N Engl J Med,2013,369(18):1691-1703.
[33] 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[J]. Anticancer Res,2018,38(7):4035-4039.
[34] 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[J]. Ann Surg Oncol,2019,26(5):1528-1534.
[35] 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[J]. Surgery,2018,163(5):1090-1096.
[36] CHAPMAN BC,GLEISNER A,RIGG D,et al. Perioperative outcomes and survival following neoadjuvant stereotactic body radiation therapy(SBRT)versus intensity-modulated radiation therapy(IMRT)in pancreatic adenocarcinoma[J]. J Surg Oncol,2018,117(5):1073-1083.
[37] KHAROFA J,MIERZWA M,OLOWOKURE O,et al. Pattern of marginal local failure in a phase ii trial of neoadjuvant chemotherapy and stereotactic body radiation therapy for resectable and borderline resectable pancreas cancer[J]. Am J Clin Oncol,2019,42(3):247-252.
[38] 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[J]. Ann Surg,2019,269(4):733-740.
[39] DHOLAKIA AS,HACKER-PRIETZ A,WILD AT,et al. Resection of borderline resectable pancreatic cancer after neoadjuvantchemoradiation does not depend on improved radiographic appearance of tumor-vessel relationships[J]. J Radiat Oncol,2013,2(4):413-425.
[40] WILLIAMS JL,KADERA BE,NGUYEN AH,et al. CA19-9normalization during pre-operative treatment predicts longer survival for patients with locally progressed pancreatic cancer[J]. J Gastrointest Surg,2016,20(7):1331-1342.
[41] TSAI S,GEORGE B,WITTMANN D,et al. Importance of normalization of CA19-9 levels following neoadjuvant therapy in patients with localized pancreatic cancer[J]. Ann Surg,2018.[Epub ahead of print]
[42] MURAKAMI Y,UEMURA K,SUDO T,et al. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact[J]. Cancer Chemother Pharmacol,2017,79(4):801-811.
[43] GALL TMH,BELETE S,KHANDERIA E,et al. Circulating tumor cells and cell-free DNA in pancreatic ductal adenocarcinoma[J]. Am J Pathol,2019,189(1):71-81.
[44] WEI T,ZHANG Q,LI X,et al. Monitoring tumor burden in response to FOLFIRINOX chemotherapy via profiling circulating cell-free DNA in pancreatic cancer[J]. Mol Cancer Ther,2019,18(1):196-203.
[45] SANDINI M,PATINO M,FERRONE CR,et al. Association between changes in body composition and neoadjuvant treatment for pancreatic cancer[J]. JAMA Surg,2018,153(9):809-815.
[46] BARNES CA,KREPLINE AN,ALDAKKAK M,et al. Is adjuvant therapy necessary for all patients with localized pancreatic cancer who have received neoadjuvant therapy?[J]. J Gastrointest Surg,2017,21(11):1793-1803.
[2] LOOS M,KLEEFF J,FRIESS H,et al. Surgical treatment of pancreatic cancer[J]. Ann N Y Acad Sci,2008,1138(1):169-180.
[3] 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[J]. JAMA,2007,297(3):267-277.
[4] DU L,WANG-GILLAM A. Trends in neoadjuvant approaches in pancreatic cancer[J]. J Natl Compr Canc Netw,2017,15(8):1070-1077.
[5] KHORANA AA,MANGU PB,BERLIN J,et al. Potentially curable pancreatic cancer:American society of clinical oncology clinical practice guideline[J]. J Clin Oncol,34(21):2541-2556.
[6] CLOYD JM,KATZ MH,PRAKASH L,et al. Preoperative therapy and pancreatoduodenectomy for pancreatic ductal adenocarcinoma:A 25-year single-institution experience[J]. J Gastrointest Surg,2017,21(1):164-174.
[7] MOKDAD AA,MINTER RM,ZHU H,et al. Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer:A propensity score matched analysis[J].J Clin Oncol,2017,35(5):515-522.
[8] 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[J]. Br J Surg,2018,105(8):946-958.
[9] HEINRICH S,PESTALOZZI BC,SCHFER M,et al. Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and cisplatin for resectable adenocarcinoma of the pancreatic head[J]. J Clin Oncol,2008,26(15):2526-2531.
[10] O'REILLY EM,PERELSHTEY NA,JARNAGIN WR,et al. A single-arm, nonrandomized phase II trial of neoadjuvant gemcitabine and oxaliplatin in patients with resectable pancreas adenocarcinoma[J]. Ann Surg,2014,260(1):142-148.
[11] MOTOI F,ISHIDA K,FUJISHIMA F,et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma:Results from a prospective multi-institutional phase 2 trial[J]. Ann Surg Oncol,2013,20(12):3794-3801.
[12] EVANS DB,VARADHACHARY GR,CRANE CH,et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head[J]. J Clin Oncol,2008,26(21):3496-3502.
[13] VARADHACHARY GR,WOLFF RA,CRANE CH,et al. Preoperative gemcitabine and cisplatin followed by gemcitabinebased chemoradiation for resectable adenocarcinoma of the pancreatic head[J]. J Clin Oncol,2008,26(21):3487-3495.
[14] CASADEI R,di MARCO M,RICCI C,et al. Neoadjuvantchemoradiotherapy and surgery versus surgery alone in resectable pancreatic cancer:A single-center prospective,randomized,controlled trial which failed to achieve accrual targets[J]. J Gastrointest Surg,2015,19(10):1802-1812.
[15] CLOYD JM,CHEN HC,WANG X,et al. Chemotherapy versus chemoradiation as preoperative therapy for resectable pancreatic ductal adenocarcinoma:A propensity score adjusted analysis[J]. Pancreas,2019,48(2):216-222.
[16] van TIENHOVEN G,VERSTEIJNE E,SUKER M,et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer(PREOPANC-1):A randomized,controlled,multicenter phase III trial[J]. J Clin Oncol,2018,36(18_Suppl):LBA4002-LBA4002.
[17] MOTOI F,KOSUGE T,UENO H,et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer(Prep-02/JSAP05)[J]. Jpn J Clin Oncol,2019,49(2):190-194.
[18] SOHAL D,McDONOUGH S,AHMAD SA,et al. SWOG S1505:Initial findings on eligibility and neoadjuvant chemotherapy experience with m FOLFIRINOX versus gemcitabine/nab-paclitaxel for resectable pancreatic adenocarcinoma[J]. J Clin Oncol,2019,39(Suppl 4):abstr414.
[19] de GEUS SW,ESKANDER MF,BLISS LA,et al. Neoadjuvant therapy versus upfront surgery for resected pancreatic adenocarcinoma:A nationwide propensity score matched analysis[J]. Surgery,2017,161(3):592-601.
[20] DATTA SK,BELINI G,SINGH M,et al. Survival outcomes between surgery with adjuvant therapy compared to neoadjuvant therapy with surgery in stage I pancreatic adenocarcinoma:Results from a large national cancer database[R]. 2019 Gastrointestinal Cancers Symposium,2019.
[21] LEE AJ,SIMONEAU E,CHIANG YJ,et al. Is early-stage pancreatic adenocarcinoma truly early:Stage migration on final pathology with surgery-first versus neoadjuvant therapy sequencing[J]. HPB(Oxford),2019.[Epub ahead of print]
[22] BAUGH KA,TRAN CAO HS,van BUREN G 2nd,et al. Understaging of clinical stage I pancreatic cancer and the impact of multimodality therapy[J]. Surgery,2019,165(2):307-314.
[23] 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[J]. Ann Surg Oncol,2019.[Epub ahead of print]
[24] 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[J]. JAMA Oncol,2018,4(7):963-969.
[25] 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[J]. JAMA Surg,2016,151(8):e161137.
[26] SUKER M,BEUMER BR,SADOT E,et al. FOLFIRINOX for locally advanced pancreatic cancer[J]. Lancet Oncol,2016,17(6):801-810.
[27] NITSCHE U,WENZEL P,SIVEKE JT,et al. Resectability after first-line FOLFIRINOX in initially unresectable locally advanced pancreatic cancer:A single-center experience[J].Ann Surg Oncol,2015,22(Suppl 3):s1212-s1220.
[28] POLISTINAF,COSTANTIN G,CASAMASSIMA F,et al. Unresectable locally advanced pancreatic cancer:A multimodal treatment using neoadjuvantchemoradiotherapy(gemcitabine plus stereotactic radiosurgery)and subsequent surgical exploration[J]. Ann Surg Oncol,2010,17(8):2092-2101.
[29] 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[J].Oncologist,2019,24(3):301-e93.
[30] BAI XL,SU RK,MA T,et al. Modified FOLFIRINOX for advanced pancreatic cancer:A tertiary center experience from China[J]. Chin J Surg,2016,54(4):270-275.(in Chinese)白雪莉,苏日嘎,马涛,等.改良FOLFIRINOX方案治疗进展期胰腺癌单中心经验[J].中华外科杂志,2016,54(4):270-275.
[31] LI X,MA T,ZHANG Q,et al. Modified-FOLFIRINOX in metastatic pancreatic cancer:A prospective study in Chinese population[J]. Cancer Lett,2017,406:22-26.
[32] von HOFF DD,ERVIN T,ARENA FP,et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine[J]. N Engl J Med,2013,369(18):1691-1703.
[33] 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[J]. Anticancer Res,2018,38(7):4035-4039.
[34] 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[J]. Ann Surg Oncol,2019,26(5):1528-1534.
[35] 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[J]. Surgery,2018,163(5):1090-1096.
[36] CHAPMAN BC,GLEISNER A,RIGG D,et al. Perioperative outcomes and survival following neoadjuvant stereotactic body radiation therapy(SBRT)versus intensity-modulated radiation therapy(IMRT)in pancreatic adenocarcinoma[J]. J Surg Oncol,2018,117(5):1073-1083.
[37] KHAROFA J,MIERZWA M,OLOWOKURE O,et al. Pattern of marginal local failure in a phase ii trial of neoadjuvant chemotherapy and stereotactic body radiation therapy for resectable and borderline resectable pancreas cancer[J]. Am J Clin Oncol,2019,42(3):247-252.
[38] 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[J]. Ann Surg,2019,269(4):733-740.
[39] DHOLAKIA AS,HACKER-PRIETZ A,WILD AT,et al. Resection of borderline resectable pancreatic cancer after neoadjuvantchemoradiation does not depend on improved radiographic appearance of tumor-vessel relationships[J]. J Radiat Oncol,2013,2(4):413-425.
[40] WILLIAMS JL,KADERA BE,NGUYEN AH,et al. CA19-9normalization during pre-operative treatment predicts longer survival for patients with locally progressed pancreatic cancer[J]. J Gastrointest Surg,2016,20(7):1331-1342.
[41] TSAI S,GEORGE B,WITTMANN D,et al. Importance of normalization of CA19-9 levels following neoadjuvant therapy in patients with localized pancreatic cancer[J]. Ann Surg,2018.[Epub ahead of print]
[42] MURAKAMI Y,UEMURA K,SUDO T,et al. Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact[J]. Cancer Chemother Pharmacol,2017,79(4):801-811.
[43] GALL TMH,BELETE S,KHANDERIA E,et al. Circulating tumor cells and cell-free DNA in pancreatic ductal adenocarcinoma[J]. Am J Pathol,2019,189(1):71-81.
[44] WEI T,ZHANG Q,LI X,et al. Monitoring tumor burden in response to FOLFIRINOX chemotherapy via profiling circulating cell-free DNA in pancreatic cancer[J]. Mol Cancer Ther,2019,18(1):196-203.
[45] SANDINI M,PATINO M,FERRONE CR,et al. Association between changes in body composition and neoadjuvant treatment for pancreatic cancer[J]. JAMA Surg,2018,153(9):809-815.
[46] BARNES CA,KREPLINE AN,ALDAKKAK M,et al. Is adjuvant therapy necessary for all patients with localized pancreatic cancer who have received neoadjuvant therapy?[J]. J Gastrointest Surg,2017,21(11):1793-1803.