术中放疗在胰腺癌中的应用进展
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摘要
虽然胰腺癌手术方式和放、化疗方案有了长足发展,但胰腺癌仍然是致死率最高的恶性肿瘤,5年总生存率仅约为4%。研究表明,胰腺癌局部复发进展是致死率高的重要原因,局部切除后失败率仍高达50%～80%。所以,如何提高胰腺癌局部控制率一直是关注的热点。由于胰腺临近的器官、组织(如骨髓、脊髓、肾脏、肝脏、肠等)较多从而限制外照射(EBRT)剂量。提高局部控制率和减少治疗毒副反应是未来治疗的趋势。术中放疗有剂量学和直视下治疗的优势,已越来越多的应用于胰腺癌的治疗,成为综合治疗中的重要部分。本文整理、总结了近年来有关胰腺癌术中放疗临床研究结果,以期为广大临床医生提供参考。
Although surgery,radiotherapy and chemotherapy have made great progress,pancreatic cancer is still the most fatal malignant tumor,with a 5-year overall survival rate of only about 4%.Many studies have demonstrated that the local recurrence of pancreatic cancer is an important cause of high mortality,and the failure rate after local excision is still as high as 50～80%.Therefore,how to improve the local control rate of pancreatic cancer has been a hot spot of concern.Due to the adjacent organs and tissues(such as bone marrow,spinal cord,kidney,liver,intestine,etc.),the dose of external irradiation(EBRT)is limited.Increasing local control rates and reducing treatment side effects are trends in future treatments.Intraoperative radiotherapy has the advantages of dosimetry and direct vision treatment to be increasingly used in the treatment of pancreatic cancer,becoming an important part of comprehensive treatment.This article summarizes the clinical research results of intraoperative radiotherapy for pancreatic cancer in recent years,in order to provide the reference for clinicians.
Although surgery,radiotherapy and chemotherapy have made great progress,pancreatic cancer is still the most fatal malignant tumor,with a 5-year overall survival rate of only about 4%.Many studies have demonstrated that the local recurrence of pancreatic cancer is an important cause of high mortality,and the failure rate after local excision is still as high as 50～80%.Therefore,how to improve the local control rate of pancreatic cancer has been a hot spot of concern.Due to the adjacent organs and tissues(such as bone marrow,spinal cord,kidney,liver,intestine,etc.),the dose of external irradiation(EBRT)is limited.Increasing local control rates and reducing treatment side effects are trends in future treatments.Intraoperative radiotherapy has the advantages of dosimetry and direct vision treatment to be increasingly used in the treatment of pancreatic cancer,becoming an important part of comprehensive treatment.This article summarizes the clinical research results of intraoperative radiotherapy for pancreatic cancer in recent years,in order to provide the reference for clinicians.
引文
1 Yamaguchi K,Okusaka T,Shimizu K,et al.Clinical practice guidelines for pancreatic cancer 2016 from the japan pancreas society:a synopsis[J].Pancreas,2017,46(5):595-604.
2 Jemal A,Murray T,Ward E,et al.Cancer statistics[J].CA Cancer,2005,55(1):10-30.
3 Wagner M,Redaelli C,Lietz M,et al.Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma[J].Br J Surg,2004,91(5):586-594.
4 Stocken DD,Buchler MW,Dervenis C,et al.Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer[J].Br J Cancer,2005,92(8):1372-1381.
5 Tsai JY,Iannitti DA,Safran H.Combined modality therapy for pancreatic cancer[J].Semin Oncol,2003,30(4Suppl 9):71-79.
6 Beger HG,Poch B,Schwarz M,et al.Pancreatic cancer:the relative importance of neoadjuvant therapy[J].Chirurg,2003,74(3):202-207.
7 Smeenk HG,Tran TC,Erdmann J,et al.Survival after surgical management of pancreatic adenocarcinoma:does curative and radical surgery truly exist[J].Langenbecks Arch Surg,2005,390(2):94-103.
8 Yeo CJ,Cameron JL,Lillemoe KD,et al.Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma,part 2:randomized controlled trial evaluating survival,morbidity,and mortality[J].Ann Surg,2002,236(3):355-366.
9 López-Tarjuelo J,Morillo-Macías V,Bouché-Babiloni A,et al.Defining action levels for in vivo dosimetry in intraoperative electron radiotherapy[J].Technol Cancer Res Treat,2016,15(3):453-459.
10 Calvo FA,Meirino RM,Orecchia R.Intraoperative radiation therapy first part:rationale and techniques[J].Crit Rev Oncol Hematol,2006,59(2):106-115.
11 Kirkpatrick JP,Meyer JJ,Marks LB.The linearquadratic model is inappropriate to model high dose per fraction effects in radiosurgery[J].Semin Radiat Oncol,2008,18(4):240-243.
12 Fuks Z,Kolesnick R.Engaging the vascular component of the tumor response[J].Cancer Cell,2005,8(2):89-91.
13 Park C,Papiez L,Zhang S,et al.Universal survival curve and single fraction equivalent dose:useful tools in understanding potency of ablative radiotherapy[J].Int J Radiat Oncol Biol Phys,2008,70(3):847-852.
14 Zaki Azzam A,Alqarni A,Tarek Mahmoud A,et al.The role of intraoperative radiotherapy(IORT)in the management of patients with pancreatic and periampullary cancer:A single center experience[J].Egypt Natl Canc Inst,2018,30(2):77-79.
15 Sindelar WF,Kinsella TJ.Studies of intraoperative radiotherapy in carcinoma of the pancreas[J].Ann Oncol,1999,10(Suppl4):226.
16 Zerbi A,Fossati V,Parolini D,et al.Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancer[J].Cancer,1994,73(12):2930-2935.
17 Alfieri S,Morganti AG,Di Giorgio A,et al.Improved survival and local control after intraoperative radiation therapy and postoperative radiotherapy:A multivariate analysis of 46 patients undergoing surgery for pancreatic head cancer[J].Arch Surg,2001,136(3):343.
18 Reni M,Panucci MG,Ferreri AJM,et al.Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma[J].Int J Radiat Oncol Biol Phys,2001,50(3):651-658.
19 Ogawa K,Karasawa K,Ito Y,et al.JROSG Working Subgroup of Gastrointestinal Cancers.Intraoperative radiotherapy for resected pancreatic cancer:a multiinstitutional retrospective analysis of 210 patients[J].Int J Radiat Oncol Biol Phys,2010,77(3):734-742.
20 Nishimura Y,Hosotani R,Shibamoto Y,et al.External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer:analysis of survival rates and complications[J].Int J Radiat Oncol Biol Phys,1997,39(1):39-49.
21 Roldan GE,Gunderson LL,Nagorney DM,et al.External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer[J].Cancer,1988,61(6):1110-1116.
22 Tepper JE,Noyes D,Krall JM,et al.Intraoperative radiation therapy of pancreatic carcinoma:a report of RTOG-8505.Radiation Therapy Oncology Group[J].Int J Radiat Oncol Biol Phys,1991,21(5):1145-1149.
23 Iacobuzio-Donahue CA,Fu B,Yachida S,et al.DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer[J].J Clin Oncol,2009,27(11):1806-1813.
24 Conroy T,Bachet JB,Ayav A,et al.Current standards and new innovative approaches for treatment of pancreatic cancer[J].Eur J Cancer,2016,57:10-22.
25 Hackert T,Sachsenmaier M,Hinz U,et al.Locally advanced pancreatic cancer:neoadjuvant therapy with folfirinox results in resectability in 60% of the patients[J].Ann Surg,2016,264(3):457-63.
26 Keane FK,Wo JY,Ferrone CR,et al.Intraoperative radiotherapy(IORT)in the era of intensive neoadjuvant chemotherapy and chemoradiotherapy for Pancreatic Adenocarcinoma[J].Clin Oncol,2018,41(6):607-612.
27 Roeder F,Timke C,Uhl M,et al.Aggressive local treatment containing intraoperative radiation therapy(IORT)for patients with isolated local recurrences of pancreatic cancer:a retrospective analysis[J].BMC Cancer,2012,12:295.
2 Jemal A,Murray T,Ward E,et al.Cancer statistics[J].CA Cancer,2005,55(1):10-30.
3 Wagner M,Redaelli C,Lietz M,et al.Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma[J].Br J Surg,2004,91(5):586-594.
4 Stocken DD,Buchler MW,Dervenis C,et al.Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer[J].Br J Cancer,2005,92(8):1372-1381.
5 Tsai JY,Iannitti DA,Safran H.Combined modality therapy for pancreatic cancer[J].Semin Oncol,2003,30(4Suppl 9):71-79.
6 Beger HG,Poch B,Schwarz M,et al.Pancreatic cancer:the relative importance of neoadjuvant therapy[J].Chirurg,2003,74(3):202-207.
7 Smeenk HG,Tran TC,Erdmann J,et al.Survival after surgical management of pancreatic adenocarcinoma:does curative and radical surgery truly exist[J].Langenbecks Arch Surg,2005,390(2):94-103.
8 Yeo CJ,Cameron JL,Lillemoe KD,et al.Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma,part 2:randomized controlled trial evaluating survival,morbidity,and mortality[J].Ann Surg,2002,236(3):355-366.
9 López-Tarjuelo J,Morillo-Macías V,Bouché-Babiloni A,et al.Defining action levels for in vivo dosimetry in intraoperative electron radiotherapy[J].Technol Cancer Res Treat,2016,15(3):453-459.
10 Calvo FA,Meirino RM,Orecchia R.Intraoperative radiation therapy first part:rationale and techniques[J].Crit Rev Oncol Hematol,2006,59(2):106-115.
11 Kirkpatrick JP,Meyer JJ,Marks LB.The linearquadratic model is inappropriate to model high dose per fraction effects in radiosurgery[J].Semin Radiat Oncol,2008,18(4):240-243.
12 Fuks Z,Kolesnick R.Engaging the vascular component of the tumor response[J].Cancer Cell,2005,8(2):89-91.
13 Park C,Papiez L,Zhang S,et al.Universal survival curve and single fraction equivalent dose:useful tools in understanding potency of ablative radiotherapy[J].Int J Radiat Oncol Biol Phys,2008,70(3):847-852.
14 Zaki Azzam A,Alqarni A,Tarek Mahmoud A,et al.The role of intraoperative radiotherapy(IORT)in the management of patients with pancreatic and periampullary cancer:A single center experience[J].Egypt Natl Canc Inst,2018,30(2):77-79.
15 Sindelar WF,Kinsella TJ.Studies of intraoperative radiotherapy in carcinoma of the pancreas[J].Ann Oncol,1999,10(Suppl4):226.
16 Zerbi A,Fossati V,Parolini D,et al.Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancer[J].Cancer,1994,73(12):2930-2935.
17 Alfieri S,Morganti AG,Di Giorgio A,et al.Improved survival and local control after intraoperative radiation therapy and postoperative radiotherapy:A multivariate analysis of 46 patients undergoing surgery for pancreatic head cancer[J].Arch Surg,2001,136(3):343.
18 Reni M,Panucci MG,Ferreri AJM,et al.Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma[J].Int J Radiat Oncol Biol Phys,2001,50(3):651-658.
19 Ogawa K,Karasawa K,Ito Y,et al.JROSG Working Subgroup of Gastrointestinal Cancers.Intraoperative radiotherapy for resected pancreatic cancer:a multiinstitutional retrospective analysis of 210 patients[J].Int J Radiat Oncol Biol Phys,2010,77(3):734-742.
20 Nishimura Y,Hosotani R,Shibamoto Y,et al.External and intraoperative radiotherapy for resectable and unresectable pancreatic cancer:analysis of survival rates and complications[J].Int J Radiat Oncol Biol Phys,1997,39(1):39-49.
21 Roldan GE,Gunderson LL,Nagorney DM,et al.External beam versus intraoperative and external beam irradiation for locally advanced pancreatic cancer[J].Cancer,1988,61(6):1110-1116.
22 Tepper JE,Noyes D,Krall JM,et al.Intraoperative radiation therapy of pancreatic carcinoma:a report of RTOG-8505.Radiation Therapy Oncology Group[J].Int J Radiat Oncol Biol Phys,1991,21(5):1145-1149.
23 Iacobuzio-Donahue CA,Fu B,Yachida S,et al.DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer[J].J Clin Oncol,2009,27(11):1806-1813.
24 Conroy T,Bachet JB,Ayav A,et al.Current standards and new innovative approaches for treatment of pancreatic cancer[J].Eur J Cancer,2016,57:10-22.
25 Hackert T,Sachsenmaier M,Hinz U,et al.Locally advanced pancreatic cancer:neoadjuvant therapy with folfirinox results in resectability in 60% of the patients[J].Ann Surg,2016,264(3):457-63.
26 Keane FK,Wo JY,Ferrone CR,et al.Intraoperative radiotherapy(IORT)in the era of intensive neoadjuvant chemotherapy and chemoradiotherapy for Pancreatic Adenocarcinoma[J].Clin Oncol,2018,41(6):607-612.
27 Roeder F,Timke C,Uhl M,et al.Aggressive local treatment containing intraoperative radiation therapy(IORT)for patients with isolated local recurrences of pancreatic cancer:a retrospective analysis[J].BMC Cancer,2012,12:295.