原发胃肠间质瘤临床病理特征及预后分析:附314例报告
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摘要
目的:分析原发胃肠间质瘤(GIST)的临床病理特征及预后情况。方法:回顾分析中南大学湘雅医院2012年1月—2018年8月期间诊治的314例原发GIST患者的临床病理及随访资料。结果:314例GIST患者中,男性169例(53.8%),女性145例(46.2%),其中位年龄为55(24～86)岁,肿瘤直径为6(1～34)cm;原发部位位于胃165例(52.6%)、十二指肠15例(4.8%)、空回肠115例(36.6%)、结直肠6例(1.9%)、其他部位13例(4.1%)。根据改良NIH分级,其中极低危11例(3.5%)、低危109例(34.7%)、中危80例(25.5%)、高危114例(36.3%)。314例均接受手术治疗,其中R_0切除305例(97.1%)、R_1切除4例(1.3%)、R_2切除5例(1.6%)。268例(85.4%)获得有效随访,中位随访时间为37(2～69)个月。194例中高危患者中67例(34.5%)术后接受伊马替尼辅助治疗,中位治疗时间为26(7～56)个月。全组1、3、5年总体无复发生存率为97.0%、92.6%、81.7%,1、3、5年总体总存活率为99.4%、95.2%、88.2%。极低危、低危、中危及高危患者其5年无复发存活率分别为100.0%、93.3%、79.1%、64.4%,5年总存活率分别为100.0%、94.1%、91.7%、74.9%。194例中高危GIST患者中,67例术后接受伊马替尼辅助治疗者及127例术后未接受伊马替尼辅助治疗者5年无复发存活率分别为73.8%、65.2%,5年总存活率分别为87.5%、71.6%。结论:原发GIST最常见发病部位是胃和小肠,完整切除并根据危险度分级予以伊马替尼辅助治疗预后较好,但还需针对不同的高危GIST患者量身定制个体化治疗方案,并且在规范辅助治疗的同时,还需严密系统地随访。
Objective: To analyze clinicopathologic features and prognosis of primary gastrointestinal stromal tumor(GIST).Methods: The clinicopathologic and follow-up data of 314 patients with primary GIST treated in Xiangya Hospital of Central South University from January 2012 to August 2018 were retrospectively analyzed.Results: Of the 314 GIST patients, 169 cases(53.8%) were males and 145 cases were(46.2%) females, with a median age of 55(24-86) years and a median tumor diameter of 6(1-34) cm; the primary site located in the stomach in 165 cases(52.6%), duodenum in 15 cases(4.8%), jejunum or ileum in 115 cases(36.6%), colorectum in 6 cases(1.9%), and other sites in 13 cases(4.1%). According to the modifi ed NIH classifi cation, the diseases of the patients were classifi ed as very low risk in 11 cases(3.5%), low risk in 109 cases(34.7%), moderate risk in 80 cases(25.5%), and high risk in 114 cases(36.3%). All the 314 patients underwent surgical treatments, of whom, 305 cases(97.1%) achieved R_0 resection, 4 cases(1.3%) received R_1 resection, and 5 cases(1.6%) had R_2 resection. Followed-up was obtained in 268 patients(85.4%) for a median time of 37(2–69) months. Of the 194 patients with moderate or high risk disease, 67 cases(34.5%) received imatinib-based adjuvant therapy aft er operation, with a median time of 26(7–56) months. In the whole group of patients, the 1-, 3-and 5-year relapsefree survival rates were 97.0%, 92.6% and 81.7%, and the 1-, 3-and 5-year overall survival rates were 99.4%, 95.2% and 88.2%, respectively. In patients with very low risk, low risk, moderate risk and high risk disease, the 5-year relapse-free survival rates were 100.0%, 93.3%, 79.1% and 64.4%, and the 5-year overall survival rates were 100.0%, 94.1%, 91.7% and 74.9%, respectively. Among the 194 patients with moderate or high risk disease, the 5-year relapse-free survival rates in the 67 cases with postoperative imatinib adjuvant therapy and the 127 cases without postoperative imatinib adjuvant therapy were 73.8% and 65.2%, and the 5-year overall survival rates were 87.5% and 71.6%, respectively.Conclusion: Primary GIST is mostly found in the stomach and small intestine. Complete resection and imatinibbased adjuvant therapy based on risk classifications can lead to better prognosis. However, individualized treatment should be tailor to specifi c patients with high risk GIST, and close and regular follow-up is still needed in addition to the standard adjuvant therapy.
Objective: To analyze clinicopathologic features and prognosis of primary gastrointestinal stromal tumor(GIST).Methods: The clinicopathologic and follow-up data of 314 patients with primary GIST treated in Xiangya Hospital of Central South University from January 2012 to August 2018 were retrospectively analyzed.Results: Of the 314 GIST patients, 169 cases(53.8%) were males and 145 cases were(46.2%) females, with a median age of 55(24-86) years and a median tumor diameter of 6(1-34) cm; the primary site located in the stomach in 165 cases(52.6%), duodenum in 15 cases(4.8%), jejunum or ileum in 115 cases(36.6%), colorectum in 6 cases(1.9%), and other sites in 13 cases(4.1%). According to the modifi ed NIH classifi cation, the diseases of the patients were classifi ed as very low risk in 11 cases(3.5%), low risk in 109 cases(34.7%), moderate risk in 80 cases(25.5%), and high risk in 114 cases(36.3%). All the 314 patients underwent surgical treatments, of whom, 305 cases(97.1%) achieved R_0 resection, 4 cases(1.3%) received R_1 resection, and 5 cases(1.6%) had R_2 resection. Followed-up was obtained in 268 patients(85.4%) for a median time of 37(2–69) months. Of the 194 patients with moderate or high risk disease, 67 cases(34.5%) received imatinib-based adjuvant therapy aft er operation, with a median time of 26(7–56) months. In the whole group of patients, the 1-, 3-and 5-year relapsefree survival rates were 97.0%, 92.6% and 81.7%, and the 1-, 3-and 5-year overall survival rates were 99.4%, 95.2% and 88.2%, respectively. In patients with very low risk, low risk, moderate risk and high risk disease, the 5-year relapse-free survival rates were 100.0%, 93.3%, 79.1% and 64.4%, and the 5-year overall survival rates were 100.0%, 94.1%, 91.7% and 74.9%, respectively. Among the 194 patients with moderate or high risk disease, the 5-year relapse-free survival rates in the 67 cases with postoperative imatinib adjuvant therapy and the 127 cases without postoperative imatinib adjuvant therapy were 73.8% and 65.2%, and the 5-year overall survival rates were 87.5% and 71.6%, respectively.Conclusion: Primary GIST is mostly found in the stomach and small intestine. Complete resection and imatinibbased adjuvant therapy based on risk classifications can lead to better prognosis. However, individualized treatment should be tailor to specifi c patients with high risk GIST, and close and regular follow-up is still needed in addition to the standard adjuvant therapy.
引文
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[8]熊建明,黄建华,李定军,等.胃肠道间质瘤临床诊治-附46例临床分析[J].现代生物医学进展,2010,10(6):1135-1137.Xiong JM,Huang JH,Li DJ,et al.Diagnosis and Treatment of Gastrointestinal Stromal Tumor:Analysis of 46 Cases[J].Progress in Modern Biomedicine,2010,10(6):1135-1137.
[9]Li J,Gong JF,Wu AW,et al.Post-operative imatinib in patients with intermediate or high risk gastrointestinal stromal tumor[J].Eur JSurg Oncol,2011,37(4):319-324.doi:10.1016/j.ejso.2011.01.005.
[10]闫顺笠,晏仲舒,廖国庆,等.十二指肠间质瘤46例临床诊治分析[J].中国普通外科杂志,2013,22(10):1324-1328.doi:10.7659/j.issn.1005-6947.2013.10.018.Yan SL,Yan ZS,Liao GQ,et al.Duodenal gastrointestinal stromal tumors:diagnosis and treatment of 46 cases[J].Chinese Journal of General Surgery,2013,22(10):1324-1328.doi:10.7659/j.issn.1005-6947.2013.10.018.
[11]García B,Ibarra J,Sola A,et al.Gastrointestinal stromal tumors.Analysis of 40 cases[J].Medicina(B Aires),2017,77(5):370-372.
[12]Blay JY,Bonvalot S,Casali P,et al.Consensus meeting for the management of gastrointestinal stromal tumors.Report of the GISTConsensus Conference of 20-21 March 2004,under the auspices of ESMO[J].Ann.Oncol,2005,16(4):566-578.doi:10.1093/annonc/mdi127.
[13]中国医师协会外科医师分会胃肠道间质瘤诊疗专业委员会,中华医学会外科学分会胃肠外科学组.胃肠间质瘤规范化外科治疗中国专家共识(2018版)[J].中国实用外科杂志,2018,38(9):965-973.doi:10.19538/j.cjps.issn.1005-2208.2018.09.01.Committee of Diagnosis and Treatment of Gastrointestinal Stromal Tumor,Chinese College of Surgeons,Gastrointestinal Surgery Group of Surgery Branch,Chinese Medical Association.Chinese expert consensus on standard surgical treatment of gastrointestinal stromal tumor(2018 edition)[J].Chinese Journal of Practical Surgery,2018,38(9):965-973.doi:10.19538/j.cjps.issn.1005-2208.2018.09.01.
[14]Valsangkar N,Sehdev A,Misra S,et al.Current management of gastrointestinal stromal tumors:Surgery,current biomarkers,mutations,and therapy[J].Surgery,2015,158(5):1149-1164.doi:10.1016/j.surg.2015.06.027.
[15]Woodall CE 3rd,Brock GN,Fan J,et al.An evaluation of 2537gastrointestinal stromal tumors for a proposed clinical staging system[J].Arch Surg,2009,144(7):670-678.doi:10.1001/archsurg.2009.108.
[16]Hohenberger P,Ronellenfitsch U,Oladeji O,et al.Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour[J].Br J Surg,2010,97(12):1854-1859.doi:10.1002/bjs.7222.
[17]Blesius A,Cassier PA,Bertucci F,et al.Neoadjuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR14 trial[J].BMC Cancer,2011,11:72.doi:10.1186/1471-2407-11-72.
[18]Wang C,Zheng B,Chen Y,et al.Imatinib as preoperative therapy in Chinese patients with recurrent or metastatic GISTs[J].Chin J Cancer Res,2013,25(1):63-70.doi:10.3978/j.issn.1000-9604.2012.12.01.
[19]Eisenberg BL,Harris J,Blanke CD,et al.Phase II trial of neoadjuvant/adjuvant imatinib mesylate(IM)for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor(GIST):early results of RTOG 0132/ACRIN 6665[J].J Surg Oncol,2009,99(1):42-47.doi:10.1002/jso.21160.
[20]Dematteo RP,Ballman KV,Antonescu CR,et al.Adjuvant imatinib mesylate after resection of localised,primary gastrointestinal stromal tumour:a randomised,double-blind,placebo-controlled trial[J].Lancet,2009,373(9669):1097-1104.doi:10.1016/S0140-6736(09)60500-6.
[21]Joensuu H,Eriksson M,Sundby Hall K,et al.One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor:a randomized trial[J].JAMA,2012,307(12):1265-1272.doi:10.1001/jama.2012.347.
[22]中国临床肿瘤学会胃肠间质瘤专家委员会.中国胃肠间质瘤诊断治疗共识(2017年版)[J].肿瘤综合治疗电子杂志,2018,4(1):31-43.Committee of Gastrointestinal Stromal Tumor,Chinese Society of Clinical Oncology.Chinese consensus on diagnosis and treatment of gastrointestinal stromal tumor(2017 edition)[J].Journal of Esophageal Surgery:Electronic Version,2018,4(1):31-43.
[23]中国研究型医院学会消化道肿瘤专业委员会,中国医师协会外科医师分会多学科综合治疗专业委员会.胃肠间质瘤多学科综合治疗协作组诊疗模式专家共识[J].中国实用外科杂志,2017,37(1):39-41.doi:10.19538/j.cjps.issn1005-2208.2017.01.13.Specialized Committee of Gastrointestinal Tumors of Chinese Research Hospital Association,Specialized Committee of Multidisciplinary Treatment of Chinese Research Hospital Association.Expert consensus on mode of multidisciplinary cooperative group for gastrointestinal stromal tumor[J].Chinese Journal of Practical Surgery,2017,37(1):39-41.doi:10.19538/j.cjps.issn1005-2208.2017.01.13.
[24]刘安文,廖国庆,郑凯,等.50例胃肠道间质瘤患者c-k i t及P D G F R-a基因检测及突变分析[J].中国现代医生,2013,51(23):54-56.Liu AW,Liao GQ,Zheng K,et al.Detection of the c-kit and PDGFRαgene mutation and mutation analysis[J].China Modern Doctor,2013,51(23):54-56.
[25]王万川,廖国庆.基因突变与胃肠道间质瘤研究进展[J].中国普通外科杂志,2007,16(9):892-894.doi:10.3969/j.issn.1005-6947.2007.09.018.Wang WC,Liao GQ.Genetic mutation of gastrointestinal stromal tumors[J].Chinese Journal of General Surgery,2007,16(9):892-894.doi:10.3969/j.issn.1005-6947.2007.09.018.
[26]糜睿,丁杰,董奇,等.胃肠道间质瘤的基因研究进展[J].中国普通外科杂志,2018,27(10):1341-1347.doi:10.7659/j.issn.1005-6947.2018.10.018.Mi R,Ding J,Dong Q,et al.Research progress of genes associated with gastrointestinal stromal tumors[J].Chinese Journal of General Surgery,2018,27(10):1341-1347.doi:10.7659/j.issn.1005-6947.2018.10.018.
[27]Lin JX,Chen QF,Zheng CH,et al.Is 3-years duration of adjuvant imatinib mesylate treatment sufficient for patients with highrisk gastrointestinal stromal tumor?A study based on long-term follow-up[J].J Cancer Res Clin Oncol,2017,143(4):727-734.doi:10.1007/s00432-016-2334-x.
[2]Mazzola P,Spitale A,Banfi S,et al.Epidemiology and molecular biology of gastrointestinal stromal tumors(GISTs):a populationbased study in the South of Switzerland,1999-2005[J].Histol Histopathol,2008,23(11):1379-1386.doi:10.14670/HH-23.1379.
[3]Cioffi A,Maki RG.GI Stromal Tumors:15 Years of Lessons From a Rare Cancer[J].J Clin Oncol,2015,33(16):1849-1854.doi:10.1200/JCO.2014.59.7344.
[4]von Mehren M,Joensuu H.Gastrointestinal Stromal Tumors[J].JClin Oncol,2018,36(2):136-143.doi:10.1200/JCO.2017.74.9705.
[5]朱从波,廖国庆,赵丁民.Ki-67对胃肠道间质瘤预后的评估价值[J].临床与病理杂志,2018,38(8):1632-1639.doi:10.3978/j.issn.2095-6959.2018.08.007.Zhu CB,Liao GQ,Zhao DM.Prognostic value of Ki-67 index in gastrointestinal stromal tumor[J].International Journal of Pathology and Clinical Medicine,2018,38(8):1632-1639.doi:10.3978/j.issn.2095-6959.2018.08.007.
[6]Shinomura Y,Kinoshita K,Tsutsui S,et al.Pathophysiology,diagnosis,and treatment of gastrointestinal stromal tumors[J].J.Gastroenterol,2005,40(8):775-780.doi:10.1007/s00535-005-1674-0.
[7]Cameron S,Beham A,Schildhaus HU.Current Standard and Future Perspectives in the Treatment of Gastrointestinal Stromal Tumors[J].Digestion,2017,95(4):262-268.doi:10.1159/000455835.
[8]熊建明,黄建华,李定军,等.胃肠道间质瘤临床诊治-附46例临床分析[J].现代生物医学进展,2010,10(6):1135-1137.Xiong JM,Huang JH,Li DJ,et al.Diagnosis and Treatment of Gastrointestinal Stromal Tumor:Analysis of 46 Cases[J].Progress in Modern Biomedicine,2010,10(6):1135-1137.
[9]Li J,Gong JF,Wu AW,et al.Post-operative imatinib in patients with intermediate or high risk gastrointestinal stromal tumor[J].Eur JSurg Oncol,2011,37(4):319-324.doi:10.1016/j.ejso.2011.01.005.
[10]闫顺笠,晏仲舒,廖国庆,等.十二指肠间质瘤46例临床诊治分析[J].中国普通外科杂志,2013,22(10):1324-1328.doi:10.7659/j.issn.1005-6947.2013.10.018.Yan SL,Yan ZS,Liao GQ,et al.Duodenal gastrointestinal stromal tumors:diagnosis and treatment of 46 cases[J].Chinese Journal of General Surgery,2013,22(10):1324-1328.doi:10.7659/j.issn.1005-6947.2013.10.018.
[11]García B,Ibarra J,Sola A,et al.Gastrointestinal stromal tumors.Analysis of 40 cases[J].Medicina(B Aires),2017,77(5):370-372.
[12]Blay JY,Bonvalot S,Casali P,et al.Consensus meeting for the management of gastrointestinal stromal tumors.Report of the GISTConsensus Conference of 20-21 March 2004,under the auspices of ESMO[J].Ann.Oncol,2005,16(4):566-578.doi:10.1093/annonc/mdi127.
[13]中国医师协会外科医师分会胃肠道间质瘤诊疗专业委员会,中华医学会外科学分会胃肠外科学组.胃肠间质瘤规范化外科治疗中国专家共识(2018版)[J].中国实用外科杂志,2018,38(9):965-973.doi:10.19538/j.cjps.issn.1005-2208.2018.09.01.Committee of Diagnosis and Treatment of Gastrointestinal Stromal Tumor,Chinese College of Surgeons,Gastrointestinal Surgery Group of Surgery Branch,Chinese Medical Association.Chinese expert consensus on standard surgical treatment of gastrointestinal stromal tumor(2018 edition)[J].Chinese Journal of Practical Surgery,2018,38(9):965-973.doi:10.19538/j.cjps.issn.1005-2208.2018.09.01.
[14]Valsangkar N,Sehdev A,Misra S,et al.Current management of gastrointestinal stromal tumors:Surgery,current biomarkers,mutations,and therapy[J].Surgery,2015,158(5):1149-1164.doi:10.1016/j.surg.2015.06.027.
[15]Woodall CE 3rd,Brock GN,Fan J,et al.An evaluation of 2537gastrointestinal stromal tumors for a proposed clinical staging system[J].Arch Surg,2009,144(7):670-678.doi:10.1001/archsurg.2009.108.
[16]Hohenberger P,Ronellenfitsch U,Oladeji O,et al.Pattern of recurrence in patients with ruptured primary gastrointestinal stromal tumour[J].Br J Surg,2010,97(12):1854-1859.doi:10.1002/bjs.7222.
[17]Blesius A,Cassier PA,Bertucci F,et al.Neoadjuvant imatinib in patients with locally advanced non metastatic GIST in the prospective BFR14 trial[J].BMC Cancer,2011,11:72.doi:10.1186/1471-2407-11-72.
[18]Wang C,Zheng B,Chen Y,et al.Imatinib as preoperative therapy in Chinese patients with recurrent or metastatic GISTs[J].Chin J Cancer Res,2013,25(1):63-70.doi:10.3978/j.issn.1000-9604.2012.12.01.
[19]Eisenberg BL,Harris J,Blanke CD,et al.Phase II trial of neoadjuvant/adjuvant imatinib mesylate(IM)for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor(GIST):early results of RTOG 0132/ACRIN 6665[J].J Surg Oncol,2009,99(1):42-47.doi:10.1002/jso.21160.
[20]Dematteo RP,Ballman KV,Antonescu CR,et al.Adjuvant imatinib mesylate after resection of localised,primary gastrointestinal stromal tumour:a randomised,double-blind,placebo-controlled trial[J].Lancet,2009,373(9669):1097-1104.doi:10.1016/S0140-6736(09)60500-6.
[21]Joensuu H,Eriksson M,Sundby Hall K,et al.One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor:a randomized trial[J].JAMA,2012,307(12):1265-1272.doi:10.1001/jama.2012.347.
[22]中国临床肿瘤学会胃肠间质瘤专家委员会.中国胃肠间质瘤诊断治疗共识(2017年版)[J].肿瘤综合治疗电子杂志,2018,4(1):31-43.Committee of Gastrointestinal Stromal Tumor,Chinese Society of Clinical Oncology.Chinese consensus on diagnosis and treatment of gastrointestinal stromal tumor(2017 edition)[J].Journal of Esophageal Surgery:Electronic Version,2018,4(1):31-43.
[23]中国研究型医院学会消化道肿瘤专业委员会,中国医师协会外科医师分会多学科综合治疗专业委员会.胃肠间质瘤多学科综合治疗协作组诊疗模式专家共识[J].中国实用外科杂志,2017,37(1):39-41.doi:10.19538/j.cjps.issn1005-2208.2017.01.13.Specialized Committee of Gastrointestinal Tumors of Chinese Research Hospital Association,Specialized Committee of Multidisciplinary Treatment of Chinese Research Hospital Association.Expert consensus on mode of multidisciplinary cooperative group for gastrointestinal stromal tumor[J].Chinese Journal of Practical Surgery,2017,37(1):39-41.doi:10.19538/j.cjps.issn1005-2208.2017.01.13.
[24]刘安文,廖国庆,郑凯,等.50例胃肠道间质瘤患者c-k i t及P D G F R-a基因检测及突变分析[J].中国现代医生,2013,51(23):54-56.Liu AW,Liao GQ,Zheng K,et al.Detection of the c-kit and PDGFRαgene mutation and mutation analysis[J].China Modern Doctor,2013,51(23):54-56.
[25]王万川,廖国庆.基因突变与胃肠道间质瘤研究进展[J].中国普通外科杂志,2007,16(9):892-894.doi:10.3969/j.issn.1005-6947.2007.09.018.Wang WC,Liao GQ.Genetic mutation of gastrointestinal stromal tumors[J].Chinese Journal of General Surgery,2007,16(9):892-894.doi:10.3969/j.issn.1005-6947.2007.09.018.
[26]糜睿,丁杰,董奇,等.胃肠道间质瘤的基因研究进展[J].中国普通外科杂志,2018,27(10):1341-1347.doi:10.7659/j.issn.1005-6947.2018.10.018.Mi R,Ding J,Dong Q,et al.Research progress of genes associated with gastrointestinal stromal tumors[J].Chinese Journal of General Surgery,2018,27(10):1341-1347.doi:10.7659/j.issn.1005-6947.2018.10.018.
[27]Lin JX,Chen QF,Zheng CH,et al.Is 3-years duration of adjuvant imatinib mesylate treatment sufficient for patients with highrisk gastrointestinal stromal tumor?A study based on long-term follow-up[J].J Cancer Res Clin Oncol,2017,143(4):727-734.doi:10.1007/s00432-016-2334-x.