胃肠道间质瘤分子靶向治疗的研究进展
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摘要
胃肠道间质瘤(gastrointestinal stromal tumor, GIST)是最常见的腹部软组织恶性肿瘤,来源于卡哈尔(Cajal)间质细胞或共同的前体细胞,由突变的KIT基因或血小板源性生长因子受体α(PDGFRα)基因驱动,均表达Ⅲ型酪氨酸激酶受体。酪氨酸激酶受体抑制剂伊马替尼用于晚期GIST的治疗取得了卓越的疗效,使得GIST成为实体肿瘤靶向药物治疗最成功的范例之一。之后随着对GIST分子生物学研究的日益深入,在精准医疗时代背景下,GIST的分子靶向治疗从晚期一线、二线、三线治疗到术后辅助治疗、术前治疗均有了清晰的脉络,从而为GIST患者提供了显著的生存获益。本文从晚期GIST到早期GIST的术前、术后分子靶向治疗进行了系统而全面的梳理,并分析问题、提出解决对策及对未来的展望,旨在为GIST临床分子靶向药物治疗提供参考。
Gastrointestinal stromal tumors(GISTs) are the most common malignant tumor of abdominal soft tissue. It originates from Cahal(Cajal) interstitial cells or common precursor cells, and is driven by the mutated KIT gene or platelet-derived growth factor receptor alpha(PDGFRa) gene, all expressing type Ⅲ tyrosine kinase receptors. Imatinib mesylate, a tyrosine kinase receptor inhibitor, has been used for the standard treatment of advanced GIST, which has achieved remarkable results. Thus, GIST has become the most successful example of target therapy for solid tumors. In the context of the era of precision medicine, with the deepening in research of GISTs molecular biology,the molecular targeted treatment of GISTs has obtained a clear venation from the first-line, second-line and third-line of the advanced stage to the postoperative auxiliary and preoperative treatment, providing significant survival benefits for GISTs patients. This article systematically and comprehensively combed the preoperative and postoperative molecular targeting therapy from advanced GIST to early GIST, and analyzed the problems, proposed solutions and prospects for the future, aiming to provide reference for clinical application of molecular targeting drug therapy for GIST.
Gastrointestinal stromal tumors(GISTs) are the most common malignant tumor of abdominal soft tissue. It originates from Cahal(Cajal) interstitial cells or common precursor cells, and is driven by the mutated KIT gene or platelet-derived growth factor receptor alpha(PDGFRa) gene, all expressing type Ⅲ tyrosine kinase receptors. Imatinib mesylate, a tyrosine kinase receptor inhibitor, has been used for the standard treatment of advanced GIST, which has achieved remarkable results. Thus, GIST has become the most successful example of target therapy for solid tumors. In the context of the era of precision medicine, with the deepening in research of GISTs molecular biology,the molecular targeted treatment of GISTs has obtained a clear venation from the first-line, second-line and third-line of the advanced stage to the postoperative auxiliary and preoperative treatment, providing significant survival benefits for GISTs patients. This article systematically and comprehensively combed the preoperative and postoperative molecular targeting therapy from advanced GIST to early GIST, and analyzed the problems, proposed solutions and prospects for the future, aiming to provide reference for clinical application of molecular targeting drug therapy for GIST.
引文
[1] HEINRICH M C, RUBIN B P, LONGLEY B J, et al. Biology and genetic aspects of gastrointestinal stromal tumors:KIT activation and cytogenic alterations[J]. Hum Pathol, 2002, 33(5):484-495. DOI:10.1016/S0165-4608(01)00395-8.
[2]贺慧颖,方伟岗,钟镐镐,等. 165例胃肠道间质瘤中KIT和PDGFRA基因突变的检测和临床诊断意义[J].中华病理学杂志, 2006, 35(5):262-266. DOI:10.3760/j.issn:0529-5807. 2006.05.003.
[3] BUCHER P, VILLIGER P, EGGER J F, et al. Management of gastrointestinal stromal tumors:From diagnosis to treatment[J]. Swiss Med Wkly, 2004, 134(11/12):145-153. DOI:2004/11/smw-10530.
[4] REICHARDT P. The story of imatinib in GIST a journey through the development of a targeted therapy[J]. Oncol Res Treat, 2018, 41(7/8):472-477. DOI:10.1159/000487511.
[5] SCIOT R, DEBIEC-RYCHTER M, DAUGAARD S, et al. Distribution and prognostic value of histopathologic data and immunohistochemical markers in gastrointestinal stromal tumours(GISTs):an analysis of the EORTC phaseⅢtrial of treatment of metastatic GISTs with imatinib mesylate[J]. Eur J Cancer, 2008, 44(13):1855-1860. DOI:10.1016/j. ejca.2008.06.003.
[6] BLANKE C D, RANKIN C, DEMETRI G D, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase:S0033[J]. J Clin Oncol, 2008, 26(4):626-632.DOI:10.1200/JCO.2007.13.4452.
[7] SCIOT R, DEBIEC-RYCHTER M, DAUGAARD S, et al. Distribution and prognostic value of histopathologic data and immunohistochemical markers in gastrointestinal stromal tumours(GISTs):an analysis of the EORTC phaseⅢtrial of treatment of metastatic GISTs with imatinib mesylate[J]. Eur J Cancer,2008, 44(13):1855-1860. DOI:10.1016/j.ejca.2008.06.003.
[8] EMILY Z, KEUNG M A. Correlation of long-term results of imatinib in advanced gastrointestinal stromal tumors with next-generation sequencing resultsanalysis of phase 3 swog intergroup trial S0033[J]. Surg Clin North Am, 2017, 97(2):437-452. DOI:10.1001/jamaoncol.2016.672.
[9] VON MEHREN M, HEINRICH MC, JOENSUU H, et al. Follow-up results after 9 years(yrs)of the ongoing, phaseⅡB2222 trial of imatinib mesylate(IM)in patients(pts)with metastatic or unresectable KIT+gastrointestinal stromal tumors(GIST)[J]. J Clin Oncol,2011, 29(2):29-35.
[10]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版)[J].肿瘤综合治疗电子杂志, 2018, 4(1):31-43. DOI:10.3760/cma.j.issn.0529-5807.2009.10.011.
[11] HERNRICH M C, MAKI R C, CORLESS C L, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor[J]. J Clin Oncol, 2008, 26(33):5352-5359. DOI:10.1200/JCO.2007.15.7461.
[12] HEINRIEH M C,CORLESS C L,BLANKE C D,et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors[J]. J Clin Oncol, 2006, 24(29):4764-4774. DOI:10.1200/JCO.2006.06.2265.
[13] ANTONESCU C R, BESMER P, GUO T, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation[J]. Clin Cancer Res, 2005,11(11):4182-4190. DOI:10.1158/1078-0432.CCR-04-2245.
[14] JOENSUU H, WARDELMANN E, SIHTO H, et al. Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib:an exploratory analysis of a randomized clinical trial[J]. JAMA Oncol, 2017, 3(5):602-609. DOI:10.1001/jamaoncol.2016.5751.
[15]曹晖,汪明.胃肠间质瘤综合诊治中若干焦点问题思考[J].中国实用外科杂志, 2018, 38(5):485-493.
[16] RíOS-MORENO M J, JARAMILLO S, DíAZ-DELGADO M,et al. Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression in gastrointestinal stromal tumors[J]. Anticancer Res, 2011, 31(9):3019-3025. DOI:10.1007/s00520-011-1232-7.
[17] LI J, DANG Y, GAO J, et al. PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors(GISTs)[J]. Med Oncol, 2015, 32(4):111-115. DOI:10.1007/s12032-015-0554-6.
[18] MIYAKE K, KAWAGUCHI K, KIYUNA T, et al. Regorafenib regresses an imatinib-resistant recurrent gastrointestinal stromal tumor(GIST)with a mutation in exons 11 and 17of KIT in a patient-derived orthotopic xenograft(PDOX)nude mouse model[J]. Cell Cycle, 2018, 17(6):722-727.DOI:10. 1080/15384101.2017.1423223.
[19] KINDLER H L, CAMPBELL N P, WROBLEWSKI K, et al.Sorafenib(SOR)in patients(pts)with imatinib(IM)and sunitinib(SU)-resistant(RES)gastrointestinal stromal tumors(GIST):final results of a university of chicago phaseⅡconsortium trial[J/OL]. J Clin Oncol, 2011, 29(suppl 15):10009[2019-01-11].http://europepmc.org/abstract/MED/27948416.DOI:10.1007/s12032-008-9058-y.
[20] KEFELI U, BENEKLI M, SEVINC A, et al. Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third-or fourth-line treatment:a retrospective multicenter experience[J]. Oncol Lett, 2013, 6(2):605-609. DOI:10.3892/ol.2013.1408.
[21] FRANCK C, ROSANIA R, FRANKE S, et al. The BRAF status may predict response to sorafenib in gastrointestinal stromal tumors resistant to imatinib, sunitinib, and regorafenib:case series and review of the literature[J]. Gastric Cancer,2015, 18(4):796-802. DOI:10.1007/s10120-014-0414-7.
[22] DEMETRI G D, CASALI P G, BLAY J Y, et al. A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors[J]. Clin Cancer Res, 2009, 15(55):5910-5916.
[23] CAUCHI C, SOMAIAH N, ENGSTROM P F, et al. Evaluation of nilotinib in advanced GIST previously treated with imatinib and sunitinib[J]. Cancer Chemother Pharmacol,2012, 69(4):977-982. DOI:10.1158/1078-0432. CCR-09-0542.
[24] DEWAELE B, WASAG B, COOLS J, et al. Activity of dasatinib, a dual SRC/ABL kinase inhibitor, and IPI-504, a heat shock protein 90 inhibitor, against gastrointestinal stromal tumor-associated PDGFRAD842V mutation[J]. Clin Cancer Res, 2008, 14(14):5749-5758. DOI:10.1158/1078-0432.CCR-08-0533.
[25] TRENT J C, WATHEN K, MEHREN M V. A phaseⅡstudy of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor(GIST)[J/OL]. J Clin Oncol, 2011, 29(suppl15):10006[2019-01-11]. http://www. ncbi. nlm. glh. gov/pmc/articles/PMC4165448.
[26] GANJOO K N, VILLALOBOS V M, KAMAYA A, et al. A multicenter phaseⅡstudy of pazopanib in patients with advanced gastrointestinal stromal tumors(GIST)following failure of at least imatinib and sunitinib[J]. Ann Oncol, 2014, 25(1):236-240. DOI:10.1093/annonc/mdt484.
[27] MONTEMURRO M, CIOFFI A, D?MONT J, et al. Longterm outcome of dasatinib first-line treatment in gastrointestinal stromal tumor:a multicenter, 2-stage phase 2 trial(Swiss Group for Clinical Cancer Research 56/07)[J/OL]. Cancer,2018, 2018:28171574[2019-01-11]. https://www. ncbi. nlm.nih.gov/pubmed/28171574. DOI:10.1093/annonc/mdu354.7.
[28] DE METRI G D, JEFFERS M, REICHARDT P, et al. Mutational analysis of plasma DNA from patients(pts)in the phaseⅢGRID study of regorafenib(REG)versus placebo(PL)in tyrosine kinase inhibitor(TKI)-refractory GIST:correlating genotype with clinical outcomes[J/OL]. J Clin Oncol, 2013, 31(suppl):10503. DOI:10.1200/jco. 2013.31.18_suppl.lba10503.
[29] YOON K K, MIN H R, BAEK Y R. BLU-285 Targets KIT/PDGFRA conformation and activating loop mutations[J].Cancer Discov, 2018, 8(1):20-28. DOI:10.1158/2159-8290.CD-RW2017-211.
[30] SUPSAMUTCHAI C, WILASRUSMEE C, HIRANYATHEB P, et al. A cohort study of prognostic factors associated with recurrence or metastasis of gastrointestinal stromal tumor(GIST)of stomach[J]. Ann Med Surg(Lond), 2018, 5(1):1-5.DOI:10.1016/j.amsu.2018.08.010.
[31] WU X, LI J, XU W, et al. Postoperative imatinib in patients with intermediate risk gastrointestinal stromal tumor[J]. Future Oncol, 2018, 14(17):1721-1729. DOI:10.1200/jco.2005. 23.16_suppl.9009.
[32] DE MATTEO R P, BALLMAN K V, ANTONESCU C R, et al.Long-term results of adjuvant imatinib mesylate in localized,high-risk, primary gastrointestinal stromal tumor:ACOSOG Z9000(Alliance)intergroup phase 2 trial[J]. Ann Surg, 2013,258(3):422-429. DOI:10.1097/SLA.0b013e 3182a15eb7.
[33] JOENSUU H, ERIKSSON M, SUNDBY H 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.
[34] RAUT C P, ESPAT J, MAKI R G, et al. Extended treatment with adjuvant imatinib for patients with high-risk primary gastrointestinal stromal tumor(GIST):The PERSIST-5 study[J]. J Clin Oncol, 2017, 35(suppl 15):556-559. DOI:10.1200/jco.2005.23.16_suppl.9009.
[35] CAMERON S.Long-term adjuvant treatment of gastrointestinal stromal tumors(GIST)with imatinib-a comment and reflection on the PERSIST-5 study[J]. Transl Gastroenterol Hepatol, 2018, 3(1):16-19. DOI:10.21037/tgh.2018.03.01.
[36]徐佳,赵文毅,庄淳,等.胃肠道间质瘤术后伊马替尼辅助治疗停药后复发的危险因素分析[J].中华普通外科杂志, 2016, 31(2):104-107. DOI:10.3760/cma.j.issn.1007-631X.2016.02.006.
[37] TANG J, ZHAO R, ZHENG X, et al. Using the recurrence risk score by Joensuu to assess patients with gastrointestinal stromal tumor treated with adjuvant imatinib:a retrospective cohort study[J/OL]. Med Bal, 2018, 97(29):e11400[2019-01-11]. DOI:10.1097/MD. 0000000000011400. https://www. researchgate.net/publication/326498771.
[38] WANG D, ZHANG Q, BLANKE C D, et al. PhaseⅡtrial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors:longterm follow-up results of radiation therapy oncology group 0132[J]. Ann Surg Oncol, 2012, 19(4):1074-1080. DOI:10.1097/MD.0000000000011400.
[39] EISENBERG B L, HARRIS J, BLANKE C D, et al. PhaseⅡtrial 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:10.1245/s10434-011-2190-5.
[40]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专家共识[J].中国实用外科杂志, 2015, 35(6):593-598.DOI:10.7504/CJPS.ISSN1005-2208.2015.06.04.
[41] PRAUSE M, NIEDERMOSER S, W?NGLER C, et al. Synthesis, in vitro and in vivo evaluation of 18F-fluoronorimatinib as radiotracer for imatinib-sensitive gastrointestinal stromal tumors[J]. Nucl Med Biol, 2017, 57(1):1-11. DOI:10.1016/j.nucmedbio.2017.11.004.
[42] SHINAGARE A B, JAGANNATHAN J P, KURRA V, et al.Comparison of performance of various tumour response criteria in assessment of regorafenib activity in advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib[J]. Eur J Cancer, 2014, 50(7):981-986. DOI:10. 1016/j.ejca.2013.11.037.
[43] HOHENBERGER P, LANGER C, WENDTNER CM, et al.Neoadjuvant treatment of locally advanced GIST:Results of APOLLON, a prospective, open label phase II study in KITor PDGFRA-positive tumors[J/OL]. J Clin Oncol, 2012, 30(suppl15):10031-10031[2018-01-20. http://ascopubs. org/doi/abs/10.1200/jco.2012.30.15_suppl.10031. DOI:10.1200/jco.2012.30.15_suppl.10031.
[2]贺慧颖,方伟岗,钟镐镐,等. 165例胃肠道间质瘤中KIT和PDGFRA基因突变的检测和临床诊断意义[J].中华病理学杂志, 2006, 35(5):262-266. DOI:10.3760/j.issn:0529-5807. 2006.05.003.
[3] BUCHER P, VILLIGER P, EGGER J F, et al. Management of gastrointestinal stromal tumors:From diagnosis to treatment[J]. Swiss Med Wkly, 2004, 134(11/12):145-153. DOI:2004/11/smw-10530.
[4] REICHARDT P. The story of imatinib in GIST a journey through the development of a targeted therapy[J]. Oncol Res Treat, 2018, 41(7/8):472-477. DOI:10.1159/000487511.
[5] SCIOT R, DEBIEC-RYCHTER M, DAUGAARD S, et al. Distribution and prognostic value of histopathologic data and immunohistochemical markers in gastrointestinal stromal tumours(GISTs):an analysis of the EORTC phaseⅢtrial of treatment of metastatic GISTs with imatinib mesylate[J]. Eur J Cancer, 2008, 44(13):1855-1860. DOI:10.1016/j. ejca.2008.06.003.
[6] BLANKE C D, RANKIN C, DEMETRI G D, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase:S0033[J]. J Clin Oncol, 2008, 26(4):626-632.DOI:10.1200/JCO.2007.13.4452.
[7] SCIOT R, DEBIEC-RYCHTER M, DAUGAARD S, et al. Distribution and prognostic value of histopathologic data and immunohistochemical markers in gastrointestinal stromal tumours(GISTs):an analysis of the EORTC phaseⅢtrial of treatment of metastatic GISTs with imatinib mesylate[J]. Eur J Cancer,2008, 44(13):1855-1860. DOI:10.1016/j.ejca.2008.06.003.
[8] EMILY Z, KEUNG M A. Correlation of long-term results of imatinib in advanced gastrointestinal stromal tumors with next-generation sequencing resultsanalysis of phase 3 swog intergroup trial S0033[J]. Surg Clin North Am, 2017, 97(2):437-452. DOI:10.1001/jamaoncol.2016.672.
[9] VON MEHREN M, HEINRICH MC, JOENSUU H, et al. Follow-up results after 9 years(yrs)of the ongoing, phaseⅡB2222 trial of imatinib mesylate(IM)in patients(pts)with metastatic or unresectable KIT+gastrointestinal stromal tumors(GIST)[J]. J Clin Oncol,2011, 29(2):29-35.
[10]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版)[J].肿瘤综合治疗电子杂志, 2018, 4(1):31-43. DOI:10.3760/cma.j.issn.0529-5807.2009.10.011.
[11] HERNRICH M C, MAKI R C, CORLESS C L, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor[J]. J Clin Oncol, 2008, 26(33):5352-5359. DOI:10.1200/JCO.2007.15.7461.
[12] HEINRIEH M C,CORLESS C L,BLANKE C D,et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors[J]. J Clin Oncol, 2006, 24(29):4764-4774. DOI:10.1200/JCO.2006.06.2265.
[13] ANTONESCU C R, BESMER P, GUO T, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation[J]. Clin Cancer Res, 2005,11(11):4182-4190. DOI:10.1158/1078-0432.CCR-04-2245.
[14] JOENSUU H, WARDELMANN E, SIHTO H, et al. Effect of KIT and PDGFRA mutations on survival in patients with gastrointestinal stromal tumors treated with adjuvant imatinib:an exploratory analysis of a randomized clinical trial[J]. JAMA Oncol, 2017, 3(5):602-609. DOI:10.1001/jamaoncol.2016.5751.
[15]曹晖,汪明.胃肠间质瘤综合诊治中若干焦点问题思考[J].中国实用外科杂志, 2018, 38(5):485-493.
[16] RíOS-MORENO M J, JARAMILLO S, DíAZ-DELGADO M,et al. Differential activation of MAPK and PI3K/AKT/mTOR pathways and IGF1R expression in gastrointestinal stromal tumors[J]. Anticancer Res, 2011, 31(9):3019-3025. DOI:10.1007/s00520-011-1232-7.
[17] LI J, DANG Y, GAO J, et al. PI3K/AKT/mTOR pathway is activated after imatinib secondary resistance in gastrointestinal stromal tumors(GISTs)[J]. Med Oncol, 2015, 32(4):111-115. DOI:10.1007/s12032-015-0554-6.
[18] MIYAKE K, KAWAGUCHI K, KIYUNA T, et al. Regorafenib regresses an imatinib-resistant recurrent gastrointestinal stromal tumor(GIST)with a mutation in exons 11 and 17of KIT in a patient-derived orthotopic xenograft(PDOX)nude mouse model[J]. Cell Cycle, 2018, 17(6):722-727.DOI:10. 1080/15384101.2017.1423223.
[19] KINDLER H L, CAMPBELL N P, WROBLEWSKI K, et al.Sorafenib(SOR)in patients(pts)with imatinib(IM)and sunitinib(SU)-resistant(RES)gastrointestinal stromal tumors(GIST):final results of a university of chicago phaseⅡconsortium trial[J/OL]. J Clin Oncol, 2011, 29(suppl 15):10009[2019-01-11].http://europepmc.org/abstract/MED/27948416.DOI:10.1007/s12032-008-9058-y.
[20] KEFELI U, BENEKLI M, SEVINC A, et al. Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third-or fourth-line treatment:a retrospective multicenter experience[J]. Oncol Lett, 2013, 6(2):605-609. DOI:10.3892/ol.2013.1408.
[21] FRANCK C, ROSANIA R, FRANKE S, et al. The BRAF status may predict response to sorafenib in gastrointestinal stromal tumors resistant to imatinib, sunitinib, and regorafenib:case series and review of the literature[J]. Gastric Cancer,2015, 18(4):796-802. DOI:10.1007/s10120-014-0414-7.
[22] DEMETRI G D, CASALI P G, BLAY J Y, et al. A phase I study of single-agent nilotinib or in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors[J]. Clin Cancer Res, 2009, 15(55):5910-5916.
[23] CAUCHI C, SOMAIAH N, ENGSTROM P F, et al. Evaluation of nilotinib in advanced GIST previously treated with imatinib and sunitinib[J]. Cancer Chemother Pharmacol,2012, 69(4):977-982. DOI:10.1158/1078-0432. CCR-09-0542.
[24] DEWAELE B, WASAG B, COOLS J, et al. Activity of dasatinib, a dual SRC/ABL kinase inhibitor, and IPI-504, a heat shock protein 90 inhibitor, against gastrointestinal stromal tumor-associated PDGFRAD842V mutation[J]. Clin Cancer Res, 2008, 14(14):5749-5758. DOI:10.1158/1078-0432.CCR-08-0533.
[25] TRENT J C, WATHEN K, MEHREN M V. A phaseⅡstudy of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor(GIST)[J/OL]. J Clin Oncol, 2011, 29(suppl15):10006[2019-01-11]. http://www. ncbi. nlm. glh. gov/pmc/articles/PMC4165448.
[26] GANJOO K N, VILLALOBOS V M, KAMAYA A, et al. A multicenter phaseⅡstudy of pazopanib in patients with advanced gastrointestinal stromal tumors(GIST)following failure of at least imatinib and sunitinib[J]. Ann Oncol, 2014, 25(1):236-240. DOI:10.1093/annonc/mdt484.
[27] MONTEMURRO M, CIOFFI A, D?MONT J, et al. Longterm outcome of dasatinib first-line treatment in gastrointestinal stromal tumor:a multicenter, 2-stage phase 2 trial(Swiss Group for Clinical Cancer Research 56/07)[J/OL]. Cancer,2018, 2018:28171574[2019-01-11]. https://www. ncbi. nlm.nih.gov/pubmed/28171574. DOI:10.1093/annonc/mdu354.7.
[28] DE METRI G D, JEFFERS M, REICHARDT P, et al. Mutational analysis of plasma DNA from patients(pts)in the phaseⅢGRID study of regorafenib(REG)versus placebo(PL)in tyrosine kinase inhibitor(TKI)-refractory GIST:correlating genotype with clinical outcomes[J/OL]. J Clin Oncol, 2013, 31(suppl):10503. DOI:10.1200/jco. 2013.31.18_suppl.lba10503.
[29] YOON K K, MIN H R, BAEK Y R. BLU-285 Targets KIT/PDGFRA conformation and activating loop mutations[J].Cancer Discov, 2018, 8(1):20-28. DOI:10.1158/2159-8290.CD-RW2017-211.
[30] SUPSAMUTCHAI C, WILASRUSMEE C, HIRANYATHEB P, et al. A cohort study of prognostic factors associated with recurrence or metastasis of gastrointestinal stromal tumor(GIST)of stomach[J]. Ann Med Surg(Lond), 2018, 5(1):1-5.DOI:10.1016/j.amsu.2018.08.010.
[31] WU X, LI J, XU W, et al. Postoperative imatinib in patients with intermediate risk gastrointestinal stromal tumor[J]. Future Oncol, 2018, 14(17):1721-1729. DOI:10.1200/jco.2005. 23.16_suppl.9009.
[32] DE MATTEO R P, BALLMAN K V, ANTONESCU C R, et al.Long-term results of adjuvant imatinib mesylate in localized,high-risk, primary gastrointestinal stromal tumor:ACOSOG Z9000(Alliance)intergroup phase 2 trial[J]. Ann Surg, 2013,258(3):422-429. DOI:10.1097/SLA.0b013e 3182a15eb7.
[33] JOENSUU H, ERIKSSON M, SUNDBY H 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.
[34] RAUT C P, ESPAT J, MAKI R G, et al. Extended treatment with adjuvant imatinib for patients with high-risk primary gastrointestinal stromal tumor(GIST):The PERSIST-5 study[J]. J Clin Oncol, 2017, 35(suppl 15):556-559. DOI:10.1200/jco.2005.23.16_suppl.9009.
[35] CAMERON S.Long-term adjuvant treatment of gastrointestinal stromal tumors(GIST)with imatinib-a comment and reflection on the PERSIST-5 study[J]. Transl Gastroenterol Hepatol, 2018, 3(1):16-19. DOI:10.21037/tgh.2018.03.01.
[36]徐佳,赵文毅,庄淳,等.胃肠道间质瘤术后伊马替尼辅助治疗停药后复发的危险因素分析[J].中华普通外科杂志, 2016, 31(2):104-107. DOI:10.3760/cma.j.issn.1007-631X.2016.02.006.
[37] TANG J, ZHAO R, ZHENG X, et al. Using the recurrence risk score by Joensuu to assess patients with gastrointestinal stromal tumor treated with adjuvant imatinib:a retrospective cohort study[J/OL]. Med Bal, 2018, 97(29):e11400[2019-01-11]. DOI:10.1097/MD. 0000000000011400. https://www. researchgate.net/publication/326498771.
[38] WANG D, ZHANG Q, BLANKE C D, et al. PhaseⅡtrial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors:longterm follow-up results of radiation therapy oncology group 0132[J]. Ann Surg Oncol, 2012, 19(4):1074-1080. DOI:10.1097/MD.0000000000011400.
[39] EISENBERG B L, HARRIS J, BLANKE C D, et al. PhaseⅡtrial 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:10.1245/s10434-011-2190-5.
[40]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专家共识[J].中国实用外科杂志, 2015, 35(6):593-598.DOI:10.7504/CJPS.ISSN1005-2208.2015.06.04.
[41] PRAUSE M, NIEDERMOSER S, W?NGLER C, et al. Synthesis, in vitro and in vivo evaluation of 18F-fluoronorimatinib as radiotracer for imatinib-sensitive gastrointestinal stromal tumors[J]. Nucl Med Biol, 2017, 57(1):1-11. DOI:10.1016/j.nucmedbio.2017.11.004.
[42] SHINAGARE A B, JAGANNATHAN J P, KURRA V, et al.Comparison of performance of various tumour response criteria in assessment of regorafenib activity in advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib[J]. Eur J Cancer, 2014, 50(7):981-986. DOI:10. 1016/j.ejca.2013.11.037.
[43] HOHENBERGER P, LANGER C, WENDTNER CM, et al.Neoadjuvant treatment of locally advanced GIST:Results of APOLLON, a prospective, open label phase II study in KITor PDGFRA-positive tumors[J/OL]. J Clin Oncol, 2012, 30(suppl15):10031-10031[2018-01-20. http://ascopubs. org/doi/abs/10.1200/jco.2012.30.15_suppl.10031. DOI:10.1200/jco.2012.30.15_suppl.10031.