关于恶性胸膜间皮瘤的病因和内科治疗的简述
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摘要
恶性胸膜间皮瘤(malignant pleural mesothelioma,MPM)是一种极高侵袭性的肿瘤,常侵袭至胸膜腔及周围结构,在临床中缺乏高效的治疗举措,预后极差,MPM同时也是胸膜原发肿瘤中最多见的类型,其在过去五十年中的发病率急剧上升,虽然胸片、CT引导下的胸膜活检、FDG-PET-CT、免疫组化标记以及双侧胸腔镜等检查方式可在一定程度上发现早期MPM,然而,绝大多数患者确诊时即处疾病的中后期,因此手术治疗效果不佳。此时,基于应用药物为主的内科治疗已成为治疗MPM的关键措施。目前,化学治疗、分子靶向治疗和免疫治疗是MPM临床治疗的主要举措。传统的化疗是MPM全面性、根治性医治的措施之一,除此之外,亦可有减缓症状、延长晚期因种种原因无法进行手术或放射治疗的MPM患者生命的手段;相比化疗而言,靶向治疗可言之为有目的、有选择地杀灭肿瘤细胞,而不累及其余正常细胞的治疗方式,成为目前MPM治疗的重要治疗方法;肿瘤免疫疗法是针对人体免疫系统、增强免疫效应来灭杀肿瘤细胞,从而治疗癌症,并成为MPM治疗的新兴力量。
Malignant pleural mesothelioma(MPM)is a highly invasive tumor that often invades into the pleural cavity and surrounding structures.It lacks effective therapeutic measures in the clinic,and the prognosis is extremely poor.MPM is also the primary pleural effusion.The most common type of tumor,its incidence has risen sharply in the past 50 years,although chest X-ray,CT-guided pleural biopsy,FDG-PET-CT,immunohistochemical markers and bilateral thoracoscopic examinations can be used.Early stage MPM was found to a certain extent.However,the vast majority of patients were diagnosed at the middle and late stages of the disease,so the surgical treatment was not effective.At this time,medical treatment based on applied drugs has become a key measure for the treatment of MPM.At present,chemotherapy,molecular targeted therapy and immunotherapy are the main measures for clinical treatment of MPM.Traditional chemotherapy is one of the measures for comprehensive and radical treatment of MPM.In addition,there are ways to slow down symptoms and prolong the life of MPM patients who cannot be operated or treated for radiation in various stages.Targeted therapy can be said to have a purposeful and selective killing of tumor cells without involving other normal cells.It has become an important treatment for MPM treatment,tumor immunotherapy is aimed at the human immune system and enhances immune effects.To kill tumor cells,thereby treating cancer and becoming an emerging force in MPM treatment.
Malignant pleural mesothelioma(MPM)is a highly invasive tumor that often invades into the pleural cavity and surrounding structures.It lacks effective therapeutic measures in the clinic,and the prognosis is extremely poor.MPM is also the primary pleural effusion.The most common type of tumor,its incidence has risen sharply in the past 50 years,although chest X-ray,CT-guided pleural biopsy,FDG-PET-CT,immunohistochemical markers and bilateral thoracoscopic examinations can be used.Early stage MPM was found to a certain extent.However,the vast majority of patients were diagnosed at the middle and late stages of the disease,so the surgical treatment was not effective.At this time,medical treatment based on applied drugs has become a key measure for the treatment of MPM.At present,chemotherapy,molecular targeted therapy and immunotherapy are the main measures for clinical treatment of MPM.Traditional chemotherapy is one of the measures for comprehensive and radical treatment of MPM.In addition,there are ways to slow down symptoms and prolong the life of MPM patients who cannot be operated or treated for radiation in various stages.Targeted therapy can be said to have a purposeful and selective killing of tumor cells without involving other normal cells.It has become an important treatment for MPM treatment,tumor immunotherapy is aimed at the human immune system and enhances immune effects.To kill tumor cells,thereby treating cancer and becoming an emerging force in MPM treatment.
引文
[1]Mancuso M R,Neal J W.Novel systemic therapy against malignant pleural mesothelioma[J].Transl Lung Cancer Res,2017,6(3):295-314.
[2]赵晖.恶性胸膜间皮瘤的治疗进展[J].中国医药导刊,2013,15(S1):94-95.
[3]Taioli E,Wolf A S,Flores R M.Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma[J].Annals of Thoracic Surgery,2015,99(2):472-480.
[4]Carbone M,Yang H.Mesothelioma:recent highlights[J].Ann Transl Med,2017,5(11):238.
[5]Neumann V,L?seke S,Nowak D,et al.Malignant pleural mesothelioma:incidence,etiology,diagnosis,treatment,and occupational health[J].Deutsches Arzteblatt International,2013,110(18):319-326.
[6]Napolitano A,Antoine D J,Pellegrini L,et al.HMGB1and its hyper-acetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients[J].Clinical Cancer Research,2016,22(12):3087-3096.
[7]Kondola S,Manners D,Nowak A K.Malignant pleural mesothelioma:an update on diagnosis and treatment options[J].Therapeutic Advances in Respiratory Disease,2016,25(142):472-486.
[8]Pellegrini L,Xue J,Larson D,et al.HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma[J].Oncotarget,2017,8(14):22649-22661.
[9]Testa J R,Cheung M,Pei J,et al.Germline BAP1 mutations predispose to malignant mesothelioma[J].Nature Genetics,2011,43(10):1022.
[10]Nasu M,Emi M,Pastorino S,et al.High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma[J].Journal of Thoracic Oncology,2015,10(4):565-576.
[11]Tsao A S,Wistuba I,Roth J A,et al.Malignant Pleural Mesothelioma[J].Journal of Clinical Oncology,2009,27(12):2081-2090.
[12]Ghanim B,Hoda M A,Klikovits T,et al.A critical update on prognostic and predictive biomarkers in malignant pleural mesothelioma[J].Magazine of European Medical Oncology,2015,8(1):52-56.
[13]Carbone M,Yang H.Mesothelioma:recent highlights[J].Ann Transl Med,2017,5(11):238.
[14]Giorgi C.BAP1 regulates IP3R3-mediated Ca2+flux to mitochondria suppressing cell transformation[J].Nature,2017,546(7659):549-553.
[15]Simone P,Carlotta G,Stefania M,et al.The endoplasmic reticulum mitochondrial calcium cross talk is downregulated in malignant pleural mesothelioma cells and plays a critical role in apoptosis inhibition[J].Oncotarget,2015,6(27):23427-23444.
[16]Huang L,Cai M,Zhang X,et al.Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma[J].Am JCancer Res,2017,7(2):203-217.
[17]王姗,王贵吉,裴迎新,等.培美曲塞在复发恶性胸膜间皮瘤患者中疗效分析[J].中国实用医刊,2013,40(7):85-87.
[18]Zalcman G,Mazieres J,Margery J,et al.Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study(MAPS):a randomised,controlled,open-label,phase 3 trial[J].Lancet,2016,387(10026):1405-1414.
[19]王昌平,黄珣,黄维,等.培美曲塞联合顺铂一线治疗恶性胸膜间皮瘤疗效[J].现代仪器与医疗,2017,23(2):97-99.
[20]Zucali P A,Simonelli M,Michetti G,et al.Second-line chemotherapy in malignant pleural mesothelioma:results of a retrospective multicenter survey[J].Lung Cancer,2012,75(3):360-367.
[21]秦茵茵,张德华,欧阳铭,等.吉西他滨联合多西他赛与培美曲塞联合顺铂治疗晚期恶性胸膜间皮瘤初步疗效对比[J].现代肿瘤医学,2017,25(21):3426-3429.
[22]Ak G,Metintas S,Akarsu M,et al.The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma[J].Bmc Cancer,2015,15(1):510.
[23]刘丹,李志斌,钟世寿,等.吉西他滨联合洛铂二线治疗恶性胸膜间皮瘤的疗效观察[J].现代肿瘤医学,2018,26(17):2711-2714.
[24]Tsuda Y,Kitamura A,Nishimura N,et al.Safety of pemetrexed ac-cording to the duration of vitamin B12 and folic acid supplementa-tion prior to the first dose of pemetrexed[J].Gan To Kagaku Ryo-ho,2015,42(4):471-475.
[25]徐晓玲,姚银丽,余新民,等.恶性胸膜间皮瘤化疗进展[J].中华肿瘤防治杂志,2015,22(2):155-160.
[26]邱海兵,冯起校.恶性胸膜间皮瘤的靶向治疗研究进展[J].职业与健康,2016,32(10):1437-1440.
[27]Mazières J,Zalcman G,CrinòL,et al.Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement:results from the EUROS1 cohort[J].Journal of Clinical Oncology,2015,33(9):992-999.
[28]Grosso F,Steele N,Novello S,et al.Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma:PhaseⅡResults From the Randomized,Placebo-Controlled LUME-Meso Trial[J].Journal of Clinical Oncology,2017,35(31):3591.
[29]Ellis P M,Coakley N,Feld R,et al.Use of the epidermal growth factor receptor inhibitors gefitinib,erlotinib,afatinib,dacomitinib,and icotinib in the treatment of non-small-cell lung cancer:a systematic review[J].Current Oncology,2015,22(3):e183.
[30]Mezzapelle R,Miglio U,Rena O,et al.Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samplesof malignant pleural mesothelioma[J].Br J Cancer,2013,108(8):1743-1749.
[31]Bersanelli M,Buti S.From targeting the tumor to targeting the immune system:Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis[J].World J Clin Oncol,2017,8(1):37-53.
[32]Buchbinder E I,Desai A.CTLA-4 and PD-1 Pathways:Similarities,Differences,and Implications of Their Inhibition[J].Am J Clin Oncol,2016,39(1):98-106.
[33]CalabròL,Morra A,Fonsatti E,et al.Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma:an open-label,single-arm,phase 2 trial[J].Lancet Oncol,2013,14(11):1104-1111.
[34]Kindler H L,Scherpereel A,CalabròL,et al.Tremelimumab as second-or third-line treatment of unresectable malignant mesothelioma(MM):Results from the global,double-blind,placebo-controlled DETERMINE study[J].J Clin Oncol 2016,34:8502.
[35]Krishnaswamy J K,Singh A,Gowthaman U,et al.Coincidental loss of DOCK8 function in NLRP10-deficient and C3H/HeJ mice results in defective dendritic cell migration[J].Proceedings of the National Academy of Sciences of the United States of America,2015,112(10):3056-3061.
[36]Kindler H L,Scherpereel A,CalabròL,et al.Tremelimumab as second-or third-line treatment of unresectable malignant mesothelioma(MM):Results from the global,double-blind,placebo-controlled determine study[J].Lancet Oncol,2017,18(9):1261-1273.
[37]Alley E W,Molife L R,Santoro A,et al.Abstract CT103:Clinical safety and efficacy of pembrolizumab(MK-3475)in patients with malignant pleural mesothelioma:Preliminary results from KEYNOTE-028[J].Cancer Research,2015,75(15Supplement):CT103.
[38]Khanna S,Thomas A,Abatedaga D,et al.Malignant Mesothelioma Effusions Are Infiltrated by CD3+T Cells Highly Expressing PD-L1 and the PD-L1+Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab[J].Journal of Thoracic Oncology Official Publication of the International Association for the Study of Lung Cancer,2016,11(11):1993-2005.
[39]Assan R,Kindler H L,Jahan T,et al.PhaseⅡclinical trial of amatuximab,a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma[J].Clin Cancer Res,2014,20(23):5927-5936.
[40]Treasure T,Lang-Lazdunski L,Waller D,et al.Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma:clinical outcomes of the mesothelioma and radical surgery(MARS)randomised feasibility study[J].Lancet Oncol,2011,12(8):763-772.
[41]Van Z N,Clarke C,Henderson D,et al.Guidelines for the diagnosis and treatment of malignant pleural mesothelioma[J].J Thorac Dis,2013,5(6):E254-E307.
[42]何一兵,姜静波,吴宏成,等.培美曲塞联合顺铂治疗八例恶性胸膜间皮瘤疗效分析[J].中国医师进修杂志,2011,34(29):42-43.
[43]Rossini M,Rizzo P,Bononi I,et al.New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma[J].Front Oncol,2018,8:91.
[2]赵晖.恶性胸膜间皮瘤的治疗进展[J].中国医药导刊,2013,15(S1):94-95.
[3]Taioli E,Wolf A S,Flores R M.Meta-analysis of survival after pleurectomy decortication versus extrapleural pneumonectomy in mesothelioma[J].Annals of Thoracic Surgery,2015,99(2):472-480.
[4]Carbone M,Yang H.Mesothelioma:recent highlights[J].Ann Transl Med,2017,5(11):238.
[5]Neumann V,L?seke S,Nowak D,et al.Malignant pleural mesothelioma:incidence,etiology,diagnosis,treatment,and occupational health[J].Deutsches Arzteblatt International,2013,110(18):319-326.
[6]Napolitano A,Antoine D J,Pellegrini L,et al.HMGB1and its hyper-acetylated isoform are sensitive and specific serum biomarkers to detect asbestos exposure and to identify mesothelioma patients[J].Clinical Cancer Research,2016,22(12):3087-3096.
[7]Kondola S,Manners D,Nowak A K.Malignant pleural mesothelioma:an update on diagnosis and treatment options[J].Therapeutic Advances in Respiratory Disease,2016,25(142):472-486.
[8]Pellegrini L,Xue J,Larson D,et al.HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma[J].Oncotarget,2017,8(14):22649-22661.
[9]Testa J R,Cheung M,Pei J,et al.Germline BAP1 mutations predispose to malignant mesothelioma[J].Nature Genetics,2011,43(10):1022.
[10]Nasu M,Emi M,Pastorino S,et al.High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma[J].Journal of Thoracic Oncology,2015,10(4):565-576.
[11]Tsao A S,Wistuba I,Roth J A,et al.Malignant Pleural Mesothelioma[J].Journal of Clinical Oncology,2009,27(12):2081-2090.
[12]Ghanim B,Hoda M A,Klikovits T,et al.A critical update on prognostic and predictive biomarkers in malignant pleural mesothelioma[J].Magazine of European Medical Oncology,2015,8(1):52-56.
[13]Carbone M,Yang H.Mesothelioma:recent highlights[J].Ann Transl Med,2017,5(11):238.
[14]Giorgi C.BAP1 regulates IP3R3-mediated Ca2+flux to mitochondria suppressing cell transformation[J].Nature,2017,546(7659):549-553.
[15]Simone P,Carlotta G,Stefania M,et al.The endoplasmic reticulum mitochondrial calcium cross talk is downregulated in malignant pleural mesothelioma cells and plays a critical role in apoptosis inhibition[J].Oncotarget,2015,6(27):23427-23444.
[16]Huang L,Cai M,Zhang X,et al.Combinational therapy of crizotinib and afatinib for malignant pleural mesothelioma[J].Am JCancer Res,2017,7(2):203-217.
[17]王姗,王贵吉,裴迎新,等.培美曲塞在复发恶性胸膜间皮瘤患者中疗效分析[J].中国实用医刊,2013,40(7):85-87.
[18]Zalcman G,Mazieres J,Margery J,et al.Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study(MAPS):a randomised,controlled,open-label,phase 3 trial[J].Lancet,2016,387(10026):1405-1414.
[19]王昌平,黄珣,黄维,等.培美曲塞联合顺铂一线治疗恶性胸膜间皮瘤疗效[J].现代仪器与医疗,2017,23(2):97-99.
[20]Zucali P A,Simonelli M,Michetti G,et al.Second-line chemotherapy in malignant pleural mesothelioma:results of a retrospective multicenter survey[J].Lung Cancer,2012,75(3):360-367.
[21]秦茵茵,张德华,欧阳铭,等.吉西他滨联合多西他赛与培美曲塞联合顺铂治疗晚期恶性胸膜间皮瘤初步疗效对比[J].现代肿瘤医学,2017,25(21):3426-3429.
[22]Ak G,Metintas S,Akarsu M,et al.The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma[J].Bmc Cancer,2015,15(1):510.
[23]刘丹,李志斌,钟世寿,等.吉西他滨联合洛铂二线治疗恶性胸膜间皮瘤的疗效观察[J].现代肿瘤医学,2018,26(17):2711-2714.
[24]Tsuda Y,Kitamura A,Nishimura N,et al.Safety of pemetrexed ac-cording to the duration of vitamin B12 and folic acid supplementa-tion prior to the first dose of pemetrexed[J].Gan To Kagaku Ryo-ho,2015,42(4):471-475.
[25]徐晓玲,姚银丽,余新民,等.恶性胸膜间皮瘤化疗进展[J].中华肿瘤防治杂志,2015,22(2):155-160.
[26]邱海兵,冯起校.恶性胸膜间皮瘤的靶向治疗研究进展[J].职业与健康,2016,32(10):1437-1440.
[27]Mazières J,Zalcman G,CrinòL,et al.Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement:results from the EUROS1 cohort[J].Journal of Clinical Oncology,2015,33(9):992-999.
[28]Grosso F,Steele N,Novello S,et al.Nintedanib Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma:PhaseⅡResults From the Randomized,Placebo-Controlled LUME-Meso Trial[J].Journal of Clinical Oncology,2017,35(31):3591.
[29]Ellis P M,Coakley N,Feld R,et al.Use of the epidermal growth factor receptor inhibitors gefitinib,erlotinib,afatinib,dacomitinib,and icotinib in the treatment of non-small-cell lung cancer:a systematic review[J].Current Oncology,2015,22(3):e183.
[30]Mezzapelle R,Miglio U,Rena O,et al.Mutation analysis of the EGFR gene and downstream signalling pathway in histologic samplesof malignant pleural mesothelioma[J].Br J Cancer,2013,108(8):1743-1749.
[31]Bersanelli M,Buti S.From targeting the tumor to targeting the immune system:Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis[J].World J Clin Oncol,2017,8(1):37-53.
[32]Buchbinder E I,Desai A.CTLA-4 and PD-1 Pathways:Similarities,Differences,and Implications of Their Inhibition[J].Am J Clin Oncol,2016,39(1):98-106.
[33]CalabròL,Morra A,Fonsatti E,et al.Tremelimumab for patients with chemotherapy-resistant advanced malignant mesothelioma:an open-label,single-arm,phase 2 trial[J].Lancet Oncol,2013,14(11):1104-1111.
[34]Kindler H L,Scherpereel A,CalabròL,et al.Tremelimumab as second-or third-line treatment of unresectable malignant mesothelioma(MM):Results from the global,double-blind,placebo-controlled DETERMINE study[J].J Clin Oncol 2016,34:8502.
[35]Krishnaswamy J K,Singh A,Gowthaman U,et al.Coincidental loss of DOCK8 function in NLRP10-deficient and C3H/HeJ mice results in defective dendritic cell migration[J].Proceedings of the National Academy of Sciences of the United States of America,2015,112(10):3056-3061.
[36]Kindler H L,Scherpereel A,CalabròL,et al.Tremelimumab as second-or third-line treatment of unresectable malignant mesothelioma(MM):Results from the global,double-blind,placebo-controlled determine study[J].Lancet Oncol,2017,18(9):1261-1273.
[37]Alley E W,Molife L R,Santoro A,et al.Abstract CT103:Clinical safety and efficacy of pembrolizumab(MK-3475)in patients with malignant pleural mesothelioma:Preliminary results from KEYNOTE-028[J].Cancer Research,2015,75(15Supplement):CT103.
[38]Khanna S,Thomas A,Abatedaga D,et al.Malignant Mesothelioma Effusions Are Infiltrated by CD3+T Cells Highly Expressing PD-L1 and the PD-L1+Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab[J].Journal of Thoracic Oncology Official Publication of the International Association for the Study of Lung Cancer,2016,11(11):1993-2005.
[39]Assan R,Kindler H L,Jahan T,et al.PhaseⅡclinical trial of amatuximab,a chimeric antimesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma[J].Clin Cancer Res,2014,20(23):5927-5936.
[40]Treasure T,Lang-Lazdunski L,Waller D,et al.Extra-pleural pneumonectomy versus no extra-pleural pneumonectomy for patients with malignant pleural mesothelioma:clinical outcomes of the mesothelioma and radical surgery(MARS)randomised feasibility study[J].Lancet Oncol,2011,12(8):763-772.
[41]Van Z N,Clarke C,Henderson D,et al.Guidelines for the diagnosis and treatment of malignant pleural mesothelioma[J].J Thorac Dis,2013,5(6):E254-E307.
[42]何一兵,姜静波,吴宏成,等.培美曲塞联合顺铂治疗八例恶性胸膜间皮瘤疗效分析[J].中国医师进修杂志,2011,34(29):42-43.
[43]Rossini M,Rizzo P,Bononi I,et al.New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma[J].Front Oncol,2018,8:91.