Significant benefits of osimertinib in treating acquired resistance to first-generation EGFR-TKIs in lung squamous cell cancer: A case report
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摘要
BACKGROUND Lung squamous cell cancer(LSCC) rarely harbors epidermal growth factor receptor(EGFR) mutations, even much rarer for acquired T790 M mutation.Although clinical trials of AURA series illustrated that non-small cell lung cancer(NSCLC) with EGFR T790 M mutation can benefit from osimertinib, only five LSCC patients were enrolled in total; moreover, the efficacy for LSCC was not shown in the results. Therefore, the response of LSCC to osimertinib is still unclear to date.CASE SUMMARY We report an LSCC case with T790 M-related acquired resistance after treatments with first-generation EGFR-tyrosine kinase inhibitors(EGFR-TKIs) and benefited from osimertinib significantly. A 63-year-old Chinese man was diagnosed with stage IV(cT2 N2 M1 b) LSCC harboring an EGFR exon 19-deletion mutation.Following disease progression after gefitinib and multi-line chemotherapy, rebiopsy was conducted. Molecular testing of EGFR by amplification refractory mutation system-polymerase chain reaction detected the exon 19-deletion without T790 M mutation. Therefore, the patient was given erlotinib, but progression developed only 3 mo later. Then the frozen re-biopsy tissue wastested by next-generation sequencing(NGS), which detected an EGFR T790 M mutation. However, he was very weak with symptoms of dysphagia and cachexia. Fortunately, osimertinib was started, leading to alleviation from the symptoms. Four months later, normal deglutition was restored and partial response was achieved. Finally, the patient achieved an overall survival time period of 29 mo.CONCLUSION Our findings highlight that EGFR T790 M mutation may also be an important acquired drug resistance mechanism for LSCC and offer direct evidence of the efficacy of osimertinib in LSCC with T790 M mutation. NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790 M detection.
BACKGROUND Lung squamous cell cancer(LSCC) rarely harbors epidermal growth factor receptor(EGFR) mutations, even much rarer for acquired T790 M mutation.Although clinical trials of AURA series illustrated that non-small cell lung cancer(NSCLC) with EGFR T790 M mutation can benefit from osimertinib, only five LSCC patients were enrolled in total; moreover, the efficacy for LSCC was not shown in the results. Therefore, the response of LSCC to osimertinib is still unclear to date.CASE SUMMARY We report an LSCC case with T790 M-related acquired resistance after treatments with first-generation EGFR-tyrosine kinase inhibitors(EGFR-TKIs) and benefited from osimertinib significantly. A 63-year-old Chinese man was diagnosed with stage IV(cT2 N2 M1 b) LSCC harboring an EGFR exon 19-deletion mutation.Following disease progression after gefitinib and multi-line chemotherapy, rebiopsy was conducted. Molecular testing of EGFR by amplification refractory mutation system-polymerase chain reaction detected the exon 19-deletion without T790 M mutation. Therefore, the patient was given erlotinib, but progression developed only 3 mo later. Then the frozen re-biopsy tissue wastested by next-generation sequencing(NGS), which detected an EGFR T790 M mutation. However, he was very weak with symptoms of dysphagia and cachexia. Fortunately, osimertinib was started, leading to alleviation from the symptoms. Four months later, normal deglutition was restored and partial response was achieved. Finally, the patient achieved an overall survival time period of 29 mo.CONCLUSION Our findings highlight that EGFR T790 M mutation may also be an important acquired drug resistance mechanism for LSCC and offer direct evidence of the efficacy of osimertinib in LSCC with T790 M mutation. NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790 M detection.
BACKGROUND Lung squamous cell cancer(LSCC) rarely harbors epidermal growth factor receptor(EGFR) mutations, even much rarer for acquired T790 M mutation.Although clinical trials of AURA series illustrated that non-small cell lung cancer(NSCLC) with EGFR T790 M mutation can benefit from osimertinib, only five LSCC patients were enrolled in total; moreover, the efficacy for LSCC was not shown in the results. Therefore, the response of LSCC to osimertinib is still unclear to date.CASE SUMMARY We report an LSCC case with T790 M-related acquired resistance after treatments with first-generation EGFR-tyrosine kinase inhibitors(EGFR-TKIs) and benefited from osimertinib significantly. A 63-year-old Chinese man was diagnosed with stage IV(cT2 N2 M1 b) LSCC harboring an EGFR exon 19-deletion mutation.Following disease progression after gefitinib and multi-line chemotherapy, rebiopsy was conducted. Molecular testing of EGFR by amplification refractory mutation system-polymerase chain reaction detected the exon 19-deletion without T790 M mutation. Therefore, the patient was given erlotinib, but progression developed only 3 mo later. Then the frozen re-biopsy tissue wastested by next-generation sequencing(NGS), which detected an EGFR T790 M mutation. However, he was very weak with symptoms of dysphagia and cachexia. Fortunately, osimertinib was started, leading to alleviation from the symptoms. Four months later, normal deglutition was restored and partial response was achieved. Finally, the patient achieved an overall survival time period of 29 mo.CONCLUSION Our findings highlight that EGFR T790 M mutation may also be an important acquired drug resistance mechanism for LSCC and offer direct evidence of the efficacy of osimertinib in LSCC with T790 M mutation. NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790 M detection.
引文
1 Gandara DR,Hammerman PS,Sos ML,Lara PN,Hirsch FR.Squamous cell lung cancer:from tumor genomics to cancer therapeutics.Clin Cancer Res 2015;21:2236-2243[PMID:25979930 DOI:10.1158/1078-0432.CCR-14-3039]
2 Pao W,Girard N.New driver mutations in non-small-cell lung cancer.Lancet Oncol 2011;12:175-180[PMID:21277552 DOI:10.1016/S1470-2045(10)70087-5]
3 Tang Y,Wang WY,Zheng K,Jiang L,Zou Y,Su XY,Chen J,Zhang WY,Liu WP.EGFR mutations in non-small cell lung cancer:an audit from West China Hospital.Expert Rev Mol Diagn 2016;16:915-919[PMID:27348572 DOI:10.1080/14737159.2016.1199961]
4 Yu HA,Arcila ME,Rekhtman N,Sima CS,Zakowski MF,Pao W,Kris MG,Miller VA,Ladanyi M,Riely GJ.Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155patients with EGFR-mutant lung cancers.Clin Cancer Res 2013;19:2240-2247[PMID:23470965 DOI:10.1158/1078-0432.CCR-12-2246]
5 Liu Y,Zhang Y,Zhang L,Liu B,Wang Y,Zhou X,Li Y,Zhao Q,Gong Y,Zhou L,Zhu J,Ding Z,Wang J,Peng F,Huang M,Li L,Ren L,Lu Y.Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for lung squamous carcinomas harboring EGFR mutation:A multicenter study and pooled analysis of published reports.Oncotarget 2017;8:49680-49688[PMID:28591695 DOI:10.18632/oncotarget.17915]
6 Cross DA,Ashton SE,Ghiorghiu S,Eberlein C,Nebhan CA,Spitzler PJ,Orme JP,Finlay MR,Ward RA,Mellor MJ,Hughes G,Rahi A,Jacobs VN,Red Brewer M,Ichihara E,Sun J,Jin H,Ballard P,AlKadhimi K,Rowlinson R,Klinowska T,Richmond GH,Cantarini M,Kim DW,Ranson MR,Pao W.AZD9291,an irreversible EGFR TKI,overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.Cancer Discov 2014;4:1046-1061[PMID:24893891 DOI:10.1158/2159-8290.CD-14-0337]
7 Rosell R,Carcereny E,Gervais R,Vergnenegre A,Massuti B,Felip E,Palmero R,Garcia-Gomez R,Pallares C,Sanchez JM,Porta R,Cobo M,Garrido P,Longo F,Moran T,Insa A,De Marinis F,Corre R,Bover I,Illiano A,Dansin E,de Castro J,Milella M,Reguart N,Altavilla G,Jimenez U,Provencio M,Moreno MA,Terrasa J,Mu?oz-Langa J,Valdivia J,Isla D,Domine M,Molinier O,Mazieres J,Baize N,Garcia-Campelo R,Robinet G,Rodriguez-Abreu D,Lopez-Vivanco G,Gebbia V,Ferrera-Delgado L,Bombaron P,Bernabe R,Bearz A,Artal A,Cortesi E,Rolfo C,Sanchez-Ronco M,Drozdowskyj A,Queralt C,de Aguirre I,Ramirez JL,Sanchez JJ,Molina MA,Taron M,Paz-Ares L;Spanish Lung Cancer Group in collaboration with Groupe Fran?ais de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica.Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer(EURTAC):a multicentre,open-label,randomised phase 3 trial.Lancet Oncol 2012;13:239-246[PMID:22285168 DOI:10.1016/S1470-2045(11)70393-X]
8 Mok TS,Wu YL,Thongprasert S,Yang CH,Chu DT,Saijo N,Sunpaweravong P,Han B,Margono B,Ichinose Y,Nishiwaki Y,Ohe Y,Yang JJ,Chewaskulyong B,Jiang H,Duffield EL,Watkins CL,Armour AA,Fukuoka M.Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.N Engl J Med 2009;361:947-957[PMID:19692680 DOI:10.1056/NEJMoa0810699]
9 Zhou C,Wu YL,Chen G,Feng J,Liu XQ,Wang C,Zhang S,Wang J,Zhou S,Ren S,Lu S,Zhang L,Hu C,Hu C,Luo Y,Chen L,Ye M,Huang J,Zhi X,Zhang Y,Xiu Q,Ma J,Zhang L,You C.Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer(OPTIMAL,CTONG-0802):a multicentre,open-label,randomised,phase 3 study.Lancet Oncol 2011;12:735-742[PMID:21783417 DOI:10.1016/S1470-2045(11)70184-X]
10 Goss G,Tsai CM,Shepherd FA,Bazhenova L,Lee JS,Chang GC,Crino L,Satouchi M,Chu Q,Hida T,Han JY,Juan O,Dunphy F,Nishio M,Kang JH,Majem M,Mann H,Cantarini M,Ghiorghiu S,Mitsudomi T.Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer(AURA2):a multicentre,open-label,single-arm,phase 2 study.Lancet Oncol 2016;17:1643-1652[PMID:27751847 DOI:10.1016/S1470-2045(16)30508-3]
11 J?nne PA,Yang JC,Kim DW,Planchard D,Ohe Y,Ramalingam SS,Ahn MJ,Kim SW,Su WC,Horn L,Haggstrom D,Felip E,Kim JH,Frewer P,Cantarini M,Brown KH,Dickinson PA,Ghiorghiu S,Ranson M.AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.N Engl J Med 2015;372:1689-1699[PMID:25923549 DOI:10.1056/NEJMoa1411817]
12 Mok TS,Wu Y-L,Ahn M-J,Garassino MC,Kim HR,Ramalingam SS,Shepherd FA,He Y,Akamatsu H,Theelen WS,Lee CK,Sebastian M,Templeton A,Mann H,Marotti M,Ghiorghiu S,Papadimitrakopoulou VA;AURA3 Investigators.Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.N Engl J Med 2017;376:629-640[PMID:27959700 DOI:10.1056/NEJMoa1612674]
13 Masago K,Fujita S,Muraki M,Hata A,Okuda C,Otsuka K,Kaji R,Takeshita J,Kato R,Katakami N,Hirata Y.Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations.BMC Cancer 2015;15:908[PMID:26572169 DOI:10.1186/s12885-015-1925-2]
14 Bugano DDG,Kalhor N,Zhang J,Neskey M,William WN.Squamous-cell transformation in a patient with lung adenocarcinoma receiving erlotinib:Co-occurrence with T790M mutation.Cancer Treat Commun 2015;4:34-36[DOI:10.1016/j.ctrc.2015.03.007]
15 Ding X,Wang L,Liu X,Sun X,Yu J,Meng X.Genetic characterization drives personalized therapy for early-stage non-small-cell lung cancer(NSCLC)patients and survivors with metachronous second primary tumor(MST):A case report.Medicine(Baltimore)2017;96:e6221[PMID:28272214 DOI:10.1097/MD.0000000000006221]
16 Graziano P,de Marinis F,Gori B,Gasbarra R,Migliorino R,De Santis S,Pelosi G,Leone A.EGFR-Driven Behavior and Intrapatient T790M Mutation Heterogeneity of Non-Small-Cell Carcinoma With Squamous Histology.J Clin Oncol 2015;33:e115-e118[PMID:24752053 DOI:10.1200/JCO.2013.49.5697]
17 Jukna A,Montanari G,Mengoli MC,Cavazza A,Covi M,Barbieri F,Bertolini F,Rossi G.Squamous Cell Carcinoma"Transformation"Concurrent with Secondary T790M Mutation in Resistant EGFR-Mutated Adenocarcinomas.J Thorac Oncol 2016;11:e49-e51[PMID:26746366 DOI:10.1016/j.jtho.2015.12.096]
18 Lai Y,Zhang Z,Li J,Sun D,Zhou Y,Jiang T,Han Y,Huang L,Zhu Y,Li X,Yan X.EGFR mutations in surgically resected fresh specimens from 697 consecutive Chinese patients with non-small cell lung cancer and their relationships with clinical features.Int J Mol Sci 2013;14:24549-24559[PMID:24351833 DOI:10.3390/ijms141224549]
19 Oh JE,An CH,Yoo NJ,Lee SH.Detection of low-level EGFR T790M mutation in lung cancer tissues.APMIS 2011;119:403-411[PMID:21635547 DOI:10.1111/j.1600-0463.2011.02738.x]
20 Haratani K,Hayashi H,Watanabe S,Kaneda H,Yoshida T,Takeda M,Shimizu T,Nakagawa K.Two cases of EGFR mutation-positive lung adenocarcinoma that transformed into squamous cell carcinoma:successful treatment of one case with rociletinib.Ann Oncol 2016;27:200-202[PMID:26483048 DOI:10.1093/annonc/mdv495]
21 Sequist LV,Soria JC,Camidge DR.Update to Rociletinib Data with the RECIST Confirmed Response Rate.N Engl J Med 2016;374:2296-2297[PMID:27195670 DOI:10.1056/NEJMc1602688]
22 Paik PK,Varghese AM,Sima CS,Moreira AL,Ladanyi M,Kris MG,Rekhtman N.Response to erlotinib in patients with EGFR mutant advanced non-small cell lung cancers with a squamous or squamous-like component.Mol Cancer Ther 2012;11:2535-2540[PMID:22896669 DOI:10.1158/1535-7163.MCT-12-0163]
23 Sorber L,Zwaenepoel K,Deschoolmeester V,Van Schil PE,Van Meerbeeck J,Lardon F,Rolfo C,Pauwels P.Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients.Lung Cancer 2017;107:100-107[PMID:27180141 DOI:10.1016/j.lungcan.2016.04.026]
24 Tuononen K,M?ki-Nevala S,Sarhadi VK,Wirtanen A,R?nty M,Salmenkivi K,Andrews JM,TelarantaKeerie AI,Hannula S,Lagstr?m S,Ellonen P,Knuuttila A,Knuutila S.Comparison of targeted nextgeneration sequencing(NGS)and real-time PCR in the detection of EGFR,KRAS,and BRAF mutations on formalin-fixed,paraffin-embedded tumor material of non-small cell lung carcinoma-superiority of NGS.Genes Chromosomes Cancer 2013;52:503-511[PMID:23362162 DOI:10.1002/gcc.22047]
2 Pao W,Girard N.New driver mutations in non-small-cell lung cancer.Lancet Oncol 2011;12:175-180[PMID:21277552 DOI:10.1016/S1470-2045(10)70087-5]
3 Tang Y,Wang WY,Zheng K,Jiang L,Zou Y,Su XY,Chen J,Zhang WY,Liu WP.EGFR mutations in non-small cell lung cancer:an audit from West China Hospital.Expert Rev Mol Diagn 2016;16:915-919[PMID:27348572 DOI:10.1080/14737159.2016.1199961]
4 Yu HA,Arcila ME,Rekhtman N,Sima CS,Zakowski MF,Pao W,Kris MG,Miller VA,Ladanyi M,Riely GJ.Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155patients with EGFR-mutant lung cancers.Clin Cancer Res 2013;19:2240-2247[PMID:23470965 DOI:10.1158/1078-0432.CCR-12-2246]
5 Liu Y,Zhang Y,Zhang L,Liu B,Wang Y,Zhou X,Li Y,Zhao Q,Gong Y,Zhou L,Zhu J,Ding Z,Wang J,Peng F,Huang M,Li L,Ren L,Lu Y.Efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors for lung squamous carcinomas harboring EGFR mutation:A multicenter study and pooled analysis of published reports.Oncotarget 2017;8:49680-49688[PMID:28591695 DOI:10.18632/oncotarget.17915]
6 Cross DA,Ashton SE,Ghiorghiu S,Eberlein C,Nebhan CA,Spitzler PJ,Orme JP,Finlay MR,Ward RA,Mellor MJ,Hughes G,Rahi A,Jacobs VN,Red Brewer M,Ichihara E,Sun J,Jin H,Ballard P,AlKadhimi K,Rowlinson R,Klinowska T,Richmond GH,Cantarini M,Kim DW,Ranson MR,Pao W.AZD9291,an irreversible EGFR TKI,overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.Cancer Discov 2014;4:1046-1061[PMID:24893891 DOI:10.1158/2159-8290.CD-14-0337]
7 Rosell R,Carcereny E,Gervais R,Vergnenegre A,Massuti B,Felip E,Palmero R,Garcia-Gomez R,Pallares C,Sanchez JM,Porta R,Cobo M,Garrido P,Longo F,Moran T,Insa A,De Marinis F,Corre R,Bover I,Illiano A,Dansin E,de Castro J,Milella M,Reguart N,Altavilla G,Jimenez U,Provencio M,Moreno MA,Terrasa J,Mu?oz-Langa J,Valdivia J,Isla D,Domine M,Molinier O,Mazieres J,Baize N,Garcia-Campelo R,Robinet G,Rodriguez-Abreu D,Lopez-Vivanco G,Gebbia V,Ferrera-Delgado L,Bombaron P,Bernabe R,Bearz A,Artal A,Cortesi E,Rolfo C,Sanchez-Ronco M,Drozdowskyj A,Queralt C,de Aguirre I,Ramirez JL,Sanchez JJ,Molina MA,Taron M,Paz-Ares L;Spanish Lung Cancer Group in collaboration with Groupe Fran?ais de Pneumo-Cancérologie and Associazione Italiana Oncologia Toracica.Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer(EURTAC):a multicentre,open-label,randomised phase 3 trial.Lancet Oncol 2012;13:239-246[PMID:22285168 DOI:10.1016/S1470-2045(11)70393-X]
8 Mok TS,Wu YL,Thongprasert S,Yang CH,Chu DT,Saijo N,Sunpaweravong P,Han B,Margono B,Ichinose Y,Nishiwaki Y,Ohe Y,Yang JJ,Chewaskulyong B,Jiang H,Duffield EL,Watkins CL,Armour AA,Fukuoka M.Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.N Engl J Med 2009;361:947-957[PMID:19692680 DOI:10.1056/NEJMoa0810699]
9 Zhou C,Wu YL,Chen G,Feng J,Liu XQ,Wang C,Zhang S,Wang J,Zhou S,Ren S,Lu S,Zhang L,Hu C,Hu C,Luo Y,Chen L,Ye M,Huang J,Zhi X,Zhang Y,Xiu Q,Ma J,Zhang L,You C.Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer(OPTIMAL,CTONG-0802):a multicentre,open-label,randomised,phase 3 study.Lancet Oncol 2011;12:735-742[PMID:21783417 DOI:10.1016/S1470-2045(11)70184-X]
10 Goss G,Tsai CM,Shepherd FA,Bazhenova L,Lee JS,Chang GC,Crino L,Satouchi M,Chu Q,Hida T,Han JY,Juan O,Dunphy F,Nishio M,Kang JH,Majem M,Mann H,Cantarini M,Ghiorghiu S,Mitsudomi T.Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer(AURA2):a multicentre,open-label,single-arm,phase 2 study.Lancet Oncol 2016;17:1643-1652[PMID:27751847 DOI:10.1016/S1470-2045(16)30508-3]
11 J?nne PA,Yang JC,Kim DW,Planchard D,Ohe Y,Ramalingam SS,Ahn MJ,Kim SW,Su WC,Horn L,Haggstrom D,Felip E,Kim JH,Frewer P,Cantarini M,Brown KH,Dickinson PA,Ghiorghiu S,Ranson M.AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.N Engl J Med 2015;372:1689-1699[PMID:25923549 DOI:10.1056/NEJMoa1411817]
12 Mok TS,Wu Y-L,Ahn M-J,Garassino MC,Kim HR,Ramalingam SS,Shepherd FA,He Y,Akamatsu H,Theelen WS,Lee CK,Sebastian M,Templeton A,Mann H,Marotti M,Ghiorghiu S,Papadimitrakopoulou VA;AURA3 Investigators.Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.N Engl J Med 2017;376:629-640[PMID:27959700 DOI:10.1056/NEJMoa1612674]
13 Masago K,Fujita S,Muraki M,Hata A,Okuda C,Otsuka K,Kaji R,Takeshita J,Kato R,Katakami N,Hirata Y.Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations.BMC Cancer 2015;15:908[PMID:26572169 DOI:10.1186/s12885-015-1925-2]
14 Bugano DDG,Kalhor N,Zhang J,Neskey M,William WN.Squamous-cell transformation in a patient with lung adenocarcinoma receiving erlotinib:Co-occurrence with T790M mutation.Cancer Treat Commun 2015;4:34-36[DOI:10.1016/j.ctrc.2015.03.007]
15 Ding X,Wang L,Liu X,Sun X,Yu J,Meng X.Genetic characterization drives personalized therapy for early-stage non-small-cell lung cancer(NSCLC)patients and survivors with metachronous second primary tumor(MST):A case report.Medicine(Baltimore)2017;96:e6221[PMID:28272214 DOI:10.1097/MD.0000000000006221]
16 Graziano P,de Marinis F,Gori B,Gasbarra R,Migliorino R,De Santis S,Pelosi G,Leone A.EGFR-Driven Behavior and Intrapatient T790M Mutation Heterogeneity of Non-Small-Cell Carcinoma With Squamous Histology.J Clin Oncol 2015;33:e115-e118[PMID:24752053 DOI:10.1200/JCO.2013.49.5697]
17 Jukna A,Montanari G,Mengoli MC,Cavazza A,Covi M,Barbieri F,Bertolini F,Rossi G.Squamous Cell Carcinoma"Transformation"Concurrent with Secondary T790M Mutation in Resistant EGFR-Mutated Adenocarcinomas.J Thorac Oncol 2016;11:e49-e51[PMID:26746366 DOI:10.1016/j.jtho.2015.12.096]
18 Lai Y,Zhang Z,Li J,Sun D,Zhou Y,Jiang T,Han Y,Huang L,Zhu Y,Li X,Yan X.EGFR mutations in surgically resected fresh specimens from 697 consecutive Chinese patients with non-small cell lung cancer and their relationships with clinical features.Int J Mol Sci 2013;14:24549-24559[PMID:24351833 DOI:10.3390/ijms141224549]
19 Oh JE,An CH,Yoo NJ,Lee SH.Detection of low-level EGFR T790M mutation in lung cancer tissues.APMIS 2011;119:403-411[PMID:21635547 DOI:10.1111/j.1600-0463.2011.02738.x]
20 Haratani K,Hayashi H,Watanabe S,Kaneda H,Yoshida T,Takeda M,Shimizu T,Nakagawa K.Two cases of EGFR mutation-positive lung adenocarcinoma that transformed into squamous cell carcinoma:successful treatment of one case with rociletinib.Ann Oncol 2016;27:200-202[PMID:26483048 DOI:10.1093/annonc/mdv495]
21 Sequist LV,Soria JC,Camidge DR.Update to Rociletinib Data with the RECIST Confirmed Response Rate.N Engl J Med 2016;374:2296-2297[PMID:27195670 DOI:10.1056/NEJMc1602688]
22 Paik PK,Varghese AM,Sima CS,Moreira AL,Ladanyi M,Kris MG,Rekhtman N.Response to erlotinib in patients with EGFR mutant advanced non-small cell lung cancers with a squamous or squamous-like component.Mol Cancer Ther 2012;11:2535-2540[PMID:22896669 DOI:10.1158/1535-7163.MCT-12-0163]
23 Sorber L,Zwaenepoel K,Deschoolmeester V,Van Schil PE,Van Meerbeeck J,Lardon F,Rolfo C,Pauwels P.Circulating cell-free nucleic acids and platelets as a liquid biopsy in the provision of personalized therapy for lung cancer patients.Lung Cancer 2017;107:100-107[PMID:27180141 DOI:10.1016/j.lungcan.2016.04.026]
24 Tuononen K,M?ki-Nevala S,Sarhadi VK,Wirtanen A,R?nty M,Salmenkivi K,Andrews JM,TelarantaKeerie AI,Hannula S,Lagstr?m S,Ellonen P,Knuuttila A,Knuutila S.Comparison of targeted nextgeneration sequencing(NGS)and real-time PCR in the detection of EGFR,KRAS,and BRAF mutations on formalin-fixed,paraffin-embedded tumor material of non-small cell lung carcinoma-superiority of NGS.Genes Chromosomes Cancer 2013;52:503-511[PMID:23362162 DOI:10.1002/gcc.22047]