Chi-Lu Chiang1,2,3, Cheng-Chia Lee2,4, Hsu-Ching Huang1,2, Chia-Hung Wu2,3,5, Yi-Chen Yeh2,6, Chia-I Shen1,2,3, Yung-Hung Luo1,2,3, Tsu-Hui Shiao1, Han Jhih Chang1, Yu-Ting Huang1, Yuh-Min Chen1,2, Teh-Ying Chou3,6, Chao-Hua Chiu7,8. 1. Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan. 2. School of Medicine, National Yang-Ming University, Taipei, Taiwan. 3. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 4. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan. 5. Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 7. Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan. jhchiou@vghtpe.gov.tw. 8. School of Medicine, National Yang-Ming University, Taipei, Taiwan. jhchiou@vghtpe.gov.tw.
Abstract
BACKGROUND: Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small-cell lung cancer (NSCLC). OBJECTIVE: The aim of this study was to evaluate the utility of cerebrospinal fluid (CSF) as a medium for epidermal growth factor receptor (EGFR) mutation testing in clinical practice. PATIENTS AND METHODS: We prospectively enrolled patients with EGFR-mutant NSCLC who underwent CSF sampling for suspected LM. The supernatant of CSF after routine cytology examination was collected. The diagnosis of LM was established according to EANO-ESMO criteria. CSF and plasma cell-free DNA (cfDNA) were retrieved for EGFR mutation testing. RESULTS: Fifty-one patients with a median age of 62.7 years were enrolled. The median duration from initial diagnosis to CSF sampling was 23.0 months and most patients (94.1%) had received at least one EGFR-tyrosine kinase inhibitor. Adenocarcinoma cells were found in 37 CSF samples (72.5%), and 48 (94.1%) patients had confirmed or probable LM. Thirty-five of these 48 patients (72.9%) had valid EGFR mutation-testing results using CSF cfDNA and tended to have higher white blood cell counts and positive cytology in their CSF compared to those with invalid mutation testing results. The overall detection rate of EGFR mutation in CSF cfDNA was 68.8%, and the T790M detection rate was 14.6%. In 37 patients with paired CSF and plasma samples, the concordance rate of the EGFR mutation results was 29.7%. CONCLUSIONS: For patients with EGFR-mutant NSCLC with LM, CSF supernatant is a valuable source for EGFR mutation testing and may provide important information.
BACKGROUND:Leptomeningeal metastasis (LM) is a fatal complication of advanced non-small-cell lung cancer (NSCLC). OBJECTIVE: The aim of this study was to evaluate the utility of cerebrospinal fluid (CSF) as a medium for epidermal growth factor receptor (EGFR) mutation testing in clinical practice. PATIENTS AND METHODS: We prospectively enrolled patients with EGFR-mutant NSCLC who underwent CSF sampling for suspected LM. The supernatant of CSF after routine cytology examination was collected. The diagnosis of LM was established according to EANO-ESMO criteria. CSF and plasma cell-free DNA (cfDNA) were retrieved for EGFR mutation testing. RESULTS: Fifty-one patients with a median age of 62.7 years were enrolled. The median duration from initial diagnosis to CSF sampling was 23.0 months and most patients (94.1%) had received at least one EGFR-tyrosine kinase inhibitor. Adenocarcinoma cells were found in 37 CSF samples (72.5%), and 48 (94.1%) patients had confirmed or probable LM. Thirty-five of these 48 patients (72.9%) had valid EGFR mutation-testing results using CSF cfDNA and tended to have higher white blood cell counts and positive cytology in their CSF compared to those with invalid mutation testing results. The overall detection rate of EGFR mutation in CSF cfDNA was 68.8%, and the T790M detection rate was 14.6%. In 37 patients with paired CSF and plasma samples, the concordance rate of the EGFR mutation results was 29.7%. CONCLUSIONS: For patients with EGFR-mutant NSCLC with LM, CSF supernatant is a valuable source for EGFR mutation testing and may provide important information.
Authors: Tony Mok; Yi-Long Wu; Jin Soo Lee; Chong-Jen Yu; Virote Sriuranpong; Jennifer Sandoval-Tan; Guia Ladrera; Sumitra Thongprasert; Vichien Srimuninnimit; Meilin Liao; Yunzhong Zhu; Caicun Zhou; Fatima Fuerte; Benjamin Margono; Wei Wen; Julie Tsai; Matt Truman; Barbara Klughammer; David S Shames; Lin Wu Journal: Clin Cancer Res Date: 2015-03-31 Impact factor: 12.531
Authors: Chetan Bettegowda; Mark Sausen; Rebecca J Leary; Isaac Kinde; Yuxuan Wang; Nishant Agrawal; Bjarne R Bartlett; Hao Wang; Brandon Luber; Rhoda M Alani; Emmanuel S Antonarakis; Nilofer S Azad; Alberto Bardelli; Henry Brem; John L Cameron; Clarence C Lee; Leslie A Fecher; Gary L Gallia; Peter Gibbs; Dung Le; Robert L Giuntoli; Michael Goggins; Michael D Hogarty; Matthias Holdhoff; Seung-Mo Hong; Yuchen Jiao; Hartmut H Juhl; Jenny J Kim; Giulia Siravegna; Daniel A Laheru; Calogero Lauricella; Michael Lim; Evan J Lipson; Suely Kazue Nagahashi Marie; George J Netto; Kelly S Oliner; Alessandro Olivi; Louise Olsson; Gregory J Riggins; Andrea Sartore-Bianchi; Kerstin Schmidt; le-Ming Shih; Sueli Mieko Oba-Shinjo; Salvatore Siena; Dan Theodorescu; Jeanne Tie; Timothy T Harkins; Silvio Veronese; Tian-Li Wang; Jon D Weingart; Christopher L Wolfgang; Laura D Wood; Dongmei Xing; Ralph H Hruban; Jian Wu; Peter J Allen; C Max Schmidt; Michael A Choti; Victor E Velculescu; Kenneth W Kinzler; Bert Vogelstein; Nickolas Papadopoulos; Luis A Diaz Journal: Sci Transl Med Date: 2014-02-19 Impact factor: 17.956
Authors: Tony K F Yung; K C Allen Chan; Tony S K Mok; Joanna Tong; Ka-Fai To; Y M Dennis Lo Journal: Clin Cancer Res Date: 2009-03-10 Impact factor: 12.531
Authors: Leticia De Mattos-Arruda; Regina Mayor; Charlotte K Y Ng; Britta Weigelt; Francisco Martínez-Ricarte; Davis Torrejon; Mafalda Oliveira; Alexandra Arias; Carolina Raventos; Jiabin Tang; Elena Guerini-Rocco; Elena Martínez-Sáez; Sergio Lois; Oscar Marín; Xavier de la Cruz; Salvatore Piscuoglio; Russel Towers; Ana Vivancos; Vicente Peg; Santiago Ramon y Cajal; Joan Carles; Jordi Rodon; María González-Cao; Josep Tabernero; Enriqueta Felip; Joan Sahuquillo; Michael F Berger; Javier Cortes; Jorge S Reis-Filho; Joan Seoane Journal: Nat Commun Date: 2015-11-10 Impact factor: 14.919