Table 1.
EGFR mutation status in primary tumors and corresponding metastases.
| Author | Country | pathology | BM type | Detection methods | EGFR mutation rate of paired tissue | Concordance of paired tissue | EGFR mutation rate of BMs | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| primary | metastasis | all patients | mutated patients | total | 19del | L858R | |||||||
| Europe and America | |||||||||||||
| A Kalikaki, 2008 (32) | Greece | ADC, SCC, LCC | NA | direct sequencing | 5/25 | Metastases: 3/25 | 19/25 (76.0%) | 1/7 (14.3%) | 3/25 (12.0%) | 1/25 (4.0%) | 0/25 (0%) | ||
| Delicia Munfus-McCray, 2011 (33) | USA | ADC | NA | Bidirectional sequencing | 3/9 | Metastases: 2/9 | 8/9 (88.9%) | 2/3 (66.7%) | 4/10 (40%) | NA | NA | ||
| Claire Villalva, 2013 (34) | France | ADC, SCC, LCC | SC | pyrosequencing | 3/8 | Brain: 3/8 | 8/8 (100%) | 3/3 (100%) | 3/77 (3.9%) | 0/77 (0.0%) | 3/77 (3.9%) | ||
| Wojas-Krawczyk Kamila, 2013 (35) | Poland | ADC, SCC, LCC, others | NA | PNA–LNA PCR clamp assays | NA | NA | NA | NA | 9/143 (6.3%) | 3/143 (2.1%%) | 6/143 (4.2%) | ||
| Marcin Nicos, 2018 (36) | Poland | ADC, SCC, LCC, others | SC | direct sequencing | 7/30 | Brain: 7/30 | 30/30 (100%) | 7/7 (100%) | 9/145 (6.2%) | NA | NA | ||
| Combined results (results of BMs) |
38/38 (100%) | 10/10 (100%) | 24/390 (6.2%) | 4/245 (1.6%) | 9/245 (3.7%) | ||||||||
| Asia | |||||||||||||
| Shingo Matsumoto, 2006 (37) | Japan | ADC | NA | direct sequencing | 6/8 | Brain: 6/8 | 8/8 (100%) | 6/6 (100%) | 12/19 (63.2%) | 10/19 (52.6%) | 2/19 (10.5%) | ||
| C.-H. Gow, 2009 (30) * | Taiwan | ADC, SCC, LCC, LLC | NA | direct sequencing, SARMS | 5/25, 11/25 | Brain: 11/25, 11/25 | 17/25 (68.0%), 22/25 (88.0%) | 4/12(33.3%), 10/12 (83.3%) | 11/25 (44.0%) | 7/25 (28.0%) | 4/25 (16.0%) | ||
| Hye-Suk Han, 2011 (31) | Korea | ADC | SC | direct sequencing | 4/5 | Brain: 3/5 | 4/5 (80%) | 3/4 (75%.0) | 3/5 (60.0%) | 1/5 (20.0%) | 2/5 (40.0%) | ||
| Dongdong Luo, 2014 (38) ** | China | ADC, ASCC, SCC, LCC | NA | SARMS | 7/15 | Brian: 8/15 | 14/15 93.3%) | 7/8 (87.5%) | 72/136 (52.9%) | 44/136 (32.4%) | 32/136 (23.5%) | ||
| Kun-Ming Rau, 2016 (39) ** | Taiwan | ADC | SC+MC | SARMS | 30/49 | Brain: 30/49 | 36/49 (73.5%) | 21/34 (61.8%) | 30/49 (61.2%) | 17/49 (34.7%) | 15/49 (30.6%) | ||
| Yun Fan, 2018 (40) | China | ADC | SC+MC | NGS | selected 19del or L858R in primary tumor or CSF. | NA | 10/11 (90.9%) | NA | NA | NA | |||
| Li Liao, 2018 (41) | China | ADC | SC | NGS | 4/6 | Brain: 4/6 | 6/6 (100%) | 4/4 (100%) | 4/6 (66.7%) | 3/6 (50.0%) | 1/6 (16.7%) | ||
| Yangchun Ma, 2018 (42) | China | ADC | NA | NGS | NA | NA | NA | NA | 6/15 (40.0%) | 2/15 (13.3%) | 4/15 (26.7%) | ||
| Hongsheng Wang, 2019 (43) | China | ADC, SCC, others | SC+MC | NGS | 24/54 | Brain: 25/54 | 50/54 (92.6%) | 23/27 (85.2%) | 26/61 (42.6%) | 15/61 (24.6%) | 7/61 (11.5%) | ||
| Ruofan Huang, 2019 (44) | China | ADC | NA | ddPCR | 22/34 | CSF: 15/34 | 25/34 (73.5%) | 14/23 (60.9%) | NA | NA | NA | ||
| Kyung-Min Kim, 2019 (45) | Korea | NA | NA | real-time PCR clamping method | 8/18 | Brain: 8/18 | 14/18 (83.8%) | 5/9 (66.7%) | 8/18 (44.4%) | 5/18 (27.8%) | 3/18 (16.7%) | ||
| Combined results | 154/180 (85.6%) | 79/104 (76.0%) | 172/334 (51.5%) | 104/334 (31.1%) | 70/334 (21.0%) | ||||||||
*The former data is based on the result only by direct sequencing, and the later by both direct sequnecing and SARMS assay.
** Both 19del and L858R subtype cohorts counts if the patients have double mutation 19del & L858R.
ADC, Adenocarcinoma; SCC, squamous cell carcinoma; LCC, large cell carcinoma; LLC, Lymphoepithelioma-like carcinoma; ASCC, Adenosquamous cell carcinoma; BM, brain metastasis; CSF, cerebrospinal fluid; NA, not available; SC, synchronous, MC, metachronous; PNA–LNA, peptide nucleic acid-locked nucleic acid; SARMS, Scorpion Amplified Refractory Mutation System; NGS, next-generation sequencing; ddPCR, droplet digital polymerase chain reaction (PCR).
“SC+MC” means the BMs developed from diagnosis of NSCLC to the death.