Table 3.
ctDNA and CTCs changes in cases of SCLC transformation of EGFR mutated or ALK-rearranged NSCLC. ABS: abstract; NA: data not available. PD: progressive disease. tSCLC: transformed SCLC.
| REF. | N. | Assay | Results |
|---|---|---|---|
| ctDNA | |||
| Vendrell 2020 [71] |
3 | ddPCR and NGS | In 2 patients, elevation of AF in ctDNA of EGFRdel19 (from 6% to 17%) and TP53
M246K (from 6% to 24%), and of EGFRL858R (from 4% to 6%) and TP53
L194R (from 3% to 6%), respectively, concurrent with evidence of tSCLC. Not available AF at the moment of transformation for the third patient. In all patients, the levels of the EGFR mutations in terms of copies/mL of plasma raised with SCLC progression. |
| Schmid 2020 [69] |
1 | NGS (Geneseeq Prime 425-gene) |
Elevation of AF in ctDNA of EGFRdel19 (from 0% to 23%), T790M (from 2% to 18%), RB1Q850X (from 0% to 5%), and TP53M237I (from 0% to 4%) concurrent with evidence of t SCLC. Subsequently, a reduction in AFs of these mutations was achieved with cisplatin-etoposide+RT. |
| Pizzutilo 2019 [64] |
1 | ddPCR (EGFR) | Elevation of AF in ctDNA of EGFRdel19 (from 25% to 60%) with reduction in T790M/del19 Ratio (from 0.24 to 0.02) and detection of C797S concurrent with evidence of tSCLC. |
| Minari 2018 [66] |
2 | ddPCR (EGFR) | Elevation of AF in ctDNA of EGFRdel19 (from 10% to 22%) and of EGFRL858R (from 20% to 81%), respectively, concurrent with evidence of tSCLC in 2 patients. |
| Iijima 2018 [67] |
1 | NGS (43 genes) | Elevation of AF in ctDNA of EGFRdel19 (from 12% to 72%) and TP53F134fs (similar AF) concurrent with evidence of tSCLC. Subsequent carboplatin-etoposide treatment led to a drop in AFs. |
| Tsui 2018 [70] |
3 | Targeted NGS and WGS | 2/3 retained EGFR activating mutation after transformation in ctDNA and tissue, 0/3 presented T790M. Elevation in AFs of EGFR concurrent with evidence of PD of SCLC. TP53 mutation was present before transformation and increased in 3/3 patients with PD of SCLC, together with the emergence of CNAs of genes such as MYCL1, SOX2, SOX4, and EGFR. |
| Nishioka 2018 [73] |
1 | NA | Evidence of EGFR T790M mutation in ctDNA after treatment for tSCLC, leading to successful therapy with osimertinib. |
| Mooradian 2017 [68] |
1 | NGS (Guardant360) |
Elevation of AF in ctDNA of EGFRdel19 (from 11% to 46%), TP53V173L (from 11% to 55%), PIK3CAE726K (from 3% to 51%), and PIK3CAE545K (from 3% to 54%), concurrent with evidence of PD of tSCLC. |
| Ou 2017 [74] |
1 | NGS (FoundationACT) |
After PD to 2° line lorlatinib in a patient with ALK rearrangement, ctDNA analysis showed persistence of ALK rearrangement (estimated AF 30–45% vs. 40–54% before lorlatinib) and disappearance of acquired G1202R, concurrent with SCLC transformation. |
| Alì 2016 [77] |
1 | PCR | Evidence of EGFR T790M in ctDNA concurrent with transformed SCLC in tissue biopsy harboring EGFR activating mutation, but not T790M. |
| Piotroska 2015 [65] |
1 | Beaming (EGFR) | Increasing levels of EGFR activating mutation, with T790M levels remaining suppressed, at the time of progression with SCLC transformation. |
| Han 2017 [72] ABS |
11 | NGS | 3/11 patients developed EGFR T790M mutation in the post-transformation ctDNA rather than in their tissue samples. |
| CTC | |||
| Zhu 2020 [76] | 14 | Aptamer-modified PEG-PLGA-nanofiber microfluidic system for CTC capture, and single-cell sequencing |
Histological transformation was reflected by CTC phenotype change from TTF1+, NapsinA+, CK7+, P63- toward CD56+, CgA+, and Syn+, with a significant reduction (p < 0.05) of the mean nuclear size of CTCs. 14/14 patients showed the same molecular characteristics for EGFR, RB1, and TP53 between CTC and tissue samples. |
| Ni 2013 [75] | 1 | CellSearch and Single-Cell Exome Sequencing in CTC |
EGFR del19 was identified in tSCLC biopsy as well as in CTCs. PIK3CA, RB1, and TP53 mutations were identified in tSCLC tissue biopsy and CTCs, with higher abundance than in the original NSCLC tissue. |