Identification of molecular subgroups has revolutionized the treatment of metastatic adenocarcinoma lung.Practice in India is to test for EGFR hotspot mutations by PCR, ALK by IHC and ROS1 by FISH (conventional testing).Tissue NGS (next generation sequencing) testing is increasing; but availability of adequate tissue is a problem.Aim of our study was to evaluate the added benefit of blood NGS testing in patients who were negative by conventional molecular testing.
This was a retrospective analysis of patients with metastatic lung cancer, who presented at Manipal hospital, Bangalore, Jan 2019 and May 2020.
108 patients, 35-75 years, were analyzed. 78 (72%) men, 30(28%) women. 87 (80.6%) had adeno and 21 (19.4%) had squamous cell carcinoma. All adenocarcinoma patients were tested on tumor tissue for EGFR hotspot mutations by PCR, ALK by IHC and ROS1 by FISH. Molecular alterations by conventional testing were found in 34 (39%) patients and 53(61%) were negative. Out of these 34, 29 (33%) had EGFR, 3 (3.1%) had ALK and 2 (2.4%) had ROS1 alterations. We further evaluated the conventionally tested negative patients to blood NGS testing (liquid biopsy). Only 20 (37%) out of the 53 conventionally tested negative patients were subjected to blood NGS testing due to logistic reasons. We found 14 (70%) out of 20 had detectable mutation on blood NGS. Out of the 14, we picked up 6(42%) EGFR (3 common, 3 uncommon), 1 (7 %) ALK, 1 (7 %) ROS1, 1 (7 %) MET exon 14 skip, 2 ( 14%) HER 2 and 3 (21 %) RAS mutations (G12C). We treated 10(50%) out of 20 subjects: 5 EGFR mutation patients with geftinib/afatinib/ osimertinib, 1 ALK with crizotinib, 1 ROS with crizotinib, 1 MET with Capmatinib, and 2 HER2 with Afatinib.
Findings of our study proves patients who are negative by conventional testing should be further evaluated with blood NGS testing. In our study, inspite of limited testing, we were able to detect additional 14 patients with driver mutations by doing blood NGS testing, thus increasing our mutation detection from 39% to 55%.Advantage of blood NGS testing is ease of sample collection, faster turnaround time, that it is able to overcome the common problem of inadequate tissue in lung cancer.
The authors.
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All authors have declared no conflicts of interest.