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Ullas Batra
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P02 - Diagnostics and Interventional Pulmonology (ID 110)
- Event: WCLC 2020
- Type: Posters
- Track: Diagnostics and Interventional Pulmonology
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P02.02 - Pulmonary Rebiopsy is ‘Here to Stay’ in Non-Small Cell Lung Carcinoma (NSCLC) Patients with Progression on Tyrosine Kinase Inhibitors (TKIs) (ID 3828)
00:00 - 00:00 | Author(s): Ullas Batra
- Abstract
Introduction
The discovery of biomarker- driven processes in non small cell lung carcinoma (NSCLC) has caused a dramatic shift in the treatment and prognosis of these patients. Liquid biopsy has emerged as a promising tool for dynamic monitoring of EGFR mutation status to assess the response to EGFR TKIs, with the advantage of high sensitivity. However, resistance eventually ensues; the most common being T790M mutation in exon 20 of the EGFR gene. A rare mechanism is small cell transformation which has been reported in 3% cases, which cannot be detected by liquid biopsy tools. Re-biopsy at progression with histopathologic evaluation is the only modality to detect the same.
Methods
This is a retrospective study which included 470 EGFR mutant NSCLC cases between 2015-2019, among whom 260 patients progressed under TKI treatment. Only 78 of these patients were subjected to an image guided re-biopsy.
Results
A total of 78 cases underwent an image guided re-biopsy at progression. The tissue was adequate in 72 (92.3%) patients with regards to diagnostic yield, and the re-biopsy procedure was well tolerated without any major complications. However, clinically insignificant pneumothorax was seen in 8 (10.2%) cases. On histomorphologic evaluation, 7 (8.9%) cases were detected to harbor a small cell transformation of NSCLC.
The median turnaround time for histopathologic evaluation was 72 hours. Among the 78 cases, 41 cases also underwent a simultaneous liquid biopsy for the detection of a T790M mutation, which was positive in 18 cases.
Conclusion
From our experience, it is evident that pulmonary tissue re-biopsy at progression should be considered as an essential tool in order to detect small cell change which is missed by sophisticated liquid biopsy tools. Additionally, this has the advantage of better diagnostic yield, comparable turnaround times when compared to liquid biopsy as well as visualization of the ongoing process.
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P37 - Pathology - Biomarker Testing (ID 107)
- Event: WCLC 2020
- Type: Posters
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P37.06 - Are all ALK Gene Rearrangements Created Equal?? (ID 3715)
00:00 - 00:00 | Presenting Author(s): Ullas Batra
- Abstract
Introduction
The knowledge of biomarker-driven processes involving EGFR, ALK and ROS1 genes, has revolutionised the therapeutic and prognostic landscape of non small cell lung carcinoma (NSCLC). ALK rearranged NSCLC accounts for 10% of these cases, and with the development and approval of ALK TKIs like crizotinib, it becomes important to promptly identify the same. Various modalities like immnohistochemistry (IHC) and fluorescence in situ hybridization (FISH) have been validated for the detection of the same. However, different fusion partners and different breakpoints may lead to fusion-oncoproteins with differential TKI sensitivities. Next generation sequencing (NGS) however has emerged as a promising tool with the advantages of higher sensitivity and throughput,and it can also detect exact chromosomal breakpoints, thus guiding therapeutic decisions.
Methods
134 ALK IHC positive stage IV NSCLC cases were detected. Of these NGS was done on 116 cases using a custom RNA panel comprising 71 ALK variants.
Results
A total of 134 were included based on the defined study end point. The median age was 53 years (range: 23-79 years) with 72 men (53.7%) and 62 (46.3%) women. Owing to depleted tissue blocks, and suboptimal yield of extracted RNA, NGS could not be performed in 24 (19.4%) cases.
Variants were detected in 92 cases, whereas 24 cases were negative on NGS. The most common variant detected was v1 in 41 (35.4%) cases, followed by v3 (24.7%) in 28 cases. There were 17 (15.04%) cases with v2, and two cases with v5a (1.7%). Four rare variants (3.5%) were encountered; three were EML4 variants, and one was a KLC1-ALK fusion.
There were no demographic differences across the variant groups. Among the variants, the median PFS of patients with v1 on crizotinib was 9.97 months as opposed to 11.87 months in v3 variant. The median overall survival in v1 was 33.07 months, whereas the same was not reached in the v3 variant group. The 1-year and 2-year survival rates on crizotinib for v1 were 78.6% and 63% respectively, as compared to 84.6% (both 1 and 2 year survival rates were same) in patients with v3. Patients with v2 variant were found to be prognostically superior to both v1 and v3 variants with a median PFS on crizotinib as 17.7 months, and a 1 year survival rate of 88.9% on crizotinib.Prognostically, the v1 group was found to be inferior with higher occurrence of brain metastases at diagnosis. (p=0.04) when compared to other variant groups. IHC positive and NGS negative cases however did not show any statistically significant differences in clinical features or response outcomes.
Conclusion
This study reports the landscape of ALK variants detected in this study cohort. Variant group V1 was found to have an overall inferior outcome with higher frequency of brain metastases when compared to V3 which is discordant with already published literature. Large scale studies are needed to validate the same in future.
