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Rohith Srivas
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-94 - The Role of Neoadjuvant Chemo-Immunotherapy in Unresectable Non-Small Cell Lung Cancer (Now Available) (ID 2873)
08:00 - 18:00 | Author(s): Rohith Srivas
- Abstract
Background
Current practices and guidelines invoke a limited role for neoadjuvant therapies in NSCLC. These strategies are not considered for use in advanced, unresectable disease. However, the development of immune checkpoint inhibitors has drastically improved the efficacy of systemic treatments for NSCLC.
Method
We describe the case of a patient who was diagnosed with squamous cell carcinoma of the lung.
Result
Imaging demonstrated a 7.9-cm right lower lobe lesion, a 1.8-cm satellite right middle lobe nodule, and ipsilateral mediastinal lymphadenopathy, consistent with stage IIIB disease. The tumor biopsy exhibited 5% PD-L1 positivity in tumor cells. Tissue next generation sequencing (NGS) revealed loss-of-function mutations in RB1, TP53, and EP300, copy number gain in PIK3CA, and tumor mutational burden of 4.3/Mb. Analysis of circulating tumor DNA (ctDNA) demonstrated a highest allele fraction of 4.1% (TP53 mutant clone). As the tumor was deemed unresectable, the patient was started on carboplatin, nab-paclitaxel, and pembrolizumab. Follow-up imaging at 12 weeks after 4 cycles showed partial response, with significant reduction in tumor size and improvement in lymphadenopathy. After tumor board discussion, the decision was made to proceed with surgical resection. A right thoracotomy with bilobectomy was successfully performed. Resected tumor demonstrated major pathologic response with less than 5% viable cancer cells. Whole-genome sequencing of plasma was also carried out on blood collected over the course of treatment. The observable cancer signal shrank to less than 5% of the baseline as early as 25 days after treatment start. Finally, repeat ctDNA analysis 6 weeks after the surgery showed no detectable somatic variants.
Conclusion
Conversion of unresectable tumors in NSCLC may be more feasible with modern treatment regimens. The potential efficacy of neoadjuvant strategies using chemoimmunotherapy warrants further clinical investigation.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-49 - Serial Changes in Whole-Genome Cell-Free DNA (cfDNA) to Identify Disease Progression Prior to Imaging in Advanced NSCLC (ID 2484)
09:45 - 18:00 | Author(s): Rohith Srivas
- Abstract
Background
Response to treatment in advanced lung cancer is usually determined by clinical and imaging assessment. We analyzed longitudinal changes in blood whole-genome cfDNA to investigate whether a molecular response assessment could provide potentially actionable information prior to imaging.
Method
We prospectively enrolled and serially collected blood from 35 patients with advanced non-small cell lung cancer (NSCLC). Baseline blood samples were drawn prior to initiation of a new treatment and at one or two additional time points, after the first cycle (median 21 days) and the second cycle (median 42 days). 4 mL of plasma was separated from peripheral blood collected in Streck tubes. Next, cfDNA was isolated from plasma and used to prepare libraries (15 with bisulfite conversion) for whole-genome sequencing at approximately 20X depth. Based on a patient-specific profile of whole-genome features, changes in the fraction of tumor-derived cfDNA were quantified over the initial course of treatment. Imaging was performed per standard practice with treatment response determined by an independent radiologist according to RECIST guidelines.
Result
Median age of patients was 72 (range 48-87), and 49% were female. 69% of patients were on their first line of therapy (range 1-5). Patients were treated with an immune checkpoint inhibitor +/- chemotherapy (22), chemotherapy alone (11), or targeted therapy (2). Patients with predicted progression by cfDNA (n=4), indicated by an increase in tumor fraction at either post-treatment blood collection, had worse progression-free survival (PFS) compared to patients who did not show an increase (n=31) (hazard ratio 22.3, [95% CI 3.9-127.8], log-rank p=9 x 10-7). For the patients who were predicted to progress, the cfDNA assay preceded clinical evaluation by a median of 34 days. Median PFS was 56 days for patients with predicted progression versus 370 days for others. All patients with predicted progression were later confirmed to progress at the first follow-up evaluation (4/4, 100% positive predictive value). For the remaining patients, 27 of 31 did not progress (87% negative predictive value). Therefore, sensitivity for the assay was 50% and specificity was 100%.
Conclusion
Analyzing tumor-derived cfDNA early in the course of a new therapy holds promise to identify patients with early disease progression across multiple types of treatment. This technology may enable early switching to other potentially effective therapies, increasing the value proposition of all delivered treatment.
