5 results on '"Cohen, Roger"'
Search Results
2. Association Between Availability of Molecular Genotyping Results and Overall Survival in Patients With Advanced Nonsquamous Non–Small-Cell Lung Cancer.
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Aggarwal, Charu, Marmarelis, Melina E., Hwang, Wei-Ting, Scholes, Dylan G., McWilliams, Tara L., Singh, Aditi P., Sun, Lova, Kosteva, John, Costello, Michael R., Cohen, Roger B., Langer, Corey J., Doucette, Abigail, Gabriel, Peter N., Shulman, Lawrence N., Rendle, Katharine A., Thompson, Jeffrey C., Bekelman, Justin E., and Carpenter, Erica L.
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NON-small-cell lung carcinoma , *OVERALL survival , *ELECTRONIC health records , *REGRESSION analysis , *LOGISTIC regression analysis - Abstract
PURPOSE: Current guidelines recommend molecular genotyping for patients newly diagnosed with metastatic nonsquamous (mNSq) non–small-cell lung cancer (NSCLC). The association between availability of molecular genotyping before first line (1L) therapy and overall survival (OS) is not known. METHODS: We conducted a real-world cohort study using electronic health records in patients newly diagnosed with mNSq NSCLC. Cox proportional-hazards multivariable regression models were constructed to examine the association between OS and test result availability before 1L therapy, adjusting for covariates. Additional analyses were conducted to assess the consistency and strength of the relationship. Multivariable logistic regression models were used to examine the association between concurrent tissue and plasma testing (v tissue alone) and result availability. RESULTS: Three hundred twenty-six patients were included, 80% (261/326) with results available before 1L (available testing group), and 20% (65/326) without results available (unavailable testing group). With 14.2-month median follow-up, patients in the available testing group had significantly longer OS relative to the unavailable testing group (adjusted hazard ratio, 0.43; 95% CI, 0.30 to 0.62; P <.0001). The adjusted odds of availability of results before 1L therapy was higher with concurrent tissue and plasma testing (v tissue testing alone; adjusted odds ratio, 2.06; 95% CI, 1.09 to 3.90; P =.026). CONCLUSION: Among patients with mNSq NSCLC in a real-world cohort, availability of molecular genotyping results before 1L therapy was associated with significantly better OS. Concurrent tissue and plasma testing was associated with a higher odds of availability of results before 1L therapy. These findings warrant renewed attention to the completion of molecular genotyping before 1L therapy. Availability of NGS results before 1L therapy for patients with mNSCLC is associated with better overall survival. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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3. Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy.
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Thompson, Jeffrey C., Carpenter, Erica L., Silva, Benjamin A., Rosenstein, Jamie, Chien, Austin L., Quinn, Katie, Espenschied, Carin R., Mak, Allysia, Kiedrowski, Lesli A., Lefterova, Martina, Nagy, Rebecca J., Katz, Sharyn I., Yee, Stephanie S., Black, Taylor A., Singh, Aditi P., Ciunci, Christine A., Bauml, Joshua M., Cohen, Roger B., Langer, Corey J., and Aggarwal, Charu
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CIRCULATING tumor DNA , *OVERALL survival , *NUCLEOTIDE sequencing , *NON-small-cell lung carcinoma , *PROGRESSION-free survival - Abstract
PURPOSE: Although the majority of patients with metastatic non–small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS: Patients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded. RESULTS: Among 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P <.001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P <.001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95% CI, 0.13 to 0.50) and overall survival (hazard ratio, 0.27; 95% CI, 0.12 to 0.64) compared with molecular nonresponders. CONCLUSION: Molecular response assessment using circulating tumor DNA may serve as a noninvasive, on-therapy predictor of response to pembrolizumab-based therapy in addition to standard of care imaging in mNSCLC. This strategy requires validation in independent prospective studies. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Serial Monitoring of Circulating Tumor DNA by Next-Generation Gene Sequencing as a Biomarker of Response and Survival in Patients With Advanced NSCLC Receiving Pembrolizumab-Based Therapy.
- Author
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Thompson, Jeffrey C., Carpenter, Erica L., Silva, Benjamin A., Rosenstein, Jamie, Chien, Austin L., Quinn, Katie, Espenschied, Carin R., Mak, Allysia, Kiedrowski, Lesli A., Lefterova, Martina, Nagy, Rebecca J., Katz, Sharyn I., Yee, Stephanie S., Black, Taylor A., Singh, Aditi P., Ciunci, Christine A., Bauml, Joshua M., Cohen, Roger B., Langer, Corey J., and Aggarwal, Charu
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CIRCULATING tumor DNA , *NON-small-cell lung carcinoma , *PROGRESSION-free survival , *PATIENTS' attitudes , *BIOMARKERS - Abstract
PURPOSE: Although the majority of patients with metastatic non–small-cell lung cancer (mNSCLC) lacking a detectable targetable mutation will receive pembrolizumab-based therapy in the frontline setting, predicting which patients will experience a durable clinical benefit (DCB) remains challenging. MATERIALS AND METHODS: Patients with mNSCLC receiving pembrolizumab monotherapy or in combination with chemotherapy underwent a 74-gene next-generation sequencing panel on blood samples obtained at baseline and at 9 weeks. The change in circulating tumor DNA levels on-therapy (molecular response) was quantified using a ratio calculation with response defined by a > 50% decrease in mean variant allele fraction. Patient response was assessed using RECIST 1.1; DCB was defined as complete or partial response or stable disease that lasted > 6 months. Progression-free survival and overall survival were recorded. RESULTS: Among 67 patients, 51 (76.1%) had > 1 variant detected at a variant allele fraction > 0.3% and thus were eligible for calculation of molecular response from paired baseline and 9-week samples. Molecular response values were significantly lower in patients with an objective radiologic response (log mean 1.25% v 27.7%, P <.001). Patients achieving a DCB had significantly lower molecular response values compared to patients with no durable benefit (log mean 3.5% v 49.4%, P <.001). Molecular responders had significantly longer progression-free survival (hazard ratio, 0.25; 95% CI, 0.13 to 0.50) and overall survival (hazard ratio, 0.27; 95% CI, 0.12 to 0.64) compared with molecular nonresponders. CONCLUSION: Molecular response assessment using circulating tumor DNA may serve as a noninvasive, on-therapy predictor of response to pembrolizumab-based therapy in addition to standard of care imaging in mNSCLC. This strategy requires validation in independent prospective studies. [ABSTRACT FROM AUTHOR]
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- 2021
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5. Influence of TP53 Mutation on Survival in Patients With Advanced EGFR-Mutant Non–Small-Cell Lung Cancer.
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Aggarwal, Charu, Davis, Christiana W., Mick, Rosemarie, Thompson, Jeffrey C., Jeffries, Seth, Bagley, Stephen, Gabriel, Peter, Evans, Tracey L., Bauml, Joshua M., Ciunci, Christine, Alley, Evan, Morrissette, Jennifer J.D., Cohen, Roger B., Carpenter, Erica L., Langer, Corey J., and Ahmed, Saman
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GENETIC mutation , *P53 protein , *EPIDERMAL growth factor receptors , *NON-small-cell lung carcinoma , *PROGRESSION-free survival , *REGRESSION analysis - Abstract
Purpose: TP53 mutation (MT) in epidermal growth factor receptor (EGFR) -MT non–small cell lung cancer (NSCLC) is associated with poor response to targeted therapy; however, its impact on survival is not clearly established. Patients and Methods: We performed an analysis of patients with stage IV EGFR MT NSCLC with available gene sequencing data. Associations between baseline characteristics; molecular profile, including TP53 MT; and survival outcomes were assessed. Results: We identified 131 consecutive patients with EGFR MT; 81 (62%) had a TP53 MT, and 55 (42%) had other coexisting oncogenic MTs. Emergent EGFR T790M MT was observed in 42 patients (32%). Overall survival (OS) was longer for younger patients (P =.003), never smokers (P =.002), those with Eastern Cooperative Oncology Group performance status 0 to 1 (P =.004), and emergent T790M MT (P =.018). TP53 MT (P =.021) and other coexisting oncogenic MTs (P = 0.011) were associated with inferior OS. In a multivariable regression analysis adjusted for age, smoking, Eastern Cooperative Oncology Group performance status, and the presence of TP53 MT (P =.063) and other coexisting MTs (P =.064) did not achieve statistical significance. Patients with EGFR T790M /TP53 double MT had worse OS compared with patients with T790M MT alone (46.4 months v 82.9 months). In our series, five patients transformed to small-cell lung cancer (5.6%). All had TP53 MT. In four patients, allelic fraction of TP53 MT increased at the time of transformation. Conclusion: The presence of TP53 and other coexisting MTs in EGFR MT NSCLC were associated with inferior OS, including patients with emergent T790M MT. An increase in TP53 mutation allelic fraction may potentially be a useful clinical predictor of small-cell transformation. [ABSTRACT FROM AUTHOR]
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- 2018
- Full Text
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