7 results on '"Nikhil T. Sebastian"'
Search Results
2. Impact of concomitant fibrates on immunotherapy outcomes for advanced non‐small cell lung cancer
- Author
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William A. Stokes, Madhusmita Behera, Renjian Jiang, David A. Gutman, Zhonglu Huang, Abigail Burns, Nikhil T. Sebastian, Vidula Sukhatme, Michael C. Lowe, Suresh S. Ramalingam, Vikas P. Sukhatme, and Drew Moghanaki
- Subjects
fibrates ,immune checkpoint inhibitors ,peroxisome proliferator‐activated receptor (PPAR) agonists ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Peroxisome proliferator‐activated receptor agonists such as fibrates restore oxidative metabolism in cytotoxic T‐lymphocytes, thereby enhancing response to immune checkpoint inhibitors (ICI) in preclinical models. However, there is no evidence in humans on the clinical impact of fibrates as an adjunct to ICI. Methods In this cohort study of Veterans with non‐small cell lung cancer (NSCLC) receiving ICI, fibrate exposure was defined as a prescription filled within 90 days of an ICI infusion. Overall survival (OS), measured from the start of ICI, was compared between exposed and unexposed Veterans. Cox multivariable analysis (MVA) was used to identify factors associated with OS. A sensitivity analysis of Veterans with stage IV NSCLC who received docetaxel without ICI was similarly performed. Results The ICI cohort included 3593 Veterans, of whom 301 (8.5%) coincidentally received a fibrate. Veterans receiving fibrates were more likely to be older, white, male, and married, and to have greater comorbidity burden, but less likely to receive chemotherapy. Coincidental fibrates were associated with improved OS both on MVA (HR 0.86, 95%CI 0.75–0.99) and in a matched subset (HR 0.75, 95%CI 0.63–0.90). In contrast, among the cohort of 968 Veterans treated with chemotherapy, fibrates did not have a significant impact on OS by MVA (HR 0.99, 95%CI 0.79–1.25) or in a matched subset (HR 1.02, 95%CI CI 0.75–1.39). Conclusions Concomitant fibrates are associated with improved OS among NSCLC patients receiving ICI but not among those receiving chemotherapy. This hypothesis‐generating observation supports a potential role for fibrates as an adjunct to immunotherapy.
- Published
- 2023
- Full Text
- View/download PDF
3. Single-Isocenter Multitarget Stereotactic Radiosurgery Is Safe and Effective in the Treatment of Multiple Brain Metastases
- Author
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Joshua D. Palmer, MD, Nikhil T. Sebastian, MD, Jacquline Chu, BS, Dominic DiCostanzo, MS, Erica H. Bell, PhD, John Grecula, MD, Andrea Arnett, MD, PhD, Dukagjin M. Blakaj, MD, PhD, John McGregor, MD, James B. Elder, MD, Lanchun Lu, PhD, Wesley Zoller, BS, Mark Addington, Russell Lonser, MD, Arnab Chakravarti, MD, PhD, Paul D. Brown, MD, and Raju Raval, MD, DPhil
- Subjects
Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Purpose: Multiple studies have reported favorable outcomes for stereotactic radiosurgery (SRS) in the treatment of limited brain metastases. An obstacle of SRS in the management of numerous metastases is the longer treatment time using traditional radiosurgery. Single-isocenter multitarget (SIMT) SRS is a novel technique that permits rapid therapy delivery to multiple metastases. There is a lack of clinical evidence regarding its efficacy and safety. We report the outcomes of patients treated with this technique. Methods and Materials: We reviewed the records of patients with intact or resected brain metastases treated with SRS in 1 to 5 fractions using SIMT technique at our institution, with at least 1 available follow-up brain magnetic resonance imaging. Survival, disease control, and toxicity were evaluated using Cox regression, logistic regression, and Kaplan-Meier analysis. Results: We identified 173 patients with 1014 brain metastases. Median follow up was 12.7 months. Median beam-on time was 4.1 minutes. The median dose to the brain was 219.4 cGy. Median overall survival and freedom from intracranial progression were 13.2 and 6.3 months, respectively. Overall survival did not differ between patients treated with greater than or less than 4 lesions (hazard ratio, 1.03; 95% confidence interval 0.66-1.61; P = .91). Actuarial 1- and 2-year local control were 99.0% and 95.1%, respectively. Rates of grade 2 and grade 3 or higher radionecrosis were 1.4% and 0.9%, respectively. Conclusions: SIMT radiosurgery delivered in 1 to 5 fractions offers excellent local control and acceptable toxicity in the treatment of multiple intact and postoperative brain metastases. This technique should be evaluated prospectively.
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- 2020
- Full Text
- View/download PDF
4. Stereotactic body radiation therapy is associated with improved overall survival compared to chemoradiation or radioembolization in the treatment of unresectable intrahepatic cholangiocarcinoma
- Author
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Nikhil T. Sebastian, Yubo Tan, Eric D. Miller, Terence M. Williams, and Dayssy Alexandra Diaz
- Subjects
Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Intrahepatic cholangiocarcinoma (ICC) is a highly lethal malignancy. For patients with locally advanced, unresectable disease, numerous liver-directed therapy options exist, including chemoradiation (CRT), stereotactic body radiation therapy (SBRT), and transarterial radioembolization (TARE). There is no randomized data to inform clinicians regarding the optimal treatment modality. Method: We used the National Cancer Database (NCDB) to study the overall survival (OS) of patients with ICC treated with CRT, SBRT, and TARE. We used Cox proportional hazards modeling and inverse probability of treatment weighting (IPTW) to account for confounding variables. Results: We identified 170 patients with unresected ICC treated with SBRT (n = 37), CRT (n = 61), or TARE (n = 72). SBRT was associated with higher OS compared to CRT (hazard ratio [HR] = 0.37; 95% confidence interval [CI] 0.20–0.68; p = 0.001) and TARE (HR = 0.40; 95% CI 0.22–0.74; p = 0.003). On multivariable analysis, SBRT remained associated with higher OS compared to CRT (HR = 0.44; 95% CI 0.21–0.91; p = 0.028) and TARE (HR = 0.42; 95% CI 0.21–0.84; p = 0.014). After IPTW (Bonferroni-adjusted significance threshold, α = 0.017), SBRT again had a statistically significant association with higher OS compared to CRT (HR = 0.22; 95% CI 0.11–0.44; p
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- 2019
- Full Text
- View/download PDF
5. Association of Pre- and Posttreatment Neutrophil–Lymphocyte Ratio With Recurrence and Mortality in Locally Advanced Non-Small Cell Lung Cancer
- Author
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Nikhil T. Sebastian, Rohit Raj, Rahul Prasad, Christian Barney, Jeremy Brownstein, John Grecula, Karl Haglund, Meng Xu-Welliver, Terence M. Williams, and Jose G. Bazan
- Subjects
neutrophil–lymphocyte ratio ,chemoradiation ,locally advanced ,non-small cell lung cancer ,vertebral body ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
ObjectivesNeutrophil–lymphocyte ratio (NLR) has been associated with mortality in non-small cell lung cancer (NSCLC), but its association with recurrence in locally advanced NSCLC (LA-NSCLC), specifically, is less established. We hypothesized pre- and posttreatment NLR would be associated with recurrence and mortality.MethodsWe studied the association of pretreatment NLR (pre-NLR) and posttreatment NLR at 1 (post-NLR1) and 3 months (post-NLR3) with outcomes in patients with LA-NSCLC treated with chemoradiation. Pre-NLR was dichotomized by 5, an a priori cutoff previously shown to be prognostic in LA-NSCLC. Post-NLR1 and post-NLR3 were dichotomized by their medians.ResultsWe identified 135 patients treated with chemoradiation for LA-NSCLC between 2007 and 2016. Median follow-up for living patients was 61.1 months. On multivariable analysis, pre-NLR ≥ 5 was associated with worse overall survival (HR = 1.82; 95% CI 1.15 – 2.88; p = 0.011), but not with any recurrence, locoregional recurrence, or distant recurrence. Post-NLR1 ≥ 6.3 was not associated with recurrence or survival. Post-NLR3 ≥ 6.6 was associated with worse overall survival (HR = 3.27; 95% CI 2.01– 5.31; p < 0.001), any recurrence (HR = 2.50; 95% CI 1.53 – 4.08; p < 0.001), locoregional recurrence (HR = 2.50; 95% CI 1.40 – 4.46; p = 0.002), and distant recurrence (HR = 2.53; 95% CI 1.49 – 4.30; p < 0.001).ConclusionPretreatment NLR is associated with worse overall survival and posttreatment NLR is associated with worse survival and recurrence. These findings should be validated independently and prospectively studied.
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- 2020
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6. The Association of Improved Overall Survival with NSAIDs in Non–Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors
- Author
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Nikhil T. Sebastian, William A. Stokes, Madhusmita Behera, Renjian Jiang, David A. Gutman, Zhonglu Huang, Abigail Burns, Vidula Sukhatme, Michael C. Lowe, Suresh S. Ramalingam, Vikas P. Sukhatme, and Drew Moghanaki
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2023
- Full Text
- View/download PDF
7. Impact of concomitant fibrates on immunotherapy outcomes for advanced <scp>non‐small</scp> cell lung cancer
- Author
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William A. Stokes, Madhusmita Behera, Renjian Jiang, David A. Gutman, Zhonglu Huang, Abigail Burns, Nikhil T. Sebastian, Vidula Sukhatme, Michael C. Lowe, Suresh S. Ramalingam, Vikas P. Sukhatme, and Drew Moghanaki
- Subjects
Cancer Research ,Oncology ,Radiology, Nuclear Medicine and imaging - Abstract
Peroxisome proliferator-activated receptor agonists such as fibrates restore oxidative metabolism in cytotoxic T-lymphocytes, thereby enhancing response to immune checkpoint inhibitors (ICI) in preclinical models. However, there is no evidence in humans on the clinical impact of fibrates as an adjunct to ICI.In this cohort study of Veterans with non-small cell lung cancer (NSCLC) receiving ICI, fibrate exposure was defined as a prescription filled within 90 days of an ICI infusion. Overall survival (OS), measured from the start of ICI, was compared between exposed and unexposed Veterans. Cox multivariable analysis (MVA) was used to identify factors associated with OS. A sensitivity analysis of Veterans with stage IV NSCLC who received docetaxel without ICI was similarly performed.The ICI cohort included 3593 Veterans, of whom 301 (8.5%) coincidentally received a fibrate. Veterans receiving fibrates were more likely to be older, white, male, and married, and to have greater comorbidity burden, but less likely to receive chemotherapy. Coincidental fibrates were associated with improved OS both on MVA (HR 0.86, 95%CI 0.75-0.99) and in a matched subset (HR 0.75, 95%CI 0.63-0.90). In contrast, among the cohort of 968 Veterans treated with chemotherapy, fibrates did not have a significant impact on OS by MVA (HR 0.99, 95%CI 0.79-1.25) or in a matched subset (HR 1.02, 95%CI CI 0.75-1.39).Concomitant fibrates are associated with improved OS among NSCLC patients receiving ICI but not among those receiving chemotherapy. This hypothesis-generating observation supports a potential role for fibrates as an adjunct to immunotherapy.
- Published
- 2022
- Full Text
- View/download PDF
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