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Your search keyword '"Stanley I. Gutiontov"' showing total 4 results
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4 results on '"Stanley I. Gutiontov"'

1. CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer

Author

Stanley I. Gutiontov, William Tyler Turchan, Liam F. Spurr, Sherin J. Rouhani, Carolina Soto Chervin, George Steinhardt, Angela M. Lager, Pankhuri Wanjari, Renuka Malik, Philip P. Connell, Steven J. Chmura, Aditya Juloori, Philip C. Hoffman, Mark K. Ferguson, Jessica S. Donington, Jyoti D. Patel, Everett E. Vokes, Ralph R. Weichselbaum, Christine M. Bestvina, Jeremy P. Segal, and Sean P. Pitroda

Subjects
Medicine, Science
Abstract

Abstract Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02–2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21–3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

Published
2021
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2. Improved outcomes after radiotherapy for prostate cancer: Anticoagulation, antiplatelet therapy, and platelet count as key factors in disease progression

Author

Stanley I. Gutiontov, Kevin S. Choe, Jonathan L. Miller, and Stanley L. Liauw

Subjects
blood platelets, prostatic neoplasms, radiotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Several studies have suggested that antiplatelet (AP) or anticoagulant (AC) therapy may improve outcome in men with prostate cancer. We evaluated the effects of AP/AC therapy and tested the hypothesis that platelet count may also be associated with outcomes. Methods A total of 482 patients received primary radiotherapy (median dose 72 Gy) for nonmetastatic prostate cancer; 49% received androgen deprivation therapy. NCCN risk was low/intermediate/high risk in 39%/39%/22%. AP/AC therapy and platelet counts were analyzed with respect to freedom from biochemical failure (FFBF, nadir+2), distant metastasis (FFDM), and cause specific survival (CSS). Results After a median follow‐up of 103 months, 10‐year FFBF, FFDM, and CSS were 77%, 92%, and 96%, respectively. The 10‐year cumulative incidence of BF and DM (with death as a competing event) was 19% and 7.0%, respectively. The 32% of men on AP/AC therapy had a lower incidence of 10‐year BF (P = .016) and a trend toward a lower incidence of DM (P = .084) and CSS (P = .091). In the entire cohort, lowest platelet quartile (platelet count

Published
2020
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3. Prostate Cancer Radiotherapy: Increased Biochemical Control and Late Toxicity in Men With Medication Allergies

Author

William Tyler Turchan, Stanley I. Gutiontov, Michael T. Spiotto, and Stanley L. Liauw

Subjects
Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Gastroenterology, Article, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Internal medicine, medicine, 030304 developmental biology, 0303 health sciences, Aspirin, Univariate analysis, business.industry, Incidence (epidemiology), Hazard ratio, medicine.disease, Confidence interval, Radiation therapy, Oncology, 030220 oncology & carcinogenesis, Toxicity, business, AcademicSubjects/MED00010, medicine.drug
Abstract

Background Given similarities in the mediators of medication allergy (MA) and tissue response to radiotherapy, we assessed whether outcomes following prostate radiotherapy differ in patients with MAs. Methods A total 587 men with known MA history and nonmetastatic prostate cancer underwent radiotherapy from 1989 to 2006. Clinicopathologic and treatment variables were analyzed for association with freedom from biochemical failure (FFBF) and late treatment–related, physician-defined Radiation Therapy Oncology Group gastrointestinal (GI) and genitourinary (GU) toxicity. Covariates identified on univariate analysis for toxicity and disease control were examined on multivariable analysis. All statistical tests were 2-sided, and a P less than .05 was considered statistically significant. Results A total of 155 of 587 men (26.4%) had 1 or more MAs, most commonly to penicillin (n = 71), sulfa (n = 35), and aspirin or nonsteroidal antiinflammatory drugs (n = 28). On univariate analysis, men with MAs had superior 10-y FFBF (71.5% vs 63.5%, P = .02) and higher incidence of late GI grade 2 or higher (G2+; 20.6% vs 13.2%, P = .04) and grade 3 or higher (G3+; 7.5% vs 3.9%, P = .08) as well as late GU G2+ (42.5% vs 33.2%, P = .04) and G3+ (7.5% vs 3.0%, P = .02) toxicity than men without MAs. On multivariable analysis, MA history remained a statistically significant predictor of FFBF (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.43 to 0.93, P = .02), late G2+ GI (HR = 1.76, 95% CI = 1.06 to 2.90, P=.03), and G3+ GU (HR = 2.69, 95% CI = 1.16 to 6.27, P = .02) toxicity after controlling for corresponding covariates in each model. Conclusions Men with MAs had improved FFBF and increased treatment-related toxicity following radiotherapy for prostate cancer. MA history could be a relevant consideration in the management of men with localized prostate cancer.

Published
2020

4. Gamma Knife Stereotactic Radiosurgery for Grade 2 Meningiomas

Author

I. Helenowksi, James P. Chandler, Sean Sachdev, Tamer Refaat, Stanley I. Gutiontov, Orin Bloch, John A. Kalapurakal, Anish Butala, Michelle S. Gentile, V. Sathiaseelan, Prarthana Dalal, and Plato Lee

Subjects
grade 2, medicine.medical_treatment, Clinical Trials and Supportive Activities, Clinical Sciences, Gamma knife radiosurgery, Gamma knife, meningioma, Radiosurgery, Vaccine Related, Meningioma, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Overall survival, otorhinolaryngologic diseases, Medicine, Effective treatment, Cancer, Neurology & Neurosurgery, Gamma Knife, business.industry, radiosurgery, medicine.disease, Institutional review board, stereotactic, Brain Disorders, nervous system diseases, Radiation necrosis, surgical procedures, operative, 030220 oncology & carcinogenesis, Neurology (clinical), sense organs, business, Nuclear medicine, 030217 neurology & neurosurgery
Abstract

Purpose This study aims to report long-term clinical outcomes after Gamma Knife radiosurgery (GKRS) for intracranial grade 2 meningiomas. Methods In this Institutional Review Board approved study, we reviewed records of all patients with grade 2 meningiomas treated with GKRS between 1998 and 2014. Results A total of 97 postoperative histopathologically confirmed grade 2 meningiomas in 75 patients were treated and are included in this study. After a mean follow-up of 41 months, 28 meningiomas had local recurrence (29.79%). Median time to local recurrence was 89 months (mean: 69, range: 47–168). The 3- and 5-year actuarial local control (LC) rates were 68.9 and 55.7%, respectively. The 3- and 5-year overall survival rates were 88.6 and 81.1%, respectively. There was a trend toward worse LC with tumors treated with radiation doses ≤ 13 versus > 13 Gy. There was no radiation necrosis or second malignant tumors noted in our series. Conclusion This report, one of the largest GKRS series for grade 2 meningiomas, demonstrates that GKRS is a safe and effective treatment modality for patients with grade 2 meningiomas with durable tumor control and minimal toxicity. Adjuvant GKRS could be considered as a reasonable treatment approach for patients with grade 2 meningiomas.

Published
2017

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