Jay Fitzgerald Dorsey
· M.D., Ph.D.University of Pennsylvania · Radiology
Active 1951–2026
About
Jay Fitzgerald Dorsey is a professor in the Department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania. The provided page text does not include specific details about his research focus, background, or key contributions. Therefore, no further biographical information is available from the given content.
Research topics
- Medicine
- Cancer research
- Biology
- Chemistry
- Oncology
Selected publications
Cancer Research · 2026-03-16
articleOpen accessThe Oncologist · 2026-02-12
articleOpen accessBACKGROUND: Melanoma brain metastases (BM) carry high morbidity and mortality despite advances in systemic therapy. Combined immune checkpoint inhibition (ICI) with ipilimumab and nivolumab (ipi/nivo) demonstrates intracranial activity, but the influence of prior systemic therapy exposure is poorly defined. This is the first real-world study evaluating outcomes of melanoma BM treated with stereotactic radiosurgery (SRS) and concurrent ipi/nivo, focusing on the impact of prior ICI or targeted therapy. PATIENTS AND METHODS: We retrospectively analyzed 68 patients with 413 melanoma BM treated with concurrent SRS and ipi/nivo from 2015 to 2025. Primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS). Secondary endpoints included local and distant control, radionecrosis, and leptomeningeal disease. Univariable and multivariable Cox models identified predictors of outcome. RESULTS: Median OS was 24.0 months (12- and 24-month OS: 64% and 50%). ICI-naive patients had longer OS (50.5 vs. 17.6 months; P = 0.007) and iPFS (15.1 vs. 5.9 months) than those with prior ICI. On multivariable analysis, prior ICI (HR 2.23, 95% confidence interval [CI] 1.13-4.41), prior BRAF/MEKi (HR 2.26, 95% CI 1.01-5.04), and ≥11 SRS-treated lesions (HR 3.22, 95% CI 1.43-7.21) predicted worse outcomes, while higher graded prognostic assessment (GPA) favored OS (HR 0.46, 95% CI 0.29-0.75). At 24 months, local progression was 11%, distant 49%, radionecrosis 7%, and leptomeningeal disease 4%. CONCLUSION: Concurrent SRS with ipi/nivo provides durable intracranial control with low toxicity. Patients with prior ICI or targeted therapy represent a high-risk subgroup with poorer outcomes, supporting exploration of intensified or novel strategies.
Journal of Neuro-Oncology · 2026-04-25
articleOpen accessGlioblastoma (WHO grade 4), defined by IDH-wildtype status and associated molecular features, carries poor prognosis, and real-world survival models incorporating molecular and immunologic variables remain limited. Severe radiation-induced lymphopenia (sRIL) is a proposed prognostic factor, but its independent effect in molecularly defined glioblastoma has not been established in the modern era. We retrospectively identified 832 adults with glioblastoma, defined as WHO 2021 grade 4 IDH-wildtype diffuse glioma treated with maximal safe resection and adjuvant radiotherapy (RT) with or without chemotherapy between 2014 and 2024. A trial-eligible subgroup was defined using Stupp criteria. Clinical, molecular, and hematologic variables were analyzed. sRIL was defined as CTCAE grade ≥ 3 lymphopenia within 4 months of RT. Multivariable Cox models incorporated LASSO for variable selection and spline regression for non-linearity. Median overall survival (OS) was 13.0 months. On multivariable analysis, sRIL (HR 1.37, 95% CI 1.16–1.63) remained an independent predictor of worse OS after adjustment for MGMT status, age, resection extent, and treatment factors. MGMT methylation predicted benefit from concurrent TMZ (pinteraction<0.001), and trial-eligible patients had longer OS across MGMT subgroups. Age and post-RT lymphocyte nadir were non-linearly associated with survival. Proton therapy was associated with a favorable but non-significant OS estimate (HR 0.87, p = 0.11), with no benefit in the trial-eligible cohort. In this large, real-world cohort, sRIL remained a strong independent prognostic factor. MGMT methylation predicted TMZ benefit, and trial eligibility conferred favorable outcomes. These findings underscore the prognostic relevance of post-treatment lymphopenia and support prospective evaluation of lymphocyte-sparing treatment strategies. • Severe post-RT lymphopenia is independently associated with worse survival in IDH-wt glioblastoma. • MGMT methylation predicts temozolomide benefit; trial-eligible patients have superior outcomes. • No survival advantage was observed for proton versus photon therapy in adjusted analyses.
Nature Cancer · 2025-02-05 · 57 citations
articleInternational Journal of Radiation Oncology*Biology*Physics · 2025-09-01
articleInternational Journal of Radiation Oncology*Biology*Physics · 2025-09-01
articleNeuro-Oncology Advances · 2025-08-01
articleOpen accessAbstract While ipilimumab/nivolumab has demonstrated promising intracranial activity among patients with melanoma brain metastases (BM), patients with prior immune checkpoint inhibition (ICI) exposure may be at higher risk of worse intracranial disease control. We evaluated outcomes of patients with melanoma BM treated with ipilimumab/nivolumab and stereotactic radiosurgery (SRS) with or without prior ICI. Overall survival (OS) and intracranial progression-free survival (iPFS) were estimated from SRS using a non-parametric method, and Cox proportional hazards models were used to test clinically relevant factors. 64 consecutive patients with 393 treated BM between 2015 and 2024 were included with median follow-up of 20.2 months from SRS. 34 (53%) patients were alive at analysis. The 2-year OS and iPFS for the entire cohort was 52.1% and 36.4%, respectively. 32 patients (50%) had prior exposure to ICI. Performance status, age, number of BM, and receipt of surgery were not significantly different among patients with or without prior ICI. Patients with prior ICI had smaller BM (largest median diameter 19 mm vs 22.5 mm, p=0.022) and were less likely to have extracranial metastases (53.1% vs 78.1%, p=0.035). Patients with prior ICI exposure trended towards worse iPFS (median iPFS 4.3 months vs 13.5 months, p = 0.29) and had worse survival after SRS (median OS 17.6 months vs 50.5 months, p = 0.017). On univariate analysis, receipt of prior ICI (HR 2.16, 95% CI 1.13 – 4.11, p = 0.019), no upfront surgery (HR 0.38, 95% CI 0.20 – 0.72, p = 0.003), and number of treated BM (HR 1.04, 95% CI 1 – 1.08, p = 0.043) were significantly associated with OS. While ipilimumab/nivolumab with SRS demonstrates encouraging intracranial control, patients with prior ICI exposure are at higher risk of poor outcomes and may benefit from additional treatment strategies.
IMMU-49. Outcomes of SRS and Ipilimumab/Nivolumab Among Patients with Melanoma Brain Metastases
Neuro-Oncology · 2025-11-01
articleOpen accessAbstract While ipilimumab and nivolumab has demonstrated promising intracranial activity among patients with melanoma brain metastases (BM), patients with prior systemic therapy exposure may be at higher risk of poor intracranial disease control and benefit from upfront local therapy. We evaluated outcomes of patients with BMs treated with ipilimumab/nivolumab and stereotactic radiosurgery (SRS). Overall survival (OS) and intracranial progression-free survival (PFS) were estimated from SRS using a non-parametric method, and Cox proportional hazards models were used to test clinically relevant factors. A total of 68 consecutive patients with 413 treated BMs between 2015 and 2025 were included with median follow-up of 19.3 months from SRS. At the time of analysis, 34 (53%) patients were alive. The 2-year OS and intracranial PFS for the entire cohort was 49.5% and 36.1%, respectively. 34 patients (50%) had prior exposure to immune checkpoint inhibition (ICI) and 13 patients (19%) had exposure to prior BRAF/MEK inhibition. On univariable analysis, factors significantly associated with worse OS included receipt of prior ICI (HR 2.3, 95% CI 1.24 - 4.26, p = 0.008) and BRAF/MEK inhibition (HR 2.37, CI 1.21-4.67, p = 0.012). Upfront brain metastasis resection was associated with improved OS (HR 0.39, 95% CI 0.21 – 0.73, p = 0.003). Patients with prior ICI exposure trended towards worse intracranial PFS (median intracranial PFS 5.9 months vs 15.1 months, p = 0.12) and had worse survival after SRS (median OS 17.6 months vs 50.5 months, p = 0.007). While ipilimumab/nivolumab demonstrates encouraging intracranial control and survival among patients with melanoma brain metastases, patients with prior ICI or targeted therapy exposure are at higher risk of poor outcomes and may benefit from additional treatment strategies.
Neuro-Oncology · 2024-11-01 · 1 citations
articleOpen accessAbstract BACKGROUND The purpose of this study was to assess the feasibility and effectiveness of AI-guided personalized precision radiation therapy (PPRT) with targeted dose escalation in enhancing outcomes for patients with newly diagnosed glioblastoma. METHODS An open-label trial was conducted at the University of Pennsylvania (NCT03477513) from August 2018 to April 2023, enrolling 20 patients with IDH-wildtype glioblastoma who underwent maximal safe resection. They were matched with a contemporaneous cohort of glioblastoma patients based on age, sex, extent of resection (EOR), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation status, and IDH status. Propensity score matching (PSM) was employed to select the control group, utilizing one-to-four nearest neighbor matching. One patient was excluded due to concurrent treatment with tumor treating fields (TTFields). The PPRT group received personalized radiation dose escalation to 75 Gy in 30 fractions guided by AI-based predictive modeling of recurrence, along with temozolomide chemotherapy. The control group received standard-of-care chemoradiotherapy, 60 Gy in 30 fractions. A previously published and evaluated (retrospectively and prospectively) predictive AI model, which has demonstrated high predictive value for neoplastic cell infiltration and future tumor recurrence using preoperative, multi-parametric MRIs, was utilized. RESULTS Median overall survival was 24.3 months in the PPRT-temozolomide group compared to 17.5 months in the standard-of-care treatment group (hazard ratio [HR]=0.30; 95% CI: 0.16-0.57; p&lt;0.001). Excluding two patients with leptomeningeal disease and bone marrow metastasis, the median survival was 35.4 months (HR=0.25; 95% CI: 0.12-0.51; p&lt;0.001). CONCLUSION AI-guided PPRT for newly diagnosed glioblastoma patients demonstrated feasibility in routine clinical practice and significantly improved overall survival compared to matched controls receiving standard-of-care treatment. These findings underscore the potential of personalized precision radiation therapy, with focused dose escalation, in improving outcomes for glioblastoma patients and emphasize the need for prospective validation in a randomized controlled clinical trial.
Science Advances · 2024-02-28 · 35 citations
articleOpen accessCancer immunity is subjected to spatiotemporal regulation by leukocyte interaction with neoplastic and stromal cells, contributing to immune evasion and immunotherapy resistance. Here, we identify a distinct mesenchymal-like population of endothelial cells (ECs) that form an immunosuppressive vascular niche in glioblastoma (GBM). We reveal a spatially restricted, Twist1/SATB1-mediated sequential transcriptional activation mechanism, through which tumor ECs produce osteopontin to promote immunosuppressive macrophage (Mφ) phenotypes. Genetic or pharmacological ablation of Twist1 reverses Mφ-mediated immunosuppression and enhances T cell infiltration and activation, leading to reduced GBM growth and extended mouse survival, and sensitizing tumor to chimeric antigen receptor T immunotherapy. Thus, these findings uncover a spatially restricted mechanism controlling tumor immunity and suggest that targeting endothelial Twist1 may offer attractive opportunities for optimizing cancer immunotherapy.
Recent grants
Targeted Modulation of the Death Receptor as a Therapeutic Strategy for Glioma
NIH · $932k · 2011–2017
Circulating Tumor Cells Analyses and Molecular Profiling for Patients Receiving Radiation Therapy
NIH · $2.2M · 2016–2022
Dissecting the biology and consequence of circulating glioma cells
NIH · $2.3M · 2020–2026
Radiation and Receptor Targeted RadioTheranostic Nanoparticles for Glioblastoma
NIH · $2.4M · 2014–2020
Summer Undergraduate Program to Educate Radiation Scientists (SUPERS)
NIH · $4.1M · 2010–2031
Frequent coauthors
- 400 shared
Daniel T. Chang
- 300 shared
J. Costello
Centre National de la Recherche Scientifique
- 300 shared
Tali Mazor
University of California, San Francisco
- 300 shared
Michael Weller
University Hospital of Zurich
- 300 shared
Olivier Gevaert
- 300 shared
Mark R. Gilbert
University of Missouri
- 300 shared
Lih‐Shen Chin
Shanghai University of Traditional Chinese Medicine
- 300 shared
N. Saito
Awards & honors
- NIH funding (past decade)
- Co-Leader of the Abramson Cancer Center's RadOnc Translation…
- Standing member of the K99/R00 transition to independence NI…
- PI and Director of SUPERS@PENN program (NIH R25-funded under…
- Funding from ASCO
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