Meredith Flynn
A5007134344- Radiopharmaceutical Chemistry and Applications
- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- History of Computing Technologies
- Obsessive-Compulsive Spectrum Disorders
- Embedded Systems Design Techniques
- Personality Disorders and Psychopathology
- Artificial Intelligence in Law
- Medical Imaging Techniques and Applications
- Mental Health and Psychiatry
- Parallel Computing and Optimization Techniques
- Experimental Learning in Engineering
Dana-Farber Cancer Institute
2024
University of Minnesota
2011
Johns Hopkins University
1974
Abstract The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity bone metastases and (P) activity. In randomized phase II study, we assessed the effect R223+P compared R223 on tumor immune infiltration, safety, clinical outcomes mCRPC. primary endpoint was differences CD4+ CD8+ T-cell infiltrate 8-week versus baseline metastasis biopsies;...
This study sought to examine personality disorders and their related clinical variables in a sample of gay, lesbian, bisexual, transgender (GLBT) individuals with substance use disorders. Study participants were 145 GLBT patients who admitted residential dual diagnosis chemical dependency treatment program. A total 136 (93.8%) had at least one disorder. The most common borderline (n = 93; 64.1%), obsessive-compulsive 82; 56.6%), avoidant 71; 49.0%) Preliminary data suggest that there is high...
<div>Abstract<p>The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity bone metastases and (P) activity. In randomized phase II study, we assessed the effect R223+P compared R223 on tumor immune infiltration, safety, clinical outcomes mCRPC. The primary endpoint was differences CD4<sup>+</sup> CD8<sup>+</sup>...
<p>Swimmer’s plot of treatments received. Number radium-223 and pembrolizumab doses received are listed to the left right bars, respectively. The brackets “[” “]” represent planned break period from dosing with representing cycle 3 day 28 4 1 when interval between these was greater than days. Patients could resume radium treatment at radiographic progression by PCWG2 criteria (“△”) if there were no new visceral metastases, but two patients (bars 7 13 below) resumed without confirmed...
<p>Maximum grade adverse events, regardless of attribution. AEs are summarized as n (%) for each maximum grade.</p>
<p>Changes in A. CD4+FoxP3- effector cells and B. ratio of CD8+ to CD4+/FoxP3+ (Treg) from baseline 8 weeks on treatment</p>
<p>Supplementary File 1</p>
<p>Maximum grade adverse events, regardless of attribution. AEs are summarized as n (%) for each maximum grade.</p>
<p>Time to event (months) clinical endpoints by baseline and change in CD4+/FoxP3- (effector) proportion, CD8+ / CD4+FoxP3- (Treg) ratio</p>
<p>Kaplan-Meier estimates of time to treatment failure (TTF), radiographic progression-free survival (rPFS), and overall (OS) by A. baseline CD4+FoxP3- (effector) proportion above (high) vs. below (low) median. B. CD8+ C. / CD4+FoxP3+ (Treg) ratio N.B. Patients were event-free for 2 months as they need have on biopsy at week 8 treatment.</p>
<p>Supplementary File 3</p>
<p>Immune cell functional states differ in clinical responders compared to non-responders. (A) Heat maps summarizing log2 fold changes resulting from statistical scaffold analysis of markers 4-1BB, CD44, CTLA-4, GITR, HLA-DR, ICOS, Ki-67, OX40, PD-1, PD-L1, PD-L2, TIGIT, TIM3 and VISTA are shown for Week 1, 5, 9, when comparing non-responders as defined by rPFS.</p>
<p>Proportion of patients who experienced any or given category symptomatic skeletal events by the treatment arms</p>
<p>Time to event (months) clinical endpoints by baseline and change in CD4+/FoxP3- (effector) proportion, CD8+ / CD4+FoxP3- (Treg) ratio</p>
<p>Summary of biopsy yield</p>
<p>Summary of biopsy yield</p>
<p>Proportion of patients who experienced any or given category symptomatic skeletal events by the treatment arms</p>
<p>Consort diagram for status of trial. Progression (PD) includes protocol defined progression and clinical/symptomatic per physician.</p>
<p>Immunofluorescence staining of PD-L1+ CD68 myeloid cells in the bone biopsies. A. RNAscope DAPI (cyan), (orange), PD-L1 (magenta), Tim3 (green), TIGIT (white) and overlay marrow metastasis. CD68+ that co-express are indicated with arrow. Tim3+ pointer. Scale bar, 20 μm. B. Scatterplot PDL1+ cell frequencies tissue imaging data CD14+ CD3-CD19- CyTOF from blood samples taken at same timepoint (baseline, n=10 patients). R2 value is based on Pearson correlation. C. TIM3+ CD68- CD3+ T...
<p>Clinical characteristics at time of randomization PSA responders vs. non-responders</p>
<p>Immunofluorescence staining of PD-L1+ CD68 myeloid cells in the bone biopsies. A. RNAscope DAPI (cyan), (orange), PD-L1 (magenta), Tim3 (green), TIGIT (white) and overlay marrow metastasis. CD68+ that co-express are indicated with arrow. Tim3+ pointer. Scale bar, 20 μm. B. Scatterplot PDL1+ cell frequencies tissue imaging data CD14+ CD3-CD19- CyTOF from blood samples taken at same timepoint (baseline, n=10 patients). R2 value is based on Pearson correlation. C. TIM3+ CD68- CD3+ T...
<p>Radium-223 was administered as 55 kBq/kg q4weeks and pembrolizumab 200 mg q3weeks. Biopsies were performed pre-treatment after 8 weeks of treatment.</p>
<p>Supplementary File 2</p>
<p>Consort diagram for status of trial. Progression (PD) includes protocol defined progression and clinical/symptomatic per physician.</p>