Scott Lindhorst
A5002485541- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Genetic factors in colorectal cancer
- Brain Metastases and Treatment
- Immunotherapy and Immune Responses
- Meningioma and schwannoma management
- Cancer Research and Treatments
- Galectins and Cancer Biology
- Cancer Mechanisms and Therapy
- Neuroendocrine Tumor Research Advances
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
- Glycosylation and Glycoproteins Research
- Neurofibromatosis and Schwannoma Cases
- Cell death mechanisms and regulation
- Mechanisms of cancer metastasis
- Lung Cancer Treatments and Mutations
- Head and Neck Surgical Oncology
- Lymphoma Diagnosis and Treatment
Medical University of South Carolina
2016-2025
MUSC Hollings Cancer Center
2016-2025
Hospital for Sick Children
2016-2021
Montreal Children's Hospital
2016
SickKids Foundation
2016
Duke Medical Center
2013
University of Alabama at Birmingham
2013
Duke University Hospital
2013
Massachusetts General Hospital
2006
Harvard University
2006
Recurrent glioblastoma multiforme (GBM) is incurable with current therapies. Biallelic mismatch repair deficiency (bMMRD) a highly penetrant childhood cancer syndrome often resulting in GBM characterized by high mutational burden. Evidence suggests that mutation and neoantigen loads are associated response to immune checkpoint inhibition.We performed exome sequencing prediction on 37 bMMRD cancers compared them adult brain neoplasms. Neoantigen was responsive from multiple tissues. Two...
Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard newly diagnosed glioblastoma.After surgery chemoradiotherapy, patients were randomized (2:1) receive temozolomide plus DCVax-L (n = 232) or placebo 99). Following recurrence, all allowed DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); secondary...
Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed.To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma.This phase 3, prospective, externally controlled nonrandomized trial compared overall (OS) in newly diagnosed (nGBM) recurrent (rGBM) treated DCVax-L plus SOC vs contemporaneous matched external...
PURPOSE To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, secondary objectives included PFS, response rate, treatment adverse events (AEs) including delayed CNS toxicities. METHODS NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT versus alone. Stratification factors age, resection, Karnofsky...
Abstract Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading (MMRD and PPD) in children harbour the highest mutational microsatellite insertion–deletion (MS-indel) burden humans. MMRD PPD cancers are commonly lethal due to inherent resistance chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed benefit previous studies, we hypothesized that hypermutation caused by will improve outcomes following ICI treatment these patients. Using an...
The aim of this study was to assess gadolinium deposition in the skin a patient with normal renal function, based on estimated glomerular filtration rate values greater than 59 mL/min/1.73 m(2) after exposure large cumulative doses gadolinium-based contrast agents (GBCAs).The underwent 61 contrasted brain MRI scans over course 11 years. Skin biopsies from forearm and lower extremity were analyzed inductively coupled plasma mass spectrometry (ICP-MS), laser ablation ICP-MS, hydrophilic...
Constitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition characterized by early-onset synchronous and metachronous multiorgan tumors. We designed surveillance protocol for early tumor detection in these individuals.Data were collected from patients with confirmed CMMRD who registered the International Replication Repair Deficiency Consortium. Tumor spectrum, efficacy of protocol, malignant transformation low-grade lesions examined entire cohort. Survival...
Although replication repair deficiency, either by mismatch deficiency (MMRD) and/or loss of DNA polymerase proofreading, can cause hypermutation in cancer, microsatellite instability (MSI) is considered a hallmark MMRD alone. By genome-wide analysis tumors with germline and somatic deficiencies repair, we reveal novel association between proofreading MSI, especially when both components are lost. Analysis indels microsatellites (MS-indels) identified five distinct signatures (MS-sigs)....
Abstract Background Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery observation reportedly exceeds 90%. Herewith we summarize outcomes patients enrolled on NRG/RTOG 0539. Methods This phase II trial allocated to one of three groups per World Health Organization grade, recurrence status, resection extent. Low-risk had either gross total (GTR) or subtotal (STR) a newly diagnosed grade 1 were observed after surgery. The primary endpoint was...
Recurrent meningiomas constitute an uncommon but significant problem after standard (surgery and radiation) therapy failure. Current chemotherapies (hydroxyurea, RU-486, interferon-α) are only of marginal benefit. There is urgent need for more effective treatments meningioma patients who have failed surgery radiation therapy. Limonin, Tangeritin, Zerumbone, 6-Gingerol, Ganoderic Acid A, DM some the plant derivatives that anti-tumorgenic properties cause cell death in cells vitro. Due to its...
Radiation-induced necrosis (RN) is a relatively common side effect of radiation therapy for glioblastoma. However, the molecular mechanisms involved and ways RN differ from regulated cell death (apoptosis) are not well understood. Here, we compare mechanism (apoptosis or necrosis) C6 glioma cells in both vitro vivo (C6 othotopically allograft) models response to low high doses X-ray radiation. Lower were used induce apoptosis, while high-dose levels chosen necrosis. Our results demonstrate...
In oncology, "immunotherapy" is a broad term encompassing multiple means of utilizing the patient's immune system to combat malignancy. Prominent among these are checkpoint inhibitors, cellular therapies including chimeric antigen receptor T-cell therapy, vaccines, and oncolytic viruses. Immunotherapy for glioblastoma (GBM) has had mixed results in early trials. this context, past, present, future oncology treatment GBM was discussed by clinical, research, thought leaders as well patient...
Glioblastoma (GB) is the most common malignant brain tumor. Drug resistance frequently develops in these tumors during chemotherapy. Therefore, predicting drug response patients remains a major challenge clinic. Thus, to improve clinical outcome, more effective and tolerable combination treatment strategies are needed. Robust experimental evidence has shown that main reason for failure of treatments signal redundancy due coactivation several functionally linked receptor tyrosine kinases...
Constitutional mismatch repair deficiency (CMMRD) is a highly penetrant cancer predisposition syndrome caused by biallelic mutations in (MMR) genes. As several syndromes are clinically similar, accurate diagnosis critical to screening and treatment. genetic confounded 15 or more pseudogenes variants of uncertain significance, robust diagnostic assay urgently needed. We sought determine whether an that directly measures MMR activity could accurately diagnose CMMRD.In vitro was quantified...
Abstract Mismatch repair (MMR) is a critical defence against mutation, but we lack quantification of its activity on different DNA lesions during human life. We performed whole-genome sequencing normal and neoplastic tissues from individuals with constitutional MMR deficiency to establish the roles components, tissue type disease state in somatic mutation rates. Mutational signatures varied extensively across genotypes, some coupled leading-strand replication, lagging-strand replication...
Glioblastoma is a form of brain tumor with very high morbidity and mortality. Despite decades research, the best treatments currently in clinical practice only extend survival by number months. A promising alternative to conventional treatment for glioblastomas immunotherapy. Although proposed over century ago, field cancer immunotherapy has historically struggled translate it into effective treatments. Better understanding needed various regulatory co-stimulatory factors glioblastoma...