Minesh P Mehta

• MBChB, FASTRO
• Deputy Director at Baptist Health South Florida

PURPOSE Survival for patients with melanoma has recently improved. The propensity of melanoma to metastasize to the brain remains a common and serious feature of this disease. The purposes of this study were to evaluate prognostic factors for patients with newly diagnosed melanoma brain metastases (MBMs) in a large cohort treated with modern multim...

Background/Objectives: Proton craniospinal irradiation (pCSI) is an emerging treatment option for selected patients with leptomeningeal disease (LMD) that may improve CNS progression-free survival (CNS-PFS) and overall survival (OS) compared to photon involved field irradiation. This study aims to report the applicability of pCSI to standard practi...

Purpose Systemic therapies are increasingly being considered as primary treatments for brain metastases (BM), deferring the upfront use of local treatment modalities. However, evidence to support this paradigm shift is difficult to interpret given the volume of data published and the intricacies of the outcomes reported. The objective of this narra...

380 Background: Node-positive prostate cancer (PCa) poses a unique treatment challenge since bowel radiation tolerance often limits the delivery of doses of 60-70Gy or more required to control gross nodal disease. IMPT is a novel therapeutic option which utilizes beam stopping properties to achieve dose sparing of normal organs with the ability to...

Background Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propos...

Background/Objectives: Over the past decade, significant advances have been made in image-guided radiotherapy (RT) particularly with the introduction of magnetic resonance (MR)-guided radiotherapy (MRgRT). However, the optimal clinical applications of MRgRT are still evolving. The intent of this analysis was to describe our institutional MRgRT util...

There is major interest in deintensifying therapy for isocitrate dehydrogenase–mutant low-grade gliomas, including with single-agent cytostatic isocitrate dehydrogenase inhibitors. These efforts need head-to-head comparisons with proven modalities, such as chemoradiotherapy. Ongoing clinical trials now group tumors by intrinsic molecular subtype, r...

Purpose This report describes routine machine quality assurance (QA) (daily, monthly, and annual QA) tests for the Zap‐X® Gyroscopic Radiosurgery® platform. Methods Following the recommendations of the American Association of Physicists in Medicine Task Group (AAPM TG)‐142 and Medical Physics Practice guideline (MPPG) 8.b, routine machine QA tests...

Background Glioblastoma (GBM) is an aggressive form of brain cancer in which treatment is associated with toxicities that can result in therapy discontinuation or death. This analysis investigated clinical and genetic markers of vascular toxicities in GBM patients during active treatment. Methods 591 Non-Hispanic White GBM patients with clinical d...

INTRODUCTION Lesions exhibiting radiation-induced contrast enhancement (RICE) may develop following cranial intensity modulated proton therapy (IMPT). The mechanisms underlying their development may be shared or amplified by existing patient comorbidities. The objective of this study was to assess a potential relationship between individual or comp...

INTRODUCTION Stereotactic radiosurgery (SRS) is a cornerstone in the treatment of brain metastasis (BM), despite a known risk of distant intracranial failure (DIF). Recent imaging advances, specifically, sensitive 3D-FSE sequences, have started to be incorporated into SRS practice; however, comparisons of outcomes to historical imaging approaches a...

Recurrent high-grade intracranial malignancies have a grim prognosis and uniform management guidelines are lacking. Re-irradiation is underused due to concerns about irreversible side effects. Pulsed-reduced dose rate radiotherapy (PRDR) aims to reduce toxicity while improving tumor control by exploiting dose-rate effects. We share our initial expe...

Background Stereotactic radiosurgery (SRS) for patients with brain metastases (BM) is associated with a risk of distant intracranial failure (DIF). This study evaluates the impact of integrating dedicated 3D-TSE sequences to MPRAGE in BM detection and DIF prolongation in a histology-agnostic patient cohort. Methods The study population included ad...

BACKGROUND Nearly 20-40% of patients with HER2-positive cancer patients develop brain metastases (BMs), where stereotactic radiosurgery (SRS) is standard for care for local disease control. Tucatinib, an oral HER2-selective tyrosine kinase inhibitor (TKI), has been demonstrated to be safe and efficacious in HER2+ breast cancer in combination with c...

Glioblastoma remains a fatal diagnosis despite continuous efforts to improve upon the current standard backbone management paradigm of surgery, radiation therapy, systemic therapy and Tumor Treating Fields. Radiation therapy (RT) plays a pivotal role, with progress recently achieved in multiple key areas of research. The evolving landscape of dose...

INTRODUCTION We introduce a method of predicting clinical outcomes in newly diagnosed brain metastases (BM) patients after upfront stereotactic radiosurgery (SRS), based on a novel metric - brain metastases distribution width (BMDW) – which measures the amount of variation in BM volume. METHODS BMDW was defined as the coefficient of variation of m...

We analyzed the impact of systemic therapy on lung cancer (LC) patients treated with stereotactic radiosurgery (SRS) for brain metastasis (BM) in terms of objective response, intracranial progression-free survival (iPFS), and overall survival (OS). Response was calculated using chi-square analysis with adjusted residuals, while iPFS and OS were com...

INTRODUCTION: Stereotactic radiosurgery (SRS) is an effective treatment for brain metastasis (BM), but patients remain at significant risk for distant intracranial failure (DIF) due to undetected lesions at the time of SRS or subsequent seeding. We implemented dedicated treatment planning imaging with novel MR sequences with the goals of enhancing...

In the current era of high-precision radiation therapy, real-time magnetic resonance (MR)-guided tracking of the tumor and organs at risk (OARs) is a novel approach that enables accurate and safe delivery of high-dose radiation. Organ tracking provides a general sense of the need for daily online adaptation but lacks precise information regarding e...

Background IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survi...

BACKGROUND Immune checkpoint inhibitors (ICIs) have efficacy in several solid tumors but limited efficacy in glioblastoma (GBM). This study evaluated the safety of anti-CTLA-4 and anti-PD-1 ICIs alone or in combination in newly diagnosed GBM after completion of standard radiochemotherapy with the subsequent intent to test combinatorial ICIs in this...

Introduction This study compares four management paradigms for large brain metastasis (LMB): fractionated SRS (FSRS), staged SRS (SSRS), resection and postoperative-FSRS (postop-FSRS) or preoperative-SRS (preop-SRS). Methods Patients with LBM (≥ 2 cm) between July 2017 and January 2022 at a single tertiary institution were evaluated. Primary endpo...

Mutations in isocitrate dehydrogenase (IDH) genes, an early step in the ontogeny of lower-grade gliomas, induce global epigenetic changes characterized by a hypermethylation phenotype and are critical to tumor classification, treatment decision making, and estimation of patient prognosis. The introduction of IDH inhibitors to block the oncogenic ne...

2008 Background: For non-small cell lung cancer (NSCLC) with brain metastases (BM) stereotactic radiosurgery (SRS) is the current preferred therapy. Due to frequent intracranial failures, there is a high unmet need for salvage therapies. Whole brain radiotherapy (WBRT) reduces intracranial failure but used less frequently due to cognitive consequen...

TPS2089 Background: 20-40% of HER-2-positive breast cancer patients develop brain metastases (BMs), for which stereotactic radiosurgery (SRS) is used for local disease control. Tucatinib, an oral HER-2-selective tyrosine kinase inhibitor (TKI), has been demonstrated to be safe and efficacious in HER-2-positive breast cancer in combination with cape...

TPS2093 Background: The receptor for advanced glycation end-products (RAGE) is a multifunctional receptor which stimulates proliferation, invasion, resistance to chemotherapy and radiotherapy, and metastatic spread when activated. One of the RAGE ligands preferentially associated with brain metastasis, S100A9, has been recently identified as a spec...

12011 Background: NRG-CC003, a phase II/III study, randomized 393 patients with small cell lung cancer to prophylactic cranial irradiation (PCI) with or without Hippocampal Avoidance (HA). “Hopefulness” is a cognitive construct based on 3 components: goals; pathways to reach those goals; and agency (i.e., motivation to embark on the pathway). Hope...

Introduction The ability to dynamically adjust target contours, derived Boolean structures, and ultimately, the optimized fluence is the end goal of online adaptive radiotherapy (ART). The purpose of this work is to describe the necessary tests to perform after a software patch installation and/or upgrade for an established online ART program. Met...

The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was c...

Purpose/Objective: Neurocognitive function assessment traditionally requires extensive pen and paper-based assessments, and is resource-intensive, precluding incorporation into routine daily clinical activities. As a pragmatic alternative, we initiated a prospective study (NCT05504681) of a novel, multi-dimensional app-based assessment of neurocogn...

Background This retrospective study compares the real-world performance of cerebrospinal fluid (CSF) CNSide™ versus cytology in leptomeningeal disease (LMD). Methods Consecutive patients with suspected LMD who underwent lumbar punctures for CSF cytology and CNSide™ from January 2020 to December 2022 were reviewed. LMD was classified by EANO criter...

Purpose/Objective: Connectomics is an evolving branch of neuroscience that evaluates structural and functional connectivity in the brain. Whole brain radiation therapy (WBRT) is used in patients with multiple brain metastases but is known to cause post-treatment neurocognitive changes. The objective of this prospective imaging study is to evaluate...

Purpose/Objective: Predicting time to local failure (LF) or development of radiation necrosis (RN) requires consideration of numerous patient-related, disease-specific, and treatment-related variables. The objective of this study was to develop machine-learning (ML) algorithms that would systematically evaluate all of these pertinent variables to e...

DNA damage response (DDR) mechanisms are critical to maintenance of overall genomic stability, and their dysfunction can contribute to oncogenesis. Significant advances in our understanding of DDR pathways have raised the possibility of developing therapies that exploit these processes. In this expert-driven consensus review, we examine mechanisms...

Intracranial tumors include a challenging array of primary and secondary parenchymal and extra-axial tumors which cause neurologic morbidity consequential to location, disease extent, and proximity to critical neurologic structures. Radiotherapy can be used in the definitive, adjuvant, or salvage setting either with curative or palliative intent. P...

Radiotherapy for ultracentral lung tumors represents a treatment challenge, considering the high rates of high-grade treatment-related toxicities with stereotactic body radiation therapy (SBRT) or hypofractionated schedules. Accelerated hypofractionated magnetic resonance-guided adaptive radiation therapy (MRgART) emerged as a potential game-change...

Background Early palliative/pre-emptive intervention improves clinical outcomes and quality of life for patients with metastatic cancer. A previous signal-seeking randomized controlled trial (RCT) demonstrated that early upfront radiotherapy to asymptomatic or minimally symptomatic high-risk osseous metastases led to reduction in skeletal-related e...

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a di...

Background and objective: Tumor treating fields (TTFields) therapy have emerged as a potentially effective treatment for various malignancies by delivering low-intensity, intermediate-frequency electrical fields that disrupt many processes inside cells, resulting in the interruption of cell division in cancer cells. Additionally, TTFields therapy...

BACKGROUND A randomized, phase II, placebo-controlled, blinded clinical trial (NCT01062425) was conducted to determine the efficacy of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, versus placebo in combination with radiation and temozolomide in newly diagnosed glioblastoma. METHODS Patients with new...

BACKGROUND 20-40% of HER-2-positive breast cancer patients develop brain metastases (BMs), for which stereotactic radiosurgery (SRS) is used for local disease control. Tucatinib, an oral HER-2-selective tyrosine kinase inhibitor (TKI), has been demonstrated to be safe and efficacious in HER-2-positive breast cancer in combination with capecitabine...

BACKGROUND The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RA...

BACKGROUND New therapies are especially needed for uMGMT nGBM. NRG Oncology BN002 (phase I) demonstrated safety and preliminary efficacy of Ipi+Nivo for nGBM, leading to BN007 as phase II/III. METHODS Adults with uMGMT nGBM (WHO 2016) and KPS ≥ 70 were randomized to RT and concurrent and adjuvant Ipi+Nivo or TMZ, stratified by glioma-recursive par...

The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve the reliability of response assessment in glioma trials. Over time some limitations of these criteria were identified, and uncertainty emerged regarding integrating features of the modified RANO (mRA...

We report the interim analysis of a phase 1, proof-of-concept study (NCT04689048), to assess the potential clinical utility of an amino acid radiotracer, 18F-fluciclovine PET/CT, as a functional integral biomarker for previously untreated patients with large brain metastases [BM] (≥1 lesion; >2cm) treated with staged stereotactic radiosurgery (SSRS...

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and...

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the interrelated priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and r...

Background and purpose: Planning on a static dataset that reflects the simulation day anatomy is routine for SBRT. We hypothesize the quality of on-table adaptive plans is similar to the baseline plan when delivering stereotactic MR-guided adaptive radiotherapy (SMART) for pancreatic cancer (PCa). Materials and methods: Sixty-seven inoperable PC...

Purpose: The purpose of this study is to investigate inter-planner plan quality variability using a manual forward planning (MFP)- or fast inverse planning (FIP, Lightning)-approach for single brain lesions treated with the Gamma Knife® (GK) Icon™. Methods: Thirty patients who were previously treated with GK stereotactic radiosurgery or radiothe...

Purpose: Lapatinib plus whole brain radiotherapy (WBRT) or Stereotactic Radiosurgery (SRS) was hypothesized to improve the 12-week intracranial complete response (CR) rate compared to either option of radiotherapy (RT) alone for patients with brain metastases from human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Methods: T...

We present the first known case of a multi-recurrent high-grade glioma patient, which after multiple salvage strategies, was treated with a novel radiation therapy technique, “Temporally-Modulated Pulsed Proton Re-irradiation” (TMPPR). This proton therapy technique has the radiobiological property to allow an enhanced tumor cell death and an increa...

e20636 Background: Patients with small cell lung cancer (SCLC) are at a particularly high risk for the development of brain metastases. Current guidelines recommend prophylactic cranial irradiation (PCI) for these patients to prevent brain metastases and prolong overall survival (OS), although the clinical evidence for recommendations stems from an...

2028 Background: Prior reports cited detection rates of leptomeningeal metastases (LM) using CNSide vs standard CSF cytology of 78% vs 55% in NSCLC and 84% vs 52% in various solid tumor cohorts. The objective of this study was to compare the real-world performance of the CNSide assay in diagnosing LM versus CSF cytology from lumbar puncture (LP) an...

2017 Background: Response Assessment in Neuro-Oncology (RANO) criteria for high-grade and low-grade glioma (HGG and LGG) were developed to improve reliability of response assessment in glioma trials. Several limitations of the original RANO criteria have been reported. Methods: To address limitations of the original RANO criteria, a large cohort of...