Publications by authors named "Rohan Ramakrishna"

The blood-brain barrier (BBB) remains an obstacle for delivery of chemotherapeutic agents to gliomas. High grade and recurrent gliomas continue to portend a poor prognosis. Multiple methods of bypassing or manipulating the BBB have been explored, including hyperosmolar therapy, convection-enhanced delivery (CED), laser-guided interstitial thermal therapy (LITT), and Magnetic Resonance Guided Focused Ultrasound (MRgFUS) to enhance delivery of chemotherapeutic agents to glial neoplasms.

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Article Synopsis
  • Precision oncology relies on biomarkers, with MGMT gene promoter methylation being a critical clinical biomarker for glioblastoma multiforme (GBM).
  • Time-consuming preanalytical processes like biospecimen storage and intratumor methylation variability can affect data reproducibility, but research showed that standard processing techniques do not significantly alter MGMT methylation assessment.
  • Despite consistent methods yielding reliable results, a significant portion of GBM specimens (26%-34%) displayed intratumor methylation heterogeneity, highlighting the necessity for multiple biopsies to accurately evaluate MGMT status.
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Objective: Our purpose was to describe our initial institutional experience using dedicated brain [18F]-Fluoroestradiol (FES) PET/CT or PET/MRI in the management of patients with estrogen-receptor-positive (ER+) breast cancer brain metastases (BCBM), and compare to [18F]-Fluorodeoxyglucose (FDG) PET and MRI.

Materials & Methods: Patients with biopsy-proven ER+ disease and MRI findings of suspected new, progressive, or recurrent BCBM were included in this retrospective study. Clinical and demographic data were collected.

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Background And Purpose: WHO grade 3 meningiomas are rare and poorly understood and have a higher propensity for recurrence, metastasis, and worsened clinical outcomes compared with lower-grade meningiomas. The purpose of our study was to prospectively evaluate the molecular profile, PET characteristics, and outcomes of patients with World Health Organization grade 3 meningiomas who were imaged with gallium 68 (Ga) DOTATATE PET/MR imaging.

Materials And Methods: Patients with World Health Organization grade 3 meningiomas enrolled in our prospective observational cohort evaluating the utility of (Ga) DOTATATE PET/MR imaging in somatostatin receptor positive brain tumors were included.

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Precision oncology is driven by molecular biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase ( ) gene DNA promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage before fixing, sampling, and processing are major sources of errors and batch effects, that are further confounded by intra-tumor heterogeneity of promoter methylation.

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Background: Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery.

Methods: Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning.

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Objective: Olfactory groove meningiomas (OGMs) often require surgical removal. The introduction of recent keyhole approaches raises the question of whether these tumors may be better treated through a smaller cranial opening. One such approach, the supraorbital keyhole craniotomy, has never been compared with more traditional open transcranial approaches with regard to outcome.

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Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM.

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Background: Chronically elevated intracranial pressure (ICP) seen in idiopathic intracranial hypertension (IIH) can cause the development of skull base encephaloceles and cerebrospinal fluid (CSF) leaks. Surgical repair and ventriculoperitoneal shunt (VPS) placement are mainstays of treatment. Venous sinus stenting (VSS) is a newly accepted treatment modality.

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Background: The introduction of Cesium-131 (Cs-131) as a radiation source has led to a resurgence of brachytherapy for central nervous system (CNS) tumors. The aim of this study was to evaluate the safety and efficacy of the largest cohort of Cs-131 patients to-date.

Methods: A retrospective review of all CNS tumors treated with resection and adjuvant Cs-131 brachytherapy at New York-Presbyterian/Weill Cornell from 2010 to 2021 was performed.

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Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate.

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Background: Clinical trials evaluating immune checkpoint inhibition (ICI) in recurrent high-grade gliomas (rHGG) report 7%-20% 6-month progression-free survival (PFS), while re-irradiation demonstrates 28%-39% 6-month PFS.

Aims: We evaluate outcomes of patients treated with ICI and concurrent re-irradiation utilizing stereotactic body radiotherapy/fractionated stereotactic radiosurgery (SBRT) compared to ICI monotherapy.

Methods And Results: Patients ≥18-years-old with rHGG (WHO grade III and IV) receiving ICI + SBRT or ICI monotherapy between January 1, 2016 and January 1, 2019 were included.

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The incidence of brain metastases continues to present a management issue despite the advent of improved systemic control and overall survival. While the management of oligometastatic disease (ie, 1-4 brain metastases) with surgery and radiation has become fairly straightforward in the era of radiosurgery, the management of patients with multiple metastatic brain lesions can be challenging. Here we review the available evidence and provide a multidisciplinary management algorithm for brain metastases that incorporates the latest advances in surgery, radiation therapy, and systemic therapy while taking into account the latest in precision medicine-guided therapies.

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Purpose: Hypothalamic obesity (HO) is a complication associated with craniopharyngioma (CP). Attempts have been made to perioperatively predict the development of this complication, which can be severe and difficult to treat.

Methods: Patients who underwent first transsphenoidal surgical resection in a single center between February 2005 and March 2019 were screened; those who have had prior surgery or radiation, were aged below 18 years, or did not have follow up body mass index (BMI) after surgery were excluded.

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Multiple approaches with [Ga]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of different approaches to quantitative brain [Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method. Patients with suspected meningioma were imaged prospectively with [Ga]-DOTATATE brain PET/MRI.

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Purpose To evaluate dynamic gallium 68 (Ga) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) brain PET/MRI as an adjunct modality in meningioma, enabling multiparametric standardized uptake value (SUV) and Patlak net binding rate constant () imaging, and to optimize static acquisition period. Materials and Methods In this prospective study (ClinicalTrials.gov no.

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Background And Purpose: Meningiomas, the most common primary intracranial tumor, are vascular neoplasms that express somatostatin receptor-2 (SSTR2). The purpose of this investigation was to evaluate if a relationship exists between tumor vascularity and SSTR2 expression, which may play a role in meningioma prognostication and clinical management.

Materials And Methods: Gallium-68-DOTATATE PET/MRI with dynamic contrast-enhanced (DCE) perfusion was prospectively performed.

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Introduction: Neurofibromatosis type 2 (NF2) is characterized by often bilateral vestibular schwannomas (VS) that result in progressive hearing loss and compression of nearby brainstem structures causing cranial nerve palsies. Treatment of these tumors remains challenging, as both surgical removal and expectant management can result in symptom progression. Stereotactic radiosurgery (SRS) has been investigated for the management of NF2-associated VS; however, the role, promises, and pitfalls of this treatment modality remain unclear.

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Article Synopsis
  • The study assesses the long-term outcomes of single-fraction stereotactic radiosurgery (SRS) for vestibular schwannoma using gamma knife (GK) versus linear accelerator (LINAC) systems, analyzing safety and efficacy over a decade.
  • A meta-analysis of 39 studies (29 GK, 10 LINAC) involving 6,516 patients found comparable tumor control rates of 93% for GK and 94% for LINAC, along with reduced chances of hearing preservation for both modalities.
  • GK showed better preservation of trigeminal nerve function, while LINAC was associated with lower rates of tinnitus, indicating distinct advantages for each treatment that require further investigation.
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Background: The role of postoperative upfront radiotherapy (RT) in the management of gross totally resected atypical meningiomas remains unclear. This single-center retrospective review of newly diagnosed histologically confirmed cases of World Health Organization (WHO) Grade II atypical meningioma at Weill Cornell Medicine from 2004 to 2020 aims to compare overall survival (OS) and progression-free survival (PFS) of postoperative upfront RT versus observation, stratified by resection status (gross total resection [GTR] vs subtotal resection [STR]).

Methods: Ninety cases of atypical meningioma were reviewed (56% women; median age 61 years; median follow-up 41 months).

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Background: Large vestibular schwannomas (VS) pose a treatment challenge for both microsurgery (MS) and stereotactic radiosurgery (SRS). Technical developments have allowed for safer irradiation of large tumors. It remains unclear if SRS can achieve appropriate tumor control and acceptable cranial nerve toxicities.

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Background: Vestibular schwannomas (VS) are tumors of the cerebellopontine angle with significant morbidity, causing hearing loss, tinnitus, and trigeminal and facial nerve compromise. An effective alternative to microsurgical resection is stereotactic radiosurgery (SRS), which can be delivered in either single-fraction (SRS) or hypofractionated stereotactic radiotherapy (hSRT) (3-5 treatments) regimens. It remains unclear which fractionation regimen provides superior outcomes.

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