Publications by authors named "Michael D Chan"

Objective: Stereotactic radiosurgery (SRS) has been used to manage patients with intracranial meningioma with contraindications to resection. Limitations to SRS traditionally include tumors > 3 cm due to the risk of posttreatment toxicity. Hypofractionated SRS (hSRS) has been proposed as an alternative for tumors exceeding volume constraints for single-fraction SRS, although how hypofractionation affects the volume versus toxicity relationship has not been reported.

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Objective: Gamma Knife radiosurgery (GKRS) is a treatment option for refractory trigeminal neuralgia (TN). However, there is a paucity of data regarding the effectiveness of GKRS for relapsing TN following microvascular decompression (MVD). The aim of this study was to characterize the response rate, complications, pain relief durability, and predictors of pain relapse for salvage GKRS following MVD for TN.

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Objective: Opportunity exists for improved local control rates of grade 2 meningiomas that recur despite maximal surgical resection and adjuvant fractionated radiotherapy (RT). We describe a dose escalation strategy of increasing the total tumor radiation dose by adding a stereotactic radiosurgery (SRS) boost targeting gross disease to fractionated RT.

Methods: A single-institution retrospective cohort of patients from 2009-2023 with grade 2 meningioma treated with surgical resection, fractionated RT, and SRS boost were evaluated for baseline characteristics, local disease control, and adverse events (AE).

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Purpose/objectives: Biomarkers for extracranial oligometastatic disease remain elusive and few studies have attempted to correlate genomic data to the presence of true oligometastatic disease.

Methods: Patients with non-small cell lung cancer (NSCLC) and brain metastases were identified in our departmental database. Electronic medical records were used to identify patients for whom liquid biopsy-based comprehensive genomic profiling (Guardant Health) was available.

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Brain metastasis is the most common intracranial malignancy in adults. The prognosis is extremely poor, partly because most patients have more than one brain lesion, and the currently available therapies are nonspecific or inaccessible to those occult metastases due to an impermeable blood-tumor barrier (BTB). Phosphatidylserine (PS) is externalized on the surface of viable endothelial cells (ECs) in tumor blood vessels.

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Treatment of non-small cell lung cancer (NSCLC) has drastically changed in recent years owing to the robust anticancer effects of immune checkpoint inhibitors (ICI). However, only 20% of the patients with NSCLC benefit from ICIs, highlighting the need to uncover the mechanisms mediating resistance. By analyzing the overall survival (OS) and mutational profiles of 424 patients with NSCLC who received ICI treatments between 2015 and 2021, we determined that patients carrying a loss-of-function mutation in neurotrophic tyrosine kinase receptor 1 (NTRK1) had a prolonged OS when compared with patients with wild-type NTRK1.

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Article Synopsis
  • The IASLC has developed a new histological grading system for invasive lung adenocarcinoma (LUAD) that aims to predict distant metastases, particularly in the brain and bones, after surgery.
  • A study analyzed data from 174 early-stage LUAD patients who underwent surgery, monitoring them for 5 years to assess metastasis-free survival rates.
  • The findings suggest that the IASLC grading system is more effective than traditional grading methods in predicting the occurrence of distant metastases and could help identify high-risk patients post-surgery.
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Article Synopsis
  • High-grade immune-related adverse events (irAEs) can limit treatment options for patients with non-small cell lung cancer (NSCLC) and predicting these events is crucial for effective therapy management.
  • A study analyzed 430 NSCLC patients who received immune checkpoint inhibitors (ICIs) to evaluate the occurrence and genetic factors associated with high-grade irAEs.
  • The findings revealed that certain genetic mutations in tumor samples were linked to a higher risk of high-grade irAEs, offering insights for treatment considerations and monitoring strategies.*
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Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI.

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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.

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Purpose: The role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM (Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas), a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas.

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The clinical efficacy and relative tolerability of adverse effects of immune checkpoint immunotherapy have led to its increasingly routine use in the management of multiple advanced solid malignancies. Radiation therapy (RT) is well-known to have both local and distant immunomodulatory effects, which has led to extensive investigation into the synergism of these 2 therapies. While the central nervous system (CNS) has historically been thought to be a sanctuary site, well-protected by the blood-brain barrier from the effects of immunotherapy, over the last several years studies have shown the benefits of these drugs, particularly in metastatic disease involving the CNS.

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Objective: The objective of this study was to examine survival outcomes in 136 patients with renal cell carcinoma with metastases to the brain who were treated with radiation combined with immunotherapy or tyrosine kinase inhibitor compared to those who were treated with radiation therapy alone.

Methods: The Wake Forest Gamma Knife prospective database was searched for all patients with renal cell carcinoma brain metastases. Outcome measurements included overall survival, determined via the Kaplan-Meier Method, and cumulative incidence of local and distant failure, determined using the Fine Gray competing risks analysis with death as a competing risk for the 136 patients included.

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Background: Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests.

Method: In this single institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA).

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Objective: Imaging changes after stereotactic radiosurgery (SRS) can occur for years after treatment, although the available data on the incidence of tumor progression and adverse radiation effects (ARE) are generally limited to the first 2 years after treatment.

Methods: A single-institution retrospective review was conducted of patients who had >18 months of imaging follow-up available. Patients who had ≥1 metastatic brain lesions treated with Gamma Knife SRS were assessed for the time to radiographic progression.

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Brain metastases is the most common intracranial tumor and account for approximately 20% of all systematic cancer cases. It is a leading cause of death in advanced-stage cancer, resulting in a five-year overall survival rate below 10%. Therefore, there is a critical need to identify effective biomarkers that can support frequent surveillance and promote efficient drug guidance in brain metastasis.

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Purpose: Brain metastases (BMs) are a common source of morbidity and mortality. Guidelines do not advise brain surveillance for locally advanced non-small cell lung cancer (LA-NSCLC). We describe the incidence, time to development, presentation, and management of BMs after definitive chemoradiotherapy (CRT).

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The brain is one of the most common metastatic sites among breast cancer patients, especially in those who have Her2-positive or triple-negative tumors. The brain microenvironment has been considered immune privileged, and the exact mechanisms of how immune cells in the brain microenvironment contribute to brain metastasis remain elusive. In this study, we found that neutrophils are recruited and influenced by c-Met high brain metastatic cells in the metastatic sites, and depletion of neutrophils significantly suppressed brain metastasis in animal models.

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Article Synopsis
  • The study investigates the outcomes of stereotactic radiosurgery (SRS) for small-cell lung cancer (SCLC) brain metastases compared to non-small cell lung cancer (NSCLC), addressing historical concerns about SCLC's prognosis and neurological risks.
  • Data from multiple centers and a clinical trial were analyzed, focusing on overall survival (OS) and central nervous system (CNS) progression for patients with SCLC and NSCLC over a 22-year period.
  • Results indicated that patients with NSCLC experienced better overall survival compared to those with SCLC, with significant differences in survival and CNS progression rates across various analyses, particularly favoring NSCLC cases.
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Different types of therapy are currently being used to treat non-small cell lung cancer (NSCLC) depending on the stage of tumor and the presence of potentially druggable mutations. However, few biomarkers are available to guide clinicians in selecting the most effective therapy for all patients with various genetic backgrounds. To examine whether patients' mutation profiles are associated with the response to a specific treatment, we collected comprehensive clinical characteristics and sequencing data from 524 patients with stage III and IV NSCLC treated at Atrium Health Wake Forest Baptist.

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Background: Improvements in therapies have led to an increasing number of long-term survivors of brain metastases. The present series compares a population of 5-year survivors of brain metastases to a generalized brain metastases population to assess for factors attributable to long-term survival.

Methods: A single institution retrospective review was performed to identify 5-year survivors of brain metastases who received stereotactic radiosurgery (SRS).

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