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Neurosurgical Review Oct 2022Tumor cyst aspiration followed by Gamma Knife radiosurgery (GKRS) for large cystic brain metastases is a reasonable and effective management strategy. However, even with... (Review)
Review
Tumor cyst aspiration followed by Gamma Knife radiosurgery (GKRS) for large cystic brain metastases is a reasonable and effective management strategy. However, even with aspiration, the target lesion tends to exceed the dimensions of an ideal target for stereotactic radiosurgery. In this case, the local tumor control rate and the risk of complication might be a critical challenge. This study is aimed to investigate whether fractionated GKRS (f-GKRS) could solve these problems. Between May 2018 and April 2021, eight consecutive patients with nine lesions were treated with f-GKRS in five or ten sessions after cyst aspiration. The aspiration was repeated as needed throughout the treatment course to maintain the cyst size and shape. The patient characteristics, radiologic tumor response, and clinical course were reviewed using medical records. The mean follow-up duration was 10.2 (2-28) months. The mean pre-GKRS volume and maximum diameter were 16.7 (5-55.8) mL and 39.0 (31-79) mm, respectively. The mean tumor volume reduction achieved by aspiration was 55.4%. The tumor volume decreased for all lesions, and symptoms were alleviated in all patients. The median overall survival was 10.0 months, and the estimated 1-year survival rate was 41.7% (95% CI: 10.9-70.8%). The local tumor control rate was 100%. No irradiation-related adverse events were observed. f-GKRS for aspirated cystic brain metastasis is a safe, effective, and less invasive management option for large cystic brain metastases.
Topics: Brain Neoplasms; Cysts; Humans; Radiosurgery; Survival Rate; Tumor Burden
PubMed: 35834076
DOI: 10.1007/s10143-022-01835-y -
Journal of Clinical Neuroscience :... Feb 2020Fluoroscopic-guided lumbar puncture (LP) is a procedure commonly performed by radiologists, which in some circumstances may be difficult or impossible using a... (Comparative Study)
Comparative Study Review
Fluoroscopic-guided lumbar puncture (LP) is a procedure commonly performed by radiologists, which in some circumstances may be difficult or impossible using a traditional posterior interspinous or interlaminar approach. Alternatives to LP include cervical and cisternal punctures, placement of an Ommaya reservoir, and lumbar laminectomy. More recently, however, there has been a move toward access of the thecal sac through a transforaminal approach in patients with challenging anatomy. This report outlines our approach and experience using transforaminal LP (TFLP) in patients with spinal muscular atrophy (SMA) with a 100% success rate. We discuss its utility in other patients with difficult access and compare TFLP with other techniques to access the intrathecal space.
Topics: Female; Fluoroscopy; Humans; Laminectomy; Male; Middle Aged; Muscular Atrophy, Spinal; Postoperative Complications; Spinal Puncture
PubMed: 31980274
DOI: 10.1016/j.jocn.2019.12.056 -
World Journal of Clinical Cases Jun 2022Glioblastoma (GBM) is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis. Leptomeningeal dissemination (LMD)...
BACKGROUND
Glioblastoma (GBM) is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis. Leptomeningeal dissemination (LMD) is a serious complication of GBM that often results in dire outcomes. There is currently no effective treatment.
AIM
To estimate the clinical outcomes of combination therapy in GBM patients with LMD.
METHODS
A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution. All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate (MTX) and systemic chemotherapy. Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.
RESULTS
Twenty-six patients were enrolled in this study. The median time from GBM diagnosis to LMD development was 9.3 mo (range: 2-59 mo). The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo (range: 2-59 mo). In the Cox univariate analysis, gross resection of tumor ( = 0.022), Karnofsky performance status (KPS) > 60 ( = 0.002), and Ommaya reservoir implant ( < 0.001) were correlated with survival. Multivariate analysis showed that KPS > 60 ( = 0.037) and Ommaya reservoir implant ( = 0.014) were positive factors correlated with survival. Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy. According to Common Terminology Criteria of Adverse Events 4.03, most of the patients presented with toxicity less than grade 3.
CONCLUSION
Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD, with mild treatment-related side effects.
PubMed: 35979103
DOI: 10.12998/wjcc.v10.i17.5595 -
Journal of Nuclear Medicine : Official... Dec 2019Radiation dose estimations are key for optimizing therapies. We studied the role of I-omburtamab (8H9) given intraventricularly in assessing the distribution and...
Radiation dose estimations are key for optimizing therapies. We studied the role of I-omburtamab (8H9) given intraventricularly in assessing the distribution and radiation doses before I-omburtamab therapy in patients with metastatic leptomeningeal disease and compared it with the estimates from cerebrospinal fluid (CSF) sampling. Patients with histologically proven malignancy and metastatic disease to the central nervous system or leptomeninges who met eligibility criteria for I-omburtamab therapy underwent immuno-PET imaging with I-8H9 followed by I-8H9 antibody therapy. Patients were imaged with approximately 74 MBq of intraventricular I-omburtamab via an Ommaya reservoir. Whole-body PET images were acquired at approximately 4, 24, and 48 h after administration and analyzed for dosimetry calculations. Peripheral blood and CSF samples were obtained at multiple time points for dosimetry estimation. Forty-two patients with complete dosimetry and therapy data were analyzed. I-omburtamab PET-based radiation dosimetry estimations revealed mean (±SD) absorbed dose to the CSF for I-8H9 of 0.62 ± 0.40 cGy/MBq, compared with 2.22 ± 2.19 cGy/MBq based on I-omburtamab CSF samples and 1.53 ± 1.37 cGy/MBq based on I-omburtamab CSF samples. The mean absorbed dose to the blood was 0.051 ± 0.11 cGy/MBq for I-omburtamab samples and 0.07 ± 0.04 cGy/MBq for I-omburtamab samples. The effective whole-body radiation dose for I-omburtamab was 0.49 ± 0.27 mSv/MBq. The mean whole-body clearance half-time was 44.98 ± 16.29 h. PET imaging with I-omburtamab antibody administered intraventricularly allows for noninvasive estimation of dose to CSF and normal organs. High CSF-to-blood absorbed-dose ratios are noted, allowing for an improved therapeutic index to leptomeningeal disease and reduced systemic doses. PET imaging-based estimates were less variable and more reliable than CSF sample-based dosimetry.
Topics: Adolescent; Adult; Antibodies, Monoclonal, Murine-Derived; Child; Child, Preschool; Female; Humans; Infant; Iodine Radioisotopes; Male; Meningeal Neoplasms; Neoplasm Metastasis; Positron-Emission Tomography; Radiometry; Tissue Distribution; Young Adult
PubMed: 31405921
DOI: 10.2967/jnumed.118.219576 -
Frontiers in Neurology 2022Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and...
BACKGROUND
Glioma is the most common primary brain tumor in adults with poor prognosis. The glioma patients benefit from STUPP strategy, including maximum and safe resection and adjuvant radiotherapy and chemotherapy. Arsenic trioxide could inhibit various tumors. However, it is a challenge to evaluate the efficiency and safety of srsenic trioxide in glioma patients.
OBJECTIVE
The arsenic trioxide has the potent therapeutic effect on glioma. However, the safety and efficacy of local interstitial chemotherapy with arsenic trioxide in newly diagnosed glioma patients is unclear.
METHODS
All patients received partial or complete tumor resection and intraoperative implantation of Ommaya reservoirs followed by standard radiotherapy. Arsenic trioxide with the starting dose 0.3 mg was administered an Ommaya reservoir catheter inserted into the tumor cavity for 5 consecutive days every 3 months for a total of eight cycles unless tumor progression or excessive toxicity was observed.
RESULTS
No hematological or grade 4 non-hematological toxicity was observed in any patient during arsenic trioxide treatment. The maximum tolerated dose of 1.5 mg of arsenic trioxide was safe and well tolerated. The median overall survival for WHO grade 3 glioma was 33.6 months, and for glioblastoma was 13.9 months. The median progression-free survival for WHO grade 2 glioma was 40.3 months, for grade 3 glioma was 21.5 months, and for glioblastoma was 9.5 months.
CONCLUSION
These results suggest that arsenic trioxide is safe and well tolerated with local delivery into the tumor cavity of the brain, and the dose recommended for a phase II trial is 1.5 mg.
PubMed: 36212657
DOI: 10.3389/fneur.2022.1001829 -
Asian Journal of Neurosurgery 2021Pediatric hydrocephalus (PH) results in significant clinical and psychosocial morbidity in pediatric population.
CONTEXT
Pediatric hydrocephalus (PH) results in significant clinical and psychosocial morbidity in pediatric population.
AIMS
The aims of the study are to evaluate clinical, surgical, and outcome perspective of PH patients of age <12 years.
SETTINGS AND DESIGN
This is a retrospective cohort study.
MATERIALS AND METHODS
This study includes 117 pediatric patients (age ≤12 years) of hydrocephalus due to various etiology admitted in our department between September 2018 and December 2020. Demographic profile, etiology, clinical presentation, management, complications and postoperative outcome characteristics were evaluated. Survival analysis was done with respect to etiology and age group.
STATISTICAL ANALYSIS USED
< 0.05 was considered statistically significant. Unpaired -test and Chi-square test were used. Kaplan-Meier curve plotting and survival analysis were also done.
RESULTS
Male-to-female ratio was 1.3:1. Most frequent etiology of PH was postinfectious (35%). Posterior fossa pilocytic astrocytoma (34.2%) was the most common neoplastic etiology. Surgical procedure performed for PH was ventriculoperitoneal shunting ( = 103), Ommaya reservoir ( = 2) placement, and endoscopic third ventriculostomy (ETV) ( = 8). Mortality was significantly ( = 0.0139) more in patients of neoplastic etiology. Cognitive deficits and delayed developmental milestones were significantly ( < 0.05) more in congenital hydrocephalus etiology. There was a nonsignificant difference in survival between age groups ( = 0.1971). However, a significant survival difference was evident ( = 0.0098) for etiology.
CONCLUSIONS
Disease-specific mortality is main cause of mortality in PH. Neoplastic etiology PH has poor survival when compared to others. Life-long routine controls are required to avoid future possible complications and enhance better rehabilitation of the child.
PubMed: 35071066
DOI: 10.4103/ajns.AJNS_132_21 -
NPJ Precision Oncology Feb 2024Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of...
Pre-surgery differential diagnosis is valuable for personalized treatment planning in intramedullary spinal cord tumors. This study assessed the performance of sequencing cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) for differential diagnosis of these tumors. Prospectively enrolling 45 patients with intramedullary spinal cord lesions, including diffuse midline glioma (DMG), H3K27-altered (14/45), glioblastoma (1/45), H3-wildtype-astrocytoma (10/45), ependymoma (11/45), and other lesions (9/45), CSF samples were collected via lumbar puncture (41/45), intraoperative extraction (3/45), and Ommaya reservoir (1/45). Then, these samples underwent targeted sequencing along with paired tissue DNA. DMG, H3K27-altered patients exhibited a higher ctDNA positivity (85.7%, 12/14) compared to patients with H3-wildtype-astrocytoma (0/8, P = 0.0003), ependymoma (2/10, P = 0.003), and glioneuronal tumor (0/3, P = 0.009). The histological-grade-IV (P = 0.0027), Ki-67 index ≥10% (P = 0.014), and tumor reaching spinal cord surface (P = 0.012) are also associated with higher ctDNA positivity. Interestingly, for patients with TERT promoter mutant tumors, TERT mutation was detectable in the CSF cfDNA of one DMG case, but not other five cases with histological-grade-II tumors. Shared copy number variants were exclusively observed in DMG, H3K27-altered, and showed a strong correlation (Correlation = 0.95) between CSF and tissue. Finally, H3K27M mutations in CSF exhibited high diagnostic efficiency for DMG, H3K27-altered (Sensitivity = 85.7%, Specificity = 100.0%, AUC = 0.929). Notably, H3K27M was detectable in CSF from patients with recurrent tumors, making it easily applicable for postoperative monitoring. In conclusion, the molecular profile from ctDNA released into CSF of malignant tumors was more frequently detected compared to relatively benign ones. Sequencing of ctDNA in CSF exhibited high efficiency for the differential diagnosis of DMG, H3K27-altered.
PubMed: 38388726
DOI: 10.1038/s41698-024-00541-w -
Neuro-oncology Practice Dec 2020The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation....
BACKGROUND
The economic burden of cancer in the United States is substantial, and better understanding it is essential in informing health care policy and innovation. Leptomeningeal carcinomatosis (LC) represents a late complication of primary cancer spreading to the leptomeninges.
METHODS
The IBM MarketScan Research databases were queried for adults diagnosed with LC from 2001 to 2015, secondary to 4 primary cancers (breast, lung, gastrointestinal, and melanoma). Health care resource utilization (HCRU) and treatment utilization were quantified at baseline (1-year pre-LC diagnosis) and 30, 90, and 365 days post-LC diagnosis.
RESULTS
We identified 4961 cases of LC (46.3% breast cancer, 34.8% lung cancer, 13.5% gastrointestinal cancer, and 5.4% melanoma). The median age was 57.0 years, with 69.7% female and 31.1% residing in the South. Insurance status included commercial (71.1%), Medicare (19.8%), and Medicaid (9.1%). Median follow-up was 66.0 days (25th percentile: 24.0, 75th percentile: 186.0) and total cumulative costs were highest for the gastrointestinal subgroup ($167 768) and lowest for the lung cancer subgroup ($145 244). There was considerable variation in the 89.6% of patients who used adjunctive treatments at 1 year, including chemotherapy (64.3%), radiotherapy (57.6%), therapeutic lumbar puncture (31.5%), and Ommaya reservoir (14.5%). The main cost drivers at 1 year were chemotherapy ($62 026), radiation therapy ($37 076), and specialty drugs ($29 330). The prevalence of neurologic impairments was 46.9%, including radiculopathy (15.0%), paresthesia (12.3%), seizure episode/convulsive disorder not otherwise specified (11.0%), and ataxia (8.0%).
CONCLUSIONS
LC is a devastating condition with an overall poor prognosis. We present the largest study of LC in this real-world study, including current treatments, with an emphasis on HCRU. There is considerable variation in the treatment of LC and significant health care costs.
PubMed: 33312678
DOI: 10.1093/nop/npaa041 -
MedRxiv : the Preprint Server For... Mar 2023D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is...
D-2-hydroxyglutarate (D-2-HG) is a well-established oncometabolite of isocitrate dehydrogenase (IDH) mutant gliomas. While prior studies have demonstrated that D-2-HG is elevated in the cerebrospinal fluid (CSF) of patients with IDH-mutant gliomas , no study has determined if CSF D-2-HG can provide a plausible method to evaluate therapeutic response. We are obtaining CSF samples from consenting patients during their disease course via intra-operative collection and Ommaya reservoirs. D-2-HG and D/L-2-HG consistently decreased following tumor resection and throughout chemoradiation in patients monitored longitudinally. Our early experience with this strategy demonstrates the potential for intracranial CSF D-2-HG as a monitoring biomarker for IDH-mutant gliomas.
PubMed: 36909488
DOI: 10.1101/2023.03.01.23286412 -
Acta Neuropathologica Communications Jun 2020Treatment with small-molecule inhibitors, guided by precision medicine has improved patient outcomes in multiple cancer types. However, these compounds are often not...
Treatment with small-molecule inhibitors, guided by precision medicine has improved patient outcomes in multiple cancer types. However, these compounds are often not effective against central nervous system (CNS) tumors. The failure of precision medicine approaches for CNS tumors is frequently attributed to the inability of these compounds to cross the blood-brain barrier (BBB), which impedes intratumoral target engagement. This is complicated by the fact that information on CNS penetration in CNS-tumor patients is still very limited. Herein, we evaluated cerebrospinal fluid (CSF) drug penetration, a well-established surrogate for CNS-penetration, in pediatric brain tumor patients. We analyzed 7 different oral anti-cancer drugs and their metabolites by high performance liquid chromatography mass spectrometry (HPLC-MS) in 42 CSF samples obtained via Ommaya reservoirs of 9 different patients. Moreover, we related the resulting data to commonly applied predictors of BBB-penetration including ABCB1 substrate-character, physicochemical properties and in silico algorithms. First, the measured CSF drug concentrations depicted good intra- and interpatient precision. Interestingly, ribociclib, vorinostat and imatinib showed high (> 10 nM), regorafenib and dasatinib moderate (1-10 nM) penetrance. In contrast, panobinostat und nintedanib were not detected. In addition, we identified active metabolites of imatinib and ribociclib. Comparison to well-established BBB-penetrance predictors confirmed low molecular weight, high proportion of free-drug and low ABCB1-mediated efflux as central factors. However, evaluation of diverse in silico algorithms showed poor correlation within our dataset. In summary, our study proves the feasibility of measuring CSF concentration via Ommaya reservoirs thus setting the ground for utilization of this method in future clinical trials. Moreover, we demonstrate CNS presence of certain small-molecule inhibitors and even active metabolites in CSF of CNS-tumor patients and provide a potential guidance for physicochemical and biological factors favoring CNS-penetration.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adolescent; Adult; Antineoplastic Agents; Biological Transport; Blood-Brain Barrier; Brain Neoplasms; Child; Drug Delivery Systems; Female; Humans; Male; Young Adult
PubMed: 32493453
DOI: 10.1186/s40478-020-00953-2