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Journal of Neurosurgery Jun 2023Leptomeningeal metastasis (LM) is a challenging scenario in non-small cell lung cancer (NSCLC). Considering that outcomes of treatment modalities stratified by LM...
OBJECTIVE
Leptomeningeal metastasis (LM) is a challenging scenario in non-small cell lung cancer (NSCLC). Considering that outcomes of treatment modalities stratified by LM chronological patterns related to brain metastasis (BM) are lacking, the aim of this study was to evaluate outcomes and explore prognostic factors.
METHODS
The authors retrospectively collected data of patients with NSCLC undergoing Ommaya reservoir implantation, ventriculoperitoneal shunt implantation, or lumboperitoneal shunt implantation. Based on radiographic findings and time from diagnosis of NSCLC to LM, the authors divided them into subtypes of LM as follows: LM without BM; LM concurrent with BM; or LM after BM. The Kaplan-Meier method was applied to analyze overall survival (OS) and multivariate Cox regression for prognostic factors.
RESULTS
Sixty-one patients with LM were included, with a median OS of 8.1 (range 0.2-70.0) months. Forty-three (70.5%) patients had EGFR-mutant disease. Forty-two (68.9%) patients had 19-del or L858R mutation, and one (1.6%) patient had G719A mutation. Fifty-seven (93.4%) patients had hydrocephalus. Twenty-one (34.4%) patients received whole-brain radiotherapy before LM diagnosis, 3 (4.9%) patients underwent operation for BMs before LM diagnosis, and 42 (68.9%) patients received EGFR tyrosine kinase inhibitor (TKI) therapy before LM diagnosis. Eleven patients were treated with chemotherapy, 10 patients were treated with TKIs, and 32 patients were treated with chemotherapy combined with TKIs before LM diagnosis. Patients with LM after BM had lower Karnofsky Performance Status (KPS) scores (KPS score 50) than did those with LM without BM (KPS score 80) or LM concurrent with BM (KPS score 70; p = 0.003). More patients with LM after BM received intrathecal methotrexate than in the other subgroups (p < 0.001). The median OS was significantly shorter in the LM after BM than in the concurrent LM and BM and the LM without BM subgroups (5.4 vs 5.5 vs 11.6 months; p = 0.019). Cox regression revealed that a KPS score ≥ 70 (HR 0.51; p = 0.027) and shunt implantation (HR 0.41; p = 0.032) were favorable prognostic factors.
CONCLUSIONS
Patients with NSCLC who had LM without BM had better survival outcomes (11.6 months) compared with those who had LM after BM or concurrent LM and BM. Aggressive shunt implantation may be favored for LM.
PubMed: 36208438
DOI: 10.3171/2022.8.JNS221175 -
Cureus Aug 2022A 50-year-old male with a history of a dull headache and neck pain for a few weeks presented to the ER with complaints of progressive weakness and difficulty walking....
A 50-year-old male with a history of a dull headache and neck pain for a few weeks presented to the ER with complaints of progressive weakness and difficulty walking. Physical examination revealed a lethargic, confused patient with abnormal tremors at rest. Initial lab work was significant for elevated hemoglobin, hematocrit, and hyponatremia. Additionally, CT imaging was significant for prominent ventricles. Several serologies and polymerase chain reaction (PCR) tests were ordered to determine the etiology of the patient's meningitis. On day 10 of admission, serology results returned positive for antibodies. The patient was started on an IV fluconazole treatment and underwent a ventriculoperitoneal shunt and Ommaya reservoir placement procedure. Cases of coccidioidal meningitis are rarely noted in recent literature. We present this clinical case of coccidioidomycosis dissemination into the central nervous system (CNS) to highlight the rare localization of the fungal infection in a baseline immunocompetent patient.
PubMed: 36120197
DOI: 10.7759/cureus.28643 -
Journal of Neuro-oncology Oct 2022Leptomeningeal metastatic disease (LMD) from advanced malignancies has poor prognoses and limited treatments. Intrathecal therapy (ITT) protocols are available, showing... (Review)
Review
PURPOSE
Leptomeningeal metastatic disease (LMD) from advanced malignancies has poor prognoses and limited treatments. Intrathecal therapy (ITT) protocols are available, showing variable outcomes. We reviewed the therapeutic and toxicity profiles of ITT in LMD.
METHODS
PubMed, EMBASE, Web-of-Science, and Scopus were searched following the PRISMA-ScR guidelines to include studies reporting ITT for LMD.
CLINICALTRIAL
gov and Cochrane were searched to identify ongoing clinical trials.
RESULTS
We included 27 published studies encompassing 2161 patients and 4 ongoing trials. LMD originated from brain metastases (85.5%), lymphomas (5.4%), high-grade gliomas (4.6%), medulloblastomas (2.3%), and leukemias (2.1%). LMD was mostly diagnosed with the co-presence of neurological-related symptoms and positive imaging and/or cerebrospinal fluid cytology (60.8%). The most common ITT agents were methotrexate (35.9%), cytarabine (21.9%), and thiotepa (8.2%), standalone or combined. Patients received a median of 6.5 ITT cycles (range, 1.0-71.0) via intraventricular (58.8%) or lumbar intrathecal (41.2%) routes. The Ommaya reservoir was implanted in 38.5% cases. Concurrent systemic chemotherapy (45.2%) and/or radiotherapy (30.6%) were used. After 1-3 cycles, 44.7% patients had improved clinical status and 29.9% converted into negative cerebrospinal fluid cytology. The most common ITT-related severe adverse events were neutropenia (6.5%), meningitis (5.2%) and encephalopathy (4.5%). Median freedom from progression was 2.4 months (range, 0.1-59.5) and median overall survival 5.5 months (range, 0.1-148.0).
CONCLUSION
Current ITT protocols are variable but effective and well-tolerated in LMD. Ongoing trials are investigating dose-limiting toxicity profiles and long-term overall survival. Future studies should analyze the therapeutic and safety profiles of ITT compared to newer systemic therapies.
Topics: Humans; Brain Neoplasms; Combined Modality Therapy; Cytarabine; Immunotherapy; Meningeal Carcinomatosis; Meningeal Neoplasms
PubMed: 35999434
DOI: 10.1007/s11060-022-04118-0 -
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 -
Operative Neurosurgery (Hagerstown, Md.) Sep 2022Normal pressure hydrocephalus (NPH) is characterized by cerebral ventriculomegaly and the triad of magnetic gait, urinary incontinence, and cognitive impairment....
Complications Associated With Ventriculoperitoneal Shunt Surgery for Normal Pressure Hydrocephalus Using Stereotactic Navigation and Abdominal Laparoscopy: A Single-Institution Case Series.
BACKGROUND
Normal pressure hydrocephalus (NPH) is characterized by cerebral ventriculomegaly and the triad of magnetic gait, urinary incontinence, and cognitive impairment. Treatment includes ventriculoperitoneal (VP) shunt surgery.
OBJECTIVE
To evaluate complication rates in a cohort of patients undergoing VP shunt surgery with stereotactic proximal catheter navigation and laparoscopic distal catheter placement.
METHODS
This study was a retrospective consecutive cohort analysis of 117 patients with NPH undergoing VP shunt placement using both stereotactic navigation and laparoscopy from 2015 to 2020. Patients with obstructive hydrocephalus and those with central nervous system infection, intraventricular hemorrhage, Ommaya reservoirs, or undergoing shunt revision at initial encounter were excluded. Variables included demographics and comorbidities, NPH symptoms, operative details, radiographic outcomes, and rates of complications, readmissions, and reoperations within 1, 3, and 12 months. Impact of demographics and comorbidities on complication rates was assessed using Fisher exact tests.
RESULTS
Zero patients required reoperation within 30 days. One intracranial hemorrhage was detected on immediate postoperative head computed tomography. Four patients ultimately required revision: 2 for catheter repositioning to alleviate abdominal pain, 1 ligation for a colectomy, and 1 removal for shunt infection. Patients with cardiac or other neurological comorbidities had higher rates of readmission and complications. Systemic complications totaled 12% in the first 30 days.
CONCLUSION
The combination of intraoperative stereotactic navigation and laparoscopic assistance leads to low rates of serious complications and reoperations for VP shunt implantation in patients with NPH. These changes to surgical technique are easy to implement and may reduce the risk for this common operation.
Topics: Humans; Hydrocephalus, Normal Pressure; Laparoscopy; Retrospective Studies; Treatment Outcome; Ventriculoperitoneal Shunt
PubMed: 35972080
DOI: 10.1227/ons.0000000000000290 -
Journal of Neuro-oncology Sep 2022Children with craniopharyngiomas (CP) can experience significant morbidities caused by extensive surgery and/or radiation. Ommaya reservoir insertion (ORI) into cystic...
INTRODUCTION
Children with craniopharyngiomas (CP) can experience significant morbidities caused by extensive surgery and/or radiation. Ommaya reservoir insertion (ORI) into cystic CP represents a minimally invasive approach allowing immediate decompression and aims to avoid additional injuries. The purpose of this study was to determine the surgical outcome and relevance of upfront ORI (± intracystic treatment) for preservation of endocrine function.
METHODS
We performed a retrospective chart review of children with CP treated at the Hospital for Sick Children between 01/01/2000 and 15/01/2020. Endocrine function was reviewed at the time of initial surgery and throughout follow-up. New endocrinological deficits related to the index procedure were defined as immediate failure (IF), whereas postoperative duration of endocrinological stability (ES) was analyzed using the Kaplan-Meier method. The rate of IF and ES was compared between the treatment groups.
RESULTS
Seventy-nine patients were included and had a median age of 8.3 years (range 2.1-18.0 years); 31 were males. Fifty-three patients with upfront surgical treatment, including 29 ORI and 24 gross total or partial resections had sufficient endocrinological follow-up data. Endocrine dysfunction occurring immediately after the index procedure (IF) was observed in 15 patients (62.5%) in the resection group compared to two patients (6.8%) in the ORI group, odds ratio: 0.05 (CI: 0.01-0.26, p < 0.0001). Excluding those with immediate endocrinological deficits, mean ES after ORI was 19.4 months (CI: 11.6-34.2), compared to 13.4 months (CI:10.6-NA) after surgical resection.
CONCLUSIONS
Endocrine function was preserved in patients with upfront ORI (± intracystic treatment), which was confirmed as a minimally invasive procedure with an overall low morbidity profile.
Topics: Adolescent; Child; Child, Preschool; Craniopharyngioma; Female; Humans; Male; Pituitary Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 35925530
DOI: 10.1007/s11060-022-04099-0 -
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 -
Pharmacological Research Aug 2022Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in hematological... (Review)
Review
Cellular therapies utilizing T cells expressing chimeric antigen receptors (CARs) have garnered significant interest due to their clinical success in hematological malignancies. Unfortunately, this success has not been replicated in solid tumors, with only a small fraction of patients achieving complete responses. A number of obstacles to effective CAR-T cell therapy in solid tumors have been identified including tumor antigen heterogeneity, poor T cell fitness and persistence, inefficient trafficking and inability to penetrate into the tumor, immune-related adverse events due to on-target/off-tumor toxicity, and the immunosuppressive tumor microenvironment. Many preclinical studies have focused on improvements to CAR design to try to overcome some of these hurdles. However, a growing body of work has also focused on the use of local and/or regional delivery of CAR-T cells as a means to overcome poor T cell trafficking and inefficient T cell penetration into tumors. Most trials that incorporate locoregional delivery of CAR-T cells have targeted tumors of the central nervous system - repurposing an Ommaya/Rickham reservoir for repeated delivery of cells directly to the tumor cavity or ventricles. Hepatic artery infusion is another technique used for locoregional delivery to hepatic tumors. Locoregional delivery theoretically permits increased numbers of CAR-T cells within the tumor while reducing the risk of immune-related systemic toxicity. Studies to date have been almost exclusively phase I. The growing body of evidence indicates that locoregional delivery of CAR-T cells is both safe and feasible. This review focuses specifically on the use of locoregional delivery of CAR-T cells in clinical trials.
Topics: Humans; Immunotherapy, Adoptive; Liver Neoplasms; Neoplasms; Receptors, Chimeric Antigen; T-Lymphocytes; Tumor Microenvironment
PubMed: 35772645
DOI: 10.1016/j.phrs.2022.106329 -
Brain Sciences Jun 2022Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. Breast cancer, lung cancer, and melanoma are the three most common causes...
Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. Breast cancer, lung cancer, and melanoma are the three most common causes of LMC, whereas it is rare in ovarian cancer. Here, we report the case of a 59-year-old woman who was diagnosed with LMC from ovarian cancer and was successfully treated with intrathecal chemotherapy via Ommaya reservoir and radiation therapy. The patient had an amelioration of symptoms and prolonged survival. Though LMC from ovarian cancer is thought to be rare, it is not going to remain a rare entity because the incidence of LMC in general is thought to be increasing, which is also the case with ovarian cancer. According to 31 cases whose treatment course is reported in literature, despite the absence of an established treatment for LMC, intrathecal (IT) chemotherapy whose survival benefit has been suggested in past studies might also prolong survival in patients with LMC from ovarian cancer. IT chemotherapy via Ommaya reservoir may be preferred to the lumbar puncture route. The presentation of non-specific symptoms of LMC in patients may hinder its diagnosis; however, early diagnosis and treatment induction is the key for patients' prolonged survival and restored useful life.
PubMed: 35741633
DOI: 10.3390/brainsci12060748 -
Frontiers in Surgery 2022Therapy for large or deep cystic brain metastases is a troublesome procedure in clinical departments. Stereotactic cyst aspiration, combined with Gamma Knife...
BACKGROUND
Therapy for large or deep cystic brain metastases is a troublesome procedure in clinical departments. Stereotactic cyst aspiration, combined with Gamma Knife radiosurgery, can be an effective treatment for cystic brain metastases. However, there is still a possibility that a reaccumulation of cystic fluid may lead to poor efficacy or even reoperation.
CASE PRESENTATION
We present a case of a 67-year-old man who was diagnosed with lung cancer brain metastasis. The intracranial lesion seen on imaging appeared to be cystic and located deep inside the brain with associated limb dysfunction. The patient did not respond well to chemotherapy and underwent cyst aspiration with Ommaya reservoir implantation under neuronavigation. Repeated cystic fluid reaccumulation and exacerbation of symptoms occurred during treatment. We performed repeated aspiration via the Ommaya reservoir to control the symptoms and combined it with radiotherapy. During the follow-up period of 14 months, the intracranial tumor was effectively and satisfactorily controlled.
CONCLUSIONS
We highlight that Ommaya reservoir implantation during stereotactic cyst aspiration is necessary to prevent fluid reaccumulation, thereby avoiding the need for a second surgical procedure.
PubMed: 35651693
DOI: 10.3389/fsurg.2022.901674