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Cureus May 2024Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been...
Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been described with immune checkpoint inhibitors as well. Glofitamab-associated ICANS with a bispecific monoclonal antibody has rarely been reported. The patient is a 63-year-old male with a history of mantle cell lymphoma, diagnosed at age 37, and aggressive large-cell B-cell lymphoma, diagnosed at age 50. Despite adequate chemotherapy, immunotherapy, autologous stem cell transplantation, and CAR T-cell therapy, there were several relapses, including meningeal carcinomatosis at age 61 and intracerebral lymphoma at age 62. For this reason, glofitamab was started. One week after the ninth cycle, the patient developed drowsiness, behavioral changes, word-finding difficulties, aphasia, focal to bilateral tonic-clonic seizures, and focal onset seizures, which resolved after 16 days with levetiracetam, valproic acid, lorazepam, and midazolam. Since there was no infectious disease, electrolyte disturbance, metabolic disorder, cardiovascular disease, or relapse of lymphoma, glofitamab-associated ICANS was suspected, and anakinra was administered. The case shows that ICANS with drowsiness, behavioral changes, aphasia, and seizures can develop with glofitamab and that patients with structural brain abnormalities may be prone to this.
PubMed: 38910651
DOI: 10.7759/cureus.60833 -
Breast Cancer Research and Treatment Aug 2024Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and...
PURPOSE
Leptomeningeal disease (LMD) is a devastating complication of metastatic breast cancer (MBC). It is critical to better understand the risk factors, natural history, and treatment outcomes, including patients in a modern cohort.
METHODS
In this single center retrospective cohort study, we identified patients with MBC and LMD who received care from 2000 to 2024 and abstracted key clinical, treatment, and survival data.
RESULTS
We identified 111 patients with MBC and LMD, including patients with the following subtypes: HR+/HER2- (n = 53, 47.7%), HER2+ (n = 30, 27.0%), and triple negative breast cancer (TNBC; n = 28, 25.2%). Median time from the diagnosis of MBC to LMD was 16.4 months (range 0-101.3 months). After the diagnosis of LMD, most patients received systemic therapy (n = 66, 59.5%) and/or central nervous system (CNS)-directed therapy (n = 94, 84.7%) including intrathecal therapy (n = 42, 37.8%) and/or CNS-directed radiation therapy (n = 70, 63.1%). In all patients, median overall survival (OS) from the diagnosis of LMD to death was 4.1 months (range 0.1-78.1 months) and varied by subtype, with HR+/HER2- or HER2+ MBC patients living longer than those with TNBC (4.2 and 6.8 months respectively vs. 2.0 months, p < 0.01, HR 2.15, 95% CI 1.36-3.39). Patients who received CNS-directed therapy lived longer than those who did not (4.2 vs. 1.3, p = 0.02 HR 0.54, 0.32-0.91). Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014 (6.4 vs. 2.9 months, p = 0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p = 0.004, HR 2.03, 95% CI 1.25-3.30).
CONCLUSION
This is one of the largest case series of patients with MBC and LMD. Patients diagnosed with LMD from 2015 to 2024 lived longer than those diagnosed from 2000 to 2014, although median OS was short overall. Patients with TNBC and LMD had particularly short OS. Novel therapeutic strategies for LMD remain an area of unmet clinical need.
Topics: Humans; Female; Middle Aged; Retrospective Studies; Aged; Adult; Breast Neoplasms; Meningeal Neoplasms; Aged, 80 and over; Meningeal Carcinomatosis; Receptor, ErbB-2; Prognosis
PubMed: 38888796
DOI: 10.1007/s10549-024-07339-1 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2024Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these...
UNLABELLED
Leptomeningeal metastases are lesions of brain and/or spinal cord sheaths by tumor cells. They occur in 5% of patients with solid tumors, although autopsies reveal these lesions much more often (10-20% of cases). Leptomengeal metastases are an unfavorable prognostic factor. Despite the modern NCCN treatment standards, including intrathecal therapy (ITT), such patients receive only irradiation of the entire brain and/or spinal cord in most cases.
OBJECTIVE
To evaluate the effectiveness of ITT in patients with leptomeningeal metastases in breast cancer.
MATERIAL AND METHODS
Twenty-five patients with breast cancer and leptomeningeal metastases underwent intrathecal administration of methotrexate between 2016 and 2022. Intrathecal chemotherapy was administered through lumbar puncture. We performed an intensive course (intrathecal methotrexate 15 mg 2 times a week for 1 month (8 injections), then intrathecal methotrexate 15 mg 1 time a week (4 injections), and then 15 mg 1 time a month until progression or unacceptable toxicity).
RESULTS
The median duration of ITT was 2.5 months. Complete neurological responses were observed in 3 out of 25 (12%) patients, partial neurological response - in 15 out of 25 (60%) patients, progression of neurological symptoms - in 7 (28%) patients. The number of complete cytological responses was observed in 6 out of 25 (24%) patients. The median overall survival after ITT was 6.7 months.
CONCLUSION
Effectiveness of ITT is confirmed by higher quality of life (72% of patients), complete cytological responses (24%) and improvement in neuroimaging data. This is an important criterion for severe patients with limited treatment options. First-stage ITT before whole-brain irradiation is preferable, as this approach increases overall survival by 3 months. Undoubtedly, ITT is a treatment option that can be used in routine clinical practice for lesions of brain and spinal cord sheaths.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Injections, Spinal; Adult; Meningeal Neoplasms; Methotrexate; Aged; Meningeal Carcinomatosis; Antimetabolites, Antineoplastic
PubMed: 38881013
DOI: 10.17116/neiro20248803131 -
Medicine Jun 2024Nasopharyngeal carcinoma has a high incidence in East and Southeast Asia, often with distant metastasis. However, leptomeningeal metastasis (LM) is extremely rare and... (Review)
Review
RATIONALE
Nasopharyngeal carcinoma has a high incidence in East and Southeast Asia, often with distant metastasis. However, leptomeningeal metastasis (LM) is extremely rare and usually has a poor prognosis. This paper reports the clinical treatment of a patient with meningeal metastasis of nasopharyngeal carcinoma (NPC) in order to improve the clinician's understanding of the disease. Early diagnosis of the disease can alleviate the pain of patients and prolong their survival time.
PATIENT CONCERNS
We report the case of a 55-year-old female with a history of NPC with LM. Brain magnetic resonance imaging showed temporal lobe enhancement, peripheral edema, and enhancement of the adjacent meninges. Cerebrospinal fluid cytology suggests the presence of malignant tumor cells.
DIAGNOSES
The patient was diagnosed with LM from NPC.
INTERVENTIONS
The patients were regularly given targeted therapy with nimotuzumab, immunotherapy with karyolizumab, and lumbar intrathecal methotrexate chemotherapy and supportive treatment.
OUTCOMES
The patient had survived for 3 years since the diagnosis of LM and was in good condition and still under active antitumor treatment.
LESSONS
Leptomeningeal metastasis of NPC is a rare disease. Although there is currently no unified treatment plan, the neurological symptoms can still be controlled and the quality of life can be improved through active treatment.
Topics: Humans; Female; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Meningeal Neoplasms; Meningeal Carcinomatosis; Magnetic Resonance Imaging
PubMed: 38847717
DOI: 10.1097/MD.0000000000037853 -
World Journal of Clinical Cases May 2024Brain metastases (BM) are very rare in gastric adenocarcinoma (GaC), and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness. However,...
BACKGROUND
Brain metastases (BM) are very rare in gastric adenocarcinoma (GaC), and patients with BMs have a higher mortality rate due to stronger tumor aggressiveness. However, its pathogenesis remains unclear. Genetic testing revealed cellular-mesenchymal epithelial transition factor receptor (MET) amplification. Therefore, treatment with savolitinib, a small molecule inhibitor of c-Met, was selected.
CASE SUMMARY
A 66-year-old woman was diagnosed with advanced GaC 6 months prior to presentation due to back pain. Cerebellar and meningeal metastases were observed during candonilimab combined with oxaliplatin and capecitabine therapy. The patient experienced frequent generalized seizures and persistent drowsiness in the emergency department. Genetic testing of cerebrospinal fluid and peripheral blood revealed increased MET amplification. After discussing treatment options with the patient, savolitinib tablets were administered. After a month of treatment, the intracranial lesions shrank considerably.
CONCLUSION
BM is very rare in advanced GaC, especially in meningeal cancer, that is characterized by rapid disease deterioration. There are very few effective treatment options available; however, technological breakthroughs in genomics have provided a basis for personalized treatment. Furthermore, MET amplification may be a key driver of BM in gastric cancer; however, this conclusion requires further investigation.
PubMed: 38817213
DOI: 10.12998/wjcc.v12.i15.2636 -
Current Oncology (Toronto, Ont.) Apr 2024Therapeutic management of patients with leptomeningeal carcinomatosis (LC) may require treatment of concomitant hydrocephalus (HC) in addition to intrathecal...
Therapeutic management of patients with leptomeningeal carcinomatosis (LC) may require treatment of concomitant hydrocephalus (HC) in addition to intrathecal chemotherapy (ITC). Ventriculoperitoneal shunts (VPS) equipped with a valve for manual deactivation of shunt function and a concomitant reservoir for application of ITC pose an elegant solution to both problems. The present study evaluates indication, feasibility, and safety of such a modified shunt/reservoir design (mS/R). All patients with LC aged ≥ 18 years who had undergone mS/R implantation between 2013 and 2020 at the authors' institution were further analyzed. ITC was indicated following the recommendation of the neuro-oncological tumor board and performed according to a standardized protocol. Sixteen patients with LC underwent mS/R implantation for subsequent ITC and concomitant treatment of HC. Regarding HC-related clinical symptoms, 69% of patients preoperatively exhibited lethargy, 38% cognitive impairment, and 38% (additional) visual disturbances. Postoperatively, 86% of patients achieved subjective improvement of HC-related symptoms. Overall, postoperative complications occurred in three patients (19%). No patient encountered cancer treatment-related complications. The present study describes a combination procedure consisting of a standard VPS-system and a standard reservoir for patients suffering from LC and HC. No cancer treatment-related complications occurred, indicating straightforward handling and thus safety.
Topics: Humans; Ventriculoperitoneal Shunt; Meningeal Carcinomatosis; Female; Male; Middle Aged; Hydrocephalus; Injections, Spinal; Adult; Aged; Feasibility Studies
PubMed: 38785461
DOI: 10.3390/curroncol31050180 -
Neuro-ophthalmology (Aeolus Press) 2024Meningeal carcinomatosis (MC) has an extremely poor prognosis and can present with various neurological symptoms. A 68-year-old man presented to our hospital with a...
Meningeal carcinomatosis (MC) has an extremely poor prognosis and can present with various neurological symptoms. A 68-year-old man presented to our hospital with a 1 month history of headache and nausea followed by sudden decrease in vision in both eyes. Whilst being examined in the ophthalmology department he lost consciousness and had a generalised tonic clonic seizure. Accordingly, he was transferred to the Emergency Department. Head magnetic resonance imaging showed hydrocephalus. Abdominal contrast-enhanced computed tomography scanning reported changes suggestive of gastric carcinoma. Cerebrospinal fluid cytological examination showed numerous atypical cells, leading to the diagnosis of MC. An upper gastrointestinal endoscopy revealed an advanced gastric tumour. Systemic chemotherapy was initiated, however, he died within 16 days of admission. At autopsy, poorly differentiated adenocarcinoma was identified in the subarachnoid space, however it had not invaded the brain parenchyma or optic chiasm. This is the first report of loss of vision being the first presenting symptom of new-onset gastric carcinoma with MC. Although rare, MC should be suspected in cases where patients present with sudden loss of vision and symptoms of meningeal irritation, where there are no ophthalmological findings to explain the vision loss.
PubMed: 38756339
DOI: 10.1080/01658107.2023.2290537 -
Clinical Lung Cancer Jul 2024EGFR-targeted therapy (ETT) and immune-checkpoint blockade (ICB) have shown promising results in treating NSCLC brain metastases (BM). However, little is known of their...
Clinical Outcomes of Patients with Non-Small Cell Lung Cancer Leptomeningeal Disease Following Receipt of EGFR-Targeted Therapy, Immune-Checkpoint Blockade, Intrathecal Chemotherapy, or Radiation Therapy Alone.
BACKGROUND
EGFR-targeted therapy (ETT) and immune-checkpoint blockade (ICB) have shown promising results in treating NSCLC brain metastases (BM). However, little is known of their effect in treating leptomeningeal disease (LMD).
PATIENTS AND METHODS
This is a retrospective review of 80 patients diagnosed with NSCLC LMD from January 2014 to March 2021. Patients were grouped based on initial LMD treatment: radiotherapy (RT) alone, ETT, ICB, and intrathecal chemotherapy (ITC).
RESULTS
EGFR mutation was present in 22 patients (28%). Twenty patients had positive cytology in cerebrospinal fluid, while 60 patients were diagnosed based on MRI with clinical correlation. The RT alone group consisted primarily of whole brain radiation (n = 20; 77%), stereotactic radiation (n = 3; 12%), and palliative spine radiation (n = 2; 7%). There were no significant differences amongst the treatment groups in age, performance status, or neurologic symptoms. Overall, the 6-month overall survival (OS) and craniospinal progression free survival (CS-PFS) were 35% and 24%, respectively. The 6-month OS for the ETT, ICB, ITC, and RT alone groups was 64%, 33%, 57%, and 29% respectively (log-rank P = .026). The 6-month CS-PFS for the ETT, ICB, ITC, and RT alone groups was 43%, 33%, 29%, and 19% respectively (log-rank P = .049). Upon univariate analysis, receipt of ETT compared to RT alone reached significance for OS (HR 0.35, P = .006) and CS-PFS (HR 0.39, P = .013).
CONCLUSIONS
The prognosis for patients with NSCLC LMD remains poor overall. However, the receipt of ETT for patients with EGFR-positive disease was associated with improved outcomes.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Male; Female; Lung Neoplasms; Retrospective Studies; Middle Aged; ErbB Receptors; Aged; Immune Checkpoint Inhibitors; Injections, Spinal; Meningeal Neoplasms; Adult; Meningeal Carcinomatosis; Molecular Targeted Therapy; Aged, 80 and over; Survival Rate; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Prognosis; Treatment Outcome; Follow-Up Studies; Mutation
PubMed: 38719648
DOI: 10.1016/j.cllc.2024.04.005 -
Cureus Apr 2024We present a case admitted for evaluation of suspected idiopathic intracranial hypertension (IIH) with an unusual but important departure from the expected algorithm. A...
We present a case admitted for evaluation of suspected idiopathic intracranial hypertension (IIH) with an unusual but important departure from the expected algorithm. A 31-year-old lady came with a two-week duration of a mild headache and one-week duration of double vision with no previously documented fever or any comorbidities. Clinically, she had papilledema and bilateral abducens palsy with no signs of meningeal irritation. MRI brain radiology was consistent with IIH. Her CSF study showed pleocytosis with elevated protein levels and normal glucose. Serology was positive for at low titers but CSF culture grew , confirming the diagnosis of neurobrucellosis. Her headache and abducens palsy improved over the first two weeks, and the papilledema resolved over two months with antibiotics. This clinical mimic is important for physicians (including neurophysicians) and Infectious Disease specialists. The radiological mimic comes from chinked (small) ventricles, unlike most meningeal diseases which can present with papilledema and abducens palsy including tuberculosis, cryptococcosis, and leptomeningeal carcinomatosis. A CSF study is mandatory in the workup of IIH despite massive improvements in imaging.
PubMed: 38707027
DOI: 10.7759/cureus.57496 -
Journal of Cancer Research and... Apr 2024Leptomeningeal metastasis (LM) is a severe lung cancer complication, with potentially fatal consequences. The use of intrathecal therapy (IT) combined with systemic...
BACKGROUND
Leptomeningeal metastasis (LM) is a severe lung cancer complication, with potentially fatal consequences. The use of intrathecal therapy (IT) combined with systemic therapy has shown promise as a treatment approach for LM. Thus, this study aimed to evaluate the features and responses to IT combined therapy and identify determinants affecting patients with leptomeningeal metastasis resulting from lung adenocarcinoma (LM-LA).
METHODS
A retrospective analysis of medical records from our hospital database was performed, covering from April 2018 to August 2022, for 37 patients diagnosed with LM-LA and treated with IT combined therapy. Patients who received IT combined therapy for LM-LA were evaluated for demographic characteristics, treatment efficacy, survival, and variables that impacted them.
RESULTS
The median overall survival (mOS) of 37 patients was 16.0 months, and the survival rates at 6 and 12 months were 75.7% and 35.1%, respectively. Among the 21 patients with LM-LA who received IT combined with tyrosine kinase inhibitors (TKIs), the mOS was 17.0 months, which was significantly longer than that of patients treated with IT combined with chemotherapy (7.0 months, P = 0.010) and the best supportive care (6.0 months, P = 0.001). However, no significant survival benefit was observed in patients treated with IT combined with TKIs when compared with those treated with IT combined with PD-1 (5.0 months, P = 0.249). Multivariate analysis indicated that the combination of TKIs was an independent favorable prognostic factor for patients with LM-LA.
CONCLUSION
Combination treatment is regarded as an additional option for patients with LM-LA. Compared with other combination therapies in our study, IT combined with TKI therapy provided a better survival outcome for patients with LM-LA.
Topics: Humans; Male; Female; Middle Aged; Adenocarcinoma of Lung; Retrospective Studies; Lung Neoplasms; Injections, Spinal; Prognosis; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Survival Rate; Meningeal Neoplasms; Treatment Outcome; Protein Kinase Inhibitors; Meningeal Carcinomatosis; Combined Modality Therapy; Aged, 80 and over
PubMed: 38687937
DOI: 10.4103/jcrt.jcrt_2071_23