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Journal of Veterinary Diagnostic... Mar 2024A 26-y-old, male, captive Humboldt penguin () was euthanized following a 3.5-mo history of weakened elimination mechanics, recurrent tenesmus, intermittent hemorrhagic...
A 26-y-old, male, captive Humboldt penguin () was euthanized following a 3.5-mo history of weakened elimination mechanics, recurrent tenesmus, intermittent hemorrhagic droppings, and a cloacal mass. Blepharospasm, of unknown cause, of the right eye was present for ~3 mo before euthanasia. Autopsy revealed a cloacal adenocarcinoma with localized coelomic carcinomatosis and distant metastases to the liver and lungs. On histopathology, a 2.6 × 1.2 × 0.5-mm, well-demarcated mass was found surrounding the right optic nerve, expanding the subdural space and wrapping the leptomeninges. The mass was composed of neoplastic spindle-to-polygonal cells consistent with a meningioma, meningothelial subtype. No evidence of neoplasia was found in the optic chiasm or brain, indicating a primary retrobulbar meningioma. Immunohistochemistry for cytokeratin AE1/AE3, vimentin, and S100 revealed robust and consistent immunoreactivity to vimentin, and weak and variable immunoreactivity to cytokeratin and S100, supporting the diagnosis. Meningiomas have been described only rarely in avian species, and we found no reports of optic nerve meningiomas in any avian species to date. The optic nerve meningioma in this case was considered a clinically incidental finding.
Topics: Male; Animals; Meningioma; Spheniscidae; Vimentin; Adenocarcinoma; Optic Nerve; Meningeal Neoplasms; Keratins
PubMed: 38212884
DOI: 10.1177/10406387231225651 -
Geburtshilfe Und Frauenheilkunde Jan 2024Around 5 percent of all patients with metastatic breast cancer go on to develop distant metastases in the meninges, also known as meningeal carcinomatosis. The median...
Around 5 percent of all patients with metastatic breast cancer go on to develop distant metastases in the meninges, also known as meningeal carcinomatosis. The median survival of these patients is between 3.5 and 4.5 months. Current treatment approaches are based on radiotherapy, systemic and intrathecal therapy. Methotrexate, liposomal cytarabine and trastuzumab are the most common substances used for intrathecal therapy. The aim of this review was to provide an overview of these intrathecal therapy options for meningeal carcinomatosis. A systematic search of the literature was carried out in PubMed using the following search terms: "meningeal metastases", "meningeal carcinomatosis", "leptomeningeal metastasis", "leptomeningeal carcinomatosis", "leptomeningeal disease", "breast cancer", "MTX", "methotrexate", "DepoCyte", "liposomal cytarabine", "trastuzumab" and "anti-HER2". This search resulted in 75 potentially relevant studies, 11 of which were included in this review after meeting the previously determined inclusion and exclusion criteria. The studies differ considerably with regards to study design, cohort size, and dosages of administered drugs. In principle, intrathecal therapy has a tolerable side-effects profile and offers promising results in terms of the median overall survival following treatment with trastuzumab for HER2-positive primary tumors. The focus when treating meningeal carcinomatosis must be on providing a multimodal individual therapeutic approach. However, comprehensive studies which compare the efficacy and side effects of individual pharmaceuticals are lacking. Because of the poor prognosis associated with meningeal carcinomatosis, an approach which treats only the symptoms (best supportive care) should always be considered and discussed with affected patients.
PubMed: 38205044
DOI: 10.1055/a-2185-0457 -
Neurology India 2023
Topics: Humans; Adenocarcinoma of Lung; Lung Neoplasms; Meningeal Carcinomatosis; Meningeal Neoplasms
PubMed: 38174510
DOI: 10.4103/0028-3886.391374 -
Neurology India 2023
Topics: Humans; Meningeal Carcinomatosis; Meningeal Neoplasms
PubMed: 38174505
DOI: 10.4103/0028-3886.391369 -
Oncology and Therapy Mar 2024
Correction: Repotrectinib's Clinical Benefit and Its Brain Penetration in a Patient with Meningeal Carcinomatosis from G2032R-Mutated ROS-1 Positive Non-Small Cell Lung Cancer.
PubMed: 38170387
DOI: 10.1007/s40487-023-00258-z -
Expert Review of Neurotherapeutics 2024Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant... (Review)
Review
INTRODUCTION
Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant therapeutic challenge owing to its aggressive nature and limited treatment options. Breast cancer is a common cause of NM among solid tumors, further highlighting the urgent need to explore effective therapeutic strategies. This review aims to provide insights into the evolving landscape of NM therapy in breast cancer by collating existing research, evaluating current treatments, and identifying potential emerging therapeutic options.
AREAS COVERED
This review explores the clinical features, therapeutic strategies, recent advances, and challenges of managing NM in patients with breast cancer. Its management includes multimodal strategies, including systemic and intrathecal chemotherapy, radiation therapy, and supportive care. This review also emphasizes targeted drug options and optimal drug concentrations, and discusses emerging therapies. Additionally, it highlights the variability in treatment outcomes and the potential of combination regimens to effectively manage NM in breast cancer.
EXPERT OPINION
Challenges in treating NM include debates over clinical trial end points and the management of adverse effects. Drug resistance and low response rates are significant hurdles, particularly inHER2-negative breast cancer. The development of more precise and cost-effective medications with improved selectivity is crucial. Additionally, global efforts are needed for infrastructure development and cancer control considering the diverse nature of the disease.
Topics: Humans; Female; Meningeal Carcinomatosis; Breast Neoplasms; Treatment Outcome; Combined Modality Therapy; Meningitis
PubMed: 38145503
DOI: 10.1080/14737175.2023.2293223 -
Einstein (Sao Paulo, Brazil) 2023To evaluate whether intrathecal chemotherapy improves clinical outcomes in patients with meningeal carcinomatosis.
OBJECTIVE
To evaluate whether intrathecal chemotherapy improves clinical outcomes in patients with meningeal carcinomatosis.
METHODS
This retrospective cohort study included consecutive patients with breast cancer diagnosed with meningeal carcinomatosis. Clinical and treatment data were collected from the patients' medical charts. The primary outcome was overall survival, and the secondary outcomes were time to neurological deterioration and reporting of clinical benefit. Logistic regression and Cox proportional hazard models adjusted for potential confounders were used to evaluate the clinical response and overall survival, respectively.
RESULTS
Overall, 109 female patients were included, 50 (45.9%) of whom received intrathecal chemotherapy with methotrexate and dexamethasone. The median treatment duration was 3 weeks (range, 1-13 weeks). Patients treated with intrathecal chemotherapy were more likely to report clinical benefit (74% versus 57.7%, adjusted odds ratio [OR] = 9.0, 95%CI=2.6-30.9, p<0.001). However, there was no difference in the time to neurologic deterioration (hazard ratio [HR] = 0.96, 95%CI= 0.57-1.59, p=0.86). Patients who received intrathecal chemotherapy did not show an increase in overall survival compared with that of patients who did not receive intrathecal chemotherapy (median overall survival = 1.8 months, 95%CI= 1.27-3.0 versus 2.5, 95%CI= 1.9-3.9, adjusted HR = 0.71, 95%CI= 0.41-1.22, p=0.21). There was a significant interaction between intrathecal chemotherapy and systemic treatment, and patients who received systemic therapy without intrathecal chemotherapy had better overall survival than that of the no-treatment group (adjusted HR = 0.38, 95%CI= 0.20-0.70, p=0.002).
CONCLUSION
Intrathecal chemotherapy did not increase overall survival or time to neurological deterioration and should not preclude or postpone systemic treatments.
Topics: Humans; Female; Breast Neoplasms; Meningeal Carcinomatosis; Retrospective Studies; Methotrexate; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38126659
DOI: 10.31744/einstein_journal/2023AO0481 -
Cancer Treatment Reviews Jan 2024Clinical data supporting the best therapeutic approach in leptomeningeal disease (LMD; also known as leptomeningeal metastases or leptomeningeal carcinomatosis) are... (Review)
Review
Clinical data supporting the best therapeutic approach in leptomeningeal disease (LMD; also known as leptomeningeal metastases or leptomeningeal carcinomatosis) are lacking. Despite the development of new agents and increasing incidence of central nervous system metastases, patients with LMD are often excluded from clinical trials in breast cancer, with very few conducted specifically in LMD. Consequently, current evidence may not provide an accurate reflection of real-world clinical practice. This review aims to provide further insight into the treatment strategies for patients with breast cancer and LMD. We explore differences between clinical and real-world studies, considering inclusion criteria, levels of evidence for LMD diagnosis, and time between diagnosis of LMD and LMD-specific treatment initiation. Patient prognosis is poor; median overall survival is limited to several months, with approximately 10% of patients alive at 12 months. Efficacy results have been reported for various systemic and intrathecal agents in LMD to date. Systemic therapies under investigation for LMD in breast cancer include tucatinib, trastuzumab deruxtecan, and paclitaxel trevatide; trastuzumab is the main intrathecal agent currently under investigation. Recent trials investigating systemic or intrathecal therapies are typically small, single-arm studies, and most are restricted to patients with human epidermal growth factor receptor 2-positive breast cancer. Moreover, the variability among inclusion criteria and response assessment tools makes the interpretation of results difficult. Large retrospective cohorts with various inclusion criteria and treatment regimens provide some real-world data. However, there remains an urgent need for randomised clinical trials which include patients with LMD across all breast cancer subtypes.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Meningeal Carcinomatosis; Prognosis; Meningeal Neoplasms
PubMed: 38118373
DOI: 10.1016/j.ctrv.2023.102653 -
Journal of Neuro-oncology Dec 2023Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the...
PURPOSE
Cerebrospinal fluid (CSF) has revealed the unique genetic characteristics of leptomeningeal metastasis (LM) from non-small cell lung cancer (NSCLC). However, the research in this area is still very limited.
METHODS
Patients with LM from NSCLC (n = 80) were retrospectively analyzed. Circulating tumor DNA (ctDNA) in CSF was tested by next-generation sequencing (NGS), with paired extracranial tissue or plasma samples included for comparison. An independent non-LM cohort (n = 100) was also analyzed for comparative purposes. Clinical outcomes were compared with Kaplan-Meier log-rank test and Cox proportional hazards methodologies.
RESULTS
An overwhelming 93.8% of patients carried druggable mutations in NSCLC LM, with EGFR (78.8%) being the most prevalent. Notably, 4 patients who tested negative for driver genes in extracranial samples surprisingly showed EGFR mutations in their CSF and subsequently benefited from targeted therapy. There was a clear difference in genetic profiles between CSF and extracranial samples, with CSF showing more driver gene detections, increased Copy Number Variations (CNVs), and varied resistance mechanisms among individuals. Abnormalities in cell-cycle regulatory molecules were highly enriched in LM (50.9% vs 31.0%, p = 0.017), and CDKN2A/2B deletions were identified as an independent poor prognostic factor for LM patients, with a significant reduction in median OS (p = 0.013), supported by multivariate analysis (HR 2.63, 95% CI 1.32-5.26, p = 0.006).
CONCLUSIONS
CSF-based ctDNA analysis is crucial for detecting and characterizing genetic alterations in NSCLC LM. The distinct genetic profiles in CSF and extracranial tissues emphasize the need for personalized treatment approaches.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Circulating Tumor DNA; DNA Copy Number Variations; Retrospective Studies; Prognosis; Meningeal Carcinomatosis; Mutation; ErbB Receptors
PubMed: 38104049
DOI: 10.1007/s11060-023-04520-2 -
Clinical Journal of Gastroenterology Apr 2024Meningeal carcinomatosis is a condition in which cancer cells diffusely metastasize to the cerebral pia mater in the cerebrospinal membrane or cerebrospinal cavity. It...
Meningeal carcinomatosis is a condition in which cancer cells diffusely metastasize to the cerebral pia mater in the cerebrospinal membrane or cerebrospinal cavity. It causes a wide array of symptoms according to the site of metastasis. The prognosis is poor, especially in metastasis from solid tumors. This study reports a case of meningeal carcinomatosis caused by advanced gastric cancer, manifested by headache and vision loss. The patient was a 69-year-old man who underwent head computed tomography (CT) and magnetic resonance imaging (MRI) for persistent headaches. No abnormal findings were found; however, his vision declined, convulsions occurred, and cerebrospinal fluid (CSF) cytology showed poorly differentiated adenocarcinoma. Therefore, meningeal carcinomatosis was diagnosed. The patient died after receiving FOLFOX therapy to relieve symptoms and prolong his life. An autopsy showed no invasion of the optic nerve or surrounding tissues. As the frequency of complications of meningeal carcinomatosis in solid cancers is rare, it is crucial to actively suspect and make an early diagnosis.
Topics: Male; Humans; Aged; Meningeal Carcinomatosis; Early Detection of Cancer; Adenocarcinoma; Stomach Neoplasms; Visual Acuity
PubMed: 38091234
DOI: 10.1007/s12328-023-01896-6