Effects of intrathecal pemetrexed on the survival of patients with leptomeningeal metastasis from lung adenocarcinoma: a propensity score matching analysis.

PURPOSE: To explore the impact of intrathecal pemetrexed (IP) on the survival of lung adenocarcinoma (LUAC) patients with leptomeningeal metastasis (LM). METHODS: We analyzed patients with LUAC and LM who received systemic therapy after LM diagnosis at the Fujian Cancer Hospital between July 2018 and March 2022. Patients who underwent IP were assigned to the IP group; those without IP treatment were designated as the non-IP group. Propensity score matching (PSM) was performed between the two groups. RESULTS: 165 patients were enrolled: 83 and 82 in the IP and non-IP groups, respectively. After 1:1 PSM, we included 114 patients in the matched cohort. Median overall survival (OS) was 13.2 months (95% CI 10.8-15.6 months) in the IP group versus 10.1 months (95% CI 5.3-14.9 months) in the non-IP group (P = 0.488). Only Eastern Cooperative Oncology Group Performance Status (ECOG PS) was confirmed as an independent predictor for OS in the matched cohort (hazard ratio (HR) 2.03; P = 0.023). Multivariate competing-risks analysis showed that IP significantly correlated with central nervous system-related death (HR 0.31; P = 0.046). When stratified by ECOG PS, IP improved survival in patients with poor ECOG PS (PS = 2) (14.3 months vs. 1.6 months; P = 0.003). CONCLUSIONS: Intrathecal pemetrexed did not enhance OS for the entire LUAC patient with LM compared to non-intrathecal chemotherapy. However, it exhibited the potential to reduce the risk of central nervous system-related mortality and improve survival in patients with poor ECOG PS.

Cranial nerve palsies in patients with hematological malignancies: a case series.

Objectives: Cranial neuropathies (CNs) can be due to a wide spectrum of causes, and the differential diagnosis is particularly challenging in patients with positive history of hematological malignancies, when neoplastic meningitis (NM) must be excluded.Patients and Methods: We retrospectively selected a series of twelve haematological patients with isolated cranial neuropathies (ICNs) or multiple cranial neuropathies (MCNs). among 71 patients that developed neurologic symptoms during different stages of the cancer, between 1 January, 2010 and 31 December, 2017. Brain and cauda equina magnetic resonance imaging (MRI) with gadolinium, cerebrospinal fluid (CSF) analysis, including flow cytometry for cell immunophenotyping and microbiological exams were performed in all patients.Results: Patients developed signs and symptoms of involvement of isolated (n = 11) or multiple (n = 1) cranial nerves, at different stages of the primary disease, and, in 5 of these cases in complete remission after hematopoietic stem cell transplantation. Among the 5 cases that eventually were diagnosed as having NM, cerebrospinal fluid was positive for neoplastic cells in 3, and MRI gadolinium-enhancement was present in 3. The other episodes were attributed to heterogeneous pathologies that were unrelated to meningeal infiltration by neoplastic cells.Conclusions: Our observations confirm that NM in haematological malignancies can yield insidious isolated signs of cranial nerves. Only a multidisciplinary approach allows prompt recognition of these conditions through a challenging process of differential diagnosis, and proper therapies.

Association of MRI findings with clinical characteristics and prognosis in patients with leptomeningeal carcinomatosis from non-small cell lung cancer.

PURPOSE: Magnetic resonance imagining (MRI) is helpful for diagnosis of leptomeningeal carcinomatosis (LMC) and localizing LMC symptoms. Goal of this study is how MRI findings of LMC are associated with clinical characteristics or prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively collected data on 283 patients with LMC from NSCLC, adenocarcinoma based on cerebrospinal fluid cytology. All patients had brain MRI with gadolinium enhancement at LMC diagnosis, and spinal MRI was performed at the physician's discretion. We evaluated the prognostic factors for overall survival (OS) of all patients and subgroup of patients with central nervous system cause of death. RESULTS: Two-hundred sixteen patients (76%) had definite or suggestive LMC findings and 67 had negative findings on brain MRI. Of the 37 patients who presented with cauda equina syndrome, 35 (95%) exhibited typical spinal MRI findings. Median OS of all patients was 3.65 months (95% confidence interval, 3.06-4.18). There was no significant difference in median OS between MRI-negative and MRI-positive groups (4.31 vs. 3.48 months, p = 0.711), whereas negative MRI finding showed longer median OS significantly in a subgroup of 77 patients with a central nervous system cause of death (p = 0.035). Considering clinical characteristics, progressive systemic disease, and altered mentality were significant prognostic factors associated with poor OS, whereas presenting symptom of headache with nausea/vomiting, intra-CSF chemotherapy, WBRT after LMC diagnosis, and concurrent RTKi treatment were significant for favorable OS in multivariable analysis. CONCLUSIONS: Positive MRI findings suggests heavier disease burden than negative MRI findings in patients with LMC who died of a central nervous system cause. Spinal MRI findings in patients with LMC correlate with cauda equina symptoms.

[A Case of Carcinomatous Meningitis Due to Gastric Cancer].

A 43-year-old man was diagnosed with gastric cancer with diaphragm invasion and multiple lymph node metastases and underwent total gastrectomy. The histological diagnosis was por2>tub2, ypT4b(diaphragm), int, INF c, ly1, v1, ypN3, yp Stage ⅢC. Three months postoperatively, computed tomography showed recurrence in the peritoneum and multiple lymph nodes, and he received chemotherapy(RAM plus PTX). After initiating the third course of chemotherapy, he was hospitalized due to loss of appetite and fatigue. On the third day of hospitalization, he lost consciousness and had a temporary convulsion seizure. Thereafter, he complained of headache and nausea. Brain magnetic resonance imaging and cerebrospinal fluid examination lead to a diagnosis of carcinomatous meningitis due to gastric cancer. An Ommaya reservoir was placed, and intrathecal infusion with methotrexate(MTX)and cytarabine(Ara-C)was planned; however, intrathecal infusion could not be administered because of hepatic injury due to acute obstructive cholangitis. He died 6 months postoperatively. Carcinomatous meningitis has a rapidly progressive course with very poor prognosis. Early diagnosis is important, and the treatment should be initiated as soon as possible. Moreover, an effective standard treatment for carcinomatous meningitis needs to be established.

Risk of leptomeningeal carcinomatosis in patients with brain metastases treated with stereotactic radiosurgery.

There is limited available literature examining factors that predispose patients to the development of LMC after stereotactic radiosurgery (SRS) for brain metastases. We sought to evaluate risk factors that may predispose patients to LMC after SRS treatment in this case-control study of patients with brain metastases who underwent single-fraction SRS between 2011 and 2016. Demographic and clinical information were collected retrospectively for 19 LMC cases and 30 controls out of 413 screened patients with brain metastases. Risk factors of interest were evaluated by univariate and multivariate logistic regression analyses and overall survival rates were evaluated by Kaplan-Meier survival analysis. About 5% of patients with brain metastases treated with SRS developed LMC. Patients with LMC (median 154 days, 95% CI 33-203 days) demonstrated a poorer overall survival than matched controls (median 417 days, 95% CI 121-512 days, p = 0.002). The most common primary tumor histologies  that lead to the development of LMC were non-small cell lung cancer (36.8%), breast cancer (26.3%), and melanoma (21.1%). No association was found between the risk of LMC and the location of the brain lesion or total volume of brain metastases. Prior surgical resection of brain metastases before SRS was associated with a 6.5 times higher odds (95% CI 1.45-29.35, p = 0.01) of developing LMC post-radiosurgery compared to those with no prior resections of brain metastases. Additionally, adjuvant WBRT may help to reduce the risk of LMC and can be considered in decision-making for patients who have had brain metastasectomy.

[A Case of Cancerous Meningitis in Juvenile Onset Gastric Cancer].

A 30-year-old woman was diagnosed with advanced gastric cancer(MUL, Circ, Type 4, por1+2, T4a, N3a, M1[LYM, P1, CY1, H0], Stage Ⅳ)on delivery. Because of unresectable, she underwent chemotherapy(first-line: S-1 plus CDDP, secondline: PTX plus Rmab, and third-line: Nmab); approximately 10 months later, she started complaining of headache. We performed a close examination, because she also developed resistance to chemotherapy. Contrast-enhanced magnetic resonance imaging of the brain revealed intense and diffuse enhancement on the brain surface, leading to the suspicion of meningeal carcinomatosis. However, hydrocephalus did not occur. She was given steroids to alleviate symptoms, but this treatment did not effective. We used neither intrathecal chemotherapy nor radiation therapy. Her symptoms gradually worsened, and she died approximately 4 weeks after the diagnosis of meningeal carcinomatosis. Meningeal carcinomatosis resulting from gastric cancer is very rare and is often difficult to diagnose. Even though this type of disease is diagnosed correctly, rapid disease progression makes the treatment difficult; therefore, patients with this type of disease have a terribly poor prognosis in daily clinical practice.

[A Case of Lung Adenocarcinoma Presenting with Leptomeningeal Carcinomatosis Successfully Treated with Afatinib after Erlotinib-Induced Hepatotoxicity].

A 65-year-old man was diagnosed with leptomeningeal carcinomatosis based on the findings of cerebrospinal fluid cytology and magnetic resonance imaging(MRI).Treatment with erlotinib and bevacizumab was initiated, and partial improvement in consciousness and MRI findings were obtained.However, it was difficult to continue the treatment because of elevation in levels of liver enzymes and melena.We switched the treatment to afatinib monotherapy, and his consciousness improved immediately.Progression -free survival and overall survival from the initiation of the treatment with afatinib were 7 and 9.4 months, respectively. This clinical course suggests activity of afatinib for central nervous system lesions of EGFRmutated lung cancer.

Malignant meningitis secondary to oesophageal adenocarcinoma presenting with sensorineural hearing loss: a series of three cases and discussion of the literature.

Malignant meningitis may rarely present to the otolaryngologist. We report our experience with 3 patients presenting with sudden, progressive bilateral sensorineural hearing loss secondary to malignant meningitis. The primary tumour in all 3 cases was oesophageal adenocarcinoma. All 3 cases were notable for the rapidity of the patients' clinical deterioration; the interval from presentation to death ranged from 21 to 28 days. We suggest that otolaryngologists should remain vigilant to the possibility of this devastating diagnosis and have a low threshold for further investigation in patients with suspicious features. It is important to note that initial MRI and lumbar puncture may be negative and repeat testing should be undertaken if there is clinical suspicion.

[A Case of Difficult-to-Diagnose Carcinomatous Meningitis Caused by Prostate Cancer Metastasis].

A 66-year-old man was referred to our hospital because of right leg pain. Computed tomography (CT) revealed multiple osteolytic changes. His serum prostate-specific antigen (PSA) level was increased to 77.83 ng/ml at the time of hospitalization. A prostate biopsy was performed, and histological examination results indicated poorly differentiated adenocarcinoma. Under the diagnosis of multiple bone metastasis of prostate cancer, androgen deprivation therapy was started. However, 1 month later, the patient was confused and lost appetite. Brain CT image demonstrated brain metastasis, and magnetic resonance image showed hydrocephalus. Although the patient underwent ventricular drainage because of a depressed level of consciousness, he died of primary disease complicated by pneumonia 3 months after the first visit. Perioperative cerebrospinal fluid cytological examination revealed adenocarcinoma cells. Therefore, a diagnosis of carcinomatous meningitis caused by prostate cancer metastasis was made.

Risk factors for leptomeningeal carcinomatosis in patients with brain metastases who have previously undergone stereotactic radiosurgery.

Our objective was to explore the hypothesis that the risk of leptomeningeal dissemination (LMD) in patients who underwent stereotactic radiosurgery (SRS) for brain metastases is influenced by the site of the primary cancer, the addition of whole brain radiation therapy (WBRT), surgical resection, and control over their systemic disease. We conducted a retrospective cohort analysis of 805 patients who were treated with SRS for brain metastases between 1999 and 2012 at the Wake Forest Baptist Medical Center, and excluded all patients with evidence of LMD before SRS. The primary outcome was LMD. Forty-nine of 795 patients developed LMD with a cumulative incidence of 6.2% (95% Confidence Interval (CI), 4.7-8.0). Median time from SRS to LMD was 7.4 months (Interquartile Range (IQR), 3.3-15.4). A colorectal primary site (Hazard Ratio (HR), 4.5; 95% CI 2.5-8.0; p < 0.0001), distant brain failure (HR, 2.0; 95% CI 1.2-3.2; p = 0.007), breast primary site (HR, 1.6; 95% CI 1.0-2.7; p = 0.05), the number of intracranial metastases at time of initial SRS (HR, 1.1; 95% CI 1.0-1.2; p = 0.02), and age (by 5-year interval) (HR, 0.9; 95% CI 0.8, 0.9; p = 0.0006) were independent factors associated with LMD. There was no evidence that surgical resection before SRS altered the risk of LMD (HR, 1.1; 95 % CI 0.6-2.0, p = 0.78). In patients who underwent SRS for brain metastases, a colorectal or breast primary site, distant brain failure, younger age, and an increased number of intracranial metastases were independently associated with LMD. Given its relative rarity as an outcome, multi-institutional prospective studies will likely be necessary to validate and quantify these relationships.

[Case of leptomeningeal carcinomatosis with esophageal carcinoma presenting with neurological signs].

A 72-year-old male was admitted because of hearing impairment, blurred vision, right hemifacial numbness, and difficulty walking. Brain magnetic resonance imaging revealed two enhancing lesions with infiltration around the cranial nerves indicating either metastatic brain tumors or meningeal carcinomatosis. Cytological examination of the cerebrospinal fluid revealed malignant cells with keratotic changes. Upper gastrointestinal endoscopy was performed, which revealed type 1 squamous cell carcinoma of the esophagus;this led to the diagnosis of leptomeningeal carcinomatosis. In this report, we present a rare case of esophageal carcinoma accompanied by meningeal carcinomatosis diagnosed on the basis of neurological symptoms.

Clinical features and prognostic factors in patients with carcinomatous meningitis secondary to breast cancer.

Prognosis in patients with carcinomatous meningitis (CM) is poor, and numerous prognostic factors for response and survival have been described, but remain controversial. In general, series are small and involve a heterogeneous type of solid neoplasms. The purpose of this study was to describe a series of patients with breast cancer-associated CM to determine the clinical features and prognostic factors associated with survival. We conducted a retrospective study on 49 patients diagnosed between January 2003 and December 2007 at the Instituto Nacional de Cancerología in Mexico City. CSF cytopathology samples were re-reviewed to confirm the diagnosis. Overall survival (OS) for patients with breast cancer with CM was 7 weeks. Factors independently associated with better OS included absence of encephalopathy at diagnosis (11 weeks versus 1 week; p = .036), low CSF protein content (15 versus 5 weeks; p = .022), and nontriple-negative receptor status in the primary breast cancer tumor (13 versus 3 weeks; p = .015). According to multivariate analysis, patients were divided into favorable and poor prognostic groups, with OS of 14 weeks and 2 weeks, respectively (p < .001). These factors can identify a subgroup of patients who are candidates for an intensive management approach.

[A patient with gastric small cell carcinoma who died from meningitis carcinomatosa after CDDP+CPT-11 chemotherapy with good response].

A-63-year-old man was admitted to our hospital because of epigastralgia. On gastrointestinal fiberscopy, a complete obstruction of the pylorus was found, and endoscopic biopsy specimens from this region revealed gastric small cell carcinoma. CT scans showed the primary tumor at the pylorus with many regional lymph node metastases invading the pancreas. We performed gastrojejunostomy, followed by chemotherapy with irinotecan plus cisplatin (CDDP 30mg/m² and CPT-11 60mg/ m² on day 1 and 15). Three courses of treatment resulted in a marked reduction of both the primary tumor and regional lymph nodes. Subsequently, the patient underwent distal gastrectomy. Micro examination, revealed that the tumor had mostly changed to necrosis and fibrosis, and the pathological TNM grading was pT3 (SS) pN0M0, stage II A. Postoperatively, three courses of the same chemotherapy were performed. However, the patient died 5 months after the second operation, due to meningitis carcinomatosa without metastases of other organs.

Leptomeningeal dissemination as a first sign of progression in metastatic melanoma: a diagnostic lesson.

One of the most serious complications of advanced melanoma is the diffusion of cancer cells to the central nervous system. The diagnosis of leptomeningeal metastasis (LMM) is notoriously challenging and requires a combination of consistent MRI and cerebrospinal fluid (CSF) cytology. In ambiguous cases, mutations like BRAF V600E in CSF-cell-free (cf)DNA may help to clarify diagnosis of LMM. Here we present the case of a young woman who developed isolated LMM after the diagnosis of a node-positive primary melanoma with normal LDH. The CSF was negative for tumour cells by cytology but positive for cfDNA BRAF V600E mutation, thus allowing us to diagnose LMM. To our knowledge, this is the first case where CSF sampling for the detection of BRAF mutation was used to identify leptomeningeal disease in the presence of negative MRI and without involvement of any other distant sites.

Primary central nervous system lymphoma causing multiple spinal cord compression and carcinomatous meningitis in a 6-year-old: a case report.

Primary central nervous system lymphoma (PCNSL) is an uncommon form of non-Hodgkin lymphoma affecting the brain, spinal cord, and leptomeninges. Carcinomatous meningitis (CM) and spinal cord compression in PCNSL are very rare and usually present in advanced stages of the disease. The average survival time of a CM patient is about 4 to 6 weeks, which may be extended to about 4 to 6 months with treatment. Here we present a case of CM and spinal cord compression by multiple PCNSL in a 6-year-old girl, who has survived 2 years and 9 months posttreatment with no recurrence. To the best of our knowledge this is the very first case reporting survival after CM. The patient presented with weakness of her right arm, right leg, and left side of the face. Examination revealed mild facial asymmetry with left facial lower motor neuron palsy and lateral gaze restriction of left eye. Magnetic resonance imaging of her spinal cord showed postcontrast enhancement of the intradural structures on the spinal canal at levels C3-C6 and L1-L5 and along with the intracranial leptomeninges. Histopathological examination of the neoplastic tissue from cauda equina revealed B-cell non-Hodgkin lymphoma. After chemotherapy her disease regressed and magnetic resonance imaging showed no evidence of recurrence or residual disease. In our experience the response to chemotherapy was remarkable and recommend that aggressive tumor resection strategies should be reserved for cases with severe signs of spinal compression.

Neoplastic meningitis.Review of a clinical series.

INTRODUCTION: The increase in the ageing population in the last decades has led to an increased frequency of cancer-associated complications. Among these, neurological disorders stand out, as they appear in 10-30% of patients with systemic neoplasia. Neoplastic meningitis accounts for 4-15% of patients with solid tumours and it has a poor prognosis. The objective of this paper is to describe the clinical, imaging and prognostic characteristics as well as cerebrospinal fluid findings in a series of neoplastic meningitis. BACKGROUND AND DEVELOPMENT: We performed a retrospective review of all patients admitted to the Hospital Universitario of Gran Canaria Dr. Negrín with clinical suspicion of neoplastic meningitis between 1990 and 2008. We selected 37 patients with an average age ranging from 15 to 75 years old. A total of 81.8% of the cases in which a primary tumour was found were associated with solid tumours (24.2% were located in the breast, and 24.2% in the lung). The most frequent sign of cranial nerve dysfunction was dyplopia, which was observed in 32.4% of the cases. The average survival rate after diagnosis was 87.9 days (12.6 weeks). The cerebrospinal fluid cytology was positive in 46.4% of the cases. CONCLUSION: Neoplastic meningitis is a severe complication of both solid and haematological tumours. We stress the importance of maintaining a high level of suspicion to achieve early diagnosis, since the average survival probability for neoplastic meningitis patients is low.

Cerebrospinal Fluid Spread in a Child with Pleomorphic Xanthoastrocytoma: Report with Cytopathologic Evidence.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA), a relatively uncommon, World Health Organization grade II tumor of astrocytic origin, occurs in children and in general carries good prognosis. The recently identified anaplastic PXA (grade III) type shows poor outcome. Rarely, these said tumors can display an aggressive clinical course with features of leptomeningeal spread. Such cases are mostly seen in adults, with rare instances reported in the pediatric age group. CASE DESCRIPTION: In this report, we describe an 8-year-old child with anaplastic PXA with a rapid downhill course due to cerebrospinal fluid spread. This child is perhaps the first pediatric report in which the cerebrospinal fluid dissemination was established on cytology. CONCLUSIONS: The case is an indicator of the need for craniospinal screening protocol in patients with PXA, especially the anaplastic variety, both at the time of initial diagnosis and follow-up.

Under-recognized toxicities of cranial irradiation.

Cranial irradiation of primary or metastatic lesions is frequent, historically with 3D-conformal radiation therapy and now with stereotactic radiosurgery and intensity modulation. Evolution of radiotherapy technique is concomitant to systemic treatment evolution permitting long time survival. Thus, physicians have to face underestimated toxicities on long-survivor patients and unknown toxicities from combination of cranial radiotherapy to new therapeutics as targeted therapies and immunotherapies. This article proposes to develop these toxicities, without being exhaustive, to allow a better apprehension of cranial irradiation in current context.