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Clinical Lung Cancer Jun 2024To analyze the factors associated with EGFR-mutated lung cancer with leptomeningeal metastasis (LM) in the real world that affects the prognosis of patients.
OBJECTIVE
To analyze the factors associated with EGFR-mutated lung cancer with leptomeningeal metastasis (LM) in the real world that affects the prognosis of patients.
MATERIALS AND METHODS
The clinical data of 123 patients with advanced EGFR mutated lung cancer combined with LM treated at Henan Cancer Hospital and confirmed by histology between January 2016 and December 2020 were retrospectively collected, and all patients were followed up until September 2021. Analyze the median overall survival (mOS) time of patients with clinical characteristics and treatment factors to explore the factors influencing the prognosis of lung cancer patients with LM.
RESULTS
A total of 123 patients with EGFR-mutated lung cancer and LM were included in this study. Overall, patients with exon 19 deletion (19del) in the classical mutation of the EGFR gene had a prolonged mOS compared to patients with exon 21 L858R mutation (21L858R) (30.1 months vs. 26.0 months); patients with primary LM (mOS 21.2 months) had a significantly shorter mOS than those with secondary LM (mOS 28.3 months); mOS was also significantly shorter in patients with combined brain metastases (mOS of 25.4 months) than in patients without combined brain metastases (mOS of 33.4 months); Patients treated with tyrosine kinase inhibitors (TKI) combined with antiangiogenic therapy (bevacizumab) experienced delayed onset of LM (mOS1: 19.4 months vs. 13.9 months), and prolonged survival after LM compared with those treated with EGFR-TKI alone (mOS2: 14.5 months vs. 10.0 months); There is no survival benefit to the patients treated with EGFR-TKI combined with chemotherapy compared to the patients treated with EGFR-TKI alone.
CONCLUSION
Among NSCLC-LM patients with EGFR mutation, receiving EGFR-TKI combined with antiangiogenic therapy may result in a better survival benefit. The factors of primary LM, combined brain metastasis may be prognostic factors for poor OS.
Topics: Humans; Male; Retrospective Studies; ErbB Receptors; Female; Lung Neoplasms; Middle Aged; Prognosis; Mutation; Aged; Adult; Survival Rate; Meningeal Neoplasms; Carcinoma, Non-Small-Cell Lung; Meningeal Carcinomatosis; Follow-Up Studies; Brain Neoplasms; Aged, 80 and over; Protein Kinase Inhibitors
PubMed: 38418264
DOI: 10.1016/j.cllc.2024.02.001 -
ESMO Open Apr 2024This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung...
BACKGROUND
This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC) who progressed from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in an expanded, prospective, single-arm, phase II clinical study (ChiCTR1800016615).
PATIENTS AND METHODS
Patients with confirmed NSCLC-LM who progressed from TKI received IP (50 mg, day 1/day 5 for 1 week, then every 3 weeks for four cycles, and then once monthly) until disease progression or intolerance. Objectives were to assess overall survival (OS), response rate, and safety. Measurable lesions were assessed by investigator according to RECIST version 1.1. LM were assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria.
RESULTS
The study included 132 patients; 68% were female and median age was 52 years (31-74 years). The median OS was 12 months (95% confidence interval 10.4-13.6 months), RANO-assessed response rate was 80.3% (106/132), and the most common adverse event was myelosuppression (n = 42; 31.8%), which reversed after symptomatic treatment. The results of subgroup analysis showed that absence of brain parenchymal metastasis, good Eastern Cooperative Oncology Group score, good response to IP treatment, negative cytology after treatment, and patients without neck/back pain/difficult defecation had longer survival. Gender, age, previous intrathecal methotrexate/cytarabine, and whole-brain radiotherapy had no significant influence on OS.
CONCLUSIONS
This study further showed that IP is an effective and safe treatment method for the EGFR-TKI-failed NSCLC-LM, and should be recommended for these patients in clinical practice and guidelines.
Topics: Humans; Female; Male; Middle Aged; Aged; Carcinoma, Non-Small-Cell Lung; Pemetrexed; Lung Neoplasms; Adult; ErbB Receptors; Injections, Spinal; Prospective Studies; Meningeal Neoplasms; Protein Kinase Inhibitors; Meningeal Carcinomatosis; Treatment Outcome
PubMed: 38377785
DOI: 10.1016/j.esmoop.2024.102384 -
Journal of Neuro-oncology Mar 2024Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor...
BACKGROUND
Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor prognosis and are challenging to treat. We described the clinicopathologic features and outcomes in the largest cohort of Central Nervous System (CNS) metastasis in GEC patients.
METHODS
single-center retrospective study of GEC treated from 2007 to 2021. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of CNS diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used.
RESULTS
Of 3283 GEC patients, 100 (3.04%) were diagnosed with BrM and 20 with LMC (0.61%). Patients with known human epidermal growth factor receptor 2 (HER2) status (N = 48), 60% were HER2 positive (defined as IHC 3 + or IHC 2+/FISH+). Among LMC patients most were signet-ring subtype (85%), and only 15% (2/13) were HER2 positive. Median survival was 0.7; 3.8; and 7.7 months in BrM patients treated with best supportive care, radiation, and surgery, respectively (p < 0.001). In LMC, median survival was 0.7 month in patients who had best supportive care (7/19) and 2.8 months for those who had whole brain radiation therapy (p = 0.015). Multivariate analysis showed worse outcomes in ECOG ≥ 2 (p = 0.002), number of BrM ≥ 4 (p < 0.001) and number of metastatic sites (p = 0.009).
CONCLUSION
HER2 expression were enriched in patients with BrM, while it is uncommon in LMC. Patients treated with surgery followed by radiation had an improved OS in BrM and WBRT benefited patients with LMC.
Topics: Humans; Meningeal Carcinomatosis; Retrospective Studies; Brain Neoplasms; Proportional Hazards Models; Carcinoma
PubMed: 38372902
DOI: 10.1007/s11060-024-04576-8 -
Asian Journal of Surgery May 2024
Topics: Humans; Meningeal Carcinomatosis; Rectal Neoplasms; Adenocarcinoma; Disease Progression; Fatal Outcome; Male; Middle Aged; Magnetic Resonance Imaging
PubMed: 38336490
DOI: 10.1016/j.asjsur.2024.01.174 -
Neurology Mar 2024Hydrocephalus is a common radiologic sign in patients with leptomeningeal metastasis (LM) from solid tumors which can be assessed using the Evans index (EI). Here, we...
BACKGROUND AND OBJECTIVES
Hydrocephalus is a common radiologic sign in patients with leptomeningeal metastasis (LM) from solid tumors which can be assessed using the Evans index (EI). Here, we explored the prognostic value of ventricular size in LM.
METHODS
We identified patients with LM from solid tumors by chart review at 3 academic hospitals to explore the prognostic associations of the EI at diagnosis, first follow-up, and progression.
RESULTS
We included 113 patients. The median age was 58.3 years (interquartile range [IQR] 46.1-65.8), 41 patients (36%) were male, and 72 patients (64%) were female. The most frequent cancers were lung cancer (n = 39), breast cancer (n = 36), and melanoma (n = 23). The median EI at baseline was 0.28 (IQR 0.26-0.31); the EI value was 0.27 or more in 67 patients (59%) and 0.30 or more in 37 patients (33%). Among patients with MRI follow-up, the EI increased by 0.01 or more in 16 of 31 patients (52%), including 8 of 30 patients (30%) without and 10 of 17 patients (59%) with LM progression at first follow-up. At LM progression, an increase of EI of 0.01 or more was noted in 18 of 34 patients (53%). The median survival was 2.9 months (IQR 1-7.2). Patients with a baseline EI below 0.27 had a longer survival than those with an EI of 0.27 or more (5.3 months, IQR 2.4-10.8, vs 1.3 months, IQR 0.6-4.1) (HR 1.70, 95% CI 1.135-2.534, = 0.0099). The median survival was 3.7 months (IQR 1.4-8.3) with an EI below 0.30 vs 1.8 months (IQR 0.8-4.1) with an EI of 0.30 or more (HR 1.40, 95% CI 0.935-1.243, = 0.1113). Among patients with follow-up scans available, the overall survival was 9.4 months (IQR 5.6-21.0) for patients with stable or decreased EI at first follow-up as opposed to 5.6 months (IQR 2.5-10.5) for those with an increase in the EI (HR 1.08, 95% CI 0.937-1.243; = 0.300).
DISCUSSION
The EI at baseline is prognostic in LM. An increase of EI during follow-up may be associated with inferior LM progression-free survival. Independent validation cohorts with larger sample size and evaluation of confounding factors will help to better define the clinical utility of EI assessments in LM.
Topics: Humans; Male; Female; Middle Aged; Prognosis; Retrospective Studies; Lung Neoplasms; Meningeal Carcinomatosis; Breast Neoplasms
PubMed: 38335471
DOI: 10.1212/WNL.0000000000207959 -
Frontiers in Neurology 2023Neurosarcoidosis (NS) is a challenging diagnosis, particularly when cases occur in low-prevalence, non-endemic geographic regions. In the United States, the highest...
BACKGROUND
Neurosarcoidosis (NS) is a challenging diagnosis, particularly when cases occur in low-prevalence, non-endemic geographic regions. In the United States, the highest incidence is in the Midwest and Northeast, compared to our Southwest location. While it is well known that NS may clinically and neuroradiographically mimic meningeal carcinomatosis, autoimmune or infectious pachymeningitis, neurosyphilis, or tuberculosis, diagnosis may be particularly challenging if systemic signs of sarcoidosis are lacking or unconfirmed or if dural-based masses are present. We reviewed our Colorado experience with NS cases, focusing our study on cases where NS represented the first histological confirmation of disease.
METHODS
A search of departmental databases was conducted with the search term "neurosarcoidosis" to identify cases 1-2008 to 12-2019, inclusive of the given case numbers. Patients were only included if their clinical and neuroimaging features were unusual and only when a biopsy of the central nervous system (CNS) represented the first confirmed diagnosis of sarcoidosis.
RESULTS
A total of 17 cases were identified, of which the biopsy of the CNS was used for the initial confirmation of the disease in 9 of them. The most unusual findings were two patients with dural-based masses, one of which had pure NS as the cause of meningioma-like lesions and the second of which had coexistent meningioma and intimately admixed non-necrotizing granulomas of NS.
CONCLUSION
NS with unusual features, especially in non-endemic areas, continues to yield diagnostic challenges for neurologists, neuroradiologists, and pathologists.
PubMed: 38274870
DOI: 10.3389/fneur.2023.1220635 -
Lung Cancer (Amsterdam, Netherlands) Feb 2024Leptomeningeal metastasis (LM) is associated with an extremely poor prognosis in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer...
BACKGROUND
Leptomeningeal metastasis (LM) is associated with an extremely poor prognosis in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The third-generation EGFR-tyrosine kinase inhibitors (TKIs), currently the preferred drug of choice, have significantly improved treatment outcomes in these patients. However, the optimal dose of third-generation EGFR-TKIs for clinical use remains undetermined in NSCLC patients with LM.
METHODS
We retrospectively analyzed the clinical characteristics and treatment outcomes of 105 patients with EGFR-mutated NSCLC and cytologically confirmed LM who had received third-generation EGFR-TKI treatment after LM diagnosis. Patients were stratified into high- and standard-dose groups based on the treatment dose of third-generation EGFR-TKI. Subsequent treatments for LM were collected, particularly the efficacy of different doses of third-generation EGFR-targeted drugs.
RESULTS
The median follow-up period was 28.7 months (range 0.6-40.2) at the cut-off date of August 27, 2023. The 105 included patients who received third-generation EGFR-TKI treatment had a clinical response rate (CRR) of 54.3 % (57/105), and the median overall survival (OS) from LM diagnosis was 12.3 months (95 % confidence interval [CI] = 10.0-15.0). Among them, 46 (43.8 %) patients received a high-dose regimen, and the remaining 59 (56.2 %) patients were treated with standard-dose drugs. Patients treated with high-dose third-generation EGFR-TKIs showed a higher CRR and longer OS than those treated with standard-dose therapy (65.2 % vs. 45.8 %, p = 0.047; 15.0 vs. 10.2 months, p = 0.014). Importantly, high-dose third-generation EGFR-TKI showed superior OS than standard-dose treatment in all subgroups (prior first-/second-generation EGFR-TKI resistance group, 19.5 vs. 9.8 months, p = 0.047; third-generation EGFR-TKI resistance group, 10.0 vs. 4.3 months, p = 0.045; EGFR-TKI naive group, not reach vs. 15.6 months, p = 0.031). Multivariate analysis revealed that high-dose third-generation EGFR-TKIs, intrathecal chemotherapy, previous TKI treatment history, and Karnofsky Performance Status score were independent predictors of OS (all p < 0.05).
CONCLUSIONS
High-dose third-generation EGFR-TKIs are effective treatments for NSCLC patients with EGFR mutations and LM, regardless of previous EGFR-TKI exposure.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Tyrosine Kinase Inhibitors; Retrospective Studies; Protein Kinase Inhibitors; Meningeal Carcinomatosis; ErbB Receptors; Mutation
PubMed: 38266613
DOI: 10.1016/j.lungcan.2024.107475 -
Journal of Neuroimmunology Feb 2024Purkinje cell cytoplasmic autoantibody type 1 (PCA1), also known as anti-Yo, is a 'high-risk' paraneoplastic antibody, associated with rapidly progressive cerebellar...
Purkinje cell cytoplasmic autoantibody type 1 (PCA1), also known as anti-Yo, is a 'high-risk' paraneoplastic antibody, associated with rapidly progressive cerebellar syndrome. In patients with this syndrome, various MRI abnormalities have been documented, including atrophy in the cerebellum and brainstem, T2 hyperintensity in the brainstem and spinal cord, and cranial nerve enhancement. This report introduces an imaging finding, cerebellar leptomeningeal enhancement, which was observed in all three cases at early stages. Despite neurological deterioration, all patients underwent immunotherapy, and subsequent follow-up MRI revealed resolution of the leptomeningeal enhancement, suggesting that this feature is distinct from meningeal carcinomatosis.
Topics: Humans; Paraneoplastic Cerebellar Degeneration; Purkinje Cells; Autoantibodies; Nerve Tissue Proteins; Cerebellum; Cerebellar Diseases; Paraneoplastic Syndromes
PubMed: 38266443
DOI: 10.1016/j.jneuroim.2024.578293 -
Gan To Kagaku Ryoho. Cancer &... Jan 2024In a 79-year-old man, upper gastrointestinal endoscopy and CT revealed an entire circumferential type 3 tumor with stenosis from the lower thoracic esophagus to the...
In a 79-year-old man, upper gastrointestinal endoscopy and CT revealed an entire circumferential type 3 tumor with stenosis from the lower thoracic esophagus to the abdominal esophagus. He was diagnosed with esophageal adenocarcinoma and underwent middle and lower esophageal resection and 2 regional lymph node dissections. The postoperative pathological diagnosis was poorly differentiated adenocarcinoma, pT3N0M0, pStage ⅡA esophagogastric junction cancer(Siewert type Ⅱ). The patient was followed-up without postoperative adjuvant chemotherapy, following the Japanese Gastric Cancer Treatment Guidelines 2021(6th edition). Six months postoperatively, contrast-enhanced CT revealed multiple lymph node, small intestinal mesenteric, and left adrenal metastases, and SOX therapy was initiated. After 4 courses of SOX therapy, the patient was brought to the emergency room and admitted with anorexia and weakness, and consciousness disorder was observed on the next day. Contrast-enhanced MRI of the head was indicative of meningeal carcinomatosis, and cytological examination of the spinal fluid revealed adenocarcinoma, which was diagnosed as meningeal carcinomatosis from esophagogastric junction carcinoma. Subsequently, his consciousness disorder worsened, and he died on the 9th day of hospitalization. We report a rare case of meningeal carcinomatosis following esophagogastric junction cancer.
Topics: Male; Humans; Aged; Meningeal Carcinomatosis; Consciousness Disorders; Esophagogastric Junction; Adenocarcinoma; Lymph Node Excision
PubMed: 38247098
DOI: No ID Found -
European Journal of Radiology Feb 2024The purpose of this study is to investigate whether the presence and pattern of enhancement at the internal acoustic canal (IAC) could help in discriminating between...
PURPOSE
The purpose of this study is to investigate whether the presence and pattern of enhancement at the internal acoustic canal (IAC) could help in discriminating between leptomeningeal carcinomatosis (LCa) and meningeal inflammation/infection (MMI).
METHODS
Magnetic resonance (MR) images of patients with leptomeningeal enhancement were retrospectively evaluated. MR images of the LCa group (n = 33), MMI group (n = 19) and control group (n = 33) were evaluated for the presence, type (moderate/prominent), and localization (unilateral/bilateral) of the IAC enhancement.
RESULTS
The presence of IAC enhancement was significantly more common in patients with LCa (p < 0.001). In 73.7 % of patients with MMI, no contrast enhancement was observed in the IAC. In patients with contrast enhancement in the IAC, the risk of LCa in the etiology is 20 times greater than the risk of having MMI. Seventy-five percent of the IAC enhancement seen in LCa patients and 20 % of the IAC enhancements seen in MMI patients was bilateral. This difference was statistically significant (p = 0.029).
CONCLUSION
Intense contrast enhancement of the IAC can be a marker for LCa.
Topics: Humans; Meningeal Carcinomatosis; Retrospective Studies; Meninges; Inflammation; Magnetic Resonance Imaging
PubMed: 38237519
DOI: 10.1016/j.ejrad.2024.111299