leptomeningeal carcinomatosis nsclc

Osimertinib has been shown to be effective for patients with non-small cell lung cancer (NSCLC) with activating EGFR mutations, and these patients are at risk for leptomeningeal disease. In this report, we present a patient of East Asian descent whose initial presentation included severe, progressive leptomeningeal carcinomatosis and a small lung mass, with limited tissue available for molecular testing. She responded to empiric, urgent initiation of osimertinib, repeat tissue sampling revealed an EGFR L858R mutation, and she has experienced durable disease improvement for 18 months on osimertinib monotherapy...

PURPOSE: Leptomeningeal carcinomatosis (LC) is a rare complication of non-small cell lung cancer (NSCLC) with highly mortality. Cerebrospinal fluid (CSF) as a special kind of tumor microenvironment (TME) better represents alterations than plasma. However, the clinical value of protein profiles of exosome in CSF as liquid biopsy remains unclear. METHODS: In this study, CSF samples of NSCLC patients with (LC group) or without (NSCLC group) LC were collected and compared to patients without tumors (normal group)...

When a patient with encephalopathy has an organic brain lesion, his symptom is easily and often mistakenly attributed to that brain lesion. However, a combination of different conditions is also possible. We present a case of autoimmune limbic encephalitis combined with leptomeningeal carcinomatosis. A 57-year-old female patient was transferred to our institute with a 1-month history of seizure and aggressive behavior. Subacute onset of psychosis with multifocal T2 high signal lesions suggested autoimmune encephalitis, and high-dose steroid pulse and immunoglobulin therapy were started...

BACKGROUND: Leptomeningeal carcinomatosis (LMC) is a rare type of cancer that settles at the meninges through metastasis of non-small cell lung cancer (NSCLC), breast cancer and melanoma. The molecular mechanism underlying LMC is not known, therefore molecular studies investigating the development of LMC are needed. Here, we aimed to identify commonly mutated genes in LMC caused by NSCLC, breast cancer, and melanoma using an in-slico approach and their interactions using integrated bioinformatic approaches/tools in this meta-analysis...

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BACKGROUND: In advanced non-small cell lung cancer (NSCLC), leptomeningeal metastases (LM) is a common consequence with rapid progression and a poor prognosis. LM affects roughly 3% to 5% of NSCLC patients, and it affects as many as 9.4% of individuals with epidermal growth factor receptor (EGFR) mutations. Cerebrospinal fluid cytology is the gold standard for diagnosing LM, while conventional cytopathology has a positive detection rate of less than 50%, resulting in a delay in diagnosis and treatment of LM...

BACKGROUND: Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal (LM) metastasis than other types of lung cancers and have a poor prognosis. Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis. CASE SUMMARY: A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital...

Leptomeningeal metastasis (LM), also known as leptomeningeal carcinomatosis (LC), is a devastating complication of metastatic cancer that occurs when neoplastic cells invade the meningeal space. Diagnosis of LM remains challenging given the heterogeneous signs and symptoms at presentation and requires thorough neurological examination, cerebrospinal fluid (CSF) analysis, and MRI of the brain and spine with gadolinium. Detecting neoplastic cells in the CSF is the gold standard for diagnosing leptomeningeal metastases; however, it has low sensitivity and may require multiple CSF samples...

Paraneoplastic cerebellar degeneration (PCD) is one of the most prevalent neurological paraneoplastic syndromes, typically associated with small cell lung cancer (SCLC). PCD is thought to be caused by proteins expressed by tumor cells which trigger an antibody-mediated immune response. Despite PCD being commonly associated with anti-Yo, anti-Hu and anti-Tr/DNER antibodies, PCD is the most prevalent paraneoplastic syndrome in patients harboring anti-Zic4 antibodies. We report what, to our knowledge, is the first known case of anti-Zic4 mediated PCD in a patient with EGFR -mutated metastatic non-small cell lung cancer (NSCLC)...

Leptomeningeal carcinomatosis is a rare complication of metastatic systemic malignancy, with lung cancer being the most common cause. We present a case of a 75-year-old man with a past medical history of right non-small cell lung carcinoma and ischemic stroke who presented with a persistent headache and swallowing difficulties. On evaluation, the patient was initially diagnosed with a subacute infarct of the right posterior frontal lobe following magnetic resonance imaging (MRI). The patient's headache and dysphagia worsened, increasing the possibility of brain metastasis...

Leptomeningeal carcinomatosis (LMC) is a known sequel of metastatic lung cancer and its treatment is challenging. Nevertheless, treatment options for LMC due to metastatic epidermal growth factor receptor-mutant ( EGFR -mutant) lung adenocarcinoma are expanding. We present a 52-year-old male patient with metastatic non-small-cell lung cancer (NSCLC). The patient was found to have L858R mutation in exon 21 of the EGFR gene. He was initially treated with erlotinib, followed by afatinib/cetuximab, followed by chemotherapy...

Immunotherapy has now been integrated as a treatment strategy for most patients with non-small cell lung cancer (NSCLC). However, the pivotal clinical trials that demonstrated its impressive efficacy often did not include patients with active, untreated brain metastases or leptomeningeal carcinomatosis. Nevertheless, NSCLC is the most common tumor to metastasize to the brain, and patients develop brain and meningeal involvement in approximately 40 and 10% of cases, respectively. Consequently, the appropriate care of these patients is a recurrent clinical concern...

Lorlatinib is a third-generation, brain-penetrant anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI) with robust intracranial activity in patients with ALK- or ROS1-positive non-small cell lung cancer (NSCLC). Data from the ongoing open-label, single-arm, multicenter, phase-1/2 study of lorlatinib in patients with metastatic ALK- or ROS1-positive NSCLC were used to further investigate the potential brain penetration of lorlatinib. Patients received escalating lorlatinib doses (10-200 mg once daily or 35-100 mg twice daily) or the approved dosing (100 mg daily)...

PURPOSE: Central nervous system metastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). The phase II ASCEND-7 (NCT02336451) study was specifically designed to assess the efficacy and safety of the ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges. PATIENTS AND METHODS: Patients with active brain metastases were allocated to study arms 1 to 4 based on prior exposure to an ALKi and/or prior brain radiation (arm 1: prior radiotherapy/ALKi-pretreated; arm 2: no radiotherapy/ALKi-pretreated; arm 3: prior radiotherapy/ALKi-naïve; arm 4: no radiotherapy/ALKi-naïve)...

Brain metastases (BMs) represent the most frequent event during the course of Non-Small Cell Lung Cancer (NSCLC) disease. Recent advancements in the diagnostic and therapeutic procedures result in increased incidence and earlier diagnosis of BMs, with an emerging need to optimize the prognosis of these patients through the adoption of tailored treatment solutions. Nowadays a personalized and multidisciplinary approach should rely on several clinical and molecular factors like patient's performance status, extent and location of brain involvement, extracranial disease control and the presence of any "druggable" molecular target...

INTRODUCTION: Approximately 25%-30% of patients with non-small cell lung cancer (NSCLC) develop central nervous system (CNS) metastases during the course of the disease; this percentage is higher in patients with epidermal growth factor receptor (EGFR) mutations. Leptomeningeal metastases, infrequent in the advanced setting, have a particularly dismal prognosis. Osimertinib, a third-generation EGFR inhibitor, can provide effective and durable response in this setting. CASE DESCRIPTION: We present a 62-year-old man with progressive vomiting, headache, short-term memory impairment, and left lower limb hyposthenia...

BACKGROUND: Cauda equina syndrome (CES) is a challenging condition and it can be caused by variable entities. Leptomeningeal carcinomatosis (LC) is a multifocal seeding of the leptomeninges by malignant cells and it is observed in 1-8% of patients with solid tumors. Diagnosis of intradural metastases of the cauda equina is often delayed due to the non-specific characteristics of this condition but also to the delay of presentation of many patients. Cauda equina metastases usually occur in advanced cancers, but rarely can be the first presentation of disease...

Leptomeningeal carcinomatosis (LMC) occurs frequently in non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and is associated with acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, the mechanism by which LMC acquires resistance to osimertinib, a third-generation EGFR-TKI, is unclear. In this study, we elucidated the resistance mechanism and searched for a novel therapeutic strategy. We induced osimertinib resistance in a mouse model of LMC using an EGFR-mutant NSCLC cell line (PC9) via continuous oral osimertinib treatment and administration of established resistant cells and examined the resistance mechanism using next-generation sequencing...

Lorlatinib treatment should be positively considered even for patients with ALK-positive NSCLC with severe neurocognitive disturbance and poor performance status due to CNS metastases, including leptomeningeal carcinomatosis.

INTRODUCTION: We report on the results of the German early access program (EAP) with the third-generation ALK- and ROS1-inhibitor lorlatinib. PATIENTS AND METHODS: Patients with documented treatment failure of all approved ALK/ROS1-specific therapies or with resistance mutations not covered by approved inhibitors or leptomeningeal carcinomatosis were enrolled and analyzed. RESULTS: In total, 52 patients were included [median age 57 years (range 32-81), 54% female, 62% never smokers, 98% adenocarcinoma]; 71% and 29% were ALK- and ROS1-positive, respectively...