Search Results (15)

Background and Clinical Significance: The mesenchymal–epithelial transition (MET) exon 14 skipping mutation (METex14) is a rare genetic alteration occurring in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) are the approved treatment for first-line therapy in a metastatic setting. However, the unusual presentation of gastrointestinal metastasis and leptomeningeal carcinomatosis (LMD) poses significant treatment challenges. Case Presentation: Here we report a case of a 72-year-old male with metastatic METex14-positive NSCLC, presenting with brain and duodenal metastases. Conclusions: The patient responded exceptionally well to first-line chemoimmunotherapy, achieving clinically complete remission for 2 years. He subsequently developed cerebellar metastasis and leptomeningeal disease (LMD) but demonstrated a remarkable response to tepotinib and continued to enjoy radiographic complete remission over 2.5 years at the time of this report. Full article

Brain and leptomeningeal metastases are complications of breast cancer with high rates of morbidity and mortality and have an estimated incidence of up to 30%. While National Comprehensive Cancer Network (NCCN) guidelines recommend screening for central nervous system metastasis in other neurotropic cancers such as non-small cell lung cancer, there are no such recommendations for asymptomatic breast cancer patients at any stage of disease. This review highlights ongoing studies into screening and diagnostics for breast cancer with brain and leptomeningeal metastasis (BCBLM) as they relate to patient outcomes and prognostication. These include imaging methods such as MRI with novel contrast agents with or without PET/CT, as well as ‘liquid biopsy’ testing of the cerebrospinal fluid and serum to analyze circulating tumor cells, genomic material, proteins, and metabolites. Given recent advances in radiation, neurosurgery, and systemic treatments for BCBLM, screening for CNS involvement should be considered in patients with advanced breast cancer as it may impact treatment decisions and overall survival. Full article

Leptomeningeal carcinomatosis (LC) is a rare site of metastasis in solid tumors, and it is associated with poor prognosis due to disabling symptoms and a scarcity of treatment options. This condition is an uncommon entity in gastric cancer (GC). We present a case of primary LC manifestation in a patient with an incidental diagnosis of localized node-negative GC. We additionally perform a literature review and discuss the diagnostic and therapeutic challenges. In conclusion, LC from GC represents a rare condition with a dramatic prognosis. Its diagnosis might be very challenging. A multidisciplinary approach appears to be the best strategy for the management of LC from GC. Full article

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. Full article

Leptomeningeal disease (LMD) is a devastating complication of cancer with a particularly poor prognosis. Among solid tumours, malignant melanoma (MM) has one of the highest rates of metastasis to the leptomeninges, with approximately 10–15% of patients with advanced disease developing LMD. Tumour cells that metastasise to the brain have unique properties that allow them to cross the blood–brain barrier, evade the immune system, and survive in the brain microenvironment. Metastatic colonisation is achieved through dynamic communication between metastatic cells and the tumour microenvironment, resulting in a tumour-permissive milieu. Despite advances in treatment options, the incidence of LMD appears to be increasing and current treatment modalities have a limited impact on survival. This review provides an overview of the biology of LMD, diagnosis and current treatment approaches for MM patients with LMD, and an overview of ongoing clinical trials. Despite the still limited efficacy of current therapies, there is hope that emerging treatments will improve the outcomes for patients with LMD. Full article

Leptomeningeal carcinomatosis is a rare but serious consequence of pre-existing tumors, such as breast, lung, and gastrointestinal carcinomas. Further, leptomeningeal carcinomatosis is more frequently diagnosed with breast cancers, if only because breast cancers are diagnosed far more often than any other carcinomas. In this paper, we present the case of a leptomeningeal carcinomatosis patient who experienced complete remission following therapy targeted at the Her-2 (human epidermal growth factor receptor 2-positive) receptor. This patient’s diagnosis was complicated by the fact that brain and column MRI imaging were clear, but analysis of the cerebrospinal fluid led to the conclusion of leptomeningeal carcinomatosis. The tests were requested because the patient, under chemotherapy for advanced breast cancer at the time, reported some neurological symptoms. Following the diagnosis of leptomeningeal carcinomatosis and subsequent T-DM1 Her-2 receptor therapy, the patient showed a complete response to leptomeningeal carcinomatosis within 30 days and survived for another 16 months. This case offers compelling evidence that the effect TDM1 Her-2 receptor therapy has on a patient’s remission and long-term survivability is considerably better than other therapies for similar pre-existing conditions diagnosed with leptomeningeal carcinomatosis. Further prospective studies should confirm these findings. Full article

Leptomeningeal carcinomatosis (LMC) is a fatal but uncommon complication occurring in 5–15% of patients with stage IV cancer. Current treatment options are ineffective at managing leptomeningeal spread, with a median overall survival (mOS) of 2–6 months. We aimed to conduct a systematic review of the literature to identify past and future therapies for LMC from solid tumors. Forty-three clinical trials (CTs) published between 1982–2022 were identified. Of these, 35 (81.4%) were non-randomized CTs and 8 (18.6%) were randomized CTs. The majority consisted of phase I (16.3%) and phase II CTs (65.1%). Trials enrolled patients with LMC from various primary histology (n = 23, 57.5%), with one CT evaluating LCM from melanoma (2.4%). A total of 21 trials evaluated a single modality treatment. Among CTs, 23.7% closed due to low accrual. Intraventricular (ITV)/intrathecal (IT) drug delivery was the most common route of administration (n = 22, 51.2%) vs. systemic drug delivery (n = 13, 30.3%). Two clinical trials evaluated the use of craniospinal irradiation for LMC with favorable results. LMC continues to carry a dismal prognosis, and over the years, increments in survival have remained stagnant. A paradigm shift towards targeted systemic therapy with continued standardization of efficacy endpoints will help to shed light on promising treatments. Full article

Central nervous system (CNS) metastasis from systemic cancers can involve the brain parenchyma, leptomeninges, or the dura. Neoplastic meningitis (NM), also known by different terms, including leptomeningeal carcinomatosis and carcinomatous meningitis, occurs due to solid tumors and hematologic malignancies and is associated with a poor prognosis. The current management paradigm entails a multimodal approach focused on palliation with surgery, radiation, and chemotherapy, which may be administered systemically or directly into the cerebrospinal fluid (CSF). This review focuses on novel therapeutic approaches, including targeted and immunotherapeutic agents under investigation, that have shown promise in NM arising from solid tumors. Full article

Leptomeningeal carcinomatosis (LC), defined as the infiltration of the leptomeninges by cancer cells, is a rare oncological event with the most common etiology being breast cancer (BC), lung cancer, and melanoma. Despite innovations in radiotherapy (RT), firm evidence of its impact on survival is lacking, and concerns are related to its possible neurotoxicity. Owing to a paucity of data, the optimal treatment strategy for LC remains unknown. This review discusses current approaches, indications, and contraindications for various forms of RT for LC in BC. A separate section is dedicated to new RT techniques, such as proton therapy. We also summarize ongoing clinical trials evaluating the role of RT in patients with LC. Full article

Complication of leptomeningeal carcinomatosis (LMC) is critical. It causes rapid neurological deterioration, and subsequently, discontinuation of the ineffective treatment even in body tumor dormancy. Large molecular chemotherapeutic agents that are unlikely to penetrate the CSF space, are more likely to not treat LMC, typically in chemo-sensitive tumors. With the introduction of novel regimens, significant advances in overall survival have been observed even in formerly chemo-resistant tumors, such as pancreatic cancer. Although such cases are still rare, the number of pancreatic cancer patients complicated with LMC are increasing, and this therefore needs more recognition. A 49-year-old woman was diagnosed with stage IVa pancreatic cancer. She underwent surgery, and subsequent adjuvant chemotherapy. After three lines of chemotherapy over a 3-year period, where the body disease remained dormant, the patient was complicated by LMC. The diagnosis was made 4 months after the onset of headache. The patient received intrathecal methotrexate treatment but succumbed shortly after treatment induction. Pancreatic cancer is still relatively chemo-resistant and is one of the least likely types of tumor to be complicated by LMC due to patients dying of the primary tumor. Advancements in treatments have led to a prolonged period of primary tumor control, but not in the CNS due to the poor penetration of chemo-agents to this site. The present case seems to be a typical result of modern era anti-cancer therapy. Therefore, we emphasize the necessity of earlier recognition of this complication so that we can initiate specific treatment targeting the CSF space, especially in this formerly chemo-resistant tumor in order to improve its prognosis. Full article

Leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced cancer. Breast cancer, lung cancer, and melanoma are the three most common causes of LMC, whereas it is rare in ovarian cancer. Here, we report the case of a 59-year-old woman who was diagnosed with LMC from ovarian cancer and was successfully treated with intrathecal chemotherapy via Ommaya reservoir and radiation therapy. The patient had an amelioration of symptoms and prolonged survival. Though LMC from ovarian cancer is thought to be rare, it is not going to remain a rare entity because the incidence of LMC in general is thought to be increasing, which is also the case with ovarian cancer. According to 31 cases whose treatment course is reported in literature, despite the absence of an established treatment for LMC, intrathecal (IT) chemotherapy whose survival benefit has been suggested in past studies might also prolong survival in patients with LMC from ovarian cancer. IT chemotherapy via Ommaya reservoir may be preferred to the lumbar puncture route. The presentation of non-specific symptoms of LMC in patients may hinder its diagnosis; however, early diagnosis and treatment induction is the key for patients’ prolonged survival and restored useful life. Full article

PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging, and longitudinal surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, and the potential pitfalls and nuances that characterize these applications. In addition, key tumor-specific clinical information and representative PET-CT images are provided to outline the role that PET-CT plays in the management of oncology patients. Hundreds of different types of tumors exist, both pediatric and adult. A discussion of the role of FDG PET for all of these is beyond the scope of this review. Rather, this series of articles focuses on the most common adult malignancies that may be encountered in clinical practice. It also focuses on FDA-approved and clinically available radiopharmaceuticals, rather than research tracers or those requiring a local cyclotron. The fifth review article in this series focuses on PET-CT imaging in head and neck tumors, as well as brain tumors. Common normal variants, key anatomic features, and benign mimics of these tumors are reviewed. The goal of this review article is to provide the imaging professional with guidance in the interpretation of PET-CT for the more common head and neck malignancies and neuro oncology, and to inform the referring providers so that they can have realistic expectations of the value and limitations of PET-CT for the specific type of tumor being addressed. Full article

Central nervous system (CNS) involvement by paraneoplastic syndromes, brain metastases, or leptomeningeal carcinomatosis (LC) in patients with neuroendocrine neoplasms (NEN) has only been described in individual case reports. We evaluated patients with LC in four neuroendocrine tumor (NET) centers (Halle/Saale, Hamburg, Heidelberg, and Marburg) and characterized them clinically. In the study, 17 patients with a LC were defined with respect to diagnosis, clinic, and therapy. The prognosis of a LC is very poor, with 10 months in median overall survival (mOS). This is reflected by an even worse course in neuroendocrine carcinoma (NEC) G3 Ki-67 >55%, with a mOS of 2 months. Motor and sensory deficits together with vigilance abnormalities were common symptoms. In most cases, targeted radiation or temozolomide therapy was used against the LC. LC appears to be similarly devastating to brain metastases in NEN patients. Therefore, the indication for CNS imaging should be discussed in certain cases. Full article

Cervical cancer is caused by a persistent infection with high-risk types of Papillomaviruses (hrHPV); HPV16 and HPV18 are associated with about 70% of the cases. In the last decades the introduction of a cervical cancer screening has allowed a decrease in cervical cancer incidence and mortality; regular adhesion to the screening procedures, by pap test or HPV test, and colposcopy, according to the international guidelines, prevents cancer development and allows for diagnosis at the early stages. Nowadays, in industrialized countries, it is not common to diagnose this pathology in advanced stages, and this occurrence is frequently associated with patient’s unattendance of cervical screening programs. We describe a case of delayed diagnosis of cervical cancer, posed only after the onset of the neurological symptoms caused by leptomeningeal metastases, despite a two-year history of abnormal cytology. The endocervical mass was analyzed by immunohistochemistry, and search and typing of HPV sequences was performed by PCR in the meningeal carcinomatous cells. A poorly differentiated squamous cell carcinoma was diagnosed, and HPV18 sequences were detected. This rapidly fatal case highlights the importance of following the evidence-based recommended protocols and the preventive role of the population-based cervical cancer screening programs. Full article

Leptomeningeal carcinomatosis (LMC) is the multifocal seeding of cerebrospinal fluid and leptomeninges by malignant cells. The incidence of LMC is approximately 5% in patients with malignant tumors overall and the rate is increasing due to increasing survival time of cancer patients. Eradication of the disease is not yet possible, so the treatment goals of LMC are to improve neurologic symptoms and to prolong survival. A standard treatment for LMC has not been established due to low incidences of LMC, the rapidly progressing nature of the disease, heterogeneous populations with LMC, and a lack of randomized clinical trial results. Treatment options for LMC include intrathecal chemotherapy, systemic chemotherapy, and radiation therapy, but the prognoses remain poor with a median survival of <3 months. Recently, molecular targeted agents have been applied in the clinic and have shown groundbreaking results in specific patient groups epidermal growth factor receptor (EGFR)-targeted therapy or an anaplastic lymphoma kinase (ALK) inhibitor in lung cancer, human epidermal growth factor receptor 2 (HER2)-directed therapy in breast cancer, and CD20-targeted therapy in B cell lymphoma). Moreover, there are results indicating that the use of these agents under proper dose and administration routes can be effective for managing LMC. In this article, we review molecular targeted agents for managing LMC. Full article