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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 -
BMC Medical Imaging Dec 2023The purpose of this study was to investigate the clinical utility of three-dimension (3D) high-resolution inversion recovery (IR)-prepared fast spoiled gradient-recalled...
PURPOSE
The purpose of this study was to investigate the clinical utility of three-dimension (3D) high-resolution inversion recovery (IR)-prepared fast spoiled gradient-recalled (SPGR) magnetic resonance imaging (MRI) in the diagnosis of cranial nerve meningeal carcinomatosis (MC).
METHODS
A total of 114 patients with MC from January 2015 to March 2020 were enrolled and their MRIs were analyzed retrospectively. All patients underwent MRIs before being administered a contrast agent. Both a 2D conventional MRI sequence and a 3D IR-prepared fast SPGR high-resolution T1-weighted (BRAVO) scan sequence were measured after contrast agent administration. The characteristics of MC and the involved cranial nerves were then examined.
RESULTS
Among the 114 MC patients, 81 (71.05%) had cranial nerve enhancement on contrast-enhanced 3D-BRAVO imaging, while only 41 (35.96%) had image enhancement on conventional MRI. The contrast-enhanced 3D-BRAVO displayed stronger image contrast enhancement of the cranial nerves than the conventional MRI (P < 0.001). Furthermore, detection rates for the facial and auditory nerves, trigeminal nerve, oculomotor nerve, sublingual nerve, optic nerve, glossopharyngeal/vagal/accessory nerve, and abductor nerve on contrast-enhanced 3D-BRAVO imaging were 58.77%, 47.37%, 9.65%, 8.77%, 5.26%, 3.51%, and 0.88%, respectively. We found a statistically significant difference between the affected facial and auditory nerves, as well as the trigeminal nerve, oculomotor nerve, sublingual nerve, and optic nerve.
CONCLUSION
In MC, contrast-enhanced 3D-BRAVO imaging displayed the cranial nerves more effectively than 2D conventional enhanced MRI. The facial, auditory, and trigeminal nerves are the primary nerves involved in MC, and improved scanning of these nerves would aid in the early detection and treatment of MC.
Topics: Humans; Contrast Media; Retrospective Studies; Meningeal Carcinomatosis; Cranial Nerves; Magnetic Resonance Imaging; Imaging, Three-Dimensional
PubMed: 38082242
DOI: 10.1186/s12880-023-01166-4 -
Cureus Nov 2023Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare neoplasm of the central nervous system (CNS) that primarily affects the leptomeninges. However, it can also...
Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare neoplasm of the central nervous system (CNS) that primarily affects the leptomeninges. However, it can also involve the brain parenchyma and spinal cord. We report the first case of metastasis of this primary CNS tumor to the lung and bone marrow. An 18-year-old male was diagnosed with DLGNT through meningeal biopsy after multiple events of transient neurologic signs and symptoms that included recurrent episodes of encephalopathy, seizures, cerebral vasospasms, cranial nerve palsy, and urinary dysfunction. Five months after diagnosis, the patient presented with pancytopenia and pulmonary effusion. At that time, he was being treated with temozolomide, after radiation treatment to the brain and spinal cord. Bone marrow biopsy and pleural cytology revealed systemic metastases from the primary CNS tumor. He was then treated with chemotherapy with carboplatin and vincristine which improved his condition for two and a half months. Unfortunately, the patient died of a high systemic metastatic burden. Primary CNS tumors rarely produce systemic metastases, and this is the first report of DLGNT with bone marrow and pulmonary metastases. Chemotherapy with carboplatin and vincristine should be considered as a treatment for patients with DLGNT, as the patient presented a systemic response with clinical and radiological improvement.
PubMed: 38050500
DOI: 10.7759/cureus.48185 -
Nature Communications Nov 2023Breast cancer leptomeningeal metastasis (BCLM), where tumour cells grow along the lining of the brain and spinal cord, is a devastating development for patients....
Breast cancer leptomeningeal metastasis (BCLM), where tumour cells grow along the lining of the brain and spinal cord, is a devastating development for patients. Investigating this metastatic site is hampered by difficulty in accessing tumour material. Here, we utilise cerebrospinal fluid (CSF) cell-free DNA (cfDNA) and CSF disseminated tumour cells (DTCs) to explore the clonal evolution of BCLM and heterogeneity between leptomeningeal and extracranial metastatic sites. Somatic alterations with potential therapeutic actionability were detected in 81% (17/21) of BCLM cases, with 19% detectable in CSF cfDNA only. BCLM was enriched in genomic aberrations in adherens junction and cytoskeletal genes, revealing a lobular-like breast cancer phenotype. CSF DTCs were cultured in 3D to establish BCLM patient-derived organoids, and used for the successful generation of BCLM in vivo models. These data reveal that BCLM possess a unique genomic aberration profile and highlight potential cellular dependencies in this hard-to-treat form of metastatic disease.
Topics: Humans; Female; Breast Neoplasms; Meningeal Carcinomatosis; Cell-Free Nucleic Acids; Genomics
PubMed: 37973922
DOI: 10.1038/s41467-023-43242-x -
Oncology and Therapy Mar 2024In this work, we report on a clinically significant response of meningeal carcinomatosis to repotrectinib in a woman with a heavily pretreated ROS1-rearranged non-small...
In this work, we report on a clinically significant response of meningeal carcinomatosis to repotrectinib in a woman with a heavily pretreated ROS1-rearranged non-small cell lung cancer (NSCLC) that harbored the concomitant solvent front G2032R mutation. Meningeal carcinomatosis has a higher incidence in oncogene addicted NSCLC due to increased life expectancy, yet no report has ever documented the activity of repotrectinib in this context. In line with its activity, we documented the presence of the drug at potentially active concentrations in the cerebrospinal fluid. Nevertheless, the short-lived response reported by our patient highlights the importance for novel ROS1-tyrosine kinase inhibitors (TKIs) to be specifically developed to be able to penetrate the blood-brain barrier.
PubMed: 37973688
DOI: 10.1007/s40487-023-00251-6 -
Cureus Oct 2023Prophylactic cranial irradiation (PCI) for limited disease small cell lung cancer is the standard of care for curative treatment of this disease. However, neurocognitive...
Prophylactic cranial irradiation (PCI) for limited disease small cell lung cancer is the standard of care for curative treatment of this disease. However, neurocognitive dysfunction is one of the late adverse events of PCI and is often problematic. Recently, hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is sometimes performed to prevent neurocognitive dysfunction after PCI. In HA-PCI, the question is whether or not metastases appear around the hippocampus that were not irradiated. We have experienced a case of perihippocampal meningeal carcinomatosis after HA-PCI. We also draw attention to the potential risks of performing HA-PCI based on this experience.
PubMed: 37927701
DOI: 10.7759/cureus.46499 -
Journal of Neuro-oncology Oct 2023The prognosis of patients with leptomeningeal metastasis (LM) remains poor. Circulating tumour DNA (ctDNA) has been proven to be abundantly present in cerebrospinal...
PURPOSE
The prognosis of patients with leptomeningeal metastasis (LM) remains poor. Circulating tumour DNA (ctDNA) has been proven to be abundantly present in cerebrospinal fluid (CSF); hence, its clinical implication as a biomarker needs to be further verified.
METHODS
We conducted a retrospective study of 35 lung adenocarcinoma (LUAD) patients with LM, and matched CSF and plasma samples were collected from all patients. All paired samples underwent next-generation sequencing (NGS) of 139 lung cancer-associated genes. The clinical characteristics and genetic profiling of LM were analysed in association with survival prognosis.
RESULTS
LM showed genetic heterogeneity, in which CSF had a higher detection rate of ctDNA (P = 0.003), a higher median mutation count (P < 0.0001), a higher frequency of driver mutations (P < 0.01), and more copy number variation (CNV) alterations (P < 0.001) than plasma. The mutation frequencies of the EGFR, TP53, CDKN2A, MYC and CDKN2B genes were easier to detect in CSF than in LUAD tissue (P < 0.05), possibly reflecting the underlying mechanism of LM metastasis. CSF ctDNA is helpful for analysing the mechanism of EGFR-TKI resistance. In cohort 1, which comprised patients who received 1/2 EGFR-TKIs before the diagnosis of LM, TP53 and CDKN2A were the most common EGFR-independent resistant mutations. In cohort 2, comprising those who progressed after osimertinib and developed LM, 7 patients (43.75%) had EGFR CNV detected in CSF but not plasma. Furthermore, patient characteristics and various genes were included for interactive survival analysis. Patients with EGFR-mutated LUAD (P = 0.042) had a higher median OS, and CSF ctDNA mutation with TERT (P = 0.013) indicated a lower median OS. Last, we reported an LM case in which CSF ctDNA dynamic changes were well correlated with clinical treatment.
CONCLUSIONS
CSF ctDNA could provide a more comprehensive genetic landscape of LM, indicating the potential metastasis-related and EGFR-TKI resistance mechanisms of LM patients. In addition, genotyping of CSF combined with clinical outcomes can predict the prognosis of LUAD patients with LM.
Topics: Humans; Lung Neoplasms; Circulating Tumor DNA; Carcinoma, Non-Small-Cell Lung; Retrospective Studies; DNA Copy Number Variations; Genotype; Adenocarcinoma of Lung; Meningeal Carcinomatosis; Mutation; ErbB Receptors; Protein Kinase Inhibitors
PubMed: 37897649
DOI: 10.1007/s11060-023-04471-8 -
Medicine Oct 2023To evaluate the correlation between contrast-enhanced (CE) MRI and cerebrospinal fluid (CSF) cytology for the evaluation of leptomeningeal metastasis (LM) on MRI after...
Increasing discrepancy of MR imaging and CSF study in patients with leptomeningeal seeding from lung adenocarcinoma after targeted therapy using a tyrosine kinase inhibitor.
PURPOSE
To evaluate the correlation between contrast-enhanced (CE) MRI and cerebrospinal fluid (CSF) cytology for the evaluation of leptomeningeal metastasis (LM) on MRI after targeted therapy with tyrosine kinase inhibitors.
METHODS
We retrospectively reviewed the data of nonsmall cell lung cancer patients registered with NCT03257124 from May 2017 to December 2018, with progressive disease despite targeted therapy. Twenty-nine patients whose MRI scans exhibited LM at the time of registration were enrolled. During the targeted therapy with osimertinib, MRI scans, and subsequent CSF examinations were performed in every 2 months. In total, 113 MRI scans and CSF cytology data after treatment were collected. For each CE MRI scan, LM positivity was evaluated on 3D T1-weighted image (T1WI) and 2D FLAIR. The correlation between MRI and CSF cytology results and the diagnostic performance of MRI with CSF cytology as a reference standard were evaluated.
RESULTS
After treatment, MRI revealed positivity for LM in 81 and negativity in 32. CSF results were positive in 69 examinations and negative in 44. The diagnostic accuracy of CE 3D T1WI and 2D FLAIR was 0.52 and 0.46, respectively. After targeted therapy, discrepancy in the CSF and MRI results tended to increase over time. The proportions of concordant MRI and CSF cytology results after targeted therapy were 66%, 58%, 62%, and 47% at the first, second, third, and fourth follow-up, respectively.
CONCLUSION
The discrepancy of MRI in evaluation of LM and CSF cytology increases over time after targeted therapy with osimertinib. LM positivity on MRI could be a surrogate imaging marker in the pre- and immediate posttargeted-treatment with Osimertinib but not after sessions of osimertinib.
Topics: Humans; Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Magnetic Resonance Imaging; Meningeal Carcinomatosis; Retrospective Studies; Tyrosine Kinase Inhibitors; Clinical Trials as Topic
PubMed: 37800766
DOI: 10.1097/MD.0000000000035387 -
Clinical and pathological factors and outcome of central nervous system metastasis in breast cancer.Frontiers in Oncology 2023In Switzerland, approximately 6000 new breast cancer cases and 1300 deaths are reported annually. Brain metastasis from breast cancer (BMBC) has a major effect on...
BACKGROUND
In Switzerland, approximately 6000 new breast cancer cases and 1300 deaths are reported annually. Brain metastasis from breast cancer (BMBC) has a major effect on prognosis. This study aimed to identify prognostic factors for overall survival (OS) in a cohort of Swiss patients with BMBC. This study evaluated the prognosis on older BMBC, which has not been completely addressed in the literature.
METHODS
We performed a retrospective chart review analysis with the primary endpoint of OS after a diagnosis of BMBC. The study population was divided into 2 groups based on an OS cut-off value of 12 months after diagnosis. Univariate and multivariate analyses of several risk factors, including age, were performed. To evaluate differences in OS according to age, we performed a secondary analysis to examine the prognostic value of clinical symptoms, metastatic pattern, and lymph node involvement in an older (≥65 years) vs. younger (<65 years) cohort.
RESULTS
From 1989 to 2019, 55 patients were identified as having BMBC, among whom 47 patients were confirmed to be dead. The median patient age was 58 years (range 25-83 years). Comorbidities were present in 45 (81.8%) patients. The median survival in the OS <12 and OS ≥12 months groups was 4.3 and 30.7 months, respectively (<0.001). Multivariate analysis revealed no significant differences in terms of comorbidities, medication use, M-stage, and symptomatology between the 2 groups. Additionally, there was no significant difference in OS in the 2 subgroups of patients aged <65 and ≥65 years.
DISCUSSION
We concluded that age should not be a decisive factor in therapy planning for advanced breast cancer patients with BMBC.
PubMed: 37795444
DOI: 10.3389/fonc.2023.1247402