Breast cancer leptomeningeal metastasis: the results of combined treatment and the comparison of methotrexate and liposomal cytarabine as intra-cerebrospinal fluid chemotherapy.

BACKGROUND: This was a prospective observational study to assess the results of the treatment of patients with breast cancer leptomeningeal metastasis (LM) and to compare the efficacy of methotrexate and liposomal cytarabine in patients treated intrathecally by lumbar puncture. PATIENTS AND METHODS: In this prospective observational study, 149 consecutive patients with breast cancer and LM treated between the years 1999 and 2011 were assessed. Multimodality treatment methods were used: systemic therapy in 77 patients, radiotherapy in 92 patients, intrathecal methotrexate in 81 patients, and intrathecal liposomal cytarabine in 15 patients. RESULTS: The median survival of all patients was 4.2 months. The median survival of patients in whom systemic intravenous/oral treatment was used was 6 months, in those who did not have systemic treatment, the median survival was 2 months (P < .001). The median survival of patients treated with intrathecal methotrexate was 4.2 months; in patients treated with intrathecal liposomal cytarabine, the median survival was 4.6 months, and in patients who did not receive intrathecal treatment, the median survival was 3.7 months (P = .717). Median survival after whole-brain radiotherapy was 4.6 months and with no radiotherapy, it was 3.2 months (P = .028). Multivariate analysis revealed a Karnofsky performance status (KPS) of > 70. Systemic intravenous/oral treatment and bone as a site of metastasis were factors prolonging survival from LM. CONCLUSION: Among treatment methods, only systemic therapy prolonged survival in patients with LM. Neither radiotherapy nor lumbar intrathecal therapy influenced survival in those patients; however, both methods alleviated signs and symptoms of LM. No difference in survival was observed in patients treated intrathecally with methotrexate and those treated with liposomal cytarabine. Treatment with both drugs was comparable.

[Diagnosis and treatment of carcinoid meningitis: a challenge to the neurologist and oncologist]. / Diagnostyka i leczenie nowotworowego zapalenia opon mózgowo-rdzeniowych wyzwaniem dla neurologa i onkologa.

BACKGROUND: Two clinical types of leptomeningeal metastases from solid tumors are observed: local and disseminated. The former (meningeal carcinomatosis) consists in nodular infiltration of leptomeninges, while the latter (carcinomatous meningitis)--in tumor cells free floating in the cerebrospinal fluid and adhering as a monolayer to the surface of neural structures. Despite the same etiology, the two types of metastasis differ in their clinical manifestation and prognosis. Meningeal carcinomatosis is more frequently diagnosed nowadays due to advances in neuroimaging techniques and the long survival of breast cancer patients. Patients with local, nodular infiltration of leptomeninges may survive many years without symptoms of the disease. On the other hand, carcinomatous meningitis, with its usually violent course and short survival, has become a major problem for oncologists and neurologists because of limited efficacy and considerable toxicity of the treatment. AIMS: The purpose of this article is to review the current knowledge about carcinomatous meningitis in breast cancer patients, taking into account pathophysiology, clinical symptoms, diagnosis, treatment and prognosis. The second aim was to present the authors' experience with the treatment of breast cancer patients suffering from carcinomatous meningitis. MATERIAL AND METHODS: 37 patients with breast cancer and carcinomatous meningitis were treated in the Oncology Center, Warsaw, in the years 2000-2002. Their mean age was 51. The diagnosis was based on results of neurological examination, MRI scan, and the presence of neoplastic cells in the cerebrospinal fluid. In a majority of cases combined treatment was applied, including intrathecal administration of cytostatics, intravenous systemic chemotherapy and radiotherapy. RESULTS: The observation period ranged from 2 to 33 months. A response to the treatment was achieved in 76% of the patients. Their median overall survival was 19 weeks, mean 18 weeks. Seven patients (19%) survived for over 6 months. CONCLUSIONS: The ever-growing incidence of carcinomatous meningitis in the course of breast cancer has become a serious clinical problem for neurologists and oncologists. Treatment results are disappointing, although the combined modality treatment appears to be the best option. New pharmacological approaches to the treatment of meningeal malignancy are required to improve the outcome of patients with carcinomatous meningitis.

Breast cancer leptomeningeal metastasis: propensity of breast cancer subtypes for leptomeninges and the analysis of factors influencing survival.

The aim of the study was to define biological subtypes of breast cancer that have the propensity to metastasize to the leptomeninges and to assess factors influencing survival from detection of leptomeningeal metastatis (LM). One hundred and eighteen consecutive breast cancer patients with LM were treated in one institution, between the years 1999 and 2009; 40.5 % of patients had triple-negative subtype, 37.5 % had luminal A subtype and 22 % had HER2-positive subtypes (luminal B and HER2). Of patients with LM, 35 % had lobular cancer. Median survival from the detection of LM was 18 weeks, and 1-year survival was 16 %. Cox multivariate analysis revealed that performance status and systemic treatment statistically significantly influenced survival of patients with LM. Triple-negative biological subtype and lobular histological type of breast cancer had the propensity to metastasize to the leptomeninges. Performance status and systemic treatment ordered after detection of LM statistically significantly influenced survival.

Breast cancer leptomeningeal metastasis--the role of multimodality treatment.

AIM: The aim of the study was to assess the efficacy of multimodality treatment of patients with Leptomeningeal metastasis (LM) and to establish which method of treatment has the greatest positive impact on survival. MATERIAL AND METHODS: Clinical material included 67 consecutive breast cancer patients with LM treated at the Cancer Center in Warsaw between the years 2000 and 2005. Intrathecal chemotherapy was given to 57 pts (85%), intravenous chemotherapy to 41 pts (61%), whole brain radiotherapy to 33 pts (49%) and radiotherapy to the spinal leptomeninges to 10 (15%). For 27 pts (40%) three methods of treatment were used. Univariate and multivariate analyses were used to evaluate the impact of the particular method of treatment on survival and to assess the efficacy of combined modalities. RESULTS: Clinical response was achieved in 49 pts (76%). Median survival calculated from the diagnosis of LM was 16 weeks (range 1-402 weeks). Univariate analysis showed positive impact of systemic intravenous chemotherapy (P = 0.0009), intrathecal chemotherapy (P = 0.008) and whole brain radiotherapy (P = 0.004) on survival. The results of Cox multivariate analysis have shown systemic chemotherapy (P < 0.001) and intrathecal chemotherapy (P = 0.001) to be significant. CONCLUSIONS: Intravenous chemotherapy and, independently, intrathecal chemotherapy improve survival in breast cancer patients with LM. Radiotherapy has a positive impact on the quality of life due to the alleviation of neurological symptoms. The role of radiotherapy in prolonging survival is questionable.