Breast Cancer Leptomeningeal Metastasis Research Articles

Clinicopathological and Treatment-Associated Prognostic Factors in Patients with Breast Cancer Leptomeningeal Metastases in Relation to Tumor Biology.

Breast cancer (BC) is one of the solid tumors most commonly associated with leptomeningeal disease (LMD). LMD carries a devastating prognosis; however, disease presentation and prognostic factors are uncertain. In order to describe patient characteristics, treatment patterns, and factors associated with survival in a contemporary multicentric cohort, 153 consecutive BC patients diagnosed with LMD at two European institutions (2002-2017) were included. Time to LMD and overall survival (OS) after LMD diagnosis were evaluated using the Kaplan-Meier method and Cox proportional hazards models. Median age at LMD diagnosis was 58 years (25-84). Tumor phenotype distribution was as follows: hormone receptor (HR) positive (HR+)/human epidermal growth receptor 2 (HER2) negative 51.0%, triple-negative 15.0%, HR+/HER2 positive (HER2+) 13.1% and HR negative/HER2+ 7.2%. Most patients received active anticancer treatments (radiation therapy [RT] n = 42, systemic therapy n = 110, intrathecal treatment n = 103).Median OS was 3.9 months (95% confidence interval [CI] 2.4-5.5). Eastern Cooperative Oncology Group performance status (ECOG PS) >2, high white blood cells count, low glucose, and high protein in cerebrospinal fluid (CSF) were poor prognostic factors. Having received RT or systemic treatment was associated with better prognosis. In multivariate analysis, ECOG PS (hazard ratio 2.22, 95% CI 1.25-3.94), CSF glucose levels (hazard ratio 1.74, 95% CI 1.05-2.88), and having received systemic treatment (hazard ratio 0.17, 95% CI 0.09-0.32) were confirmed as independent prognostic factors. In HER2+ BC patients, having received systemic HER2-targeted therapy was the only factor maintaining independent prognostication (hazard ratio 0.12, 95% CI 0.02-0.67) in multivariate analysis. Despite being limited by their retrospective nature, these results highlight the need for clinical trials in BC LMD, stratified on tumor biology. Leptomeningeal disease (LMD) is a devastating complication of breast cancer (BC), and its optimal therapy is still not defined. Here, patient characteristics, treatment patterns, and prognostic factors from a contemporary cohort of 153 BC-related LMD patients are reported. In multivariate analysis, Eastern Cooperative Oncology Group performance status, cerebrospinal fluid glucose levels, and having received systemic treatment were confirmed as independent prognostic factors in the overall population, whereas in human epidermal growth receptor 2 (HER2) positive BC patients, having received systemic HER2-targeted therapy was the only factor maintaining independent prognostication in multivariate analysis. These results highlight the need to consider stratification on tumor biology in the treatment of BC LMD.

Comparing the performance of CA 15–3 CSF to cytology in a cohort of patients with breast cancer leptomeningeal metastasis

Background and objectiveLeptomeningeal metastasis (LM) can occur as a late manifestation of breast cancer and has traditionally been diagnosed by CSF cytology; however, cytology suffers from low sensitivity and it is believed that many cases of LM go undiagnosed. Some studies have suggested the use of CA 15–3 in CSF (CA 15–3 CSF) to aid in the detection of LM. The purpose of this study was to compare the performance of CA 15–3 CSF to cytology for the detection and treatment monitoring of breast cancer LM. MethodsCA 15–3 CSF requests between 2014 and 2016 were retrospectively reviewed. Fifty-two measurements from nine patients were from our health system and had corresponding CSF cytology measurements. Concordance between CA 15–3 CSF and CSF cytology was calculated. For patients with quantifiable CA 15–3 CSF, sequential determinations of CA 15–3 and cytology were compared over time to assess correlation of CA 15–3 CSF concentration and cytology with disease status. ResultsAt the time of initial testing, seven of the nine patients (78%) had positive cytology. Two samples (22%) had quantifiable CA 15–3, both of which were also positive by cytology. The positive concordance between all cytology and CA 15–3 measurements was 9% (2/22), while negative concordance was 100% (30/30). Sequential CA 15–3 and cytology measurements showed a decrease in CA 15–3 that paralleled changes observed with cytology. ConclusionsIn this cohort of patients, CA 15–3 CSF performance was neither superior nor complementary to cytology for the detection of LM, nor did the combination of CA 15–3 CSF and cytology improve performance over cytology alone.

Clinical significance of detecting CSF-derived tumor cells in breast cancer patients with leptomeningeal metastasis.

Despite marked advances in breast cancer therapy, breast cancer-associated leptomeningeal metastasis (LM), a particularly aggressive syndrome with multifocal seeding of the leptomeninges by tumor cells, still carries an abysmal prognosis. A major problem with breast cancer LM surveillance is the lack of an effective and sensitive means to track dynamic changes of the disease. Cytology detection of cerebrospinal fluid (CSF) is considered the gold standard for LM diagnosis but has a high false-negative rate with a limited sensitivity. Here we applied subtraction enrichment and immunostaining-fluorescence in situ (SE-i•FISH) method, a technique previously used for isolating circulating tumor cells (CTCs) from the peripheral blood, to detect, enumerate, and track cerebrospinal fluid-derived tumor cells (CSFTCs) in CSF samples from 8 breast cancer patients. Comparing with cytology test, we found SE-i•FISH method can accurately and feasibly detect CSFTCs for the diagnosis of breast cancer-associated LM and monitor the disease progression. We also isolated and cultured CSFTCs from these cancer patients and performed genomic sequencing on CSFTCs of two patients. Genomic analysis of CSFTCs against corresponding archival primary breast tumors revealed clonal relationships with some ongoing evolution. Further drug sensitivity test on cultured CSFTCs based on genomic analysis data helped identify promising treatment options for the patient tested. Together, our results suggest that CSFTCs detection using SE-i•FISH platform could serve as a sensitive and accurate method to make the diagnosis and a promising approach to monitor tumor dynamics and treatment response for breast cancer-associated LM.

Leptomeningeal metastases in breast cancer patients — current rules of diagnosis and treatment

Leptomeningeal metastases (LM) presents a challenge because of the difficulty in determining the diagnosis and lack of optimal therapy. Nowadays, LM are more frequently diagnosed as a consequence of the long survival of patients with breast cancer and the improvement in image analysis. LM is a deleterious complication of breast cancer leading to death of patients within less than 3–6 months from the diagnosis. No generally accepted standard of care in the treatment of breast cancer LM exists. The treatment of patients with breast cancer and LM is of limited efficacy and substantial toxicity. Usually it requires focal radiotherapy to symptomatic sites or areas of bulky disease, intra-cerebrospinal fluid chemotherapy, or systemic intravenous/oral therapy, but the data regarding the sequence and efficacy of particular types of treatment are disputable. The management of breast cancer patients with LM was reviewed based on the data from literature. Additionally, the results of randomised clinical trials were reviewed.

BMET-25RESULTS OF THE INTERIM SAFETY ANALYSIS OF THE DEPOSEIN TRIAL IN LEPTOMENINGEAL METASTASES FROM BREAST CANCER

The Deposein trial (NCT01645839) was designed to evaluate the impact of the intra-CSF liposomal cytarabine on neurological progression free survival (PFS) in breast cancer leptomeningeal metastases (LM). Patients are randomized between systemic treatment alone (arm A) and systemic treatment plus intra-CSF liposomal cytarabine (arm B). The results of the first safety interim analysis on 20 patients (10 per arm) are presented here. At LM diagnosis, median age of patients was 51.5 years in arm A, 56.5 in arm B. Tumors were triple negative in 20% in arm A, 22.2% in arm B and overexpressed HER2 in 80% in arm A, 50% in arm B. Brain metastases were present in 50% in arm A, 10% in arm B. Patients had previously received a median of 2 lines of chemotherapy in arm A, 3 lines in arm B. CSF cytological analysis showed malignant cells in 80% in both arms. MRI LM involvement was observed in 100% in arm A, 80% in arm B. Capecitabine was the most common chemotherapy for LM treatment in both arms (20% in arm A, 30% in arm B). The median number of systemic chemotherapy cycles was 2 (range1-5) in arm A, 6 (range 2-27) in arm B. A median of 6 (range 4-20) liposomal cytarabine injections was administered in arm B. Focal radiotherapy was realized in 10%. Grade 3/4 were observed in 67% of patients of arm A (treatment-related in 22%), and in all patients of arm B (treatment-related in 50% - all due to systemic treatment). The most frequent grade 3/4 complications were neurological disorders (37.5%) in arm A, infections (41%) and haematological disorders (29.5%) in arm B. No chemical meningitis was observed in arm B. These first results need further confirmation. Data on the 42 patients enrolled since the initiation of the study will be presented.

Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer.

Circulating tumor cells are commonly observed in the peripheral blood of advanced breast cancer patients. We tested the feasibility of tumor cell detection in the cerebrospinal fluid (CSF) and studied its clinical relevance in leptomeningeal metastasis (LM) of breast cancer. CSF samples were collected from 38 metastatic breast cancer patients known or suspected to have LM. Control CSF samples were collected from 14 individuals without solid tumor malignancy. We used a modified CellSearch™ assay and an alternative EPCAM-based method involving immunomagnetic enrichment followed by flow cytometry (IE/FC) to enumerate CSF tumor cells (CSFTCs). CSFTCs were assayed at time of LM diagnosis and over the course of LM-directed therapy. We analyzed a total of 102 CSF samples with modified CellSearch™. The CSFTC counts were strongly correlated with the corresponding IE/FC results (Pearson's r=0.94). Twenty-eight out of 30 samples in which malignant cells were identified by CSF cytology were CSFTC-positive by modified CellSearch™. Baseline CSFTC levels from 21 patients eventually diagnosed with LM were significantly higher than the controls (p=0.0202), whereas 13 patients deemed not to have LM showed CSFTC results indistinguishable from the controls. In patients with serial samples, it was possible to monitor CSFTC levels as a potential biomarker of treatment response. CSFTC detection using a modified CellSearch™ assay demonstrated high sensitivity in detecting malignant cells in CSF and may be a promising method for diagnosing LM and monitoring LM during treatment.

Breast Cancer Leptomeningeal Metastasis: The Results of Combined Treatment and the Comparison of Methotrexate and Liposomal Cytarabine As Intra–Cerebrospinal Fluid Chemotherapy

BackgroundThis 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 MethodsIn 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. ResultsThe 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. ConclusionAmong 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.

Detection and quantification of CSF malignant cells by the CellSearch® technology in patients with melanoma leptomeningeal metastasis

Melanoma is the most frequent solid tumor associated with leptomeningeal metastasis (LM). The usual diagnostic tools, that is, cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium-enhanced MRI of the entire neuraxis both lack effectiveness. The CellSearch Veridex technology for the detection of circulating tumor cells (CTC) in blood was designed for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer, which express EpCAM markers. We have previously adapted this technology to detect malignant cells in the CSF of breast cancer LM. Our objective here was to check if this technology would also allow the detection and the enumeration of CTC in the CSF of melanoma patients presenting with LM although melanoma does not express EpCAM markers. On the occasion of the intrathecal treatment of LM in 2 melanoma patients, 5 mL of CSF and 7.5 mL of blood were collected on CellSave Preservative Tubes and analyzed within 3 days after CSF sampling using a melanoma-dedicated kit. The CellSearch Veridex technology was then adapted to direct enrichment, enumeration, and visualization of melanoma cells in the CSF. CD146+, HMW-MAA+, CD34-, and CD45- cells with typical morphology could be observed and enumerated sequentially with reproducible results, corresponding to CSF melanoma cells (CSFMC). In contrast to the current gold standard cytomorphological analysis, this new approach allowed a precise quantification of CSFMC in all samples concomitantly analyzed. This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of melanoma patients with LM.

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.

e11524 Background: Breast cancer leptomeningeal metastasis(BLM) occurs in approximately 5% of patients with metastatic breast cancer and, due to the lack of an established treatment, these patients have an extremely poor prognosis. Methods: The clinical characteristics of BML and outcomes were investigated in 14 patients at our Center between 2004 and 2010. The present study investigates the clinical characteristics of the disease and the treatment outcomes obtained at our Center. Results: The clinical characteristics of breast cancer leptomeningeal metastasis was as follows. The mean age of subjects was 50.8 years.T stage, 4 patients were T1, 4 patients were T2, 5 patients were T4, and 1 patient was unknown. N stage, 0 patients were N0, 5 patients were N1, 3 patients were N2, and 6 patients were N3. By histopathological type, invasive ductal carcinoma occurred in 13 patients and invasive lobular carcinoma in 1 patient. By histological grade, 0 patients were assessed as low, 2 patient as intermediate, 9 patients as high, and 3 patients as unknown. Triple-negative phenotype accounted for 50% of patients.13 patients underwent treatment with intrathecal methotrexate (MTX) via an Ommaya reservoir and whole-brain radiation.The changes from baseline in symptoms were as follows. At the onset of BLM, headache was reported in 9 patients, vomiting in 4 patients, dizziness in 3 patients, light-headed feeling in 3 patients, anorexia and nausea in 2 patient, disorientation in 2 patient, strange sensation in left ear in 1 patient, and double vision in 1 patient. In 8 of 13 patients, the symptoms had resolved at discharge following treatment, 5 patients had mild symptoms. In all cases, however, the symptoms relieved and they were once discharged.The median survival period at our Center for the 11 treated subjects was 9.5 months. Conclusions: A treatment regimen of intrathecal MTX via on Ommaya reservoir and whole-brain radiation makes it possible to alleviate symptoms and for patients to be discharged from hospital, with an improved QOL and a longer survival period reported in some patients.

Prospective follow-up of 96 patients with breast cancer with leptomeningeal metastasis recruited from 2007 to 2010.

2089 Background: Around 5% of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). Incidence of LM may increase. The aim of this study was to report the outcome of patients diagnosed with BC LM. Methods: 96 consecutive female BC patients diagnosed with LM were prospectively followed up in our institution from 2007 to 2010. Characteristics and outcomes of patients were reported. Correlations between characteristics and overall survival (OS) were analyzed using usual statistical methods (Kaplan Meier, Log-rank, Cox). Results: Median time between BC and LM was 42,5 months. BC were invasive ductal carcinoma in 72%. Estrogen and progesterone receptors were detected in respectively 61,5 and 43% of the tumors. HER2 expression was observed in 26,5%. 24% were triple negative. At LM diagnosis, median age was 52 and median Performance Status (PS) was 2. CSF cytology and cerebrospinal MRI were positive in respectively 72% and 87%. Median time between LM diagnosis and 1st intrathecal (IT) was 3 days. 80 LM patients received IT liposomal cytarabine (ventricular device in 55%) associated with systemic treatment in 52 cases and whole brain radiotherapy in 12 cases. Clinical stabilization or improvement was observed in 46%, CSF response in 37%, MRI stabilization or improvement in 67,5%. 12 patients were staying alive. Median OS of the whole cohort and the 80 treated patients were respectively 2,8 and 3,5 months. Initial PS was the mainly variable correlated with OS (p<0,0001). Median OS of the whole cohort was 5 months in 0-2 PS patients (n=56), 24 days in 3-4 PS patients (n=40). Median OS of the treated patients was 5,6 months in 0-2 PS patients (n=50), 31 days in 3-4 PS patients (n=30). Other significant predictors of survival were: RP and triple negative status RP (p=0,01/p=0,004), time between LM diagnosis and 1st IT injection (p), systemic and IT treatment (p<0,0001/p=0,0002), radiotherapy (p=0,0076), clinical, cytological and MRI responses (p<0,0001/p=0,0366/p=0,0343). Conclusions: Our results confirm the importance of an early diagnosis and the interest of the association of IT and systemic treatment in treating BC LM.

Value of CA 15-3 detection in cerebrospinal fluid (CSF) of breast cancer leptomeningeal metastases.

2075 Background: An increased incidence of leptomeningeal metastases (LM) is reported in breast cancer (BC), which is the predominant etiology of LM in solid tumors Our aim was to assess the significance of intra-CSF CA 15-3 measure in the early diagnosis of BC LM. Methods: Serum and CSF levels of CA 15-3 and albumine were evaluated in 4 groups of 20 patients recruited from April 2008 to January 2011: group A (new diagnosis of BC LM), group B (new diagnosis of various other solid tumors LM), group C (progression of intraparenchymal brain metastasis of BC) and group D (controls without any cancer). CA 15-3 was assessed by automatic immune-enzymatic technology (Kryptor, BRAHMS Biomarkers). Non parametric analysis of variance with Bonferroni correction was used for comparisons of means. Results: In group A, median age was 51,5 years (30-70). LM and intraparenchymal metastases were observed at the MRI in 80% and 75% of patients respectively. CSF cytology was positive in 85% of cases. Median proteinorachia was 1,03 g/l (0,22-16,12). Median CSF/serum albumine ratio were 0,02 (0,006-0,62) in group A; 0,01 (0,004-0,05) in group B; 0,01 (0,004–0,05) in group C; 0,006 (0,002-0,04) in group D. Median rates of inra-CSF CA 15-3 were 8,65 U/ml (0,1-250,9) in group A; 0,55 U/ml (<0,3-213,5) in group B; 0,55 U/ml (<0,3-18,5) in group C; 0,30 U/ml (<0,3-0,3) in group D. Median rates of CA 15-3 in serum were 51,4 U/ml (11,9-2819) in group A; 21,1 U/ml (7,5-296,4) in group B; 30,4 U/ml (11,9-4999) in group C; 40,2 U/ml (6,2-23,8) in group D. Median CSF/serum CA 15-3 ratio were 0,18 (0,004-4,39) in group A; 0,03 (0-3,79) in group B; 0,015 (0,002-0,53) in group C; 0,02 (0,007-0,19) in group D. In group A, intra-CSF and serum 15-3 rates were statistically significantly different from the 3 other groups (p<0,0001). Conclusions: Intra-CSF CA 15-3 assessment may be helpful for early diagnosis of BC LM. The reproducibility of this tool will be validated. Futures studies will be planned to determine a threshold rate for BC LM diagnosis.

Clinical improvement and survival in breast cancer leptomeningeal metastasis correlate with the cytologic response to intrathecal chemotherapy

Leptomeningeal meningitis occurs in approximately 5% of metastatic breast cancers, and there is no standard treatment for this complication. We retrospectively analyzed the clinical data and cerebrospinal fluid of 24 patients treated with high-dose intrathecal methotrexate for breast cancer leptomeningeal meningitis (BLM). Cytologic response (CSF cytology without neoplastic cells after treatment) was observed in 11 patients (46%) and related to survival (P = 0.005). In addition, clinical symptoms improved in all 11 patients who had a cytologic response and in 7 patients (54%) without cytologic response (P = 0.02). The predictive value of cytologic response needs further confirmation. Cytologic response could be helpful in the management of intrathecal chemotherapy in patients with BLM.

Triple negative breast cancer with isolated leptomeningeal metastasis

AbstractIsolated Leptomeningeal metastasis in breast cancer is rare. The diagnosis requires T1W MR scan of brain with gadolinium enhancement and demonstration of malignant cells in CSF. The treatment is palliative, which includes whole brain radiotherapy and chemotherapy.

The role of HER2/neu, estrogen, and progesterone receptor status in the risk and survival of breast cancer leptomeningeal metastasis

11512 Background: Leptomeningeal metastasis (LM) is a dreaded complication of breast cancer with a median survival of approximately 4 months from the time of LM diagnosis. HER2/neu (HER2), estrogen (ER), and progesterone (PR) receptor status are routinely used to determine prognosis and guide treatment. There is emerging data regarding the influence of these receptors on the risk and prognosis of parenchymal brain metastasis. However, the role of these receptors in LM is unknown. We performed a retrospective analysis of 61 patients with breast cancer to determine the risk and survival of LM as a function of receptor status. Methods: Of patients with breast cancer evaluated in our department for possible LM between 2003 and 2006, those requiring CSF analysis were included in this study. Of these 61 patients, 27 were diagnosed with LM and 34 were found to be negative for LM, based on analysis of CSF and MRI. Information regarding HER2 receptor status was unavailable in 3 patients (1 with LM) due to technical issues with the assay. ER, PR, and survival data were available for all patients. Odds ratio of developing LM was calculated based on each receptor status. The Fisher exact test was used to determine significance. For the 27 patients with LM, receptor status was used to stratify survival from the time of LM diagnosis using Kaplan-Meyer analysis; significance was evaluated using the log-rank test. Results: The odds ratios of developing LM in patients with positive HER2, ER, and PR were 1.89, 0.32, and 0. 825, respectively. P values were 0.378, 0.056, and 0.799. In the 27 patients with LM, survival from the time of LM diagnosis was not significantly different when stratified by receptor status; p values were 0.983, 0.317, and 0.625 respectively. Conclusions: Our retrospective analysis suggests that HER2/neu-positive and ER-negative breast cancer may be associated with a higher risk of LM, although this approached statistical significance only for ER. For patients with confirmed LM, there were no significant differences in survival based on receptor status, although there was a trend favoring ER-positive disease. Larger studies are needed to clarify the role of these receptors in the risk and prognosis of breast cancer LM. No significant financial relationships to disclose.

Breast cancer leptomeningeal metastasis—the role of multimodality treatment

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. 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. 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. 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.

The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study

To assess the benefit of intraventricular chemotherapy, patients with leptomeningeal metastasis (LM) from breast cancer were randomised to treatment including intraventricular (IT) chemotherapy ( n = 17) or to non-intrathecal (non-IT) treatment ( n = 18). Appropriate systemic therapy and involved field radiation therapy (RT) were given in both arms. Intention-to-treat analysis showed neurological improvement or stabilisation in 59% of the IT and in 67% of the non-IT group, with median time to progression of 23 weeks (IT) and 24 weeks (non-IT). Median survival of IT patients was 18.3 weeks and 30.3 weeks for non-IT patients (difference 12.9 weeks; 95% Confidence Interval (CI) −5.5 to +34.3 weeks; P = 0.32). Neurological complications of treatment occurred in 47% (IT) vs 6% (non-IT) ( P = 0.0072). In conclusion, standard systemic chemotherapy with involved field RT for LM from breast cancer is feasible. Addition of intraventricular chemotherapy does not lead to survival benefit or improved neurological response, and is associated with an increased risk of neurotoxicity.