Treatment and prognosis of leptomeningeal disease secondary to metastatic breast cancer: a single-centre experience

Kingston, Catherine A.; Kayhanian, Hamzeh; Brooks, C.; Cox, Nick; Chaabouni, Narda; Redana, Stefania; Kalaitzaki, E.; Smith, Ian C. P.; O’Brien, Michael; Johnston, S.; Allen, Michael J.; Parton, Marina; Noble, Jillian; Stanway, Susannah; Ring, Alistair; Turner, Nicholas C.; Okines, Alicia

doi:10.1016/s0959-8049(17)30124-7

Cited by 5 publications

(15 citation statements)

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“…Our results confirm that BC patients diagnosed with LMD have a dismal prognosis, with a median OS of 3.9 months only . The major clinical characteristic impacting prognosis was ECOG PS (in the overall population, as well as in the HER2+ and HER2− cohorts separately), consistently with reports from previous studies .…”

Section: Discussionsupporting

confidence: 90%

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

et al. 2018

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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.

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Section: Discussionsupporting

confidence: 90%

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

et al. 2018

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“…The number of long‐term survivors in our group (OS12, 35.5%, OS24, 19.4%) also compares favorably with that previously reported(OS12, 8%‐31%) 19,22,23,31 . Note is made that preliminary data for intra‐CSF trastuzumab in treatment of Her2 + LM patients has been promising (median PFS, 5.7‐7.5 months; PFS6 = 41%; median OS, 13.5‐10.6 months) 20,21 …”

Section: Discussionsupporting

confidence: 85%

“…In our study, the observed neurologic PFS6 of 39% and median OS 6.9 months are notable, particularly when compared with prior reports involving breast cancer patients with LM treated with a variety of systemic or intra‐CSF agents, given alone or in combination with systemic therapy and/or radiotherapy. In those reports, PFS6 was reported of 26%, and median OS, 3.3‐5.4 mo) 17‐25,27‐32 . The number of long‐term survivors in our group (OS12, 35.5%, OS24, 19.4%) also compares favorably with that previously reported(OS12, 8%‐31%) 19,22,23,31 .…”

Section: Discussionsupporting

confidence: 78%

“…Since this parameter has not typically been reported in prior series, it is difficult to make comparisons. It is likely that local‐field radiation therapy at baseline for bulky or symptomatic disease (74%), concomitant hormonal (50%) or systemic chemotherapy (46%) might have influenced outcome; however, it is noted that these concomitant therapies have been provided in conjunction with intra‐CSF therapy in previously reported studies 4,17‐19,21,22,27‐32 . Given that 74% of our patients received local field RT at baseline, we acknowledge that the results likely reflect that achievable with the combination of RT (when clinically warranted) followed by intraventricular topotecan, and not just due to topotecan alone.…”

Section: Discussionmentioning

confidence: 90%

“…Following intra‐CSF treatment of patients with LM and breast cancer, survival has typically ranged from 2.9‐5.4 months, 4,15‐24 and up to 13.6 months in HER2+ patients treated with intra‐CSF trastuzumab 25 . Prior studies with intra‐CSF TOPO treatment have reported clearing of malignant CSF cells in 38% of children with refractory leptomeningeal leukemia 6 and 82% (9/11) of patients with primary CNS tumors 8 ; however, the duration of CSF clearing in those studies was not reported.…”

Section: Discussionmentioning

confidence: 99%

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Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

et al. 2020

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Background There are few treatment options for patients with leptomeningeal metastases (LM). Methods We report a case series of patients with breast cancer and LM treated with intra‐CSF topotecan (TOPO). Outcome was assessed by clinical exam and MRI at baseline, at end of induction (4‐5 weeks), then every 3 months; CSF cytology was determined at baseline and with each treatment. Results Thirty‐one women [median age, 58 (37‐81); median KPS 60 (40‐100)] received treatment. At baseline, 68% had positive CSF cytology, and 90%, leptomeningeal enhancement on MRI. 84% of patients also received focal RT (not during TOPO) and 77% received concomitant systemic hormonal or chemotherapy. Median number of TOPO treatments was 14.5 (range, 3‐71); median duration of treatment, 11 weeks (1‐176); and median OS, 6.9 months (range, 0.9‐48.8). Patients remaining progression‐free during 4‐6 weeks of induction (81%) had a median OS of 11.5 months (range, 1.8‐48.8). Overall neurologic PFS at 6, 12, and 24 months was 39%, 26%, and 6%, respectively. Clearing of CSF malignant cells for >3 consecutive samples occurred in 10/21 (48%) patients with positive CSF cytology at baseline, remaining clear for a median duration of 15.9 months (range, 1.4‐34.5). Grade 3 adverse events included headache or vomiting (3pts), T2 hyperintensity surrounding the ventricular catheter (2 pts), and meningitis (2 pts). Conclusions Intra‐CSF TOPO, with focal RT as needed for symptomatic areas of enhancement produced durable clearing of CSF malignant cells in 48% of patients positive at baseline, with promising median PFS and OS.

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Leptomeningeal metastases in patients with human epidermal growth factor receptor 2 positive breast cancer: Real‐world data from a multicentric European cohort

Ratoša

Dobnikar

Bottosso

et al. 2022

Intl Journal of Cancer

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In patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer, leptomeningeal metastases (LM) are a rare but often a fatal clinical scenario. In this multicentric study, clinical and pathologic characteristics of patients with HER2+ breast cancer developing LM were described, as well as survival outcomes. Data were gathered retrospectively from medical records of 82 patients with advanced HER2+ breast cancer and LM treated between August 2005 and July 2020. Following LM diagnosis, 79 (96.3%) patients received at least one line of anti‐HER2 therapy, 25 (30.5%) patients received intrathecal therapy and 58 (70.7%) patients received radiotherapy. Overall survival (OS) was 8.3 months (95% confidence interval [CI] 5.7‐11), 1‐year OS was 42%, and 2‐year OS was 21%. At univariate analysis, patients who were treated after 2010, had better Karnofsky performance status, were free of neurological symptoms, had better prognostic, received chemotherapy (OS difference 9.4 months, P = .024), or monoclonal antibodies (trastuzumab ± pertuzumab; OS difference 6.1 months; P = .013) after LM diagnosis, had a statistically significantly longer OS. Presence of neurological symptoms (hazard ratio 3.32, 95% CI 1.26‐8.73; P = .015) and not having received radiotherapy (hazard ratio 2.02, 95% CI 1.09‐3.72; P = .024) were all associated with poorer OS at multivariate analysis. To summarize, not having neurological symptoms and receiving RT at LM diagnosis were associated with prolonged OS in our cohort. Survival seemed to be prolonged with multimodality treatment, which included targeted therapy, chemotherapy, and RT to the LM sites.

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Treatment and prognosis of leptomeningeal disease secondary to metastatic breast cancer: a single-centre experience

Cited by 5 publications

References 0 publications

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

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

Intra‐CSF topotecan in treatment of breast cancer patients with leptomeningeal metastases

Leptomeningeal metastases in patients with human epidermal growth factor receptor 2 positive breast cancer: Real‐world data from a multicentric European cohort

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