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

Niwińska, Anna; Rudnicka, H; Murawska, Magdalena

doi:10.1016/j.clbc.2014.07.004

Cited by 53 publications

(39 citation statements)

References 25 publications

(55 reference statements)

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“…This considerable high proportion was to be expected due to the dismal prognosis of leptomeningeal metastases in most malignancies, with a median survival of only several weeks. The survival times recorded here (median PFS of 8.5 weeks and median OS of 13.5 weeks) are in accordance with the data documented in the literature [ 28 , 29 , 30 , 31 , 32 ].…”

Section: Discussionsupporting

confidence: 91%

Ventriculoperitoneal Shunts Equipped with On-Off Valves for Intraventricular Therapies in Patients with Communicating Hydrocephalus due to Leptomeningeal Metastases

Burger

Wagner

Franz

et al. 2018

JCM

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Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually switch off the shunt function can be used for intraventricular injections of therapeutics in patients suffering from a communicating hydrocephalus caused by leptomeningeal metastases. These shunt devices avoid the risk of injecting therapeutics through the distal leg of the shunt system into the intraperitoneal space, which may cause toxicity. Furthermore, regular intraventricular injections of chemotherapeutics help to maintain sufficient concentrations in the ventricular space. Therefore, ventriculoperitoneal shunts equipped with an on-off valve are a useful tool to reliably inject chemotherapeutics into the ventricles. In order to systematically assess feasibility, safety, and efficacy of this procedure, we performed a retrospective analysis of all patients with leptomeningeal metastases who had received a shunt system at our institution. In total, six adult patients had a ventriculoperitoneal shunt equipped with an on-off valve implanted. Out of these six patients, two patients subsequently received intraventricular injections of chemotherapeutics. The configuration of the valve setting and the intraventricular injections were easily feasible in the setting of a neuro-oncology department. The complication of a shunt leakage occurred in one patient following the first intraventricular injection. No extra-central nervous system (CNS) toxicities were observed. In summary, ventriculoperitoneal shunts with on-off valves are useful tools for reliable intraventricular administration of therapeutics.

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Section: Discussionsupporting

confidence: 91%

Ventriculoperitoneal Shunts Equipped with On-Off Valves for Intraventricular Therapies in Patients with Communicating Hydrocephalus due to Leptomeningeal Metastases

Burger

Wagner

Franz

et al. 2018

JCM

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“…Indeed, 30% of HER2+ LC cases are diagnosed as the first manifestation of cancer after a substantial disease-free interval13, 15, 16, 17. Unfortunately, although it was discovered nearly 150 years ago18, HER2+ LC remains incurable, with few treatment options and response rates often <20%19, 20,21,22,23,24,25. At present, HER2+ LC management is multidisciplinary and includes radiotherapy (RT) and intrathecal chemotherapy (ITC) 26,27,28,29. Methotrexate (MTX), a DNA alkylating drug, is frequently used as palliative ITC for HER2+ LC9, 30, 31, 32, 33. However, this approach has very limited success and causes serious side effects26, 27,28,29.…”

Section: Introductionmentioning

confidence: 99%

“…At present, HER2+ LC management is multidisciplinary and includes radiotherapy (RT) and intrathecal chemotherapy (ITC) 26,27,28,29. Methotrexate (MTX), a DNA alkylating drug, is frequently used as palliative ITC for HER2+ LC9, 30, 31, 32, 33. However, this approach has very limited success and causes serious side effects26, 27,28,29. Furthermore, patients with HER2+ LC are excluded from clinical trials because of their poor prognosis and to minimize results that are not reproducible1, 34,35,36.…”

Section: Introductionmentioning

confidence: 99%

GM-CSF signaling is critical for HER2+ breast leptomeningeal carcinomatosis

Ansari¹,

Bhan²,

Chen³

et al. 2020

Preprint

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Leptomeningeal carcinomatosis (LC), when tumor cells spread to leptomeninges surrounding the brain and spinal cord. HER2+ breast cancer is the most common origin of LC. HER2+ LC remains incurable, with few treatment options and response rates of <20%. One major limitation in development of HER2+ LC therapies has been lack of clinically relevant HER2+ LC primary cell-lines and animal models. To address this, we generated cell lines and patient-derived xenograft models using nodular HER2+ LC. This led to identification of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an oncogenic autocrine driver of HER2+ LC. We observed that oligodendrocyte progenitor cells (OPCs) inhibit growth of HER2+ LC in vitro and in vivo. Furthermore, OPC-derived factor TPP1 degrades GM-CSF, decreasing GM-CSF signaling and suppressing HER2+ LC growth. Lastly, we determined that synergistic inactivation of GM-CSF signaling via the intrathecal delivery neutralizing anti-GM-CSF antibodies and a pan-Aurora kinase inhibitor (CCT137690) antagonizes development of HER2+ LC in vivo.

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“…In our case, we considered thiotepa as a cell cyclenonspecific alkylat ing agent based on activity of alkylat ing agents in the triple-negative BC [8]. Niwińska et al [9] in their prospective observational study compared the efficacy of MTX and liposomal cytarabine in patients treated intrathecally. Among treatment methods, only systemic ther apy prolonged survival in patients with LM.…”

Section: Klúčové Slovámentioning

confidence: 99%

Leptomeningeal Metastasis in a Breast Cancer Treated with Two Lines of Intrathecal Chemotherapy – a Case Report

Mikudova¹,

Rejleková²,

Gyarfás³

et al. 2019

Klin Onkol

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Background: Leptomeningeal metastasis (LM) in breast cancer is associated with a poor prognosis. Although no randomised trial has demonstrated that intrathecal chemotherapy actually prolongs survival, this treatment is considered standard of care in this setting. The prognosis of patients with LM is poor, with a median overall survival time of less than 6 months. Methods: Herein, we report a case of a young woman with breast cancer who presented with LM at the time of relapse and was subsequently treated with two lines of intrathecal chemotherapy that prolonged survival. Results: A 28-year old woman without a significant past medical history was diagnosed with triple-negative invasive ductal carcinoma. Eight months after adjuvant treatment she developed multiple brain metastases and LM developed subsequently 1 month after finishing whole brain irradiation. Initially, she was treated with a combination of methotrexate, cytarabine and dexamethasone intrathecally but after 3 months she presented with a worsening clinical status and increased numbers of cancer cells in cerebrospinal fluid. Subsequently, she received a combination of thiotepa and methotrexate intrathecally, which resulted in a prolonged response lasting 10 months. The patient died 32 months after initial diagnosis and 18 months from LM infiltration due to disease progression in the liver and lungs as well as LM. Conclusion: The prognosis of patients with LM remains poor because of the limited effectiveness of currently available therapies; however, intrathecal chemotherapy could substantially prolong survival in selected patients.

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

Cited by 53 publications

References 25 publications

Ventriculoperitoneal Shunts Equipped with On-Off Valves for Intraventricular Therapies in Patients with Communicating Hydrocephalus due to Leptomeningeal Metastases

Ventriculoperitoneal Shunts Equipped with On-Off Valves for Intraventricular Therapies in Patients with Communicating Hydrocephalus due to Leptomeningeal Metastases

GM-CSF signaling is critical for HER2+ breast leptomeningeal carcinomatosis

Leptomeningeal Metastasis in a Breast Cancer Treated with Two Lines of Intrathecal Chemotherapy – a Case Report

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