Determinants of prolonged survival for breast cancer patient groups with leptomeningeal metastasis (LM)

Niwińska, Anna; Pogoda, Katarzyna; Michalski, Wojciech; Kunkiel, Michał; Jagiełło-Gruszfeld, Agnieszka

doi:10.1007/s11060-018-2790-z

Cited by 36 publications

(45 citation statements)

References 27 publications

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“…In fact, the only randomized clinical trial specifically designed to assess the role of IT chemotherapy in BC‐related LMD showed no benefit . Data from a recent retrospective series suggest that the association of systemic therapy and radiation therapy with better prognosis might be stronger than that of intrathecal therapy . These results are consistent with our data showing that both systemic treatment and radiotherapy associated with better outcome at univariate analysis in the overall population, whereas IT treatment did not.…”

Section: Discussionsupporting

confidence: 89%

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: 89%

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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“…Recently, molecularly targeted substances such as tyrosine kinase inhibitors (TKI) have produced encouraging results with proven activity in the CNS (41). In this context, primary histology and molecular analyses play an important role in recent data, since they decisively influence the range of available substances for systemic and LC treatment (33, 42, 43).…”

Section: Discussionmentioning

confidence: 99%

“…Estimated OS ranged from 10 to 17 weeks, and the application of ITC, as well as the combination with systemic chemo- or antihormonal therapy, was prognostic for a favorable outcome. On the other hand, high-grade histology, poor clinical performance and triple-negative tumors had a significant negative impact on survival (11, 43, 49).…”

Section: Discussionmentioning

confidence: 99%

“…As discussed above, with the availability of new histology-dependent and molecularly targeted therapies, oncologic prognosis is critically influenced by medicamentous treatment, while the focus of radiotherapy lies on symptom control (41). Accordingly, prolonged survival may be observed in histologies for which efficacious substances are available, such as breast cancer and adeno-NSCLC (42, 43). As the patients in our current collective have been treated over a period of 10 past years, only a minority received treatment with newer substances for which a substantial impact on survival can be expected.…”

Section: Discussionmentioning

confidence: 99%

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Palliative Radiotherapy for Leptomeningeal Carcinomatosis–Analysis of Outcome, Prognostic Factors, and Symptom Response

et al. 2019

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Introduction: The purpose of this article is to report our institution's 10-year experience on palliative radiotherapy for the treatment of leptomeningeal carcinomatosis (LC), assessing survival, neurologic outcome, and prognostic factors.Patients and methods: We retrospectively analyzed 110 patients who received palliative radiotherapy for LC between 2008 and 2018. The most common histologies were breast cancer (n = 43, 39.1%) and non-small cell lung cancer (NSCLC) (n = 31, 28.2%). Radiotherapy was administered as whole-brain radiotherapy (WBRT) (n = 51, 46.4%), focal spinal RT (n = 11, 10.0%) or both (n = 47, 42.7%). Twenty-five patients (22.7%) were selected for craniospinal irradiation. Clinical performance and neurologic function were quantified on the neurologic function scale (NFS) before and in response to therapy. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for survival.Results: Ninety-eight patients (89.1%) died and 12 (10.9%) were alive at the time of analysis. Median OS from LC diagnosis and from the beginning of RT was 13.9 weeks (IQR: 7.1–34.0) and 9.9 weeks (IQR: 5.3–26.3), respectively. In univariate analysis, prognostic of longer OS were a Karnofsky performance scale index (KPI) of ≥70% (HR 0.20, 95%-CI: [0.13; 0.32], p < 0.001), initially moderate neurological deficits (NFS ≤2) (HR 0.32, 95% CI: [0.19; 0.52], p < 0.001), symptom response to RT (HR 0.41, 95%-CI: [0.26; 0.67], p < 0.001) and the administration of systemic therapy (HR 0.51, 95%-CI: [0.33; 0.78], p = 0.002). Prognostic of inferior OS were high-grade myelosuppression (HR 1.78, 95% CI: [1.06; 3.00], p = 0.03) and serum LDH levels >500 U/l (HR 3.62, 95% CI: [1.76; 7.44], p < 0.001). Clinical performance, symptom response and serum LDH stayed independently prognostic for survival in multivariate analysis. RT was well-tolerated and except for grade III myelosuppression in 19 cases (17.3%), no high-grade acute toxicities were observed. Neurologic symptom stabilization was achieved in 83 cases (75.5%) and a sizeable improvement in 39 cases (35.5%).Conclusion: Radiotherapy is a well-tolerated and efficacious means of providing symptom palliation for patients with LC, delaying neurologic deterioration while probably not directly influencing survival. Prognostic factors such as clinical performance, neurologic response and serum LDH can be used for patient stratification to facilitate treatment decisions.

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“…The median over all survival (OS) of patients after LM dia gnosis does not exceed 6 months [3]. The factors associated with increased survival are Karnofsky performance score ≥ 70, age > 53, luminal bio logical subtype of BC (ER+ PR+ HER2-), systemic ther apy, intrathecal ther apy and RT [4].…”

Section: Discussionmentioning

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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Determinants of prolonged survival for breast cancer patient groups with leptomeningeal metastasis (LM)

Cited by 36 publications

References 27 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

Palliative Radiotherapy for Leptomeningeal Carcinomatosis–Analysis of Outcome, Prognostic Factors, and Symptom Response

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

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