Whole brain radiotherapy in management of non-small-cell lung carcinoma associated leptomeningeal carcinomatosis: evaluation of prognostic factors

Özdemir, Yurday; Yıldırım, Berna Akkuş; Topkan, Erkan

doi:10.1007/s11060-016-2179-9

Cited by 25 publications

(9 citation statements)

References 28 publications

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“…Patient selection is evidently crucial in the context of LC to avoid the burden of over-treatment in a highly palliative situation with severely limited prognosis: The body of literature discussed above widely agrees on the prognostic value of initial clinical performance, represented by the KPI (12–14, 49, 61, 62). We could confirm the impact of this prognosticator in our analysis, while additionally providing a quantitative functional assessment in the form of the NFS.…”

Section: Discussionmentioning

confidence: 99%

“…Frequently, focal radiotherapy of symptomatic spinal lesions is performed to preserve neurologic function and control symptoms (13). This approach is often combined with whole brain radiotherapy (WBRT), which can positively affect survival, especially in the presence of additional brain metastases (13, 14). In addition to supportive corticosteroids, medicamentous treatment has been established primarily in the form of intrathecal chemotherapy (15–17).…”

Section: Introductionmentioning

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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Adenocarcinomas are the most common tumors to metastasize to the leptomeninges. Of the patients with NSCLC, 30–64% have CNS metastases, of which 4–7% have LMD [ 5 , 8 , 9 ].…”

Section: Epidemiologymentioning

confidence: 99%

Leptomeningeal disease: current diagnostic and therapeutic strategies

et al. 2017

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Leptomeningeal disease has become increasingly prevalent as novel therapeutic interventions extend the survival of cancer patients. Although a majority of leptomeningeal spread occurs secondary to breast cancer, lung cancer, and melanoma, a wide variety of malignancies have been reported as primary sources. Symptoms on presentation are equally diverse, often involving a combination of neurological deficits with the possibility of obstructive hydrocephalus. Diagnosis is definitively made via cerebrospinal fluid cytology for malignant cells, but neuro-imaging with high quality T1-weighted magnetic resonance imaging can aid diagnosis and localization. While leptomeningeal disease is still a terminal, late-stage complication, a variety of treatment modalities, such as intrathecal chemotherapeutics and radiation therapy, have improved median survival from 4–6 weeks to 3–6 months. Positive prognosticative factors for survival include younger age, high performance scores, and controlled systemic disease. In looking to the future, diagnostics that improve early detection and chemotherapeutics tailored to the primary malignancy will likely be the most significant advances in improving survival.

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“…A probable reason for this discrepancy between the survival impacts of WBRT may be a mixture of patients with a diversity of clinical and molecular biological background. In fact, the therapeutic response to WBRT varies with the number of factors including the Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1, time to leptomeningeal metastasis following NSCLC diagnosis, as well as lack of brain metastasis [26]. Our study reported a doubling of OS with statistical marginal difference between patients who received WBRT and the non-WBRT group (11.4 vs. 5.0 months, P = 0.051).…”

Section: Discussionmentioning

confidence: 65%

Whole brain radiotherapy (WBRT) for leptomeningeal metastasis from NSCLC in the era of targeted therapy: a retrospective study

et al. 2020

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Background and purpose: Leptomeningeal metastasis (LM) is a rare but detrimental complication in patients with non-small cell lung cancer (NSCLC). Although whole brain radiotherapy (WBRT) is used to eliminating cancer cells or microscopic foci, it is becoming less favorable due to the concerns over neurocognitive toxicity. This study aimed to re-evaluate the role of WBRT in the setting of modern targeted therapy. Materials and methods: From December 2014 to March 2019, 80 NSCLC patients with cytologically and/or radiologically proven LM diagnosis were retrospectively analyzed. Results: The median OS (mOS) after diagnosis of LM was 8.0 (95%CI: 4.4 to 11.6) months, and the one-year OS was 39.4%. The mOS for EGFR-mutated LM patients was 12.6 (3.0 to 22.2) months versus only 4.1 (2.8 to 5.4) for patients with wild-type EGFR (P < 0.001). Younger patients (< 53.5 yrs.) appeared to have a better OS than older patients (≥53.5 yrs.) (12.6 vs. 6.1, P = 0.041). No survival benefits were found in EGFR-mutated patients who received WBRT (P = 0.490). In contrast, mOS was significantly prolonged in wild-type EGFR patients with WBRT versus non-WBRT (mOS: 8.0 vs. 2.1, P = 0.002). Multivariate analysis indicated that WBRT (P = 0.025) and younger age (P = 0.048) were independent prognostic factors that predicted prolonged survival for wild-type EGFR LM patients from NSCLC. Conclusion: Our study demonstrated that WBRT has clear survival advantages for patients with wild-type EGFR, and molecular biological stratification of LM patients for WBRT is highly recommended.

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Whole brain radiotherapy in management of non-small-cell lung carcinoma associated leptomeningeal carcinomatosis: evaluation of prognostic factors

Cited by 25 publications

References 28 publications

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

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

Leptomeningeal disease: current diagnostic and therapeutic strategies

Whole brain radiotherapy (WBRT) for leptomeningeal metastasis from NSCLC in the era of targeted therapy: a retrospective study

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