Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices

Bernhardt, Denise; König, Laila; Aufderstrasse, Sophie; Krisam, Johannes; Hoerner-Rieber, Juliane; Adeberg, Sebastian; Bozorgmehr, Farastuk; Shafie, Rami A El; Lang, Kristin; Kappes, Jutta; Thomas, Michael; Herth, Felix J.F.; Warth, Arne; Marcrom, S.; Debus, Jürgen; Steins, Martin; Rieken, Stefan

doi:10.1016/j.cllc.2017.12.004

Cited by 19 publications

(21 citation statements)

References 27 publications

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“…In the unmatched whole group of patients, the pretreatment variables associated with poor prognosis included age >65 years old, lower KPS scores, more BM, and extracranial metastases. This is consistent with previous reports (32)(33)(34). Nonetheless, the factors of synchronous vs. metachronous BM and age >65 years old were not associated with the outcomes.…”

Section: Discussionsupporting

confidence: 92%

Best Supportive Care Versus Whole-Brain Irradiation, Chemotherapy Alone, or WBRT Plus Chemotherapy in Patients With Brain Metastases From Small-Cell Lung Cancer: A Case-Controlled Analysis

Xue

Xiao-lin

et al. 2021

Front. Oncol.

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BackgroundWBRT and systemic chemotherapy are the mainstay treatments for small-cell lung cancer (SCLC) brain metastases (BM). However, current recommendations are mainly based on evidence from retrospective analyses. A recent randomized trial found no benefits from WBRT compared with best supportive care (BSC) in patients with more than three BM from non-small-cell lung cancer (NSCLC). Herein, we aimed to evaluate the roles of WBRT and chemotherapy further in the management of BM from SCLC.Materials and MethodsThere were 698 patients with BM from SCLC included. Of these, 580 received anti cancer treatment (Group 1), including 178 who received WBRT only (Group 1a), 129 who received chemotherapy only (Group 1b), and 273 who received WBRT plus chemotherapy (Group 1c). The other 118 received BSC (Group 2). Propensity score matching (PSM) analysis was used to compare Group 2 with each of the other groups.ResultsAfter PSM, compared with Group 2 (n = 118), patients in Group 1 (n = 440) had a prolonged overall survival (OS) in both univariate and multivariate tests, with a median survival time of 10 months (95% CI = 9−11) in Group 1 and 3.5 months (95% CI = 2−7) in Group 2 (p < 0.001). In subgroup analyses, patients who received WBRT plus chemotherapy were more likely to benefit from treatment (p < 0.001). Chemotherapy alone or WBRT alone did not show survival benefits.ConclusionWBRT plus chemotherapy improved OS in patients with BM from SCLC as compared to BSC. Chemotherapy alone and WBRT alone did not show survival benefits. This retrospective study suggests that SCLC patients with BM who receive WBRT combined with chemotherapy have a better outcome than those receiving BSC alone.

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Section: Discussionsupporting

confidence: 92%

Best Supportive Care Versus Whole-Brain Irradiation, Chemotherapy Alone, or WBRT Plus Chemotherapy in Patients With Brain Metastases From Small-Cell Lung Cancer: A Case-Controlled Analysis

Xue

Xiao-lin

et al. 2021

Front. Oncol.

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“…Metastasis is an indicator of poor prognosis in lung cancer patients, and decreasing the metastatic potential of lung cancer cells significantly prolonged the survival of xenograft-bearing mice. 27,28 Recently, Liu Z reported significantly higher risk of metastasis in the KRAS mutant versus wild-type lung cancer patients. 29 Consistent with this, Anlotinib markedly decreased the migratory and invasive abilities of KRAS mutant lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway</p>

Liu

Tan

et al. 2020

CMAR

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Background: With a high frequency of 30%, KRAS mutations in patients with non-small cell lung cancer (NSCLC) often lead to their poor response to most anti-cancer therapies. As a multi-target tyrosine kinase inhibitor, Anlotinib shows clinical efficacy against several types of cancer. However, its effects on KRAS mutant NSCLC and the underlying molecular mechanisms remain unclear. Materials and Methods: Cell counting Kit-8 assay, colony formation assay, flow cytometry analysis, wound healing scratch assay, Transwell assay and xenograft mouse model were used to evaluate the anti-cancer effects of Anlotinib. The potential molecular mechanisms were determined by immunohistochemistry (IHC) and Western blotting. Results: Anlotinib inhibited proliferation of KRAS mutant lung cancer cells and induced apoptosis in vitro. In addition, the migration and invasion abilities of these cells were also decreased after treatment with Anlotinib. It significantly suppressed tumor growth in vivo and prolonged the survival of the xenograft-bearing mice, which correlated to lower expression levels of Ki67 in the tumor tissues. Mechanistically, Anlotinib downregulated MEK and ERK as well as their phosphorylated forms in the KRAS mutant lung cancer cells. Conclusion: Anlotinib inhibits the growth of KRAS mutant lung cancer cells partly via the suppression of the MEK/ERK pathway. Our findings provide novel insights into treating recalcitrant KRAS mutated NSCLC.

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“…Several prognostic index systems were previously published including 1997, Gaspar et al created recursive partitioning analysis (RPA), in 2004, basic score for brain metastases (BSBM) proposed by Lorenzoni et al and Sperduto et al Constructed the revised diagnosis-specific graded prognostic assessment (DS-GPA) in 2010; however, these index studies enrolled a small number of SCLC patients (12)(13)(14). In 2018, Bernhardt et al developed a new prognostic evaluation system specifically for SCLC BM treated with WBRT: the BMS-Score, this is the first prognostic index for small cell lung cancer with brain metastases and it includes three factors: KPS, synchronous BM or metachronous BM, and ECM state (15). These three factors are assigned a different weight points: 2 points for KPS ≥70, 1 point for synchronous BM, 1 point for ECM state stable, the scores of each patient was the sum of points in each factor.…”

Section: Original Articlementioning

confidence: 99%

Validation of a novel prognostic index: BMS-Score for patients with brain metastases of small cell lung cancer

Cao

et al. 2021

Ann Palliat Med

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Background: A new disease-specific prognostic score (Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer termed BMS-Score) was published to clarify the prognosis of patients with brain metastasis (BM) of small cell lung cancer (SCLC) treated with whole brain radiotherapy (WBRT). The purpose of the present study was to validate the prognostic value of the newly proposed BMS-Score through comparison with three other previously published prognostic indices. Methods: In total, 451 patients with BM of SCLC treated with WBRT at the Shanxi Province Cancer Hospital from January 2010 to December 2019 were included. The clinical characteristics of all patients were recorded and follow-up was through April 2020. Overall survival (OS) was calculated by Kaplan-Meier analysis, and univariate and multivariate analyses were used to calculate the prognostic cofactors. The concordance index (C-index) was used to assess the prognostic value of the following four prognostic systems: recursive partitioning analysis (RPA), diagnosis-specific graded prognostic assessment (DS-GPA), basic score for brain metastases (BSBM), and the newly proposed BMS-Score. Results: The independent factors affecting the prognosis of SCLC patients with BM included the Karnofsky performance score (KPS), number of brain metastases, extracranial metastases (ECM) state, and whether treatment had been received before BM. RPA, BSBM, DS-GPA, and BMS-Score log-rank test P values were all less than 0.001 among each group (P<0.001). The C-indices of the four groups were 0.554, 0.584, 0.588, and 0.643, respectively. Conclusions: The four prognostic scoring systems exhibited medium predictive value for SCLC. The BMS-Score had the best applicability compared with the other three prognosis indices.

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Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices

Cited by 19 publications

References 27 publications

Best Supportive Care Versus Whole-Brain Irradiation, Chemotherapy Alone, or WBRT Plus Chemotherapy in Patients With Brain Metastases From Small-Cell Lung Cancer: A Case-Controlled Analysis

Best Supportive Care Versus Whole-Brain Irradiation, Chemotherapy Alone, or WBRT Plus Chemotherapy in Patients With Brain Metastases From Small-Cell Lung Cancer: A Case-Controlled Analysis

<p>Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway</p>

Validation of a novel prognostic index: BMS-Score for patients with brain metastases of small cell lung cancer

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