To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors.ASCO convened an Expert Panel and conducted a systematic review of the literature.Thirty-two randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base.Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non-small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy.Additional information is available at www.asco.org/neurooncology-guidelines. 

Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline

Systemic treatment of brain metastases in non-small cell lung cancer

Aim: We aimed to evaluate the prognostic values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) and systemic immune-inflammation index (SII) in patients with brain metastases from non-small-cell lung cancer (NSCLC). Materials & methods: We conducted Kaplan-Meier analysis and multivariable Cox analysis to evaluate the prognostic values of NLR, PLR, LMR and SII. Results: Kaplan-Meier analysis showed that the patients in low LMR, high NLR, PLR and SII groups were associated with shorter overall survival. Multivariable Cox analysis revealed LMR and SII were independent prognostic factors for overall survival (p = 0.002 and p = 0.004, respectively). Conclusion: LMR and SII are of significant values in clinical prognostic evaluation for patients with brain metastases from NSCLC.

Prognostic value of lymphocyte-to-monocyte ratio and systemic immune-inflammation index in non-small-cell lung cancer patients with brain metastases.

MicroRNA-6077 enhances the sensitivity of patients-derived lung adenocarcinoma cells to anlotinib by repressing the activation of glucose transporter 1 pathway

Randomized controlled trials have failed to report any survival advantage for WBRT combined with SRS in the management of brain metastases, despite the enhanced local and distant control in comparison to each treatment alone. Literature review have revealed important role of primary histology of the tumor when dealing with brain metastases. NSCLC responds better to combined approach even when there was only single brain metastasis present while breast cancer has registered better survival with SRS alone probably due to better response of primary tumor to advancement in surgical and chemotherapeutic agents. Furthermore, mutation status (EGFR/ALK) in lung cancer and receptor status (ER/PR/HER2) in breast cancer also exhibit diversity in their response to radiotherapy. Radioresistant tumors like renal cell carcinoma and melanoma brain metastases have achieved better results when treated with SRS alone. Secondly, single brain metastasis may benefit from local and distant brain control achieved with combined treatment. These diverse outcomes suggest a primary histology-based analysis of the radiotherapy regimens (WBRT, SRS, or their combination) would more ideally establish the role of radiotherapy in the management of brain metastases. Molecularly targeted therapeutic and immunotherapeutic agents have revealed synergism with radiation therapy particularly SRS in treating cancer patients with brain metastases. Clinical updates in this regard have also been reviewed.

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Tumor Primary Site and Histology Subtypes Role in Radiotherapeutic Management of Brain Metastases.

Background It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) presented better efficacy than brain radiotherapy (brain RT) in the treatment of brain metastasis (BM) in EGFR mutated NSCLC patients. However, whether the combination of EGFR-TKIs and brain RT is better than EGFR-TKIs alone remains unclear. We aim to compare the outcomes of adding brain RT to EGFR-TKIs and to screen for the beneficial population by a meta-analysis of currently available data. Methods A systematic search for relevant articles was conducted in six databases. The outcomes were overall survival (OS) and intracranial progression-free survival (iPFS) between groups, both were measured as hazard ratios (HRs). Meta-regression and dominant subgroup analysis were used to explore advantageous subgroups. Results A total of 12 retrospective studies involving 1,553 EGFR mutated patients with BM at the first diagnosis were included. EGFR-TKIs plus brain RT showed a significant prolonged OS (HR =0.64, 95% CI: 0.52-0.78; P<0.001) and iPFS (HR =0.62, 95% CI: 0.50-0.78; P<0.001) compared to EGFR-TKIs alone. Meta-regression analyses showed that potential factors contributed to the heterogeneity were the proportion of ECOG performance score (2+ vs. 0-1, P=0.070) and brain symptomatic patients (no vs. yes, P=0.077) regarding iPFS and was age (younger vs. older, P=0.075) for OS. Dominant subgroup analyses suggested that symptomatic patients (HR 0.46 vs. 0.74, interaction P=0.01) for iPFS, and older patients (HR 0.55 vs. 0.75, interaction P=0.03) and 19Del mutation (HR 0.55 vs. 0.74, interaction P=0.04) for OS, seemed to benefit more from the combination therapy than their counterparts. However, direct subgroup results based on only two studies did not show significant difference in iPFS benefit between age, mutation type and sex subgroup. Conclusions EGFR-TKIs plus brain RT is superior to EGFR-TKIs alone in the management of EGFR-mutated NSCLC patients with BM, of which the benefits might be influenced by age, BM-related symptoms and mutation type.

Kai Dong

Papers

EGFR-TKI plus brain radiotherapy versus EGFR-TKI alone in the management of EGFR-mutated NSCLC patients with brain metastases.