Management of brain metastases in lung cancer: evolving roles for radiation and systemic treatment in the era of targeted and immune therapies

Abstract Brain metastases are a common occurrence in both non-small cell and small cell lung cancer with the potential to affect quality of life and prognosis. Due to concerns about the accessibility of the central nervous system by systemic chemotherapy agents, the management of brain metastases has historically relied on local therapies including surgery and radiation. However, novel targeted and immune therapies that improve overall outcomes in lung cancer have demonstrated effective intracranial activity. As a result, the management of brain metastases in lung cancer has evolved, with both local and systemic therapies now playing an important role. Factors such as tumor histology (non-small versus small cell), oncogenic driver mutations, and symptom burden from intracranial disease impact treatment decisions. Here, we review the current management of brain metastases in lung cancer, highlighting the roles of stereotactic radiosurgery and novel systemic therapies as well as the ongoing questions that remain under investigation.

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Challenges and Novel Opportunities of Radiation Therapy for Brain Metastases in Non-Small Cell Lung Cancer

Cancers ◽

10.3390/cancers13092141 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2141

Author(s):

Paola Anna Jablonska ◽

Joaquim Bosch-Barrera ◽

Diego Serrano ◽

Manuel Valiente ◽

Alfonso Calvo ◽

...

Keyword(s):

Lung Cancer ◽

Radiation Therapy ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

The Past ◽

Systemic Treatments ◽

Systemic Therapies

Approximately 20% patients with non-small cell lung cancer (NSCLC) present with CNS spread at the time of diagnosis and 25–50% are found to have brain metastases (BMs) during the course of the disease. The improvement in the diagnostic tools and screening, as well as the use of new systemic therapies have contributed to a more precise diagnosis and prolonged survival of lung cancer patients with more time for BMs development. In the past, most of the systemic therapies failed intracranially because of the inability to effectively cross the blood brain barrier. Some of the new targeted therapies, especially the group of tyrosine kinase inhibitors (TKIs) have shown durable CNS response. However, the use of ionizing radiation remains vital in the management of metastatic brain disease. Although a decrease in CNS-related deaths has been achieved over the past decade, many challenges arise from the need of multiple and repeated brain radiation treatments, which carry along not insignificant risks and toxicity. The combination of stereotactic radiotherapy and systemic treatments in terms of effectiveness and adverse effects, such as radionecrosis, remains a subject of ongoing investigation. This review discusses the challenges of the use of radiation therapy in NSCLC BMs in view of different systemic treatments such as chemotherapy, TKIs and immunotherapy. It also outlines the future perspectives and strategies for personalized BMs management.

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Optimal Timing And Technique Of Local Therapy For Brain Metastases From Non-Small Cell Lung Cancer With Driver Mutations

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2020.07.096 ◽

2020 ◽

Vol 108 (3) ◽

pp. e718

Author(s):

R. El Shafie ◽

T. Eichkorn ◽

D. Weber ◽

F. Bozorgmehr ◽

L. König ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Local Therapy ◽

Small Cell ◽

Driver Mutations ◽

Optimal Timing ◽

Small Cell Lung

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MLTI-02. Impact of driver mutations on timing, pattern, treatment, and outcome in patients with brain metastases from non-small cell lung cancer

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab071.051 ◽

2021 ◽

Vol 3 (Supplement_3) ◽

pp. iii13-iii13

Author(s):

Stephanie Jünger ◽

Marie-Lisa Eich ◽

Anna-Katharina Meissner ◽

Maximilian Ruge ◽

Roland Goldbrunner ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Stereotactic Radiosurgery ◽

Cell Lung Cancer ◽

Systemic Treatment ◽

Small Cell ◽

Driver Mutations ◽

Small Cell Lung ◽

Cerebral Control

Abstract Objective To assess the impact of driver mutations in non-small cell lung cancer (NSCLC) on the formation and treatment outcome of brain metastases (BM). Patients and methods We retrospectively analyzed patients with BM from NSCLC with respect to driver mutations and assessed timing and pattern of BM development as well as local cerebral control and survival after BM treatment. Results We included 253 patients. Histology was adenocarcinoma in 223, squamous cell carcinoma in 25 and not otherwise specified (NOS) in five patients. All tumors were analyzed for known alterations in NSCLC by panel sequencing and fluorescence in situ hybridization (FISH). An activating KRAS mutation (n=85) was the most prevalent mutation, followed by activating EGFR mutation (n=31) and MET amplification (n=29). Other mutations were detected in 27 patients. No alterations were found in 102 patients. Time to BM development did not differ between the molecular groups (p=.22), nor did the number (p=.72) or location (supra- vs. infratentorial; p=.76) of the BM. Patients underwent multimodal cerebral treatment comprising surgery followed by radiotherapy and/or stereotactic radiosurgery (n=138), whole brain radiotherapy (n=13) or stereotactic radiosurgery alone (n=102). Systemic treatment was initiated or continued after BM therapy in 169 patients and its frequency did not differ significantly between genotypes (p=.08) while the modality of medical treatment depended on genotype (p<0.0001). The latter showed longer local cerebral control rates compared to other mutations (0.23) and a longer overall survival compared to KRAS and wild type genotypes (p=.015). Systemic treatment (HR 2.1 95%CI 1.4–3.0; p<.0001) and a good clinical status (HR 2.1 95%CI 1.2–3.7; p=0.014) were the only independent factors for further survival. Conclusion The actual known driver mutations do not influence BM formation. Specific genotypes show a better oncological course, presumably due to available molecular treatment.

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Real-world disease burden and outcomes of brain metastases in EGFR mutation-positive non-small-cell lung cancer

Future Oncology ◽

10.2217/fon-2020-0280 ◽

2020 ◽

Author(s):

Eric Nadler ◽

Janet L Espirito ◽

Melissa Pavilack ◽

Bismark Baidoo ◽

Ancilla Fernandes

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Real World ◽

Service Use ◽

Egfr Mutation ◽

Symptom Burden ◽

Small Cell ◽

Small Cell Lung

Aim: To evaluate the real-world impact of brain metastases (BM) among patients with EGFR mutation-positive ( EGFRm) metastatic non-small-cell lung cancer (NSCLC). Materials & methods: This retrospective, observational matched cohort electronic health record study assessed adults with EGFRm metastatic NSCLC with/without BM. Results: Among 402 patients split equally between both cohorts (±BM), the majority were Caucasian (69%), female (65%) and with adenocarcinoma (92%). Overall symptom burden and ancillary support service use were higher and median overall survival from metastatic diagnosis was significantly shorter in BM patients (11.9 vs 16 months; p = 0.017). Conclusion: BM in EGFRm NSCLC patients can negatively impact clinical outcomes. New targeted therapies that can penetrate the blood–brain barrier should be considered for treating these patients.

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