Modern Stereotactic Radiotherapy for Brain Metastases from Lung Cancer: Current Trends and Future Perspectives Based on Integrated Translational Approaches

Abstract

Brain metastases (BMs) represent the most frequent metastatic event in the course of lung cancer patients, occurring in approximately 50% of patients with non-small-cell lung cancer (NSCLC) and in up to 70% in patients with small-cell lung cancer (SCLC). Thus far, many advances have been made in the diagnostic and therapeutic procedures, allowing improvements in the prognosis of these patients. The modern approach relies on the integration of several factors, such as accurate histological and molecular profiling, comprehensive assessment of clinical parameters and precise definition of the extent of intracranial and extracranial disease involvement. The combination of these factors is pivotal to guide the multidisciplinary discussion and to offer the most appropriate treatment to these patients based on a personalized approach. Focal radiotherapy (RT), in all its modalities (radiosurgery (SRS), fractionated stereotactic radiotherapy (SRT), adjuvant stereotactic radiotherapy (aSRT)), is the cornerstone of BM management, either alone or in combination with surgery and systemic therapies. We review the modern therapeutic strategies available to treat lung cancer patients with brain involvement. This includes an accurate review of the different technical solutions which can be exploited to provide a “state-of-art” focal RT and also a detailed description of the systemic agents available as effective alternatives to SRS/SRT when a targetable molecular driver is present. In addition to the validated treatment options, we also discuss the future perspective for focal RT, based on emerging clinical reports (e.g., SRS for patients with many BMs from NSCLC or SRS for BMs from SCLC), together with a presentation of innovative and promising findings in translational research and the combination of novel targeted agents with SRS/SRT.

Phytochemical Screening, In Silico Molecular Docking, ADME Properties, and In Vitro Antioxidant, Anticancer, and Antidiabetic Activity of Marine Halophyte Suaeda maritima (L.) Dumort

“…4 Although numerous modern treatment methods have been developed, cancer is frequently futile due to medication resistance and distant metastases. 5 Further, chemically produced medications are used to mitigate the effects of diabetes, causing unwanted side effects such as obesity, gastrointestinal difficulties, and heart diseases. Consequently, contemporary synthetic and chemical medicines are cautiously approached due to their propensity to manifest adverse effects.…”

Fifteen-Fraction Radiosurgery Followed by Reduced-Dose Whole-Brain Irradiation With a Total Biologically Effective Dose of >90-100 Gy for a Locally Invasive Brain Metastasis From Lung Adenocarcinoma With a High Dissemination Potential

“…Brain metastases (BMs) without locoregional or any other distant tumor seeding are a pattern of recurrence after definitive surgery of non-small cell lung cancer (NSCLC) [1]. Local treatment such as external-beam radiotherapy (EBRT) or surgical resection is generally preferred over systemic therapy for oligo-BMs [2][3][4]. A single isolated BM requires long-term control (local curability) and safety with localized treatment, which can significantly affect prognosis [1,3].…”

“…Local treatment such as external-beam radiotherapy (EBRT) or surgical resection is generally preferred over systemic therapy for oligo-BMs [2][3][4]. A single isolated BM requires long-term control (local curability) and safety with localized treatment, which can significantly affect prognosis [1,3].…”

“…Stereotactic radiosurgery (SRS) is preferred over whole-brain radiotherapy (WBRT) for relatively small and limited (oligo-) BMs [2,3]. In the meantime, surgical resection is prioritized over SRS for a BM with a >4-5 cm diameter, given the brain tolerance limits to SRS and occurrence of immediate decompression requirements [2].…”