Treatment of Brain Metastases in Lung Cancer: Strategies to Avoid/Reduce Late Complications of Whole Brain Radiation Therapy

Abstract

Brain metastases occur in 20-40 % of lung cancer patients. The use of whole brain radiation therapy (WBRT) has been shown to ameliorate many neurological symptoms, facilitate corticosteroid reduction, enhance quality of life (QOL), and prolong survival. The acute and early delayed side effects of WBRT are generally mild and inconsequential, whereas late complications often are progressive, irreversible, and may have a profound effect on neurocognitive function and QOL. Nevertheless, WBRT remains the cornerstone for treatment of multiple brain metastases due to its efficacy and the paucity of other treatment options. In avoidance of WBRT and its potential toxicity, patients of good performance status and ≤3 metastases may be treated reasonably with focal therapy alone (surgery or radiosurgery) without a compromise in survival. In patients with multiple brain metastases and those undergoing prophylactic cranial irradiation (PCI), established methods to mitigate the late complications of WBRT include total dose observation, dose per fraction restrictions, and avoidance of concomitant chemotherapy. Current areas of active research that hold great potential for benefit include hippocampal-sparing radiotherapy and the use of neuroprotective agents.

Clinical Observation of Whole Brain Radiotherapy Concomitant with Targeted Therapy for Brain Metastasis in Non-small Cell Lung Cancer Patients with Chemotherapy Failure

“…Clinical research found that BBB pass rate of Erlotinib = cerebral spinal fluid concentration (Ccsf)/plasma concentration, which was about 7% while that of active metabolite of Erlotinib (OSI-420) was about 9%. The concentration of Erlotinib in intracranial metastasis was obviously concentrated, which was evidently higher than in normal brain parenchyma (Harth et al, 2013;Shaw et al, 2013). And Erlotinib marked by isotope C11 was selected as PET-CT tracer, being capable in revealing its distribution in brains of NSCLC patients.…”

Clinical study of the treatment of multiple brain metastases from adenocarcinoma of the lung by simultaneous integrated boost intensity-modulated radiotherapy

“…According to previous studies [11], whole brain radiotherapy 30Gy/10 times could improve symptoms and extend survival time for those patients with poor general condition and symptomatic multiple metastases. For those with fine general condition, SRS, HFRT or SRS/HFRT in brain metastases plus whole brain radiotherapy both have satisfactory efficacy.…”

Methods and results of locoregional treatment of brain metastases in patients with non-small cell lung cancer

“…In patients with non-small cell lung cancer (NSCLC), accounting for 80–85% of all lung cancers, the risk of development of brain metastases (BMF-NSCLC) throughout the course of the disease is 30–50%; brain metastases are found in 7–10% of patients with NSCLC at diagnosis [7–18]. The risk of BMF-NSCLC development is significantly higher in patients with advanced NSCLC (stage III and IV) and in patients with adenocarcinoma and large-cell carcinoma, as compared to squamous-cell carcinoma histology [12–14, 19, 20]. Hsiao et al ., in an analysis of 482 patients with stage IIIb–IV NSCLC, found that the risk of brain metastasis was statistically significantly higher in women, patients aged less than 60 years and in patients with adenocarcinoma histology [7].…”

“…The following methods are used in the treatment of BMF-NSCLC: surgery, SRS, WBRT, systemic treatments (chemotherapy, immunotherapy) and various combinations of these methods [1, 2, 4–6, 8, 9, 11, 12, 17–19, 26, 28–35]. In general, local (surgery, SRS) [1, 4, 6, 8, 17, 18, 28–30, 35] or regional (WBRT) [1, 4, 19, 28–30, 33–35] treatment is preferred, including combination of surgery and radiotherapy.…”

“…In general, local (surgery, SRS) [1, 4, 6, 8, 17, 18, 28–30, 35] or regional (WBRT) [1, 4, 19, 28–30, 33–35] treatment is preferred, including combination of surgery and radiotherapy. There is a growing importance of systemic treatment, in particular of immunotherapy [1, 2, 4, 11, 12, 30–32].…”