Non small cell lung cancer intracranial metastases radiosurgery
Multisession radiosurgery (M-GKS) may be an effective alternative for large brain metastases from Non small cell lung cancer (NSCLC). Specifically, severe radiation induced toxicity (≥ grade 3) did not occur in M-GKS for large-volume metastases. Although the long-term effects and results from larger samples remain unclear, M-GKS may be a suitable palliative treatment for preserving neurological function 1).
Traditionally, whole brain radiotherapy (WBRT) has been the cornerstone of Non small cell lung cancer intracranial metastases treatment, but its indication is a matter of debate. A randomized trial has shown that for patients with a poor prognosis, WBRT does not add quality of life (QoL) nor survival over the best supportive care. In recent decades, stereotactic radiosurgery (SRS) has become an attractive non-invasive treatment for patients with BM. Only the BM is irradiated to an ablative dose, sparing healthy brain tissue. Intracranial recurrence rates decrease when WBRT is administered following SRS or resection but does not improve overall survival and comes at the expense of neurocognitive function and QoL. The downside of SRS compared with WBRT is a risk of radionecrosis (RN) and a higher risk of developing new BM during follow-up. Currently, SRS is an established treatment for patients with a maximum of four BM. Several promising strategies are currently being investigated to further improve the indication and outcome of SRS for patients with BM: the effectivity and safety of SRS in patients with more than four BM, combining SRS with systemic therapy such as targeted agents or immunotherapy, shared decision-making with SRS as a treatment option, and individualized isotoxic dose prescription to mitigate the risk of RN and further enhance local control probability of SRS.
The review of Hartgerink et al., discusses the current indications of SRS and future directions of treatment for patients with BM of NSCLC with focus on the value of SRS 2).
Radiosurgery for multiple BMs is controversial, yet patients with EGFR Non small cell lung cancer intracranial metastases and Anaplastic lymphoma kinase non small cell lung cancer may be uniquely suited to benefit from this approach. These results support single and multiple courses of radiosurgery without WBRT for patients with oncogene-addicted NSCLC with four or more BMs 3).
Brain metastases outcome
Overall prognosis depends on age, extent and activity of the systemic disease, number of brain metastases and performance status. In about half of the patients, especially those with widespread and uncontrolled systemic malignancy, death is heavily related to extra-neural lesions, and treatment of cerebral disease doesn’t significantly improve survival.
In such patients the aim is to improve or stabilize the neurological deficit and maintain quality of life. Corticosteroids and whole brain radiotherapy usually fulfill this purpose. By contrast, patients with limited number of brain metastases, good performance status and controlled or limited systemic disease, may benefit from aggressive treatment as both quality of life and survival are primarily related to treatment of brain lesions.
Strong positive prognostic factors include good functional status, age <65 years, no sites of metastasis outside of the central nervous system (CNS), controlled primary tumor 1), the presence of a single metastasis in the brain, long interval from primary diagnosis to brain relapse, and certain cancer subtypes such as HER2 positive breast cancer brain metastasesand EGFR Non small cell lung cancer intracranial metastases (NSCLC) 2) 3) 4)
In a study of the Royal North Shore Hospital, on univariate analysis, number of metastases (P = 0.04), symptomatic extracranial disease (P = 0.04) and early CNS relapse within 6 months (P < 0.01) had worse survival. No grade 3-4 toxicityevents were noted in 129 patients undergoing RT 6).
It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment 7).