Small-cell lung cancer (SCLC) has a high propensity to metastasize into the brain. Radiotherapy plays a major role in the treatment of brain metastases (BM) from SCLC. Whole-brain radiotherapy (WBRT) is the standard treatment of BM from SCLC. However, the neurocognitive toxicity and modest efficacy of this approach have led to the increased use of stereotactic radiosurgery. We have no strong evidence for the use of different forms of radiation (WBRT vs. radiosurgery) in SCLC, because BM from this primary tumor were excluded from clinical trials. In this review, the use of radiation in form of WBRT or radiosurgery is discussed in distinct clinical indications: as a primary treatment and at relapse; without prior use of prophylactic cranial irradiation (PCI); and after PCI. Combinations of radiotherapy with chemotherapy are discussed as BM in SCLC occur rarely as a sole event.

Brain metastasis are the most common intracranial malignancy in the adult population. Their incidence has increased dramatically over the last 20 years, as a result of the increasing number of cases stemming from lung and breast cancer together with the higher cancer survival rates due to diagnostic and therapeutic advances. More than 40% of cancer patients develop brain metastases during the course of their disease: specifically, they appear in 50% of patients with lung cancer, more than 25% of patients with breast cancer, and 20% of patients with melanoma. Diagnosis is made using different imaging approaches, such as computed tomography and magnetic resonance imaging, accompanied by clinical manifestations and a history of malignancy supporting the diagnosis of a brain metastasis. Current treatment options should be oriented to the patient’s current performance, the number of intracranial and extracranial lesions, and related factors. Although surgical resection and whole-brain radiotherapy have been standard treatments for many years, numerous treatment modalities have become more easily available and accepted worldwide, producing more favorable and reliable results. Among these is stereotactic radiosurgery, and the latest clinical trials support this treatment.

Aim: Volumetric modulated arc therapy (VMAT) has been utilized to plan and treat multiple cranial metastases using a single isocenter due to its ability to provide steep dose gradients around targets as well as low doses to critical structures. VMAT treatment is delivered in a much shorter time compared to using a single isocenter for the treatment of each lesion. However, there is a need to develop methods to reduce the treatment planning time for these cases while also standardizing the plan quality. In this work we demonstrate the use of RapidPlan, which is knowledge-based treatment (KBP) planning software to plan multiple cranial SRS cases.

Methods: The 66 patient plans with 125 lesions (range 1-4, median 1) were used to train a model. In addition, the model was validated using 10 cases that were previously treated and chosen randomly. The clinical plans were compared to plans generated by RapidPlan for target coverage and critical organ dose.

Results: Coverage to the target volume, gradient index, conformity index and minimum dose to the target showed no significant difference between the original clinical plan vs. the plan generated by KBP. A comparison of doses to the critical organs namely the brainstem, brain, chiasm, eyes, optic nerves and lenses showed no significant difference. Target dose homogeneity was slightly better with the clinical plan, however this difference was also statistically insignificant.

Conclusion: This work demonstrates that KBP can be trained and efficiently utilized to help not only speed up the planning process but also help standardize the treatment plan quality.

The emergence of novel systemic therapies has spurred a dramatic paradigm shift in lung cancer treatment. Research has revealed greater intracranial efficacy in targeted agents and immune checkpoint inhibitors (ICI) compared to conventional chemotherapy. Concurrently, advances in stereotactic radiosurgery (SRS) have contributed to the increased use of this highly localized, minimally-invasive treatment modality for local tumor control. In this era of precision medicine, the combination of these novel agents and SRS demands further prospective exploration - particularly as questions regarding their sequence of administration and the risk of neurotoxicity remain unanswered. Presently, although data are limited and largely retrospective, literature supports the concurrent administration of ICI and radiation, with no observed increases in immune-related adverse events or acute neurologic toxicities. In the case of patients with driver mutations, newer generations of tyrosine kinase inhibitors (TKI) display improved intracranial efficacy and are currently preferred alone upfront in patients with asymptomatic brain metastases (BM) due to lack of data. Evidence of combining TKI and SRS is limited with mixed results. In this review, we explore the evidence regarding the use of novel systemic agents and SRS for treatment of lung cancer BM. Clinical practice will continue to be refined as larger, prospective studies yield results.

Brain metastases risk at the time of diagnosis or during the course of disease is high in non-small cell lung cancer (NSCLC). Even the incidence of brain metastases has increased in recent years, due to detection of smaller asymptomatic lesions with MRI screening as well as improved survival as a consequence of developments in systemic therapies. In the last decade, there have been many trials in the management of NSCLC patients with brain metastases, questioning the role of adjuvant whole brain radiotherapy (WBRT) after surgery or stereotactic radiosurgery (SRS), WBRT, compared to best supportive care in patients not amenable to surgery, aggressive local therapies in solitary brain metastases, postsurgical cavity SRS, SRS in non-oligometastatic patients, cranial radiotherapy in patients with driver mutations, thyrosine kinase inhibitors, immune check point inhibitors and the impact of therapies on neurocognitive functions and quality of life. The main objective of this review is to provide an update on current trends in radiotherapy in the management of newly diagnosed brain metastases from NSCLC.

One strategy to reduce neurocognitive deterioration in patients after brain irradiation is the use of neuroprotective medication. To generate up-to date knowledge regarding neuroprotective agents we performed a systematic review on the clinical effectiveness of three agents that were reported to have neuroprotective characteristics: memantine, methylphenidate and donepezil. The use of memantine after brain irradiation showed a delay in cognitive deterioration, although at 24 weeks this did not reach significance (P = 0.059). Lack of significance is likely to be the result of the limited statistical power of 35% and memantine did show significant differences in secondary outcomes. The study on methylphenidate was not conclusive. Donepezil revealed significant differences in a few cognitive tests however no difference in global cognition was found. In addition, larger effects were observed in individuals with greater cognitive dysfunction prior to treatment.