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Page 2 of 4 Kepka. J Cancer Metastasis Treat 2020;6:12 I http://dx.doi.org/10.20517/2394-4722.2020.35

The optimal management of patients with BM from lung cancer should consider both patient (performance
status, age, comorbidities, cognitive function, patient’s preferences) and tumor (number/volume of BM,
location, molecular subtype, extracranial disease control and systemic treatment available) related factors.
There is always a trade-off between better intracranial control of disease offered by WBRT and better
preservation of cognition with SRS but at the price of poorer intracranial control. This requires a detailed
discussion with the patient and shared decision-making is recommended in such cases. Numerous
strategies have been employed to preserve neurocognition after WBRT such as the use of neuroprotective
medication and/or hippocampal avoidance (HA). Recently, the results of a randomized phase III trial
comparing WBRT (30 Gy in 10 fractions)/memantine/HA to WBRT/memantine in 518 patients with
multiple BM referred for WBRT were published. It was reported that WBRT with HA preserves cognitive
function better after treatment compared to WBRT without HA, with no difference in intracranial control
and overall survival. Thus HA should be a standard approach in all good performance status patients with
[11]
BM undergoing WBRT with no metastases in the HA zone .
This special issue of the Journal of Cancer Metastasis and Treatment aims to summarize the current
knowledge on the treatment of BM from lung cancer with radiation by presenting the available evidence
[12]
and discussing new perspectives and areas of research. The review articles by Kirakli and Yilmaz
and Gutiérrez-Valencia et al. highlight the latest developments and evidence available for the use of
[13]
radiotherapy in BM, and question the role of adjuvant WBRT after surgery or SRS. The issue of extending
the use of SRS for more than 3-4 BM is also discussed, as we do not have evidence that directly compares
such an approach to WBRT.

[14]
The planning and delivery of radiotherapy to multiple BM is a complex issue. Dumane et al. present their
experience with the use of knowledge-based planning, which is a new approach to treatment planning and
this may lead to a fully automated planning process. Knowledge-based planning utilizes dose distributions
from prior treatment plans to build a model that can predict the same for new patients. The authors then
demonstrated that such an approach might be used efficiently for the complex planning involved in the use
of volumetric modulated arc therapy to treat multiple BM using a single isocenter.

A comprehensive review by Mudra et al. provides the evidence regarding the use of novel systemic
[15]
agents in combination with SRS for the management of BM from lung cancer. Limited evidence is available
however, on the use of systemic therapy (targeted therapy, immune checkpoint inhibitors) as firstline
treatment with the omission of radiation and the authors warn that such an approach should be used with
caution and only for very selected patients. On the other hand, the sequence of use of systemic agents and
radiation remains uncertain and is still under investigation.

In SCLC, about 40%-50% of patients will develop BM during the course of their disease. Owing to the
distinct clinical characteristics of BM from SCLC, these patients are usually excluded from prospective
trials on the value of WBRT and local ablative treatments such as surgery or SRS. Instead, WBRT in
combination with chemotherapy has long been a standard approach in the setting of SCLC. However,
data on the neurocognitive toxicity of WBRT, occurrence of BM after earlier use of prophylactic cranial
irradiation, as well as the increasing availability of stereotactic radiotherapy technologies, have all led to the
increasing use of SRS and omission of WBRT in SCLC. Various issues arising from the use of radiation for
[16]
BM from SCLC in numerous clinical scenarios are discussed .
Finally, this issue also contains a systematic review on the clinical effectiveness of neuroprotective agents
given during WBRT: memantine, methylphenidate and donepezil. Some evidence to support the use of
memantine to delay cognitive decline in patients undergoing brain irradiation was demonstrated, although
at 24 weeks this did not reach statistical significance (P = 0.059). Despite fairly large usage of memantine