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Page 2 of 12 Kirakli et al. J Cancer Metastasis Treat 2019;5:10 I http://dx.doi.org/10.20517/2394-4722.2018.73

INTRODUCTION
Brain metastases are the most frequent malign brain tumors. Lung cancer is the leading primary tumor
[1,2]
composing 40%-50% of cases . In non-small cell lung cancer (NSCLC) brain metastases risk at the time
of diagnosis is 15%-20%, even the risk increases to 50%-60% during their course of disease in patients with
[3,4]
epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) rearrangement .
Incidence of brain metastases has increased in recent years as a result of detection of smaller asymptomatic
lesions with MRI screening as well as improved survival as a consequence of developments in systemic
therapies. In addition to these, improvements in imaging technology, surgery, radiotherapy, targeted
therapies, even immunotherapy and deep understanding of treatment related toxicities have resulted in
[5,6]
evolvement of current trends in management of brain metastases .
[7,8]
Althoughbrain metastases is an indicator of poor outcome , it’s shown that a subgroup might have longer
[4,9]
survival, e.g., EGFR mutated and ALK rearranged NSCLC . In this context, to assist the selection of
personalized therapy several prognostic indices have been developed; e.g., recursive partitioning analysis,
diagnosis-spesific graded prognostic assessment (DS-GPA) and more recently graded prognostic assessment
for lung cancer using molecular markers (Lung-mol GPA) [10-12] . Optimal treatment planning should consider
both patient (age, performance status, expected life span) and tumor related factors (number and volume of
brain metastases, extracranial disease control, molecular subtype).

Historically, whole brain radiotherapy (WBRT) or best supportive care were the only treatment modalities
for patients with brain metastases. The aim of WBRT was to treat both microscopic and macroscopic
metastases. But treatment to whole brain parenchyme reduces distant in-brain recurrences with the cost of
[6]
cognitive toxicity . In the last decade, there have been many trials in management of NSCLC patients with
brain metastases, questioning the role of adjuvant 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 metastasis, postsurgical cavity SRS, SRS in non-oligometastatic patients, cranial radiotherapy
in patients with driver mutations, TKI, immune check point inhibitors and the impact of therapies on
neurocognitive functions (NCF) and quality of life (QOL).

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.

Solitary metastasis: WBRT vs. WBRT plus surgery
[13]
Until Patchell et al. randomized trial of surgical resection followed by WBRT vs. WBRT only in patients
with solitary brain metastasis, WBRT was the standard treatment. The findings of increased median suvival
(10 months vs. 4-6 months), decreased brain recurrences (20% vs. 52%), increased functional independence
and lower risk of neurological deaths with surgery in conjunction to WBRT, lead to increased role of
aggressive local therapies in selected patients with solitary and oligo brain metastases [14-17] .

Solitary metastasis: adjuvant WBRT plus surgery vs. surgery only
The success of aggressive local treatment and fear of long-term neurologic toxicity led the authors to question
[18]
the role of adjuvant WBRT in oligometastatic patients. Patchell et al. randomized the patients with solitary
brain matastasis after surgery to WBRT or observation. Postoperative WBRT reduced both local and distant
brain failure rates significantly compared to observation arm (10% vs. 46%, P < 0.001), (14% vs. 37%, P < 0.01),
respectively. Neurologic death rate was 3 times higher in the observation arm. But overall survival (OS) and
[18]
survival with functional independence were the same .