Lung cancer is the most frequent source of metastatic brain tumors. It occurs in 17–65% of patients with primary lung cancer [3, 8]. The rate of lung cancer brain metastasis has been increasing in recent years [3]. According to previously published studies, the prognosis for patients with lung cancer brain metastasis is poor, median OS of lung cancer brain metastasis was reported from 1 to 12 months despite treatment [4–6]. However, there are significant advances in the management of lung cancer, to our study, the median OS was over 12 months.
To prolong the survival and improve the quality of life of lung cancer brain metastasis, neurological symptom and relief intracranial hypertension, the treatment of brain metastasis is critical in patients with lung cancer. Thus, the role of a neurosurgeon is considerably important in the treatment of lung cancer brain metastasis. From the perspective of a neurosurgeon in brain metastasis treatment, decreasing local and distant recurrence with maintaining or improving the life of quality are the most important considerations. Surgery, stereotactic radiosurgery, conventional radiation therapy, and systemic chemotherapy are the possible treatment strategies in brain metastasis. The efficacy of radiosurgery for small-sized oligometastasis has been proved [7]. Moreover, Chon et al. reported the feasibility of fractionated radiosurgery for medium-sized brain metastasis [9]. However, for medium to large tumors, surgical resection is still an essential tool. Moreover, surgery is the only option for large tumors with mass effect, establishing pathological confirmation, progression after radiosurgery, or radiotherapy. Recently, we have performed surgical resection at our institute of not only single metastasis or oligo-metastasis but also multiple metastases. Surgery with adjunctive radiosurgery or radiotherapy were performed to prolong survival or relieving symptoms related to brain metastasis.
In this study, we focused on analyzing predictors for local and distant recurrence of the brain from a neurosurgeon’s perspective. Total resection of metastatic brain tumor was performed for 97% of patients. To reduce local recurrence, “en-bloc”-resection showed a better outcome than “piecemeal resection” [10]. Furthermore, Yoo et al. reported plus 5 mm adjacent white matter resection reduced local recurrence [11]. In our series, we did gross total resection without plus normal tissue resection. Although, all tumors could not be feasible, to reduce local recurrence rate, “en-bloc”-fashion resection plus white matter is pursued for non-eloquent area tumors.
Postoperative radiotherapy and SRS for reducing local recurrence could be applied in the resection cavity. SRS and WBRT showed comparable results for local recurrence in brain metastasis [6, 12] In the previous report, the efficacy of SRS and WBRT are comparable [6, 12, 13]. WBRT has been needed for disseminated metastasis and it harbored a unique role, however, considering the neuro-cognitive complications including learning and memory dysfunction, SRS may be a more suitable tool for resection bed irradiation [14].
Theoretically, resection bed irradiation may provide good local control, but poor distant recurrence control. However, in our series, resection bed radiotherapy and radiosurgery did not affect the local recurrence of both NSCLC and SCLC brain metastasis. Additionally, postoperative WBRT failed to affect the distant recurrence. It implicated adjuvant radiotherapy and radiosurgery may not be mandatory after surgical resection for lung cancer brain metastasis. In the previous studies, only WBRT for brain metastasis impact survival from 1 to 3 months [15, 16]. Applying WBRT for reducing distant recurrence in lung cancer brain metastasis considering its survival benefit and neurocognitive impairment is still debatable. According to our result, WBRT did not improve the PFS for distant recurrence.
At our institute, there was no consensus for applying adjuvant radiotherapy or SRS, it depends on the opinion of individual oncologists. Standard cytotoxic chemotherapy used in lung cancer, mainly platinum agents is not effective for lung cancer brain metastasis owing to poor penetration of the blood-brain barrier [4]. Molecular targeted therapy showed the promising effect of lung cancer-NSCLC brain metastasis [4, 17]. EGFR mutation, ALK rearrangement, and PD-L1 are targetable mutations. They have shown effectiveness in intracranial disease control; moreover, a recent clinical trial reported the promising result of EGFR-targeted therapy for the leptomeningeal disease [18]. However, still, they are not suitable for symptomatic and immediate life-threatening brain metastasis, it could be applied for small metastasis and disseminated disease. At our institute, we have used a molecular targeted agent after surgical resection of metastatic brain tumor according to the status of targetable gene mutation. We evaluated the difference of local recurrence and distant recurrence concerning EGFR, ALK-1, and PD-L1 in the NSCLC group. There was no statistically significant difference in local and distant recurrence. EGFR mutant NSCLC brain metastasis group showed superior OS rate, which may be attributed to extracranial disease control by EGFR-target agent. The efficacy of molecular target agent after brain metastatic tumor resection should be evaluated at the future study.
The maintenance of the quality of life of patients with cancer is an important consideration. Considering the lower chance of cure of disease in patients with lung cancer brain metastasis, the postoperative complication significantly impacting the performance status of patients should be minimized. In recent studies, the eloquent location of metastatic brain tumors could be managed using radiosurgery [7, 9]. Declining of performance status due to postoperative neurological deficits not only restrict further chemotherapy or radiation therapy but also leads to other medical complications, which jeopardize the survival of patients with lung cancer. In our study, the postoperative complication group showed a significantly lower OS rate. We should minimize the postoperative complication in lung cancer brain metastasis surgery, and consider that the complication critically influences survival.
Study limitations and strengths
Our current study had some limitations. In the first instance, it was a retrospective investigation that included 224 patients with lung cancer brain metastasis. Along with the limitations inherent to any retrospective design, this precluded less meaningful multivariate analysis of survival outcomes or predictors of local and distant recurrence. This study series spanned around 10 years; therefore, the treatment methods varied. Additionally, the management strategy of lung cancer brain metastasis was varied according to individual neurosurgeons, which made it challenging to conclude on the optimal intervention strategies and outcomes in these cases.
Our study also had some notable strengths. However, including our finding that the SCLC and postoperative complication groups have a significantly shorter OS than the adjuvant resection bed RT and SRS, usage of targeted therapy after resection may not be a predictive factor for local and distant recurrence in lung cancer brain metastasis. Although we could not draw any meaningful conclusions to assist with future treatment guidelines, our analysis indicates that female sex, SCLC histology, and postoperative complications are prognostic indicators in terms of survival, and require careful consideration to improve survival and maintain the quality of life in metastasis. Therefore, we believe that the data from our current single-center series make a valuable contribution to the available literature on these extremely rare tumors and to a future meta-analysis of this disease.