Treatment Outcome of the Brain Metastases in Peri-Rolandic Area: Comparison Between Surgery and Stereotactic Radiosurgery.

BACKGROUND: Brain metastases of peri-Rolandic area is crucial as it directly impacts the quality of life for cancer patients. Surgery or stereotactic radiosurgery (SRS) is considered for peri-Rolandic brain metastases as for other brain metastases. However, the benefit of each treatment modality on functional outcome has not been clearly defined for this tumor. The purpose of this study is to compare the functional course of each treatment and to suggest an effective treatment for patients' quality of life. METHODS: Fifty-two patients who had undergone SRS or surgery for brain metastasis confirmed by enhanced MRI were enrolled retrospectively. Overall survival (OS), progression free survival (PFS), and functional outcomes were estimated using the Kaplan-Meier method, univariate, multivariate analysis, and Cox proportional hazards regression. RESULTS: Median OS and PFS were 13.3 months and 8.9 months in our study population. Treatment modalities were not significant factors for OS and PFS. Extracranial systemic cancer progression was significant factor for both parameters (p=0.030 for OS and p=0.040 for PFS). Median symptom improvement (improvement of at least 1 grade after surgery compared to preoperative state) time was significantly shorter in surgery group than in the SRS group (10.5 days vs. 37.5 days, p=0.034). CONCLUSION: Surgery for brain metastases can contribute to a positive quality of life for the remaining duration of the patient's life.

Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.

BACKGROUND: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. METHODS: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). RESULTS: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). CONCLUSION: GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

The therapeutic effects on U87 and SAS cells using Proton Linac based Boron Neutron Capture Therapy in Korea.

A proton linac based boron neutron capture therapy system (A-BNCT, 10MeV, 4mA) was successfully developed in Korea. We performed in vitro experiments with U87 and SAS cells and revealed the efficacy of a binary therapy BNCT using epithermal neutrons and boronophenylalanine (BPA). The results revealed that BNCT showed cancer cell selectivity and caused cell death. Further in vitro studies can be a valuable method to characterize an A-BNCT system. We expect BNCT to become a treatment option for cancer patients.

Preliminary Study on Natural Killer Cell Activity for Interferon-Gamma Production after Gamma Knife Radiosurgery for Brain Tumors.

OBJECTIVE: High-dose radiation is well known to induce and modulate the immune system. This study was performed to evaluate the correlation between clinical outcomes and changes in natural killer cell activity (NKA) after Gamma Knife Radiosurgery (GKS) in patients with brain cancer. METHODS: We performed an open-label, prospective, cross-sectional study of 38 patients who were treated with GKS for brain tumors, including metastatic and benign brain tumors. All of the patients underwent GKS, and blood samples were collected before and after GKS. NKA was measured using an enzyme-linked immunosorbent assay kit, to measure interferon-gamma (IFNγ) secreted by ex vivo-stimulated NK cells from whole blood. We explored the correlations between NK cell-produced IFNγ (NKA-IFNγ) levels and clinical parameters of patients who were treated with GKS for brain tumors. RESULTS: NKA-IFNγ levels were decreased in metastatic brain tumor patients compared to those with benign brain tumors (p<0.0001). All the patients who used steroid treatment to reduce brain swelling after GKS had an NKA-IFNγ level of zero except one patient. High NKA-IFNγ levels were not associated with a rapid decrease in brain metastasis and did not increase after GKS. CONCLUSION: The activity of NK cells in metastatic brain tumors decreased more than that in benign brain tumors after GKS.

Long-Term Outcomes of Bilateral Subthalamic Nucleus Deep Brain Stimulation for Patients With Parkinson's Disease: 10 Years and Beyond.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents an effective treatment for severe Parkinson's disease (PD), but little is known about the long-term benefit. OBJECTIVE: To investigate the survival rate and long-term outcome of DBS. METHODS: We investigated all 81 patients including 37 males and 44 females who underwent bilateral STN DBS from March 2005 to March 2008 at a single institution. The current survival status of the patients was investigated. Preoperative and postoperative follow-up assessments were analyzed. RESULTS: The mean age at the time of surgery was 62 (range 27-82) years, and the median clinical follow-up duration was 145 months. Thirty-five patients (43%) died during the follow-up period. The mean duration from DBS surgery to death was 110.46 ± 40.8 (range 0-155) months. The cumulative survival rate is as follows: 98.8 ± 1.2% (1 year), 95.1 ± 2.4% (5 years), and 79.0 ± 4.5% (10 years). Of the 81 patients, 33 (40%) were ambulatory up to more than 11 years. The Unified Parkinson's Disease Rating Scale (UPDRS) score was significantly improved until 5 years after surgery although it showed a tendency to increase again after 10 years. The patient group with both electrodes located within the STN showed a higher rate of survival and maintained ambulation. CONCLUSION: STN DBS is a safe and effective treatment for patients with advanced PD. This study based on the long-term follow-up of large patient populations can be used to elucidate the long-term fate of patients who underwent bilateral STN DBS for PD.

Radiotherapy for brain metastasis and long-term survival.

Patients with brain metastases (BM) can benefit from radiotherapy (RT), although the long-term benefits of RT remain unclear. We searched a Korean national health insurance claims database and identified 135,740 patients with newly diagnosed BM during 2002-2017. Propensity score matching (PSM) was used to evaluate survival according to RT modality, which included whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS). The 84,986 eligible patients were followed for a median interval of 6.6 months, and 37,046 patients underwent RT (43.6%). After the PSM, patients who underwent RT had significantly better overall survival after 1 year (42.4% vs. 35.3%, P < 0.001), although there was no significant difference at 2.6 years, and patients who did not undergo RT had better survival after 5 years. Among patients with BM from lung cancer, RT was also associated with a survival difference after 1 year (57.3% vs. 32.8%, P < 0.001) and a median survival increase of 3.7 months. The 1-year overall survival rate was significantly better for SRS than for WBRT (46.4% vs. 38.8%, P < 0.001). Among Korean patients with BM, especially patients with primary lung cancer, RT improved the short-term survival rate, and SRS appears to be more useful than WBRT in this setting.

Long-term Outcome of Microscopic Transsphenoidal Surgery for Prolactinomas as an Alternative to Dopamine Agonists.

BACKGROUND: Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy. METHODS: In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA). RESULTS: The median age and median follow-up period were 31 (16-73) years and 139.1 (12.2-319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality. CONCLUSION: TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.

Clinical outcome prediction from analysis of microelectrode recordings using deep learning in subthalamic deep brain stimulation for Parkinson`s disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for improving the motor symptoms of advanced Parkinson's disease (PD). Accurate positioning of the stimulation electrodes is necessary for better clinical outcomes. OBJECTIVE: We applied deep learning techniques to microelectrode recording (MER) signals to better predict motor function improvement, represented by the UPDRS part III scores, after bilateral STN DBS in patients with advanced PD. If we find the optimal stimulation point with MER by deep learning, we can improve the clinical outcome of STN DBS even under restrictions such as general anesthesia or non-cooperation of the patients. METHODS: In total, 696 4-second left-side MER segments from 34 patients with advanced PD who underwent bilateral STN DBS surgery under general anesthesia were included. We transformed the original signal into three wavelets of 1-50 Hz, 50-500 Hz, and 500-5,000 Hz. The wavelet-transformed MER was used for input data of the deep learning. The patients were divided into two groups, good response and moderate response groups, according to DBS on to off ratio of UPDRS part III score for the off-medication state, 6 months postoperatively. The ratio were used for output data in deep learning. The Visual Geometry Group (VGG)-16 model with a multitask learning algorithm was used to estimate the bilateral effect of DBS. Different ratios of the loss function in the task-specific layer were applied considering that DBS affects both sides differently. RESULTS: When we divided the MER signals according to the frequency, the maximal accuracy was higher in the 50-500 Hz group than in the 1-50 Hz and 500-5,000 Hz groups. In addition, when the multitask learning method was applied, the stability of the model was improved in comparison with single task learning. The maximal accuracy (80.21%) occurred when the right-to-left loss ratio was 5:1 or 6:1. The area under the curve (AUC) was 0.88 in the receiver operating characteristic (ROC) curve. CONCLUSION: Clinical improvements in PD patients who underwent bilateral STN DBS could be predicted based on a multitask deep learning-based MER analysis.

Ameliorating effect of CpG-ODN (oligodeoxynucleotide) against radiation-induced lung injury in mice.

While radiation-induced lung injury (RILI) is known to be progressed by Th2 skewed, pro-inflammatory immune response, there have been few therapeutic attempts through Th1 immune modulation. We investigated whether the immunostimulant CpG-oligodeoxynucleotide (CpG-ODN) would be effective against RILI by way of measuring reactive oxygen species (ROS) and nitric oxides (NO), histopathology, micro-three-dimensional computer tomography (CT), and cytokine profiling. We found that KSK CpG-ODN (K-CpG) significantly reduced histopathological fibrosis when compared to the positive control (PC) group (p < 0.01). The levels of ROS production in serum and splenocyte of PC group were significantly higher than that of K-CpG group (p < 0.01). The production of nitric oxide (NO) in CpG-ODNs group was higher than that of PC group. Last, cytokine profiling illustrated that the protein concentrations of Th1-type cytokines such as IL-12 and TNF-α as well as Th2-type cytokine IL-5 in K-CpG group inclined to be significantly (p < 0.001 or p < 0.01) higher than those of in PC group. Collectively, our study clearly indicates that K-CpG is effective against RILI in mice by modulating the innate immune response. To our knowledge, this is the first note on anti-RILI effect of human type, K-CpG, clinically implying the potential of immunotherapy for RILI control.

Bilateral Subthalamic Nucleus Deep Brain Stimulation under General Anesthesia: Literature Review and Single Center Experience.

Bilateral subthalamic nucleus (STN) Deep brain stimulation (DBS) is a well-established treatment in patients with Parkinson's disease (PD). Traditionally, STN DBS for PD is performed by using microelectrode recording (MER) and/or intraoperative macrostimulation under local anesthesia (LA). However, many patients cannot tolerate the long operation time under LA without medication. In addition, it cannot be even be performed on PD patients with poor physical and neurological condition. Recently, it has been reported that STN DBS under general anesthesia (GA) can be successfully performed due to the feasible MER under GA, as well as the technical advancement in direct targeting and intraoperative imaging. The authors reviewed the previously published literature on STN DBS under GA using intraoperative imaging and MER, focused on discussing the technique, clinical outcome, and the complication, as well as introducing our single-center experience. Based on the reports of previously published studies and ours, GA did not interfere with the MER signal from STN. STN DBS under GA without intraoperative stimulation shows similar or better clinical outcome without any additional complication compared to STN DBS under LA. Long-term follow-up with a large number of the patients would be necessary to validate the safety and efficacy of STN DBS under GA.

Single-Session versus Multisession Gamma Knife Radiosurgery for Large Brain Metastases from Non-Small Cell Lung Cancer: A Retrospective Analysis.

PURPOSE: To evaluate the efficacy of Gamma Knife radiosurgery (GKS) in patients with large brain metastases by comparing single-session radiosurgery (S-GKS) and multisession radiosurgery (M-GKS), we retrospectively analyzed the clinical outcomes of patients who underwent GKS for brain metastases from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between January 2010 and December 2016, 66 patients with 74 lesions ≥10 cm3 from large brain metastases from only NSCLC were included. Fifty-five patients with 60 lesions were treated with S-GKS; 11 patients with 14 lesions were treated with M-GKS. Median doses were 16 Gy (range, 11-18 Gy) for the S-GKS group and 8 Gy (range, 7-10 Gy) in three fractions for the M-GKS group. RESULTS: With a mean follow-up period of 13.1 months (range, 1.3-76.4 months), the median survival duration was 21.1 months for all patients. Median tumor volume was 14.3 cm3 (range, 10.0-58.3 cm3). The local control rate was 77.0% and the progression-free survival rate was 73.6% at the last follow-up. There were no significant between-group differences in terms of local control rate (p = 0.10). Compared with S-GKS, M-GKS did not differ significantly in radiation-induced complications (38.1 vs. 45.4%, p =0.83). While 8 patients who underwent S-GKS experienced major complications of grade ≥3, no toxicity was observed in patients treated with M-GKS. CONCLUSIONS: M-GKS may be an effective alternative for large brain metastases from 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.

Long-Term Outcome of Gamma Knife Radiosurgery for Symptomatic Brainstem Cavernous Malformation.

OBJECTIVE: We sought to analyze the long-term outcome of Gamma Knife radiosurgery (GKS) for symptomatic brainstem cavernous malformation (s-BSCM). METHODS: Forty-five patients (14 males, 31 females) were treated with GKS for s-BSCM from January 1998 to December 2011. All patients were followed up for >5 years, and their clinical data were analyzed retrospectively. All patients had a history of symptomatic bleeding once or more before GKS. These hemorrhages caused neurologic deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, or chorea. The mean target volume of s-BSCM was 1.82 cm3, and the median prescribed marginal dose of radiation was 13 Gy. The mean clinical and imaging follow-up period was 9.31 years (range 5.1-19.4 years). RESULTS: The 45 patients had 69 hemorrhagic events before GKS. During the follow-up period after GKS, 35 patients had no hemorrhagic event, 6 patients had 1 episode of symptomatic hemorrhage, and 4 patients had 2 episodes. The calculated annual hemorrhage rate was 40.06% at pre-GKS, 3.3% at 2 years after GKS, 1.48% at 5 years after GKS, and 4.64% at >5 years after GKS. In this study of 45 patients, symptomatic radiation-induced complications developed in only 1 patient (2.2%). No patients had died at the last follow-up. CONCLUSIONS: GKS for s-BSCM is a safe and effective alternative to surgical resection for reducing the rate of recurrent hemorrhage. Because the annual hemorrhage rate increases >5 years after GKS, clinicians should monitor patients closely to determine their subsequent treatment.

Modified Supraorbital Keyhole Approach to Anterior Circulation Aneurysms.

OBJECTIVE: To select a surgical approach for aneurysm clipping by comparing 2 approaches. MATERIALS AND METHODS: 204 patients diagnosed with subarachnoid hemorrhage treated by the same neurosurgeon at a single institution from November 2011 to October 2013, 109 underwent surgical clipping. Among these, 40 patients with Hunt and Hess or Fisher grades 2 or lower were selected. Patients were assigned to Group 1 (supraorbital keyhole approach) or Group 2 (modified supraorbital approach). The prognosis according to the difference between the two surgical approaches was retrospectively compared. RESULTS: Supraorbital keyhole approach (Group 1) was performed in 20 aneurysms (50%) and modified supraorbital approach (Group 2) was used in 20 aneurysms. Baseline characteristics of patients did not differ significantly between two groups. Total operative time (p = 0.226), early ambulation time (p = 0.755), length of hospital stay (p = 0.784), Glasgow Coma Scale at discharge (p = 0.325), and Glasgow Outcome Scale scores (p = 0.427) did not show statistically significant differences. The amount of intraoperative hemorrhage was significantly lower in the supraorbital keyhole approach (p < 0.05). CONCLUSION: The present series demonstrates the safety and feasibility of the two minimal invasive surgical techniques for clipping the intracranial aneurysms. The modified supraorbital keyhole approach was associated with more hemorrhage than the previous supraorbital keyhole approach, but did not exhibit differences in clinical results, and provided a better surgical view and convenience for surgeons in patients with Hunt and Hess or Fisher grades 2 or lower.

Implication of immunokine profiling for cancer staging.

Tumor may arise from the dysregulation of immune system, which plays pivotal roles in counteracting tumor colonization, late-stage tumors, and metastases. In the midst of the establishment of cancer in vivo, immune cells are activated to release a multitude of immunokines, such as cytokines, and chemokines. Thus, since cytokine levels in tumor bearing host would be differential among local (intratumoral lesion, peritumoral normal tissue), and systemic sample site (serum), these differences might be significantly correlated to prognosis and treatment outcome for cancer patients. Previously, despite small number of patients, we demonstrated the feasibility of this proposition via only cytokine profiling. Based on this, herein we propose that immunokine profiling would be used as a surrogate, predictive tool for cancer staging, and progression.

Influence of different boost techniques on radiation dose to the left anterior descending coronary artery.

PURPOSE: The purpose of this study is to compare the dosimetry of electron beam (EB) plans and three-dimensional helical tomotherapy (3DHT) plans for the patients with left-sided breast cancer, who underwent breast conserving surgery. MATERIALS AND METHODS: We selected total of 15 patients based on the location of tumor, as following subsite: subareolar, upper outer, upper inner, lower lateral, and lower medial quadrants. The clinical target volume (CTV) was defined as the area of architectural distortion surrounded by surgical clip plus 1 cm margin. The conformity index (CI), homogeneity index (HI), quality of coverage (QC) and dose-volume parameters for the CTV, and organ at risk (OAR) were calculated. The following treatment techniques were assessed: single conformal EB plans; 3DHT plans with directional block of left anterior descending artery (LAD); and 3DHT plans with complete block of LAD. RESULTS: 3DHT plans, regardless of type of LAD block, showed significantly better CI, HI, and QC for the CTVs, compared with the EB plans. However, 3DHT plans showed increase in the V1Gy at skin, left lung, and left breast. In terms of LAD, 3DHT plans with complete block of LAD showed extremely low dose, while dose increase in other OARs were observed, when compared with other plans. EB plans showed the worst conformity at upper outer quadrants of tumor bed site. CONCLUSION: 3DHT plans offer more favorable dose distributions to LAD, as well as improved target coverage in comparison with EB plans.