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Taek-Kyun Nam, Jung-Il Lee, Young-Jo Jung, Yong-Seok Im, Hee-Ye An, Do-Hyun Nam, Kwan Park and Jong-Hyun Kim

Object. This study was performed to evaluate the role of gamma knife surgery (GKS) in patients with a large number (four or more) of metastatic brain lesions.

Methods. The authors retrospectively reviewed the outcome in 130 patients who underwent GKS for metastatic lesions. Eighty-four patients presented with one to three lesions (Group A) and 46 presented with four or more lesions (Group B). The overall median survival time after GKS was 35 weeks. The median survival time in Group A (48 weeks) was significantly longer (p = 0.005) than the survival time in Group B (26 weeks). The recursive partitioning analysis (RPA) class was the only significant prognostic factor identified in multivariate analysis. The median survival for patients in RPA Classes I, II, and III was 72, 48, and 19 weeks, respectively, in Group A and 36 and 13 weeks for Classes II and III in Group B. The number of lesions, tumor volume, whole brain radiotherapy, primary tumor site, age, and sex did not affect survival significantly.

Conclusions. It is suggested that GKS provides an increase in survival time even in patients with a large number (four or more) of metastatic lesions. Concerning the selection of patients for GKS, RPA class should be considered as the most important factor and multiplicity of the lesions alone should not be a reason for withholding GKS.

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Doo-Sik Kong, Do-Hyun Nam, Jung-Il Lee, Kwan Park and Jong Hyun Kim

Object

The authors conducted a retrospective study to evaluate the efficacy of Gamma Knife surgery (GKS) followed by radiotherapy for the treatment of unresectable glioblastomas multiforme (GBMs) on patient survival and quality of life.

Methods

A total of 19 patients with unresectable GBMs located in eloquent areas of the brain were eligible for this study. Beginning in January 2002, 10 patients underwent GKS followed by fractionated radiotherapy. Nine patients who had undergone radiotherapy alone after biopsy-proven diagnosis served as the control group. The mean patient ages were 53 years and 56 years, respectively. Preoperative Karnofsky Performance Scale (KPS) scores were 80 (range 60–100) and 90 (range 50–100), respectively. The median margin dose for GKS was 12 Gy (9–16 Gy), and the total dose for radiotherapy was 60 Gy in 30 fractions. The mean follow-up duration was 7.2 months, the median patient survival time was 52 weeks (95% confidence interval [CI] 22–110.6 weeks) in the GKS group, and the median overall survival time was 28 weeks (95% CI 22.5–33.5 weeks) in the control group. The difference was not statistically significant (p = 0.0758). The estimated progression-free survival rate at 3 months was 75% in the GKS group and 45% in the control group (p = 0.082). The posttreatment KPS scores were either unchanged or improved in the GKS group, whereas it deteriorated by 20 or more points in six of nine patients of the control group (p = 0.004).

Conclusions

Gamma Knife surgery prior to radiotherapy may be helpful in preserving patients' daily activities in the adjuvant management of unresectable GBM.

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Byung Sup Kim, Yuil Kim, Doo-Sik Kong, Do-Hyun Nam, Jung-Il Lee, Yeon-Lim Suh and Ho Jun Seol

OBJECTIVE

The authors conducted this retrospective study to investigate the clinical outcomes of intracranial solitary fibrous tumor (SFT) and hemangiopericytoma (HPC), defined according to the 2016 WHO classification of central nervous system (CNS) tumors.

METHODS

Histopathologically proven intracranial SFT and HPC cases treated in the period from June 1996 to September 2014 were retrospectively reviewed and analyzed. Two neuropathologists reviewed pathological slides and regraded the specimens according to the 2016 WHO classification. Factors associated with progression-free survival (PFS) and overall survival (OS) were statistically evaluated with uni- and multivariate analyses.

RESULTS

The records of 47 patients—10 with SFT, 33 with HPC, and 4 with anaplastic HPC—were reviewed. A malignant transition from conventional SFT to WHO grade III SFT/HPC was observed in 2 cases, and 13 HPC cases were assigned grade III SFT/HPC. Mean and median follow-ups were 114.6 and 94.7 months, respectively (range 7.1–366.7 months). Gross-total resection (GTR) was significantly associated with longer PFS and OS (p = 0.012 for both), and adjuvant radiation therapy versus no such therapy led to significantly longer PFS (p = 0.018). Extracranial metastases to the liver, bone, lung, spine, and kidney occurred in 10 patients (21.3%). Grade III SFT/HPC was strongly correlated with the development of extracranial metastases (p = 0.031).

CONCLUSIONS

The 2016 WHO classification of CNS tumors reflected the different types of pathological malignant progression and clinical outcomes better than prior classifications. Gross-total resection should be the primary treatment goal in patients with SFT/HPC, regardless of the pathological grade, and radiation can be administered as adjuvant therapy for patients with SFT/HPC that shows an aggressive phenotype or that is not treated with GTR.

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Chiman Jeon, Kyung Rae Cho, Jung Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

This study was performed to evaluate the role of Gamma Knife radiosurgery (GKRS) as a primary treatment for central neurocytomas (CNs).

METHODS

The authors retrospectively assessed the treatment outcomes of patients who had undergone primary treatment with GKRS for CNs in the period between December 2001 and December 2018. The diagnosis of CN was based on findings on neuroimaging studies. The electronic medical records were retrospectively reviewed for additional relevant preoperative data, and clinical follow-up data had been obtained during office evaluations of the treated patients. All radiographic data were reviewed by a dedicated neuroradiologist.

RESULTS

Fourteen patients were treated with GKRS as a primary treatment for CNs in the study period. Seven patients (50.0%) were asymptomatic at initial presentation, and 7 (50.0%) presented with headache. Ten patients (71.4%) were treated with GKRS after the diagnosis of CN based on characteristic MRI findings. Four patients (28.6%) initially underwent either stereotactic or endoscopic biopsy before GKRS. The median tumor volume was 3.9 cm3 (range 0.46–18.1 cm3). The median prescription dose delivered to the tumor margin was 15 Gy (range 5.5–18 Gy). The median maximum dose was 30 Gy (range 11–36 Gy). Two patients were treated with fractionated GKRS, one with a prescription dose of 21 Gy in 3 fractions and another with a dose of 22 Gy in 4 fractions. Control of tumor growth was achieved in all 14 patients. The median volume reduction was 26.4% (range 0%–78.3%). Transient adverse radiation effects were observed in 2 patients but resolved with improvement in symptoms. No recurrences were revealed during the follow-up period, which was a median of 25 months (range 12–89 months).

CONCLUSIONS

Primary GKRS for CNs resulted in excellent tumor control rates without recurrences. These results suggest that GKRS may be a viable treatment option for patients with small- to medium-sized or incidental CNs.

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Kyung Hwan Kim, So Jeong Kang, Jung-Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

This study aimed to verify the effect of proactive Gamma Knife surgery (GKS) in the treatment of asymptomatic meningioma compared with the natural course without any therapeutic intervention.

METHODS

From January 2006 to May 2017, 354 patients newly diagnosed with asymptomatic meningioma were reviewed and categorized into GKS (n = 153) and observation (n = 201) groups. Clinical and radiological progression rates were examined, and changes in volume were analyzed.

RESULTS

Clinical progression (i.e., clinician-judged progression), combining symptomatic progression (n = 43) and clinician-judged increase in size using images routinely acquired (n = 34), occurred in 4 patients (2.6%) and 73 patients (36.3%) in the GKS and observation groups, respectively (p < 0.001). The clinical progression-free survival (PFS) rates in the GKS and observation groups were 98.7% and 64.6%, respectively, at 5 years (p < 0.001), and 92.9% and 42.7%, respectively, at 10 years (p < 0.001). The radiological tumor control rate was 94.1% in the GKS group, and radiological progression was noted in 141 patients (70.1%) in the observation group. The radiological PFS rates in the GKS and observation groups were 94.4% and 38.5%, respectively, at 5 years (p < 0.001), and 88.5% and 7.9%, respectively, at 10 years (p < 0.001). Young age, absence of calcification, peritumoral edema, and high T2 signal intensity were correlated with clinical progression in the observation group. Volumetric analysis showed that untreated tumors gradually increased in size. However, GKS-treated tumors shrank gradually, although transient volume expansion was observed in the first 6 months. Adverse events developed in 26 of the 195 GKS-treated patients (13.3%), including 1 (0.5%) major event requiring microsurgery due to severe edema after GKS. Peritumoral edema was related to the development of adverse events (p = 0.004).

CONCLUSIONS

Asymptomatic meningioma is a benign disease; however, nearly two-thirds of patients experience tumor growth and one-third of untreated patients eventually require neurosurgical interventions during watchful waiting. GKS can control tumors clinically and radiologically with high probability. Although the risk of transient adverse events exists, proactive GKS may be a reasonable treatment option when there are no comorbidities limiting life expectancy.

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Chiman Jeon, Sang Duk Hong, Kyung In Woo, Ho Jun Seol, Do-Hyun Nam, Jung-Il Lee and Doo-Sik Kong

OBJECTIVE

Orbital tumors are often surgically challenging because they require an extensive fronto-temporo-orbital zygomatic approach (FTOZ) and a multidisciplinary team approach to provide the best outcomes. Recently, minimally invasive endoscopic techniques via a transorbital superior eyelid approach (ETOA) or endoscopic endonasal approach (EEA) have been proposed as viable alternatives to transcranial approaches for orbital tumors. In this study, the authors investigated the feasibility of 360° circumferential access to orbital tumors via both ETOA and EEA.

METHODS

Between April 2014 and June 2019, 16 patients with orbital tumors underwent either ETOA or EEA at the authors’ institution. Based on the neuro-topographic “four-zone model” of the orbit with its tumor epicenter around the optic nerve in the coronal plane, ETOA (n = 10, 62.5%) was performed for tumors located predominantly superolateral to the nerve and EEA (n = 6, 37.5%) for those located predominantly inferomedial to the nerve. Eight patients (50%) presented with intraconal tumors and 8 (50%) with extraconal ones. The orbital tumors included orbital schwannoma (n = 6), cavernous hemangioma (n = 2), olfactory groove meningioma (n = 1), sphenoorbital meningioma (n = 1), chondrosarcoma (n = 1), trigeminal schwannoma (n = 1), metastatic osteosarcoma (n = 1), mature cystic teratoma (n = 1), sebaceous carcinoma (n = 1), and ethmoid sinus osteoma (n = 1). The clinical outcomes and details of surgical techniques were reviewed.

RESULTS

Gross-total resection was achieved in 12 patients (75%), near-total resection in 3 (18.8%), and subtotal resection in 1 (6.2%). Eight (88.9%) of the 9 patients with preoperative proptosis showed improvement after surgery, and 4 (66.7%) of the 6 patients with visual symptoms demonstrated improvement. Four (40%) of the 10 patients treated with ETOA experienced partial third nerve palsy immediately after surgery (3 transient and 1 persistent). There have been no postoperative CSF leaks or infections in this series.

CONCLUSIONS

Without transcranial approaches requiring temporalis muscle dissection and orbitozygomatic osteotomy, the selection of ETOA or EEA based on a concept of a four-zone model with its epicenter around the optic nerve successfully provides a minimally invasive 360° circumferential access to the entire orbit with acceptable morbidity.

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Doo-Sik Kong, Do-Hyun Nam, Jung-Il Lee, Kwan Park, Jong Hyun Kim and Hyung Jin Shin

Object

It is important to differentiate growing teratoma syndrome (GTS) from tumor recurrence in the setting of an enlarging residual mass present after treatment of intracranial germ cell tumors (GCTs). The aim of this study was to determine the incidence of intracranial GTS and present its clinical manifestations in detail.

Methods

The authors performed a retrospective cohort study of 52 consecutive patients with newly diagnosed intracranial GCTs who presented between January 2000 and December 2006. The records were screened to identify a study cohort in which all patients had regrowing tumor mass despite normalization of tumor markers during or after treatment of GCTs.

Results

In 6 (11.5%) of 52 patients the pathological diagnosis was GTS. The median patient age at diagnosis was 14.5 years (range 2 months–17 years), and the primary tumors included 4 mixed GCTs and 2 immature teratomas. After second-look surgery, histological testing revealed the lesions to be mature teratoma in all patients. Three of 6 patients subsequently underwent radiation therapy and 1 patient received additional chemotherapy for spinal seeding.

Conclusions

In enlarging residual masses after treatment of intracranial GCTs, GTS should be kept in mind in the differential diagnosis of tumor recurrence especially if there is a radiographic mismatch with serum marker test results. If technically feasible, second-look surgery may be necessary for an accurate diagnosis.

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Jung-Il Lee, Do-Hyun Nam, Jong Soo Kim, Seung-Chyul Hong, Hyung-Jin Shin, Kwan Park, Whan Eoh, Yeon-Lim Suh and Jong Hyun Kim

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Kyung Hwan Kim, Doo-Sik Kong, Kyung Rae Cho, Min Ho Lee, Jung-Won Choi, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM.

METHODS

The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival.

RESULTS

Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5–25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%–29%) in the 9-Gy group, and 37% (95% CI 1%–58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1–51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1–29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups.

CONCLUSIONS

In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

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Kyung-Il Jo, Yong Seok Im, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam, Yoon-Duck Kim and Jung-Il Lee

Object

The goal of this study was to investigate the safety and efficacy of multisession Gamma Knife surgery (GKS) in the treatment of benign orbital tumors.

Methods

Twenty-three patients who retained their vision despite having tumors touching their optic nerve were treated with multisession (4-fraction) GKS. The median tumor volume was 2800 mm3 (range 211–10,800 mm3), and the median cumulative margin dose was 20 Gy (range 18–22 Gy).

Results

The median clinical follow-up duration in these patients was 38 months (range 9–74 months). No patient experienced tumor progression in this study. In particular, a higher degree of tumor shrinkage was found in the 7 patients with cavernous hemangiomas than in patients with other types of lesions (p < 0.05). Of the 23 patients whose preoperative vision was preserved, 11 showed improvement in visual acuity and/or visual field and 12 showed stable visual acuity. No GKS-related adverse events were noted during or after treatment.

Conclusions

Multisession radiosurgery using the Gamma Knife may be a good strategy for tumors in direct contact with the optic nerve. A cumulative margin dose of up to 22 Gy delivered in 4 sessions is safe for preservation of visual function with a high probability of tumor control.