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Purpose This study aimed to evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).Materials and Methods A total of 133 patients with histologically confirmed HPC were included from eight institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 patients (64%). The prognostic effects of sex, age, performance, World Health Organization (WHO) grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.Results The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p < 0.001) and PFS (p < 0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001), or STR (p < 0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).Conclusion This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.

Purpose We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.Materials and Methods Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.Results The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.Conclusion De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

PurposeThis study was designed to investigate the incidence of interim disease progression (IPD) and volumetric changes of the surgical cavity (SC) during the surgery-to-radiotherapy interval (SRI), and eventually assess the value of magnetic resonance imaging (MRI) at the time of radiotherapy (RT) planning in newly diagnosed anaplastic gliomas.Materials and MethodsAmong 195 anaplastic glioma patients who underwent RT, 121 were evaluable with two separate MRIs during SRI. The presence of IPD was determined using the updated Response Assessment in Neuro-Oncology size criteria. In 84 patients who underwent surgical resection, each SC was contoured by a radiation oncologist and the volumetric changes of the SCs were calculated between the two separate MRIs. Daily rate of change in the SC volume was calculated assuming an exponential and linear change.ResultsFive of 121 patients (4.13%) demonstrated IPD during SRI, and the incidence was significantly higher in patients undergoing biopsy (vs. surgical resection, 12.9% vs. 1.1%, p=0.015) and in patients with remnant contrast-enhancing tumor after surgery (15.8 vs. 2.0%, p=0.027). The mean daily rate of absolute change in SC was 1.06% (95% confidence interval [CI], 0.89 to 1.23) and 0.89% (95% CI, 0.77 to 1.02) according to the exponential and linear model, respectively. The expected mean volumetric change at 2 weeks were 16.64% (95% CI, 13.77 to 19.52) and 12.51% (95% CI, 10.77 to 14.26), respectively.ConclusionIPD during the SRI is rare in surgically resected anaplastic gliomas. However, pre-RT MRI is essential for accurate RT-target delineation and disease evaluation for patients initiating RT beyond postoperative 2 weeks and undergoing biopsy, respectively.

Purpose This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL). Materials and methods Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years. Results The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years. Conclusion rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.

Purpose To assess the efficacy of upfront chemotherapy followed by response-adapted reduced-dose/reduced-volume radiotherapy (RT) for intracranial germinoma. Materials and methods Ninety-one patients from five institutions were registered in the KSPNO G051/G081 Protocol. Germinomas were classified as solitary or multiple/disseminated diseases, and upfront chemotherapy was administered. For all patients with multiple or disseminated disease, and patients with partial response after chemotherapy, 19.5–24 Gy of craniospinal irradiation plus 10.8–19.8 Gy of tumor bed boost were planned. For patients with complete response (CR), reduced-dose RT (30.6 Gy) was planned, along with a reduced field for solitary lesions. Results The median patient age was 14 (range, 3–30) years. Sixty-five patients (71.4%) had a solitary lesion. The median follow-up duration was 67.9 (range, 6.6–119.3) months. Recurrence was not observed in 32 patients in the protocol compliant group. Four patients (4.4%) in the protocol non-compliant group experienced relapse after CR and one patient died of the disease. The 5-year and 7-year overall survival rates were 98.8% and 98.8%, while the corresponding event-free survival rates were 96.6% and 93.8%, respectively. All three patients with basal ganglia germinomas who were treated with local RT experienced recurrence outside the RT field. Among the 23 patients with pineal or suprasellar lesions who received whole-ventricle RT, there was no recurrence. Conclusions Currently used upfront chemotherapy followed by reduced-dose, reduced-volume RT appears acceptable, when whole-ventricle RT for pineal or suprasellar tumors and, at minimum, whole-brain RT for basal ganglia/thalamus lesions are applied.

Purpose To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. Materials and Methods Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. Results The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). Conclusion PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.

Purpose The purpose of this study was to investigate the effectiveness and safety of spinal stereotactic radiosurgery (SRS) in treating spinal metastasis with epidural spinal cord compression (ESCC). Materials and methods During 2013-2016, 149 regions of spinal metastasis in 105 patients treated with singlefraction (12-24 Gy) spinal SRS were reviewed. Cord compression of Bilsky grade 2 (with visible cerebrospinal fluid [CSF]) or 3 (no visible CSF) was defined as ESCC. Local progression (LP) and vertebral compression fracture (VCF) rates after SRS were evaluated using multivariate competing-risk regression analysis. Results The 1-year cumulative incidences of LP for Bilsky grades 0 (n=80), 1 (n=39), 2 (n=21), and 3 (n=9) were 3.0%, 8.4%, 0%, and 24.9%, respectively. Bilsky grade 2 ESCC did not significantly increase the LP rate (no LP for grade 2). The 1-year cumulative incidences of VCF for Bilsky grades 0, 1, 2, and 3 were 6.6%, 5.2%, 17.1%, and 12.1%, respectively. ESCC may increase VCF risk (subhazard ratio [SHR] for grade 2, 5.368; p=0.035; SHR for grade 3, 2.215; p=0.460). Complete or partial pain response rates after SRS were 79%, 78%, 53%, and 63% for Bilsky grades 0, 1, 2, and 3, respectively (p=0.008). No neurotoxicity of grade ≥ 3 was observed. Conclusion Spinal SRS for spinal metastasis with Bilsky grade 2 ESCC did not increase the LP rate, was not associated with severe neurotoxicity, and showed moderate VCF and pain response rates. Bilsky grade 3 had a high LP rate.

The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 hours post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon-γ signals began to increase significantly at 24 hours and were upregulated until 48 hours after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon-γ signaling in cancer cells. In conclusions, In the glioblastoma cell line, immune-related signals were significantly upregulated at 24 hours after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.

Background Central nervous system germ cell tumors (CNS GCTs) are a heterogeneous group of brain tumors, which are more common in Asian countries. There have been different therapeutic strategies in treating germinoma and non-germinomatous germ cell tumors (NGGCT), depending on prognosis. Moreover, long-term follow up should be emphasized due to higher late complication rates. Here, we investigated long-term outcomes and complication profiles of 127 CNS GCT patients who received uniform upfront chemotherapy. Methods We retrospectively evaluated outcomes of CNS GCT patients treated in Seoul National University Children’s Hospital from August 2004 to April 2019. Patients were classified as low risk (LR) or high risk (HR) based on pathologic diagnosis and tumor markers. Most patients received upfront systemic chemotherapy with carboplatin, cyclophosphamide, etoposide, and/or bleomycin, followed by either proton or photon radiation therapy according to patients’ choice. Results The median age at diagnosis was 11.9 (range, 3.8–25.1) years, and 54.3% of patients were LR. Photon and proton radiation therapy were administered to 73.2 and 25.2% of patients, respectively. In both LR and HR groups, there were no significant differences in survival between photon and proton radiation therapy. The 10-year relapse incidences were 9.3 and 5.6% in the LR and HR groups, respectively. All recurrences, except one, were local relapse. Six secondary malignancies occurred; the 10-year incidences of secondary malignancy were 2.2 and 7.6% in the LR and HR groups, respectively. The 10-year overall survival rates were 98.3 ± 1.7 and 91.8 ± 3.9% in the LR and HR groups, respectively. In a subgroup analysis of HR group, pathologically diagnosed NGGCT patients (n = 20) showed worse 10-year EFS (65.9 ± 11.9%, p p = 0.024) rates compared to other HR patients who were not pathologically diagnosed or were confirmed as germinoma with elevated tumor markers. All mortalities were related to disease progression or secondary malignancy. Conclusion The strategy of treating CNS GCTs with upfront chemotherapy according to risk groups resulted in good clinical outcomes and acceptable relapse incidence. However, further modification in the definition of the HR group is needed to reduce long-term complications.

To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II-III intracranial ependymoma (IEPN).A total of 172 pathologically confirmed adult grade II-III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis.The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P = 0.002), PFS (P = 0.002), and OS (P = 0.043). Older age (P 0.001), WHO grade III (P 0.001), larger tumor size (P = 0.004), and lesser surgical extent (P 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P = 0.010), PFS (P = 0.007), and OS (P = 0.069) on multivariate analysis for grade II IEPNs.This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II-III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.

The optimal radiotherapy regimen in elderly patients with glioblastoma treated by chemoradiation needs to be addressed. We provide the results of a comparison between conventionally fractionated standard radiotherapy (CRT) and short-course radiotherapy (SRT) in those patients treated by temozolomide-based chemoradiation.Patients aged 65 years or older from the GBM-molRPA cohort were included. Patients who were planned for a ≥ 6-week or ≤ 4-week radiotherapy were regarded as being treated by CRT or SRT, respectively. The median RT dose in the CRT and SRT group was 60 Gy in 30 fractions and 45 Gy in 15 fractions, respectively.A total of 260 and 134 patients aged older than 65 and 70 years were identified, respectively. CRT- and SRT-based chemoradiation was applied for 192 (73.8%) and 68 (26.2%) patients, respectively. Compared to SRT, CRT significantly improved MS from 13.2 to 17.6 months and 13.3 to 16.4 months in patients older than 65 years (P 0.001) and 70 years (P = 0.002), respectively. Statistical significance remained after adjusting for age, performance status, surgical extent, and MGMT promoter methylation in both age groups. The benefit was clear in all subgroup analyses for patients with Karnofsky performance score 70-100, Karnofsky performance score ≤ 60, gross total resection, biopsy, methylated MGMT promoter, and unmethylated MGMT promoter (all P 0.05).CRT significantly improved survival compared to SRT in elderly glioblastoma patients treated with chemoradiation in selected patients amenable for chemoradiation. This study is hypothesis-generating and a prospective randomized trial is urgently warranted.

Introduction A majority of high-grade gliomas relapse despite combined surgery, radiotherapy and chemotherapy. There is no consensus on standard treatment for recurrent high-grade gliomas, or defined efficacy of adjuvant re-RT after re-Op. This retrospective study evaluated the benefit and safety of re-RT after re-Op (re-Op/RT). Materials and methods A total of 84 patients with recurrent high-grade gliomas who underwent reoperation from 2009 to 2015 were analyzed. All patients received neurosurgical intervention and adjuvant radiotherapy previously before recurrence. At recurrence and after reoperation, treatment options were discussed in multidisciplinary clinic or brain tumor joint conference. For re-RT, cumulative EQD2 (equivalent dose in 2 Gy fractions at α/β = 2) was below 106.9 Gy. Result Median progression free survival (PFS) was 6.5 months; 3.5 months with re-Op, 9.0 months with re-Op/RT (p = 0.025). Age 50, WHO grade IV, and unmethylated promoter of MGMT) were significantly associated with poor OS in multivariate analysis. Benefit of re-RT in both OS and PFS was established in patients carrying 2 or more risk factors. During re-RT, 4 patients (8%) had grade 2 or higher toxicity, and 3 patients (6%) did not complete re-RT. No radionecrosis was observed. Conclusion Re-RT after re-Op was tolerable with a cumulative median EQD2 of 99.3 Gy and resulted in clear benefit in PFS and marginal gain in OS. Survival gain with re-Op/RT was more prominent in patients with two or more risk factors (age ≥50, WHO pathologic grade IV, unmethylated MGMT promoter), and needs to be validated.

Purpose We investigated the clinical characteristics of patients who developed thyroid dysfunction and evaluated the risk factors for hypothyroidism following radiotherapy and chemotherapy in pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). Methods The medical records of 66 patients (42 males) treated for medulloblastoma (n=56) or PNET (n=10) in childhood between January 2000 and December 2014 at Seoul National University Children's Hospital were retrospectively reviewed. A total of 21 patients (18 high-risk medulloblastoma and 3 PNET) underwent high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR). Results During the median 7.6 years of follow-up, 49 patients (74%) developed transient (n=12) or permanent (n=37) hypothyroidism at a median 3.8 years of follow-up (2.9-4.6 years). Younger age (l5 years) at radiation exposure (P=0.014 vs. ≥9 years) and HDCT (P=0.042) were significantly predictive for hypothyroidism based on log-rank test. However, sex, type of tumor, and dose of craniospinal irradiation (less vs. more than 23.4 Gy) were not significant predictors. Cox proportional hazard model showed that both younger age (l5 years) at radiation exposure (hazard ratio [HR], 3.1; vs. ≥9 years; P=0.004) and HDCT (HR, 2.4; P=0.010) were significant predictors of hypothyroidism. Conclusion Three-quarters of patients with pediatric medulloblastoma or PNET showed thyroid dysfunction, and over half had permanent thyroid dysfunction. Thus, frequent monitoring of thyroid function is mandatory in all patients treated for medulloblastoma or PNET, especially, in very young patients and/or high-risk patients recommended for HDCT/ASCR.

We performed this study to identify the treatment patterns of patients with low-grade gliomas (LGG) in Korea. A total of 555 patients diagnosed as WHO grade II gliomas between 2000 and 2010 at 14 Korean institutions were included. The patients were divided into four adjuvant treatment groups: adjuvant fractionated radiotherapy (RT, N = 204), adjuvant chemotherapy (N = 20), adjuvant fractionated RT and chemotherapy (N = 65), and non-adjuvant treatment (N = 266) groups. We examined differences among the groups and validated patient/tumor characteristics associated with the adjuvant treatments. Astrocytoma was diagnosed in 210 patients (38%), oligoastrocytoma in 85 patients (15%), and oligodendroglioma in 260 patients (47%). Gross total resection was performed in 200 patients (36%), subtotal resection in 153 (28%), partial resection in 71 patients (13%), and biopsy in 131 patients (24%). RT was most commonly applied as an adjuvant treatment. The use of chemotherapy with or without RT decreased after 2008 (from 38 to 4%). The major chemotherapeutic regimen was procarbazine, lomustine, and vincristine (PCV); however, the proportion of temozolomide increased since 2005 (up to 69%). Patient/tumor characteristics related with RT were male gender, non-seizure, multiple lobes involvement, and non-gross total resection. Chemotherapy was associated with non-gross total resection and non-astrocytoma. A preference for RT and increased use of temozolomide was evident in the treatment pattern of LGG. The extent of resection was associated with a decision to perform RT and chemotherapy. To establish a robust guideline for LGG, further studies including molecular information are needed.

We retrospectively evaluated an efficacy of adjuvant radiotherapy (RT) in the intracranial hemangiopericytoma (HPC) and analyzed prognostic factors influencing treatment outcomes. Among 49 patients diagnosed as localized intracranial HPC between 1995 and 2016, 31 patients received adjuvant RT after surgery; 26 with fractionated RT and 5 with stereotactic radiosurgery using Gamma Knife. After gross total resection (GTR) (n = 32) and subtotal resection (STR) (n = 17), histopathological grade was confirmed to be grade II (n = 9) or grade III (n = 40). The median follow-up period was 50 months (range 3–216 months). The local recurrence was defined as intracranial relapse within 15 mm and regional recurrence as beyond 15 mm from the margin of surgical bed. The 10-year overall survival (OS) and progression-free survival (PFS) were 69.9 and 34.4%, respectively. The 10-year local, regional, and distant failure-free rates were 56.6, 88.2, and 73.3%, respectively. Local tumor control was better with GTR followed by RT than GTR alone (p = 0.056), while there was no difference in OS. Local tumor control and OS after STR plus RT were equivalent to those after GTR alone. There were no differences in distant metastasis-free survival (DMFS) among GTR plus RT, GTR alone, and STR plus RT. Tumor volume > 40 cm3 was associated with poor PFS (p = 0.024). The local tumor recurrence was reduced by adjuvant RT after surgery. But OS or DMFS was not improved with adjuvant RT. PFS was better in the tumor with small volume at diagnosis.

We analyzed patterns of care and outcomes for patients with primary central nervous system lymphoma (PCNSL) in this multi-institutional retrospective study. Between January 2000 and December 2011, 220 patients with PCNSL received radiotherapy (RT). Among these patients, 26 patients received RT alone; 179 patients were treated with chemotherapy and radiotherapy; the rest of the patients (N = 15) initially underwent chemotherapy alone, then received RT as a salvage treatment. Most of the patients (N = 188) received methotrexate-based chemotherapy. The median follow up duration was 38 months (range 3-179 months). The median RT dose and whole brain RT (WBRT) dose were 45.0 Gy (range 20.0-59.4) and 30.6 Gy (range 18.0-45.0), respectively. Seventy-seven (35%) patients received WBRT alone, and 143 patients (65%) underwent WBRT plus boost RT. Total RT dose and WBRT dose decreased during the study period. The median survival was 64 months and actuarial 5-year overall survival was 51.4%. In multivariate analysis, age (P

Radiation necrosis (RN) in brain tumor patients is often symptomatic, persistent without immediate resolution, and confused with tumor recurrence. Cerebral vascular pericytes are essential for endothelial function, vascular integrity, and angiogenesis. In this study, we showed that the loss of pericytes is involved in the pathogenesis of RN. From a brain tumor tissue repository, we identified three patients since 2011 with pathologically confirmed RN after the standard treatment for glioblastoma (GBM). The RN and their preradiation GBM tissues were serially processed for Western blotting using cell-type-specific antibodies against endothelial (CD31, active RhoA), pericyte [platelet-derived growth factor receptor-beta (PDGFR-β)], alpha-smooth muscle actin (α-SMA), astrocyte (GFAP), myelin sheath protein (MBP), and microglial markers (Iba1). Normal brain tissues from a brain bank were used as normal controls. The expressions of PDGFR-β and α-SMA were remarkably reduced in the RN, compared to those of GBM. However, the levels of CD31 or RhoA were not different between the two groups, which suggest that there was no change in the number of endothelial cells or their cytoskeletal assembly. The RN tissues showed a decreased ratio of pericyte/endothelial markers and an increased level of Iba1 compared to the GBM and even to the normal brain. The levels of GFAP and MBP were not changed in the RN. In the histopathology, the RN tissues showed a loss of markers (PDGFR-β), whereas the GBM tissues had abundant expression of the markers. The loss of pericytes and vascular smooth muscle cells, and the unsupported endothelial cells might be the cause of the leaky blood-brain barrier and tissue necrosis.

To analyze the treatment outcomes and the effects of adjuvant radiotherapy (RT) in patients with synovial sarcoma (SS). The medical records of 103 patients treated with definitive surgery for SS, with/without RT, from August 1982 to July 2013 were reviewed retrospectively. The median age of the patients was 33 years (range, 5 to 72 y). The most frequent tumor location was the extremities (79 patients, 77%). Seventy-five patients (73%) received adjuvant RT and 26 (25%) did not. The median dose of adjuvant RT was 61.2 Gy (range, 45 to 66.6 Gy). The median follow-up period was 5.4 years (range, 0.2 to 31.0 y). The 5- and 10-year overall survival rates were 77 % and 65%, respectively. The progression-free survival (PFS) rates at 5 and 10 years were 52% and 43%, respectively. The most common site of initial failure was the lung (24 patients), followed by local recurrence (14 patients). The 5-year local-recurrence-free survival (LRFS) and distant-metastasis-free survival (DMFS) rates were 80% and 63%, respectively. On multivariate analysis, a mitosis count of

Although craniospinal irradiation (CSI) of 2340 cGy plus tumor booster with chemotherapy have been established as a standard treatment of childhood average-risk (AvR) medulloblastoma (MBL) in Western counties, there are a few recent reports in outcomes of AvR MBL using this strategy in Korean and other Asian children. We investigated the outcome of the Korean children with AvR MBL who were treated with CSI

PURPOSE We aimed to refine the radiotherapy (RT) volume and dose determinant for disease failures and long-term sequelae in the intracranial germinoma. METHODS The main treatment for intracranial germinoma was craniospinal RT only (n=51) during 1981–1992 and RT with upfront chemotherapy (CRT) (n=152) during 1992–2015 in Seoul National University Hospital. All 187 cases were confirmed histologically. RT fields included craniospinal, whole-ventricle (WV), whole-brain (WB), and focal radiotherapy. RT dose was dependent on the M status and combination of chemotherapy. The median follow-up duration was 115 months (range, 3–358). RESULTS The 10-year overall and recurrence-free survival was 94.5% and 91.4%. The complete response rate after chemotherapy was 62.6%. For the patients with complete response, WV RT 16–20 Gy, and focal boost of 25–36 Gy after upfront chemotherapy showed no in-field recurrence. The causes of death were progression (n=3), 2nd malignancy (n=6), treatment-related complications (n=7), and others (n=8). For non-sellar tumors, the rate of hormonal replacement treatment was significantly related to WB RT and WB/WV RT dose ≥ 30 Gy (p=.030, and .026). After a latency of the median 20 years, ten patients (5.3%) developed 2nd malignancy. WB RT and WB/WV dose ≥ 30 Gy were significantly correlated with the 2nd malignancy (p=.024, and .004). The rate of severe neurocognitive dysfunction was significantly associated with WB/WV dose ≥ 30 Gy (p=.027). CONCLUSION: CONCLUSION RT with or without upfront chemotherapy exhibits the excellent control rate of disease. However, the intensity and volume of RT are critical for managing treatment toxicities. Adaptation and further de-intensification of RT should be followed.

Purpose To identify the clinical usefulness of serum M protein and to establish a rationale for regular follow-up with serum protein electrophoresis in solitary plasmacytoma. Materials and methods Sixty-nine patients with solitary plasmacytoma and solitary plasmacytoma with minimal marrow involvement according to the International Myeloma Working Group criteria were retrospectively reviewed. Results At a median follow-up of 6.2 years, 5-year local control (LC), 5-year multiple myeloma-free survival (MMFS), 5-year failure-free survival (FFS), and 5-year overall survival (OS) were 82.6%, 44.1%, 41.8%, and 85.1%, respectively. Among the patients whose initial serum M protein was present or not evaluated, 37.3% of patients showed disappearance of serum M protein after various treatment. MMFS of these patients were comparable to non-secretory plasmacytoma with undetectable levels of M protein, and significantly better than patients with persistent M protein. Increase of serum M protein ≥0.1 g/dL was most predictive of treatment failure with area under the curve of 0.731. Conclusion Patients who eventually showed persistence of serum M protein after treatment showed worse MMFS and FFS compared to those whose serum M protein disappeared or who had initially non-secretory disease. The increase of serum M protein level ≥0.1 g/dL from current nadir was predictive of treatment failure. Therefore, regular follow-up with serum M protein is highly recommended especially unless the patient had initially non-secretory disease.

To optimize and validate a current (NRG [a newly constituted National Clinical Trials Network group through National Surgical Adjuvant Breast and Bowel Project [NSABP], the Radiation Therapy Oncology Group [RTOG] and the Gynecologic Oncology Group (GOG)]) nomogram for glioblastoma patients as part of continuous validation. We identified patients newly diagnosed with glioblastoma who were treated with temozolomide-based chemoradiotherapy between 2006 and 2016 at three large-volume hospitals. The extent of resection was determined via postoperative MRI. The discrimination and calibration abilities of the prediction algorithm were assessed; if additional factors were identified as independent prognostic factors, updated models were developed using the data from two hospitals and were externally validated using the third hospital. Models were internally validated using cross-validation and bootstrapping. A total of 837 patients met the eligibility criteria. The median overall survival (OS) was 20.0 (95% CI 18.5–21.5) months. The original nomogram was able to estimate the 6‑, 12-, and 24-month OS probabilities, but it slightly underestimated the OS values. In multivariable Cox regression analysis, MRI-defined total resection had a greater impact on OS than that shown by the original nomogram, and two additional factors—IDH1 mutation and tumor contacting subventricular zone—were newly identified as independent prognostic values. An updated nomogram incorporating these new variables outperformed the original nomogram (C-index at 6, 12, 24, and 36 months: 0.728, 0.688, 0.688, and 0.685, respectively) and was well calibrated. External validation using an independent cohort showed C‑indices of 0.787, 0.751, 0.719, and 0.702 at 6, 12, 24, and 36 months, respectively, and was well calibrated. An updated and validated nomogram incorporating the contemporary parameters can estimate individual survival outcomes in patients with glioblastoma with better accuracy.

// Tae-Hyung Kim 1 , Tae Jin Yun 1,2 , Chul-Kee Park 3 , Tae Min Kim 4 , Ji-Hoon Kim 1,2 , Chul-Ho Sohn 1,2 , Jae Kyung Won 5 , Sung-Hye Park 5 , Il Han Kim 6 and Seung Hong Choi 1,2,7 1 Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea 2 Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea 3 Department of Department of Neurosurgery, Seoul National University Hospital, Seoul, Republic of Korea 4 Department of Internal Medicine, Cancer Research Institute, Seoul National University Hospital, Seoul, Republic of Korea 5 Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea 6 Department of Radiation Oncology, Cancer Research Institute, Seoul National University Hospital, Seoul, Republic of Korea 7 Center for Nanoparticle Research, Institute for Basic Science, Seoul, Republic of Korea Correspondence to: Seung Hong Choi, email: // Keywords : magnetic resonance imaging, radionecrosis, recurrence, susceptibility-weighted magnetic resonance imaging sequences, dynamic susceptibility contrast perfusion-weighted imaging Received : June 30, 2016 Accepted : October 28, 2016 Published : November 03, 2016 Abstract Purpose was to assess predictive power for overall survival (OS) and diagnostic performance of combination of susceptibility-weighted MRI sequences (SWMRI) and dynamic susceptibility contrast (DSC) perfusion-weighted imaging (PWI) for differentiation of recurrence and radionecrosis in high-grade glioma (HGG). We enrolled 51 patients who underwent radiation therapy or gamma knife surgeryfollowed by resection for HGG and who developed new measurable enhancement more than six months after complete response. The lesions were confirmed as recurrence ( n = 32) or radionecrosis ( n = 19). The mean and each percentile value from cumulative histograms of normalized CBV (nCBV) and proportion of dark signal intensity on SWMRI (proSWMRI, %) within enhancement were compared. Multivariate regression was performed for the best differentiator. The cutoff value of best predictor from ROC analysis was evaluated. OS was determined with Kaplan-Meier method and log-rank test. Recurrence showed significantly lower proSWMRI and higher mean nCBV and 90th percentile nCBV (nCBV90) than radionecrosis. Regression analysis revealed both nCBV90 and proSWMRI were independent differentiators. Combination of nCBV90 and proSWMRI achieved 71.9% sensitivity (23/32), 100% specificity (19/19) and 82.3% accuracy (42/51) using best cut-off values (nCBV90 > 2.07 and proSWMRI≤15.76%) from ROC analysis. In subgroup analysis, radionecrosis with nCBV > 2.07 ( n = 5) showed obvious hemorrhage (proSWMRI > 32.9%). Patients with nCBV90 > 2.07 and proSWMRI≤15.76% had significantly shorter OS. In conclusion, compared with DSC PWI alone, combination of SWMRI and DSC PWI have potential to be prognosticator for OS and lower false positive rate in differentiation of recurrence and radionecrosis in HGG who develop new measurable enhancement more than six months after complete response.

PURPOSE The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

High-dose chemotherapy (HDC) and autologous stem-cell transplantation (auto-SCT) are used to improve the survival of children with high-risk brain tumors who have a poor outcome with the standard treatment. This study aims to evaluate the outcome of HDC/auto-SCT with topotecan–thiotepa–carboplatin and melphalan–etoposide–carboplatin (TTC/MEC) regimens in pediatric brain tumors. We retrospectively analyzed the data of 33 children (median age 6 years) who underwent HDC/auto-SCT (18 tandem and 15 single) with uniform conditioning regimens. Eleven patients aged

Background This study evaluated the effect of radiation dose rate in patients with hematolymphoid malignancies undergoing myeloablative conditioning with total body irradiation (TBI), for hematopoietic stem cell transplantation. Methods The incidence of pulmonary toxicity (PT) and treatment efficacy were compared between the conventional (≥ 6 cGy/min) and reduced dose rate (

Tumor hypoxia and aerobic glycolysis are well-known resistance factors for anticancer therapies. Here, we demonstrate that tumor-associated macrophages (TAM) enhance tumor hypoxia and aerobic glycolysis in mice subcutaneous tumors and in patients with non–small cell lung cancer (NSCLC). We found a strong correlation between CD68 TAM immunostaining and PET 18fluoro-deoxyglucose (FDG) uptake in 98 matched tumors of patients with NSCLC. We also observed a significant correlation between CD68 and glycolytic gene signatures in 513 patients with NSCLC from The Cancer Genome Atlas database. TAM secreted TNFα to promote tumor cell glycolysis, whereas increased AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1-alpha in TAM facilitated tumor hypoxia. Depletion of TAM by clodronate was sufficient to abrogate aerobic glycolysis and tumor hypoxia, thereby improving tumor response to anticancer therapies. TAM depletion led to a significant increase in programmed death-ligand 1 (PD-L1) expression in aerobic cancer cells as well as T-cell infiltration in tumors, resulting in antitumor efficacy by PD-L1 antibodies, which were otherwise completely ineffective. These data suggest that TAM can significantly alter tumor metabolism, further complicating tumor response to anticancer therapies, including immunotherapy. Significance: These findings show that tumor-associated macrophages can significantly modulate tumor metabolism, hindering the efficacy of anticancer therapies, including anti-PD-L1 immunotherapy.

OBJECTIVE Spinal epidural lymphoma with compressive myelopathy is a rarely found condition. The aims of this study are to describe the clinical features and to analyze its treatment outcome and prognostic factors. METHODS We searched for all pediatric patients with newly diagnosed spinal epidural lymphoma from 1999 to 2014 in our institution. We evaluated the clinical features, including neurologic status, time interval to treatment, treatment modality, and outcomes. RESULTS Twelve of 302 pediatric patients with lymphoma (4.0%) presented with compressive myelopathy, and they were all found to have spinal epidural lymphoma. In 11 patients, epidural space was the only site of lymphoma involvement. The median age was 9 years (range, 5-15 years). Common initial symptoms were back pain and low extremity weakness. Surgery was performed on 9 patients, biopsy on 2 patients, and radiation therapy on 1 patient. In 9 patients who received surgery, 6 patients with preoperative motor power grade ≥II attained improvement in weakness. Three patients with preoperative motor power grade

Although some existing evidence supports the addition of chemotherapy (CT) to radiation therapy (RT) for anaplastic oligodendroglioma treatment, controversy about both the criteria for suitable candidates and the optimal treatment schedule remains. We reviewed data from 376 newly diagnosed anaplastic oliogodendroglial tumor patients from nine Korean institutes were reviewed from 2000 to 2010. Total tumor removal was performed in 146 patients. More than 85% of the entire patients received postoperative RT, and 59% received CT. Approximately 50% (n = 189) received CT in addition to RT and 9% (n = 32) received CT only. A multivariate analysis revealed that younger age, frontal lobe location of the tumor, gross total removal, 1p/19q codeletion, and initial RT were associated with longer progression-free and overall survival rates. No difference was observed in outcomes from the treatment that included either temozolomide or PCV (procarbazine, lomustine, and vincristine) in addition to RT regardless of the 1p/19q deletion status. A clear improvement in progression-free and overall survival was observed for RT and combined CT/RT in compared with CT only. Postoperative RT appears to improve survival for entire group thus total removal and 1p/19q codeletion may not be sufficient criteria to omit RT as a treatment option. These results suggest that RT should continue to be offered as the standard treatment option for patients with anaplastic oligodendroglial tumors.

Purpose The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P =.004; OS, P =.004) and ILRT (PFS, P =.021; OS, P =.014) were favorable prognosticators of PFS and OS. A bulky tumor ( P =.027) and response to R-CHOP ( P =.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P =.014; OS, P =.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P =.004; OS, P =.012). Conclusions Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

Purpose We aimed to evaluate clinical outcomes including progression-free survival (PFS), overall survival (OS), partial response, and complete response in patients who underwent radiation therapy (RT) for mycosis fungoides (MF). Also, we sought to find prognostic factors for clinical outcomes. Materials and. Methods Total 19 patients confirmed with MF between 1999-2015 were retrospectively reviewed. Clinical and treatment characteristics, clinical outcomes, and and toxicities were analyzed. Results Eleven patients were treated with total skin electron beam radiotherapy (TSEBT) and 8 patients with involved field radiation therapy (IFRT) with median dose of 30 Gy, respectively. The median time interval from diagnosis to RT was 2.6 months (range, 0.4 to 87.3 months). The overall response rate was 100%; 11 patients (57.9%) had a complete response and 8 patients (42.1%) a partial response. The presence of positive lymph node at the time of consultation of RT was associated with lower OS (p = 0.043). In multivariate analysis, PFS was significantly lower for patients with increased previous therapies experienced following RT (p = 0.019) and for patients showing PR during RT (p = 0.044). There were no reported grade 3 or more skin toxicities related with RT. Conclusion Both IFRT and TSEBT are effective treatment for MF patients. Patients with short disease course before RT or complete response during RT are expected to have longer PFS. Positive lymph node status at the initiation of RT was associated woth poor OS, suggesting other treatment modalities such as low-dose RT for patients with low life-expectancy.

Background Fluid collection (FC) of lymph or blood may accumulate at the site of excision after surgery for soft tissue sarcoma, with reported incidence rates from 10% to 36%. The purpose of this study is to analyze the impact of FC on local recurrence (LR) and wound complication rates after adjuvant postoperative radiotherapy (PORT) in lower extremity soft tissue sarcoma (LE-STS). Methods Eighty-eight patients diagnosed with LE-STS were curatively treated with wide excision and PORT. FC developed in 51.1% of patients. Full FC volumes were included in the irradiation field throughout the full course of PORT for 36 patients (80.0%). A median of 61.2 and 63 Gy was prescribed for patients with and without FC, respectively. Results After a median follow-up of 4.3 years, patients with and without FC had 5-year local control rates of 77.7% and 90.8% (P = 0.105). Eight patients with FC had LR, of which six patients had recurrent tumors at or within 4 cm of the FC wall and three of these patients had out-of-field LR. Wound complication occurred after RT in 3 (6.7%) of 45 patients with FC and 1 (2.3%) of 43 patients without FC. Conclusions FC presents a potential risk for increased LR, particularly near the FC wall. Based on reasonable wound complication rates, we suggest the need and feasibility of fully including FC volumes in the irradiation field.

To evaluate whether the cerebral blood volume (CBV) measurement with leakage correction from dynamic susceptibility contrast perfusion weighted imaging can be useful in predicting prognosis for primary central nervous system lymphoma (PCNSL). 46 PCNSL patients were included and classified by radiation therapy (RT) stratification into RT (n = 30) and non-RT (n = 16) groups. The corresponding histogram parameters of normalized CBV (nCBV) maps with or without leakage correction were calculated on contrast-enhanced T1 weighted image (CE T1WI) or on fluid attenuated inversion recovery image. The 75th percentile nCBV with leakage correction based on CE T1WI (T1 nCBVL75%) had a significant difference between the short and long progression free survival (PFS) subgroups of the RT group and the non-RT group, respectively. Based on the survival analysis, patients in the RT group with high T1 nCBVL75% had earlier progression than the others with a low T1 nCBVL75%. However, patients in the non-RT group with a high T1 nCBVL75% had slower progression than the others with a low T1 nCBVL75%. Based on RT stratification, the CBV with leakage correction has potential as a noninvasive biomarker for the prognosis prediction of PCNSL to identify high risk patients and it has a different correlation with the PFS based on the presence of combined RT.

The treatment modalities for uveal melanoma (UM) include surgery and radiotherapy (RT). The utilization of RT as a strategy for organ preservation has been increasing, but the survival difference between the two aforementioned treatment modalities has not been reported. An observational and cohort study was performed using a propensity score with an already existing public database. Patients diagnosed with UM within the period from 2004–2013 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. One-to-one matching and inverse probability of treatment weighting (IPTW) using the propensity score were used to estimate and compare survival rates. Overall, 3291 patients were treated: 2503 received RT only (RT group) and 788 received surgical resection only (surgery group). The RT group had an improved crude 5‑year overall survival (OS) rate compared with the surgery group (76% vs. 60%, P < 0.001), and an improved 5‑year melanoma-specific survival (MSS) rate (89% vs. 73%, P < 0.001). Compared to the surgery group, the RT group was associated with improved OS (hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.38–0.73, P < 0.001) and MSS (HR 0.48, 95% CI 0.35–0.65, P < 0.001) in the matched cohort. The survival benefit of the RT group maintained after adjustment with IPTW, both in OS and MSS. To our knowledge, the present study was the first to demonstrate the survival difference between the two treatment modalities for UM using both the propensity score matching and weighting methods with the SEER database. The current study suggests that RT may provide a survival advantage over surgery in the treatment of UM.

This study was designed to investigate the impact of interim progression of disease (PD) during the surgery-to-radiotherapy interval (SRI) and its predictors in glioblastoma based on MRIs. A total of 222 patients were planned for radiotherapy (RT) and 166 of them were evaluable for the presence of interim PD by 2 separate MRIs. The size criteria from the updated Response Assessment in Neuro-Oncology criteria was adopted to determine interim PD. 32 (19.3%) patients experienced interim PD, and their median survival (MS) was shorter than patients without PD in univariate (11.3 vs. 19.6 months, p

PURPOSE This study was conducted in order to validate the radiosensitization effect of valproic acid, a biologically available histone deacetylase inhibitor, for fractionated radiation. MATERIALS AND METHODS Radiosensitization effect of valproic acid was tested for the A549 cell line and U87MG cell line in vitro. Fractionated irradiation of 12 Gy in four fractions was administered on D2-5 with valproic acid, 150 mg/Kg, ip, bid for six consecutive days (D1-6) to A549 and U87MG tumors implanted in BALB/c-nude mice. A growth delay curve was formulated. RESULTS Radiosensitization effect of valproic acid was found for both cell lines; A549 at 1.5 mM and 3.0 mM concentration and U87MG at 3.0 mM concentration. In growth delay analysis, a statistically significant radiosensitization effect was observed for both tumors (p < 0.001 for both tumors). Difference for change in slope for control and valproic acid versus radiotherapy and radiotherapy plus valproic acid showed borderline significance for the U87MG cell line (p=0.065), indicating beyond additive effect, whereas this difference was statistically insignificant for A549 tumor (p=0.951), indicating additive effect. CONCLUSION Results of this study indicate that a radiosensitizing effect for fractionated radiotherapy of valproic acid for A549 and U87MG tumors in vivo is evident and that it may be more than additive for U87MG tumors. Further exploitation of histone deacetylase inhibitors in clinical trials is warranted.

PURPOSE: The purpose of this study is to evaluate the outcome of low-dose whole brain radiotherapy (WBRT) with tumor bed boost after methotrexate-based chemotherapy in the management of primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS: We retrospectively analyzed 64 patients with pathologically proven PCNSL between 2000 and 2011. Methotrexate-based chemotherapy with a median of five cycles was followed by radiotherapy to the whole brain and to the initial tumor bed. The median dose to the whole brain and to the tumor bed was 27 Gy (range, 18 to 36 Gy) and 50.4 Gy (range, 45 to 54 Gy), respectively. RESULTS: With a median follow-up period of 27 months, 55 patients (85.9%) achieved complete response (CR). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 52.6% and 39.3%, respectively. In univariate analysis, factors associated with OS were age, performance status, involvement of deep structure, and CR to sequential chemoradiotherapy (CRT). These variables remained as significant factors for OS in multivariate analysis. CR to sequential CRT was the only positive factor associated with PFS (p=0.009). Neurologic toxicity was more common in elderly patients older than 60 years (p=0.025). CONCLUSION: Low-dose WBRT with tumor bed boost after methotrexate-based chemotherapy might be an effective method for management of PCNSL.

The aim of this study was to assess the feasibility and efficacy of high-dose, single-fraction electron beam radiotherapy for therapy-resistant keloids. Before 2010, intractable keloids were treated at our institution with post-operative irradiation of 6-15 Gy in 3-5 fractionations. For convenience and cost effectiveness, we have changed our treatment protocol to high-dose single-fraction radiotherapy. A total of 12 patients with 16 keloid lesions were treated from January 2010 to January 2013 in our department. A 10-Gy dose of electron irradiation was given within 72 h of the surgical excision. The mean follow-up period was 20 months. Treatments were well tolerated, and there was no recurrence in any of the patients. Severe adverse effects were not observed. Surgical excision of the keloid, followed by immediate, single-fraction, high-dose radiotherapy, is both safe and effective in preventing recurrence of therapy-resistant keloids.

This study was done to evaluate the association of cyclooxygenase 2 (COX-2) and brain fatty acid binding protein (BFABP) with tumor grade and outcome of grades I-II meningiomas treated with radiotherapy. From 1996 to 2008, 40 patients with intracranial grades I-II meningiomas were treated with radiotherapy. Immunohistochemical staining for COX-2 and BFABP were performed on formalin-fixed paraffin-embedded tissues. COX-2 expression was significantly associated with BFABP status and both COX-2 (P < 0.01) and BFABP (P = 0.01) expression were stronger in the grade II meningiomas than in grade I tumors. Among the clinicopathologic factors, age and COX-2 status were prognostic in progression-free survival. Patients with moderate or strong COX-2 expression had worse outcome than those with negative or weak COX-2 expression (P = 0.03) after controlling for potential confounders. Our results suggest that the molecular biomarker COX-2 has prognostic significance in intracranial grades I-II meningiomas following radiotherapy.

The object of this study was to analyze treatment outcomes and to identify the prognostic factors, with a focus on the role of adjuvant radiotherapy (ART), predicting disease progression in atypical meningiomas. From 1997 to 2011, 83 patients with meningioma were included in this study. All patients were histologically confirmed as atypical meningioma and were treated with surgical resection with or without ART. As primary therapy, 27 patients received surgical resection followed by ART, and 56 received no adjuvant therapy. Of 83 evaluable patients, 55 (66.3 %) patients underwent complete resection. The median ART dose was 61.2 Gy and their median age was 52 years. The 5- and 10-year actuarial overall survival rates were 90.2 and 62.0 %, and the 5- and 10-year progression-free survival (PFS) rates were both 48.0 %, with a median follow-up of 43.0 months. Addition of ART (p = 0.016) and complete tumor resection (p = 0.002) were associated with superior PFS. When stratified to four groups according to resection status and ART, the groups of patient with incomplete resection without ART showed significantly worse PFS compared to other three groups (p < 0.001). In conclusion, surgical resection followed by ART led to lower local tumor progression in patients with atypical meningioma defined by the updated 2000/2007 WHO classification. Our results may contribute to the routine use of ART, especially after incomplete resection, until the outcomes of ongoing prospective trials are available.

Purpose There has been no definite consensus on standard treatment, either local or systemic, for the Kaposi's sarcoma (KS). Radiotherapy (RT) can be a good local therapeutic choice especially in non-AIDS associated KS (NAKS) for its indolent behavior. Materials and methods Medical records of 17 KS patients treated with RT at the Seoul National University Hospital from February 1998 to January 2012 were retrospectively reviewed. One human immunodeficiency virus (HIV)+ patient with 3 lesions was excluded. The total number of the lesion was 23 among the 16 patients. The median follow-up period was 27.9 months. Correlation between response and variables was analyzed using the logistic regression model. Median age of the patients was 75 years. All the 23 lesions were located at the extremities. Fourteen (61%) of those had pain or local swelling as the initial presentation. Ten patients had possible causes of immunodeficiency and were regarded as iatrogenic, and other 6 were classic KS. Median dose of RT was 36 Gy. Results No KS-related death was observed. Excluding 2 with short-term follow-up only, complete response and partial response were obtained in 2 (9%) and 19 (73%) lesions, respectively. Of those, 3 lesions underwent local progression. Six had out-of-field recurrence after RT. Symptom improvement was achieved in 13 (93%) of 14 patients. Grade 2 skin toxicities were found in 9 lesions but all got improvement after treatment. When divided into responsive and progressive group, free from progression was not related to any of the possible variables. Conclusion RT is effective in local control of NAKS resulting great response rate.

time. Methods: A cylindrical device made of aluminum was conceptually proposed as an energy modulator. The frame of the device was connected with 20 tubes through which mercury could be injected or drained to adjust the thickness of mercury along the beam axis. In Monte Carlo (MC) simulations, a flattening filter of 6 or 10 MV linac was replaced with the device. The thickness of mercury inside the device varied from 0 to 40 mm at the field sizes of 5 � 5c m 2 (FS5), 10 � 10 cm 2 (FS10), and 20 � 20 cm 2 (FS20). At least 5 billion histories were followed for each simulation to create phase space files at 100 cm source to surface distance (SSD). In-water beam data were acquired by additional MC simulations using the above phase space files. A treatment planning system (TPS) was commissioned to generate a virtual machine using the MC-generated beam data. Intensity modulated radiation therapy (IMRT) plans for six clinical cases were generated using conventional 6 MV, 6 MV flattening filter free, and energy-modulated photon beams of the virtual machine. Results: As increasing the thickness of mercury, Percentage depth doses (PDD) of modulated 6 and 10 MV after the depth of dose maximum were continuously increased. The amount of PDD increase at the depth of 10 and 20 cm for modulated 6 MV was 4.8% and 5.2% at FS5, 3.9% and 5.0% at FS10 and 3.2%‐4.9% at FS20 as increasing the thickness of mercury from 0 to 20 mm. The same for modulated 10 MV was 4.5% and 5.0% at FS5, 3.8% and 4.7% at FS10 and 4.1% and 4.8% at FS20 as increasing the thickness of mercury from 0 to 25 mm. The outputs of modulated 6 MV with 20 mm mercury and of modulated 10 MV with 25 mm mercury were reduced into 30%, and 56% of conventional linac, respectively. The energy-modulated IMRT plans had less integral doses than 6 MV IMRT or 6 MV flattening filter free plans for tumors located in the periphery while maintaining the similar quality of target coverage, homogeneity, and conformity. Conclusions: The MC study for the designed energy modulator demonstrated the feasibility of energy-modulated photon beams available during beam-on time. The planning study showed an advantage of energy-and intensity modulated radiotherapy in terms of integral dose without sacrificing any quality of IMRT plan. V C 2012 American Association of Physicists in Medicine. [DOI: 10.1118/1.3682172]

Despite active and aggressive therapeutic measures, atypical teratoid/rhabdoid tumors (AT/RTs) are without doubt one of the most malignant brain tumors that occur during childhood. These tumors are more prevalent in children less than 3 years of age, and the prognosis is worse in these young children. Medical records of 14 patients diagnosed at our institution were reviewed. Patients diagnosed with AT/RT at our institution between 1997 and 2009 were identified. Clinical data for those patients with pathologic confirmation of AT/RTs were reviewed regarding surgery, adjuvant treatment, and survival. A total of 14 patients were identified. One patient who died 3 days after initial surgery was excluded, and 13 patients were recruited. Of the 13 patients, 7 were less than 1 year of age, and only 2 were over 3 years of age. Nine patients showed dissemination at diagnosis. Four patients were treated with radiation therapy (RTx), and 2 of these were less than 3 years of age. Ten patients had chemotherapy (CTx), and 3 of these underwent high dose chemotherapy and autologous peripheral blood stem cell transplantation. The median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Univariable analysis revealed age more than 1 year, CTx, and RTx to be significant factors for better PFS and OS. None of the variables were significant in multivariable analysis. Young patients with AT/RT have a bad prognosis. An aggressive therapeutic strategy needs to be profiled for this age group.

This prospective study was performed to determine the efficacy, safety, and tolerability of concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy with temozolomide (TMZ) in the treatment of patients with WHO grade III gliomas. Thirty-three adult patients with WHO grade III glioma and aged >17 years were enrolled from three institutions between 2003 and 2008. The median age was 41 years (range, 17–60 years). The pathological diagnoses were anaplastic astrocytomas in 21 patients and anaplastic oligodendrogliomas in 12 patients. The preoperative Karnofsky performance scale score was >60 for all patients. The patients received fractionated focal irradiation in daily fractions of 2 Gy administered five days per week for six weeks, for a total of 60 Gy, in combination with continuous daily TMZ, followed by six cycles of adjuvant TMZ. The median dose of radiotherapy was 59.4 Gy (range, 28.8–61.2 Gy) and the duration of CCRT was 7.0 weeks (range, 3.1–8.3 weeks). A median of 6.2 cycles (range, 2–12 cycles) of TMZ chemotherapy were performed during the period of adjuvant chemotherapy. The response rate was 61% and the tumor-control rate was 82%. Mean progression-free survival (PFS) was 48.7 months (95% CI, 36.0–61.4) and the 12, 24, and 36-month PFS was 74%, 60%, and 50%, respectively. Mean overall survival (OS) was 66.4 months (95% CI, 56.4–76.4) and the 12 and 24-month OS was 97% and 77%, respectively. The extent of surgical resection was a significant prognostic factor for PFS and OS (hazard ratio, 0.24; 95% CI, 0.02–0.73; and hazard ratio, 0.12; 95% CI, 0.01–0.88, respectively; P

Object Glioblastoma is the most common primary malignant brain tumor; however, glioblastoma in children is less common than in adults, and little is known about its clinical outcome in children. The authors evaluated the long-term outcome of glioblastoma in children. Methods Twenty-seven children were confirmed to have harbored a glioblastoma between 1985 and 2007. The clinical features and treatment outcomes were reviewed retrospectively. All patients underwent resection; complete resection was performed in 12 patients (44%), subtotal resection in 12 patients (44%), and biopsy in 3 patients (11%). Twenty-four patients (89%) had radiation therapy, and 14 (52%) patients received chemotherapy plus radiation therapy. Among the latter, 5 patients had radiation therapy concurrent with temozolomide chemotherapy. Four patients with small-size recurrent glioblastoma received stereotactic radiosurgery. Results The median overall survival (OS) was 43 months, and the median progression-free survival was 12 months. The OS rate was 67% at 1 year, 52% at 2 years, and 40% at 5 years. The median OS was significantly associated with tumor location (52 months for superficially located tumors vs 7 months for deeply located tumors; p = 0.017) and extent of removal (106 months for completely resected tumors vs 11 months for incompletely resected tumors; p < 0.0001). Conclusions The prognosis of glioblastoma is better in children than in adults. Radical resection followed by concurrent chemoradiation therapy may be the initial treatment of choice.

The efficacy and toxicity of high-dose chemotherapy and autologous stem cell transplantation (HDCT/ASCT) were investigated for improving the outcomes of patients with relapsed medulloblastoma. A total of 15 patients with relapsed medulloblastoma were enrolled in the KSPNO-S-053 study from May 2005 to May 2007. All patients received approximately 4 cycles of salvage chemotherapy after relapse. Thirteen underwent HDCT/ASCT; CTE and CM regimen were employed for the first HDCT (HDCT1) and second HDCT (HDCT2), respectively, and 7 underwent HDCT2. One transplant related mortality (TRM) due to veno-occlusive disease (VOD) occurred during HDCT1 but HDCT2 was tolerable with no further TRM. The 3-yr overall survival probability and event-free survival rates +/-95% confidence intervals (CI) were 33.3+/-12.2% and 26.7% +/-11.4%, respectively. When analysis was confined to only patients who had a complete response (CR) or partial response (PR) prior to HDCT, the probability of 3-yr overall survival rates +/-95% CI was 40.0+/-15.5%. No patients with stable disease (SD) or progressive disease (PD) survived. Survival rates from protocol KSPNO-S-053 are encouraging and show that tumor status prior to HDCT/ASCT is an important factor to consider for improving survival rates of patients with relapsed medulloblastoma.

This study evaluated the clinical and radiological characteristics, as well as the treatment outcomes, for the rare phenomenon known as intracranial growing teratoma syndrome (iGTS). One hundred seventy patients diagnosed with intracranial germ cell tumours (GCT) between 1997 and 2008 were enrolled in this retrospective analysis. Thorough reviews of medical records, brain magnetic resonance images (MRI), pathological findings and tumour markers [alpha-fetoprotein (αFP) and beta-human chorionic gonadotropin (βHCG)] were performed to identify the incidence of iGTS cases and to clarify their clinical characteristics. Eleven out of the 170 intracranial GCT patients (6.5%) were identified as having iGTS. All instances of iGTS originated from non-germinomatous GCT (NGGCT), with incidence rate of 21% (11/52). Six iGTS cases developed from mixed GCTs, four from immature teratomas (ITs) and one from yolk sac tumour. All 11 iGTS patients showed honeycomb-shaped multi-cystic growth patterns on MRI, which is a typical characteristic of iGTS. Surgical excision was performed in all patients, and complete excision was possible in nine patients. Eight of them are alive with no evidence of recurrence; however, two patients who had residual masses died owing to progression of iGTS. Early recognition and suspicion of iGTS, during or after adjuvant therapy of NGGCT, is crucial to ensure that surgical intervention can be performed in a timely manner. Early radical excision may be the treatment of choice for better iGTS prognosis.

This prospective study was performed to determine the efficacy and safety of temozolomide (TMZ) plus thalidomide during and after radiation therapy (RT) in pediatric patients with newly diagnosed diffuse pontine glioma (DPG). Seventeen patients with pediatric DPG were enrolled between November 2004 and March 2008. The median age was eight years (range, 3-16 years); seven patients were male and ten were female. With the exception of one glioblastoma case, which was diagnosed via open biopsy, all diagnoses were established using neuroradiological studies. The authors used the Korean Society for Pediatric Neuro-Oncology (KSPNO)-A053 protocol. The mean follow-up period was 12 months (range, 8.5-25 months). Five patients were withdrawn from the study. The rates of response to treatment and survival were analyzed in 12 patients. Ten out of the 12 patients showed a partial response (PR), whereas one patient exhibited stable disease (SD) and another patient had progressive disease (PD). The tumor control rate was 92% (11/12) and the response rate was 83% (10/12). The median progression-free survival (PFS) of the 12 patients was 7.2 months (95% confidence interval (CI), 3.6-10.7). Six-month and twelve-month PFS were 58.3 and 16.7%, respectively. Overall survival (OS) was 12.7 months (95% CI, 10.4-15.1). One and two-year survival were 58.3 and 25%, respectively. The main adverse effect was hematological toxicity, with four patients exhibiting grade 3 or 4 toxicity. All patients tolerated the regimen well enough to continue the adjuvant chemotherapy. No Pneumocystis jiroveci pneumonia was noted. The TMZ plus thalidomide regimen was safe and tolerated well enough to be administered on an outpatient basis. Larger studies are required to demonstrate the efficacy of this regimen.

Germinoma in the basal ganglia (BG) is notorious for its diagnostic difficulty. Clinical and radiological features of this disease are quite diverse, but have not been well characterized with respect to prognosis. We retrospectively reviewed the clinical course and treatment outcomes of 17 patients with a BG germinoma. The initial magnetic resonance imaging (MRI) features were classified. Clinical features and treatment outcomes were then analyzed with this classification scheme. A Type 1 lesion was defined as a subtle lesion with faint or no contrast enhancement (six patients). Type 2, 3, and 4 lesions were defined as contrast-enhancing lesions and were differentiated by the lesion size and the presence of subependymal seeding (11 patients). Type 1 lesions were distinct from the other lesions. Patients with a Type 1 lesion had a significantly longer time from the initial MRI to diagnosis than patients with Type 2, 3, and 4 lesions (P = 0.012). The actuarial progression-free survival and overall survival of patients 5 years after diagnosis were 66 and 77%, respectively. The presence of a Type 1 lesion (P = 0.004), a longer time delay in the diagnosis (P = 0.038), and radiation therapy without complete ventricular coverage (P = 0.010) were significantly associated with tumor progression. Profound motor deficits at diagnosis were associated with deterioration in motor function after tumor remission (P = 0.035). Early diagnosis of BG germinomas could affect the ability to control a tumor and neurological outcomes. In particular, high clinical suspicion and active diagnostic procedures are recommended. For optimal treatment, radiation fields should include entire ventricles even if there is no subependymal seeding.

Purpose To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma. Methods and Materials Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months. Results The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT—three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106). Conclusions The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.