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Budidaya ikan nila telah menjadi sumber protein penting untuk konsumsi manusia. Namun, keberhasilan penangkaran ikan nila sangat bergantung pada sistem aerasi yang digunakan di kolam penangkaran. Tujuan dari penelitian ini adalah untuk mengevaluasi efektivitas penggunaan microbubble venturi untuk sistem aerasi di kolam penangkaran ikan nila. Eksperimen dilakukan di dua kolam dengan dimensi yang sama, satu kolam menggunakan sistem microbubble venturi dan kolam lainnya menggunakan sistem aerasi tradisional. Penelitian berlangsung selama enam bulan, selama itu parameter kualitas air, kinerja pertumbuhan ikan, dan tingkat kelangsungan hidup dipantau. Hasil penelitian menunjukkan bahwa sistem microbubble venturi secara signifikan meningkatkan parameter kualitas air di tambak, termasuk oksigen terlarut, pH, dan total amonia nitrogen. Selain itu, kinerja pertumbuhan dan tingkat kelangsungan hidup ikan secara signifikan lebih tinggi di kolam dengan sistem venturi microbubble dibandingkan dengan sistem aerasi tradisional. Hasil penelitian ini menunjukkan bahwa sistem microbubble venturi merupakan sistem aerasi yang efektif untuk kolam penangkaran ikan nila, karena meningkatkan kualitas air dan performa pertumbuhan ikan, serta dapat dipertimbangkan sebagai teknologi alternatif untuk budidaya ikan nila.

Purpose: Glioblastoma, the most common malignant brain tumor, was associated with a median survival of <1 year in the pre-temozolomide (TMZ) era. Despite advances in molecular and genetic profiling studies identifying several predictive biomarkers, none has been translated into routine clinical use. Our aim was to investigate the prognostic significance of a panel of diverse cellular molecular markers of tumor formation and growth in an annotated glioblastoma tissue microarray (TMA)., Methods and Materials: A TMA composed of archived glioblastoma tumors from patients treated with surgery, radiation, and non-TMZ chemother-apy, was provided by RTOG. RAD51, BRCA-1, phosphatase and tensin homolog tumor suppressor gene (PTEN), and miRNA-210 expression levels were assessed using quantitative in situ hybridization and automated quantitative protein analysis. The objectives of this analysis were to determine the association of each biomarker with overall survival (OS), using the Cox proportional hazard model. Event-time distributions were estimated using the Kaplan-Meier method and compared by the log-rank test., Results: A cohort of 66 patients was included in this study. Among the 4 biomarkers assessed, only BRCA1 expression had a statistically significant correlation with survival. From univariate analysis, patients with low BRCA1 protein expression showed a favorable outcome for OS (p = 0.04; hazard ratio = 0.56) in comparison with high expressors, with a median survival time of 18.9 versus 4.8 months., Conclusions: BRCA1 protein expression was an important survival predictor in our cohort of glioblastoma patients. This result may imply that low BRCA1 in the tumor and the consequent low level of DNA repair cause vulnerability of the cancer cells to treatment., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objectives/hypothesis: The purpose of this study was to investigate the association of demographic factors, tumor stage, and treatment modalities for overall survival in patients with sinonasal mucosal melanoma (SNMM)., Study Design: Retrospective database review., Methods: The National Cancer Database was queried for patients of all ages with SNMM between 2004 and 2015. Univariate Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the association of suspected prognostic factors with overall survival., Results: A total of 1,874 patients with SNMM were included in the analysis. The 5-year overall survival was 24%. Prognostic factors associated with decreased survival include advanced age (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.01-1.03), T4 disease (HR: 1.44, 95% CI: 1.09-1.89), and presence of distant metastases (HR: 3.22. 95% CI: 2.06-5.04). Improved survival was associated with surgical resection only when margins were negative (HR: 0.44; 95% CI: 0.30-0.65). In patients with metastatic disease, administration of immunotherapy (HR: 0.14; 95% CI: 0.04-0.49) was associated with improved survival. Surgical approach, radiotherapy, and chemotherapy were nonsignificant predictors of survival., Conclusions: This investigation is the largest to date to analyze the association of treatment modalities with overall survival in SNMM. Surgery remains the mainstay of treatment in patients with SNMM. However, administration of immunotherapy may confer survival benefit to patients with metastatic disease., Level of Evidence: NA Laryngoscope, 130:275-282, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: To investigate the impact of proton radiotherapy (PBT) on overall survival (OS) and evaluate PBT usage trends for patients with gliomas in the National Cancer Data Base (NCDB). Methods: Patients with a diagnosis of World Health Organization (WHO) Grade I-IV glioma treated with definitive radiation therapy (RT) between the years of 2004-13 were identified. Patients were stratified based on WHO Grade and photon radiotherapy (XRT) vs. PBT. Univariate (UVA) and multivariable analysis (MVA) with OS were performed by Cox proportional hazards model and log-rank tests. Propensity score (PS) weighting was utilized to account for differences in patient characteristics and to minimize selection bias. Results: There were a total of 49,405 patients treated with XRT and 170 patients treated with PBT. Median follow-up time was 62.1 months. On MVA, the following factors were associated with receipt of PBT (all p < 0.05): WHO Grade I-II gliomas, treatment at an academic/research program, west geographic facility location, and surgical resection. After PS weighting, all patients treated with PBT were found to have superior median and 5 year survival than patients treated with XRT: 45.9 vs. 29.7 months ( p = 0.009) and 46.1 vs. 35.5% ( p = 0.0160), respectively. Conclusions: PBT is associated with improved OS compared to XRT for patients with gliomas. This finding warrants verification in the randomized trial setting in order to account for potential patient imbalances not adequately captured by the NCDB, such as tumor molecular characteristics and patient performance status. Importance of the Study: This is the first study that compares the outcomes of patients treated with photon based radiotherapy vs. proton based radiotherapy for patients with gliomas. In this retrospective analysis, the results demonstrate that proton therapy is associated with improved outcomes which support ongoing prospective, randomized clinical trials comparing the two modalities in patients with gliomas.

The purpose of this study was to determine the influence of insurance status on treatment and outcomes in oral cavity cancer. Patients were identified in the National Cancer Database (NCDB). Data were collected and analyzed using χ 2 tests, Kaplan-Meier methods, and multivariable Cox regression models. Those uninsured or on Medicaid were more likely to be younger (P<0.001), minority race (P<0.001), have a lower median household income (P<0.001), lower educational attainment (P<0.001), not undergo primary resection (P<0.001), present with higher T (P<0.001),N (P<0.001), and M (P<0.001) stage of disease, and have a higher tumor grade (P<0.001). On univariate analysis, those with private insurance had significantly better overall survival than those uninsured (hazard ratio (HR) 1.481), under Medicaid (HR 2.006), or on Medicare (HR 1.921). On multivariable Cox regression analysis, insurance status remained an independent prognosticator even after accounting for multiple demographic, socioeconomic, treatment, and clinicopathological factors. These data suggest that insurance status is associated with treatment and outcomes in patients with oral cavity cancer. Being uninsured or on Medicaid was found to be associated with a higher risk of a poorer prognosis when compared to private insurance, and the data suggest the need to expand comprehensive medical coverage and optimize access to adequate medical care in vulnerable patient populations., (Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: The purpose of this study was to determine the impact of adjuvant radiotherapy (RT) in locoregionally advanced oral cavity cancer., Methods: Data were extracted from the National Cancer Data Base, of which overall survival (OS) is the only outcome variable available. The chi-square test and Cox regression models were used., Results: A total of 6654 patients were identified. The utilization of adjuvant RT has increased over time. A propensity matched cohort included 3946 patients, exactly one-half of whom received adjuvant RT. Independent predictors associated with receipt of adjuvant RT included age, Charlson/Deyo comorbidity score, extracapsular extension, surgical margins, and T and N classifications. On multivariable analysis, adjuvant RT remained an independent prognosticator for OS., Conclusion: Receipt of adjuvant RT is a prognostic factor associated with improved OS, its utilization has increased over time, and it should be considered for clinically suitable patients who have undergone resection for the disease., (© 2018 Wiley Periodicals, Inc.)

The objective of our study is to determine the impact of adjuvant chemoradiation on overall survival (OS) for gliosarcoma in septuagenarians and octogenarians. Data were extracted from the National Cancer Data Base (NCDB). Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 23.0 (Armonk, NY: IBM Corp.) for data analyses. 210 patients with gliosarcoma who underwent resection were identified. 168 (80.0%) patients received adjuvant chemoradiation, and 42 (20.0%) received adjuvant RT alone. Patients were more likely to receive adjuvant chemoradiation if they were male vs. female (85.3% vs. 71.6%, p=0.016). There was no significant difference in receipt of adjuvant therapy by year of diagnosis, age at diagnosis, race, Charlson/Deyo Score, treatment facility type, tumor size, or extent of surgery. Those who received adjuvant chemoradiation had significantly better one-year OS than those who received adjuvant radiation alone (35.3% vs. 16.2%, p<0.001). On subset analysis, this significant one-year OS benefit was observed in septuagenarians, those with Charlson/Deyo Score of 0, and in those with tumor size ≤5cm. On multivariate analysis, receipt of adjuvant chemoradiation and greater extent of resection were independent prognostic factors for improved OS. Our data suggests that adjuvant chemoradiation is an independent prognostic factor for improved OS in elderly patients with gliosarcoma, and the results of our study can serve as estimated benchmarks for outcome in this growing and important patient population. Its benefit, however, may be limited to septuagenarians and those with lower comorbidity burden., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Chronic rhinosinusitis (CRS) is a commonly observed sequela after radiation therapy to the paranasal sinuses. The histopathologic features of radiation-induced CRS have yet to be determined and may have major implications in disease management., Methods: A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery (FESS). Histopathology variables, Lund-Mackay score (LMS), and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared among patients with radiation-induced CRS (CRSr), CRS without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP)., Results: Fifteen CRSr, 43 CRSsNP, and 56 CRSwNP patients who underwent FESS were analyzed. Compared with CRSsNP, CRSr cases had increased squamous metaplasia (40.0% vs 9.3%, p < 0.013) and subepithelial edema (53.3% vs. 2.3%, p < 0.001). Compared with CRSwNP, CRSr cases had fewer eosinophils per high-power field (20.0% vs 50.0%, p < 0.034), less basement membrane thickening (33.3% vs 76.8%, p < 0.002), and fewer eosinophil aggregates (0.0% vs 30.4%, p < 0.009). CRSr had significantly greater mean LMS (13.47 ± 5.13 vs 7.07 ± 4.79, p < 0.001) compared with CRSsNP., Conclusion: Radiation-induced CRS patients exhibited greater squamous metaplasia and subepithelial edema when compared with a cohort of patients with CRSsNP, and decreased eosinophilia and basement membrane thickening compared with a cohort of CRSwNP patients. CRSr cases demonstrated no difference in eosinophilia or neutrophilia compared with CRSsNP, and decreased eosinophilia compared with CRSwNP, lending further credence to the unique nature of radiation in the development of CRS in this patient group. These findings may have major implications with regard to extent of surgical intervention and medical management., (© 2017 ARS-AAOA, LLC.)

Importance: Community-level socioeconomic status, particularly insurance status, is increasingly becoming important as a possible determinant in patient outcomes., Objective: To determine the association of insurance and community-level socioeconomic status with outcome for patients with pharyngeal squamous cell carcinoma (SCC)., Design, Setting, and Participants: This study extracted data from more than 1500 Commission on Cancer-accredited facilities collected in the National Cancer Database. A total of 35 559 patients diagnosed with SCC of the pharynx from 2004 through 2013 were identified. The χ2 test, Kaplan-Meier method, and Cox regression models were used to analyze data from April 1, 2016, through April 16, 2017., Main Outcomes and Measures: Overall survival was defined as time to death from the date of diagnosis., Results: Among the 35 559 patients identified (75.6% men and 24.4% women; median age, 61 years [range, 18-90 years]), 15 146 (42.6%) had Medicare coverage; 13 061 (36.7%), private insurance; 4881 (13.7%), Medicaid coverage; and 2471 (6.9%), no insurance. Uninsured patients and Medicaid recipients were more likely to be younger, black, or Hispanic; to have lower median household income and lower educational attainment; to present with higher TNM stages of disease; and to start primary treatment at a later time from diagnosis. Those with private insurance (reference group) had significantly better overall survival than uninsured patients (hazard ratio [HR], 1.72; 95% CI, 1.59-1.87), Medicaid recipients (HR, 1.99; 95% CI, 1.88-2.12), or Medicare recipients (HR, 2.07; 95% CI, 1.99-2.16), as did those with median household income of at least $63 000 (reference) vs $48 000 to $62 999 (HR, 1.19; 95% CI, 1.13-1.26), $38 000 to $47 999 (HR, 1.31; 95% CI, 1.24-1.38), and less than $38 000 (HR, 1.51; 95% CI, 1.43-1.59). On multivariable analysis, insurance status and median household income remained independent prognostic factors for overall survival even after accounting for educational attainment, race, Charlson/Deyo comorbidity score, disease site, and TNM stage of disease., Conclusions and Relevance: Insurance status and household income level are associated with outcome in patients with SCC of the pharynx. Those without insurance and with lower household income may significantly benefit from improving access to adequate, timely medical care. Additional investigations are necessary to develop targeted interventions to optimize access to standard medical treatments, adherence to physician management recommendations, and subsequently, prognosis in these patients at risk.

To determine the impact of insurance status and income for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base. Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4325 patients with AA diagnosed from 2004 to 2013 were identified. 2781 (64.3%) had private insurance, 925 (21.4%) Medicare, 396 (9.2%) Medicaid, and 223 (5.2%) were uninsured. Those uninsured were more likely to be Black or Hispanic versus White or Asian (p < 0.001), have lower median income (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). 1651 (38.2%) had income ≥$63,000, 1204 (27.8%) $48,000-$62,999, 889 (20.5%) $38,000-$47,999, and 581 (13.4%) had income <$38,000. Those with lower income were more likely to be Black or Hispanic versus White or Asian (p < 0.001), uninsured (p < 0.001), reside in a rural area (p < 0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p < 0.001). Those with private insurance had significantly higher overall survival (OS) than those uninsured, on Medicaid, or on Medicare (p < 0.001). Those with income ≥$63,000 had significantly higher OS than those with lower income (p < 0.001). On multivariate analysis, age, insurance status, income, and adjuvant therapy were independent prognostic factors for OS. Being uninsured and having income <$38,000 were independent prognostic factors for worse OS in AA. Further investigations are warranted to help determine ways to ensure adequate medical care for those who may be socially disadvantaged so that outcome can be maximized for all patients regardless of socioeconomic status.

The objective of our study is to determine the influence of race on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi-square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1643 patients with AO were identified. 1386 (84.3%) were White, 83 (5.0%) Black, 133 (8.1%) Hispanic, and 41 (2.5%) were Asian. White and Black patients were significantly older than Hispanic and Asian patients (49.3% vs. 49.4% vs. 33.1% vs. 39.0%, p=0.003). Black patients were significantly less likely to be insured than White patients (12.8 vs. 7.2%, p<0.001) and significantly more likely to have lower income than other races (p<0.001). A trend towards higher comorbidity burden and lower rate of gross total resection was seen in Black patients. Black patients had significantly worse five-year OS compared to White, Hispanic, and Asian patients (40.3% vs. 52.3% vs. 67.8% vs. 67.7%, p=0.028). Of those who received adjuvant chemoRT, Black patients still had significantly worse OS compared to White patients (p=0.021). On multivariate analysis, Black race, older age at diagnosis, and not receiving adjuvant chemoradiotherapy were independent prognostic factors for worse OS in anaplastic oligodendroglioma. Future studies are warranted to help determine predictors for unfavorable molecular status, ways to optimize management of comorbidities, and interventions to help ensure adequate access to medical care for all patients to better care for those who may be at more risk for poorer outcome., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

To determine the receipt and impact of adjuvant therapy on overall survival (OS) for anaplastic astrocytoma (AA). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 4807 patients with AA diagnosed from 2004 to 2013 who underwent surgery were identified. 3243 (67.5 %) received adjuvant chemoRT, 525 (10.9 %) adjuvant radiotherapy (RT) alone, 176 (3.7 %) adjuvant chemotherapy alone and 863 (18.0 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 (p = 0.022), were ≤ 50 years (p < 0.001), were male (p = 0.043), were Asian or White race (p < 0.001), had private insurance (p < 0.001), had income ≥$38,000 (p < 0.001), or underwent total resection (p < 0.003). Those who received adjuvant chemoRT had significantly better 5-year OS than the other adjuvant treatment types (41.8 % vs. 31.2 % vs. 29.8 % vs. 27.4 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age at diagnosis. Of those undergoing adjuvant chemoRT, those receiving ≥59.4 Gy had significantly better 5-year OS than those receiving <59.4 Gy (44.4 % vs. 25.9 %, p < 0.001). There was no significant difference in OS when comparing 59.4 Gy to higher RT doses. On multivariate analysis, receipt of adjuvant chemoRT, age at diagnosis, extent of disease, and insurance status were independent prognostic factors for OS. Adjuvant chemoRT is an independent prognostic factor for improved OS in AA and concomitant chemoRT should be considered for all clinically suitable patients who have undergone surgery for the disease.

The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9 %) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0 %) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4 %) adjuvant RT alone, and 401 (23.7 %) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004-2008 (p < 0.001), had Karnofsky Performance Status >70 vs. <70 (p = 0.018), had private insurance vs. Medicaid vs. no insurance (p < 0.001), or had median income ≥$63,000 vs. <$63,000 (p = 0.014). Those who received adjuvant chemoRT (concomitant or sequential) had significantly better 5-year OS than those who received adjuvant RT alone or no adjuvant therapy (59.8 % vs. 65.0 % vs. 44.9 % vs. 45.6 %, p < 0.001). This significant 5-year OS benefit was also observed regardless of age. There was no difference in OS when comparing concomitant chemoRT to sequential RT and chemotherapy (p = 0.481). On multivariate analysis, receipt of adjuvant chemoRT (concomitant or sequential) remained an independent prognostic factor for improved OS. Adjuvant chemoRT (concomitant or sequential) is an independent prognostic factor for improved OS in anaplastic oligodendroglioma and should be considered for all clinically suitable patients who have undergone surgery for the disease.

Objective: The purpose of this study was to determine dose delivered to individual mandibular tooth-bearing regions during adjuvant intensity-modulated radiotherapy for laryngeal cancers., Study Design: Twenty patients with laryngeal cancer treated with intensity-modulated radiotherapy were included. Individual mandibular tooth-borne areas were manually contoured. Average doses were calculated for individual teeth., Results: Doses to individual teeth increased with more posterior location. Highest dose was observed for third molar (M3) (43.1 Gy; P < .001). Doses to molars and premolars correlated with T- and N-stage (P = .007; P < .001, respectively). For ipsilateral nodal disease, there was no difference between the doses to ipsilateral teeth and contralateral teeth. Only in N2 c tumors, dose was above our threshold for extraction for M3 only (51.5 Gy)., Conclusions: T- and N-stage drive dose to individual mandibular tooth-borne areas. With the exception of the posterior molars, particularly in node-positive patients, radiation exposure falls below the threshold reported for pre-RT tooth extractions (50 Gy). We concluded that a more conservative approach to prophylactic tooth extraction with a greater emphasis on dental management may be warranted for the prevention of osteoradionecrosis in patients with laryngeal cancer receiving adjuvant RT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Ondine׳s curse is a rare, potentially life-threatening disorder characterized by loss of automatic breathing during sleep and preserved voluntary breathing. It is seldom encountered in the radiotherapy clinic but can pose significant technical challenges and safety concerns in the delivery of a prescribed radiation course. We report a unique case of successful delivery of radiotherapy for ependymoma in a patient with Ondine׳s curse. A 53-year-old gentleman presented with vertigo when lying down. Brain magnetic resonance imaging revealed an enhancing mass in the floor of the fourth ventricle. He underwent maximal safe resection. Pathology revealed ependymoma. The patient was referred for radiotherapy. Computed tomography simulation was performed in supine position with 3-point thermoplastic mask immobilization. Sequential TomoTherapy plans were developed. At first scheduled treatment, shortly after mask placement, his arms went limp and he was unresponsive. Vitals showed oxygen saturation 83%, pulse 127, and blood pressure 172/97mmHg. He was diagnosed with Ondine׳s curse thought secondary to previous brainstem damage; the combination of lying flat and pressure from the mask was causing him to go into respiratory arrest. As supine positioning did not seem clinically advisable, he was simulated in prone position. A RapidArc plan and a back-up conformal plan were developed. Prescriptions were modified to meet conservative organs-at-risk constraints. Several strategies were used to minimize uncertainties in set-up reproducibility associated with prone positioning. He tolerated prone RapidArc treatments well. The report highlights the importance of applying practical patient safety and treatment planning/delivery strategies in the management of this challenging case., (Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Background. For large basal cell carcinomas (BCCs) of the head and neck, definitive surgery often requires extensive resection and reconstruction that may result in prolonged recovery and limited cosmesis. Vismodegib, a small-molecule inhibitor of the hedgehog pathway, is approved for advanced and metastatic BCCs. We present a case of advanced BCC treated with combination of vismodegib, radiotherapy, and local excision resulting in excellent response and cosmesis. Case Presentation. A 64-year-old gentleman presented with a 5-year history of a 7 cm enlarging right cheek mass, with extensive vascularization, central ulceration, and skin, soft tissue, and buccal mucosa involvement. Biopsy revealed BCC, nodular type. Up-front surgical option involved a large resection and reconstruction. After multidisciplinary discussion, we recommended and he opted for combined modality of vismodegib, radiotherapy, and local excision. The patient tolerated vismodegib well and his right cheek lesion decreased significantly in size. He was then treated with radiotherapy followed by local excision that revealed only focal residual BCC. Currently, he is without evidence of disease and has excellent cosmesis. Conclusions. We report a case of locally advanced BCC treated with trimodality therapy with vismodegib, radiotherapy, and local excision, resulting in excellent outcome and facial cosmesis, without requiring extensive resection or reconstructive surgery.

This article gives a brief historical overview of the development of standard management for high-grade gliomas (HGGs). The current standard of care, trimodality therapy with maximal safe resection followed by involved-field radiotherapy (RT) with concomitant/adjuvant temozolomide, confers median survival of 14.6 months, and a modest but measurable proportion (9.8%) of patients survives 5 or more years. We review the toxicities associated with irradiation of the central nervous system for patients with HGG, with focus on the pathophysiology, clinical manifestations, and potential preventative strategies for long-term neurocognitive dysfunction, which remains a pervasive, progressive, and clinically devastating sequela of trimodality therapy. Treatment of cognitive decline after RT is limited, and strategies for preventing this complication are being investigated., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: This report focuses on the overall survival and complications associated with treatment of cerebral metastases with surgical resection followed by stereotactic radiosurgery (SRS). Management and complications of corticosteroid therapy are underreported in the literature but represent an important source of morbidity for patients., Methods: Fifty-nine consecutive patients underwent surgical resection of a cerebral metastasis followed by SRS to the cavity. Patient charts were reviewed retrospectively to ascertain overall survival, local control, surgical complications, SRS complications, and corticosteroid complications., Results: Our mean follow-up was 14.4 months (median 12.0 months, range 0.9-62.9 months). Median overall survival in this series was 15.25 months and local control was 98.3%. There was a statistically significant survival benefit conferred by Radiation Therapy Oncology Group recursive partitioning analysis Classes 1 and 2. The surgical complication rate was 6.8% while the SRS complication rate was 2.4%. Corticosteroid complications are reported and dependence at 1 month was 20.3%, at 3 months 6.8%, at 6 months 1.7%, and at 12 months no patients remained on corticosteroid therapy., Conclusions: Overall survival and local control with this treatment paradigm compare well to the other published literature. Complications associated with this patient population are low. A corticosteroid tapering protocol is proposed and demonstrated lower rates of steroid-related complications and dependence than previously reported.

Introduction: We compared integral dose with uninvolved brain (IDbrain ) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit., Methods: We prepared four PBRT treatment plans for four patients with high-grade gliomas (60 Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and IDbrain for all plans., Results: There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. IDbrain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean IDbrain 23.64 Gy vs. 28 Gy and 18.7 Gy vs. 24.5 Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7 Gy vs. 23.64 Gy and 24.5 Gy vs. 28 Gy, respectively)., Conclusions: In the setting of PBRT for high-grade gliomas, IMRT reduces IDbrain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces IDbrain compared with STD PBRT delivered with either traditional IMRT or HT., (© 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.)

Background: Despite improvements in surgical technique, radiation therapy delivery, and options for systemic cytotoxic therapy, the median survival for patients with newly diagnosed glioblastoma multiforme remains poor at 15 months with trimodality therapy. Multiple immunologic approaches are being tested to enhance the response of these tumors to existing therapy and/or to stimulate innate immune responses., Methods: We review the existing data that support the continued development of immunologic therapy in the treatment armamentarium against glioblastoma multiforme, with a focus on clinical data documenting outcomes., Results: In phase I and phase II trials, antitumor vaccines (dendritic and formalin-fixed) have demonstrated clinical efficacy with mild toxicity, suggesting that innate immune responses can be amplified and directed against these tumors. Suicide gene therapy (gene-mediated cytotoxic therapy) using a number of viral vectors and molecular pathways has also shown efficacy in completed phase I and ongoing phase II trials. In addition, neural stem cells are being investigated as vectors in this approach., Conclusions: Although phase III data are needed before immunologic therapies can be widely implemented into clinical practice, the existing phase I and phase II data suggest that these therapies can produce meaningful and sometimes durable responses in patients with glioblastoma multiforme with mild toxicity compared with other existing therapies.

Introduction: The aim of this study was to assess the feasibility of sparing contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and limbic circuit during partial brain radiotherapy (PBRT)., Methods and Materials: Treatment plans were generated for five hemispheric high-grade gliomas, five hemispheric low-grade gliomas and two brainstem gliomas (12 patients). For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as IMRT plans which spared contralateral (hemispheric cases) or bilateral (brainstem cases) limbic circuit, hippocampus, and NSC. Biologically equivalent dose for late effects (BED(late effects)) was generated for limbic circuit, hippocampus and NSC. Per cent relative reduction in mean physical dose and BED was calculated for each plan (standard vs. sparing)., Results: We were able to reduce physical dose and BED(late effects) to these critical structures by 23.5-56.8% and 23.6-66%, respectively., Conclusion: It is possible to spare contralateral limbic circuit, NSC and hippocampus during PBRT for both high- and low-grade gliomas using IMRT, and to spare the hippocampus bilaterally during PBRT for brainstem low-grade gliomas. This approach may reduce late cognitive sequelae of cranial radiotherapy., (© 2011 The Authors. Journal of Medical Imaging and Radiation Oncology © 2011 The Royal Australian and New Zealand College of Radiologists.)

Objectives: To assess possible improved efficacy of Boron Neutron Capture Therapy (BNCT) for glioblastoma multiforme (GBM) using prolonged infusion and a correspondingly higher dose of l-boronophenylalanine, as the fructose complex (BPA-f)., Materials and Methods: The benefit of prolonged infusion was analyzed by comparing the results from a Phase II study using 6 h infusion of BPA-f with those obtained from a Phase I/II study using 2 h of infusion. Median survival time (MST) from diagnosis, patient baseline characteristics, salvage treatment and severe adverse events were considered in the comparison., Results: MST increased significantly, from 12.8 (95% confidence interval or CI: 10.3-14.0) months with 2 h infusion to 17.7 (95% CI: 13.6-19.9) months with 6 h of infusion. The fraction of patients with WHO grade 3-4 adverse events was similar in the two studies at 13% and 14%, respectively., Conclusion: Prolonged infusion was found to be beneficial for the efficacy of BNCT and it is suggested that 6 h infusion of BPA-f should be used in future trials of BNCT for GBM. BNCT, which is a single-day treatment with mild side effects, should be assessed in a controlled trial, as an alternative to 30 daily fractions of conventional fractionated photon therapy over a period of 6 weeks.

Object: The purpose of this study was to assess the durability and completeness of pain relief in patients treated using stereotactic gamma knife surgery (GKS) for trigeminal neuralgia (TN)., Methods: Thirty-eight patients with refractory TN were treated with stereotactic GKS. All patients received a prescription radiation dose of 35, 40, or 45 Gy to the 50% isodose surface through a 4-mm collimator helmet. The group was assessed regularly based on physician-directed interviews for a median follow up of 24 months (range 6-27 months). Pain relief was classified as excellent (no pain without medication), good (well-controlled pain with continued medication), fair (decreased but residual pain with continued medication), or poor (unimproved or increased pain with the same or increased medication). Three months after treatment, pain relief was good or excellent in 71% of patients. By 24 months post-GKS, 50% of the original cohort had poor pain relief, 21% continued to have either excellent or good relief, 3% had fair relief, and 26% had not reached the 24-month follow up. Based on their status at the last follow up, 29% of patients had excellent and 16% had good pain relief. Thirty-seven percent experienced facial numbness, which was dose related. In addition, there was a significantly higher rate of complete pain relief in patients who had facial numbness following treatment (p = 0.003)., Conclusions: Stereotactic GKS is an effective treatment in patients with TN; however, the durability of pain relief and the time to treatment response are limiting factors. As with other types of ablative treatment, facial numbness is strongly associated with better treatment response.

Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumor tissue. The key to effective BNCT of tumors such as glioblastoma multiforme (GBM) is the homogeneous preferential accumulation of 10B in the tumor, including the infiltrating GBM cells, as compared to that in the vital structures of the normal brain. Provided that sufficiently high tumor 10B concentration (approximately 10(9) boron-10 atoms/cell) and an adequate thermal neutron fluence (approximately 10(9) neutrons/cm2) are achieved, it is the ratio of the 10B concentration in tumor cells to that in the normal brain cells and the blood that will largely determine the therapeutic gain of BNCT.

A numerical model with a memory effect was created to describe the kinetics of 10B in blood after a single 4-dihydroxyborylphenylalanine-fructose complex (BPA-F) infusion in boron neutron capture therapy (BNCT). The model formulation was based on the averaged data from 10 glioma patients from the Brookhaven National Laboratory (BNL) BNCT-trials. These patients received a 2 h i.v. infusion of a BPA-fructose complex that delivered 290 mg BPA/kg body weight. The model was validated by fitting the original BNL patient data and new patient data from the Finnish BNCT-trials. The new 3-parameter non-linear model provided mean absolute differences between the measured and estimated 10B concentrations in blood that were less than 3.9% when used to simulate actual patient irradiations that comprised two irradiation fields separated by a break to reposition the patient. The flexibility of the model was successfully tested with two different infusion protocols. The patient data were modelled with a two-compartment model and a bi-exponential fit for comparison. The 3-parameter model is better than previously described models in predicting the time course of blood 10B concentration after cessation of intravenous infusion of BPA-fructose.

Purpose: To create simple and reliable models for clinical practice for estimating the blood (10)B time-concentration curve after p-boronophenylalanine fructose complex (BPA-F) infusion in patients during neutron irradiation in boron neutron capture therapy (BNCT)., Methods and Materials: BPA-F (290 mg BPA/kg body weight) was infused i.v. during two hours to 10 glioblastoma multiforme patients. Blood samples were collected during and after the infusion. Compartmental models and bi-exponential function fit were constructed based on the (10)B blood time-concentration curve. The constructed models were tested with data from six additional patients who received various amounts of infused BPA-F and data from one patient who received a one-hour infusion of 170 mg BPA/kg body weight., Results: The resulting open two-compartment model and bi-exponential function estimate the clearance of (10)B after 290 mg BPA/kg body weight infusion from the blood with satisfactory accuracy during the first irradiation field (1 ppm, i.e., 7%). The accuracy of the two models in predicting the clearance of (10)B during the second irradiation field are for two-compartment model 1.0 ppm (8%) and 0.2 ppm (2%) for bi-exponential function. The models predict the average blood (10)B concentration with an increasing accuracy as more data points are available during the treatment., Conclusion: By combining the two models, a robust and practical modeling tool is created for the estimation of the (10)B concentration in blood after BPA-F infusion.

Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumour tissue. Boron-10 nuclei capture slow 'thermal' neutrons preferentially and, upon capture, promptly undergo 10B(n,alpha)7Li reaction. The ionization tracks of energetic and heavy lithium and helium ions resulting from this reaction are only about one cell diameter in length (approximately 14 microm). Because of their high linear energy transfer (LET) these ions have a high relative biological effectiveness (RBE) for controlling tumour growth. The key to effective BNCT of tumours, such as glioblastoma multiforme (GBM), is the preferential accumulation of boron-10 in the tumour, including the infiltrating GBM cells, as compared with that in the vital structures of the normal brain. Provided that a sufficiently high tumour boron-10 concentration (approximately 10(9) boron-10 atoms/cell) and an adequate thermal neutron fluence (approximately 10(12) neutrons/cm2) are achieved, it is the ratio of the boron-10 concentration in tumour cells to that in the normal brain cells that will largely determine the therapeutic gain of BNCT.

OBJECTIVE: The primary objective of these Phase I/II dose-escalation studies is to evaluate the safety of boronophenylalanine (BPA)-fructose-mediated boron neutron capture therapy (BNCT) for patients with glioblastoma multiforme (GBM). A secondary purpose is to assess the palliation of GBM by BNCT, if possible. METHODS: Thirty-eight patients with GBM have been treated. Subtotal or gross total resection of GBM was performed for 38 patients (median age, 56 yr) before BNCT. BPA-fructose (250 or 290 mg BPA/kg body weight) was infused intravenously, in 2 hours, approximately 3 to 5 weeks after surgery. Neutron irradiation was begun between 34 and 82 minutes after the end of the BPA infusion and lasted 38 to 65 minutes. RESULTS: Toxicity related to BPA-fructose was not observed. The maximal radiation dose to normal brain varied from 8.9 to 14.8 Gy-Eq. The volume-weighted average radiation dose to normal brain tissues ranged from 1.9 to 6.0 Gy-Eq. No BNCT-related Grade 3 or 4 toxicity was observed, although milder toxicities were seen. Twenty-five of 37 assessable patients are dead, all as a result of progressive GBM. No radiation-induced damage to normal brain tissue was observed in postmortem examinations of seven brains. The minimal tumor volume doses ranged from 18 to 55 Gy-Eq. The median time to tumor progression and the median survival time from diagnosis (from Kaplan-Meier curves) were 31.6 weeks and 13.0 months, respectively. CONCLUSION: The BNCT procedure used has been safe for all patients treated to date. Our limited clinical evaluation suggests that the palliation offered by a single session of BNCT is comparable to that provided by fractionated photon therapy. Additional studies with further escalation of radiation doses are in progress.