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Purpose: Acute skin toxicity is one of the most common side effects of breast cancer radiotherapy. To date, no one has estimated the nonmedical out-of-pocket expenses associated with this side effect. The primary aim of the present descriptive, exploratory study was to assess the feasibility of a newly developed skin toxicity costs questionnaire. The secondary aims were to: (1) estimate nonmedical out-of-pocket costs, (2) examine the nature of the costs, (3) explore potential background predictors of costs, and (4) explore the relationship between patient-reported dermatologic quality of life and expenditures.Methods: A total of 50 patients (mean age = 54.88, Stage 0-III) undergoing external beam radiotherapy completed a demographics/medical history questionnaire as well as a seven-item Skin Toxicity Costs (STC) questionnaire and the Skindex-16 in week 5 of treatment.Results: Mean skin toxicity costs were $131.64 (standard error [SE] = $23.68). Most frequently incurred expenditures were new undergarments and products to manage toxicity. Education was a significant unique predictor of spending, with more educated women spending more money. Greater functioning impairment was associated with greater costs. The STC proved to be a practical, brief measure which successfully indicated specific areas of patient expenditures and need.Conclusions: Results reveal the nonmedical, out-of-pocket costs associated with acute skin toxicity in the context of breast cancer radiotherapy. To our knowledge, this study is the first to quantify individual costs associated with this treatment side effect, as well as the first to present a scale specifically designed to assess such costs.Relevance: In future research, the STC could be used as an outcome variable in skin toxicity prevention and control research, as a behavioral indicator of symptom burden, or as part of a needs assessment. [ABSTRACT FROM AUTHOR]

Background/Objectives : Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. Methods : We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. Results : In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively ( p = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively ( p = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ 2 test, p = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ 2 test, p = 0.0018). Conclusions : We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality.

Background: Prostate-specific membrane antigen (PSMA) is a membrane-bound metallopeptidase highly expressed in the neovasculature of many solid tumors including gliomas. It is a particularly enticing therapeutic target due to its ability to internalize, thereby delivering radioligands or pharmaceuticals to the intracellular compartment. Targeting the neovasculature of gliomas using PSMA for diagnosis and management has been a recent area of increased study and promise. The purpose of this review is to synthesize the current state and future directions of PSMA use in the histopathologic study, imaging, and treatment of gliomas., Methods: PubMed and Scopus databases were used to conduct a literature review on PSMA use in gliomas in June 2023. Terms searched included "PSMA," "Prostate-Specific Membrane Antigen" OR "PSMA" OR "PSMA PET" AND "glioma" OR "high grade glioma" OR "glioblastoma" OR "GBM.", Results: Ninety-four publications were screened for relevance with 61 studies, case reports, and reviews being read to provide comprehensive context for the historical, contemporary, and prospective use of PSMA in glioma management., Conclusions: PSMA PET imaging is currently a promising and accurate radiographic tool for the diagnosis and management of gliomas. PSMA histopathology likely represents a viable tool for helping predict glioma behavior. More studies are needed to investigate the role of PSMA-targeted therapeutics in glioma management, but preliminary reports have indicated its potential usefulness in treatment., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Brain metastases pose a significant therapeutic challenge in the field of oncology, necessitating treatments that effectively control disease progression while preserving neurological and cognitive functions. Among various interventions, brachytherapy, which involves the direct placement of radioactive sources into or near tumors or into the resected cavity, can play an important role in treatment. Current literature describes brachytherapy's capacity to deliver targeted, high-dose radiation while minimizing damage to adjacent healthy tissues-a crucial consideration in the choice of treatment modality. Furthermore, advancements in implantation techniques as well as in the development of different isotopes have expanded its efficacy and safety profile. This review delineates the contemporary applications of brachytherapy in managing brain metastases, examining its advantages, constraints, and associated clinical outcomes, and provides a comprehensive understanding of advances in the use of brachytherapy for brain metastasis treatment, with implications for improved patient outcomes and enhanced quality of life.

Background: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients., Methods: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery., Results: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001)., Conclusions: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Radionecrosis describes a rare but serious complication of radiation therapy. In clinical practice, stereotactic radiosurgery (SRS) is increasingly used in combination with systemic therapy, including chemotherapy, immune checkpoint inhibitor and targeted therapy, either concurrently or sequentially. There is a paucity of literature regarding radionecrosis in patients receiving whole brain radiation therapy (WBRT) alone (without additional SRS) in combination with immunotherapy or targeted therapies. It is observed that certain combinations increase the overall radiosensitivity of the tumorous lesions. We present a rare case of symptomatic radionecrosis almost 1 year after WBRT in a patient with non-squamous non-small cell lung cancer on third-line chemoimmunotherapy. We discuss available research regarding factors that may lead to radionecrosis in these patients, including molecular and genetic profiles, specific drug therapy combinations and their timing or increased overall survival., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Purpose: Full-length vaginal (FLV) brachytherapy for patients with endometrial cancer and high-risk features should be considered as per the American Brachytherapy Society to reduce distal vaginal recurrence in patients with endometrial cancers with papillary serous/clear cell histologies, grade 3 status, or extensive lymphovascular invasion. We sought to investigate this patient population and report outcomes of treatment with high-dose-rate (HDR) brachytherapy in women treated with FLV brachytherapy versus partial-length vaginal (PLV) brachytherapy., Methods and Materials: With institutional review board approval, we identified patients with endometrial cancer meeting American Brachytherapy Society criteria of high-risk features treated with adjuvant HDR between 2004 and 2010. HDR doses were 21Gy in 3 fractions delivered to either the full-length or partial-length vagina. Acute and late toxicities were evaluated using the Radiation Therapy Oncology Group scale and Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer grading, respectfully. Vaginal recurrences were assessed by physical examination and pap smears. Statistical analyses were performed using SPSS version 23 software., Results: Of 240 patients treated with HDR brachytherapy, 121 were treated with FLV brachytherapy, and 119, with PLV brachytherapy. The median follow-up was 9.5 years (range, 8-11 years) for FLV patients and 8.5 years (range, 7-10 years) for PLV patients; 0% of patients had vaginal recurrences, and 1.4% and 0.9% had proximal vaginal recurrences, respectively (P = .54). All patients treated with FLV brachytherapy developed grade 3 mucositis of the lower vagina/introitus (P < .0001) and had increased analgesics use compared with those treated with PLV brachytherapy (P < .0001). In total, 23% of patients treated with FLV brachytherapy developed grade 3 stenosis of the lower vagina/introitus, in contrast to 0% of patients treated with PLV brachytherapy (P < .0001)., Conclusions: PLV brachytherapy is as effective as FLV brachytherapy in reducing local recurrence and causes a significantly lower incidence of acute and late toxicities. The results of this study caution radiation oncologists regarding the careful use of FLV brachytherapy in patients with endometrial cancer and high-risk features., Competing Interests: Disclosures The work of all the listed parties was completed while they were affiliated with Weill Medical College of Cornell University, New York, New York; however, current affiliations are listed., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The incidence of brain metastases (BM) amongst cancer patients has been increasing due to improvements in therapeutic options and an increase in overall survival. Molecular characterization of tumors has provided insights into the biology and oncogenic drivers of BM and molecular subtype-based screening. Though there are currently some screening and surveillance guidelines for BM, they remain limited. In this comprehensive review, we review and present epidemiological data on BM, their molecular characterization, and current screening guidelines. The molecular subtypes with the highest BM incidence are epithelial growth factor receptor -mutated non-small cell lung cancer (NSCLC), BRCA1 , triple-negative (TN), and HER2+ breast cancers, and BRAF -mutated melanoma. Furthermore, BMs are more likely to present asymptomatically at diagnosis in oncogene-addicted NSCLC and BRAF -mutated melanoma. European screening standards recommend more frequent screening for oncogene-addicted NSCLC patients, and clinical trials are investigating screening for BM in hormone receptor+, HER2+, and TN breast cancers. However, more work is needed to determine optimal screening guidelines for other primary cancer molecular subtypes. With the advent of personalized medicine, molecular characterization of tumors has revolutionized the landscape of cancer treatment and prognostication. Incorporating molecular characterization into BM screening guidelines may allow physicians to better identify patients at high risk for BM development and improve patient outcomes., Competing Interests: The authors report no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Purpose: We systematically reviewed visual outcomes over the last three decades in patients undergoing treatment for base of skull (BOS) meningiomas and provide recommendations to preserve vision., Methods: In accordance with the PRISMA guidelines for systematic reviews, a search was conducted from 6/1/2022-9/1/2022 using PubMed and Web of Science. Inclusion criteria included (1) patients treated for BOS meningiomas (2) treatment modality specified (3) specifics of surgical techniques and/or dose/fractions of radiotherapy (4) individual patient outcomes of treatment. Each study was assessed for bias based on study design and heterogeneity of results., Results: A total of 50 studies were included (N = 2911). When comparing improved vision versus unchanged or worsened vision, studies investigating surgery alone published from 2006 and onward had significantly better visual outcomes compared to pre-2006 studies (p = 0.02). When comparing improved vision versus unchanged or worsened vision, studies investigating combined therapy with surgery and radiation published from 2008 and onward had significantly better visual outcomes compared to pre-2008 studies (p < 0.01). Combined modality therapy was less likely to worsen vision compared to either surgery or radiation monotherapy (p < 0.01). However, surgery and radiation monotherapy were more likely to actually improve outcomes compared to combination therapy (p < 0.01)., Conclusion: For over a decade we have observed improvement in visual outcomes in patients managed for meningioma of BOS, likely attributing the innovation in microsurgical and more targeted and conformal radiation techniques. Combination therapy may be the safest option for preventing worsening of vision, but the highest rates of improving visual function are achieved through monotherapy when indicated., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We systematically reviewed the current landscape of hippocampal-avoidance radiotherapy, focusing specifically on rates of hippocampal tumor recurrence and changes in neurocognitive function., Methods: PubMed was queried for studies involving hippocampal-avoidance radiation therapy and results were screened using PRISMA guidelines. Results were analyzed for median overall survival, progression-free survival, hippocampal relapse rates, and neurocognitive function testing., Results: Of 3709 search results, 19 articles were included and a total of 1611 patients analyzed. Of these studies, 7 were randomized controlled trials, 4 prospective cohort studies, and 8 retrospective cohort studies. All studies evaluated hippocampal-avoidance whole brain radiation treatment (WBRT) and/or prophylactic cranial irradiation (PCI) in patients with brain metastases. Hippocampal relapse rates were low (overall effect size = 0.04; 95% confidence interval [0.03, 0.05]) and there was no significant difference in risk of relapse between the five studies that compared HA-WBRT/HA-PCI and WBRT/PCI groups (risk difference = 0.01; 95% confidence interval [- 0.02, 0.03]; p = 0.63). 11 out of 19 studies included neurocognitive function testing. Significant differences were reported in overall cognitive function and memory and verbal learning 3-24 months post-RT. Differences in executive function were reported by one study, Brown et al., at 4 months. No studies reported differences in verbal fluency, visual learning, concentration, processing speed, and psychomotor speed at any timepoint., Conclusion: Current studies in HA-WBRT/HA-PCI showed low hippocampal relapse or metastasis rates. Significant differences in neurocognitive testing were most prominent in overall cognitive function, memory, and verbal learning. Studies were hampered by loss to follow-up., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The introduction of Cesium-131 (Cs-131) as a radiation source has led to a resurgence of brachytherapy for central nervous system (CNS) tumors. The aim of this study was to evaluate the safety and efficacy of the largest cohort of Cs-131 patients to-date., Methods: A retrospective review of all CNS tumors treated with resection and adjuvant Cs-131 brachytherapy at New York-Presbyterian/Weill Cornell from 2010 to 2021 was performed. Overall survival (OS) and local control (LC) were assessed with Kaplan-Meier methodology. Univariable analysis was conducted to identify patient factors associated with local recurrence or radiation necrosis., Results: Adjuvant Cs-131 brachytherapy following resection was performed in 119 patients with a median follow-up time of 11.8 (IQR 4.7-23.6) months and a mean of 22.3 +/-30.3 months. 1-year survival rates were 53.3% (95%CI 41.9-64.6%) for brain metastases (BrM), 45.9% (95%CI 24.8-67.0%) for gliomas, and 73.3% (95%CI 50.9-95.7%) for meningiomas. 1-year local control rates were 84.7% for BrM, 34.1% for gliomas, and 83.3% for meningiomas (p < 0.001). For BrM, local control was superior in NSCLC relative to other BrM pathologies (90.8% versus 76.5%, p = 0.039). Radiographic radiation necrosis (RN) was identified in 10 (8.4%) cases and demonstrated an association with smaller median tumor size (2.4 [IQR 1.8-2.7 cm] versus 3.1 [IQR 2.4-3.8 cm], p = 0.034). Wound complications occurred in 14 (11.8%) patients., Conclusions: Cs-131 brachytherapy demonstrated a favorable safety and efficacy profile characterized by high rates of local control for all treated pathologies. The concept of brachytherapy has seen a resurgence given the excellent results when Cs-131 is used as a source., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The phenomenon of radiation therapy (RT) causing regression of targeted lesions as well as lesions outside of the radiation field is known as the abscopal effect and is thought to be mediated by immunologic causes. This phenomena has been described following whole brain radiation (WBRT) and stereotactic radiosurgery (SRS) of brain metastasis (BM) in advanced melanoma and non-small-cell lung cancer (NSCLC). We systematically reviewed the available literature to identify which radiation modality and immunotherapy (IT) combination may elicit the abscopal effect, the optimal timing of RT and IT, and potential adverse effects inherent to the combination of RT and IT., Methods: Using PRISMA guidelines, a search of PubMed, Medline, and Web of Science was conducted to identify studies demonstrating the abscopal effect during treatment of NSCLC or melanoma with BM., Results: 598 cases of irradiated BM of melanoma or NSCLC in 18 studies met inclusion criteria. The most commonly administered ITs included PD-1 or CTLA-4 immune checkpoint inhibitors (ICI), with RT most commonly administered within 3 months of ICI. Synergy between ICI and RT was described in 16 studies including evidence of higher tumor response within and outside of the irradiated field. In the 12 papers (n = 232 patients) that reported objective response rate (ORR) in patients with BM treated with RT and concurrent systemic IT, the non-weighted mean ORR was 49.4%; in the 5 papers (n = 110 patients) that reported ORR for treatment with RT or IT alone, the non-weighted mean ORR was 27.8%. No studies found evidence of significantly increased toxicity in patients receiving RT and ICI., Conclusion: The combination of RT and ICIs may enhance ICI efficacy and induce more durable responses via the abscopal effect in patients with brain metastases of melanoma or NSCLC., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Cesium-131 radioactive isotope has favored the resurgence of intracavitary brachytherapy in neuro-oncology, minimizing radiation-induced complications and maximizing logistical and clinical outcomes. We reviewed the literature on cesium-131 brachytherapy for brain tumors., Methods: PubMed, Web-of-Science, Scopus, Clinicaltrial.gov, and Cochrane were searched following the PRISMA extension for scoping reviews to include published studies and ongoing trials reporting cesium-131 brachytherapy for brain tumors., Results: We included 27 published studies comprising 279 patients with 293 lesions, and 3 ongoing trials. Most patients had brain metastases (63.1%), followed by high-grade gliomas (23.3%), of WHO Grade III (15.2%) and Grade IV (84.8%), and meningiomas (13.6%), mostly of WHO Grade II (62.8%) and Grade III (27.9%). Most brain metastases were newly diagnosed (72.3%), while most gliomas and meningiomas were recurrent (95.4% and 88.4%). Patients underwent gross-total (91.1%) or subtotal (8.9%) resection, with median postoperative cavity size of 3.5 cm (range 1-5.8 cm). A median of 20, 28, and 16 seeds were implanted in gliomas, meningiomas, and brain metastases, with median seed activity of 3.8 mCi (range 2.4-5 mCi). Median follow-up was 16.2 months (range 0.6-72 months). 1-year freedom from progression rates were local 94% (range 57-100%), regional 85.1% (range 55.6-93.8%), and distant 53.5% (range 26.3-67.4%). Post-treatment radiation necrosis, seizure, and surgical wound infection occurred in 3.4%, 4.7%, and 4.3% patients., Conclusion: Initial data suggest that cesium-131 brachytherapy is safe and effective in primary or metastatic malignant brain tumors. Ongoing trials are evaluating long-term locoregional tumor control and future studies should analyze its role in multimodal systemic tumor management., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective The goal of this study is to compare the effectiveness of three different meditation techniques (two internal focus techniques and one external focus technique) using a low-cost portable electroencephalography (EEG) device, namely, MUSE, for an objective comparison. Methods This is an IRB-approved retrospective study. All participants in the study were healthy adults. Each study participant (n = 34) was instructed to participate in three meditation sessions: mantra (internal), breath (internal), and external point. The MUSE brain-sensing headband (EEG) was used to document the "total time spent in the calm state" and the "total time spent in the calm or neutral state" (outcomes) in each three-minute session to conduct separate analyses for the meditation type. Separate generalized linear models (GLM) with unstructured covariance structures were used to examine the association between each outcome and the explanatory variable (meditation type). For all models, if there was a significant association between the outcome and the explanatory variable, pairwise comparisons were carried out using the Tukey-Kramer correction. Results The median time (in seconds) spent in the calm state while practicing mantra meditation was 131.5 (IQR: 94-168), while practicing breath meditation was 150 (IQR: 113-164), and while practicing external-point meditation was 100 (IQR: 62-126). Upon analysis, there was a significant association between the meditation type and the time spent in the calm state (p-value = 0.0006). Conclusion This is the first study comparing "internal" versus "external" meditation techniques using an objective measure. Our study shows the breath and mantra technique as superior to the external-point technique as regards time spent in the calm state. Additional research is needed using a combination of "EEG" and patient-reported surveys to compare various meditative practices. The findings from this study can help incorporate specific meditation practices in future mindfulness-based studies that are focused on healthcare settings and on impacting clinical outcomes, such as survival or disease outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Sharma et al.)

Purpose: For resected brain metastases (BMs), stereotactic radiosurgery (SRS) is often offered to minimize local recurrence (LR). Although the aim is to deliver SRS within a few weeks of surgery, a variety of socioeconomic, medical, and procedural issues can cause delays. We evaluated the relationship between timing of postoperative SRS and LR., Methods and Materials: We retrospectively identified a consecutive series of patients with BM managed with resection and SRS or fractionated SRS at our institution from 2012 to 2018. We assessed the correlation of time to SRS and other demographic, disease, and treatment variables with LR, local recurrence-free survival, distant recurrence, distant recurrence-free survival, and overall survival., Results: A total of 133 patients met inclusion criteria. The median age was 64.5 years. Approximately half of patients had a single BM, and median BM size was 2.9 cm. Gross total resection was achieved in 111 patients (83.5%), and more than 90% of patients received fractionated SRS. The median time to SRS was 37.0 days, and the LR rate was 16.4%. Time to SRS was predictive of LR. The median time from surgery to SRS was 34.0 days for patients without LR versus 61.0 days for those with LR (P < .01). The LR rate was 2.3% with SRS administered ≤4 weeks postoperatively, compared with 23.6% if SRS was administered >4 weeks postoperatively (P < .01). Local recurrence-free survival was also improved for patients who underwent SRS at ≤4 weeks (P = .02). Delayed SRS was also predictive of distant recurrence (P = .02) but not overall survival., Conclusions: In this retrospective study, the strongest predictor of LR after postoperative SRS for BM was time to SRS, and a cutoff of 4 weeks was a reliable predictor of recurrence. These findings merit investigation in a prospective, randomized trial., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Re-irradiation of recurrent glioblastoma (GBM) may delay further recurrence but re-irradiation increases the risk of radionecrosis (RN). Salvage therapy should focus on balancing local control (LC) and toxicity. We report the results of using intraoperative Cesium-131 (Cs-131) brachytherapy for recurrent GBM in a population of patients who also received bevacizumab., Methods and Materials: Twenty patients with recurrent GBM underwent maximally safe neurosurgical resection with Cs-131 brachytherapy between 2010 and 2015. Eighty Gy was prescribed to 0.5 cm from the surface of the resection cavity. All patients previously received adjuvant radiotherapy and temozolomide, and received bevacizumab before or after salvage brachytherapy. Seven of 20 (35%) tumors were multiply recurrent and had been previously salvaged with external beam radiotherapy. Patients received MRI scans every 2 months monitored for recurrence, progression, and RN., Results: Median tumor diameter was 4.65 cm (range, 1.2-6.3 cm). Median number of seeds pace was 41 (range, 20-74) with total seed activity 96.8U (range, 41.08-201.3U). At a median followup of 19 months, crude LC was 85% and median overall survival was 9 months (range, 5-26 months). There were two postoperative wound infections (10%), three seizures (15%), and 0% incidence of RN., Conclusions: Our study demonstrates that while LC and survival are similar to other studies of postoperative external beam radiotherapy, no RN occurred in any of these patients, including 7 multiply re-irradiated patients. Of interest, there were patients with multiple recurrences whose survival extended beyond 20 months. These findings suggest that the use of highly conformal Cs-131 brachytherapy is a promising treatment for patients with recurrent GBM with minimal risk of development of RN., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare treatment plans and evaluate dosimetric characteristics of permanent cesium-131 ( 131 Cs) vs. iodine-125 ( 125 I) implants used in brain brachytherapy., Material and Methods: Twenty-four patients with 131 Cs implants from a prospective phase I/II trial were re-planned with 125 I implants. In order to evaluate the volume of brain tissue exposed to radiation therapy (RT), the dose volume histogram was generated for both radioisotopes. To evaluate the dosimetric differences of the two radioisotopes we compared homogeneity (HI) and conformity indices (CI), and dose covering 100% (D 100 ), 90% (D 90 ), 80% (D 80 ), and 50% (D 50 ) of the clinical target volume (CTV)., Results: At the 100%, 90%, 80%, and 50% isodose lines, the 131 Cs plans exposed less mean volume of brain tissue than the 125 I plans ( p < 0.001). The D 100 , D 90 , D 80 , and D 50 were smaller for 131 Cs ( p < 0.001). The HI and CI for 131 Cs vs. 125 I were 19.71 vs. 29.04 and 1.31 vs. 1.92, respectively ( p < 0.001)., Conclusions: Compared to 125 I, 131 Cs exposed smaller volumes of brain tissue to equivalent doses of radiation and delivered lower radiation doses to equivalent volumes of the CTV. 131 Cs exhibited a higher HI, indicating increased uniformity of doses within the CTV. Lastly, 131 Cs presented a CI closer to 1, indicating that the total volume receiving the prescription dose was closer to the desired CTV volume. These results suggest that 131 Cs is dosimetrically superior to 125 I and may explain the reason for the 0% incidence of radiation necrosis (RN) in our previously published prospective study using 131 Cs., Competing Interests: The authors report no conflict of interest., (Copyright © 2020 Termedia.)

Objective: Adjuvant radiation therapy (RT), such as cesium-131 (Cs-131) brachytherapy or stereotactic radiosurgery (SRS), reduces local recurrence (LR) of brain metastases (BM). However, SRS is less efficacious for large cavities, and the delay between surgery and SRS may permit tumor repopulation. Cs-131 has demonstrated improved local control, with reduced radiation necrosis (RN) compared to SRS. This study represents the first comparison of outcomes between Cs-131 brachytherapy and SRS for resected BM., Methods: Patients with BM treated with Cs-131 and SRS following gross-total resection were retrospectively identified. Thirty patients who underwent Cs-131 brachytherapy were compared to 60 controls who received SRS. Controls were selected from a larger cohort to match the patients treated with Cs-131 in a 2:1 ratio according to tumor size, histology, performance status, and recursive partitioning analysis class. Overall survival (OS), LR, regional recurrence, distant recurrence (DR), and RN were compared., Results: With a median follow-up of 17.5 months for Cs-131-treated and 13.0 months for SRS-treated patients, the LR rate was significantly lower with brachytherapy; 10% for the Cs-131 cohort compared to 28.3% for SRS patients (OR 0.281, 95% CI 0.082-0.949; p = 0.049). Rates of regional recurrence, DR, and OS did not differ significantly between the two cohorts. Kaplan-Meier analysis with log-rank testing showed a significantly higher likelihood of freedom from LR (p = 0.027) as well as DR (p = 0.018) after Cs-131 compared to SRS treatment (p = 0.027), but no difference in likelihood of OS (p = 0.093). Six (10.0%) patients who underwent SRS experienced RN compared to 1 (3.3%) patient who received Cs-131 (p = 0.417)., Conclusions: Postresection patients with BM treated with Cs-131 brachytherapy were more likely to achieve local control compared to SRS-treated patients. This study provides preliminary evidence of the potential of Cs-131 to reduce LR following gross-total resection of single BM, with minimal toxicity, and suggests the need for a prospective study to address this question.

The role of radiation therapy in melanoma has evolved over the last few decades. There has been a dramatic improvement in radiation delivery with the introduction of intensity-modulated radiation therapy, image-guided radiation therapy, stereotactic radiosurgery, and stereotactic body radiation therapy/stereotactic radiation therapy. More recently, with the introduction of immunotherapy in various malignancies, including melanoma, the role of radiation therapy is being reevaluated. This article describes the evolution of the role of radiation therapy from nonimmunotherapy to the era of immunotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose/objective(s) In early-stage, node negative oral tongue cancer, there is limited data supporting tumor depth of invasion (DOI) as an indication for post-operative radiotherapy (PORT) to the primary site. The primary aim of this study is to examine the effect of tumor DOI and PORT on overall survival (OS). Materials and methods The National Cancer Database (NCDB) was used to query patients with AJCC stage I and II oral tongue cancer (2006-2013). Patients were stratified by receipt of PORT, elective neck dissection (ND), and DOI (≤4 mm or >4 mm). Kaplan-Meier analysis was performed to compare OS (using the log-rank test) between PORT versus no-PORT. Multivariable Cox proportional hazards regression model performed to evaluate the independent effect of PORT and neck dissection on OS. Results Among 939 patients, 69.3% were clinical stage I, 67.4% received ND, 23.4% had DOI >4 mm, and 10.4% received PORT. The addition of PORT did not improve OS with tumor DOI ≤4 mm (p = 0.634) or >4 mm (p = 0.816). The addition of elective neck dissection improved OS for DOI >4 mm (p = 0.010), but not for ≤4 mm (p = 0.128). On multivariable analysis, ND improved OS if DOI >4 mm (HR, 0.37; 95% CI, 0.17-0.81 [p = .012]), when also controlling for age, sex, PORT status, clinical stage, and pathological stage. Conclusion Tumor DOI should not be used as a sole indication for PORT in early stage oral tongue cancers. Elective neck dissection at the time of excision of the primary tumor results in higher OS for tumors with DOI >4 mm., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Mann et al.)

After maximally safe neurosurgical resection of brain metastases, stereotactic radiosurgery (SRS) is now recommended as an alternative to whole-brain radiation therapy (WBRT), which has been associated with cognitive decline. One complicating factor associated with SRS is that postoperative cavity dynamics can change dramatically, creating significant variability in the recommended timing of SRS. While SRS has been shown to improve local control (LC) in smaller tumor cavities, achieving excellent LC rates still remains a challenge in larger ones. Furthermore, factors predicting the optimal timing of SRS in relation to the cavity size need to be defined and implemented. Variables such as the delay between postoperative MRI and treatment are critical but poorly understood. One potential treatment option that may improve outcomes is brachytherapy, but the widespread implementation of this technique has been slow. This critical review analyzes the relationship between preoperative tumor volume, resection cavity size, and timing of SRS and explores how these variables must be understood in order to achieve the highest LC possible., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Yuan et al.)

As our surgical, radiation, chemotherapeutic and supportive therapies for brain malignancies improve, and overall survival is prolonged, appropriate symptom management in this patient population becomes increasingly important. This review summarizes the published literature and current practice patterns regarding prophylactic and perioperative anti-epileptic drug use. As a wide range of anti-epileptic drugs is now available to providers, evidence guiding appropriate anticonvulsant choice is reviewed. A particular focus of this article is radiation therapy for brain malignancies. Toxicities and seizure risk associated with cranial irradiation will be discussed. Epilepsy management in patients undergoing radiation for gliomas, glioblastoma multiforme, and brain metastases will be addressed. An emerging but inconsistent body of evidence, reviewed here, indicates that anti-epileptic medications may increase radiosensitivity, and therefore improve clinical outcomes, specifically in glioblastoma multiforme patients., (Copyright © 2019 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Checkpoint immunotherapy (CIT) is an emerging and exciting treatment modality for the treatment of cancer. Much excitement has ensued in the potential of CIT to revolutionize the treatment and prognosis of brain metastases. The combination of stereotactic radiosurgery (SRS) and CIT has also been studied and showed promise compared with either treatment modality alone. However, several questions have arisen, in particular, the timing at which SRS and CIT should be administered relative to each other. We reviewed the reported data and attempted to offer a potential answer to this question., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mindfulness is being used increasingly in various aspects of cancer management. Benefits of mindfulness practices are being observed to manage the adverse effects of treatment, symptoms from cancer progression, and the cost-effectiveness compared to conventional contemporary management strategies. In this review article, we present clinical trial data showing the benefits of mindfulness in various aspects of cancer management as well as techniques that have been commonly used in this practice., Competing Interests: The authors have declared that no competing interests exist.

Objective: To analyze outcomes and survival for BRCA1/2+ patients treated with accelerated partial breast irradiation (APBI)., Materials and Methods: Retrospective review was performed on 341 women treated with intracavitary APBI (Mammosite or Contura) postlumpectomy from 2002 to 2013. Patients were treated to 34.0 Gy in 10 BID fractions. Of 341 treated patients, 11 (3.2%) had BRCA1/2 mutations, 5 of whom had an oophorectomy. Ipsilateral breast tumor recurrence (IBTR), contralateral breast tumor recurrence (CBTR), and breast tumor recurrence progression-free survival were analyzed using SPSS-17. BRCA1/2+ patient outcomes were compared with a general population treated cohort., Results: Median age at diagnosis was 66 years, for BRCA1/2+ women it was 61 years. Median follow-up was 8.4 years and for BRCA1/2+ patients it was 8.8 years. IBTR for the entire cohort was 3.5%, while CBTR was 1.2%. Both IBTR and CBTR for the BRCA1/2+ group were 0%. The 5-year IBTR-free survival was 97.3% (95% confidence interval [CI]=94.9%, 98.6%), and the CBTR-free survival was 99.4% (95% CI=97.6%, 99.9%). The 5-year breast tumor recurrence-free survival was 96.7% (95% CI=94.1%, 98.2%). As no patients with BRCA1/2+ mutation died of metastatic breast cancer or recurrence during follow-up and review, overall survival could not be evaluated., Conclusions: To date, BRCA1/2+ patients treated with APBI sustained no recurrences, or second cancers. Most patients had an ER+ status and underwent oophorectomy, which may be a protective mechanism for recurrence. This is the first outcomes report in the literature of BRCA1/2 mutations treated with APBI technique.

Brain metastases occur in a large portion of patients with cancer. Although advances in radiotherapy have helped to improve survival, they have also raised questions regarding the best modality for retreatment in the context of recurrent disease. The spectrum of treatment options for recurrent intracranial metastatic disease after previous radiotherapy includes salvage stereotactic radiosurgery, whole brain radiotherapy, and brachytherapy. We have comprehensively reviewed the existing data on the efficacy and toxicity of the various reirradiation treatment modalities. We examined the key clinical considerations that guide patient selection, such as dose, tumor size, interval to retreatment, and local control and survival rates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Brain metastases are the most common intracranial malignancies in adults. Surgical resection is the preferred treatment approach when a pathological diagnosis is required, for symptomatic patients who are refractory to steroids, and to decompress lesions causing mass effect. Radiotherapy is administered to improve local control rates after surgical resection. After a brief review of the literature describing the treatment of brain metastases using whole-brain radiotherapy, postoperative stereotactic radiosurgery, preoperative radiosurgery, and brachytherapy, we compare patient-related, technical, practical, and radiobiological considerations of each technique. Finally, we focus our discussion on intraoperative brachytherapy, with an emphasis on the technical aspects, benefits, efficacy, and outcomes of studies utilizing permanent Cs-131 implants., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

There are few therapeutic options available for the treatment of recurrent meningiomas that have failed treatment with surgery and external-beam radiation therapy (EBRT). As additional EBRT is clinically risky, brachytherapy offers an important alternative for optimizing local control. In skull base meningiomas, the endoscopic endonasal approach (EEA) has demonstrated an excellent extent of resection. However, in the case of recurrent, atypical, or residual meningiomas, the EEA alone may not be adequate to address microscopic, residual, highly proliferative disease. In this situation, local radioactive seed brachytherapy has been shown to improve control, but few reports of this technique exist. A 48-year-old right-handed man presented on multiple occasions with recurrence of an anaplastic skull base meningioma, after multiple prior gross-total resections and multiple rounds of radiotherapy had failed. The authors performed a maximally safe neurosurgical tumor resection via EEA supplemented by the intraoperative implantation of 131Cs low-dose permanent brachytherapy seeds. They describe a technique for permanent implantation of brachytherapy seeds and provide operative video of this technique. The authors submit that utilizing this technique in combination with EEA tumor resection renders a minimally invasive approach to improving local control in a patient with a recurrent anaplastic or atypical meningioma of the skull base.

Purpose To analyze differences in esophageal cancer survival by geographic region of the U.S. from the 1970s to the 2000s, and attribute the causes of these discrepancies. Methods Raw data were obtained from the Surveillance Epidemiology and End Results (SEER) program of the National Cancer Institute. Patients were stratified by decade of diagnosis and by geographic region (East, Hawaii/Alaska, Midwest, Southwest, and West), containing SEER registries. The Kaplan-Meier method with the log-rank test was used to compare the overall survival (OS) among these geographic groups. A multivariate Cox Proportional Hazard analysis was conducted to evaluate the impact of the following factors on differences in survival: patient age, gender, race, tumor stage, site, histology, treatment method, and metropolitan size. Results A total of 87,834 patients were identified. OS has increased significantly since 1973, with five-year OS improving from 4.9% (the 1970s) to 15.3% (2000s) ( P <0.001). Residence in the East was prognostic for higher OS compared to all the other regions, with a median OS of six months in the 1970s and 12 months in the 2000s ( P <0.001). The multivariate analysis revealed increased age, African American race, distant disease, non-distal tumor location, squamous cell histology, and no radiation therapy were associated with worse OS. The West and East had the highest amount of cancer centers (12 and seven, respectively). And the East had the highest number of cancer centers per person (5.7E-07) while the South had the lowest (1.6E-07). Conclusions There are disparities in esophageal cancer survival and quality of care through different geographic regions of the U.S., which may be attributed to a combination of the unbalanced distribution of medical resources, the regional differences in cancer biology, and other lifestyle and socioeconomic factors. More research should be conducted to further characterize regional differences and guide the implementation of improvements in survival., Competing Interests: The authors have declared that no competing interests exist.

Purpose This study evaluates regional poverty level-dependent differences in lung cancer (LC) survival, focusing on patients receiving radiation therapy (RT). Methods and materials The Surveillance, Epidemiology, and End Results (SEER) database was used to retrospectively identify patients diagnosed with LC between 2000 and 2009. Patients were divided into socioeconomic status (SES) quintiles, with quintiles 1 and 5 representing the highest and lowest SES cohorts, respectively. The Kaplan-Meier method with the log-rank test was used to compare overall survival (OS) from diagnosis between demographic and clinical factor levels. Multivariate (MVA) Cox proportional hazards regression was used to examine the association of quintile and mortality, adjusting for demographic and clinical factors. Results Compared to those not receiving RT, the univariate (UVA) results showed a higher mortality associated with receiving RT (HR:1.091; CI:1.081-1.102) while the MVA demonstrated a protective effect (HR:0.882; CI:0.873-0.891). The MVA revealed that men had higher mortality rates than women (HR:1.192; CI:1.180-1.203). Caucasians had a lower mortality rate as compared to African Americans (adjusted HR:0.932; CI:0.918-0.947) while Asians, Pacific Islanders, and Native Americans had the highest overall survival rates (adjusted HR:0.752, CI:0.734-0.771). Among the entire study population, quintile 2 (HR:1.059, CI:1.043-1.076), quintile 3 (HR:1.091, CI:1.075-1.108), quintile 4 (HR:1.094, CI:1079-1.110), and quintile 5 (HR:1.201, CI:1.181-1.221) reported increased mortality rates compared with quintile 1. This trend was also observed among those undergoing RT, with quintile 2 (HR:1.034, CI:1.010-1.059), quintile 3 (HR:1.045; CI:1.021-1.069), quintile 4 (HR:1.056; CI:1.033-1.080), and quintile 5 (HR:1.153; CI:1.124-1.183) demonstrating incrementally worse OS. Conclusions Upon accounting for age, gender, race, SES, and tumor stage, RT may provide a positive survival benefit among those who received treatment. Minimal differences existed among SES quintiles regarding diagnoses made by tumor stage or patients receiving RT. An incrementally worse OS rate was associated with increasing regional poverty level. This trend persevered among those receiving RT., Competing Interests: The authors have declared that no competing interests exist.

High-grade glioma is the most common primary brain tumor, with glioblastoma multiforme (GBM) accounting for 52% of all brain tumors. The current standard of care (SOC) of GBM involves surgery followed by adjuvant fractionated radiotherapy and chemotherapy. However, little progress has been made in extending overall survival, progression-free survival, and quality of life. Attempts to characterize and customize treatment of GBM have led to mitigating the deleterious effects of radiotherapy using hypofractionated radiotherapy, as well as various immunotherapies as a promising strategy for the incurable disease. A combination of radiotherapy and immunotherapy may prove to be even more effective than either alone, and preclinical evidence suggests that hypofractionated radiotherapy can actually prime the immune system to make immunotherapy more effective. This review addresses the complications of the current radiotherapy regimen, various methods of immunotherapy, and preclinical and clinical data from combined radioimmunotherapy trials.

External beam radiotherapy (RT) has long played a crucial role in the treatment of glioblastoma. Over the past several decades, significant advances in RT treatment and image-guidance technology have led to enormous improvements in the ability to optimize definitive and salvage treatments. This review highlights several of the latest developments and controversies related to RT, including the treatment of elderly patients, who continue to be a fragile and vulnerable population; potential salvage options for recurrent disease including reirradiation with chemotherapy; the latest imaging techniques allowing for more accurate and precise delineation of treatment volumes to maximize the therapeutic ratio of conformal RT; the ongoing preclinical and clinical data regarding the combination of immunotherapy with RT; and the increasing evidence of cancer stem-cell niches in the subventricular zone which may provide a potential target for local therapies. Finally, continued development on many fronts have allowed for modestly improved outcomes while at the same time limiting toxicity.

Purpose/objectives: In stereotactic radiosurgery (SRS), the multiple isocenters for multiple targets dynamic conformal arc (MIMT DCA) technique is traditionally used to treat multiple brain metastases, with one isocenter for each target. The single isocenter for multiple targets (SIMT) technique has recently been adopted to reduce the treatment time at the cost of plan quality. The objective of this study was to develop a restricted single isocenter for multiple targets DCA (RSIMT DCA) technique that can significantly reduce the treatment time but still maintain similar plan quality as the MIMT DCA technique., Materials and Methods: Treating multiple brain metastases with a single isocenter poses a challenge to SRS planning using DCA beams that are intrinsically 3D and do not modulate the beam intensity to spare the normal tissue between targets. To address this obstacle, we have developed a RSIMT DCA technique and used it to treat SRS patients with multiple brain metastases since February 2015. This planning approach is similar to the SIMT technique except that the number of targets for each isocenter is restricted and the distance between the isocenter and target is limited. In this technique, the targets are first split into batches so that all targets in a batch are within a chosen distance (e.g., 7 cm) of each other. All targets in a batch are combined into one target and the geometric center of the combined target is the isocenter for the group of DCA beams associated with that batch. Each DCA group typically consists of 3-4 DCA beams to irradiate 1-3 targets. For each DCA beam, the collimator angle is adjusted to minimize the exposure of normal tissue between targets. The dose of each treatment group is normalized so that the maximal point dose to the combined target is 125% of the prescription dose, which is equivalent to normalize the prescription dose to 80% isodose line. If the maximal point dose of a target is <123%, an additional beam is used to boost the maximal point dose of that target to 125%. To evaluate the plan quality, we randomly selected 10 cases planned with the RSIMT DCA technique, and re-planned them using the MIMT DCA technique. There were in total 38 PTVs, and 22 isocenters were used to treat all of these targets. The prescription for each target was 20 Gy with a maximal point dose of 25 Gy. Plan quality indexes were calculated and compared. Paired sample t-test was performed to determine if the mean normalized difference, (RSIMT-MIMT)/MIMT of each plan index was statistically significantly (p-value < 5%) larger than 0., Results: Satisfactory PTV coverage (V20Gy>95% and V19Gy=100%) was achieved for all plans using either technique. Most PTVs have a maximal point dose between 24.9 and 25.1 Gy, with 2 PTVs between 24.5 and 24.9 Gy. Overall, the plan quality was slightly better for the MIMT DCA technique and the normalized difference was statistically significantly larger than 0 for all investigated dose quality indexes. The normalized difference of body mean dose and conformity index (CI) between the RSIMT and MIMT techniques was respectively 4.2% (p=0.002) and 9.4% (p=0.001), indicating similar plan quality globally and in the high dose area. The difference was more pronounced for the mid-to-low dose spillage with the ratios of V12Gy and V10Gy/VPTV being 13.9% (p=3.8×10 -6 ) and 14.9% (p=1.3×10 -5 ), respectively. The treatment time was reduced by 30%-50% with the RSIMT DCA technique., Conclusion: The RSIMT DCA technique can produce satisfactory SRS plans for treating multiple targets and can significantly reduce the treatment time., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors have nothing to disclose.

Purpose: Studies on adjuvant stereotactic radiosurgery to the cavity of resected brain metastases have suggested that larger tumors (>2.0 cm) have greater rates of recurrence and radionecrosis (RN). The present study assessed the effect of permanent low-dose 131 Cs brachytherapy on local control and RN in patients treated for large brain metastases., Methods and Materials: After institutional review board approval, 42 patients with 46 metastases ≥2.0 cm in preoperative diameter were accrued to a prospective trial from 2010 to 2015. Patients underwent surgical resection with intraoperative placement of stranded 131 Cs seeds as permanent volume implants in the resection cavity. The primary endpoint was local freedom from progression (FFP). Secondary endpoints included regional and distant FFP, overall survival (OS), and RN rate. Failures 5 to 20 mm from the cavity and dural-based failures were considered regional. A separate analysis was performed for metastases >3.0 cm., Results: Of the 46 metastases, 18 were >3.0 cm in diameter. The median follow-up period was 11.9 months (range 0.6-51.9). The metastases had a median preoperative diameter of 3.0 cm (range 2.0-6.8). The local FFP rate was 100% for all tumor sizes. Regional recurrence developed in 3 of 46 lesions (7%), for a 1-year regional FFP rate of 89% (for tumors >3.0 cm, the FFP rate was 80%, 95% confidence interval 54%-100%). Distant recurrences were found in 19 of 46 lesions (41%), for a 1-year distant FFP rate of 52%. The median OS was 15.1 months, with a 1-year OS rate of 58%. Lesion size was not significantly associated with any endpoint on univariate or multivariate analysis. Radioresistant histologic features resulted in worse survival (P=.036). No cases of RN developed., Conclusions: Intraoperative 131 Cs brachytherapy is a promising and effective therapy for large brain metastases requiring neurosurgical intervention, which can offer improved local control and lower rates of RN compared with stereotactic radiosurgery to the resection cavity., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction Patients with glioblastoma multiforme (GBM) over age 65 represent nearly half of those diagnosed per annum. They have a different tumor markers profile, physiologic reserve, and a median survival as low as three to four months. An optimal treatment strategy in older GBM patients remains undefined, with many patients receiving radiation in 30 treatments over six weeks, a regimen based on trials originally excluding patients over age 70. Recent studies have suggested reducing the number of treatments to 10-15 over two to three weeks with similar efficacy. We present an elderly population of patients treated with six radiation treatments. Methods After IRB approval, we reviewed the electronic medical records of 20 consecutive patients over the age 60 at diagnosis with GBM, treated with maximally safe neurosurgical resection, and adjuvant hypofractionated radiation (HFRT) and temozolomide (TMZ) between 2012 and 2015. HFRT was given every other weekday for two weeks, in a total of six fractions (6 × 6 Gy to contrast-enhancing tumor +5 mm and 6 × 4 Gy to fluid-attenuated inversion recovery (FLAIR) +2 cm) with concurrent TMZ (75 mg/m2 daily), followed by adjuvant TMZ (150-200 mg/m2 in 5/28 days). The response was assessed using the Macdonald and Revised Assessment in Neuro-Oncology (RANO) criteria, radiology reports, physician notes, and tumor board consensus notes. Descriptive statistics, overall survival (OS), progression-free survival (PFS), toxicity, and steroid use were calculated and compared to the historical controls of patients treated with a six-week radiation regimen of 60 Gy in 30 fractions with TMZ.   Results The median age at diagnosis was 70.5 years (range: 61 - 82 years). Median pre-radiation Karnofsky performance scale (KPS) was 60 (range: 40 - 90). The median preoperative maximum gross tumor diameter on MRI was 3.6 cm (range: 1.8 - 6 cm). Six patients (30%) had a gross total resection (GTR), eight (40%) had a subtotal resection (STR), and six (30%) had biopsy only. The median progression-free survival was five months (95% (confidence interval) CI: 2.8, 16.4) and median OS of 14 months (95% CI: 5.0, upper limit not estimable). Of the 19 patients tested for isocitrate dehydrogenase-1 (IDH), 100% were negative. Of the eight patients who had MGMT methylation status results, four (50%) were positive for O 6 -methylguanine-DNA methyltransferase (MGMT) methylation. In the 18 patients who completed radiation, the HFRT treatment was well tolerated without any Grade 3/4 acute toxicities. Conclusions The accelerated adjuvant course of HFRT with TMZ used for the elderly with GBM decreases radiation treatment days to six. It was well tolerated in patients over 60 years of age and provided similar OS, PFS, minimal toxicity, and decreased steroid usage compared to historical controls treated with six or even two to three weeks of radiotherapy., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To elucidate the role of radiation therapy (RT) in the treatment of surgically resected limited-stage small cell lung carcinoma (LSCLC)., Methods: We queried the SEER database from 1998 to 2012 to identify patients who were diagnosed with LSCLC as their only primary tumor. Kaplan-Meier analysis was utilized to determine disease-specific survival (DSS) and overall survival (OS), while multivariate analysis was used to compare survival in terms of patients and treatment characteristics., Results: Eight hundred twenty-three LSCLC patients were identified for inclusion within the study. 12-month DSS for patients who did not receive surgery or RT was 31.9% (95% CI 27.7-36.3), 93.3% (95% CI 71.6-90.5) for surgery alone, and 81.0% (95% CI 69.3-88.6) for surgery + RT. 12-month OS was 27.2% (95% CI 23.4-31.1), 74.7% (95% CI 62.6-83.4), and 78.3% (95% CI 66.4-86.4) for no surgery or RT, for surgery alone, and for surgery + RT, respectively. In terms of multivariate analysis, patients receiving surgery alone and patients receiving surgery + RT had a better DSS and OS than those who received neither treatment. However, OS (HR 1.60; 95% CI 0.93-2.75, p = 0.09) and DSS (HR 1.34; 95% CI 0.72-2.51, p = 0.37) were not significantly associated with patients receiving surgery alone compared to surgery + RT., Conclusions: Surgery alone and surgery + RT were positively associated with DSS and OS compared to patients who did not receive surgery or RT. However, the addition of RT to surgery did not significantly predict DSS or OS compared to surgery alone.

Introduction: To compare patients' survival of second primary malignancy (SPM) after head and neck squamous cell carcinoma (HNSCC)., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was utilized (1973-2011). The Kaplan-Meier method with log-rank test was used to compare the overall survival (OS) and cause-specific survival (CSS) among treatment methods from the time of diagnosis of SPMs. Cox proportional regression models were used to adjust the impact for risk factors on CSS., Results: A total of 3,038 patients were identified (5-yr OS 22.6% (21.0-24.3%)). For head and neck (HN) SPMs, the patients who received 'conservative surgery with radiation' had the best 5-yr OS (65.2% (48.9-86.9%)); and the 'conservative surgery' group had the best 5-yr CSS (89.9% (85.6-94.5%)). For lung SPMs, the 'radical surgery' group showed the best survival (2-yr OS 60.8% (56.0-66.1%), 2-yr CSS 70.6% (65.8-75.8%), respectively). Esophagus SPMs had poor prognosis, with no difference among the treatment groups. In lung SPMs, younger age (p<0.001) and black race (p<0.05) were most favorable CSS predictors., Conclusions: The prognosis of SPMs after HNSCC is worse compared with corresponding primary tumor. Conservative surgery with or without radiation showed the most favorable outcomes in HN SPMs.​., Competing Interests: The authors have declared financial relationships, which are detailed in the next section.

Cesium-131 (Cs) brachytherapy is a safe and convenient treatment option for patients with resected brain tumors. This study prospectively analyzes radiation exposure in the patient population who were treated with a maximally safe neurosurgical resection and Cs brachytherapy. Following implantation, radiation dose rate measurements were taken at the surface, 35 cm, and 100 cm distances. Using the half-life of Cs (9.69 d), the dose rates were extrapolated at these distances over a period of time (t = 30 d). Data from dosimetry badges and rings worn by surgeons and radiation oncologists were collected and analyzed. Postoperatively, median dose rate was 0.2475 mSv h, 0.01 mSv h, and 0.001 mSv h and at 30 d post-implant, 0.0298 mSv h, 0.0012 mSv h, and 0.0001 mSv h at the surface, 35 cm, and 100 cm, respectively. All but one badge and ring measured a dose equivalent corresponding to ~0 mSv h, while 1 badge measured 0.02/0.02/0.02 mSv h. There was a significant correlation between the number of seeds implanted and dose rate at the surface (p = 0.0169). When stratified by the number of seeds: 4-15 seeds (n = 14) and 20-50 seeds (n = 4) had median dose rates of 0.1475 mSv h and 0.5565 mSv h, respectively (p = 0.0015). Using National Council on Radiation Protection guidelines, this study shows that dose equivalent from permanent Cs brachytherapy for the treatment of brain tumors is limited, and it maintains safe levels of exposure to family and medical personnel. Such information is critical knowledge for the neurosurgeons, radiation oncologists, nurses, hospital staff, and family as this method is gaining nationwide popularity.

OBJECTIVE Managing patients whose intraparenchymal brain metastases recur after radiotherapy remains a challenge. Intraoperative cesium-131 (Cs-131) brachytherapy performed at the time of neurosurgical resection may represent an excellent salvage treatment option. The authors evaluated the outcomes of this novel treatment with permanent intraoperative Cs-131 brachytherapy. METHODS Thirteen patients with 15 metastases to the brain that recurred after stereotactic radiosurgery and/or whole brain radiotherapy were treated between 2010 and 2015. Stranded Cs-131 seeds were placed as a permanent volume implant. Prescription dose was 80 Gy at 5-mm depth from the resection cavity surface. The primary end point was resection cavity freedom from progression (FFP). Resection cavity freedom from progression (FFP), regional FFP, distant FFP, median survival, overall survival (OS), and toxicity were assessed. RESULTS The median duration of follow-up after salvage treatment was 5 months (range 0.5-18 months). The patients' median age was 64 years (range 51-74 years). The median resected tumor diameter was 2.9 cm (range 1.0-5.6 cm). The median number of seeds implanted was 19 (range 10-40), with a median activity per seed of 2.25 U (range 1.98-3.01 U) and median total activity of 39.6 U (range 20.0-95.2 U). The 1-year actuarial local FFP was 83.3%. The median OS was 7 months, and 1-year OS was 24.7%. Complications included infection (3), pseudomeningocele (1), seizure (1), and asymptomatic radionecrosis (RN) (1). CONCLUSIONS After failure of prior irradiation of brain metastases, re-irradiation with intraoperative Cs-131 brachytherapy implants provides durable local control and limits the risk of RN. The authors' initial experience demonstrates that this treatment approach is well tolerated and safe for patients with previously irradiated tumors after failure of more than 1 radiotherapy regimen and that it results in excellent response rates and minimal toxicity.

The goal of the study was to examine expression of prostate-specific membrane antigen (PSMA) in neovasculature of gynecologic cancers, as PSMA-targeted therapy has showed a promise in treatment of advanced carcinomas. The study included cervical carcinoma (n=28), vulvar carcinoma (n=20), endometrial carcinoma (n=23), primary ovarian carcinoma (n=21), metastatic ovarian carcinoma (n=25), and normal cervix (n=12) as negative control. All cases were immunostained using anti-CD31 antibody to delineate capillary endothelial cells. In parallel, all cases were immunostained using anti-PSMA antibody. The PSMA staining was assessed in tumor capillaries and in normal tissues and scored as a percentage of CD31 staining. PSMA expression was found in the tumor neovasculature, and no significant expression was identified in vasculature of normal tissues. The extent of PSMA staining in tumor capillaries varied from high expression in ovarian and endometrial cancers, to medium expression in cervical squamous cell carcinomas, and low expression in cervical adenocarcinomas and vulvar cancers. All (100%) cases of primary ovarian carcinoma, ovarian carcinoma metastases, and primary endometrial carcinoma showed PSMA expression in tumor vasculature, which was diffuse in majority of cases. The expression of PSMA in ovarian cancer metastases was similar among different metastatic foci of the same tumor. Fifteen percent of cervical squamous cell carcinoma, 50% of cervical adenocarcinoma, and 75% of vulvar carcinomas showed no capillary expression of PSMA. In conclusion, PSMA is highly and specifically expressed in the neovasculature of ovarian, endometrial, and cervical squamous carcinoma, rendering it a potential therapeutic vascular target.

Objectives: Limited work, either retrospective or prospective, has been done to investigate whether or not there is a cause-specific mortality (CSM) or all-cause mortality (ACM) benefit to adding surgery following neoadjuvant treatment for Stage IIIB NSCLC., Methods: We extracted patients with Stage IIIB NSCLC from the Survival, Epidemiology, and End Results Program (SEER) database treated from 2004 to 2012 with either radiation alone or radiation followed by surgery. Other variables extracted were age, sex, race, and tumor location. The impact of patient and treatment variables on CSM and ACM was explored using Cox multivariable regression analysis., Results: A total of 14,065 patients were extracted from the SEER database. On multivariable analysis, even after adjustment for age, gender, race, and site, radiation followed by surgery was associated with a reduction in cause-specific mortality compared to radiation alone (adjusted HR 0.46; 95 % CI 0.41, 0.52; p < 0.0001). Median overall survival was 11 months in the radiotherapy alone arm versus 29 months in the radiotherapy plus surgery arm (p < 0.0001 by log-rank test). After adjustment for these same factors, radiation followed by surgery was also associated with a reduction in all-cause mortality compared with radiation alone (adjusted HR 0.47; 95 % CI 0.42, 0.52; p < 0.0001). Median cause-specific survival was 12 months in the radiotherapy alone arm versus 33 months in the radiotherapy plus surgery arm (p < 0.0001 by log-rank test)., Discussion: In the SEER database, there appears to be both a CSM and ACM benefit to adding surgery following radiation for Stage IIIB NSCLC.

Glioblastoma is not only the most common primary brain tumor, but also the most aggressive. Currently, the most effective treatment of surgery, chemotherapy and radiation therapy allows for a modest median survival of 15 months. Here, we report a case of a 57-year-old male with histologically confirmed glioblastoma with unfavorable prognostic characteristics (poor performance status and persistent neurological symptoms after surgery), whose expected 5-year survival is 0%. Further genetic analysis offered a mixed prognostic picture with positive methylation of 0-6-methylguinine-DNA (deoxyribonucleic acid) methyltransferase (MGMT; favorable prognosis) and wild-type isocitrate dehydrogenase 1 (IDH-1; unfavorable prognosis). Remarkably, the patient showed a progression-free survival of 5.5 years and a total survival of 6.5 years. In the context of recently published literature, the authors hypothesize that the patient's use of the antipsychotic medication risperidone may have had a potential antitumor effect. Risperidone antagonizes the dopamine-2 receptor and the serotonin-7 receptor, both of which have been individually implicated in the growth and progression of glioblastoma. To the authors' knowledge, this is the first clinical case in the literature to explore this association., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Seed migration after interstitial prostate brachytherapy has been well documented in the literature. However, there have been no detailed reports of seed migration after permanent interstitial brachytherapy to treat cerebral malignancies. In this article, the authors report a rare case of seed migration after adjuvant cesium-131 ((131)Cs) brachytherapy was used to treat a large paraventricular brain metastasis., Methods and Materials: The patient was a 63-year-old man with a 5.8-cm right frontal metastasis abutting the right lateral ventricle and causing severe edema and mass effect. The patient was enrolled in an ongoing clinical trial at our institution to receive permanent intraoperative (131)Cs brachytherapy in an effort to prevent tumor recurrence in the resection cavity. Stranded seeds were covered with Surgicel, and the cavity was filled with Tisseel to prevent seed migration., Results: Imaging obtained at 54 days postsurgery showed no seed migration, but imaging obtained at 158 days revealed 12 brachytherapy seeds in the spinal canal from T11 to S2. The seeds were left in place because they were inactive at this time due to the short half-life of (131)Cs (9.7 days); they remained stable on followup imaging, and the patient was asymptomatic., Conclusions: Although the clinical consequences remain unclear, the migration of inactive seeds is not currently considered to be a complication of intracerebral brachytherapy and we do not believe that additional measures must be taken to prevent it., (Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Standard treatment for glioblastoma consists of surgical resection followed by radiation therapy with concurrent and adjuvant chemotherapy. Conventional radiation clinical treatment volumes include a 2- to 3-cm margin around magnetic resonance imaging or computed tomography enhancing abnormalities in the brain as well as a margin around the T2 or fluid-attenuated inversion recovery abnormality. However, there remains significant variability with respect to whether such extensive margins are necessary. Collectively, we as authors of this manuscript also use different margins, with A.G.W. employing European Organization for Research and Treatment of Cancer recommendations of a 2- to 3-cm margin on T1 enhancement for 60 Gy and M.P.M. using Radiation Therapy Oncology Group recommendations of 2 cm on T2 signal abnormality for the initial 46 Gy and 2.5-cm margin on T1 enhancement for a 14-Gy boost. Our experiences reflect the heterogeneity of margin definition and selection for this disease and underscore an important area of further research to minimize this variability. In this article, we review studies exploring recurrence patterns and outcomes in patients treated using both conventional and more limited margins. We conclude that treating to "smaller" margins does not alter recurrence patterns nor does it result in inferior survival, but whether this is because of the inherently limited benefit of radiation therapy in the first place, or whether it is truly because microscopic tumor control at larger distances is not an issue, remains unestablished., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) is both the most common and the most devastating primary cancer of the central nervous system, with an expected overall survival in most patients of about 14 months. Despite extensive research, outcomes for GBM have been largely unchanged since the introduction of temozolomide in 2005. We believe that in order to achieve a breakthrough in therapeutic management, we must begin to identify subtypes of GBM, and tailor treatment to best target a particular tumor's vulnerabilities. Our group has recently produced an examination of the clinical outcomes of radiation therapy directed at tumors that contact the subventricular zone (SVZ), the 3-5 mm lateral border of the lateral ventricles that contains the largest collection of neural stem cells in the adult brain. We find that SVZ-associated tumors have worse progression free and overall survival than tumors that do not contact the SVZ, and that they exhibit unique recurrence and migration patterns. However, with minimal basic science research into SVZ-associated GBM, it is currently impossible to determine if the clinicobehavioral uniqueness of this group of tumors represents a true disease subtype from a genetic perspective. We believe that further translational research into SVZ-associated GBM is needed to establish a therapeutic profile.