Neuroprotection in Cerebral Cortex Induced by the Pregnancy Hormone Estriol.

In multiple sclerosis (MS), demyelination occurs in the cerebral cortex, and cerebral cortex atrophy correlates with clinical disabilities. Treatments are needed in MS to induce remyelination. Pregnancy is protective in MS. Estriol is made by the fetoplacental unit, and maternal serum estriol levels temporally align with fetal myelination. Here, we determined the effect of estriol treatment on the cerebral cortex in the preclinical model of MS, experimental autoimmune encephalomyelitis (EAE). Estriol treatment initiated after disease onset decreased cerebral cortex atrophy. Neuropathology of the cerebral cortex showed increased cholesterol synthesis proteins in oligodendrocytes, more newly formed remyelinating oligodendrocytes, and increased myelin in estriol-treated EAE mice. Estriol treatment also decreased the loss of cortical layer V pyramidal neurons and their apical dendrites and preserved synapses. Together, estriol treatment after EAE onset reduced atrophy and was neuroprotective in the cerebral cortex.

The Rise of Open Access Journals in Radiation Oncology: Influence on Resident Research, 2015 to 2019.

Purpose: While a rising share of scientific research articles are being published in open access (OA) journals, their impact on resident research in radiation oncology is unknown. Thus, we sought to determine the number, content, and costs of first-author, PubMed-searchable articles radiation oncology residents in the United States (US) published in OA journals in recent years. Methods and Materials: We built a database of first-author, PubMed-searchable articles published by US radiation oncology residents who graduated between 2015 and 2019. We then classified each journal in which these articles appeared as either OA or non-OA and obtained the current article-processing charge (APC) for each publication that appeared in an OA journal. Results: The residents in this study published 2637 first-author, PubMed-searchable articles, 555 of which (21.0%) appeared in 138 OA journals. The number of publications in OA journals per resident increased from 0.47 for the class of 2015 to 0.79 for the class of 2019. Publications in OA journals garnered fewer citations than those in non-OA journals (8.9 vs 14.9, P < .01). Furthermore, 90.6% of OA journals levy an APC for original research reports (median, $1896), which is positively correlated with their 2019 impact factor (r = 0.63, P < .01). Aggregate APCs totaled $900,319.21 and appeared to increase over the study period. Conclusions: The number of first-author, PubMed-searchable articles published by graduating US radiation oncology residents in OA journals rose significantly between 2015 and 2019. To maximize the benefits of OA publishing in the future, US radiation oncology residents will need to ensure that they use vetted OA journals to publish their research findings and avoid predatory journals.

The Holman Research Pathway in Radiation Oncology: 2010 to 2019.

PURPOSE: There has not been an assessment of the Holman Research Pathway (HRP) in radiation oncology (RO) in nearly 10 years. In this study, we sought to review the demographic characteristics, research productivity during and after residency, job placements, and National Institutes of Health (NIH) grant funding of RO residents who completed the HRP in the modern era. METHODS AND MATERIALS: We created a comprehensive database of RO residents who completed the HRP between 2010 and 2019. Using a variety of data sources, we obtained demographic information, first-author manuscripts published in residency, and first- and last-author manuscripts published in the first 30 months after residency for each resident. In addition, we identified the first and current job and NIH grant funding for each resident. RESULTS: Ninety-seven RO residents who graduated from 50 medical schools and 25 residency programs were included. The majority were male (82.5%), had a PhD (92.8%), and identified as white (64.9%). Collectively, these residents published 212 first-author, PubMed-searchable manuscripts during residency (mean: 2.2) and 142 first- or last-author, PubMed-searchable manuscripts in the first 30 months after completion of residency (mean: 1.5). The number of first-author publications authored by HRP graduates during residency was highly correlated (r = 0.62; P < .01) with the number of first- and last-author publications they authored during the first 30 months after completing residency. Ninety-six of the 97 residents (99.0%) were employed in full-time clinical positions after completing residency. Seventy-six HRP residents (78.4%) obtained an academic position as their first job after residency, only 4 of whom have since left academia, and 20 (20.6%) obtained a nonacademic position. Of the 75 HRP graduates currently employed in an academic position, 39 (52.0%) have their own laboratories. Twenty-three of the 96 HRP residents (24.0%) who secured employment in full-time clinical positions after residency switched jobs over the study period. Lastly, 33 of the 97 HRP residents (34.0%) have thus far received 47 extramural NIH research grants, 15 of which were R-01 grants. CONCLUSIONS: Over the past decade, the HRP has proven successful in training a new cohort of physician investigators in RO. Although productive, HRP residents have had relatively homogenous sex, educational, and racial backgrounds. Ensuring sufficient representation of residents from a variety of backgrounds in the HRP in the future will be crucial.

Redefining risk of contralateral cervical nodal disease in early stage oropharyngeal cancer in the human papillomavirus era.

BACKGROUND: The optimal extent of surgery and/or radiation to the contralateral lymph node region is unknown in early-stage human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). METHODS: To investigate the pathologic incidence of and risk factors for contralateral nodal disease (CND) in cT1-T2 HPV-related OPSCC treated with transoral robotic surgery (TORS) and bilateral neck dissection (BND), the records of 120 patients were reviewed. RESULTS: Eleven patients displayed pathologic contralateral nodal disease (pCND), including 7.1% of tonsil and 10.9% of base of tongue (BOT) cases. Medial hemistructure involvement and cN2 disease were significantly associated with pCND. Zero cN0 patients had pCND, and on multivariate analysis only cN classification remained significantly associated with pCND. Four percent of BOT patients and 2% of tonsil patients with a well-lateralized primary and cN0/N1 neck demonstrated pCND. CONCLUSIONS: HPV-related OPSCC that are cN0-N1 have exceedingly low rates of pCND. Well-lateralized HPV-related BOT primaries with limited clinical nodal disease may be candidates for ipsilateral only treatment.

Radiopharmaceuticals for Bone Metastases.

As a single organ distributed diffusely throughout the body, bones represent both a unique challenge and unique opportunity for the treatment of symptomatic metastatic disease. While the multifocality of bone metastases often prevents effective complete treatment with focal radiotherapy, the similar pathophysiology of these diffuse sites of disease opens the door to targeted systemic therapy. The relatively rapid dose fall-off from beta- or alpha-emitting particles, if correctly and reliably targeted to osseous metastases, might reduce tumor burden and enhance pain control or improve survival. Radioisotopes have thus been studied keenly with the first generation of primarily beta-emitting radioisotopes, strontium-89 and samarium-153, which reached early FDA approval based on successful endpoints of pain control. More recently, an alpha-emitting therapy, radium-223, has demonstrated a successful endpoint of improved overall survival in patients with a burden of symptomatic, metastatic castrate-resistant prostate cancer (mCRPC) confined to the bones. With this discovery, an additional survival-improving tool beyond systemic and hormonal agents was added to the treatment arsenal for mCRPC for suitable candidates. With an improved understanding of the optimization of hormonal and systemic therapies in the context of mCRPC, there is lingering uncertainty regarding the safety and efficacy of combinatorial use of alpha and beta-emitting therapies with the current generation of systemic agents. In this narrative review, we will highlight the current understanding of the relative utility and clinical paradigms involving alpha- and beta-emitting radioisotopes. We discuss fundamental mechanisms for antineoplastic activity, initial clinical trials validating their use, the use of concurrent antiresorptive therapies to provide bone protection, and ongoing clinical trials targeted at best utilization of these agents in the broader context of mCRPC treatment.

Radiation Oncology Resident Research Productivity in the United States: 2015 to 2019.

PURPOSE: Multiple efforts have been made in recent years to establish national benchmarks for research productivity among US radiation oncology residents. Morgan et al found a mean of 1.01 first-author, PubMed-searchable articles published by US radiation oncology residents over 4 years of residency between 2002 and 2007, whereas Verma et al found a mean of 1.97 first-author, PubMed-searchable articles published by members of the graduating US radiation oncology residency classes of 2014 and 2015. In this study, we sought to establish new national benchmarks for US radiation oncology resident research productivity and characterize the scholarly work produced by graduating US radiation oncology residents. METHODS AND MATERIALS: We built a database of US radiation oncology residents who graduated between 2015 and 2019 using multiple sources of publicly available data. We subsequently searched the PubMed database to identify all first-author publications for every resident in our database from the start of residency until 3 months after the completion of residency. Publications were categorized by type (original research, review, case report, or commentary) and content. We performed a secondary analysis to identify factors associated with an increased probability of publishing during residency. RESULTS: We identified 909 US radiation oncology residency graduates from 89 residency programs between 2015 and 2019. Collectively, these graduates published 2637 first-author, PubMed-searchable articles (mean: 2.90; median: 2.0; range, 0-58; interquartile range, 1-4) in 392 distinct peer-reviewed journals during their residency, and 69.7% of the first-author publications comprised original research. On multivariable analysis, only residency size was predictive of publishing a first-author manuscript during residency. Among residents with at least 1 first-author manuscript, male sex, lack of a doctorate degree, and residency size were all significant predictors of the number of first-author manuscripts published during residency. CONCLUSIONS: US radiation oncology resident research productivity, as measured by the number of first-author, PubMed-searchable publications, has increased compared with historical data. However, substantial variability exists in resident research productivity nationwide.

Dosimetric differences between cesium-131 and iodine-125 brachytherapy for the treatment of resected brain metastases.

PURPOSE: To compare treatment plans and evaluate dosimetric characteristics of permanent cesium-131 (131Cs) vs. iodine-125 (125I) implants used in brain brachytherapy. MATERIAL AND METHODS: Twenty-four patients with 131Cs implants from a prospective phase I/II trial were re-planned with 125I 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% (D100), 90% (D90), 80% (D80), and 50% (D50) of the clinical target volume (CTV). RESULTS: At the 100%, 90%, 80%, and 50% isodose lines, the 131Cs plans exposed less mean volume of brain tissue than the 125I plans (p < 0.001). The D100, D90, D80, and D50 were smaller for 131Cs (p < 0.001). The HI and CI for 131Cs vs. 125I were 19.71 vs. 29.04 and 1.31 vs. 1.92, respectively (p < 0.001). CONCLUSIONS: Compared to 125I, 131Cs exposed smaller volumes of brain tissue to equivalent doses of radiation and delivered lower radiation doses to equivalent volumes of the CTV. 131Cs exhibited a higher HI, indicating increased uniformity of doses within the CTV. Lastly, 131Cs 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 131Cs is dosimetrically superior to 125I and may explain the reason for the 0% incidence of radiation necrosis (RN) in our previously published prospective study using 131Cs.

Understanding the Deactivation Phenomena of Small-Pore Mo/H-SSZ-13 during Methane Dehydroaromatisation.

Small pore zeolites have shown great potential in a number of catalytic reactions. While Mo-containing medium pore zeolites have been widely studied for methane dehydroaromatisation (MDA), the use of small pore supports has drawn limited attention due to the fast deactivation of the catalyst. This work investigates the structure of the small pore Mo/H-SSZ-13 during catalyst preparation and reaction by operando X-ray absorption spectroscopy (XAS), in situ synchrotron powder diffraction (SPD), and electron microscopy; then, the results are compared with the medium pore Mo/H-ZSM-5. While SPD suggests that during catalyst preparation, part of the MoOx anchors inside the pores, Mo dispersion and subsequent ion exchange was less effective in the small pore catalyst, resulting in the formation of mesopores and Al2(MOO4)3 particles. Unlike Mo/H-ZSM-5, part of the Mo species in Mo/H-SSZ-13 undergoes full reduction to Mo0 during MDA, whereas characterisation of the spent catalyst indicates that differences also exist in the nature of the formed carbon deposits. Hence, the different Mo speciation and the low performance on small pore zeolites can be attributed to mesopores formation during calcination and the ineffective ion exchange into well dispersed Mo-oxo sites. The results open the scope for the optimisation of synthetic routes to explore the potential of small pore topologies.

Cs-131 brachytherapy for patients with recurrent glioblastoma combined with bevacizumab avoids radiation necrosis while maintaining local control.

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.

Sagittal and Frontal Plane Gait Initiation Kinetics in Healthy, Young Subjects.

The study purposes were to record the lower extremity sagittal and frontal joint moments and powers during gait initiation (GI); evaluate GI support moments in both planes; and analyze planar energy patterns in a group of 15 healthy, young adults. 3D motion and ground reaction force data were used to calculate support moments (SM) and joint moments and powers as well as center of mass (COM) kinematics. STEP1 had no visible SM. It appeared in STEP2 and, by STEP3, resembled that seen in steady-state gait. Joint moments demonstrated a similar development towards typical patterns over the three steps. Correlations of moment data between planes indicate that the frontal plane component of the SM acts to keep the COM centered. It is suggested that Winter's 1980 SM definition be extended to include both a support (sagittal) component and a centering (frontal) component. Energy was calculated for individual bursts of joint powers in both planes and each step had characteristic patterns in each plane, with patterns resembling steady-state gait appearing in the third step. Test-retest reliability (ICC range: 0.796 - 0.945) was high with CV values in the sagittal plane (36.6 - 37.5%) being less variable than in the frontal plane (39.0 - 82.0%). COM kinematics revealed that acceleration peaked in STEP2 (ICC range: 0.950 - 0.980, CV < 20.0%). Data supported hypotheses regarding the dominance of the frontal plane power in STEP1, with substantial power coming from hip flexors. As well, powers in the sagittal plane were generally of larger magnitude than in the frontal plane.

Increased Incidence of Central Venous Catheter-Related Infection in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy.

Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) is a complex surgical intervention with associated risks. Central venous catheter (CVC) line sepsis is one of a number of potential morbidities. The aim of this study was to calculate the incidence of catheter-related infection (CRI) in a CRS and HIPEC patient population and to assess its influence on length of hospital stay. Methods: Data were collected on consecutive patients who underwent CRS HIPEC between August 2013 and October 2017. Data included patient demographics, timing of CVC insertion/removal, time spent in critical care, and CVC tip/blood culture results. Charts were reviewed for patients with both positive CVC culture and positive blood cultures to assess for evidence of catheter related infection and systemic inflammatory response syndrome (SIRS). Results: Data on 100 consecutive CRS HIPEC operations performed between August 2013 and October 2017 was analyzed. There were 11 CRIs in 100 CVCs, resulting in a CRI rate of 16.2 per 1,000 CVC days. Patients within the CRI group had a longer high-dependency unit (HDU) stay compared with the non-septic group (6 days vs. 4.07 days, p < 0.05). The CVC duration for the CRI and non-CRI group was 8.4 and 7.6 days, respectively (p = 0.12). The CRI group also had an increased total hospital length of stay (LOS; 20.8 days vs. 15.4 days, p < 0.05). On average, CRIs occurred eight days post-operative and four days post-HDU discharge. There was no association identified with longer CVC duration (p = 0.34). There has been an annual decline in CRI rates in CRS and HIPEC patients over the duration of the study period from 19.1 per 1,000 CVC days in 2016 to 8.2 per 1,000 CVC days in 2017. Conclusion: This is the first study to report on CRI rates in patients undergoing CRS and HIPEC. The CRI rate of 16.2 per 1,000 CVC days is higher than the overall national figure of 5.2 per 1,000 for CVC lines inserted in the operating room. Patients who developed line sepsis had longer HDU and longer overall hospital stay. Catheter-related infection was noted post-HDU discharge in all cases. Implementation of a CVC care bundle in the later years of the study period coincided with a reduction in CRI rates.

Radiation and Immunotherapy in High-grade Gliomas: Where Do We Stand?

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.

Accelerated Hypofractionated Radiotherapy in the Era of Concurrent Temozolomide Chemotherapy in Elderly Patients with Glioblastoma Multiforme.

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 O6-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.

Clinical Outcomes of Large Brain Metastases Treated With Neurosurgical Resection and Intraoperative Cesium-131 Brachytherapy: Results of a Prospective Trial.

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 131Cs 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 131Cs 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 131Cs 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.

Cesium-131 brachytherapy for recurrent brain metastases: durable salvage treatment for previously irradiated metastatic disease.

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.

Subventricular zone-associated glioblastoma: A call for translational research to guide clinical decision making.

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.

Neural stem cells, the subventricular zone and radiotherapy: implications for treating glioblastoma.

Over the past decade, advances in neuroscience have suggested that neural stem cells resident in specific regions of the adult brain may be involved in development of both primary and recurrent glioblastoma. Neurogenesis and malignant transformation occurs in the subventricular zone adjacent to the lateral ventricles. This region holds promise as a potential target for therapeutic intervention with radiotherapy. However, irradiation of a larger brain volume is not without risk, and significant side effects have been observed. The current literature remains contradictory regarding the efficacy of deliberate intervention with radiation to the subventricular zone. This critical review discusses the connection between neural stem cells and development of glioblastoma, explores the behavior of tumors associated with the subventricular zone, summarizes the discordant literature with respect to the effects of irradiation, and reviews other targeted therapies to this intriguing region.

Glioblastoma: Radiation treatment margins, how small is large enough?

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.