Understanding the Effect of Prescription Isodose in Single-Fraction Stereotactic Radiosurgery on Plan Quality and Clinical Outcomes for Solid Brain Metastases.

BACKGROUND AND OBJECTIVES: There is wide variation in treatment planning strategy for central nervous system (CNS) stereotactic radiosurgery. We sought to understand what relationships exist between intratumor maximum dose and local control (LC) or CNS toxicity, and dosimetric effects of constraining hotspots on plan quality of multiple metastases volumetric modulated arc therapy radiosurgery plans. METHODS: We captured brain metastases from 2015 to 2017 treated with single-isocenter volumetric modulated arc therapy radiosurgery. Included tumors received single-fraction stereotactic radiosurgery, had no previous surgery or radiation, and available follow-up imaging. Our criterion for local failure was 25% increase in tumor diameter on follow-up MRI or pathologic confirmation of tumor recurrence. We defined significant CNS toxicity as Radiation Therapy Oncology Group irreversible Grade 3 or higher. We performed univariate and multivariate analyses evaluating factors affecting LC. We examined 10 stereotactic radiosurgery plans with prescriptions of 18 Gy to all targets originally planned without constraints on the maximum dose within the tumor. We replanned each with a constraint of Dmax 120%. We compared V50%, mean brain dose, and Dmax between plans. RESULTS: Five hundred and thirty tumors in 116 patients were available for analysis. Median prescription dose was 18 Gy, and median prescription isodose line (IDL) was 73%. Kaplan-Meier estimate of 12-month LC only tumor volume (HR 1.43 [1.22-1.68] P < .001) was predictive of local failure on univariate analysis; prescription IDL and histology were not. In multivariate analysis, tumor volume impacted local failure (HR 1.43 [1.22-1.69] P < .001) but prescription IDL did not (HR 0.95 [0.86-1.05] P = .288). Only a single grade 3 and 2 grade 4 toxicities were observed; tumor volume was predictive of CNS toxicity (HR 1.58 [1.25-2.00]; P < .001), whereas prescription IDL was not (HR 1.01 [0.87-1.17] P = .940). CONCLUSION: The prescription isodose line had no impact on local tumor control or CNS toxicity. Penalizing radiosurgery hotspots resulted in worse radiosurgery plans with poorer gradient. Limiting maximum dose in gross tumor causes increased collateral exposure to surrounding tissue and should be avoided.

A roadmap for implementation of kV-CBCT online adaptive radiation therapy and initial first year experiences.

PURPOSE: Online Adaptive Radiation Therapy (oART) follows a different treatment paradigm than conventional radiotherapy, and because of this, the resources, implementation, and workflows needed are unique. The purpose of this report is to outline our institution's experience establishing, organizing, and implementing an oART program using the Ethos therapy system. METHODS: We include resources used, operational models utilized, program creation timelines, and our institutional experiences with the implementation and operation of an oART program. Additionally, we provide a detailed summary of our first year's clinical experience where we delivered over 1000 daily adaptive fractions. For all treatments, the different stages of online adaption, primary patient set-up, initial kV-CBCT acquisition, contouring review and edit of influencer structures, target review and edits, plan evaluation and selection, Mobius3D 2nd check and adaptive QA, 2nd kV-CBCT for positional verification, treatment delivery, and patient leaving the room, were analyzed. RESULTS: We retrospectively analyzed data from 97 patients treated from August 2021-August 2022. One thousand six hundred seventy seven individual fractions were treated and analyzed, 632(38%) were non-adaptive and 1045(62%) were adaptive. Seventy four of the 97 patients (76%) were treated with standard fractionation and 23 (24%) received stereotactic treatments. For the adaptive treatments, the generated adaptive plan was selected in 92% of treatments. On average(±std), adaptive sessions took 34.52 ± 11.42 min from start to finish. The entire adaptive process (from start of contour generation to verification CBCT), performed by the physicist (and physician on select days), was 19.84 ± 8.21 min. CONCLUSION: We present our institution's experience commissioning an oART program using the Ethos therapy system. It took us 12 months from project inception to the treatment of our first patient and 12 months to treat 1000 adaptive fractions. Retrospective analysis of delivered fractions showed that the average overall treatment time was approximately 35 min and the average time for the adaptive component of treatment was approximately 20 min.

Body composition and mortality in men receiving prostate radiotherapy: A pooled analysis of NRG/RTOG 9406 and NRG/RTOG 0126.

PURPOSE: To validate the association between body composition and mortality in men treated with radiation for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to classify patients by risk of all-cause mortality. MATERIALS AND METHODS: Participants of NRG/Radiation Therapy Oncology Group (RTOG) 9406 and NRG/RTOG 0126 with archived computed tomography were included. Muscle mass and muscle density were estimated by measuring the area and attenuation of the psoas muscles on a single slice at L4-L5. Bone density was estimated by measuring the attenuation of the vertebral body at mid-L5. Survival analyses, including Cox proportional hazards models, assessed the relationship between body composition and mortality. Recursive partitioning analysis (RPA) was used to create a classification tree to classify participants by risk of death. RESULTS: Data from 2066 men were included in this study. In the final multivariable model, psoas area, comorbidity score, baseline prostate serum antigen, and age were significantly associated with survival. The RPA yielded a classification tree with four prognostic groups determined by age, comorbidity, and psoas area. Notably, the classification among older (≥70 years) men into prognostic groups was determined by psoas area. CONCLUSIONS: This study strongly supports that body composition is related to mortality in men with localized PCa. The inclusion of psoas area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men. More research is needed to determine the clinical impact of body composition on prognostic models in men with PCa.

Hypofractionated radiation leads to more rapid bleeding cessation in women with vaginal bleeding secondary to gynecologic malignancy.

BACKGROUND: Vaginal bleeding (VB) is common in women with gynecologic (GYN) malignancies. Radiation therapy (RT) is used for the definitive treatment of GYN cancers and palliation of bleeding. The historical dogma is that high dose-per-fraction radiation leads to more rapid bleeding cessation, yet there is scant data supporting this claim. We sought to examine the effect of RT fraction size on VB via retrospective analysis of patients receiving hypofractionated radiation (HFRT) compared to conventionally fractionated radiation (CFRT) for control of bleeding secondary to GYN malignancies. METHODS: We identified patients receiving external beam RT for continuous VB from GYN malignancy treated in our department from 2012 to 2020. RT was classified as HFRT (> 2.0 Gy/fx) or CFRT (1.8-2.0 Gy/fx). Demographic information, disease characteristics, and treatment details were collected. The primary endpoint was days from RT initiation until bleeding resolution. Characteristics between groups were compared via Fisher's exact test. Time to bleeding cessation was assessed via Kaplan-Meier and log-rank test. Univariable and multivariable Cox-proportional hazards were used to identify factors associated with bleeding cessation. RESULTS: We identified 43 patients meeting inclusion criteria with 26 and 17 patients receiving CFRT and HFRT, respectively. Comparison of baseline characteristics revealed patients receiving HFRT were older (p = 0.001), more likely to be post-menopausal (p = 0.002), and less likely to receive concurrent chemotherapy (p = 0.004). Time to bleeding cessation was significantly shorter for patients receiving HFRT (log-rank p < 0.001) with median time to bleeding cessation of 5 days (HFRT) versus 16 days (CFRT). Stratification by dose-per-fraction revealed a dose-response effect with more rapid bleeding cessation with increased dose-per-fraction. While HFRT, age, recurrent disease, prior pelvic RT, and prior systemic therapy were associated with time to bleeding cessation on univariable analysis, HFRT was the only factor significantly associated with time to bleeding cessation in the final multivariable model (HR 3.26, p = 0.008). CONCLUSIONS: Patients with continuous VB from GYN tumors receiving HFRT experienced more rapid bleeding cessation than those receiving CFRT. For patients with severe VB, initiation of HFRT to control malignancy related bleeding quickly may be warranted.

Selection of brachytherapy applicators based on tumor size and shape for cervical cancer: simulation analysis of pear-shaped isodose dimensions.

The purpose of study is to measure Point A pear-shaped isodose dimensions of the conventional intracavitary brachytherapy with various sizes of colpostats and analyze which size of tumor is the optimal for 3-D interstitial brachytherapy. CT simulation was performed with Fletcher type applicator using various sizes of colpostats (2.0, 2.5, and 3.0 cm diameter). The Manchester standard loading (dwell time) system was used to generate pear-shaped isodose envelopes with high-dose rate iridium-192 according to the colpostat sizes. The size of the pear-shaped envelope was measured at 5 different levels: A-level (center of the colpostats), B-level (top of the colpostats), C-level (between B and D), D-level (Point A), and E-level (1.0 cm above Point A). In this study, it was assumed that uterine tandem was located at the center of tumor. For width of pear-shape: At the A-level, 6.4, 7.3, and 8.0 cm for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the B-level, 5.8, 6.4, and 6.8 cm for 2, 2.5, and 3.0 cm colpostats, respectively. At the C-level, 4.6, 4.8, and 4.8 for 2.0, 2.5, and 3.0 cm colpostats, respectively. At the D-level, 4.0 cm for all different size. At the E-level, 3.8 cm for all 3 different size colpostats. A-level was the largest dimension of pear-shape. However, it was located in the upper vagina below the main cervical mass. The center of the effective pear-shape size for tumor was between the C and D levels. For thickness, all 5 different levels were ranging 3.7 to 4.0 cm. For height, the length of height was dependent on the tandem length. Therefore, the pear-shape envelope was able to accommodate up to 4.0 cm diameter volume. According to our analysis of conventional pear-shape dimension, 3-D interstitial brachytherapy should be considered for tumors larger than 4.0 cm for symmetrical tumor.

Control and Toxicity in Melanoma Versus Other Brain Metastases in Response to Combined Radiosurgery and PD-(L)1 Immune Checkpoint Inhibition.

PURPOSE: Prior studies have mixed conclusions about the efficacy and central nervous system (CNS) toxicity profile of combining radiosurgery with anti-programed cell death 1 (PD-1) immune checkpoint inhibition (ICI) for brain metastases. This study evaluates the safety and efficacy of combined radiosurgery and anti-PD-1 ICI for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) brain metastases (BM). METHODS AND MATERIALS: Forty-one patients with 153 radiation naïve melanoma BM and 33 patients with 118 BM of NSCLC and RCC origin from 2014 through 2019 received radiosurgery and either anti PD-1 receptor inhibition or anti PD-L1 inhibition targeting the PD-1 ligand with less than 4 months separating either therapy. Similar to Radiation Therapy Oncology Group 9005, high-grade CNS toxicity was defined as irreversible grade 3 or any grade 4/5 neurologic event. Salvage resection revealing necrosis and viable tumor was considered grade 4 toxicity and local failure. An increase in greatest cross-sectional diameter of 25% on contrasted magnetic resonance imaging was designated as a local failure. RESULTS: Median follow-up was 10 months (range, 1-41 months). Local control was estimated to be 90.3% at 1 year. Distant control was 38.8% at 1 year, and neither local nor distant control were significantly influenced by limiting steroids to the day of treatment (P = .55, .52 respectively). One-year freedom from high-grade toxicity was 90.4% for patients and 94.6% for tumors. Though melanoma accounted for 41 (55%) patients and 153 (56%) tumors, it accounted for all high-grade toxicities (P = .03). These patients had some combination of high tumor burden, aggressive steroid taper, and treatment with ipilimumab. CONCLUSIONS: Stereotactic radiosurgery combined with anti-PD-1 ICI appears to result in a high rate of local tumor control and a low rate of high-grade CNS toxicity, comparable to historical series with radiosurgery alone. High-grade toxicity is more likely in melanoma than RCC and NSCLC. Coming prospective studies will shed light on further questions about treatment timing, steroids, and response.

Leptomeningeal disease and neurologic death after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis.

PURPOSE: Postoperative stereotactic radiosurgery (SRS) is associated with up to 30% risk of subsequent leptomeningeal disease (LMD). Radiographic patterns of LMD (classical sugarcoating [cLMD] vs. nodular [nLMD]) in this setting has been shown to be prognostic. However, the association of these findings with neurologic death (ND) is not well described. METHODS AND MATERIALS: The records for patients with brain metastases who underwent surgical resection and adjunctive SRS to 1 lesion (SRS to other intact lesions was allowed) and subsequently developed LMD were combined from 7 tertiary care centers. Salvage radiation therapy (RT) for LMD was categorized according to use of whole-brain versus focal cranial RT. RESULTS: The study cohort included 125 patients with known cause of death. The ND rate in these patients was 79%, and the rate in patients who underwent LMD salvage treatment (n = 107) was 76%. Univariate logistic regression demonstrated radiographic pattern of LMD (cLMD vs. nLMD, odds ratio: 2.9; P = .04) and second LMD failure after salvage treatment (odds ratio: 3.9; P = .02) as significantly associated with ND. The ND rate was 86% for cLMD versus 68% for nLMD. Whole-brain RT was used in 95% of patients with cLMD and 52% with nLMD. In the nLMD cohort (n = 58), there was no difference in ND rate based on type of salvage RT (whole-brain RT: 67% vs. focal cranial RT: 68%, P = .92). CONCLUSIONS: LMD after surgery and SRS for brain metastases is a clinically significant event with high rates of ND. Classical LMD pattern (vs. nodular) and second LMD failure after salvage treatment were significantly associated with a higher risk of ND. Patients with nLMD treated with salvage focal cranial RT did not have higher ND rates compared with WBRT. Methods to decrease LMD and the subsequent high risk of ND in this setting warrant further investigation.

Students' Perspectives and Concerns for the 2020 to 2021 Radiation Oncology Interview Season.

PURPOSE: Recently, the Coalition for Physician Accountability Work Group on Medical Students in the Class of 2021 recommended limiting visiting medical student rotations, conducting virtual residency interviews, and delaying the standard application timeline owing to the ongoing corona virus disease 2019 (COVID-19) pandemic. These changes create both challenges and opportunities for medical students and radiation oncology residency programs. We conducted a comprehensive needs assessment to prepare for a virtual recruitment season, including a focus group of senior medical students seeking careers in oncology. METHODS AND MATERIALS: A single 1.5-hour focus group was conducted with 10 third- and fourth-year medical students using Zoom videoconferencing software. Participants shared opinions relating to visibility of residency programs, virtual clerkship experiences, expectations for program websites, and remote interviews. The focus group recording was transcribed and analyzed independently by 3 authors. Participants' statements were abstracted into themes via inductive content analysis. RESULTS: Inductive content analysis of the focus group transcript identified several potential challenges surrounding virtual recruitment, including learning the culture of a program and/or city, obtaining accurate information about training programs, and uncertainty surrounding the best way to present themselves during a virtual interview season. In the present environment, the focus group participants anticipate relying more on departmental websites and telecommunications because in-person interactions will be limited. In addition, students perceived that the educational yield of a virtual clerkship would be low, particularly if an in-person rotation had already been completed at another institution. CONCLUSIONS: With the COVID-19 crisis limiting visiting student rotations and programs transitioning to hosting remote interviews, we recommend programs focus resources toward portraying the culture of their program and city, accurately depicting program information, and offering virtual electives or virtual interaction to increase applicant exposure to residency program culture.

Surface guided imaging during stereotactic radiosurgery with automated delivery.

PURPOSE: To report on the use of surface guided imaging during frameless intracranial stereotactic radiotherapy with automated delivery via HyperArcTM (Varian Medical Systems, Palo Alto, CA). METHODS: All patients received intracranial radiotherapy with HyperArcTM and were monitored for intrafraction motion by the AlignRT® (VisionRT, London, UK) surface imaging (SI) system. Immobilization was with the EncompassTM (Qfix, Avondale, PA) aquaplast mask device. AlignRT® log files were correlated with trajectory log files to correlate treatment parameters with SI reported offsets. SI reported offsets were correlated with gantry angle and analyzed for performance issues at non-zero couch angles and during camera-pod blockage during gantry motion. Demographics in the treatment management system were used to identify race and determine if differences in SI reported offsets are due to skin tone settings. RESULTS: A total of 981 fractions were monitored over 14 months and 819 were analyzed. The median AlignRT® reported motion from beginning to the end of treatment was 0.24 mm. The median offset before beam on at non-zero couch angles was 0.55 mm. During gantry motion when camera pods are blocked, the median magnitude was below 1 mm. Median magnitude of offsets at non-zero couch angles was not found to be significantly different for patients stratified by race. CONCLUSIONS: Surface image guidance is a viable alternative to scheduled mid-treatment imaging for monitoring intrafraction motion during stereotactic radiosurgery with automated delivery.

Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease.

PURPOSE: Surgery is often used for large or symptomatic brain metastases but is associated with risk of developing leptomeningeal dissemination. Emerging data suggest that fractionated stereotactic radiation therapy (FSRT) is an effective management strategy in large brain metastases. We sought to retrospectively compare leptomeningeal disease (LMD) and local control (LC) rates for patients treated with surgical resection followed by radiosurgery (S + SRS) versus FSRT alone. METHODS AND MATERIALS: We identified all patients with a brain metastasis ≥3 cm in diameter treated from 2004 to 2017 with S + SRS or FSRT alone (25 or 30 Gy in 5 fractions) who had follow-up imaging. LMD was defined as focal or diffuse leptomeningeal enhancement that was >5 mm from the index metastasis. Categorical baseline characteristics were compared with the χ2 test. LMD and LC rates were evaluated by the Kaplan-Meier (KM) method, with the log-rank test used to compare subgroups. RESULTS: A total of 125 patients were identified, including 82 and 43 in the S + SRS and FSRT alone groups, respectively. Median pretreatment Graded Prognostic Assessment in the S + SRS and FSRT groups was 2.5 and 1.5, respectively (P < .001). Median follow-up was 7 months. The KM estimate of 12-month LMD rate in the S + SRS and FSRT groups was 45% and 19%, respectively (P = .048). The KM estimate of 12-month local control in the S + SRS and FSRT groups was 70% and 69%, respectively (P = .753). The 12-month KM estimate of grade ≥3 toxicity was 1.4% in S + SRS group versus 6.3% in the FSRT alone group (P = .248). After adjusting for graded prognostic assessment (GPA), no overall survival difference was observed between groups (P = .257). CONCLUSIONS: Surgery is appropriate for certain brain metastases, but S + SRS may increase LMD risk compared with FSRT alone. Because S + SRS and FSRT seem to have similar LC, FSRT may be a viable alternative to S + SRS in select patients with large brain metastases.

A multi-institutional analysis of presentation and outcomes for leptomeningeal disease recurrence after surgical resection and radiosurgery for brain metastases.

BACKGROUND: Radiographic leptomeningeal disease (LMD) develops in up to 30% of patients following postoperative stereotactic radiosurgery (SRS) for brain metastases. However, the clinical relevancy of this finding and outcomes after various salvage treatments are not known. METHODS: Patients with brain metastases, of which 1 was resected and treated with adjunctive SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. LMD pattern was categorized as nodular (nLMD) or classical ("sugarcoating," cLMD). RESULTS: The study cohort was 147 patients. Most patients (60%) were symptomatic at LMD presentation, with cLMD more likely to be symptomatic than nLMD (71% vs. 51%, P = 0.01). Salvage therapy was whole brain radiotherapy (WBRT) alone (47%), SRS (27%), craniospinal radiotherapy (RT) (10%), and other (16%), with 58% receiving a WBRT-containing regimen. WBRT was associated with lower second LMD recurrence compared with focal RT (40% vs 68%, P = 0.02). Patients with nLMD had longer median overall survival (OS) than those with cLMD (8.2 vs 3.3 mo, P < 0.001). On multivariable analysis for OS, pattern of initial LMD (nodular vs classical) was significant, but type of salvage RT (WBRT vs focal) was not. CONCLUSIONS: Nodular LMD is a distinct pattern of LMD associated with postoperative SRS that is less likely to be symptomatic and has better OS outcomes than classical "sugarcoating" LMD. Although focal RT demonstrated increased second LMD recurrence compared with WBRT, there was no associated OS detriment. Focal cranial RT for nLMD recurrence after surgery and SRS for brain metastases may be a reasonable alternative to WBRT.

Brachytherapy Training Survey of Radiation Oncology Residents.

PURPOSE: As brachytherapy utilization rates decline, we sought to evaluate the state of brachytherapy training during radiation oncology residency. METHODS AND MATERIALS: US radiation oncology residents in the Association of Residents in Radiation Oncology database were sent an online questionnaire regarding brachytherapy training. Survey questions addressed a wide array of topics, and responses were often given on a 1 to 5 Likert-type scale that reflected strength of opinion. Postgraduate year (PGY) 4/5 respondents' answers were analyzed. Descriptive statistics were generated, and rank correlation analyses (Kendall's τ coefficient and Wilcoxon signed-rank test) were used for comparisons. RESULTS: The survey was completed by 145 of 567 residents (62% being PGY4/5). Of PGY4/5 respondents, 96% (86 of 90) believed learning brachytherapy during residency was important, and 72% (65 of 90) felt their program valued brachytherapy training. Resident brachytherapy comfort varied by site, decreasing as follows: gynecologic, prostate, breast, skin. The current intracavitary 15-case minimum was believed adequate by most, but only a minority believed the 5-case interstitial minimum was adequate. Most respondents (59%) believed that caseload was the greatest barrier to achieving independence in brachytherapy. Significant support exists for American Brachytherapy Society training courses and on-the-job education to enhance training, but enthusiasm about pursuing brachytherapy fellowship training was low. Most respondents expressed confidence in developing a brachytherapy practice (54%); however, this was significantly lower than the rate of those confident in developing a stereotactic body radiation therapy/stereotactic radiosurgery program (97%) (P < .001). Furthermore, there was an association between aggregate number of brachytherapy cases performed and resident confidence in starting a brachytherapy practice (τ = 0.37; P < .001). CONCLUSIONS: Brachytherapy is an important component of residency training that is valued by residents and programs. Because caseload was the greatest perceived barrier in brachytherapy training, with confidence correlated with case volume, attempts should be made to expand opportunities for training experiences that are feasible to complete during residency.

Quality of prostate cancer screening information on the websites of nationally recognized cancer centers and health organizations.

PURPOSE: The purpose of this study was to survey the accessibility and quality of prostate-specific antigen (PSA) screening information from National Cancer Institute (NCI) cancer center and public health organization Web sites. METHODS AND MATERIALS: We surveyed the December 1, 2016, version of all 63 NCI-designated cancer center public Web sites and 5 major online clearinghouses from allied public/private organizations (cancer.gov, cancer.org, PCF.org, USPSTF.org, and CDC.gov). Web sites were analyzed according to a 50-item list of validated health care information quality measures. Web sites were graded by 2 blinded reviewers. Interrater agreement was confirmed by Cohen kappa coefficient. RESULTS: Ninety percent of Web sites addressed PSA screening. Cancer center sites covered 45% of topics surveyed, whereas organization Web sites addressed 70%. All organizational Web pages addressed the possibility of false-positive screening results; 41% of cancer center Web pages did not. Forty percent of cancer center Web pages also did not discuss next steps if a PSA test was positive. Only 6% of cancer center Web pages were rated by our reviewers as "superior" (eg, addressing >75% of the surveyed topics) versus 20% of organizational Web pages. Interrater agreement between our reviewers was high (kappa coefficient = 0.602). CONCLUSION: NCI-designated cancer center Web sites publish lower quality public information about PSA screening than sites run by major allied organizations. Nonetheless, information and communication deficiencies were observed across all surveyed sites. In an age of increasing patient consumerism, prospective prostate cancer patients would benefit from improved online PSA screening information from provider and advocacy organizations. Validated cancer patient Web educational standards remain an important, understudied priority.

Fractionated stereotactic radiation therapy for intact brain metastases.

PURPOSE: Limited data exist on fractionated stereotactic radiation therapy (FSRT) for brain metastases. We sought to evaluate the safety and efficacy of FSRT and further define its role in brain metastasis management. METHODS AND MATERIALS: A total of 72 patients were treated with linear accelerator-based FSRT to 182 previously untreated, intact brain metastases. Targets received 25 or 30 Gy in 5 fractions. All targets within the same course received the same prescription regardless of size. Toxicity was recorded per Radiation Therapy Oncology Group central nervous system toxicity criteria. RESULTS: The median follow-up was 5 months (range, 1-71 months). The Kaplan-Meier estimate of 12-month local control was 86%. Tumors <3 cm in diameter demonstrated improved 12-month local control of 95% compared with 61% in tumors ≥3 cm (P < .001). The Kaplan-Meier estimate of 12-month local control was 91% in tumors treated with 30 Gy and only 75% in tumors treated with 25 Gy (P = .015). Tumor diameter ≥3 cm resulted in increased local failure, and a 30 Gy prescription resulted in decreased local failure on multivariate analysis (hazard ratio [HR], 8.11 [range, 2.09-31.50; P = .003] and HR, 0.26 [range, 0.07-0.93; P = .038]). Grade 4 central nervous system toxicity occurred in 4 patients (6%) requiring surgery, and no patient experienced irreversible grade 3 or 5 toxicity. Increasing tumor diameter was associated with increased toxicity risk (HR, 2.45 [range, 1.04-5.742; P = .04]). CONCLUSIONS: FSRT for brain metastases appears to demonstrate a high rate of local control with minimal risk of severe toxicity. Local control appears to be associated with smaller tumor sizeand a higher prescription dose. FSRT is a viable option for those who are poor single-fraction candidates.

Accessibility, availability, and quality of online information for US radiation oncology residencies.

PURPOSE: Radiation oncology (RO) residency applicants commonly use Internet resources for information on residency programs. The purpose of this study is to assess the accessibility, availability, and quality of online information for RO graduate medical education. METHODS AND MATERIALS: Accessibility of online information was determined by surveying databases for RO residency programs within the Fellowship Residency Electronic Interactive Data Access System (FREIDA) of the American Medical Association, the Accreditation Council for Graduate Medical Education (ACGME), and Google search. As of June 30, 2015, websites were assessed for presence, accessibility, and overall content availability based on a 55-item list of desired features based on 13 program features important to previously surveyed applicants. Quality scoring of available content was performed based on previously published Likert scale variables deemed desirable to RO applicants. Quality score labels were given based on percentage of desired information presented. RESULTS: FREIDA and ACGME databases listed 89% and 98% of program websites, respectively, but only 56% and 52% of links routed to a RO department-specific website, respectively. Google search obtained websites for 98% of programs and 95% of links routed to RO department-specific websites. The majority of websites had program descriptions (98%) and information on staff. However, resident information was more limited (total number [42%], education [47%], previous residents [28%], positions available [35%], contact information [13%]). Based on quality scoring, program websites contained only 47% of desired information on average. Only 13% of programs had superior websites containing 80% or more of desired information. CONCLUSIONS: Compared with Google, the FREIDA and ACGME program databases provide limited access to RO residency websites. The overall information availability and quality of information within RO residency websites varies widely. Applicants and programs may benefit from improved content accessibility and quality from US RO program websites in the residency application process.

Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma.

BACKGROUND: We hypothesized that chronic inhibition of epidermal growth factor receptor (EGFR) by cetuximab, a monoclonal anti-EGFR antibody, induces up-regulation of its ligands resulting in resistance and that microRNAs (miRs) play an important role in the ligand regulation in head and neck squamous cell carcinoma (HNSCC). METHODOLOGY/PRINCIPAL FINDINGS: Genome-wide changes in gene and miR expression were determined in cetuximab-sensitive cell line, SCC1, and its resistant derivative 1Cc8 using DNA microarrays and RT-PCR. The effects of differentially expressed EGFR ligands and miRs were examined by MTS, colony formation, ELISA, and western blot assays. Heparin-binding EGF-like growth factor (HB-EGF) and its regulator, miR-212, were differentially expressed with statistical significance when SCC1 and 1Cc8 were compared for gene and miR expression. Stimulation with HB-EGF induced cetuximab resistance in sensitive cell lines. Inhibition of HB-EGF and the addition of miR-212 mimic induced cetuximab sensitivity in resistant cell lines. MicroRNA-212 and HB-EGF expression were inversely correlated in an additional 33 HNSCC and keratinocyte cell lines. Six tumors and 46 plasma samples from HNSCC patients were examined for HB-EGF levels. HB-EGF plasma levels were lower in newly diagnosed HNSCC patients when compared to patients with recurrent disease. CONCLUSIONS/SIGNIFICANCE: Increased expression of HB-EGF due to down-regulation of miR-212 is a possible mechanism of cetuximab resistance. The combination of EGFR ligand inhibitors or miR modulators with cetuximab may improve the clinical outcome of cetuximab therapy in HNSCC.