Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combination with chemoradiotherapy for unresected, locally advanced head and neck squamous cell carcinoma.

Chemoradiotherapy (CRT) for locally-advanced head and neck squamous cell carcinoma (LA-HSNCC) yields 5-year survival rates near 50% despite causing significant toxicity. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase metabolic inhibitor, reduces tumor lactate production and has been used in cancer therapy previously. The safety of adding this agent to CRT is unknown. Our randomized, placebo-controlled, double-blind phase II study added DCA to cisplatin-based CRT in patients with LA-HNSCC. The primary endpoint was safety by adverse events (AEs). Secondary endpoints compared efficacy via 3-month end-of-treatment response, 5-year progression-free and overall survival. Translational research evaluated pharmacodynamics of serum metabolite response. 45 participants (21 DCA, 24 Placebo) were enrolled from May 2011-April 2014. Higher rates of all-grade drug related fevers (43% vs 8%, p = 0.01) and decreased platelet count (67% vs 33%, p = 0.02) were seen in DCA versus placebo. However, there were no significant differences in grade 3/4 AE rates. Treatment compliance to DCA/placebo, radiation therapy, and cisplatin showed no significant difference between groups. While end-of-treatment complete response rates were significantly higher in the DCA group compared to placebo (71.4% vs 37.5%, p = 0.0362), survival outcomes were not significantly different between groups. Treatment to baseline metabolites demonstrated a significant drop in pyruvate (0.47, p < 0.005) and lactate (0.61, p < 0.005) in the DCA group. Adding DCA to cisplatin-based CRT appears safe with no detrimental effect on survival and expected metabolite changes compared to placebo. This supports further investigation into combining metabolic agents to CRT. Trial registration number: NCT01386632, Date of Registration: July 1, 2011.

Fertility Awareness-Based Methods for Family Planning: A Literature Review.

A review of 23 research articles to examine fertility awareness-based methods revealed biologic indicators and tracking methods to identify the fertile window in reproductive-aged women. This literature review indicated that a woman's cycle regularity is a major determinant of which method is best. Additionally, the woman's desire to achieve a pregnancy and her preference regarding the intensity of training are factors in method choice. Some evidence suggests that use of at least two biologic indicators is most effective for determining the fertility window. Recommended web and mobile applications also are discussed.

Electron cryotomography of Mycoplasma pneumoniae mutants correlates terminal organelle architectural features and function.

The Mycoplasma pneumoniae terminal organelle functions in adherence and gliding motility and is comprised of at least eleven substructures. We used electron cryotomography to correlate impaired gliding and adherence function with changes in architecture in diverse terminal organelle mutants. All eleven substructures were accounted for in the prkC, prpC and P200 mutants, and variably so for the HMW3 mutant. Conversely, no terminal organelle substructures were evident in HMW1 and HMW2 mutants. The P41 mutant exhibits a terminal organelle detachment phenotype and lacked the bowl element normally present at the terminal organelle base. Complementation restored this substructure, establishing P41 as either a component of the bowl element or required for its assembly or stability, and that this bowl element is essential to anchor the terminal organelle but not for leverage in gliding. Mutants II-3, III-4 and topJ exhibited a visibly lower density of protein knobs on the terminal organelle surface. Mutants II-3 and III-4 lack accessory proteins required for a functional adhesin complex, while the topJ mutant lacks a DnaJ-like co-chaperone essential for its assembly. Taken together, these observations expand our understanding of the roles of certain terminal organelle proteins in the architecture and function of this complex structure.

Evidence of temporal niche separation via low flowering time overlap in an old-field plant community.

Flowering time is a trait that reflects the timing of specific resource requirements by plants. Consequently, several predictions have been made related to how species are assembled within communities according to flowering time. Strong overlap in flowering time among coexisting species may result from clustered abiotic resources, or contribute to improved pollination success. Conversely, low flowering time overlap (asynchrony) among coexisting species may reduce competition for soil, light, or pollinator resources and alleviate interspecific pollen transfer. Here, we present evidence that coexisting species in an old-field community generally overlap less in flowering time than expected under a commonly used and statistically validated null model. Flowering time asynchrony was more pronounced when abundance data were used (compared to presence-absence data), and when analyses focused on species that share bees as pollinators. Control and herbivore-exclusion plots did not differ in flowering time overlap, providing no evidence of the reduction in overlap expected to result from increased competition. Our results varied with the randomization algorithm used, emphasizing that the choice of algorithm can influence the outcome of null models. Our results varied between 2 years, with patterns being less clear in the second year, when both growing season and flowering times were contracted. Finally, we found evidence that further supports a previous finding that higher plot-level flowering time overlap was associated with higher proportions of introduced species. Reduced flowering time overlap among species in our focal community may promote coexistence via temporal niche differentiation and reduced competition for pollinators and other abiotic resources.

Starvation and recovery in the deep-sea methanotroph Methyloprofundus sedimenti.

In the deep ocean, the conversion of methane into derived carbon and energy drives the establishment of diverse faunal communities. Yet specific biological mechanisms underlying the introduction of methane-derived carbon into the food web remain poorly described, due to a lack of cultured representative deep-sea methanotrophic prokaryotes. Here, the response of the deep-sea aerobic methanotroph Methyloprofundus sedimenti to methane starvation and recovery was characterized. By combining lipid analysis, RNA analysis, and electron cryotomography, it was shown that M. sedimenti undergoes discrete cellular shifts in response to methane starvation, including changes in headgroup-specific fatty acid saturation levels, and reductions in cytoplasmic storage granules. Methane starvation is associated with a significant increase in the abundance of gene transcripts pertinent to methane oxidation. Methane reintroduction to starved cells stimulates a rapid, transient extracellular accumulation of methanol, revealing a way in which methane-derived carbon may be routed to community members. This study provides new understanding of methanotrophic responses to methane starvation and recovery, and lays the initial groundwork to develop Methyloprofundus as a model chemosynthesizing bacterium from the deep sea.

Effect of application score strategy on interviews offered to postgraduate year 1 pharmacy residency applicants.

OBJECTIVES: Residency programs may need to spend a large amount of time on the application review process in order to invite the best candidates for interviews. By using a different scoring strategy, this process could be made more efficient while still resulting in selection of the most appropriate candidates to interview. The objective of this study was to explore hypothetical scoring strategies for past residency applicants and to determine the percentage of these applicants that would have received an interview offer compared with the program's standard scoring strategy. METHODS: Two years of residency applications to a postgraduate year 1 (PGY1) program providing the majority of clinical experience in ambulatory care were analyzed. Four models were explored: 1) standard model (original method); 2) simplified model (derived from statistical methods); 3) intuition model (criteria thought to best exemplify program success); and 4) objective model (criteria easy to objectively record, e.g., grade point average). All 3 new models were compared with the standard model to determine the percentage of candidates who would have received an interview if their applications had been scored according to the new model. RESULTS: A total of 110 applications were reviewed (42 interviews offered). After a multivariable analysis, academics, leadership, interest in ambulatory care, and professionalism were included in the simplified model, which predicted 81% of the interviews offered through the standard model. The intuition and objective models predicted 71% and 48% of interviews offered through the standard model, respectively. CONCLUSION: Models scoring only 4 of the initial 12 criteria would have likely predicted 71% to 81% of original interview offers. Residency programs should consider periodically reviewing their application review processes to determine areas for improved efficiency.

Veterans' Preferences for Remote Management of Chronic Conditions.

BACKGROUND: The Veterans Health Administration (VA) is investing considerable resources into providing remote management care to patients for disease prevention and management. Remote management includes online patient portals, e-mails between patients and providers, follow-up phone calls, and home health devices to monitor health status. However, little is known about patients' attitudes and preferences for this type of care. This qualitative study was conducted to better understand patient preferences for receiving remote care. METHODS: Ten focus groups were held comprising 77 patients with hypertension or tobacco use history at two VA medical centers. Discussion questions focused on experience with current VA remote management efforts and preferences for receiving additional care between outpatient visits. RESULTS: Most participants were receptive to remote management for referrals, appointment reminders, resource information, and motivational and emotional support between visits, but described challenges with some technological tools. Participants reported that remote management should be personalized and tailored to individual needs. They expressed preferences for frequency, scope, continuity of provider, and mode of communication between visits. Most participants were open to nonclinicians contacting them as long as they had direct connection to their medical team. Some participants expressed a preference for a licensed medical professional. All groups raised concerns around confidentiality and privacy of healthcare information. Female Veterans expressed a desire for gender-sensitive care and an interest in complementary and alternative medicine. CONCLUSIONS: The findings and specific recommendations from this study can improve existing remote management programs and inform the design of future efforts.

Association Between End-of-Rotation Resident Transition in Care and Mortality Among Hospitalized Patients.

IMPORTANCE: Shift-to-shift transitions in care among house staff are associated with adverse events. However, the association between end-of-rotation transition (in which care of the patient is transferred) and adverse events is uncertain. OBJECTIVE: To examine the association of end-of-rotation house staff transitions with mortality among hospitalized patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective multicenter cohort study of patients admitted to internal medicine services (N = 230 701) at 10 university-affiliated US Veterans Health Administration hospitals (2008-2014). EXPOSURES: Transition patients (defined as those admitted prior to an end-of-rotation transition who died or were discharged within 7 days following transition) were stratified by type of transition (intern only, resident only, or intern + resident) and compared with all other discharges (control). An alternative analysis comparing admissions within 2 days before transition with admissions on the same 2 days 2 weeks later was also conducted. MAIN OUTCOMES AND MEASURES: The primary outcome was in-hospital mortality. Secondary outcomes included 30-day and 90-day mortality and readmission rates. A difference-in-difference analysis assessed whether outcomes changed after the 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour regulations. Adjustments included age, sex, race/ethnicity, month, year, length of stay, comorbidities, and hospital. RESULTS: Among 230 701 patient discharges (mean age, 65.6 years; men, 95.8%; median length of stay, 3.0 days), 25 938 intern-only, 26 456 resident-only, and 11 517 intern + resident end-of-rotation transitions occurred. Overall mortality was 2.18% in-hospital, 9.45% at 30 days, and 14.43% at 90 days. Adjusted hospital mortality was significantly greater in transition vs control patients for the intern-only group (3.5% vs 2.0%; odds ratio [OR], 1.12 [95% CI, 1.03-1.21]) and the intern + resident group (4.0% vs 2.1%; OR, 1.18 [95% CI, 1.06-1.33]), but not for the resident-only group (3.3% vs 2.0%; OR, 1.07 [95% CI, 0.99-1.16]). Adjusted 30-day and 90-day mortality rates were greater in all transition vs control comparisons (30-day mortality: intern-only group, 14.5% vs 8.8%, OR, 1.17 [95% CI, 1.13-1.22]; resident-only group, 13.8% vs 8.9%, OR, 1.11 [95% CI, 1.04-1.18]; intern + resident group, 15.5% vs 9.1%, OR, 1.21 [95% CI, 1.12-1.31]; 90-day mortality: intern-only group, 21.5% vs 13.5%, OR, 1.14 [95% CI, 1.10-1.19]; resident-only group, 20.9% vs 13.6%, OR, 1.10 [95% CI, 1.05-1.16]; intern + resident group, 22.8% vs 14.0%, OR, 1.17 [95% CI, 1.11-1.23]). Duty hour changes were associated with greater adjusted hospital mortality for transition patients in the intern-only group and intern + resident group than for controls (intern-only: OR, 1.11 [95% CI, 1.02-1.21]; intern + resident: OR, 1.17 [95% CI, 1.02-1.34]). The alternative analyses did not demonstrate any significant differences in mortality between transition and control groups. CONCLUSIONS AND RELEVANCE: Among patients admitted to internal medicine services in 10 Veterans Affairs hospitals, end-of-rotation transition in care was associated with significantly higher in-hospital mortality in an unrestricted analysis that included most patients, but not in an alternative restricted analysis. The association was stronger following institution of ACGME duty hour regulations.

Panel Management to Improve Smoking and Hypertension Outcomes by VA Primary Care Teams: A Cluster-Randomized Controlled Trial.

BACKGROUND: Panel Management can expand prevention and chronic illness management beyond the office visit, but there is limited evidence for its effectiveness or guidance on how best to incorporate it into practice. OBJECTIVE: We aimed to test the effectiveness of incorporating panel management into clinical practice by incorporating Panel Management Assistants (PMAs) into primary care teams with and without panel management education. DESIGN: We conducted an 8-month cluster-randomized controlled trial of panel management for improving hypertension and smoking cessation outcomes among veterans. PATRICIPANTS: Twenty primary care teams from the Veterans Affairs New York Harbor were randomized to control, panel management support, or panel management support plus education groups. Teams included 69 clinical staff serving 8,153 hypertensive and/or smoking veterans. INTERVENTIONS: Teams assigned to the intervention groups worked with non-clinical Panel Management Assistants (PMAs) who monitored care gaps and conducted proactive patient outreach, including referrals, mail reminders and motivational interviewing by telephone. MAIN MEASURES: Measurements included mean systolic and diastolic blood pressure, proportion of patients with controlled blood pressure, self-reported quit attempts, nicotine replacement therapy (NRT) prescriptions, and referrals to disease management services. KEY RESULTS: Change in mean blood pressure, blood pressure control, and smoking quit rates were similar across study groups. Patients on intervention teams were more likely to receive NRT (OR = 1.4; 95% CI 1.2-1.6) and enroll in the disease management services MOVE! (OR = 1.2; 95% CI 1.1-1.6) and Telehealth (OR = 1.7, 95% CI 1.4-2.1) than patients on control teams. CONCLUSIONS: Panel Management support for primary care teams improved process, but not outcome variables among veterans with hypertension and smoking. Incorporating PMAs into teams was feasible and highly valued by the clinical staff, but clinical impact may require a longer intervention.

Challenges With Acute Care and Response to Treatment Among Adult Patients With Cyclic Vomiting Syndrome.

Cyclic vomiting syndrome is a chronic gastrointestinal tract disorder. The symptoms include cycles of extreme nausea, vomiting, and abdominal pain separated by periods of wellness. Previous research suggests a quality gap in early recognition and appropriate management of adults with cyclic vomiting syndrome. The purpose of this study was to explore and describe adult patients' experiences with cyclic vomiting syndrome, including challenges receiving a diagnosis and responses to treatment. This study was conducted using a phenomenological research design. A purposeful sample included 16 adult patients with cyclic vomiting syndrome. All data were collected electronically via Survey Monkey and analyzed using content analysis and constant comparison techniques. Two global themes emerged from the data. These were perceived lack of knowledge among healthcare providers and responses to cyclic vomiting syndrome-related treatments. Perceived lack of healthcare provider knowledge contributed to diagnostic delay, inappropriate treatment, and avoidance of care. A combination of medications aimed at managing symptoms and inducing sleep was the most effective abortive medical regimen described. Marijuana use was common. Hot-water bathing was practiced by users and nonusers of marijuana.

The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer.

Our group has previously published the Diagnosis-Specific Graded Prognostic Assessment (GPA) showing the prognostic factors associated with survival in patients with brain metastases (BM). The purpose of this study is to investigate the relationship of breast cancer subtype to the time interval from primary diagnosis (PD) to development of BM (TPDBM), number of BM at initial BM presentation and survival. We analyzed our previously described multi-institutional retrospective database of 865 breast cancer patients treated for newly-diagnosed BM from 1993 to 2010. Several factors found to be associated with survival were incorporated into the Breast-GPA, including tumor subtype. The GPA database was further analyzed to determine if the subtype correlated with the TPDBM, number of BM, and survival from PD. After exclusions for incomplete data, 383 patients remained eligible for analysis. The subtypes were approximated as follows: Luminal B: triple positive; HER2: HER2 positive/ER/PR negative; Luminal A; ER/PR positive/HER2 negative; Basal: triple negative. Patients with Basal (90), HER2 (119), Luminal B (98) and Luminal A (76) tumor subtypes had a median TPDBM of 27.5, 35.8, 47.4 and 54.4 months (p < 0.01), median survival from PD of 39.6, 66.4, 90.3 and 72.7 months (p < 0.01) and median survival from BM of 7.3, 17.9, 22.9 and 10.0 months (p < 0.01), respectively. Tumor subtype is an important prognostic factor for survival in patients with breast cancer and BM. Although TPDBM is not an independent prognostic factor for survival (and thus not part of the Breast-GPA), the TPDBM does correlate with tumor subtype but does not correlate with the number of BM. Patients with Basal and HER2 tumor subtypes have short TPDBM. Prospective studies are needed to determine if screening brain MRIs are indicated in patients with Basal or HER2 subtypes.

Developing a toolkit for panel management: improving hypertension and smoking cessation outcomes in primary care at the VA.

BACKGROUND: As primary care practices evolve into medical homes, there is an increasing need for effective models to shift from visit-based to population-based strategies for care. However, most medical teams lack tools and training to manage panels of patients. As part of a study comparing different approaches to panel management at the Manhattan and Brooklyn campuses of the VA New York Harbor Healthcare System, we created a toolkit of strategies that non-clinician panel management assistants (PMAs) can use to enhance panel-wide outcomes in smoking cessation and hypertension. METHODS: We created the toolkit using: 1) literature review and consultation with outside experts, 2) key informant interviews with staff identified using snowball sampling, 3) pilot testing for feasibility and acceptability, and 4) further revision based on a survey of primary care providers and nurses. These steps resulted in progressively refined strategies for the PMAs to support the primary care team. RESULTS: Literature review and expert consultation resulted in an extensive list of potentially useful strategies. Key informant interviews and staff surveys identified several areas of need for assistance, including help to manage the most challenging patients, providing care outside of the visit, connecting patients with existing resources, and providing additional patient education. The strategies identified were then grouped into 5 areas - continuous connection to care, education and connection to clinical resources, targeted behavior change counseling, adherence support, and patients with special needs. CONCLUSIONS: Although panel management is a central aspect of patient-centered medical homes, providers and health care systems have little guidance or evidence as to how teams should accomplish this objective. We created a toolkit to help PMAs support the clinical care team for patients with hypertension or tobacco use. This toolkit development process could readily be adapted to other behaviors or conditions. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01677533.

Advanced glycation end product (AGE) targeting antibody SIWA318H is efficacious in preclinical models for pancreatic cancer.

SIWA318H is a novel monoclonal antibody that selectively targets an advanced glycation end product biomarker found in damaged/dysfunctional cells exhibiting (a) aerobic glycolysis, and (b) oxidative stress. Cells with this biomarker are dysfunctional and are associated with stresses and/or damages relating to aging, cancer and other disease processes. In this study, we evaluated the biological effects and antitumor activity of SIWA318H in preclinical models for pancreatic cancer. SIWA318H binds to pancreatic cancer cells and cancer-associated fibroblasts, as well as tumor xenografts derived from pancreatic cancer patients. Furthermore, SIWA318H induced significant antibody-dependent cell-mediated cytotoxicity (ADCC) against pancreatic cancer cells. In a humanized CD34+ NSG mouse xenograft model for pancreatic cancer, tumors in mice treated with SIWA318H grew significantly slower compared to those in control mice (p < 0.001). After 3 weeks of treatment with SIWA318H, the tumor growth was suppressed by 68.8% and 61.5% for the high and low dose regimens, respectively, when compared to the isotype antibody control (ANOVA p < 0.002). Moreover, a significant increase in complete remission (CR) rate was observed in mice receiving the high dose (60%, p < 0.04) or low dose (77.8%, p < 0.02) of SIWA318H treatment compared with control mice (6.7%). Immunohistochemical analyses of the tumor tissues showed a significant decrease in senescent cells in the tumor microenvironment of SIWA318H treated mice compared to that of control treated mice (p < 0.05). These results provide compelling evidence that SIWA318H is a promising novel therapeutic against pancreatic cancer.

Developing Connections Between LINC00298 RNA and Alzheimer's Disease Through Mapping Its Interactome and Through Biochemical Characterization.

BACKGROUND: Long non-coding RNAs are ubiquitous throughout the human system, yet many of their biological functions remain unknown. LINC00298 RNA, a long intergenic non-coding RNA, has been shown to have preferential expression in the central nervous system where it contributes to neuronal differentiation and development. Furthermore, previous research has indicated that LINC00298 RNA is known to be a genetic risk factor for the development of Alzheimer's disease. OBJECTIVE: To biochemically characterize LINC00298 RNA and to elucidate its biological function within hippocampal neuronal cells, thereby providing a greater understanding of its role in Alzheimer's disease pathogenesis. METHODS: LINC00298 RNA was in vitro transcribed and then subjected to structural analysis using circular dichroism, and UV-Vis spectroscopy. Additionally, affinity column chromatography was used to capture LINC00298 RNA's protein binding partners from hippocampal neuronal cells, which were then identified using liquid chromatography and mass spectrometry (LC/MS). RESULTS: LINC00298 RNA is comprised of stem-loop secondary structural elements, with a cylindrical tertiary structure that has highly dynamic regions, which result in high positional entropy. LC/MS identified 24 proteins within the interactome of LINC00298 RNA. CONCLUSION: Through analysis of LINC00298 RNA's 24 protein binding partners, it was determined that LINC00298 RNA may play significant roles in neuronal development, proliferation, and cellular organization. Furthermore, analysis of LINC00298 RNA's interactome indicated that LINC00298 RNA is capable of intracellular motility with dual localization in the nucleus and the cytosol. This biochemical characterization of LINC00298 RNA has shed light on its role in Alzheimer's disease pathogenesis.

Examining the relative influence of dispersal and competition on co-occurrence and functional trait patterns in response to disturbance.

Disturbance gradients are particularly useful for understanding the relative influences of competition and dispersal. Shortly after disturbance, plant composition should be influenced more strongly by dispersal than competition; over time, this should reverse, with competition becoming more important. As such, we predicted that plant functional traits associated with high dispersal ability would be over-represented shortly after a disturbance event occurs, while those associated with high competitive ability would have increased representation as time progresses. Additionally, it has been suggested that competitive interactions may contribute to negative co-occurrence patterns; if this is the case, negative co-occurrence patterns should also increase as time-since-disturbance increases. Here, we examine how functional trait and co-occurrence patterns change over time following a herbicide-based disturbance, compared to undisturbed vegetation, in a temperate, old-field grassland dominated by herbaceous perennials. In our study system, negative co-occurrence patterns were most pronounced in disturbed plots one year after herbicide application, consistent with several lines of evidence that dispersal can strongly impact both composition and co-occurrence patterns. Over three years post-disturbance, co-occurrence patterns in disturbed plots decreased, becoming more similar to control plots. This pattern is inconsistent with the expectation that competition contributes to negative co-occurrence patterns, at least over three growing seasons. More pronounced negative co-occurrence patterns were associated with higher species evenness among plots. Functional traits related to increased dispersal (mean seed mass, and proportion of stoloniferous/rhizomatous species) and competitive ability (mean species height, and mean specific leaf area) did not differ significantly across treatments, with the exception of mean height in the third-year post-disturbance; however, the overall trajectory of this trait was inconsistent with theoretical expectations. Overall, co-occurrence patterns changed across the gradient of time-since disturbance, but not as expected; functional trait patterns (trait means, functional diversity measures) were not responsive to our experimental disturbance gradient.

Stereotactic radiosurgery in the management of brain metastases from primary thyroid cancers.

Patients with metastatic well-differentiated thyroid cancer have a generally favorable long-term outcome although multi-organ involvement is a known marker of poor prognosis. Brain metastases are rare, occurring in less than 1% of patients with thyroid cancer. Few patients have been managed with stereotactic radiosurgery (SRS). A retrospective database of 5,067 patients treated for brain metastases between 1985 and 2007 was generated from 11 institutions. Thyroid cancer patients were identified in this database and, when possible, additional information was obtained from further chart review. Patients were excluded if they had incomplete treatment or follow-up information. Two validated prognostic indices, Graded prognostic Assessment (GPA) and Recursive Partitioning Analysis (RPA), were calculated for each patient. The overall survival times were calculated by the Kaplan-Meier method. Twenty-three thyroid cancer patients were identified (51% male, 48% female). Median age was 63 years (range 20-81). Pathology of the primary thyroid disease was available for twelve patients; the majority were diagnosed with differentiated thyroid cancer (n = 9 papillary, n = 2 Hürthle cell; 92%) and one had medullary subtype (8%). Median time from diagnosis of primary disease to brain metastasis was 41.8 months (range 0-516). Fifteen (65%) patients underwent SRS as part of their initial treatment with a median number of lesions treated of 1.5 (range 1-9). The median follow-up time for living patients was 35.2 months. Overall median survival time was 20.8 months (40% alive at last follow-up) and 37.4 months for SRS-treated patients (P = NS). A poor Karnofsky performance status was predictive of worse outcome (P = 0.001). GPA and RPA did not provide additional prognostic information. In conclusion, patients treated with SRS for brain metastases from primary thyroid cancer have a favorable prognosis with an expected median survival greater than 3 years. It is unclear as to whether current prognostic indices are relevant to this patient population.

Long-term results of radiation prophylaxis for heterotopic ossification in the temporomandibular joint.

PURPOSE: To assess the long-term efficacy and toxicity of radiation therapy (RT) for postoperative prophylaxis of recurrent heterotopic ossification (HO) in the temporomandibular joint (TMJ). PATIENTS AND METHODS: Twelve patients (18 joints) with bony ankylosis of the TMJ from HO were referred to undergo RT after arthrotomy with osseous recontouring, gap arthroplasty, or costochondral grafting. Treatment consisted of 10 Gy in 5 daily fractions to a field encompassing the TMJ with an adequate margin. RT was initiated 1 to 3 days postoperatively. Response to therapy was assessed by routine x-ray films obtained preoperatively, immediately postoperatively, and at follow-up by use of the Turlington-Durr grading system. Treatment efficacy was defined as freedom from HO re-formation requiring further surgical intervention. Efficacy and toxicity data were obtained from review of the medical records and were augmented by telephone interview of patients when possible (6 patients, all with follow-up >16 years). Efficacy rates by patient were estimated by the Kaplan-Meier method. RESULTS: The median follow-up after RT was 16.4 years (range, 2.5-19.2 years). Symptomatic re-formation of HO requiring further surgery occurred in 5 patients (7 joints). Treatment efficacy rates were 71% (95% confidence interval [CI], 44-99) at 5 years and 48% (95% CI, 15-80) at 10 years. Of the 6 patients contacted regarding late toxicity, 2 had clinical xerostomia (grade 1, CTCAE v3.0) attributable to RT; no other late RT-related toxicities were noted. None of the 12 patients had malignancy attributable to RT. CONCLUSIONS: Postoperative RT prevented re-formation of TMJ HO in 50% of treated patients long term. Late toxicities from RT were mild and infrequent.