Modified cell trace violet proliferation assay preserves lymphocyte viability and allows spectral flow cytometry analysis.

In this study we describe three different methods for labeling T lymphocytes with cell trace violet (CTV), in order to track cell division in mouse and human cells, in both the in vitro and in vivo setting. We identified a modified method of CTV labeling that can be applied directly to either conventional or spectral flow cytometry, that maintained lymphocyte viability and function, yet minimized dye spill-over into other fluorochrome channels. Our optimized method for CTV labeling allowed us to identify up to eight cell divisions and the replication index for in vitro-stimulated mouse and human lymphocytes, and the co-expression of T-cell subset markers. Furthermore, the homeostatic trafficking, expansion and division of CTV-labeled congenic donor T cells could be detected using spectral cytometry, in an adoptive T-cell transfer mouse model. Our optimized CTV method can be applied to both in vitro and in vivo settings to examine the behavior and phenotype of activated T cells.

National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: challenges and recommended priorities.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.

Ibrutinib protects T cells in patients with CLL from proliferation-induced senescence.

BACKGROUND: The development of Bruton's tyrosine kinase inhibitors (BTKi) for the treatment of chronic lymphocytic leukaemia (CLL) has provided a highly effective and relatively non-toxic alternative to conventional chemotherapy. Some studies have shown that BTKi can also lead to improvements in T cell immunity in patients despite in vitro analyses suggesting an immunosuppressive effect of BTKi on T cell function. METHODS: In this study, we examined both the in vitro effect and long-term in vivo effect of two clinically available BTKi, ibrutinib and zanubrutinib. Additional in vitro assessments were undertaken for a third BTKi, acalabrutinib. Immune subset phenotyping, cytokine secretion, T cell degranulation and proliferation assays were performed on peripheral blood mononuclear cells isolated from untreated CLL patients, and CLL patients on long-term (> 12 months) BTKi treatment. RESULTS: Similar to prior studies we observed that long-term BTKi treatment normalises lymphocyte subset frequency and reduces PD-1 expression on T cells. We also observed that T cells from patients taken prior to BTKi therapy showed an abnormal hyper-proliferation pattern typical of senescent T cells, which was normalised by long-term BTKi treatment. Furthermore, BTKi therapy resulted in reduced expression of the T cell exhaustion markers PD-1, TIM3 and LAG3 in late generations of T cells undergoing proliferation. CONCLUSIONS: Collectively, these findings indicate that there are critical differences between the in vitro effects of BTKi on T cell function and the effects derived from long-term BTKi exposure in vivo. Overall long-term exposure to BTKi, and particularly ibrutinib, resulted in improved T cell fitness in part due to suppressing the abnormal hyper-proliferation of CLL T cells and the associated development of T cell senescence.

Potentially Traumatic Events and the Association Between Gender Minority Stress and Suicide Risk in a Gender-Diverse Sample.

Transgender and gender diverse (TGD) individuals are at an elevated risk of trauma exposure and other negative mental and physical health outcomes. The present study examined the interaction between minority stressors, reported potentially traumatic events (PTEs), and suicide risk (i.e., ideation and behavior) in a TGD sample. A convenience sample of 155 self-identified TGD individuals completed questionnaires assessing distal (e.g., gender-related discrimination) and proximal (e.g., internalized transphobia) gender identity-related stressors, lifetime PTE history, and suicide risk. The results of a mediation analysis demonstrated that proximal stressors partially mediated the association between distal stressors and suicide risk, B = 1.12, t(152) = 3.72, p < .01, 95% CI [0.53, 1.72], and the results of a moderated mediation analysis showed that the interaction term was not significant, and that the number of PTEs did not moderate the mediation model that examined proximal stressors as a mediator of the association between distal stressors and suicide risk, F(3, 151) = 18.74, MSE = 0.75, R2 = 0.27, B = 0.07, t(151) = 0.89, p = .371, 95% CI [-0.08, 0.21]. These findings suggest that minority stressors may contribute to suicide risk in a TGD population above and beyond the impact of trauma exposure. Risk reduction efforts for suicide risk may be enhanced by attending to minority stressors in addition to PTEs.

Differentiating the symptoms of posttraumatic stress disorder and bipolar disorders in adults: Utilizing a trauma-informed assessment approach.

In adult populations, bipolar disorders (BDs) and posttraumatic stress disorder (PTSD) have overlapping symptoms, potentially leading to misdiagnosis. This misdiagnosis or failure to diagnose both co-occurring disorders can result in individuals not receiving the proper treatment to address their symptoms. This article highlights how trauma-informed psychological assessment can assist in differential diagnosis and improve the timely delivery of appropriate treatments. The overlapping symptoms of PTSD and BD are discussed to assist in differential diagnosis, and we suggest guidelines for conducting trauma-informed, evidence-based assessments to help clarify these diagnoses.

Cognitive Processing Therapy With an Older Woman Veteran During COVID-19: A Case Study.

With advances in technology, telehealth has become an acceptable way of conducting psychotherapy. During the COVID-19 pandemic, telehealth and ways to modify treatments for delivery via telehealth have become increasingly important. Researchers and clinicians have issued recommendations on providing telehealth-based care in response to the COVID-19 global pandemic. However, recommendations are limited for audio only telephone-based care, which may be the only option for specific clients. This is a case study of an older adult who completed Cognitive Processing Therapy (CPT) for military sexual trauma. Halfway through her treatment, COVID-19 resulted in transitioning from in-person services to a virtual format. Client X did not have video capabilities aside from her cell phone, and it was determined she would complete treatment via telephone-based sessions. Client X's outcome data is presented, and the reductions in her PTSD and depressive symptoms provide preliminary support suggesting that telephone-based care may be an acceptable method of receiving CPT. Recommendations for telephone-based CPT are provided.

The impact of exposure, relaxation, and rescripting therapy for post-trauma nightmares on suicidal ideation.

OBJECTIVE: This study investigated whether a brief psychotherapy for post-trauma nightmares (exposure, relaxation, and rescripting therapy [ERRT]), reduced suicidal ideation (SI). We hypothesized that: (a) nightmare frequency and severity, post-traumatic stress disorder (PTSD), depression, and sleep quality would be related to SI at pretreatment; (b) SI would decrease from pre- to post-treatment; and (c) the decrease in SI would remain after controlling for change in PTSD and depression. METHOD: Seventy-five individuals exposed to a traumatic event and who experienced frequent nightmares (minimum one per week) participated in ERRT. Participants were not required to have a psychological diagnosis. Thirty percent endorsed SI at pretreatment. RESULTS: Depression and PTSD were related to SI at pretreatment. SI decreased following treatment; however, the third hypothesis was not supported. CONCLUSION: Results suggest brief psychotherapy targeting post-trauma nightmares may decrease SI. More research is necessary to determine what factors contribute to decreases in SI.

An Assessment of Medical Practitioners' Knowledge of, Experience with, and Treatment Attitudes Towards Sleep Disorders and Nightmares.

Sleep disorders are frequently under assessed and not well understood by medical practitioners. This study investigated medical practitioners' knowledge of, experience with, and treatment considerations for sleep disorders, with a particular emphasis on nightmares. Eighty-eight individuals practicing medicine in the United States completed a survey eliciting information in three domains: (a) professional experience with nightmares, (b) knowledge of nightmares, and (c) attitudes about treatment of sleep disturbances. Seventy percent of participants reported a lack of professional experience with nightmares, 78% endorsed inaccurate definitions of a nightmares, and 82% considered sleep disorders to be a secondary problem, with 75% considering nightmares a secondary problem. Seventy-two percent of participants reported they would be likely to consider psychological treatment for nightmares. Results suggest that medical practitioners may not be receiving updated and/or adequate education about sleep disorders, including nightmares. This lack of information may contribute to sleep disorders being under assessed and untreated.

A relative weights comparison of trauma-related shame and guilt as predictors of DSM-5 posttraumatic stress disorder symptom severity among US veterans and military members.

OBJECTIVES: Veterans and military service members have increased risk for post-traumatic stress disorder (PTSD) and consequent problems with health, psychosocial functioning, and quality of life. In this population and others, shame and guilt have emerged as contributors to PTSD, but there is a considerable need for research that precisely demonstrates how shame and guilt are associated with PTSD. This study examined whether a) trauma-related shame predicts PTSD severity beyond the effects of trauma-related guilt and b) shame accounts for a greater proportion of variance in PTSD symptoms than guilt. DESIGN: We collected cross-sectional self-report data on measures of PTSD symptom severity based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, trauma-related shame, and trauma-related guilt via online survey. METHOD: Participants included 61 US veterans and active duty service members. Hierarchical multiple regression and relative weights analysis were used to test hypotheses. RESULTS: In step 1 of regression analysis, guilt was significantly associated with PTSD. However, when shame was added to the model, the effect of guilt became non-significant, and only shame significant predicted PTSD. Results from relative weights analysis indicated that both shame and guilt predicted PTSD, jointly accounting for 46% of the variance in PTSD. Compared to guilt, trauma-related shame accounted for significantly more explained variance in PTSD. CONCLUSIONS: This study provided evidence that among US veterans and service members, trauma-related shame and guilt differ in their association with PTSD and that trauma-related shame, in particular, is associated with the severity of PTSD. PRACTITIONER POINTS: Trauma-related shame and guilt explained almost half of the observed variance in PTSD symptom severity among this sample of US military veterans and service members. Trauma-related shame and guilt each made a unique contribution to PTSD severity after accounting for the similarity between these two emotions; however, shame was particularly associated with increased PTSD severity. These results highlight the importance of assessing and addressing trauma-related shame and guilt in PTSD treatment among military populations. We suggest that emotion- and compassion-focused techniques may be particularly relevant for addressing trauma-related shame and guilt. Limitations of the study Cross-sectional data does not allow for determination of causal relationships. Although sufficiently powered, the sample size is small. The present sample self-selected to participate in a study about stress and emotions.

Understanding the effectiveness and mechanisms of a social prescribing service: a mixed method analysis.

BACKGROUND: Evidence of the effectiveness of social prescribing is inconclusive causing commissioning challenges. This research focusses on a social prescribing scheme in Northern England which deploys 'Wellbeing Coordinators' who offer support to individuals, providing advice on local groups and services in their community. The research sought to understand the outcomes of the service and, in addition, the processes which supported delivery. METHODS: Quantitative data was gathered from service users at the point they entered the service and also at the point they exited. Qualitative interviews were also undertaken with service users to gather further understanding of the service and any positive or negative outcomes achieved. In addition, a focus group discussion was also conducted with members of social prescribing staff to ascertain their perspectives of the service both from an operational and strategic perspective. RESULTS: In total, 342 participants provided complete wellbeing data at baseline and post stage and 26 semi-structured qualitative interviews were carried out. Improvements in participants' well-being, and perceived levels of health and social connectedness as well as reductions in anxiety was demonstrated. In many cases, the social prescribing service had enabled individuals to have a more positive and optimistic view of their life often through offering opportunities to engage in a range of hobbies and activities in the local community. The data on reductions in future access to primary care was inconclusive. Some evidence was found to show that men may have greater benefit from social prescribing than women. Some of the processes which increased the likelihood of success on the social prescribing scheme included the sustained and flexible relationship between the service user and the Wellbeing Coordinator and a strong and vibrant voluntary and community sector. CONCLUSIONS: Social prescribing has the potential to address the health and social needs of individuals and communities. This research has shown a range of positive outcomes as a result of service users engaging with the service. Social prescribing should be conceptualised as one way to support primary care and tackle unmet needs.

Preliminary validation of a brief measure of the frequency and severity of nightmares: The Trauma-Related Nightmare Survey.

Nightmares and sleep disturbances are gaining attention as targets of treatment interventions for trauma-exposed populations. Measures in trials evaluating these interventions tend to utilize proprietary measures of nightmare characteristics, which makes it challenging to compare findings across studies. The Trauma-Related Nightmare Survey is a questionnaire that was initially developed for utilization in efficacy studies of Exposure, Relaxation, and Rescripting Therapy. Preliminary examinations of the psychometric properties have demonstrated good test-retest reliability and convergent validity. The present brief report provides an updated examination of these properties and offers the first open publication of the measure for general use. Results support previous findings that the Trauma-Related Nightmare Survey demonstrates good test-retest reliability (r = .73) and moderate to strong convergent validity (rs = .44-.78) with other commonly utilized measures of sleep and mood symptoms.

A radio-resistant perforin-expressing lymphoid population controls allogeneic T cell engraftment, activation, and onset of graft-versus-host disease in mice.

Immunosuppressive pretransplantation conditioning is essential for donor cell engraftment in allogeneic bone marrow transplantation (BMT). The role of residual postconditioning recipient immunity in determining engraftment is poorly understood. We examined the role of recipient perforin in the kinetics of donor cell engraftment. MHC-mismatched BMT mouse models demonstrated that both the rate and proportion of donor lymphoid cell engraftment and expansion of effector memory donor T cells in both spleen and BM were significantly increased within 5 to 7 days post-BMT in perforin-deficient (pfn(-/-)) recipients, compared with wild-type. In wild-type recipients, depletion of natural killer (NK) cells before BMT enhanced donor lymphoid cell engraftment to that seen in pfn(-/-) recipients. This demonstrated that a perforin-dependent, NK-mediated, host-versus-graft (HVG) effect limits the rate of donor engraftment and T cell activation. Radiation-resistant natural killer T (NKT) cells survived in the BM of lethally irradiated mice and may drive NK cell activation, resulting in the HVG effect. Furthermore, reduced pretransplant irradiation doses in pfn(-/-) recipients permitted long-term donor lymphoid cell engraftment. These findings suggest that suppression of perforin activity or selective depletion of recipient NK cells before BMT could be used to improve donor stem cell engraftment, in turn allowing for the reduction of pretransplant conditioning.

Best of the Radiosurgery Society® Scientific Meeting 2014: stereotactic radiosurgery/stereotactic body radiotherapy treatment of extracranial and intracranial lesions.

The SRS/SBRT Scientific Meeting 2014, Minneapolis, MN, USA, 7-10 May 2014. The Radiosurgery Society(®), a professional medical society dedicated to advancing the field of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), held the international Radiosurgery Society Scientific Meeting, from 7-10 May 2014 in Minneapolis (MN, USA). This year's conference attracted over 400 attendants from around the world and featured over 100 presentations (46 oral) describing the role of SRS/SBRT for the treatment of intracranial and extracranial malignant and nonmalignant lesions. This article summarizes the meeting highlights for SRS/SBRT treatments, both intracranial and extracranial, in a concise review.

Improved local control following dose-escalated stereotactic ablative radiation therapy (SABR) for metastatic sarcomas: An international multi-institutional experience.

BACKGROUND: We aimed to characterize local control (LC) and overall survival (OS) following stereotactic ablative radiation therapy (SABR) for extracranial sarcoma metastases. METHODS: A prospectively-maintained institutional registry was queried for patients with metastases from sarcoma primaries managed with SABR. Kaplan-Meier analysis was utilized for univariate analyses to assess potential prognostic factors regarding LC and OS. A Cox proportional hazards multivariate (MVA) model was employed to further assess initially identified independent variables. RESULTS: A total of 94 patients with 118 lesions with LC information were identified. Common metastatic sites treated were lung (77), non-spinal bone (15), and spine (10). The median biologically effective dose (BED4) was 175 Gy4 (range56.3 Gy4-360 Gy4) with a median dose/fractionation schedule of 50 Gy/5 fractions. One- and 2-year OS rates were 81.3 % (95 % CI: 71.2-88.1 %6) and 50.5 % (95 % CI: 38.6-61.3 %, respectively. On Cox MVA, advanced age and non-lung metastases were associated with inferior OS (p < 0.03) with patients with 0-2 of these risk factors having estimated 2-year OS of 65.1 %, 38.9 %, and N/A, respectively. One- and 2-year LC rates were 85.3 % (95 % CI: 77.7-90.9 %) and 78.2 % (95 % CI: 67.9-85.6 %), respectively. On MVA, only BED4 < 175 Gy was associated with inferior LC (hazard ratio (HR) = 3.33; p = 0.01). Ten of 118 treated lesions had treatment-related toxicities (all Grade 1-2). CONCLUSION: Age and lung vs. non-lung metastases were prognostic of OS and should be considered in patient selection for SABR. Dose escalation when feasible with BED4 ≥ 175 Gy is recommended given durable LC achieved without a subsequent increase in toxicity.

The challenge of delivering endocrine care and successful transition to adult services in adolescents with congenital adrenal hyperplasia: experience in a single centre over 18 years.

BACKGROUND: Congenital adrenal hyperplasia (CAH) has implications throughout a patient's life. The challenges of organizing transition from paediatric to adult care in endocrinology are recognized. OBJECTIVE: To evaluate whether young people with CAH have been successfully transitioned from paediatric care to specialist adult services and the influence of the introduction of a Young Person Clinic (YPC) where the young person is introduced to the adult endocrinologist. DESIGN, PATIENTS AND MEASUREMENTS: Patients aged 16+ years with CAH who had attended the adrenal clinic at Royal Manchester Children's Hospital between 1992 and 2009 were identified. Clinical information, attendance data in paediatric and adult services were obtained from patient records and the electronic appointment system. RESULTS: A total of 61 patients (27 men) were identified. Thirty-six patients were referred to specialist adult services from the paediatric service; eighteen of these (50%) were lost to follow-up (two were never offered an appointment). Only 53% of the whole group attended their first new and subsequent second appointment (i.e. good early attenders). There was no difference in engagement with adult services in those who transitioned through the YPC. Good early attenders were less likely to get lost to follow-up compared with poor early attenders (11-33% lost to follow-up compared with 63-71%). CONCLUSIONS: Half of all young people with CAH referred to specialist adult services are no longer attending. Introducing the adult endocrinologist prior to transfer had no positive effect on engagement with adult services. Attendance at the first two appointments in the adult services should be seen as an indicator of 'reasonable' engagement.

Adverse childhood experiences, posttraumatic stress disorder symptoms, and emotional intelligence in partner aggression.

Intimate partner violence (IPV) has been linked to childhood abuse, posttraumatic stress disorder (PTSD), and low emotional intelligence (EI). Relationships among adverse childhood experiences (ACE), PTSD symptoms, and partner aggression (i.e., generalized tendency to aggress toward one's partner) were assessed in 108 male IPV offenders. It was hypothesized that ACE is positively correlated with partner aggression, PTSD mediates the ACE-aggression relationship, and the ACE-PTSD-aggression mediation varies by selected EI facets. Results indicate that ACE has an indirect effect on partner aggression via PTSD and PTSD mediates the ACE-aggression link when emotional self-regulation is low and when intuition (vs. reason) is high. Trauma-exposed IPV offenders may benefit from comprehensive treatments focusing on PTSD symptoms, emotional control, and reasoning skills to reduce aggression.

A phase 1 clinical trial of the repurposable acetyllysine mimetic, n-methyl-2-pyrrolidone (NMP), in relapsed or refractory multiple myeloma.

BACKGROUND: N-methyl-2-pyrrolidone (NMP) is an epigenetically active chemical fragment and organic solvent with numerous applications including use as a drug-delivery vehicle. Previously considered biologically inert, NMP demonstrates immunomodulatory and anti-myeloma properties that are partly explained by acetyllysine mimetic properties and non-specific bromodomain inhibition. We therefore evaluated orally administered NMP in a phase 1 dose-escalation trial to establish its maximum tolerated dose (MTD) in patients with relapsed/refractory multiple myeloma (RR-MM). Secondary endpoints were safety, pharmacokinetics (PK), overall response rate and immunological biomarkers of activity. RESULTS: Thirteen patients received NMP at starting doses between 50 and 400 mg daily. Intra-patient dose escalation occurred in five patients, with one attaining the ceiling protocolised dose of 1 g daily. Median number of monthly cycles commenced was three (range 1-20). Grade 3-4 adverse events (AEs) were reported in seven (54%; 95% CI 25-81%) patients. Most common AEs (> 30% of patients) of any grade were nausea and musculoskeletal pain. The only dose limiting toxicity (DLT) was diarrhoea in a patient receiving 200 mg NMP (overall DLT rate 8%; 95% CI 0-36%). Hence, the MTD was not defined. Median progression-free and overall survival were 57 (range 29-539) days and 33 (95% CI 9.7- > 44) months, respectively. The best response of stable disease (SD) was achieved in nine patients (69%; 95% CI 39-91%). PK analysis demonstrated proportional dose-concentrations up to 400 mg daily, with a more linear relationship above 500 mg. Maximum plasma concentrations (Cmax) of 16.7 mg/L at the 800 mg dose were below those predicted to inhibit BET-bromodomains. Peripheral blood immune-profiling demonstrated maintenance of natural killer (NK) cells, and a gene expression signature suggestive of enhanced T, B and NK cell functions; a subject with prolonged exposure manifested sustained recovery of B and NK cells at 12 months. CONCLUSIONS: NMP demonstrated potential disease stabilising and immunomodulatory activity at sub-BET inhibitory plasma concentrations and was well tolerated in RR-MM; an MTD was not determined up to a maximum dose of 1 g daily. Further dose-finding studies are required to optimise NMP dosing strategies for therapeutic intervention.

Implications of language use in posttraumatic nightmares on psychological symptoms.

OBJECTIVE: The current study sought to understand how language use in posttrauma nightmare (PTNM) reports may be related to psychological symptoms over the course of treatment. METHOD: Multiple regression analyses were conducted to examine the relationship between language use in PTNMs and psychological symptoms. Specifically, cognitive processing words (CPW) and emotional tone (ET) measured in PTNMs were analyzed in their relationship to posttraumatic stress disorder (PTSD) and depression symptom severity, as well as nightmare frequency and distress measured at the midtreatment and last treatment sessions. Follow-up hierarchical regressions were used to assess the relationship of language to nightmare severity when controlling for both PTSD and depression severity. The sample consisted of treatment-seeking predominately Caucasian females from the community with a history of criterion A trauma and weekly nightmares. RESULTS: CPW in the nightmare were negatively associated with PTSD and depression symptom severity, as well as nightmare frequency, at the time of the exposure session. Decreased CPW and negative ET within the nightmare remained significantly associated with nightmare frequency at the time of the exposure session, when controlling for PTSD and depression symptom severity. CPW in the rescripted PTNM were negatively associated with PTSD and depression symptom severity at the time of the last treatment session. CONCLUSIONS: These results suggest that language use in nightmares may reveal important information about underlying cognitive and emotional processes that may help understand the etiology and maintenance of PTSD symptoms, as well as support PTNMs as co-occurring symptoms requiring targeted treatment, and not merely secondary symptoms of PTSD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Stereotactic Body Radiation Therapy (SBRT) for Spinal Metastases: Real-world Outcomes From an International Multi-institutional SBRT Registry.

OBJECTIVE: The objective of this study was to compare clinical outcomes following single fraction versus fractionated stereotactic body radiotherapy (SBRT) for spinal metastases. MATERIALS AND METHODS: A multi-institutional registry was queried for patients with spinal metastases treated with single-fraction or fractionated SBRT. Potential predictive factors of local control (LC) and overall survival were evaluated. Pretreatment and posttreatment Visual Analog Scale scores were analyzed to examine initial and durable pain responses and complete response (CR) rates. Logistic regression was utilized to assess potential correlations between pain response, biologically effective dose (BED), and fractionation. RESULTS: Four hundred sixty-six patients with 514 lesions treated with SBRT were identified; 209 and 104 lesions had information on LC and pain, respectively. The median pain score of patients with symptoms was 6 (range: 3 to 10). The median follow-up was 8.9 months (range: 0.4 to 125.5 mo). Utilizing Karnofsky Performance Score, age, and primary site (lung and/or nonbreast), 1-year overall survival rates were 76.1%, 59.1%, 54.9%, 37.2%, and 23.5% for patients with 0 to 4 of these factors, respectively (P<0.0001). One- and 2-year LC rates were 79.9% and 73.6%, respectively. Eighty-six patients (82.7%) had an initial pain response with a median decline of 3.5 and a CR rate of 47.1%. Sixty-five patients (62.5%) had a durable pain response with a median decline of 2 and a CR rate of 20.2%. Higher initial CR rates were observed with BED10 ≥51 Gy10 (58.7% vs. 37.9%; P=0.04). CONCLUSIONS: Following SBRT, encouraging palliative responses with >80% and 60% of patients having initial and durable pain responses, respectively. Dose escalation may result in improved initial CR rates. Performance status, age, and primary histology are factors to consider in the absence of pain.

A multi-institutional analysis of outcomes following stereotactic body radiation therapy for management of metastases from squamous cell carcinomas of the head and neck.

Background: There is limited data on clinical outcomes following SBRT for patients with metastatic head and neck squamous cell carcinoma (mHNC). Method: An international SBRT registry was utilized to identify patients. LC and OS were evaluated with the Kaplan-Meier method and a Cox-proportional hazards model for multivariate analysis (MVA) to assess potential prognostic factors. Results: We identified 81 patients with 98 lesions treated with SBRT. Areas treated included the lung (53.0%), non-regional lymph nodes (16.0%), and spine (12.3%). OS rates at 1 year and 2 years were 66.4% and 43.1%, respectively. Utilizing KPS, spinal disease, and GTV, 1-year OS estimates were 90.9%, 70.4%, 54.5%, and 25% for patients with 0-3 of these factors, respectively (p = 0.002). One-year and 2-year LC rates were both 93.3%. Roughly 17% of patients reported toxicities (none Grade 3+). Conclusions: SBRT resulted in promising LC for mHNC patients. Spinal disease, GTV, and KPS should be considered in selecting patients with mHNC that may benefit from SBRT.