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.

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.

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.

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.

Who needs, receives and misses out on palliative and end-of-life care? A population-based study to identify needs and gaps in a regional health service.

Objective The aim of this study was to assess the unmet need for palliative and other end-of-life care, as well as the sociodemographic and diagnostic factors associated with suboptimal access, among residents in an Australian region. Methods A cross-sectional descriptive and analytical study was performed using non-identifiable linked data from four administrative and two clinical datasets. The study population comprised 3175 patients aged ≥15 years who died in hospital in 2016 and 2017. The main outcome measures were the proportion of decedents potentially benefitting from end-of-life care and receiving end-of-life care. Results An estimated 74.8% of decedents needed palliative or other end-of-life care in the year before death. Approximately 13.3% did not receive any end-of-life care despite its potential benefit. The highest proportions with 'unmet need' were decedents with chronic obstructive pulmonary disease (31.0%) and heart failure (26.3%). Adjusting for sociodemographic and diagnostic factors, access was lowest among those aged <65 years (adjusted odds ratio (aOR) 0.44; 95% confidence interval (CI) 0.31-0.64) and those with heart failure (aOR 0.58; 95% CI 0.47-0.72). Conclusions Estimates of need and access provide a sound basis for planning local palliative and end-of-life care services. These methods can be used on an ongoing basis to monitor service delivery. What is known about this topic? There is a small but expanding literature on estimating the need for palliative care at a population level. There is a lack of data regarding access to palliative and other end-of-life care across multiple settings (e.g. home, specialist palliative care unit, hospital) and patient groups (e.g. defined by sociodemographics and diagnostics). What does this paper add? The study builds on previously used methods for estimating the need for palliative care, with some refinements, including the addition of 'other clinical indications' and the use of weights to derive more realistic estimates. The estimates of need are consistent with recent estimates from Australia and overseas, whereas the estimates of access are similar to a recent Australian estimate, but higher than estimates from overseas. The gaps in access are highest among those with the major types of chronic organ failure, particularly heart and respiratory. What are the implications for practitioners? The study demonstrates how routinely collected data at a regional level can be used to estimate need and access to palliative and end-of-life care, in the hospital and in the community. These methods of estimating need and unmet need can be used to inform the planning and development of services, as well as to monitor progress with implementation of changes in service provision.

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.

Venetoclax or Ruxolitinib in Pre-Transplant Conditioning Lowers the Engraftment Barrier by Different Mechanisms in Allogeneic Stem Cell Transplant Recipients.

Allogeneic stem cell transplantation (alloSCT) is utilised to cure haematological malignancies through a combination of conditioning regimen intensity and immunological disease control via the graft versus tumour (GVT) effect. Currently, conventional myeloablative chemotherapeutic or chemoradiation conditioning regimens are associated with significant side effects including graft versus host disease (GVHD), infection, and organ toxicity. Conversely, more tolerable reduced intensity conditioning (RIC) regimens are associated with unacceptably higher rates of disease relapse, partly through an excess incidence of mixed chimerism. Improvement in post-alloSCT outcomes therefore depends on promotion of the GVT effect whilst simultaneously reducing conditioning-related toxicity. We have previously shown that this could be achieved through BCL-2 inhibition, and in this study, we explored the modulation of JAK1/2 as a strategy to lower the barrier to donor engraftment in the setting of RIC. We investigated the impact of short-term treatment of BCL2 (venetoclax) or JAK1/2 (ruxolitinib) inhibition on recipient natural killer and T cell immunity and the subsequent effect on donor engraftment. We identified striking differences in mechanism of action of these two drugs on immune cell subsets in the bone marrow of recipients, and in the regulation of MHC class-II and interferon-inducible gene expression, leading to different rates of GVHD. This study demonstrates that the repurposed use of ruxolitinib or venetoclax can be utilised as pre-transplant immune-modulators to promote the efficacy of alloSCT, whilst reducing its toxicity.

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.

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.

Physical and sexual violence on college campuses: considerations for international students.

OBJECTIVE: Physical and sexual violence are pervasive concerns on college campuses. Previous research indicates minority populations may be at increased risk for exposure to violence, therefore, international students may represent a vulnerable population. The present study examined differences between international and domestic students regarding the experience of violence and variables related to violence intervention. Participants: Domestic and international colleges students (n = 829) at a Midwestern university in the United States participated in an online survey. Method: Questions assessed experiences of physical and sexual violence, rape myth acceptance, bystander confidence, and readiness to help. Descriptive statistics, chi squares, and independent sample t-tests were conducted to determine differences between groups. Results: Analyses showed no association between international student status and lifetime exposure to violence. Differences were found on acceptance of rape myths and bystander confidence. Conclusions: This study demonstrates the potential benefit of tailored violence prevention and intervention efforts.

Post-Sexual Assault Mental Health: A Randomized Clinical Trial of a Video-Based Intervention.

The current study assessed the efficacy of a brief video intervention (Prevention of Post-Rape Stress [PPRS]) delivered in the emergency department to recent sexual assault (SA) victims. PPRS was compared to treatment as usual (TAU) and an active control condition (Pleasant Imagery and Relaxation Instruction [PIRI]). Primary outcomes were posttraumatic stress disorder (PTSD) symptoms and perceived present control. Prior SA was examined as a moderator of treatment effects. Women (n = 233; aged 15 years and older; 59.70% identified as a racial or ethnic minority) who received a post-SA medical forensic exam participated in the study (NCT01430624). Participants were randomized to watch the PPRS video (n = 77), the PIRI video (n = 77), or receive TAU (n = 79). Participants completed measures of PTSD symptoms and perceived present control 1.5-, 3-, and 6-months post-SA. An interaction between condition and prior SA was found on PTSD symptom frequency and on perceived present control. Among women with a prior SA, women in the PPRS versus TAU condition reported less frequent PTSD symptoms 6-months post-SA. Those in the PPRS condition had lower perceived present control than those in the TAU condition among those with no prior SA 3-months post-SA. However, at 6-months post-SA, among women with a prior SA, women in the PPRS reported higher perceived present control than those in TAU. These findings partially replicate a prior study in which PPRS was found to be beneficial in mitigating the development of PTSD symptoms, but only for women with a prior SA.

Intimate Partner Violence and Psychological Maladjustment: Examining the Role of Institutional Betrayal Among Survivors.

Research has found that a majority of individuals, irrespective of gender, experienced their first intimate partner violence (IPV) victimization between the ages of 18 and 24 years. Indeed, researchers have found that college students' experiences of IPV are comparable if not higher than that of the general population. IPV victimization also places individuals at a higher risk for developing psychological conditions. In addition, when IPV experiences occur on college campuses, there are a variety of institutional factors that may impact the outcome of the traumatic event for the survivor. The present study seeks to examine whether institutional betrayal moderates the relationship between IPV and different psychological outcomes (i.e., depression, posttraumatic stress, anxiety). The study analyzed survey responses from a sample of 316 undergraduate students attending a Midwestern University. Three separate hierarchical regression analyses were conducted for each of the maladaptive psychological outcomes. Results showed that institutional betrayal was positively correlated with depressive symptoms, posttraumatic stress symptoms, and anxiety symptoms. Interestingly, institutional betrayal was a significant predictor of depressive symptoms, posttraumatic stress symptoms, and anxiety symptoms when controlling for the effects of physical violence, sexual violence, and psychological aggression. The present study highlights the significance of the impact of institutional betrayal, independent of interpersonal betrayal, on mental health.

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.

Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy.

Combination venetoclax plus ibrutinib for the treatment of mantle cell lymphoma (MCL) has demonstrated efficacy in the relapsed or refractory setting; however, the long-term impact on patient immunology is unknown. In this study, changes in immune subsets of MCL patients treated with combination venetoclax and ibrutinib were assessed over a 4-year period. Multiparameter flow cytometry of peripheral blood mononuclear cells showed that ≥12 months of treatment resulted in alterations in the proportions of multiple immune subsets, most notably CD4+ and CD8+ effector and central memory T cells and natural killer cells, and normalization of T-cell cytokine production in response to T-cell receptor stimulation. Gene expression analysis identified upregulation of multiple myeloid genes (including S100 and cathepsin family members) and inflammatory pathways over 12 months. Four patients with deep responses stopped study drugs, resulting in restoration of normal immune subsets for all study parameters except myeloid gene/pathway expression, suggesting long-term combination venetoclax and ibrutinib irreversibly affects this population. Our findings demonstrate that long-term combination therapy is associated with immune recovery in MCL, which may allow responses to subsequent immunotherapies and suggests that this targeted therapy results in beneficial impacts on immunological recovery. This trial was registered at www.clinicaltrials.gov as #NCT02471391.

Stereotactic body radiation therapy (SBRT) for metastatic renal cell carcinoma: A multi-institutional experience.

Objectives: Examine local control(LC), overall survival(OS), and toxicity following stereotactic body radiation therapy(SBRT) for patients with metastatic renal cell carcinoma(mRCC). Methods: A multi-institutional registry was queried. Potential predictive factors of LC and OS were evaluated with a Cox-proportional hazards model for multivariate analysis(MVA). Results: We identified 115 mRCC patients with 181 lesions. Median biologically effective dose (BED7) was 72.9 Gy7 (range: 42.9-231.4 Gy7) with a median dose/fraction of 10 Gy (range: 5-24 Gy). Utilizing both Karnofsky Performance Score (KPS) and presence of osseous metastatic disease as prognostic indicators, estimated 2-year OS rates were 67.7% (95% CI: 49.9-89.5%), 31.8% (95% CI: 19.0-45.3%), and 20% (95% CI: 1.4-54.7%; p=0.0012). One- and 2-year LC rates were 88.2% and 82.7%, respectively, with no prognostic factors identified. Roughly 13% of patients reported toxicities with one Grade 3-5 toxicity. Conclusion: SBRT was well-tolerated with promising LC. Both KPS and osseous metastatic disease should be considered in determining which patients with mRCC may preferentially benefit from SBRT.