An Evaluation of the Sharing Dance Public School Program on Physical Literacy.

Introduction: Physical literacy (PL) is a multidimensional concept that includes the domains of movement competence, positive affect, social participation, and the confidence, motivation, and knowledge and understanding necessary for regular engagement in physical activity. The Sharing Dance Public School Program was created by Canada's National Ballet School specifically designed to promote PL through dance. The objective of this study was to evaluate the effectiveness of the program to improve PL in grade 4 to 6 children over the course of a school year. Methods: Children were initially recruited from two schools including an intervention and a control school. However, due to the COVID-19 pandemic, data collection was prematurely terminated which resulted in baseline and mid-point data from the intervention group only. As such, participants included 57 children (n = 28 females, Mage = 10.34 ± 0.85 years) that engaged in the dance program once per week for 50 minutes. Assessments of PL included a direct measure of movement competence (PLAYfun) and a self-report measure (survey) to assess the other domains of PL. Results: Significant improvements were found in movement competence. However, significant decreases were found for fun and enjoyment, confidence, and social participation. No changes were observed for knowledge and understanding or overall PL. Conclusions: Findings from the present study are encouraging as they provide initial evidence for the support of community-based PL programs, such as the Sharing Dance Public School Program, to help children develop their movement competence. Future research is needed to further evaluate the effectiveness of the Sharing Dance Public School Program over a school year, and when compared to a control group, as was initially intended.

The contribution and interplay of implicit and explicit processes on physical activity behavior: empirical testing of the physical activity adoption and maintenance (PAAM) model.

The adoption and maintenance of physical activity (PA) is an important health behavior. This paper presents the first comprehensive empirical test of the Physical Activity Adoption and Maintenance (PAAM) model, which proposes that a combination of explicit (e.g., intention) and implicit (e.g., habit,, affect) self-regulatory processes is involved in PA adoption and maintenance. Data were collected via online questionnaires in English, German, and Italian at two measurement points four weeks apart. The study included 422 participants (Mage= 25.3, SDage= 10.1; 74.2% women) from Germany, Switzerland, Italy, Canada, and the U.S. The study results largely supported the assumptions of the PAAM model, indicating that intentions and habits significantly mediate the effects of past PA on future PA. In addition, the effect of past PA on future PA was shown to be significant through a mediation chain involving affect and habit. Although the hypothesis that trait self-regulation moderates the intention-behavior relationship was not supported, a significant moderating effect of affect on the same relationship was observed. The results suggest that interventions targeting both explicit and implicit processes may be effective in promoting PA adoption and maintenance.

Association of Cabozantinib Dose Reductions for Toxicity With Clinical Effectiveness in Metastatic Renal Cell Carcinoma (mRCC): Results From the Canadian Kidney Cancer Information System (CKCis).

BACKGROUND: Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated efficacy in metastatic renal cell carcinoma (mRCC). The association between toxicity and therapeutic effectiveness has been established with other TKIs. We investigated whether cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, were associated with improved clinical outcomes in mRCC. METHODS: Employing the CKCis database, we analyzed patients treated with cabozantinib in the second line or later between 2011 to 2021. The cohort was stratified into those needing dose reductions (DR) during treatment and those not (no-DR). Outcomes, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS), were compared based on dose reduction status. The influence of the initial dose on outcomes was also explored. RESULTS: Among 319 cabozantinib-treated patients, 48.3% underwent dose reductions. Response rates exhibited no significant difference between the DR and no-DR groups (15.1% vs. 18.2%, P = .55). Patients with DR had superior median OS (26.15 vs. 15.47 months, P = .019) and TTF (12.74 vs. 6.44 months, P = .022) compared to no-DR patients. These differences retained significance following adjustment for IMDC risk group (OS HR = 0.67, P = .032; TTF HR = 0.65, P = .008). There was no association between the initial dose and ORR, OS, or TTF. CONCLUSION: This study highlights the link between cabozantinib dose reductions due to toxicity and improved survival and time to treatment failure in mRCC patients. These findings underscore the potential of using on-treatment toxicity as an indicator of adequate drug exposure to individualize dosing and optimize treatment effectiveness. Larger studies are warranted to validate these results and develop individualized strategies for cabozantinib when given alone or in combination with immunotherapy.

Long-term Survival Among Patients With De Novo Human Epidermal Growth Receptor 2-Positive Metastatic Breast Cancer in Manitoba.

OBJECTIVES: Although metastatic breast cancer (MBC) is considered incurable, human epidermal growth receptor 2 (HER2)-directed therapy has improved outcomes significantly, with some patients experiencing durable responses to treatment. The aim of this study was to identify potential predictors of long-term survival (LTS) among patients with de novo HER2-positive MBC who received HER2-directed treatment. METHODS: Eligible patients from 2008 to 2018 were identified using the Manitoba Cancer Registry. LTS was defined as survival ≥5 years from the time of diagnosis. Univariate logistic regression models were performed to assess variables of clinical interest and the odds of LTS. Overall survival (OS) was defined as the time from diagnosis of MBC to death of any cause. OS was estimated using the Kaplan-Meier method with log-rank comparative analyses as a univariate analysis. A Cox proportional hazards model was used for OS estimates in a univariate analysis. RESULTS: A total of 62 patients were diagnosed with de novo HER2-positive MBC and received HER2-directed therapy. Eighteen (29%) achieved LTS. The median OS of the whole cohort was 50.2 months (95% CI: 28.6-not reached). Radiographic response to first-line treatment was associated with LTS; complete and partial responses were both associated with higher odds of LTS (odds ratio: 28.33 [95% CI: 2.47-4006.71, P = 0.0043] and odds ratio: 7.80 [95% CI: 0.7317-1072.00, P = 0.0972], respectively). The best radiographic response was associated with improved OS. CONCLUSIONS: Radiographic response to first-line HER2-directed therapy is a predictor for LTS in patients with de novo HER2-positive MBC. Larger studies are needed to identify patients who can safely discontinue HER2-targeted therapy.

Real-world Assessment of Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma with or Without Sarcomatoid Features Treated with First-line Systemic Therapies.

BACKGROUND AND OBJECTIVE: Metastatic renal cell carcinoma (mRCC) patients have been reported to have better outcomes when treated with immunotherapies (IO) compared to targeted therapies (TT). This study aims to evaluate the impact of first-line systemic therapies on survival of mRCC patients with or without sarcomatoid features using real-world data. METHODS: Metastatic RCC patients of International mRCC Database Consortium (IMDC) intermediate or high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system. Patients were classified by initial treatment: (1) targeted therapy (TT) used alone or (2) immunotherapy (IO)-based systemic therapies used in combination of either IO-IO or IO-TT. The inverse probability of treatment weighting using propensity scores was used to balance for covariates. Cox proportional hazard models were used to assess the impact of initial treatment received on overall survival (OS). KEY FINDINGS AND LIMITATIONS: Of the 1202 eligible patients, 791 were treated with TT and 411 with IO combinations. Of the patients, 76% were male, and the majority (91%) had a nephrectomy before systemic therapy. In nonsarcomatoid patients (639 TT and 320 IO patients), treatment with IO was associated with improved OS compared with patients treated with TT (median of 72 vs 48 mo, hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.50-0.80, objective response rate [ORR] of 38.5% for IO and 23.5% for TT). In sarcomatoid patients (152 TT and 91 IO patients), treatment with IO was associated with improved OS (median of 48 vs 18 mo, HR 0.41, 95% CI 0.26-0.64, ORR of 49.5% for IO and 13.8% for TT). Similar results were observed in patients with synchronous metastatic disease only. CONCLUSIONS AND CLINICAL IMPLICATIONS: IO treatment was associated with improved survival in mRCC patients. The magnitude of benefit is increased in patients with sarcomatoid mRCC, consequently, identifying the sarcomatoid status early on could help healthcare providers make a better treatment decision. PATIENT SUMMARY: Metastatic renal cell carcinoma (mRCC) patients of International mRCC Database Consortium intermediate and high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system (CKCis). In this study, treatment with immunotherapy was associated to an improved survival and response rates for mRCC patients with and without sarcomatoid features. The magnitude of benefit is increased in patients with sarcomatoid mRCC.

Advances in navigating to the nodule and targeting.

PURPOSE OF REVIEW: The multitude of available platforms and imaging modalities for navigational bronchoscopy, in combination with the various sampling tools that can be used intra-procedurally, is complex. This review seeks to describe the recent developments in peripheral bronchoscopy in regards to navigation, imaging, and sampling target lesions in the pulmonary parenchyma. RECENT FINDINGS: Robotic assisted bronchoscopy has improved navigation to the peripheral airways for sampling of peripheral parenchymal lesions. These navigational platforms use innovative technology utilizing electromagnetic navigation and shape-sensing technology for guidance. The greatest improvement has been the stabilization of the robotic scope in the periphery to allow for accurate sampling. Despite improvements in these platforms, limitations of CT to body divergence continue to impact navigation to the lesion and therefore diagnostic yield of the procedure. Advanced intraprocedural imaging with cone beam CT or augmented fluoroscopy has been a recent focus to improve this area. Further, the adoption of newer sampling tools, such as cryobiopsy, offers the possibility of increased diagnostic yield. SUMMARY: The developments in advanced bronchoscopy will impact the role of biopsy in the diagnosis of peripheral pulmonary parenchymal lesions.

Effectiveness and Safety of Immune Checkpoint Inhibitors in Cancer Patients With Autoimmune Disease: A Retrospective Cohort Study.

Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, patients with pre-existing autoimmune diseases (PADs) have largely been excluded from clinical trials evaluating this drug class. This study evaluates the effectiveness and safety of ICI therapy in individuals with PAD in a real-world setting. A retrospective study of patients exposed to ICI therapy between 2012 and 2019 was conducted. Patients with PAD were identified and matched to an ICI-exposed group without PAD based on age, sex, and cancer type. Primary outcomes included toxicity, time to treatment failure, overall survival, and objective response rate. The association between PAD status and outcomes was determined using Cox and logistic regression modeling. A total of 813 patients exposed to ICI therapy were identified, of which 8.2% (N=67) had a PAD. When compared with a matched cohort without PAD (N=132), there was no significant difference in the rates of new immune-related adverse events (irAEs, 42.4% in the non-PAD group vs. 47.8% in the PAD group, P=0.474). After controlling for the type of ICI, there was no significant association between PAD status and irAE (odds ratio 1.67, 95% CI: 0.9-3.21 P=0.1). There was no significant association between overall survival and PAD status (hazard ratio 1.12, 95% CI: 0.76-1.66. P=0.56) or between time to treatment failure and PAD status (hazard ratio 0.82, 95% CI: 0.6-1.12, P=0.22). There was an association between PAD status and objective response rate (odds ratio 3.28, 95% CI: 1.28-8.38, P=0.013). In summary, PAD status was not associated with enhanced toxicity when compared with patients without PAD, with similar oncologic effectiveness between these 2 groups.

Trends of Utilization of Systemic Therapies for Metastatic Renal Cell Carcinoma in the Canadian Health Care System.

PURPOSE: Standard-of-care therapies for metastatic renal cell carcinoma (mRCC) have greatly evolved. However, the availability of emerging options in global health care systems can vary. We sought to describe the integration and usage of systemic therapies for mRCC in Canada since 2011. METHODS: We included patients with mRCC enrolled in the Canadian Kidney Cancer Information System, a prospective cohort of patients from 14 Canadian academic centers, who received systemic therapy from January 1, 2011, to December 31, 2021. Patients were stratified by treatment era (cohort 1: 2011-2015, cohort 2: 2016-2021). Stacked bar charts were used to present treatment proportions; Sankey diagrams were used to show the evolution of treatment sequencing between the two cohorts. RESULTS: Four thousand one hundred seven patients were diagnosed with mRCC, of whom 2,752 (67%) received systemic therapy. Among these patients, mean age was 64 years, 74% were male, 75% had clear cell histology, and International Metastatic RCC Database Consortium risk classification was favorable, intermediate, and poor in 16%, 56%, and 28%, respectively. Utilization of immune checkpoint inhibition (ICI)-based treatments has increased in Canada and reflects global and local patterns of approval and adoption. The use of therapies after doublet ICI has mostly shifted toward vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) that were previously used in first line with subsequent treatments reflecting approved and available agents after previous VEGF-TKI. Clinical trial participation among patients who received systemic therapy was 18% in first, 21% in second, and 24% in third line. CONCLUSION: In Canada's publicly funded health care system, availability of standard mRCC therapies broadly reflects access from government-funded clinical trials and compassionate access program sources. In an evolving therapeutic landscape, ongoing advocacy is required to continue to facilitate patient access to efficacious therapies.

The golden ratio in baseball: the influence of historical eras on winning percentages in major league baseball.

Introduction: The golden section or golden ratio (61.8% or 0.618) is a mathematical phenomenon that appears in art, literature, music and nature with such ubiquity that it is thought to be a fundamental principle of aesthetic organisation. The golden ratio also manifests in sport, particularly as the proportion of wins to losses required to win a Major League Baseball championship. This study extends early work on the golden ratio in baseball by incorporating more than three decades of additional data. Methods: This study involved a historically contextualized examination of how winning percentages have changed across the seven historical eras of modern baseball, including analyses of the relative contribution of offensive and defensive statistics to championship winning teams. Data was extracted from Baseball Reference and included statistics for 398 championship winning teams from both the American and National Leagues between 1901 and 2019. Pearson correlation coefficients were computed for winning percentage with indicators of offensive and defensive performance during each era. Main and interaction effects of Era and League on winning percentage were examined using factorial ANOVA, with follow-up analyses examining whether the golden ratio was included in each factor's 95% confidence interval. Results: Our findings suggest that winning percentages for championship teams were closest to the golden ratio during eras where the relative contribution of offense and defense was most closely balanced: the Integration Era (1942-1960) and the Expansion Era (1961-1976). Discussion: Previous scholarship theorizes that the golden ratio represents an aesthetic ideal or a Gestalt archetype. If this aesthetic theory is applied to sporting competition, these results suggest that baseball may be most aesthetically appealing to fans when offense and defense is balanced in such a way as to ensure that championship teams win 61.8% of their games.

Adjuvant therapy for renal cell carcinoma: 2023 Canadian Kidney Cancer Forum consensus statement.

INTRODUCTION: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. METHODS: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. RESULTS: A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. CONCLUSIONS: This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.

Development and evaluation of the IPLAY program: A protocol for a mixed-methods feasibility study targeting newcomer youth.

BACKGROUND: Physical Literacy (PL) is a synthesis construct that ties together movement competencies with affective, motivational, and knowledge-based elements. It is considered foundational to the development of physical activity-related outcomes. Many diverse organizations and programs have embraced the concept and are implementing programs targeting each of those core elements. However, research has lagged behind its interest and adoption. Among the more prominent gaps is the design and evaluation of programs that aim to increase PL within special populations such as new immigrants or refugee youth. METHODS: The Immigrant-focused Physical Literacy for Youth (IPLAY) program is a co-developed evidence-informed 8-week PL program designed for new immigrant and refugee youths who have recently settled in Calgary, Alberta, Canada. This study aims to use a convergent parallel mixed-methods approach to collect, analyse, and interpret quantitative and qualitative data in the evaluation and iteration of the IPLAY program. DISCUSSION: PL programs can be used as a tool to build confidence and physical competencies among newcomer youth. Furthermore, academic-community collaborations in the design and delivery of PL programs can help improve the access and interest for PL programs among newcomer youth. These partnerships are critical and timely considering the recent and upcoming waves of immigration to "arrival cities" across Canada.

Evaluating the impact of early identification of asymptomatic brain metastases in metastatic renal cell carcinoma.

BACKGROUND: Brain metastases (BM) in metastatic renal cell carcinoma (mRCC) have been reported to be present in up to 25% of patients diagnosed with mRCC. There is limited published literature evaluating the role of routine intra-cranial imaging for the screening of asymptomatic BM in mRCC. AIMS: To evaluate the potential utility of routine intra-cranial imaging, a retrospective cohort study was conducted to characterize the outcomes of mRCC patients who presented with asymptomatic BM, as compared to symptomatic BM. METHODS AND RESULTS: The Canadian Kidney Cancer Information System (CKCis) database was used to identify mRCC patients diagnosed with BM. This cohort was divided into two groups based on the presence or absence of BM symptoms. Details regarding patient demographics, disease characteristics, systemic treatments, BM characteristics and survival outcomes were extracted. Statistical analysis was through chi-square tests, analysis of variance, and Kaplan-Meier method to characterize survival outcomes. A p-value of <0.05 was considered statistically significant for all analyses. A total of 267 mRCC patients with BM were identified of which 106 (40%) presented with asymptomatic disease. The majority of patients presented with multiple (i.e., >1) BM (75%) with no significant differences noted in number of BM or BM-directed therapy received in symptomatic, as compared to asymptomatic BM patients. Median [95% confidence interval (CI)] overall survival (OS) from mRCC diagnosis was 42 months (95% CI: 32-62) for patients with asymptomatic BM, and 39 months (95% CI: 29-48) with symptomatic BM (p = 0.10). OS from time of BM diagnosis was 28 months (95% CI: 18-42) for the asymptomatic BM group, as compared to 13 months (95% CI: 10-21) in the symptomatic BM group (p = 0.04). CONCLUSIONS: Given a substantial proportion of patients may present with asymptomatic BM, limiting intra-cranial imaging to patients with symptomatic BM, may be associated with a missed opportunity for timely diagnosis and treatment. The utility of routine intra-cranial imaging in patients with renal cell carcinoma, warrants further prospective evaluation.

A mixed method investigation of teacher-identified barriers, facilitators and recommendations to implementing daily physical activity in Ontario elementary schools.

BACKGROUND: Fewer than 17% of children worldwide are meeting the international recommendations for daily physical activity. Since most children are in school for the bulk of their day, the classroom has been identified as an ideal space to incorporate physical activity opportunities. In Ontario (Canada), the Daily Physical Activity (DPA) policy aims to ensure all elementary school children receive a minimum of 20 min of moderate to vigorous physical activity each school day during instructional time. However, a 2015 evaluation found that only half of Ontario teachers were meeting this expectation; this work advocated for additional research to monitor implementation and its predictors and to further identify fidelity recommendations. Thus, the current study investigated contemporary factors influencing DPA fidelity in Ontario elementary schools and provides teacher-identified recommendations to support DPA implementation. METHODS: The first part of the study was a quantitative approach surveying 186 elementary school teachers across Ontario. Descriptive statistics including frequencies and means were used to characterize barriers, facilitators, and recommendations to DPA implementation. Spearman's correlations were used to assess the relation between the likelihood of DPA implementation and intrapersonal factors of gender, teaching experience, prior DPA training and personal physical activity participation. The second part of the study consisted of a qualitative approach using teacher interviews to explore in-depth teachers' recommendations to support DPA implementation. A thematic analysis was used to analyze the transcripts and identify recommendations for DPA. RESULTS: Survey results showed that only 23% of teachers met the mandated 20 min of DPA per day. Barriers to implementation included space and time constraints, inadequate training, student behavioural issues and low self-efficacy. Gender, teaching experience and prior DPA training were not related to the likelihood of DPA implementation. Teachers who rated themselves as more physically fit were more likely to implement DPA. Teacher interviews elucidated key areas for improving DPA implementation including greater DPA training opportunities, resources, community partnerships, accountability and strategies that support school-wide implementation. CONCLUSION: The current study demonstrated that fidelity to the DPA policy in Ontario elementary schools is on the decline. This work highlights unique factors implicated in DPA fidelity and brings to the forefront teacher recommendations to improve DPA implementation.

Effect of cognitively engaging physical activity on executive functions in children.

Purpose: Physical activity (PA) has been shown to enhance executive functions (EFs) in children, and PA involving a cognitive component may confer additional benefit. The purpose of this study was to investigate whether cognitively engaging PA impacts EF, and whether affect and fitness act as either mediators or moderators of this relationship. Methods: A randomized controlled trial was utilized to assess changes in EFs between a 20-min Dual Task (intervention condition), a PA Task (control condition), and a Cognitive Task (control condition). Children were scheduled for two visits in the INfant and Child Health (INCH) Lab at the University of Toronto. Physical fitness was assessed using the 20 m shuttle run, standing long jump, and grip strength tests. EFs were assessed using the Stroop Task, Trail Making Task (TMT), and Forward Working Memory Task (FWMT). Results: 38 children (Mage = 11.95 years, SD = 0.49, 61% female) participated. Repeated measures ANOVA showed main interactions between time on inhibition scores (p < 0.05, η p 2 = 0.489), and positive affect scores (p < 0.01, η p 2 = 0.284). Interaction effects between condition and time were not significant (p = 0.787, η p 2 = 0.014, p = .333, η p 2 = 0.061, p = 0.799, η p 2 = 0.013 for inhibition, switching, and passive working memory, respectively). Results showed no significant mediation effect of affect (95% CI = -0.5915, 2.147), or moderating effect between fitness and EF changes. Conclusion: Possible explanations for these findings include inadequate cognitive engagement, lack of EF transfer, and statistical power. Results suggest any of these interventions may be beneficial for improving inhibition and positive affect in children.

Cabozantinib after prior checkpoint inhibitor therapy in patients with solid tumors: A systematic literature review.

INTRODUCTION: We conducted a systematic literature review to identify evidence for cabozantinib activity in patients with solid tumors after prior checkpoint inhibitor (CPI) therapy. METHODS: The review was conducted according to PRISMA guidelines and registered with PROSPERO (CRD42021259873). MEDLINE®, Embase, and the Cochrane Library were searched on 19 May 2021 to identify publications reporting the efficacy/effectiveness and safety/tolerability of cabozantinib in patients with solid tumors who had received prior CPI-based therapy. Publications were screened by one reviewer with uncertainties resolved by a second and/or the full author group. Risk of bias was assessed using Gradingof Recommendations Assessment, Development and Evaluation (GRADE) for clinical trials and the Newcastle-Ottawa Scale (NOS) for observational studies. RESULTS: Of 669 publications screened, 21 were eligible: 18 reported data on renal cell carcinoma, and one each for hepatocellular carcinoma, metastatic urothelial carcinoma, and non-small cell lung cancer. Of six trial publications, three reported moderate-quality evidence and three low-quality evidence. Of 15 observational studies, NOS scores ranged from 3 to 6, suggesting a high potential for uncertainty. The studies consistently reported clinical activity for cabozantinib after CPI therapy, across treatment lines and tumor types, with no new safety signals. The findings were limited by the quality and quantity of available data. CONCLUSION: Cabozantinib appears to have anti-tumor activity after prior CPI therapy in patients with solid tumors. Our results are driven largely by studies in renal cell carcinoma. Evidence from ongoing phase 3 trials is required to establish further the role of cabozantinib after CPI therapy.

Outcomes of Radiation Therapy Plus Immunotherapy in Metastatic Renal Cell Carcinoma: Results From the Canadian Kidney Cancer Information System.

Purpose: With the integration of immunotherapy (IO) agents in the management of metastatic renal cell carcinoma (mRCC), there has been interest in the combined use with radiation therapy (RT). However, real world data are limited. The purpose of this study was to evaluate outcomes in patients with mRCC receiving both RT and IO compared with IO alone. Methods and Materials: Data were collected from Canadian Kidney Cancer Information System from January 2011 to September 2019 across 14 academic centers. Patients with mRCC who received IO as first- or second-line therapy were included. RT was categorized as radical dose or palliative dose. Kaplan-Meier estimates were reported for overall survival (OS) and time to treatment failure. Cox proportional hazard models were used adjusted for age and International Metastatic RCC Database Consortium risk categories. Results: In total, 505 patients were included in the study: 179 received RT + IO and 326 received IO alone. Two-year OS for the RT + IO group was 55.0% compared with 66.4% in the IO alone cohort (adjusted hazard ratio [aHR], 1.38; P = .07). At 2 years, 12.2% of the RT + IO patients remained on therapy versus 30.9% in the IO alone group (aHR, 1.30; P = .02). For patients receiving first-line therapy, 2-year OS in the RT + IO group was 56.4% versus 78.4% in the IO alone arm, though this difference was not statistically significant (aHR, 1.23; P = .56). For patients receiving radical dose and palliative dose, 2-year OS was 57.0% and 53.9%, respectively (aHR, 0.86; P = .63). Conclusions: In this descriptive analysis, more than one-third of patients with mRCC received RT and demonstrated inferior outcomes compared with IO alone. Potential explanations include greater presence of adverse metastatic sites in those receiving RT. Prospective clinical trials evaluating potential benefits of RT in an IO era remain an important need.

Outcomes of patients with advanced non-clear cell renal cell carcinoma treated with first-line immune checkpoint inhibitor therapy.

BACKGROUND: Immune checkpoint inhibitors (ICI) have demonstrated impressive activity in metastatic clear-cell renal cell carcinoma (ccRCC) and have become standard treatment options for patients with advanced disease. Data supporting the effectiveness of ICI-based therapy in advanced non-clear cell RCC (nccRCC) is more limited. METHODS: We performed a retrospective analysis using the International Metastatic RCC Database Consortium (IMDC) to evaluate the outcomes of patients with advanced nccRCC. Patients were classified into three groups based on first-line therapy: ICI-based therapy (monotherapy or combination), vascular endothelial growth factor (VEGF) inhibitor monotherapy, or mammalian target of rapamycin (mTOR) inhibitor monotherapy. The primary outcome was overall survival (OS). Secondary outcomes were time to treatment failure (TTF) and objective response rate (ORR). We used the Kaplan-Meier method to compare OS and TTF between treatment groups and Cox proportional hazards models to adjust for prognostic covariates. RESULTS: We identified a total of 1145 patients with metastatic nccRCC. The most common subtype was papillary RCC (54.9%). For first-line therapy, 74.3% received VEGF monotherapy, 15% received mTOR monotherapy, and 10.7% received ICI-based therapy. Median OS in the ICI group was 28.6 months, versus 16.4 months in the VEGF group and 12.2 months in the mTOR group. Median TTF in the ICI group was 6.9 months, versus 5.0 months in the VEGF group and 3.9 months in the mTOR group. ORR was 27.2% in the ICI group, 14.5% in the VEGF group, and 9% in the mTOR group. After adjusting for the IMDC risk group, histological subtype, and age, the hazard ratio for OS was 0.57 (95% CI 0.42-0.78, p < 0.0001) for ICI versus VEGF and 0.50 (95% CI 0.36-0.71, p < 0.0001) for ICI versus mTOR. CONCLUSIONS: In advanced nccRCC, first-line ICI-based treatment appears to be associated with improved OS compared to VEGF and mTOR targeted therapy. These results should be confirmed in prospective randomised trials.