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Background: Nivolumab plus cabozantinib (NIVO + CABO) was approved for first-line treatment of advanced renal cell carcinoma (aRCC) based on superiority versus sunitinib (SUN) in the phase III CheckMate 9ER trial (18.1 months median survival follow-up per database lock date); efficacy benefit was maintained with an extended 32.9 months of median survival follow-up. We report updated efficacy and safety after 44.0 months of median survival follow-up in intent-to-treat (ITT) patients and additional subgroup analyses, including outcomes by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk score., Patients and Methods: Patients with treatment-naïve aRCC received NIVO 240 mg every 2 weeks plus CABO 40 mg once daily or SUN 50 mg for 4 weeks (6-week cycles), until disease progression/unacceptable toxicity (maximum NIVO treatment, 2 years). Primary endpoint was progression-free survival (PFS) per blinded independent central review (BICR). Secondary endpoints were overall survival (OS), objective response rate (ORR) per BICR, and safety and tolerability., Results: Overall, 323 patients were randomised to NIVO + CABO and 328 to SUN. Median PFS was improved with NIVO + CABO versus SUN [16.6 versus 8.4 months; hazard ratio (HR) 0.59; 95% confidence interval (CI) 0.49-0.71]; median OS favoured NIVO + CABO versus SUN (49.5 versus 35.5 months; HR 0.70; 95% CI 0.56-0.87). ORR (95% CI) was higher with NIVO + CABO versus SUN [56% (50% to 62%) versus 28% (23% to 33%)]; 13% versus 5% of patients achieved complete response, and median duration of response was 22.1 months versus 16.1 months, respectively. PFS and OS favoured NIVO + CABO over SUN across intermediate, poor and intermediate/poor IMDC risk subgroups; higher ORR and complete response rates were seen with NIVO + CABO versus SUN regardless of IMDC risk subgroup. Any-grade (grade ≥3) treatment-related adverse events occurred in 97% (67%) versus 93% (55%) of patients treated with NIVO + CABO versus SUN., Conclusions: After extended follow-up, NIVO + CABO maintained survival and response benefits; safety remained consistent with previous follow-ups. These results continue to support NIVO + CABO as a first-line treatment for aRCC., Trial Registration: ClinicalTrials.gov, NCT03141177., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The incidence of severe immune-related adverse events (irAEs) in cancer subjects receiving immune checkpoint inhibitors (ICIs) following COVID-19 vaccination and the relationship between the incidence of severe irAE and the interval between COVID-19 vaccination and ICI dose have not been established. We performed a retrospective study evaluating the incidence of irAEs in solid tumor subjects receiving ICI therapy who received any COVID-19 vaccinations since FDA authorization. irAEs were defined as severe with one or more grade 3 or above events (CTCAE v5.0), multiple organ involvement, or requiring hospitalization for management. Two hundred and eighty-four subjects who received COVID vaccinations from December 2020 and February 2022 were included in this analysis [median age at vaccination 67 years (IQR 59.0-75.0); 67.3% male]. Twenty-nine subjects (10.2%) developed severe irAEs, of which 12 subjects (41.4%) received ICI monotherapy, 10 subjects (34.5%) received combination ICI therapy with nivolumab and ipilimumab, and 7 subjects (24.1%) received ICI plus VEGFR-TKI therapy. Hospitalization occurred in 62% of subjects with severe irAEs, with a median duration of 3 days (IQR: 3.0-7.5 days). Immunosuppressive therapy was required in 79.3%, with a median duration of 103 days (IQR: 42.0-179.0). ICI therapy was discontinued in 51.7% of subjects with severe irAE; dosing was held or interrupted in 34.5%. Among severe irAEs, the median interval between vaccination and ICI treatment closest to the occurrence of severe irAE was 15.5 days (IQR: 10.0-23.0). In solid tumor cancer subjects receiving ICIs, COVID-19 vaccination is not associated with an increased incidence of severe irAEs compared to historical data and may be safely administered during ICI cancer therapy in subjects who lack contraindications.

In Colorado, medical aid in dying (MAiD) is legal, allowing a terminally ill person to request a prescription and self-administer a medication to end their life. Such requests are granted under certain circumstances, including a malignant neoplasm diagnosis, with a goal of peaceful death. This study examined differences in attitudes and actual participation in MAiD between oncologists and non-oncologists, using data from a recent survey of physicians regarding MAiD., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: Immune checkpoint inhibitor and VEGFR inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC). This phase I/II clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in patients with mRCC., Experimental Design: Eligible patients had mRCC with clear-cell or non-clear cell histology, adequate organ function, Eastern Cooperative Oncology Group 0-1 performance status, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase II dose (RP2D). Secondary endpoints included safety, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS)., Results: Forty-five patients were enrolled. A total of 40 patients were treated at the RP2D of pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally once daily, 38 of which were evaluable for response. The ORR was 65.8% [95% confidence interval (CI), 49.9-78.8] for all evaluable patients [78.6% as first-line therapy, 58.3% as second-line therapy]. The DCR was 97.4% (95% CI, 86.5-99.9). Median DoR was 8.3 months (interquartile range, 4.6-15.1). At a median follow-up of 23.54 months, the median PFS was 10.45 months (95% CI, 6.25-14.63) and median OS was 30.81 months (95% CI, 24.2-not reached). The most common grade 1 and/or 2 treatment-related adverse events (TRAE) were diarrhea, anorexia, dysgeusia, weight loss, and nausea. The most common grade 3 and/or 4 TRAEs were hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue. There was one grade 5 TRAE of reversible posterior encephalopathy syndrome related to cabozantinib., Conclusions: Pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable with other available checkpoint inhibitor-tyrosine kinase inhibitor combinations., Trial Registration: ClinicalTrials.gov Identifier: NCT03149822 https://clinicaltrials.gov/ct2/show/NCT03149822., Significance: This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC. The safety profile was manageable. The combination showed promising activity with an objective response rate of 65.8%, median PFS of 10.45 months, and median OS of 30.81 months., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Background: Approximately 20% of the US population live in states where MAiD is a legal, though highly contentious, practice. Little generalizable data exists on the experiences of MAiD providers who comprise a small, and intentionally hidden, population., Objective: To examine the nature, extent, and consequences of physicians' participation in MAiD., Design: An anonymous, multi-wave, mailed survey (RR= 55%)., Participants: An enriched sample (n=583) of Colorado physicians caring for potential MAiD patients., Main Measures: Physician willingness, preparedness, and participation in a continuum of MAiD activities. Other outcomes include the effects of providing MAiD and the barriers physicians face related to MAiD., Key Results: Overall, 81.1% of respondents were willing to discuss MAiD with a patient, 88.3% to refer for MAiD, 46.3% to be a consultant, and 28.1% to be an attending. Fewer felt prepared to discuss MAiD (54.4%), provide a MAiD referral (62.8%), be a consultant (30.7%), or be an attending (18.0%). More than half of respondents (52.3%) had discussed MAiD with a patient, 27.3% provided a MAiD referral, 12.8% had been a MAiD consultant, and 8.5% had been a MAiD attending. Among MAiD consultants and attendings, 75% reported that their most recent MAiD case was emotionally fulfilling and professionally rewarding, though 75% also reported that it was time consuming and 46.9% reported that it was ethically challenging. Common barriers to physician participation in MAiD include lack of knowledge about MAiD (46.8%), the emotional (45.6%) and time (41.7%) investments, and ethical concerns (41.7%)., Conclusions: Many physicians in our sample are both willing and prepared to discuss MAiD with patients and to provide MAiD referrals. Fewer are prepared and willing to serve as an attending or consultant and fewer have provided these services. MAID consultants and attendings largely report the experience to be emotionally fulfilling and professionally rewarding, but all respondents reported multiple barriers to participation., (© 2021. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Background: Bladder cancer is one of the top 10 cancers diagnosed in Americans with a median age of 73. This is the patient population that tends to be older with multiple medical conditions, and previously described variability in treatment in the earlier stages of the disease. This study aimed to evaluate the first-line therapeutic choices for older adults newly diagnosed with advanced bladder cancer. In addition, this work evaluated predictors of response as well as the role of events of functional importance in relation to treatment assignment., Methods: A population-based cohort study was conducted using the SEER-Medicare database of patients with advanced stage bladder cancer not eligible for curative intent therapy between 2010 and 2013. Patient groups of interest were compared via univariate and multivariate associations. Additionally, a latent class analysis was applied to identify classes with similar features in reference to events of functional importance-events linked to the maintenance or improvement of physical function status., Results: Within the sample, we noted that a minority of patients received a standard cisplatin-containing regimen (14.77%) and a majority did not receive any chemotherapy (59.69%). Most patients were over age 75. The adjusted odds ratio of no chemo versus cisplatin in patients aged 76 and older compared to patients 66-75 was 6.61 (4.79-9.13; p < 0.0001). We applied latent class analysis methods to the dataset, and three classes demonstrated very low and moderate levels of functional events in the 12 months prior to a person's first outpatient visit for advanced bladder cancer care., Conclusions: Patients with new diagnosis of advanced bladder cancer largely do not receive the recommended first-line systemic therapy of cisplatin chemotherapy, and a significant majority does not receive any treatment. When evaluating the association between class assignment and predictors of chemotherapy use, such as comorbidity and age, patients with "low usage overall" were more likely to receive chemotherapy. Yet even patients who received chemotherapy had some events of functional importance., Competing Interests: CONFLICT OF INTEREST The authors have no conflicts of interest to report related to the data presented.

Physicians who participate in medical-aid-in-dying (MAID) cannot be easily identified and studied due to cost and anonymity barriers. We developed and empirically tested a novel methodology to identify and survey physicians highly likely to participate in MAID activities. We used a state-level comprehensive administrative claims database to identify a cohort of patients with diagnoses and hospice enrollment similar to those known to have filled a prescription for MAID from 2017-2018. We then identified physicians who provided routine outpatient care to these patients using National Provider Identifier numbers. We surveyed these physicians in 3 waves (n = 583 total surveys), ranking physicians in order of their likelihood of being asked about MAID for each wave based on characteristics including specialty and the number of unique patients they had provided care to. We re-ranked physicians in waves 2 and 3 based on responses from prior waves. Physicians were surveyed only once and there was no follow-up to preserve anonymity. Surveys assessed the proportion of respondents who participated in MAID activities (discussions, referrals, and/or prescriptions). We identified 6369 physicians that provided care to 2960 patients. In survey waves one, two, and three respectively, response rates (55%, 52%, and 55%; p = 0.98) and the proportion of respondents that participated in MAID activities (58%, 56%, and 42%; p = 0.05) were similar. Small adjustments made to physician ranking criteria in waves two and three did not increase the proportion of physicians that participated in MAID activities. We used a novel methodology using administrative data to identify and survey physicians at high likelihood of participating in MAID activities. We achieved good overall response rates (52%), and a high proportion of respondents that participated in MAID activities (52%), demonstrating that it is possible to overcome cost and anonymity barriers to conducting quantitative research on MAID. This methodology could be used in larger scale studies of MAID or other bioethical issues with "hidden" physician populations., (© 2022. The Author(s).)

Background: Following a prostate cancer (PC) diagnosis, treatment-related symptoms may result in diminished quality of life (QoL). Improved diet and increased exercise may improve QoL in men with PC., Methods: We conducted a 4-arm pilot randomized trial to assess feasibility and acceptability of a 3-month web-based diet and exercise intervention, among men (>18 years of age) with PC (reported elsewhere). The purpose of this study is to describe the change in QoL measured by surveys (eg, QLQ-C30, PROMIS Fatigue) at enrollment and following the intervention. Men were randomized 1:1:1:1 to increasing levels of web-based behavioral support: Level 1: website; Level 2: Level 1 plus personalized diet and exercise prescription; Level 3: Levels 1-2 plus Fitbit and text messages; Level 4: Levels 1-3 plus 2 30-minute coaching calls. T -tests were used to compare pre-post change in mean QoL scores between each Level and Level 1., Results: Two hundred and two men consented and were randomized (n = 49, 51, 50, 52 for Levels 1-4, respectively). Men were predominantly white (93%), with a median age of 70 years (Intra-quartile Range [IQR]: 65,75) and 3 years (IQR: 1,9) post primary treatment for mostly localized disease (74% with T1-2). There were no meaningful changes in QoL, but there were notable trends. Level 3 participants had small improvements in QLQ-C30 Global Health (5.46; 95% CI: -0.02, 10.95) compared to Level 1. In contrast, Level 2 participants trended toward decreasing Global QoL (-2.31, 95% CI: -8.05, 3.42), which may reflect declines in function (eg, Cognitive: -6.94, 95% CI: -13.76, -0.13) and higher symptom burden (eg, Diarrhea: 4.63, 95% CI: -1.48, 10.74)., Conclusions: This short, web-based intervention did not appear to have an impact on PC survivors' QoL. Most men were several years past treatment for localized disease; the potential for this approach to reduce symptoms and improve QoL in men who have worse health may still be warranted.

Background: Diet and exercise may be associated with quality of life and survival in men with prostate cancer., Objective: This study aimed to determine the feasibility and acceptability of a remotely delivered web-based behavioral intervention among men with prostate cancer., Methods: We conducted a multi-site 4-arm pilot randomized controlled trial of a 3-month intervention (TrueNTH Community of Wellness). Eligibility included self-reported prostate cancer diagnosis, having a personal device that connected to the internet, age ≥18 years, and ability to read English and receive text messages and emails. Men receiving chemotherapy or radiation, or those who reported contraindications to exercise, could participate with physician clearance. Participants were randomized (1:1:1:1) to additive intervention levels: website; website and personalized diet and exercise prescription; website, personalized prescription, Fitbit, and text messages; and website, personalized prescription, Fitbit, text messages, and 2 30-minute phone calls-one with an exercise trainer and one with a registered dietician. Primary outcomes were feasibility (accrual and attrition) and acceptability (survey data and website use). We described self-reported diet and exercise behavior at the time of enrollment, 3 months, and 6 months as secondary outcomes., Results: In total, 202 men consented and were randomized between August 2017 and September 2018 (level 1: 49, level 2: 51, level 3: 50, level 4: 52). A total of 160 men completed the onboarding process and were exposed to their randomly assigned intervention (38, 38, 42, and 42 in levels 1, 2, 3, and 4, respectively). The follow-up rate was 82.7% (167/202) at 3 months and 77.2% (156/202) at 6 months. Participants had a median age of 70 years and were primarily White and college educated. Website visit frequency over the 3-month intervention period increased across levels (median: 2, 9, 11, and 16 visits for levels 1, 2, 3, and 4, respectively). Most were satisfied or very satisfied with the intervention (20/39, 51%; 27/42, 64%; 23/44, 52%; and 27/42, 64% for levels 1, 2, 3, and 4, respectively). The percentage of men who reported being very satisfied was highest among level 4 participants (10/42, 24% vs 4/39, 10%; 5/42, 12%; and 5/44, 11% for levels 1, 2, and 3, respectively). Dissatisfaction was highest in level 1 (5/39, 13% vs 1/42, 2%; 3/44, 7%; and 2/42, 5% for levels 2, 3, and 4, respectively). We observed small improvements in diet and physical activity at 3 months among men in level 4 versus those in level 1., Conclusions: A web-based, remotely delivered, tailored behavioral intervention for men with prostate cancer is feasible. Future studies are warranted to increase the effect of the intervention on patient behavior while maintaining sustainability and scalability as well as to design and implement interventions for more diverse populations., Trial Registration: ClinicalTrials.gov NCT03406013; http://clinicaltrials.gov/ct2/show/NCT03406013., (©June M Chan, Erin L Van Blarigan, Crystal S Langlais, Shoujun Zhao, Justin W Ramsdill, Kimi Daniel, Greta Macaire, Elizabeth Wang, Kellie Paich, Elizabeth R Kessler, Tomasz M Beer, Karen S Lyons, Jeanette M Broering, Peter R Carroll, Stacey A Kenfield, Kerri M Winters-Stone. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 31.12.2020.)

Background: Exercise and a healthy diet can improve the quality of life and prognosis of prostate cancer survivors, but there have been limited studies on the feasibility of web-based lifestyle interventions in this population., Objective: This study aims to develop a data-driven grounded theory of web-based engagement by prostate cancer survivors based on their experience in the Community of Wellness, a 12-week randomized clinical trial designed to support healthy diet and exercise habits., Methods: TrueNTH's Community of Wellness was a four-arm pilot study of men with prostate cancer (N=202) who received progressive levels of behavioral support (level 1: website; level 2: website with individualized diet and exercise recommendations; level 3: website with individualized diet and exercise recommendations, Fitbit, and text messages; and level 4: website with individualized diet and exercise recommendations, Fitbit and text messages, and separate phone calls with an exercise trainer and a registered dietitian). The primary aim of the study is to determine the feasibility and estimate the effects on behaviors (results reported in a separate paper). Following the 12-week intervention, we invited participants to participate in 4 focus groups, one for each intervention level. In this report, we used grounded theory analyses including open, axial, and selective coding to generate codes and themes from the focus group transcripts. Categories were refined across levels using embodied categorization and constant comparative methods., Results: In total, 20 men with prostate cancer participated in the focus groups: 5, 4, 5, and 6 men in levels 1, 2, 3, and 4, respectively. Participants converged on 5 common factors influencing engagement with the intervention: environment (home environment, competing priorities, and other lifestyle programs), motivation (accountability and discordance experienced within the health care system), preparedness (technology literacy, health literacy, trust, and readiness to change), program design (communication, materials, and customization), and program support (education, ally, and community). Each of these factors influenced the survivors' long-term impressions and habits. We proposed a grounded theory associating these constructs to describe the components contributing to the intuitiveness of a web-based lifestyle intervention., Conclusions: These analyses suggest that web-based lifestyle interventions are more intuitive when we optimize participants' technology and health literacy; tailor interface design, content, and feedback; and leverage key motivators (ie, health care providers, family members, web-based coach) and environmental factors (ie, familiarity with other lifestyle programs). Together, these grounded theory-based efforts may improve engagement with web-based interventions designed to support prostate cancer survivorship., (©Elizabeth Y Wang, Rebecca E Graff, June M Chan, Crystal S Langlais, Jeanette M Broering, Justin W Ramsdill, Elizabeth R Kessler, Kerri M Winters-Stone, Erin L Van Blarigan, Stacey A Kenfield. Originally published in JMIR Cancer (http://cancer.jmir.org), 10.11.2020.)

Background: Most oncology trainees are not taught about the needs of older patients, who make up the majority of patients with cancer. Training of health care providers is critical to improve the care of older adults with cancer. There is no consensus about which geriatric oncology (GO) competencies are important for medical oncology trainees. Our objective was to identify GO competencies medical oncology trainees should acquire during training., Materials and Methods: A modified Delphi consensus of experts in oncology medical education and GO was conducted. Experts categorized at what training stage proposed competencies should be attained: internal medicine, oncology, or GO training. Consensus was obtained if two thirds of experts agreed on the training stage at which the competency should be attained., Results: A total of 78 potential competencies were identified, of which 35 (44.9%) proposed competencies were felt to be appropriate to be acquired during oncology training. The majority of the identified competencies pertained to prescribing of systemic therapy (n = 12) and psychosocial and supportive care (n = 13). No competencies related to geriatric assessment were identified for acquisition during oncology training., Conclusion: Experts in oncology education and geriatric oncology agreed upon a set of GO competencies appropriate for oncology trainees. These results provide the foundation for developing a GO curriculum for medical oncology trainees and will hopefully lead to better care of older adults with cancer., Implications for Practice: The aging population will drive the projected rise in cancer incidence. Although aging patients make up the majority of patients diagnosed with cancer, oncologists rarely receive training on how to care for them. Training of health care providers is critical to improving the care of older adults with cancer. The results of this study will help form the foundation of developing a geriatric oncology curriculum for medical oncology trainees., (© AlphaMed Press 2020.)

Background: Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO., Methods: We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival., Results: During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015)., Conclusions: Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.

Background: Plant derivatives have been studied as therapies for prostate cancer based on their purported anti-inflammatory and antioxidant properties and low toxicities. The acai berry is an example of a plant rich in phytochemicals, which may slow the growth of prostate cancer., Methods: This was a phase II, Simon 2-stage clinical trial in patients with biochemically recurrent prostate cancer with a primary endpoint of prostate-specific antigen (PSA) response. Patients were asymptomatic, with a rising PSA of at least 0.2 ng/mL, and were treated with twice daily intake of Acai Juice Product until PSA progression, with a primary endpoint of PSA response., Results: Twenty-one patients were enrolled in the first stage of the trial. One of those patients had a PSA response within the study time period. The PSA doubling time was lengthened in 71% of patients (95% confidence interval = 48% to 89%) on the trial, and in a small number of responders, this was sustained over an extended time., Conclusions: This study did not meet its primary endpoint of 50% PSA response. Nevertheless, the overall tolerability and effects on PSA stabilization warrant further exploration in a biochemically recurrent population.

Background: More than 3.1 million men in the United States are prostate cancer survivors. These men may improve their physical function, quality of life, and potentially their prognosis by adopting healthier lifestyle habits. The internet provides a scalable mechanism to deliver advice and support about improving physical activity and dietary habits, but the feasibility and acceptability of a Web-based lifestyle intervention and the dose of support necessary to improve health behaviors are not yet known., Objectives: The Community of Wellness is a Web-based intervention focused on supporting exercise and healthy dietary practices for men with prostate cancer. The objectives of this study were to determine the feasibility, acceptability, and preliminary efficacy of the Community of Wellness Web portal among prostate cancer survivors by conducting a randomized controlled trial (RCT) comparing 4 levels of additive Web-based content and interaction with participants: Level 1 (Teaching; Control), Level 2 (Teaching + Tailoring), Level 3 (Teaching + Tailoring + Technology), and Level 4 (Teaching + Tailoring + Technology + Touch)., Methods: This is a single-blinded RCT comparing 3 levels of behavioral support within the Community of Wellness Web portal intervention (Levels 2 to 4) with each other and with the control condition (Level 1). The control condition receives general static Web-based educational information only on physical activity and dietary habits, self-efficacy for behavior change, motivation for physical activity, and changes in anxiety and treatment-related side effects. We will enroll and randomize 200 men with prostate cancer equally to 4 levels of the Community of Wellness Web-based intervention for 3 months (50 men per level). Surveys will be completed by self-report at baseline, 3 months (immediately postintervention), and 6 months (3 months postintervention). Feasibility and acceptability will be assessed by enrollment statistics, Web-based usage metrics, and surveys at the 3-month time point. We will also conduct focus groups after the postintervention follow-up assessment in a sample of enrolled participants to evaluate elements of usability and acceptability that cannot be obtained via surveys., Results: Enrollment is ongoing, with 124 enrolled. Study completion (6-month follow-up) is expected by July 2019., Conclusions: The goal of the study is to identify the level of support that is feasible, acceptable, promotes behavior change, and improves health in men with prostate cancer to inform future efforts to scale the program for broader reach., Trial Registration: ClinicalTrials.gov NCT03406013; https://clinicaltrials.gov/ct2/show/NCT03406013 (Archived by WebCite at http://www.webcitation.org/73YpDIoTX)., International Registered Report Identifier (irrid): PRR1-10.2196/11257., (©Kerri M Winters-Stone, Stacey A Kenfield, Erin L Van Blarigan, Esther L Moe, Justin W Ramsdill, Kimi Daniel, Greta Macaire, Kellie Paich, Elizabeth R Kessler, Omer Kucuk, Theresa W Gillespie, Karen S Lyons, Tomasz M Beer, Jeanette M Broering, Peter R Carroll, June M Chan. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.11.2018.)

Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC., Competing Interests: Competing interests: ETL receives kidney cancer clinical trial funding from Argos, Bristol-Myers Squibb, Calithera, Genentech, Merck, Peloton, Pfizer, and Roche; has served as a consultant for Bristol-Myers Squibb; and serves on the Independent Data Monitoring Board for Calithera. ERK receives kidney cancer clinical trial funding from Bristol-Myers Squibb. TWF receives clinical trial funding from Bristol-Myers Squibb, Novartis, Pfizer, Bavarian Nordic, Cougar Biotechnology, Dendreon, GTx, Janssen Oncology, Medivation, Sanofi, Genentech, Roche, Exelixis, Aragon Pharmaceuticals, Sotio, Tokai Pharmaceuticals, Astra-Zeneca/MedImmune, Lilly, Astellas, Agensys, and Seattle Genetics and has served as a consultant for GTx.No competing interests were disclosed.No competing interests were disclosed.

An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d + GD3 + tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3. We show that DNA encoding α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (SIAT8) introduced by gene gun vaccination in vivo leads to overexpression of GD3 and delays tumor growth. Delayed tumor growth is dependent on CD1d expression by host immune cells, as shown in experiments engaging CD1d knockout mice. A trend toward greater NKT cell populations among tumor-infiltrating lymphocytes is associated with SIAT8 vaccination. A single adenoviral vaccination introduces anti-tumor activity similarly to repeated vaccination with naked DNA. Here, greater NKT tumor infiltrates were accompanied by marked overexpression of IL-17 in the tumor, later switching to IL-4. Our results suggest that a single intramuscular adenoviral vaccination introduces overexpression of GD3 by antigen-presenting cells at the injection site, recruiting NKT cells that provide an inflammatory anti-tumor environment. We propose adenoviral SIAT8 (AdV-SIAT8) can slow the growth of GD3 expressing tumors in patients.

Prostate cancer is the most common non-cutaneous cancer in US men and mainly affects elderly patients, with most new diagnoses occurring in those over 65. As the geriatric population in the US continues to grow, the incidence of this disease is likewise expected to rise. Many older patients are diagnosed with advanced disease or are treated only when their disease becomes symptomatic or metastatic. The treatment options for advanced prostate cancer have increased dramatically in the last decade. It is important to understand the nuances of caring for an elderly cancer patient in order to optimally treat prostate cancer, such as the importance of using a geriatric assessment to uncover overlooked or under-reported vulnerabilities. In addition, many of the newly approved agents for the treatment of advanced prostate cancer have a unique mechanism of action and toxicities that warrant consideration when choosing therapies for older patients. This review focuses on the importance of a geriatric assessment as well as the considerations of treating elderly patients with the newer agents approved for prostate cancer.