Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma.

BACKGROUND: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).

Conscience-Based Barriers to Medical Aid in Dying: A Survey of Colorado Physicians.

BACKGROUND: Approximately 20% of the United States' population lives in a state or jurisdiction where medical aid in dying (MAiD) is legal. It is unknown how physicians' own barriers are associated with their provision of the spectrum of MAiD services. OBJECTIVE: To measure physicians' religious and/or ethical barriers to providing MAiD services and how such barriers relate to physicians' intentions and behaviors. DESIGN: Three-wave cross-sectional survey fielded in Colorado in 2020-2021. PARTICIPANTS: Physicians providing care to patients likely clinically eligible for MAiD according to probabilistic sampling. MAIN MEASURES: Physicians self-reported barriers to their own participation in MAiD. We considered large ethical and/or religious barriers to be conscience-based barriers. We measured physicians' self-reported intention to participate and self-reported prior participation in MAiD since it was legalized in Colorado in 2017. We estimated differences in intention and behavior outcomes according to presence of conscience-based barriers, adjusting for physician gender, race/ethnicity, time in practice, and specialty. KEY RESULTS: Among 300 respondents, 26% reported "large" ethical and/or religious barriers to their involvement in MAiD. Physicians with longer time in practice and those identifying as non-White were more likely to report conscience-based barriers to MAiD. Comparing physicians with and without conscience-based barriers to MAiD, we found no difference in ancillary participation (discussing, referring) but significant differences in direct participation (serving as consultant [5% vs. 31%] or attending [0% vs. 22%]). CONCLUSIONS: Approximately one-quarter of physicians likely to care for MAiD-eligible patients in Colorado reported religious and/or ethical barriers to MAiD. Despite religious and/or ethical barriers, the vast majority of physicians were willing to discuss MAiD and/or refer patients seeking MAiD services. These data provide important empirical foundation for policy from hospitals and health systems as well as medical specialty groups with official positions on MAiD.

Specialty Differences in Medical Aid in Dying Experiences: Results of a Survey of Physicians in Colorado.

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.

Disseminated Ureaplasma polyarthritis in a renal transplant recipient.

BACKGROUND: The risk of infection following kidney transplant increases substantially in the setting of hypogammaglobulinemia and T-cell-depleting therapy. Ureaplasma has been described to cause invasive disease in immunocompromised hosts with humoral immunodeficiency. We describe a kidney transplant recipient with history of antineutrophil cytoplasmic autoantibody (ANCA) vasculitis remotely treated with rituximab who developed Ureaplasma polyarthritis following transplant. The purpose of this report is to highlight the unique risks that kidney transplant patients face particularly if hypogammaglobulinemic. CASE REPORT: Patient is a 16-year-old female with history of granulomatosis with polyangiitis (GPA) treated with maintenance dose of rituximab 13 months prior to transplant. Patient underwent deceased donor kidney transplant with thymoglobulin induction. IgG was 332 mg/dL and CD20 was zero at the time of transplant. One month posttransplant, the patient developed polyarticular arthritis without fever, pyuria, or evidence of GPA reactivation. MRI had diffuse tenosynovitis, myositis, fasciitis, cellulitis, and effusions of three involved joints. Bacterial, fungal, and AFB cultures remained negative, but 16 s ribosomal PCR testing from joint aspirates detected Ureaplasma parvum. The patient was treated with levofloxacin for 12 weeks with the resolution of symptoms. CONCLUSIONS: Ureaplasma infection is an under-recognized pathogen in kidney transplant patients. A high index of clinical suspicion should be employed to identify Ureaplasma infection, especially in those with secondary hypogammaglobulinemia, as this is often missed due to its lack of growth on standard media and the need for molecular testing. In patients with prior B-cell depletion, routine monitoring for B-cell recovery to identify risk factors for opportunistic infections is indicated.

TNF inhibition in vasculitis management in adenosine deaminase 2 deficiency (DADA2).

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited autoinflammatory disorder caused by a loss of functional ADA2 protein. TNF inhibition (TNFi) has proven to be highly effective in treating inflammatory manifestations. OBJECTIVE: We sought to explore the pathophysiology and the underlying mechanisms of TNF-inhibitor response in these patients. METHODS: We performed Sanger sequencing of the ADA2 gene. We used flow cytometry, intracellular cytokine staining, transcriptome analysis, immunohistochemistry, and cell differentiation experiments to define an inflammatory signature in patients with DADA2 and studied their response to TNF-inhibitor treatment. RESULTS: We demonstrated increased inflammatory signals and overproduction of cytokines mediated by IFN and nuclear factor kappa B pathways in patients' primary cells. Treatment with TNFi led to reduction in inflammation, rescued the skewed differentiation toward the proinflammatory M1 macrophage subset, and restored integrity of endothelial cells in blood vessels. We also report 8 novel disease-associated variants in 7 patients with DADA2. CONCLUSIONS: Our data explore the cellular mechanism underlying effective treatment with TNFi therapies in DADA2. DADA2 vasculitis is strongly related to the presence of activated myeloid cells, and the endothelial cell damage is rescued with anti-TNF treatment.

A pilot randomized study of a telephone-based cognitive-behavioral stress-management intervention to reduce distress in phase 1 oncology trial caregivers.

OBJECTIVES: Caregivers of adult phase 1 oncology trial patients experience high levels of distress and face barriers to in-person supportive care. The Phase 1 Caregiver LifeLine (P1CaLL) pilot study assessed the feasibility, acceptability, and general impact of an individual telephone-based cognitive behavioral stress-management (CBSM) intervention for caregivers of phase I oncology trial patients. METHODS: The pilot study involved 4 weekly adapted CBSM sessions followed by participant randomization to 4 weekly cognitive behavioral therapy sessions or metta-meditation sessions. A mixed-methods design used quantitative data from 23 caregivers and qualitative data from 5 caregivers to examine the feasibility and acceptability outcomes. Feasibility was determined using recruitment, retention, and assessment completion rates. Acceptability was assessed with self-reported satisfaction with program content and participation barriers. Baseline to post-intervention changes in caregiver distress and other psychosocial outcomes were assessed for the 8-session intervention. RESULTS: The enrollment rate was 45.3%, which demonstrated limited feasibility based on an a priori criterion enrollment rate of 50%. Participants completed an average of 4.9 sessions, with 9/25 (36%) completing all sessions and an 84% assessment completion rate. Intervention acceptability was high, and participants found the sessions helpful in managing stress related to the phase 1 oncology trial patient experience. Participants showed reductions in worry and isolation and stress. SIGNIFICANCE OF RESULTS: The P1CaLL study demonstrated adequate acceptability and limited feasibility and provided data on the general impact of the intervention on caregiver distress and other psychosocial outcomes. Caregivers of phase 1 oncology trial patients would benefit from supportive care services; a telephone-based intervention may have more utilization and thus make a larger impact.

Nivolumab plus cabozantinib versus sunitinib in first-line treatment for advanced renal cell carcinoma (CheckMate 9ER): long-term follow-up results from an open-label, randomised, phase 3 trial.

BACKGROUND: In the primary analysis of CheckMate 9ER, nivolumab plus cabozantinib showed superior progression-free survival, overall survival, and objective response over sunitinib in patients with previously untreated advanced renal cell carcinoma (median follow-up of 18·1 months). Here, we report extended follow-up of overall survival and updated efficacy and safety. METHODS: This open-label, randomised, phase 3 trial was done in 125 hospitals and cancer centres across 18 countries. We included patients aged 18 years or older with previously untreated advanced or metastatic clear-cell renal cell carcinoma, a Karnofsky performance status of 70% or higher, measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by the investigator, any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk category, and available tumour tissue for PD-L1 testing. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks plus cabozantinib (40 mg) orally once daily or sunitinib (50 mg orally) once daily (4 weeks per 6-week cycle). Randomisation, stratified by IMDC risk status, tumour PD-L1 expression, and geographical region, was done by permuted block within each stratum using a block size of four, via an interactive response system. The primary endpoint was progression-free survival by blinded independent central review. Overall survival was a secondary endpoint (reported here as the preplanned final analysis according to the protocol). Efficacy was assessed in all randomly assigned patients; safety was assessed in all patients who received at least one dose of any study drug. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT03141177. FINDINGS: Between Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to the nivolumab plus cabozantinib group and 328 to the sunitinib group. With an extended follow-up (data cutoff of June 24, 2021; median 32·9 months [IQR 30·4-35·9]), median overall survival was 37·7 months (95% CI 35·5-not estimable) in the nivolumab plus cabozantinib group and 34·3 months (29·0-not estimable) in the sunitinib group (hazard ratio [HR] 0·70 [95% CI 0·55-0·90], p=0·0043) and updated median progression-free survival was 16·6 months (12·8-19·8) versus 8·3 months (7·0-9·7; HR 0·56 [95% CI 0·46-0·68], p<0·0001). Grade 3-4 treatment-related adverse events occurred in 208 (65%) of 320 patients with nivolumab plus cabozantinib versus 172 (54%) of 320 with sunitinib. The most common grade 3-4 treatment-related adverse events were hypertension (40 [13%] of 320 patients in the nivolumab plus cabozantinib group vs 39 [12%] of 320 in the sunitinib group), palmar-plantar erythrodysaesthesia (25 [8%] vs 26 [8%]), and diarrhoea (22 [7%] vs 15 [5%]). Grade 3-4 treatment-related serious adverse events occurred in 70 (22%) of 320 patients in the nivolumab plus cabozantinib group and 31 (10%) of 320 in the cabozantinib group. One additional treatment-related death occurred with sunitinib (sudden death). INTERPRETATION: With extended follow-up and preplanned final overall survival analysis per protocol, nivolumab plus cabozantinib demonstrated improved efficacy versus sunitinib, further supporting the combination in the first-line treatment of advanced renal cell carcinoma. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.

Physicians' Attitudes and Experiences with Medical Aid in Dying in Colorado: a "Hidden Population" Survey.

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.

Non-pharmacologic therapies in treatment of childhood-onset systemic lupus erythematosus: A systematic review.

BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is a complex multisystem autoimmune disease often associated with pain, fatigue, and mood-related disturbances. cSLE is associated with increased disease severity and higher rates of mortality as compared to adult onset SLE. Therefore, a multi-faceted approach to care, including the use of non-pharmacologic therapies, is essential to ensure optimal patient outcomes. The use of non-pharmacologic therapies as adjunctive treatments has been shown to be beneficial in adults with SLE, yet, their use and effect is less well understood in cSLE. This is the first systematic review to explore the use and quality of evidence of non-pharmacologic approaches to treat cSLE. METHODS: A literature review was performed using PRISMA guidelines. Studies until March 2021 with participants diagnosed with cSLE were included. The quality of the evidence was graded via OCEBM levels of evidence guidelines and bias assessed using Cochrane guidelines. Completed clinical trials (via clinicaltrials.gov) were also searched to identify unpublished results. RESULTS: Eleven published studies consisting of 1152 patients met inclusion criteria for this review, as well as three additional studies with unpublished data on clinicaltrial.gov. Of the published trials, four studies used patient education/support, three studies used dietary supplementation, three used forms of psychotherapy (e.g., Cognitive behavioral therapy), and 1 used aerobic exercise to target the following issues: treatment adherence (n = 3), quality of life (n = 3), fatigue (n = 2), pain (n = 2), depressive symptoms (n = 1), anxiety (n = 1), and health-related outcomes including disease severity (n = 3), cardiovascular disease risk (Cardiovascular disease; n = 3), and muscle function (n = 1). Across investigations, the quality of the evidence based on study design was moderate/low. In terms of potential outcomes, dietary supplementation methods were successful in 2 of 3 studies and were associated with improvements in disease activity and fatigue. Aerobic exercise was effective in decreasing resting heart rate and increasing cardiorespiratory capacity. Patient education/support was related to significantly increased treatment adherence and decreased cardiovascular risk markers. Two of the three studies examining the impact of psychotherapy showed improvements (e.g., in treatment adherence, depression and fatigue). CONCLUSION: This review identifies several promising non-pharmacologic therapies to use as adjunctive treatments to traditional pharmacologic regimens in health and mental health-related outcomes in patients with cSLE. Future well controlled clinical trials would be beneficial to more rigorously evaluate the effects of non-pharmacologic therapies in pediatric populations.

NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Prostate Cancer in Older Adults: Risk of Clinically Meaningful Disease, the Role of Screening and Special Considerations.

PURPOSE OF REVIEW: Prostate cancer is the second most common cancer in men in the USA and several studies suggest more aggressive disease in older patients. However, screening remains controversial, especially in the older patient population. RECENT FINDINGS: Aggressive prostate cancers are more common in older men. Screening trial results are conflicting but data suggest an improvement in prostate cancer mortality and increased detection of metastatic disease with screening. When PSA is utilized with multiparametric MRI and biomarker assays, patients at significant risk of clinically meaningful prostate cancer can be appropriately selected for biopsy. A thoughtful and individualized approach is central when considering prostate cancer screening in older men. This approach includes life expectancy estimation, use of appropriate geriatric assessment tools, use of multiparametric MRI and biomarkers in addition to PSA, and most importantly shared decision-making with patients.

Technology's Palette: Voyager's Eyes and the Hyperchromatic Enhancement of Jupiter and Saturn.

In the late 1970s and early 1980s, NASA's Voyager mission offered the first clear pictures of Jupiter and Saturn. These images show the planets in strikingly brilliant, recognizably engineered, psychedelic colors: technology's palette. The use of color was justified on epistemological grounds; it made visible scientifically compelling features. But color palette also has a history, one that has not been previously considered. This article takes up this history and adds to the literature on the visual culture of science. It establishes that the Jet Propulsion Laboratory's pioneering role in digital image processing, the color conventions adopted for representing Earth, and American counterculture of the 1960s and its attitudes toward technology together created the conditions that allowed for hyperchromatic views of the planets. Technology's palette enhanced the scientific understanding of Jupiter and Saturn, while simultaneously celebrating technologically enhanced vision and the promise of seeing by means of humanmachine collaborations.

Identifying Geriatric Oncology Competencies for Medical Oncology Trainees: A Modified Delphi Consensus Study.

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.

Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Data supporting neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma are scant. In this multi-institution, prospective, phase II trial we investigated pathological complete responses after neoadjuvant chemotherapy of high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Patients with high grade upper tract urothelial carcinoma in whom nephroureterectomy was planned were assigned to 4 neoadjuvant chemotherapy cycles of accelerated methotrexate, vinblastine, doxorubicin and cisplatin in those with baseline creatinine clearance greater than 50 ml per minute or gemcitabine and carboplatin in those with creatinine clearance 30 to 50 ml per minute or less. The study primary end point was a pathological complete response (ypT0N0). The accrual goal was 30 patients per arm. An 18% pathological complete response was considered worth further study while a 4% pathological complete response would not have justified pursuing this regimen. With 28 eligible patients per arm success was defined as 3 or more pathological complete responses (10.7%) in a given arm. Secondary end points included safety, renal function and oncologic outcomes. RESULTS: A total of 30 patients enrolled in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm from 2015 to 2017. Six patients enrolled in the gemcitabine and carboplatin arm, which closed due to poor accrual. Of the 29 patients eligible for accelerated methotrexate, vinblastine, doxorubicin and cisplatin, including 23 men and 6 women with a median age of 65 years (range 40 to 84), 80% completed all planned treatments, 3 (10.3%) achieved ypT0N0 and 1 achieved ypT0Nx for a pathological complete response in 13.8% (90% CI 4.9-28.8). In 1 patient receiving accelerated methotrexate, vinblastine, doxorubicin and cisplatin nephroureterectomy was deferred due to grade 4 sepsis. The grade 3-4 toxicity rate was 23% in the accelerated methotrexate, vinblastine, doxorubicin and cisplatin arm with no grade 5 event. CONCLUSIONS: Accelerated methotrexate, vinblastine, doxorubicin and cisplatin neoadjuvant chemotherapy in patients with high grade upper tract urothelial carcinoma and creatinine clearance greater than 50 ml per minute was safe and demonstrated predefined activity with a 14% pathological complete response rate. Final pathological stage ypT1 or less in more than 60% of patients is encouraging. Together the results of this prospective trial support the use of neoadjuvant chemotherapy in eligible patients with high grade upper tract urothelial carcinoma.

Treating Elderly Patients With Muscle-Invasive Bladder Cancer.

Bladder cancer is an extremely common cancer that primarily affects individuals aged >65 years. In caring for patients with bladder cancer, clinicians must also consider care of older persons in general. Management of muscle-invasive bladder cancer (MIBC) involves multidisciplinary treatment planning, because curative-intent therapy includes either surgery or radiation, with consideration of the role of systemic therapy. As clinicians develop a treatment plan, considering a geriatric oncology perspective may enhance patient care and influence outcomes for this large and growing population. Similarly, treatment plan development must also consider aspects unique to an older patient population, such as altered organ function, increased comorbidity, decreased functional reserve, and perhaps altered goals of treatment. Thus a thorough evaluation inclusive of disease assessment and geriatric assessment is essential to care planning. Population-based data show that as patients with MIBC age, use of standard therapies declines. Given the complexities of coordinating a multidisciplinary care plan, as well the complexities of treating a heterogeneous and potentially vulnerable older patient population, clinicians may benefit from upfront assessments to inform and guide the process. This review highlights the unique treatment planning considerations for elderly patients diagnosed with MIBC.

Feasibility and Acceptability of a Remotely Delivered, Web-Based Behavioral Intervention for Men With Prostate Cancer: Four-Arm Randomized Controlled Pilot Trial.

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.

Management of Metastatic Prostate Cancer in Frail/Elderly Patients.

As the world population ages, we can expect to care for an increasing number of older cancer patients. Prostate cancer is inherently a condition that affects patients of advanced age. In caring for these patients who have advanced prostate cancer, it is important to first assess the health status of the patient and his goals of care. As this is established, likely through a geriatric assessment, this will inform how to modify or mold the treatment plan to fit a patient's needs and vulnerabilities. These vulnerabilities may surface as patients undergo treatment such as androgen deprivation therapy-the backbone of systemic therapy for advanced disease. Androgen deprivation therapy leads to long-term adverse effects; therefore, providers should carefully consider its use and proactively manage toxicity. It is important to assess patients before starting treatment and to adjust the choice of therapy, or supportive services, in order to maximize benefit and minimize potential harms.

Phase I trial of vandetanib in combination with gemcitabine and capecitabine in patients with advanced solid tumors with an expanded cohort in pancreatic and biliary cancers.

BACKGROUND: Vandetanib is a multitargeted tyrosine kinase inhibitor that affects vascular endothelial growth factor receptor (VEGF), epidermal growth factor (EGF), and rearranged during transfection (RET) mediated receptors which are important for growth and invasion of biliary and pancreatic cancers. This phase I study evaluated the safety profile of vandetanib in combination with standard doses of gemcitabine and capecitabine in order to determine the maximum tolerated dose (MTD). METHODS: In this single center phase I trial, patients received gemcitabine intravenously (i.v.) at 1000 mg/m2 days 1, 8, 15 in a 28 day cycle, capecitabine orally at 850 mg/m2 twice daily on days 1-21, and escalating doses of vandetanib (200 or 300 mg orally daily). Once the MTD was defined, an expansion cohort of patients with advanced biliary cancers and locally advanced or metastatic pancreatic cancer was enrolled. Blood samples were also collected at predetermined time points for biomarker analysis. RESULTS: Twenty-three patients were enrolled: 9 in the dose escalation and 14 in the dose expansion cohort. One dose limiting toxicity (DLT), of grade 4 neutropenia, occurred in the 200 mg vandetanib cohort. The most common adverse effects were diarrhea (39 %), nausea and vomiting (34%), and rash (33%). There were 3 partial responses and stable disease of >2 months (range 2-45, median 5) was observed in 15/23 patients. There was no association between changes in biomarker analytes and disease response. CONCLUSION: The combination of gemcitabine, capecitabine and vandetanib is well tolerated at the recommended phase II dose of gemcitabine 1000 mg/m2 weekly for three consecutive weeks, capecitabine 850 mg/m2 BID days 1-21, and vandetanib 300 mg daily, every 28 days. This combination demonstrated promising activity in pancreaticobiliary cancers and further evaluation is warranted in these diseases. NCT00551096.

Treatment of Metastatic Prostate Cancer in Older Adults.

The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as "fit," "vulnerable," and "frail" according to comprehensive geriatric assessment.