Association between Cognitive Function and Physical Function, Frailty, and Quality of Life in Older Breast Cancer Survivors.

BACKGROUND: Older cancer survivors in general are at greater risk for cancer-related cognitive impairment (CRCI), yet few studies have explored its association with health outcomes. This study examined the association between subjective and objective measures of cognitive function and physical function, frailty, and quality of life (QoL) among older breast cancer survivors. MATERIALS AND METHODS: Older breast cancer survivors who reported cognitive concerns completed surveys on patient-reported cognitive function, physical function, frailty, and QoL as well as objective tests of visuospatial working memory and sustained attention. Data were analyzed using descriptive statistics and separate linear regression models. RESULTS: A total of 219 female breast cancer survivors completed the study. Perceived cognitive abilities were associated with better physical function, frailty, and QoL (p ≤ 0.001) while cognitive concerns were negatively related with these metrics (p ≤ 0.001). Poorer visuospatial working memory and sustained attention were linked to increased frailty (p ≤ 0.001-0.01), whereas poorer sustained attention was associated with poorer physical function (p < 0.01). CONCLUSIONS: Older breast cancer survivors with perceived cognitive impairment and poorer cognitive performance reported poorer physical functioning, increased frailty, and poorer QoL. These findings underscore the importance of assessing cognitive concerns and their associated outcomes in older breast cancer survivors.

A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.

BACKGROUND: The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF­06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.03-6 mg) or placebo in six sequential single ascending dose (SAD) cohorts. In Part B, patients received repeat doses of subcutaneous PF-06835375 (dose range: 0.3-10 mg) or placebo on Days 1 and 29 in five multiple ascending dose (MAD) cohorts. Tetanus/Diphtheria (Td) and Meningococcal B (MenB/Trumenba™) vaccines were administered at Day 4 (Td and MenB) and Week 8 (MenB only) to assess PF-06835375 functional effects. Endpoints included treatment-emergent adverse events (TEAEs), pharmacokinetic parameters, pharmacodynamic effects on B and cTfh cells, and biomarker counts, vaccine response, and exploratory differential gene expression analysis. Safety, pharmacokinetic, and pharmacodynamic endpoints are summarized descriptively. The change from baseline of B and Tfh cell-specific genes over time was calculated using a prespecified mixed-effects model, with a false discovery rate < 0.05 considered statistically significant. RESULTS: In total, 73 patients were treated (SAD cohorts: SLE, n = 17; RA, n = 14; MAD cohorts: SLE, n = 22; RA, n = 20). Mean age was 53.3 years. Sixty-two (84.9%) patients experienced TEAEs (placebo n = 17; PF-06835375 n = 45); most were mild or moderate. Three (9.7%) patients experienced serious adverse events. Mean t1/2 ranged from 3.4-121.4 h (SAD cohorts) and 162.0-234.0 h (MAD cohorts, Day 29). B and cTfh cell counts generally showed dose-dependent reductions across cohorts (range of mean maximum depletion: 67.3-99.3%/62.4-98.7% [SAD] and 91.1-99.6%/89.5-98.1% [MAD], respectively). B cell-related genes and pathways were significantly downregulated in patients treated with PF-06835375. CONCLUSIONS: These data support further development of PF-06835375 to assess the clinical potential for B and Tfh cell depletion as a treatment for autoimmune diseases. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03334851.

Testing the feasibility of mobile ecological momentary assessment for symptom burden and management among metastatic cancer patients.

Background: Individuals who have metastatic cancer experience substantial physical and psychological distress (e.g., pain, depression, anxiety) from their disease and its treatment compared to patients with less advanced disease. As the burden of symptoms varies over time, ecological momentary assessment (EMA) may be used to better understand patients' symptom trajectories, complimenting traditional longitudinal data collection methods. However, few have used EMA in patients with metastatic disease. The current study adds to the existing literature by exploring interrelated, common cancer-related symptoms of pain, anxiety, and depression and use of cannabis-based products, opioid medications, other (nonopioid) pain medications, and medications for anxiety or depression. Methods: An eight-day prospective observational feasibility study was conducted among 50 patients with metastatic cancer recruited from seven solid cancer clinics at The Ohio State University Comprehensive Cancer Center. Participants completed a week of interval-contingent mobile EMA, administered daily at 9 a.m., 3 p.m., and 8 p.m., and a comprehensive interviewer-administered questionnaire on Day 8. Participants were queried on their symptom burden and management strategies (i.e., use of medications and cannabis). We considered EMA to be feasible if a priori retention (80%) and adherence goals (75%) were met. Results: Seventy-nine percent of eligible patients contacted enrolled in the study (n = 50 of 63). Among those enrolled, 92% were retained through Day 8 and 80% completed >90% of EMAs, exceeding a priori objectives. Participants' average pain, anxiety, and depressive symptoms across the week of EMA ranged from 1.7 to 1.8 (1 to 5 scale). Symptoms varied little by day or time of administration. On Day 8, significant proportions of participants reported past-week use of medications and cannabis for symptom management. Conclusions: Participants exceeded a priori adherence and retention objectives, indicating that mobile EMA is feasible among metastatic cancer patients, addressing a gap in the existing literature and informing future research. Restricting eligibility to participants with a minimum cutoff of symptom burden may be warranted to increase observations of symptom variability and provide opportunities for future health interventions. Future research is needed to test the acceptability and quality of data over a longer study period in this patient population.

Comorbid Dementia and Cancer Therapy Decision-Making: A Scoping Review.

Comorbid dementia complicates cancer therapy decision-making in older adults. We aimed to synthesize the recent literature (<5 years) on the challenges associated with cancer therapy decision-making among older people living with dementia (PLWD) and their caregivers. Of the 20,763 references, 8767 had their title and abstract screened, and eight met the inclusion criteria. Six studies were qualitative, one study employed mixed methods, and one study was quasi-experimental. Most studies were conducted in the UK (89%) and reported homogeneity in race and geography. Breast (56%) and prostate (45%) were the most frequent reported cancers. Five studies (56%) reported multiple types of dementia, with two (22%) indicating stages. The studies indicated that communication between patients, caregivers, and clinical teams might alleviate stress caused by worsening health prospects and potential ethical concerns. Information from this review can lead to better-informed, patient-centered treatment decision processes among older PLWD and cancer, their caregivers, and clinicians.

Current cannabis use and pain management among US cancer patients.

BACKGROUND: National studies reporting the prevalence of cannabis use have focused on individuals with a history of cancer without distinction by their treatment status, which can impact symptom burden. While pain is a primary motivation to use cannabis in cancer, the magnitude of its association with cannabis use remains understudied. METHODS: We examined cannabis use and pain management among 5523 respondents of the Behavioral Risk Factor Surveillance System with a cancer history. Survey-weighted prevalence proportions of respondents' cannabis use are reported, stratified on cancer treatment status. Regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of cancer-related pain and cannabis use. RESULTS: Cannabis use was slightly more prevalent in those undergoing active treatment relative to those who were not undergoing active treatment (9.3% vs. 6.2%; P=0.05). Those under active treatment were more likely to use cannabis medicinally (71.6% vs. 50.0%; P=0.03). Relative to those without cancer-related pain, persons with pain under medical control (OR 2.1, 95% CI, 1.4-3.2) or uncontrolled pain were twice as likely to use cannabis (OR 2.0, 95% CI, 1.1-3.5). CONCLUSIONS: Use of cannabis among cancer patients may be related to their treatment and is positively associated with cancer-related pain. Future research should investigate the associations of cannabis use, symptom burden, and treatment regimens across the treatment spectrum to facilitate interventions.

Marijuana and Cannabidiol Use Prevalence and Symptom Management Among Patients with Cancer.

Symptoms such as pain, nausea, and anxiety are common in individuals with cancer. Treatment of these issues is often challenging. Cannabis products may be helpful in reducing the severity of these symptoms. While some studies include data on the prevalence of cannabis use among patients with cancer, detailed data remain limited, and none have reported the prevalence of cannabidiol (CBD) use in this population. Adult patients with cancer attending eight clinics at a large, NCI-designated Comprehensive Cancer Center completed a detailed, cannabis-focused questionnaire between 2021 and 2022. Eligible participants were diagnosed with invasive cancer and treated in the past 12 months. Summary statistics were calculated to describe the sample regarding cannabis use. Approximately 15% (n = 142) of consented patients (n = 934) reported current cannabis use (defined as use within the past 12 months). Among which, 75% reported cannabis use in the past week. Among current cannabis users, 39% (n = 56; 6% overall) used CBD products. Current users reported using cannabis a median of 4.5 (interquartile range: 0.6­7.0) days/week, 2.0 (1.0­3.0) times per use/day, and for 3 years (0.8­30.0). Use patterns varied by route of administration. Patients reported moderate to high relief of symptoms with cannabis use. This study is the most detailed to date in terms of cannabis measurement and provides information about the current state of cannabis use in active cancer. Future studies should include complete assessments of cannabis product use, multiple recruitment sites, and diverse patient populations. SIGNIFICANCE: Clinicians should be aware that patients are using cannabis products and perceive symptom relief with its use.

Delirium Among Patients With Cancer in the Intensive Care Unit: Prognostic Sign or Opportunity for Intervention.

Delirium continues to be challenging for medical providers, patients, and caregivers. In a recent editorial, the authors review a retrospective analysis of critically ill, nonterminal patients with cancer admitted to a mixed medical-surgical ICU and discuss how these findings offer opportunities for intervention and goals-of-care conversations.

Assessing the Impact of Provider Training and Perceived Barriers on the Provision of Spiritual Care: a Mixed Methods Study.

The current study evaluated formal training around spiritual care for healthcare providers and the relationships between that training, perceived barriers to spiritual care, and frequency of inquiry around spiritual topics. A mixed methods explanatory sequential design was used. Quantitative methods included an online survey administered to providers at The Ohio State University Comprehensive Cancer Center. Main and interactive effects of formal training and barriers to spiritual care on frequency of inquiry around spiritual topics were assessed with two-way ANOVA. Qualitative follow-up explored provider strategies to engage spiritual topics. Among 340 quantitative participants, most were female (82.1%) or White (82.6%) with over one-half identifying as religious (57.5%). The majority were nurses (64.7%) and less than 10% of all providers (n = 26) indicated formal training around spiritual care. There were main effects on frequency of inquiry around spiritual topics for providers who indicated "personal discomfort" as a barrier (p < 0.001), but not formal training (p = 0.526). Providers who indicated "personal discomfort" as a barrier inquired about spirituality less frequently, regardless of receiving formal training (M = 8.0, SD = 1.41) or not (M = 8.76, SD = 2.96). There were no interactive effects between training and "may offend patients" or "personal discomfort" (p = 0.258 and 0.125, respectively). Qualitative analysis revealed four strategies with direct and indirect approaches: (1) permission-giving, (2) self-awareness/use-of-self, (3) formal assessment, and (4) informal assessment. Training for providers should emphasize self-awareness to address intrapersonal barriers to improve the frequency and quality of spiritual care for cancer patients.

2021 White Paper on Recent Issues in Bioanalysis: ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry (Part 2 - Recommendations on Biomarkers/CDx Assays Development & Validation, Cytometry Validation & Innovation, Biotherapeutics PK LBA Regulated Bioanalysis, Critical Reagents & Positive Controls Generation).

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included three Main Workshops and seven Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "context of use" [COU]); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 3 (TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness) are published in volume 14 of Bioanalysis, issues 9 and 11 (2022), respectively.

Gynecologic Oncology and Inclusion of Women Into the Surgical Workforce: The Canary in This Coal Mine.

Objective: Women make up a majority of the gynecologic oncology workforce. Increasing the numbers of women in leadership has been proposed as a path towards professional gender equity. This study examined whether leadership gender and departmental infrastructure impact the work environment for women gynecologic oncologists. Methods: Members of a 472-member private Facebook group "Women of Gynecologic Oncology" (WGO) who self-identified as women gynecologic oncologists provided demographics, practice infrastructure, personal experience with workplace bullying, gender discrimination, microaggressions using a REDcap survey platform. Results: Of 250 (53%) respondents to this survey, most were younger than age 50 years (93.6%); White (82.2%) and non-Hispanic (94.3%); married (84.7%); and parenting (75.2%). Practice environments included academic (n=152, 61.0%), hospital employed (n=57, 22.9%), and private practice (n=31, 12.4%), and 89.9% supervised trainees. A significant percent of respondents had experienced bullying (52.8%), gender discrimination (57%) and microaggressions (83%). Age, race, ethnicity, practice setting, or mentorship were not statistically significantly associated with these experiences. Reported perpetrators were varied and included colleagues (84%), patients (44%), staff (41%), administrators (18%), and trainees (16%). Prevalence of bullying (55.0 vs 47.7%, p=0.33), gender discrimination (59.1 vs 52.3%, p=0.33) and microaggressions (83.3 vs 83.0%, p=1.00) were similar irrespective of departmental leadership gender. Conclusions: Women gynecologic oncologists report a high prevalence of workplace bullying, gender discrimination and microaggressions regardless of the gender of their immediate leadership. Proactive and deliberate structural interventions to improve the work environment for surgeons who are women are urgently needed.

Effects of a perioperative geriatric intervention for older adults with Cancer: A randomized clinical trial.

BACKGROUND: Older adults with gastrointestinal cancers undergoing surgery often experience poor outcomes, such as prolonged postoperative hospital length of stay (LOS), intensive care unit (ICU) use, hospital readmissions, and complications. Involvement of geriatricians in the care of older adults with cancer can improve outcomes. We conducted a randomized trial of a perioperative geriatric intervention (PERI-OP) in older patients with gastrointestinal cancer undergoing surgery. METHODS: From 9/2016-4/2019, we randomly assigned patients age ≥ 65 with gastrointestinal cancer planning to undergo surgical resection to receive PERI-OP or usual care. Patients assigned to PERI-OP met with a geriatrician preoperatively in the outpatient setting and postoperatively as an inpatient consultant. The primary outcome was postoperative hospital LOS. Secondary outcomes included postoperative ICU use, 90-day hospital readmission rates, and complication rates. We conducted intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: ITT analyses included 137/160 patients who underwent surgery (usual care = 68/78, intervention = 69/82). PP analyses included the 68 usual care patients and the 30/69 intervention patients who received the preoperative and postoperative intervention components. ITT analyses demonstrated no significant differences between intervention and usual care in postoperative hospital LOS (7.23 vs 8.21 days, P = 0.374), ICU use (23.2% vs 32.4%, P = 0.257), 90-day hospital readmission rates (21.7% vs 25.0%, P = 0.690), or complication rates (17.4% vs 20.6%, P = 0.668). In PP analyses, intervention patients had shorter postoperative hospital LOS (5.90 vs 8.21 days, P = 0.024), but differences in ICU use (13.3% vs 32.4%, P = 0.081), 90-day hospital readmission rates (16.7% vs 25.0%, P = 0.439), and complication rates (6.7% vs 20.6%, P = 0.137) remained non-significant. CONCLUSIONS: In this randomized trial, PERI-OP did not have a significant impact on postoperative hospital LOS, ICU use, hospital readmissions, or complications. However, the subgroup who received PERI-OP as planned experienced encouraging results. Future studies of PERI-OP should include efforts, such as telehealth, to ensure the intervention is delivered as planned.

Multidisciplinary Approach to Older Adults with Hematologic Malignancies-a Paradigm Shift.

Hematologic malignancies are most likely to present in the seventh and eighth decades of life. Continued population growth will lead to increasing numbers of older adults with hematologic malignancies. Oncology care for older adults is complex and must account for the effect of aging on disease biology and treatment tolerance. Multidisciplinary oncology care has been utilized in solid tumor oncology for decades, initially driven by the need for multi-modality treatment. In this review, we make the case for multidisciplinary oncogeriatric care for older adults with hematologic malignancies in order to best navigate the intersection of aging and blood cancer.

Spiritual Motivations to Practice Medicine: A Survey of Cancer Care Providers.

BACKGROUND: There is increased interest in the role of spirituality in the cancer care context, but how it may inspire individuals to pursue a career as a healthcare provider is unknown. We sought to determine the relationship between intrinsic religiosity, religious identity, provider role, and spiritual motivations to practice medicine. METHODS: A cross-sectional survey was administered to healthcare providers at a large, Midwest Comprehensive Cancer Center. The relationship between provider type, intrinsic religiosity, religious identity, and spiritual motivations to practice medicine was assessed with binary logistic regression. RESULTS: Among 340 participants, most were female (82.1%) or Caucasian (82.6%) and identified as being religious (57.5%); median age was 35 years (IQR: 31-48). Providers included nurses (64.7%), physicians (17.9%), and "other" (17.4%). Compared with physicians, nurses were less likely to agree that they felt responsible for reducing pain and suffering in the world (OR: 0.12, p = 0.03). Similarly, "other" providers were less likely than physicians to believe that the practice of medicine was a calling (OR: 0.28, p = 0.02). Providers with a high self-reported intrinsic religiosity demonstrated a much greater likelihood to believe that the practice of medicine is a calling (OR:1.75, p = 0.001), as well as believe that personal R&S beliefs influence the practice of medicine (OR:3.57, p < 0.001). Provider religious identity was not associated with spiritual motivations to practice medicine (all p > 0.05). CONCLUSION: Intrinsic religiosity had the strongest relationship with spiritual motivations to practice medicine. Understanding these motivations may inform interventions to avoid symptoms of provider burnout in cancer care.

Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer.

Vigil® is a personalized vaccine that enhances tumor neoantigen expression. We investigated for the first time safety and efficacy of Vigil in combination with atezolizumab in relapsed ovarian cancer (OC) patients. This is a randomized, Phase 1 study of Vigil, an autologous tumor tissue transfected vaccine encoding for GMCSF and bi-shRNA-furin thereby creating enhanced immune activation and TGFß expression control. Part 1 is a safety assessment of Vigil (1 × 10e7 cells/mL/21 days) plus atezolizumab (1200 mg/21 days). Part 2 is a randomized study of Vigil first (Vigil-1st) or atezolizumab first (Atezo-1st) for two cycles followed by the combination of both agents. The primary endpoint of the study was the determination of safety. Twenty-four patients were enrolled in the study; three patients to Part 1 and 21 to Part 2. Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. Twenty-one patients were randomized (1:1) to Part 2 to Vigil-1st (n = 11) or Atezo-1st (n = 10). Grade 3/4 treatment-related adverse events of Atezo-1st vs. Vigil-1st were 17.2% vs. 5.1%. Median overall survival (OS) was not reached (NR) (Vigil-1st) vs. 10.8 months (Atezo-1st) (hazard ratio [HR] 0.33). The exploratory subset analysis of BRCAwt suggested improved OS benefit [NR in Vigil-1st vs. 5.2 months in Atezo-1st, HR 0.16, p 0.027]. The Vigil-1st combination therapy with atezolizumab was safe and results in support continued investigation in BRCAwt patients.

Integration of a Geriatric Assessment With Intervention in the Care of Older Adults With Hematologic Malignancies.

The incidence of hematologic malignancies (HMs) is highest in the seventh decade of life and coincides with increasing occult, age-related vulnerabilities. Identification of frailty is useful in prognostication and treatment decision-making for older adults with HMs. This real-world analysis describes 311 older adults with HMs evaluated in a multidisciplinary oncogeriatric clinic. The accumulation of geriatric conditions [1-unit increase, hazards ratio (HR) = 1.13, 95% CI 1.00-1.27, p = 0.04] and frailty assessed by the Rockwood Clinical Frailty Scale (CFS, mild/moderate/severe frailty vs. very fit/well, HR = 2.59, 95% CI 1.41-4.78, p = 0.002) were predictive of worse overall survival. In multivariate analysis, HM type [acute leukemia, HR = 3.84, 95% CI 1.60-9.22, p = 0.003; myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN)/bone marrow failure, HR = 2.65, 95% CI 1.10-6.35, p = 0.03], age (per 5-year increase, HR = 1.46, 95% CI 1.21-1.76, p < 0.001), hemoglobin (per 1 g/dl decrease, HR = 1.21, 95% CI 1.05-1.40, p = 0.009), deficit in activities of daily living (HR = 2.20, 95% CI 1.11-4.34, p = 0.02), and Mini Nutrition Assessment score (at-risk of malnutrition vs. normal, HR = 2.00, 95% CI 1.07-3.73, p = 0.03) were independently associated with risk of death. The most commonly prescribed geriatric interventions were in the domains of audiology (56%) and pharmacy (54%). The Rockwood CFS correlated with prescribed interventions in nutrition (p = 0.01) and physical function (p < 0.001) domains. Geriatric assessment with geriatric intervention can be practically integrated into the routine care of older adults with HMs.

Impact of Age on Consent in a Geriatric Orthopaedic Trauma Patient Population.

INTRODUCTION: Persistent misconceptions of frailty and dementia in geriatric patients impact physician-patient communication and leave patients vulnerable to disempowerment. Physicians may inappropriately focus the discussion of treatment options to health care proxies instead of patients. Our study explores the consenting process in a decision-making capable orthogeriatric trauma patient population to determine if there is a relationship between increased patient age and surgical consent by health care proxy. METHODS: Patients aged 65 and older who underwent operative orthopaedic fracture fixation between 1 of 2 Level 1 Trauma Centers were retrospectively reviewed. Decision-making capable status was defined as an absence of patient history of cognitive impairment and a negative patient pre-surgical Confusion Assessment Method (CAM) and Mini-Cog Assessment screen. Provider of surgical consent was the main outcome and was determined by signature on the consent form. RESULTS: 510 patients were included, and 276 (54.1%) patients were deemed capable of consent. In 27 (9.8%) of 276 decision-capable patients, physicians obtained consent from health care proxies. 20 of these 27 patients (74.1%) were 80 years of age or older. However, in patients aged 70 to 79, only 7 health care proxies provided consent. (p = 0.07). For every unit increase in age, the log odds of proxy consent increased by .0008 (p < 0.001). Age (p < 0.001), income level (p = 0.03), and physical presence of proxy at consult (p < 0.001) were factors associated with significantly increased utilization of health care proxy provided consent. Language other than English was a significant predictor of proxy-provided consent (p = 0.035). 48 (22%) decision-making incapable patients provided their own surgical consent. DISCUSSION: The positive linear association between age and health care proxy provided consent in cognitively intact geriatric orthopaedic patients indicates that increased patient age impacts the consenting process. Increased physician vigilance and adoption of institutional consenting guidelines can reinforce appropriate respect of geriatric patients' consenting capacity.

Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-ß1 and TGF-ß2. The aim of this study was to determine the safety and efficacy of gemogenovatucel-T in front-line ovarian cancer maintenance. METHODS: This randomised, double-blind, placebo-controlled, phase 2b trial involved 25 hospitals in the USA. Women aged 18 years and older with stage III/IV high-grade serous, endometrioid, or clear cell ovarian cancer in clinical complete response after a combination of surgery and five to eight cycles of chemotherapy involving carboplatin and paclitaxel, and an Eastern Cooperative Oncology Group status of 0 or 1 were eligible for inclusion in the study. Patients were randomly assigned (1:1) to gemogenovatucel-T or placebo by an independent third party interactive response system after successful screening using randomly permuted block sizes of two and four and stratified by extent of surgical cytoreduction and neoadjuvant versus adjuvant chemotherapy. Gemogenovatucel-T (1 × 107 cells per injection) or placebo was administered intradermally (one per month) for a minimum of four and up to 12 doses. Patients, investigators, and clinical staff were masked to patient allocation until after statistical analysis. The primary endpoint was recurrence-free survival, analysed in the per-protocol population. All patients who received at least one dose of gemogenovatucel-T were included in the safety analysis. The study is registered with ClinicalTrials.gov, NCT02346747. FINDINGS: Between Feb 11, 2015, and March 2, 2017, 310 patients consented to the study at 22 sites. 217 were excluded. 91 patients received gemogenovatucel-T (n=47) or placebo (n=44) and were analysed for safety and efficacy. The median follow-up from first dose of gemogenovatucel-T was 40·0 months (IQR 35·0-44·8) and from first dose of placebo was 39·8 months (35·5-44·6). Recurrence-free survival was 11·5 months (95% CI 7·5-not reached) for patients assigned to gemogenovatucel-T versus 8·4 months (7·9-15·5) for patients assigned to placebo (HR 0·69, 90% CI 0·44-1·07; one-sided p=0·078). Gemogenovatucel-T resulted in no grade 3 or 4 toxic effects. Two patients in the placebo group had five grade 3 toxic events, including arthralgia, bone pain, generalised muscle weakness, syncope, and dyspnea. Seven patients (four in the placebo group and three in the gemogenovatucel-T group) had 11 serious adverse events. No treatment-related deaths were reported in either of the groups. INTERPRETATION: Front-line use of gemogenovatucel-T immunotherapy as maintenance was well tolerated but the primary endpoint was not met. Further investigation of gemogenovatucel-T in patients stratified by BRCA mutation status is warranted. FUNDING: Gradalis.

Pilot Randomized Trial of a Transdisciplinary Geriatric and Palliative Care Intervention for Older Adults With Cancer.

BACKGROUND: Oncologists often struggle with managing the unique care needs of older adults with cancer. This study sought to determine the feasibility of delivering a transdisciplinary intervention targeting the geriatric-specific (physical function and comorbidity) and palliative care (symptoms and prognostic understanding) needs of older adults with advanced cancer. METHODS: Patients aged ≥65 years with incurable gastrointestinal or lung cancer were randomly assigned to a transdisciplinary intervention or usual care. Those in the intervention arm received 2 visits with a geriatrician, who addressed patients' palliative care needs and conducted a geriatric assessment. We predefined the intervention as feasible if >70% of eligible patients enrolled in the study and >75% of eligible patients completed study visits and surveys. At baseline and week 12, we assessed patients' quality of life (QoL), symptoms, and communication confidence. We calculated mean change scores in outcomes and estimated intervention effect sizes (ES; Cohen's d) for changes from baseline to week 12, with 0.2 indicating a small effect, 0.5 a medium effect, and 0.8 a large effect. RESULTS: From February 2017 through June 2018, we randomized 62 patients (55.9% enrollment rate [most common reason for refusal was feeling too ill]; median age, 72.3 years; cancer types: 56.5% gastrointestinal, 43.5% lung). Among intervention patients, 82.1% attended the first visit and 79.6% attended both. Overall, 89.7% completed all study surveys. Compared with usual care, intervention patients had less QoL decrement (-0.77 vs -3.84; ES = 0.21), reduced number of moderate/severe symptoms (-0.69 vs +1.04; ES = 0.58), and improved communication confidence (+1.06 vs -0.80; ES = 0.38). CONCLUSIONS: In this pilot trial, enrollment exceeded 55%, and >75% of enrollees completed all study visits and surveys. The transdisciplinary intervention targeting older patients' unique care needs showed encouraging ES estimates for enhancing patients' QoL, symptom burden, and communication confidence.