Search

Objectives: To test the feasibility of sleep hygiene education and longitudinal wrist actigraph sleep metrics measurement alone versus in combination with telehealth-delivered cognitive behavioral therapy for insomnia (teleCBT-I) for people with prostate cancer (PC) receiving androgen deprivation therapy (ADT)., Sample & Setting: 45 men with PC receiving ADT were recruited from a midwestern comprehensive cancer center., Methods & Variables: Participants were provided with wrist actigraphs, their individual sleep metrics data, and sleep hygiene education. Half the sample was randomized to a four-week teleCBT-I intervention. Outcomes were collected at baseline, one month, and two months. Exit interviews were conducted to glean participants' feedback about the study., Results: Feasibility was demonstrated. Physical function, sleep efficiency, fatigue, and health-related quality of life improved for participants receiving teleCBT-I., Implications for Nursing: Assessment of sleep disturbance, access to sleep hygiene education, and teleCBT-I may benefit people with PC receiving ADT.

Background and Objective: Treatment burden refers to the overall impact of medical treatments on a patient's well-being and daily life. Our objective is to evaluate the impact of treatment burden on quality of life (QoL) in patients with genitourinary (GU) malignancies, highlighting the importance of patient-reported outcomes (PROs) in clinical trials to inform treatment decisions and improve patient care., Methods: We conducted a narrative review of clinical trials focused on GU malignancy (prostate, bladder, and kidney) between January 2000 and June 2024, analyzing related PROs and findings regarding treatment burden., Key Findings and Limitations: Recent landmark clinical trials demonstrate significant improvements in overall survival across GU malignancies with novel therapies. However, the reporting of QoL outcomes in these trials is often inadequate, with many lacking comprehensive data or long-term impact. Current publications are increasingly evaluating treatment burden and its impact on patient well-being as a critical outcome, but most clinical trials to date have failed to assess treatment burden across key domains including financial, time and travel, and medication management., Conclusions and Clinical Implications: While advancements in treatment have extended longevity in patients with GU malignancies, the treatment burden associated with the receipt of novel agents and its implications for QoL remain inadequately uncharacterized., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: High-intensity end-of-life (EoL) care can be burdensome for patients, caregivers, and health systems and does not confer any meaningful clinical benefit. Yet, there are significant knowledge gaps regarding the predictors of high-intensity EoL care. In this study, we identify risk factors associated with high-intensity EoL care among older adults with the four most common malignancies, including breast, prostate, lung, and colorectal cancer., Materials and Methods: Using SEER-Medicare data, we conducted a retrospective analysis of Medicare beneficiaries aged 65 and older who died of breast, prostate, lung, or colorectal cancer between 2011 and 2015. We used multivariable logistic regression to identify clinical, demographic, socioeconomic, and geographic predictors of high-intensity EoL care, which we defined as death in an acute care hospital, receipt of any oral or parenteral chemotherapy within 14 days of death, one or more admissions to the intensive care unit within 30 days of death, two or more emergency department visits within 30 days of death, or two or more inpatient admissions within 30 days of death., Results: Among 59,355 decedents, factors associated with increased likelihood of receiving high-intensity EoL care were increased comorbidity burden (odds ratio [OR]:1.29; 95% confidence interval [CI]:1.28-1.30), female sex (OR:1.05; 95% CI:1.01-1.09), Black race (OR:1.14; 95% CI:1.07-1.23), Other race/ethnicity (OR:1.20; 95% CI:1.10-1.30), stage III disease (OR:1.11; 95% CI:1.05-1.18), living in a county with >1,000,000 people (OR:1.23; 95% CI:1.16-1.31), living in a census tract with 10%-<20% poverty (OR:1.09; 95% CI:1.03-1.16) or 20%-100% poverty (OR:1.12; 95% CI:1.04-1.19), and having state-subsidized Medicare premiums (OR:1.18; 95% CI:1.12-1.24). The risk of high-intensity EoL care was lower among patients who were older (OR:0.98; 95% CI:0.98-0.99), lived in the Midwest (OR:0.69; 95% CI:0.65-0.75), South (OR:0.70; 95% CI:0.65-0.74), or West (OR:0.81; 95% CI:0.77-0.86), lived in mostly rural areas (OR:0.92; 95% CI:0.86-1.00), and had poor performance status (OR:0.26; 95% CI:0.25-0.28). Results were largely consistent across cancer types., Discussion: The risk factors identified in our study can inform the development of new interventions for patients with cancer who are likely to receive high-intensity EoL care. Health systems should consider incorporating these risk factors into decision-support tools to assist clinicians in identifying which patients should be referred to hospice and palliative care., Competing Interests: Declaration of Competing Interest Dr. Wulff-Burchfield reports receiving grants from Pfizer Global Medical Grants, personal fees from Astellas, personal fees from Aveo Oncology, personal fees from Bristol Myers Squibb, personal fees from Exelixis, personal fees from Janssen, personal fees from Targeted Oncology, personal fees from Aptutide Health, grant and non-financial support from Acer Therapeutics, other from Immunomedics, other from Nektar, outside the submitted work. Dr. Vyas reports receiving research grants from Merck & Co, Inc. and Rhode Island Department of Health. Dr. Olszewski reports receiving research funding from Precision Bio, Adaptive Biotechnologies, Celdex, Acrotech Biopharma, TG Therapeutics, Genmab, and Genentech and consultancy fees from Schrodinger, TG Therapeutics and Genmab. Courtney Baird, Pamela Egan, Lee Hugar, Nikolaos Trikalinos, Michael Liu, Emmanuelle Bélanger, and Orestis Panagiotou have no conflicts or disclosures to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Improved rates of cancer control have increased the head and neck cancer survivor population. Cancer survivorship clinics are not widely available in the USA, and longitudinal supportive care for patients undergoing multimodal therapy has not advanced at a pace commensurate with improvements in cancer control. Consequently, a large head and neck cancer survivor population whose quality of life may be chronically and/or permanently diminished presently exists. This lack of awareness perpetuates under-recognition and under-investigation, leaving survivors' (mostly detrimental) experiences largely uncharted. We conducted a qualitative exploration of survivors' experiences, aiming to unpack the profound impact of late systemic symptoms on daily life, encompassing work, relationships, and self-identity in the head and neck cancer survivor community. The study included 15 remitted head and neck survivors, ≥12 months from their final treatment, who participated in semi-structured interviews conducted by a medical oncologist. Data analysis comprised qualitative thematic analysis, specifically inductive hierarchical linear modeling, enriched by a deductive approach of anecdotal clinical reporting. Results highlighted that 43.36% of all quotation material discussed in the interviews pertained to chronic emotion disturbance with significant implications for other domains of life. A central symptom cluster comprised impairments in mood/emotions, daily activity, and significant fatigue. Dysfunction in sleep, other medical conditions, and cognitive deficits comprised a secondary cluster. Physical dysfunctionality, encompassing pain, appetite, and eating, and alterations in experienced body temperature, constituted a tertiary cluster, and perhaps were surprisingly the least discussed symptom burden among head and neck cancer survivors. Symptoms causing heightened long-term survivor burden may be considered epiphenomenal to central physical dysfunctionality, albeit being presently the least represented in cancer survivor care programs. Moving forward, the development of targeted and multi-dimensional treatment programs that encompass physical, psychosocial, and spiritual domains are needed to increase clinical specificity and effective holistic long-term solutions that will foster a more compassionate and informed future of care for the cancer survivorship community.

Background: Sarcopenia is associated with adverse outcomes for patients with muscle invasive bladder cancer (MIBC), but less is known about its impact in the setting of non-muscle invasive bladder cancer (NMIBC). Sarcopenia, skeletal muscle density, and adipose tissue area have been studied as markers of malnutrition and can be determined radiographically. The purpose of this study is to characterize the prevalence of sarcopenia in patients with NMIBC receiving intravesical Bacillus Calmette-Guérin (BCG)., Methods: Following institutional review board approval, patients with NMIBC having received intravesical BCG were identified using institutional pharmacy records. Patients having undergone computed tomography (CT) of the abdomen and pelvis within 90 days of treatment were included in the analysis. Using sliceOmatic 5.0 software, skeletal muscle area (cm 2 ) was measured at the L3 level to calculate skeletal muscle index (SMI), a marker of sarcopenia. Subcutaneous, visceral, and intramuscular adipose tissue areas in addition to skeletal muscle density were also measured. Frailty was evaluated as a secondary aim using the 5-Item Modified Frailty Index (mFI-5). Using predefined cutoffs, the prevalence of sarcopenia was determined. Descriptive statistics were used to characterize frailty and secondary body composition characteristics. Statistical analysis was performed to evaluate the impact of sarcopenia on recurrence rate and progression., Results: A total of 308 patients having received BCG between 2015 and 2020 were identified, of which 90 met criteria for analysis. Nearly all (94%) patients completed at least 5 out of 6 BCG induction instillations. Median body mass index (kg/m 2 ) was 27.64 (IQR 24.9, 30.5) for females and 27.7 (IQR 24.9, 30.66) for males. Median SMI (cm 2 /m 2 ) was 49.44 (IQR 39.39, 55.17) for females and 49.58 (IQR 40.25, 55.58) for males. A majority (61%) of patients were found to be sarcopenic. High-risk frailty was identified 36% of patients. There was no association between sarcopenia and recurrence rate or progression., Conclusions: Sarcopenia and frailty are highly prevalent amongst patients with NMIBC. A diagnosis of NMIBC represents a window of opportunity to identify and intervene on modifiable risk factors such as sarcopenia and frailty, which are associated with adverse outcomes in more advanced disease states., Competing Interests: Declaration of Competing Interest The author has no competing interests to disclose, financial or otherwise., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Precision medicine holds enormous potential to improve outcomes for cancer patients, offering improved rates of cancer control and quality of life. Not all patients who could benefit from targeted cancer therapy receive it, and some who may not benefit do receive targeted therapy. We sought to comprehensively identify determinants of targeted therapy use among community oncology programs, where most cancer patients receive their care., Methods: Guided by the Theoretical Domains Framework, we conducted semi-structured interviews with 24 community cancer care providers and mapped targeted therapy delivery across 11 cancer care delivery teams using a Rummler-Brache diagram. Transcripts were coded to the framework using template analysis, and inductive coding was used to identify key behaviors. Coding was revised until a consensus was reached., Results: Intention to deliver precision medicine was high across all participants interviewed, who also reported untenable knowledge demands. We identified distinctly different teams, processes, and determinants for (1) genomic test ordering and (2) delivery of targeted therapies. A key determinant of molecular testing was role alignment. The dominant expectation for oncologists to order and interpret genomic tests is at odds with their role as treatment decision-makers' and pathologists' typical role to stage tumors. Programs in which pathologists considered genomic test ordering as part of their staging responsibilities reported high and timely testing rates. Determinants of treatment delivery were contingent on resources and ability to offset delivery costs, which low- volume programs could not do. Rural programs faced additional treatment delivery challenges., Conclusions: We identified novel determinants of targeted therapy delivery that potentially could be addressed through role re-alignment. Standardized, pathology-initiated genomic testing may prove fruitful in ensuring patients eligible for targeted therapy are identified, even if the care they need cannot be delivered at small and rural sites which may have distinct challenges in treatment delivery. Incorporating behavior specification and Rummler-Brache process mapping with determinant analysis may extend its usefulness beyond the identification of the need for contextual adaptation., (© 2023. The Author(s).)

Acanthamoeba species, Naegleria fowleri , and Balamuthia mandrillaris are opportunistic pathogens that cause a range of brain, skin, eye, and disseminated diseases in humans and animals. These pathogenic free-living amoebae (pFLA) are commonly misdiagnosed and have sub-optimal treatment regimens which contribute to the extremely high mortality rates (>90%) when they infect the central nervous system. To address the unmet medical need for effective therapeutics, we screened kinase inhibitor chemotypes against three pFLA using phenotypic drug assays involving CellTiter-Glo 2.0. Herein, we report the activity of the compounds against the trophozoite stage of each of the three amoebae, ranging from nanomolar to low micromolar potency. The most potent compounds that were identified from this screening effort were: 2d ( A. castellanii EC 50 : 0.92 ± 0.3 μM; and N. fowleri EC 50 : 0.43 ± 0.13 μM), 1c and 2b ( N. fowleri EC 50 s: <0.63 μM, and 0.3 ± 0.21 μM), and 4b and 7b ( B. mandrillaris EC 50 s: 1.0 ± 0.12 μM, and 1.4 ± 0.17 μM, respectively). With several of these pharmacophores already possessing blood-brain barrier (BBB) permeability properties, or are predicted to penetrate the BBB, these hits present novel starting points for optimization as future treatments for pFLA-caused diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferrins, Buskes, Kapteyn, Engels, Enos, Lu, Klug, Singh, Quotadamo, Bachovchin, Tear, Spaulding, Forbes, Bag, Rivers, LeBlanc, Burchfield, Armand, Diaz-Gonzalez, Ceballos-Perez, García-Hernández, Pérez-Moreno, Bosch-Navarrete, Ruiz-Pérez, Gamarro, González-Pacanowska, Navarro, Mensa-Wilmot, Pollastri, Kyle and Rice.)

Background: To examine differences in survival outcomes for muscle-invasive bladder cancer patients stratified by new mental health diagnosis., Methods: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer between 2008 and 2014. Our primary outcome was cancer-specific and overall hazards of mortality. As a secondary outcome, we reported predictors of developing a new mental health diagnosis after bladder cancer diagnosis. We used Cox proportional hazards models to determine the impact of palliative care and mental health diagnoses on survival outcomes after adjusting for grade, stage, comorbidity index, and baseline demographics., Results: Of the 3794 patients who met inclusion criteria, 1193 (31%) were diagnosed with a mental health illness after their bladder cancer diagnosis during the 6 years in the study period. The most common diagnoses were depression (13%), alcohol and drug abuse (12%), and anxiety (11%). Patients with a post-bladder cancer mental health diagnosis had a 57% higher hazard of overall mortality (HR 1.57, P = .048) and an 80% higher hazard of bladder cancer-specific mortality (HR 1.81, P = .037) CONCLUSIONS: New mental health diagnoses are associated with worse survival in patients with muscle invasive bladder cancer. This suggests that a multimodal approach to bladder cancer treatment should include addressing the non-oncologic needs of the patient to optimize survival outcomes., Competing Interests: Disclosure The remaining authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: COVID-19 particularly impacted patients with co-morbid conditions, including cancer. Patients with melanoma have not been specifically studied in large numbers. Here, we sought to identify factors that associated with COVID-19 severity among patients with melanoma, particularly assessing outcomes of patients on active targeted or immune therapy., Methods: Using the COVID-19 and Cancer Consortium (CCC19) registry, we identified 307 patients with melanoma diagnosed with COVID-19. We used multivariable models to assess demographic, cancer-related, and treatment-related factors associated with COVID-19 severity on a 6-level ordinal severity scale. We assessed whether treatment was associated with increased cardiac or pulmonary dysfunction among hospitalized patients and assessed mortality among patients with a history of melanoma compared with other cancer survivors., Results: Of 307 patients, 52 received immunotherapy (17%), and 32 targeted therapy (10%) in the previous 3 months. Using multivariable analyses, these treatments were not associated with COVID-19 severity (immunotherapy OR 0.51, 95% CI 0.19 - 1.39; targeted therapy OR 1.89, 95% CI 0.64 - 5.55). Among hospitalized patients, no signals of increased cardiac or pulmonary organ dysfunction, as measured by troponin, brain natriuretic peptide, and oxygenation were noted. Patients with a history of melanoma had similar 90-day mortality compared with other cancer survivors (OR 1.21, 95% CI 0.62 - 2.35)., Conclusions: Melanoma therapies did not appear to be associated with increased severity of COVID-19 or worsening organ dysfunction. Patients with history of melanoma had similar 90-day survival following COVID-19 compared with other cancer survivors., (© 2023. The Author(s).)

Background: The 21 st Century Cures Act Interoperability and Information Blocking Rule was created to increase patient access to health information. This federally mandated policy has been met with praise and concern. However, little is known about patient and clinician opinions of this policy within cancer care., Methods: We conducted a convergent parallel mixed methods study to understand patient and clinician reactions to the Information Blocking Rule in cancer care and what they would like policy makers to consider. Twenty-nine patients and 29 clinicians completed interviews and surveys. Inductive thematic analysis was used to analyze the interviews. Interview and survey data were analyzed separately, then linked to generate a full interpretation of the results., Results: Overall, patients felt more positive about the policy than clinicians. Patients wanted policy makers to understand that patients are unique, and they want to individualize their preferences for receiving health information with their clinicians. Clinicians highlighted the uniqueness of cancer care, due to the highly sensitive information that is shared. Both patients and clinicians were concerned about the impact on clinician workload and stress. Both expressed an urgent need for tailoring implementation of the policy to avoid unintended harm and distress for patients., Conclusions: Our findings provide suggestions for optimizing the implementation of this policy in cancer care. Dissemination strategies to better inform the public about the policy and improve clinician understanding and support are recommended. Patients who have serious illness or diagnoses such as cancer and their clinicians should be included when developing and enacting policies that could have a significant impact on their well-being. Patients with cancer and their cancer care teams want the ability to tailor information release based on individual preferences and goals. Understanding how to tailor implementation of the Information Blocking Rule is essential for retaining its benefits and minimizing unintended harm for patients with cancer., (© 2023. The Author(s).)

The carbazole CBL0137 ( 1 ) is a lead for drug development against human African trypanosomiasis (HAT), a disease caused by Trypanosoma brucei . To advance 1 as a candidate drug, we synthesized new analogs that were evaluated for the physicochemical properties, antitrypanosome potency, selectivity against human cells, metabolism in microsomes or hepatocytes, and efflux ratios. Structure-activity/property analyses of analogs revealed eight new compounds with higher or equivalent selectivity indices ( 5j , 5t , 5v , 5w , 5y , 8d , 13i , and 22e ). Based on the overall compound profiles, compounds 5v and 5w were selected for assessment in a mouse model of HAT; while 5v demonstrated a lead-like profile for HAT drug development, 5w showed a lack of efficacy. Lessons from these studies will inform further optimization of carbazoles for HAT and other indications.

Objectives: Patients undergoing radical cystectomy with ileal conduit formation usually receive training on the use of their stoma during their initial hospitalization - while actively recovering from surgery - often with little follow-up or reinforcement. Many of these patients are not equipped to deal with these significant body changes, which can lead to additional clinic visits, stoma-related complications, and decreased patient satisfaction/health-related quality of life (HRQOL). In an effort to improve patient education, we sought to evaluate the feasibility of implementing a preoperative comprehensive stoma education session termed the "stoma bootcamp" for patients scheduled for a radical cystectomy and ileal conduit (RCIC). We tracked patient related outcomes to determine its impact., Methods: We performed a longitudinal, quality-improvement feasibility study at the University of Kansas Health System. All patients who were scheduled to undergo a RCIC for bladder cancer were offered enrollment into the study at their preoperative clinic visit. The "stoma boot camp" consisted of a 3-hour group session within 2 weeks of the surgery date. Patients were given a short presentation by residents and advanced practice providers regarding the operation, recovery, and expectations for their post-operative care. Ostomy nurses then demonstrated basic urostomy care - pouching, sizing, emptying - along with trouble-shooting tips for common ostomy problems. Measurements of HRQOL questionnaires were completed at the initial visit, after "boot camp," and at defined time points after surgery for 12 weeks. This included using an ostomy adjustment score. Length of stay, unplanned stoma-related interventions, and re-admissions within 30 days were also tracked., Results: In this initial pilot program, 51 patients participated in the stoma bootcamp. The patients had an average ostomy adjustment score (OAS) of 150.4 (95% CI 142.0, 158.8) at discharge from the hospital, and these high OAS levels persisted throughout the 12 weeks of follow-up data without any significant decline. Short-form 36 (SF-36) scores demonstrated numerical improvements in each individual category at the 6-week mark above baseline. These improvements persisted at the 12-week mark., Conclusions: In this study we were able to establish the feasibility of implementing a preoperative comprehensive stoma education session for patients scheduled for a RCIC. Additionally, we were able to document favorable HRQOL data and improved ostomy adjustment scores surrounding the education session., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19., Methods: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed., Results: of 281 patients, 49% ( n = 139) were hospitalized, 33% ( n = 93) received supplemental oxygen, 11% ( n = 31) were admitted to the ICU, and 6% ( n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity., Conclusions: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

Purpose: How care delivery influences urban-rural disparities in cancer outcomes is unclear. We sought to understand community oncologists' practice settings to inform cancer care delivery interventions., Methods: We conducted secondary analysis of a national dataset of providers billing Medicare from June 1, 2019 to May 31, 2020 in 13 states in the central United States. We used Kruskal-Wallis rank and Fisher's exact tests to compare physician characteristics and practice settings among rural and urban community oncologists., Findings: We identified 1,963 oncologists practicing in 1,492 community locations; 67.5% practiced in exclusively urban locations, 11.3% in exclusively rural locations, and 21.1% in both rural and urban locations. Rural-only, urban-only, and urban-rural spanning oncologists practice in an average of 1.6, 2.4, and 5.1 different locations, respectively. A higher proportion of rural community sites were solo practices (11.7% vs 4.0%, P<.001) or single specialty practices (16.4% vs 9.4%, P<.001); and had less diversity in training environments (86.5% vs 67.8% with <2 medical schools represented, P<.001) than urban community sites. Rural multispecialty group sites were less likely to include other cancer specialists., Conclusions: We identified 2 potentially distinct styles of care delivery in rural communities, which may require distinct interventions: (1) innovation-isolated rural oncologists, who are more likely to be solo providers, provide care at few locations, and practice with doctors with similar training experiences; and (2) urban-rural spanning oncologists who provide care at a high number of locations and have potential to spread innovation, but may face high complexity and limited opportunity for care standardization., (© 2022 National Rural Health Association.)

Purpose: Many older patients with advanced lung cancer have functional limitations and require skilled nursing home care. Function, assessed using activities of daily living (ADL) scores, may help prognostication. We investigated the relationship between ADL impairment and overall survival among older patients with advanced non-small-cell lung cancer (NSCLC) receiving care in nursing homes., Methods: Using the SEER-Medicare database linked with Minimum Data Set assessments, we identified patients age 65 years and older with NSCLC who received care in nursing homes from 2011 to 2015. We used Cox regression and Kaplan-Meier survival curves to examine the relationship between ADL scores and overall survival among all patients; among patients who received systemic cancer chemotherapy or immunotherapy within 3 months of NSCLC diagnosis; and among patients who did not receive any treatment., Results: We included 3,174 patients (mean [standard deviation] age, 77 [7.4] years [range, 65-102 years]; 1,664 [52.4%] of female sex; 394 [12.4%] of non-Hispanic Black race/ethnicity), 415 (13.1%) of whom received systemic therapy, most commonly with carboplatin-based regimens (n = 357 [86%] patients). The median overall survival was 3.1 months for patients with ADL score < 14, 2.8 months for patients with ADL score between 14 and 17, 2.3 months for patients with ADL score between 18-19, and 1.8 months for patients with ADL score 20+ (log-rank P < .001). The ADL score was associated with increased risk of death (hazard ratio [HR], 1.20; 95% CI, 1.16 to 1.25 per standard deviation). One standard deviation increase in the ADL score was associated with lower overall survival rate among treated (HR, 1.14; 95% CI, 1.02 to 1.27) and untreated (HR, 1.20; 95% CI, 1.15 to 1.26) patients., Conclusion: ADL assessment stratified mortality outcomes among older nursing home adults with NSCLC, and may be a useful clinical consideration in this population., Competing Interests: Jessica OgarekOther Relationship: Personal Feels from American Hospital Association Elizabeth Wulff-BurchfieldStock and Other Ownership Interests: Nektar, ImmunomedicsConsulting or Advisory Role: Astellas Scientific and Medical Affairs Inc, Exelixis, Bristol Myers Squibb, Janssen OncologyResearch Funding: Pfizer Adam OlszewskiResearch Funding: Genentech/Roche (Inst), TG Therapeutics (Inst), Spectrum Pharmaceuticals (Inst), Celldex (Inst), Adaptive Biotechnologies, Precision Biosciences (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/111328 Orestis A. PanagiotouConsulting or Advisory Role: International Consulting AssociatesNo other potential conflicts of interest were reported.

Background: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer., Patients and Methods: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19)., Results: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19., Conclusions: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future., Competing Interests: Disclosure ALS reports non-financial support from Astellas, non-financial support from Pfizer, outside the submitted work. CL reports research support from Genentech/imCORE, outside the submitted work. ZB reports non-financial support from Bristol Myers Squibb, grants from Genentech/imCORE, personal fees from UpToDate, outside the submitted work. CYH reports personal fees from NashBio, outside the submitted work. SAB reports personal fees from Exelixis, personal fees from Seattle Genetics, personal fees from Pfizer, personal fees from Bristol Myers Squibb, outside the submitted work. CRF reports research grants from the Merck Foundation and National Comprehensive Cancer Network (NCCN)/Pfizer, outside the submitted work. EAG reports personal fees and other from Alexion Pharmaceuticals, personal fees and non-financial support from Novartis Pharmaceuticals, personal fees, non-financial support and other from Astex/Otsuka Pharmaceuticals, other from Apellis Pharmaceuticals, personal fees, non-financial support, and other from Celgene/Bristol Myers Squibb, grants and personal fees from AbbVie/Genentech, other from Celldex Therapeutics, personal fees from Boston Biomedical, outside the submitted work. JEH reports research funding paid to her institution from Dendreon Pharmaceuticals LLC, research funding paid to her institution from Regeneron Pharmaceuticals, personal fees from Genzyme, personal fees from Seagen, outside the submitted work. RRM reports grants and personal fees from Bayer, grants from Pfizer, grants from Tempus, personal fees from AVEO, personal fees from Caris, personal fees from Bristol Myers Squib, personal fees from Exelixis, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from Sanofi, personal fees from Tempus, personal fees from Dendreon, personal fees from Vividion, personal fees from AstraZeneca, personal fees from Calithera, personal fees from Merck, outside the submitted work. OAP reports personal fees from International Consulting Associates, Inc., outside the submitted work. EMW-B reports personal fees from Astellas, personal fees from AVEO Oncology, personal fees from Bristol Myers Squibb, other from Exelixis, grants from Pfizer Global Medical Grants, other from Nektar, other from Immunomedics, outside the submitted work. SM reports personal fees from National Geographic, outside the submitted work. DF reports a grant from Merck to study COVID-19 in immunocompromised patients, outside of the submitted work. YS reports personal fees from Novartis, personal fees from Roche, personal fees from Pfizer, personal fees from Janssen, personal fees from Eisai, personal fees from AstraZeneca, outside of the submitted work. JLW reports personal fees from Westat, personal fees from Roche, personal fees from Melax Tech, personal fees from Flatiron Health, other from HemOnc.org LLC (ownership), outside the submitted work. TKC reports institutional and personal, paid and unpaid support for research, advisory boards, consultancy, and honoraria from AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVIA, Ipsen, Kanaph, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi/Aventis, Takeda, Tempest, UpToDate, CME events (Peerview, OncLive and others), outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer., Methods: In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models., Findings: 5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients., Interpretation: The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality., Funding: US National Institutes of Health National Cancer Institute Cancer Center., Competing Interests: The following authors declare competing interests not related to the current work: ZB reports grants from Genentech/imCORE, non-financial support from Bristol Myers Squibb, and personal fees from UpToDate. AE reports salary support from the Canadian Institute of Health Research, the Detweiler Travelling Fellowship (Royal College of Physicians and Surgeons of Canada), and the Henry R Shibata Fellowship (Cedar's Cancer Foundation). CRF reports grants from Merck Foundation, NCCN/Pfizer, and National Cancer Institute, and other support from National Cancer Institute and the Patient-Centered Outcomes Research Institute. PGri reports personal fees and non-financial support from AstraZeneca, personal fees from Astellas Pharma, personal fees from Bayer, grants and personal fees from Bristol Myers Squibb, grants and non-financial support from Clovis Oncology, personal fees from Dyania Health, grants and personal fees from EMD Serono, personal fees from Exelixis, personal fees from Foundation Medicine, personal fees from Genentech/Roche, personal fees from Genzyme, grants and personal fees from GlaxoSmithKline, personal fees from Guardant Health, grants and personal fees from Immunomedics/Gilead, personal fees from Infinity Pharmaceuticals, personal fees from Janssen, grants and personal fees from Merck, grants and personal fees from Mirati Therapeutics, grants and personal fees from Pfizer, grants and personal fees from QED Therapeutics, personal fees from Regeneron Pharmaceuticals, personal fees from Seattle Genetics, personal fees from 4D Pharma, personal fees from UroGen, grants from Bavarian Nordic, and grants from Debiopharm. SGup reports grants and personal fees from Bristol Myers Squibb, personal fees from Merck, Janssen, Seattle Genetis, EMD Sorono, and Pfizer, and grants from Astellas and BMS. CHw reports grants from Merck, Bayer, and AstraZeneca, and personal fees from Tempus and EMD Sorono, and other support from Johnson and Johnson. AK reports other support from TESARO, Fibrogen, Geistlich Pharma, Astellas Pharma, Rafael Pharmaceuticals, and Novocure. ARK reports other support from Merck and Sanofi, personal fees from OncLive, grants from ASCO Conquer Cancer Foundation, and grants from Bladder Cancer Advocacy Network. HK reports position on advisory board of Sanofi Genzyme NSCLC Northeast. NMK reports personal fees from BMS, Janssen, Seattle Genetics, Celldex, Sandoz, Invitae, Beyond Spring, Spectrum G1 Therapeutics, and Total Health, and grants from Amgen, Jazz Therapeutics, G1 Therapeutics, and Samsung. CL reports grants from imCORE/Genentech. RRM reports serving on advisory board or as a consultant for Astrazeneca, Aveo, Bayer, BMS, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, and Tempus. RRM received institutional research funding from Pfizer, Bayer, Tempus. SM reports personal fees from National Geographic. OAP reports grants from National Institutes of Health (NIH) and Agency for Healthcare Research and Quality, and personal fees from International Consulting Associates. NAP reports personal fees from AstraZeneca, Merck, Pfizer, Eli Lilly, Genentech, BMS, Amgen, Inivata, G1 Therapeutics, Xencor, Mirati, Janssen, Boehringer Ingelheim, and Sanofi-Genzyme-Regeneron. RPR reports grants from BMS and Janssen, and personal fees from BMS, Janssen, Dova, and Inari. MAT reports personal fees from VIA Oncology, GSK, and Adaptive Advisory Board, other support from Syapse, UpToDate, Takeda, Celgene, Doximity, AbbVie, BMS, CRAB CTC, Denovo, Hoosier Research Network, Lilly, LynxBio, Strata Oncology, and TG Therapeutics. JLW reports personal fees from Roche, Westat, Flatiron Health, Melax Tech, and IBM Watson Health, other support from HemOnc and Janssen, and grants from AACR. TMW reports personal fees from Carevive, and personal fees from Sanofi, and Seattle Genetics. TMW-D reports grants from BMS, Merck, Janssen, and GSK/Tesaro, personal fees from Exicure, Shattuck Labs, Merck, Caris Life Science, and SITC, and other support from High Enroll. EW-B reports grants from Pfizer Global Medical Grants, personal fees from Astellas, Aveo Oncology Bristol Myers Squibb, Exelixis, and Janssen, and other support from Immunomedics and Nektar. The following authors declare competing interests during the conduct of the study: SM reports grants and other support from National Cancer Institute and from the International Association for the Study of Lung Cancer. DPS reports grants from American Cancer Society and Hope Foundation for Cancer Research and from NIH. LT reports grants from NIH. JLW reports grants from NIH. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

Outcomes are improving for patients with advanced cancer, in part because of increasing diversity and efficacy of systemic therapy, often described as "palliative chemotherapy." Patients with advanced cancer receiving systemic treatment sometimes require surgical interventions, and their cancer care teams must collaborate to optimally manage medical and surgical challenges while also considering patients' goals and values. Structured communication can overcome the inherent ambiguity of the term "palliative chemotherapy" and facilitate optimal quality of care and quality of life for patients with advanced cancer who require surgical interventions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To determine the relationship of self-care task disabilities with the use of systemic cancer therapies for advanced non-small cell lung cancer (NSCLC) in nursing home patients., Materials and Methods: Using the Surveillance, Epidemiology, and End Results-Medicare database linked with Minimum Data Set assessments, we identified nursing home residents with advanced NSCLC from 2011 to 2015. We considered disability in activities of daily living (ADL) including dressing, personal hygiene, toilet use, locomotion on unit, transfer, bed mobility, and eating. We estimated the association between ADL disabilities and receipt of systemic cancer therapies within 3 months of diagnosis., Results: Of the 3174 patients, 2702 (85.2%) experienced disability in one or more ADLs and 64.7% had disability in 5-7 ADLs. A total of 415 (13.1%) patients received systemic therapy. There was a strong association between disability in each ADL and receipt of therapy including dressing (OR, 0.52 [95% CI, 0.42-0.65]), toileting (odds ratio, OR, 0.52 [95% confidence interval, CI, 0.42-0.65]), personal hygiene (OR, 0.48 [95% CI, 0.39-0.59]), transfers (OR, 0.51 [95% CI, 0.41-0.64]), bed mobility (OR, 0.55 [95% CI, 0.44-0.69]), locomotion (OR, 0.57 [95% CI, 0.46-0.71]), or eating (OR, 0.45 [95% CI, 0.31-0.67]). Compared to patients having no ADL disability, patients were less likely to receive chemotherapy if they had disability in 1-2 ADLs (OR, 0.95 [95% CI, 0.66-1.37]), 3-4 ADLs (OR, 0.81 [95% CI, 0.56-1.15]), or 5-7 ADLs (OR, 0.43 [95% CI, 0.33-0.56])., Conclusions: Systemic cancer therapy is not commonly used in this population and is strongly predicted by disability in self-care tasks., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Whether there is sex-bias within the adverse outcomes associated with COVID-19 in the cancer population is unknown. In this regard, several published studies have examined this question, but the results are inconclusive and inconsistent. To evaluate the sex-difference in the risk of adverse outcomes associated with COVID-19 in the cancer population, we have conducted a systematic review and meta-analysis., Methods: Published articles evaluating adverse outcomes associated with COVID-19 in the cancer population from inception to June 2020 were identified by searching PubMed and EMBASE, ASCO 2020 Virtual Annual Conference, AACR 2020 COVID-19 and Cancer, ESMO conferences held from January to June 2020, and medRxiv and bioRxiv. Prospective or retrospective analyses in English, providing outcomes data with sex differences in the cancer population were included. The primary outcomes of interest were pooled ORs of severe illness, all-cause death, and the composite of severe illness and death attributable to COVID-19 in males versus females in cancer patients., Findings: Overall, 3968 patients (17 studies) were analyzed in retrospective study settings. Overall, pooled ORs of the composite of severe illness and all-cause death in the setting of COVID-19 in males versus females was 1.60 (95% CI, 1.38-1.85). The risk of severe illness or death were both independently increased in males versus females., Interpretation: Male sex was associated with a higher risk of severe illness and death attributable to COVID-19. This finding has implications in informing the clinical prognosis and decision making in the care of cancer patients., Funding: This study received no funding., Competing Interests: The authors report no conflicts of interest pertaining to this study., (© 2020 The Authors.)

Background: Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness., Methods: In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing., Findings: Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality., Interpretation: Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments., Funding: American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The systemic effects and manifestations of disease and treatment have been of interest for millennium. Until recently, basic and clinical research is just now reaching a watershed. Systemic symptoms usually do not occur in isolation but rather in clusters; however, much of the cutting-edge research pertaining to the etiology, mechanism, manifestations, and moderators of systemic symptoms in humans has been directed at individual symptoms, thus creating silos of knowledge. Breaching these silos and bridging the knowledge from disparate arenas of investigation to build a comprehensive depiction of acute and chronic systemic symptoms has been a challenge. In addition, much of the recent work in systemic symptoms has been conducted in the setting of nonmalignant disease. The degree to which the findings from other chronic disease processes can be translated into the oncologic realm is unknown. This article will explore inflammation as a major contributing factor to systemic symptoms and sickness behavior, discuss the most common manifestations in cancer survivors, and, where available, discuss specific data pertaining to head and neck cancer survivors., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Neuroinflammation and central sensitization from cancer and its therapy may result in chronic systemic symptoms (CSS) such as fatigue, sleep disturbance, chronic widespread pain, mood disorders, neuropsychiatric symptoms, and temperature dysregulation. We undertook a cross-sectional study of CSS in head and neck cancer (HNC) survivors to determine their frequency, severity, and impact., Methods: HNC patients without evidence of recurrence who were at least 12 months post-treatment completed a one-time battery of self-report measures including the Vanderbilt Head and Neck Symptom survey plus the General Symptom Subscale, the Body Image Quality of Life Inventory, Neurotoxicity Rating Scale, the Profile of Mood States, and a five-item quality of life measure., Results: One hundred five patients completed the surveys. Forty-eight point four percent of patients experienced one or more moderate-to-severe systemic symptom. The frequency of individual symptoms was between 20% and 56% with almost half of patients rating symptoms as moderate-to-severe in intensity. Low and high systemic symptom burden populations were identified. Previously undescribed chronic neuropsychiatric symptoms were also found to be frequent and severe. The vigor score on the POMS was low. Body image was not adversely impacted. At least 40% of HNC survivors have diminished quality of life, and up to 15% have a poor quality of life., Conclusions: CSS are common among HNC survivors and are frequently moderate to severe in intensity. Of note, previously underrecognized neuropsychiatric symptoms were endorsed by a significant cohort of patients warranting further study. Quality of life was diminished in a significant cohort.