Loneliness in older adults living with cancer: A scoping review of the quantitative and qualitative evidence on behalf of the International Society of Geriatric Oncology Nursing and Allied Health Interest Group.

INTRODUCTION: Loneliness is common in older adults. Cancer and its treatments can heighten loneliness and result in poor outcomes. However, little is known about loneliness in older adults with cancer. Our objective was to provide an overview of the prevalence of loneliness, contributing factors, evolution during the cancer trajectory, impact on treatment, and interventions to reduce loneliness. MATERIALS AND METHODS: We conducted a scoping review including studies on loneliness in adults with cancer aged ≥65. Original, published studies of any designs (excluding case reports) were included. A two-step screening process was performed. RESULTS: Out of 8,720 references, 19 studies (11 quantitative, 6 qualitative, 2 mixed-methods), mostly from the United States, Netherlands, and/or Belgium, and most published from 2010, were included. Loneliness was assessed by the De Jong Gierveld Loneliness Scale, and the UCLA loneliness scale. Up to 50% of older adults felt lonely. Depression and anxiety were often correlated with loneliness. Loneliness may increase over the first 6-12 months during treatment. One study assessed the feasibility of an intervention aiming at reducing primarily depression and anxiety and secondarily, loneliness in patients with cancer aged ≥70 after five 45-min sessions with a mental health professional. No studies investigated the impact of loneliness on cancer care and health outcomes. DISCUSSION: This review documents the scarcity of literature on loneliness in older adults with cancer. The negative impacts of loneliness on health in the general population are well known; a better understanding of the magnitude and impact of loneliness in older adults with cancer is urgently warranted.

Outcomes Following Abiraterone versus Enzalutamide for Prostate Cancer: A Scoping Review.

Abiraterone acetate (AA) and enzalutamide (ENZ) are commonly used for metastatic prostate cancer. It is unclear how their outcomes and toxicities vary with patient-specific factors because clinical trials typically exclude patients with significant comorbidities. This study aims to fill this knowledge gap and facilitate informed treatment decision making. A registered protocol utilizing PRISMA scoping review methodology was utilized to identify real-world studies. Of 433 non-duplicated publications, 23 were selected by three independent reviewers. ENZ offered a faster and more frequent biochemical response (30-50% vs. 70-75%), slowed progression (HR 0.66; 95% CI 0.50-0.88), and improved overall survival versus AA. ENZ was associated with more fatigue and neurological adverse effects. Conversely, AA increased risk of cardiovascular- (HR 1.82; 95% CI 1.09-3.05) and heart failure-related (HR 2.88; 95% CI 1.09-7.63) hospitalizations. Ultimately, AA was associated with increased length of hospital stay, emergency department visits, and hospitalizations (HR 1.26; 95% CI 1.04-1.53). Accordingly, total costs were higher for AA, although pharmacy costs alone were higher for ENZ. Existing data suggest that AA and ENZ have important differences in outcomes including toxicities, response, disease progression, and survival. Additionally, adherence, healthcare utilization, and costs differ. Further investigation is warranted to inform treatment decisions which optimize patient outcomes.

Understanding the role of sex on outcomes for the cancer patient undergoing treatment with immune checkpoint inhibitors: a scoping review protocol.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for multiple cancer types. Sex plays an important role in both the development of cancer as well as the functioning of the immune system. Though a difference in response to immune therapy is emerging between men and women it is unclear how this difference affects cancer outcomes and what the potential underlying mechanisms are for those effects. The objective of this study is to describe the influence that sex has on the outcomes experienced by cancer patients on ICI therapy and to identify and analyse any knowledge gaps in the field. METHOD AND ANALYSIS: The framework for this methodology was guided by the Joanna Briggs Institute Manual for Evidence Synthesis. The search and review will be conducted from January 2022 to June 2022. Two independent researchers will screen titles and abstracts followed by full-text screening for manuscript inclusion. Full length studies published between 2010 and December 2021 found in PubMed, Cochrane, CINAHL, and Scopus describing the influence of sex differences on cancer outcomes in patients treated with ICIs will be included. After data are extracted it will be summarised for presentation. ETHICS AND DISSEMINATION: The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on the potential differential impacts of ICIs. All data are from published openly accessible sources and therefore no ethical clearance is necessary.

Current and projected number of years of life lost due to prostate cancer: A global study.

BACKGROUND: Prostate cancer is an important cause of death worldwide. The number of years of life lost (YLL) due to prostate cancer is a metric of the toll of prostate cancer and using projections of demographic changes, can be used to measure future burden. METHODS: Prostate cancer mortality data by country and world region was retrieved from the Global Cancer Observatory and the World Health Organization mortality data set, and life expectancy was from the United Nations Department of Economic and Social Affairs. We estimated YLL as the difference between age at death in people with prostate cancer and remaining life expectancy for people of the same age in the general population. We also estimated the age-standardized YLL rates per 100,000 males over 50 and the average annual percentage change in YLL rates over the period 2000-2019 and the number of YLL for the year 2040 by applying population projections to the 2020 YLL rates. RESULTS: In 2020, 3.5 million person-years of life were lost due to prostate cancer in males over 50, and 40% of YLL were in those aged over 75. Age-standardized rates varied greatly between and within regions. Over the last two decades, rates of YLL have increased in many Asian and African countries while they have decreased in northern American and European countries. Globally, YLL are anticipated to double by 2040 to reach 7.5 million, with the greatest increases in Africa, Asia, and Latin America and the Caribbean. CONCLUSION: There are wide variations in the burden of prostate cancer globally as measured by YLL. The burden of prostate cancer is projected to increase over time and appears to be highest in Sub-Saharan Africa, Eastern Europe, and Latin America and the Caribbean. It will be critical to plan and implement programs to reduce the burden of prostate cancer globally.

Is Timing of Steroid Exposure Prior to Immune Checkpoint Inhibitor Initiation Associated with Treatment Outcomes in Melanoma? A Population-Based Study.

Immune checkpoint inhibitors (ICIs) harness the immune system and are the therapy of choice for multiple cancers. Although immunosuppressive agents such as steroids are also used in many cancers, it is unknown how their timing affects treatment outcomes. Thus, we investigated the relationship between the timing of steroid exposure preceding ICI administration and subsequent treatment outcomes in melanoma. This population-based study utilized the SEER-Medicare-linked database to identify patients diagnosed with melanoma between 1991 and 2015 and receiving ICIs between 2010 and 2016, examining last steroid exposure in the 12 months preceding ICI. The main outcome was all-cause mortality (ACM) after ICIs. Modifications of the Cox proportional hazards model were used to calculate time-dependent hazards. Of 1671 patients with melanoma receiving ICIs, 907 received steroids. Compared with no steroids, last steroid exposures ≤1 month and 1-3 months prior to ICIs were associated with a 126% and 51% higher ACM within 3 months post ICI initiation, respectively (hazard ratio (HR): 2.26, 95% CI: 1.65-3.08; and HR: 1.51, 95% CI: 1.01-2.27). Steroid exposure within 3 months of initiating ICIs was associated with increased mortality up to 6 months after ICI. Further investigation is warranted to elucidate mechanisms affecting outcomes due to steroids.

International trends in cancer incidence in middle-aged and older adults in 44 countries.

OBJECTIVE: We examine international incidence trends of lung, colorectal, prostate, and breast cancers, as well as all cancers combined excluding non-melanoma skin cancer (NMSC) in adults aged 50 and older, over a fifteen-year period using data from 113 high quality population-based cancer registries included in the Cancer in Five Continents (CI5) series and NORDCAN. MATERIALS AND METHODS: We calculated annual incidence rates between 1998 and 2012 for ages 50-64, 65-74, and 75+, by sex and both sexes combined. We estimated average annual percentage change (AAPC) in rates using quasi-Poisson regression models. RESULTS: From 1998 to 2012, incidence trends for all cancers (excluding NMSC) have increased in most countries across all age groups, with the greatest increase observed in adults aged 75+ in Ecuador (AAPC = +3%). Colorectal cancer incidence rates increased in the majority of countries, across all age groups. Lung cancer rates among females have increased but decreased for males. Prostate cancer rates have sharply increased in men aged 50-64 with AAPC between 5% and 15% in 24 countries, while decreasing in the 75+ age group in 21 countries, by up to -7% in Bahrain. Female breast cancer rates have increased across all age groups in most countries, especially in the 65-74 age group and in Asia with AAPC increasing to 7% in the Republic of Korea. CONCLUSIONS: These findings assist with anticipating changing patterns and needs internationally. Due to the specific needs of older patients, it is urgent that cancer systems adapt to address their growing number.

Association Between Sex and Immune Checkpoint Inhibitor Outcomes for Patients With Melanoma.

Importance: Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment and are now standard of care. Although sex is associated with immune function and immune-related diseases, the interaction between sex and ICIs is understudied. Objective: To examine whether cancer immunotherapy effectiveness varies between female and male patients with advanced melanoma treated with either nivolumab plus ipilimumab combination therapy or anti-programmed cell death protein 1 (PD-1) therapy (namely, pembrolizumab or nivolumab). Design, Setting, and Participants: The study population consisted of 1369 older adults (aged ≥65 years) with a record of melanoma diagnosis from January 1, 1991, to December 31, 2015, in the Surveillance, Epidemiology, and End Results-Medicare linked database. Patients with a diagnosis of stage III or stage IV melanoma and a claims record showing nivolumab plus ipilimumab combination therapy or anti-PD-1 therapy (ie, pembrolizumab or nivolumab) as their last type of ICI prescribed were included in the analyses. Patients were followed up through December 31, 2017, for the overall survival analysis. Statistical analysis was performed from September 19, 2019, to February 20, 2021. Exposures: Sex, last prescribed ICI, and prior use of ipilimumab. Main Outcomes and Measures: The primary outcome was overall survival, defined as time from the index date until death from any cause, with patients censored at the end of the study (December 31, 2017). Cox proportional hazards regression modeling was used to examine the association of sex with ICI outcomes while adjusting for prior use of ipilimumab, age at ICI initiation, Charlson Comorbidity Index, cancer stage at the time of diagnosis, and autoimmune disease diagnosis. Results: Among the 1369 patients in the study (982 men [71.7%]; median age, 75 years [IQR, 69-82 years]), the outcome of nivolumab plus ipilimumab combination therapy depended on sex (Wald χ2 = 9.48; P = .009 for interaction). The mortality hazard ratio (HR) for women with prior ipilimumab use receiving combination therapy was 2.06 times (95% CI, 1.28-3.32; P = .003) higher than their male counterparts. No significant difference was observed between women and men receiving anti-PD-1 therapy with (HR, 0.97 [95% CI, 0.68-1.38]; P = .85) or without prior ipilimumab use (HR, 0.85 [95% CI, 0.67-1.07]; P = .16). For women with prior ipilimumab use, combination therapy was associated with 2.82 times higher mortality hazards than anti-PD-1 therapy (95% CI, 1.73-4.60). No statistically significant difference was seen in mortality risk between anti-PD-1 therapy and combination therapy for men. Conclusions and Relevance: This cohort study suggests that female patients with advanced melanoma may not benefit as much from combination ICIs as male patients would. Tumor mutation burden or estrogen level may serve as an important biomarker associated with ICI response in metastatic melanoma.

The Effects of Physical Activity on Cancer Patients Undergoing Treatment with Immune Checkpoint Inhibitors: A Scoping Review.

BACKGROUND: Cancer therapies are associated with multiple adverse effects, including (but not limited to) cancer-related fatigue (CRF). Fatigue is one of the most common side effects of immune checkpoint inhibitors (ICIs), occurring in up to 25% of patients. Physical activity has been shown to help reduce CRF through modulating the immune system, and may synergistically aid in the anti-tumor effects of ICIs. This review describes the nature and scope of evidence for the effects associated with concurrent physical activity while undergoing ICI therapy. METHOD: Scoping review methodology was utilized to identify studies, extract data, and collate and summarize results. RESULTS: In literature published from January 2010 through to August 2021, only one human study and three pre-clinical studies met inclusion criteria. CONCLUSION: Existing evidence supports that physical activity is associated with decreased treatment-related toxicities such as CRF. However, further investigation is warranted. The dearth of clinical studies illustrates the need for more research to address this question, to guide patients and their providers in the application of appropriate physical activity interventions in those patients undergoing ICI.

Transplant-ineligible newly diagnosed multiple myeloma: Current and future approaches to clinical care: A Young International Society of Geriatric Oncology Review Paper.

Multiple myeloma is the second most common hematological malignancy in the USA and Europe. Despite improvements in the 5-year and overall survival rates over the past decade, older adults (aged ≥65 years) with multiple myeloma continue to experience disproportionately worse outcomes than their younger counterparts. These differences in outcomes arise from the increased prevalence of vulnerabilities such as medical comorbidities and frailty seen with advancing age that can influence treatment-delivery and tolerance and impact survival. In general, geriatric assessments can help identify those patients more likely to benefit from enhanced toxicity risk-prediction and aid treatment decision-making. Despite the observed benefits of geriatric assessments and other screening frailty tools, provider and systems-level barriers continue to influence the overall perception of the feasibility of geriatric assessments in clinical practice settings. Clinical trials are underway evaluating the efficacy and safety of various multiple myeloma therapies in less fit/frail older adults, with a minority examining fitness-based/risk-adapted approaches. Thus, significant gaps exist in knowing which myeloma therapies are most appropriate for older and more vulnerable adults with multiple myeloma. The purpose of this Review is to discuss how geriatric assessments can be used to guide the management of transplant-ineligible patients; and to highlight frontline therapies for standard-risk and high-risk cytogenetic abnormalities [i.e., t(4;14), t(14;16), and del(17p)] associated with multiple myeloma. We also discuss the current shortcomings of the existing clinical approaches to care and highlight ongoing clinical trials evaluating newer fitness-based approaches to managing transplant-ineligible patients.

Relationship between polypharmacy and inpatient hospitalization among older adults with cancer treated with intravenous chemotherapy.

OBJECTIVES: Polypharmacy (≥5 concurrent medications) is common among older patients with cancer (48%-80%) and associated with increased frailty, morbidity, and mortality. This study examined the relationship between polypharmacy and inpatient hospitalization among older adults with cancer treated with intravenous (IV) chemotherapy. MATERIALS AND METHODS: The main data source was the Surveillance, Epidemiology, and End Results-Medicare linked files. Patients (≥65 years) were included if they were diagnosed with prostate (n = 1430), breast (n = 5490), or lung cancer (n = 7309) in 1991-2013 and received IV chemotherapy in 2011-2014. The number of medications during the six-month window pre-IV chemotherapy initiation determined polypharmacy status. Negative binomial models were used to assess the association between polypharmacy and post-chemotherapy inpatient hospitalization. The results were presented as incidence rate ratios. RESULTS: We identified 13,959 patients with prostate, breast, or lung cancer treated with IV chemotherapy. The median number of prescription medications during the six-month window pre-IV chemotherapy initiation was high: ten among patients with prostate cancer, nine among patients with breast cancer, and eleven among patients with lung cancer. Compared to patients taking <5 prescriptions, post-chemotherapy hospitalization rate for patients with prostate cancer was 42%, 75%, and 114% higher among those taking 5-9, 10-14, and 15+ medications, respectively. Patients with breast and lung cancer demonstrated similar patterns. CONCLUSION: This large population-based study found that polypharmacy during the six-month window pre-IV chemotherapy is highly predictive of post-chemotherapy inpatient hospitalization. Further studies are needed to evaluate whether medication management interventions can reduce post-chemotherapy inpatient hospitalization among older patients with cancer.

Mortality and Hospitalization Risk Following Oral Androgen Signaling Inhibitors Among Men with Advanced Prostate Cancer by Pre-existing Cardiovascular Comorbidities.

BACKGROUND: Elderly patients (≥65yr) with advanced prostate cancer and cardiovascular disease (CVD) conditions are often excluded from clinical trials of abiraterone acetate (AA) or enzalutamide (ENZ). Consequently, little is known about the effects of these medications on these vulnerable patients. OBJECTIVE: To assess the short-term outcomes of AA and ENZ in patients with pre-existing CVDs. DESIGN, SETTING, AND PARTICIPANTS: A population-based retrospective study. The Surveillance, Epidemiology, and End Results-Medicare-linked database was used to identify prostate cancer patients using AA or ENZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 6-mo all-cause mortality, analyzed using modified Poisson regression modeling of relative risk (RR) adjusted for confounders and comorbidities. RESULTS AND LIMITATIONS: Among eligible patients (2845 with AA and 1031 with ENZ), 67% had at least one pre-existing CVD. Compared with those without pre-existing CVDs, having one to two pre-existing CVDs was associated with 16% higher 6-mo mortality (RR=1.16, 95% confidence interval [CI]: 1.00-1.36), and the risk increased further among those having three or more CVDs (RR=1.56, 95% CI: 1.29-1.88). Most of the differences in survival of patients with pre-existing CVD condition occurred within the first 6mo of treatment. CONCLUSIONS: After treatment with AA or ENZ, elderly prostate cancer patients with pre-existing CVDs experienced higher short-term mortality than otherwise similar patients without CVDs. Mortality associated with CVDs did not depend on having received AA versus ENZ. PATIENT SUMMARY: Patients with pre-existing cardiovascular diseases (CVDs) experienced higher short-term mortality after abiraterone acetate or enzalutamide than those without pre-existing CVDs. It is recommended that a multidisciplinary team, including a cardiologist, evaluate patients having pre-existing CVDs in the process of making treatment decisions and monitoring potential side effects.