Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

Cancer statistics for adults aged 85 years and older, 2019.

Adults aged 85 years and older, the "oldest old," are the fastest-growing age group in the United States, yet relatively little is known about their cancer burden. Combining data from the National Cancer Institute, the North American Association of Central Cancer Registries, and the National Center for Health Statistics, the authors provide comprehensive information on cancer occurrence in adults aged 85 years and older. In 2019, there will be approximately 140,690 cancer cases diagnosed and 103,250 cancer deaths among the oldest old in the United States. The most common cancers in these individuals (lung, breast, prostate, and colorectum) are the same as those in the general population. Overall cancer incidence rates peaked in the oldest men and women around 1990 and have subsequently declined, with the pace accelerating during the past decade. These trends largely reflect declines in cancers of the prostate and colorectum and, more recently, cancers of the lung among men and the breast among women. We note differences in trends for some cancers in the oldest age group (eg, lung cancer and melanoma) compared with adults aged 65 to 84 years, which reflect elevated risks in the oldest generations. In addition, cancers in the oldest old are often more advanced at diagnosis. For example, breast and colorectal cancers diagnosed in patients aged 85 years and older are about 10% less likely to be diagnosed at a local stage compared with those diagnosed in patients aged 65 to 84 years. Patients with cancer who are aged 85 years and older have the lowest relative survival of any age group, with the largest disparities noted when cancer is diagnosed at advanced stages. They are also less likely to receive surgical treatment for their cancers; only 65% of breast cancer patients aged 85 years and older received surgery compared with 89% of those aged 65 to 84 years. This difference may reflect the complexities of treating older patients, including the presence of multiple comorbidities, functional declines, and cognitive impairment, as well as competing mortality risks and undertreatment. More research on cancer in the oldest Americans is needed to improve outcomes and anticipate the complex health care needs of this rapidly growing population.

Association of polypharmacy and potential drug-drug interactions with adverse treatment outcomes in older adults with advanced cancer.

BACKGROUND: Polypharmacy is common in older adults who are starting cancer treatment and is associated with an increased risk of potentially inappropriate medications (PIMs) and potential drug-drug interactions (PDIs). The authors evaluated the association of medication measures with adverse outcomes in older adults with advanced cancer who were receiving systemic therapy. METHODS: This secondary analysis from GAP 70+ Trial (ClinicalTrials.gov identifier NCT02054741; principal investigator, Supriya G. Mohile) enrolled patients aged 70 years and older with advanced cancer who planned to start a new treatment regimen (n = 718). Polypharmacy was assessed before the initiation of treatment and was defined as the concurrent use of eight or more medications. PIMs were categorized using 2019 Beers Criteria and the Screening Tool of Older Persons' Prescriptions. PDIs were evaluated using Lexi-Interact Online. Study outcomes were assessed within 3 months of treatment and included: (1) the number of grade ≥2 and ≥3 toxicities according to the National Cancer Institute Common Toxicity Criteria, (2) treatment-related unplanned hospitalization, and (3) early treatment discontinuation. Multivariable regression models examined the association of medication measures with outcomes. RESULTS: The mean patient age was 77 years, and 57% had lung or gastrointestinal cancers. The median number of medications was five (range, 0-24 medications), 28% of patients received eight or more medications, 67% received one or more PIM, and 25% had one or more major PDI. The mean number of grade ≥2 toxicities in patients with polypharmacy was 9.8 versus 7.7 in those without polypharmacy (adjusted ß = 1.87; standard error, 0.71; p <.01). The mean number of grade ≥3 toxicities in patients with polypharmacy was 2.9 versus 2.2 in patients without polypharmacy (adjusted ß = 0.59; standard error, 0.29; p = .04). Patients with who had one or more major PDI had 59% higher odds of early treatment discontinuation (odds ratio, 1.59; 95% confidence interval, 1.03-2.46; p = .03). CONCLUSIONS: In a cohort of older adults with advanced cancer, polypharmacy and PDIs were associated with an increased risk of adverse treatment outcomes. Providing meaningful screening and interventional tools to optimize medication use may improve treatment-related outcomes in these patients.

Cancer survivorship challenges of rural older adults: a qualitative study.

BACKGROUND: Although research has advanced the field of oncologic geriatrics with survivors to assess their cancer-related needs and devise patient-centered interventions, most of that research has excluded rural populations. This study aimed to understand the survivorship challenges and recommendations in the perspective of rural older adults. METHODS: This was a qualitative study that explored the survivorship challenges and recommendations of rural older adults who have completed curative intent chemotherapy for a solid tumor malignancy in the 12 months prior to enrollment in the present study. RESULTS: Twenty-seven older adult survivors from rural areas completed open-ended semi-structured interviews. The mean age was 73.4 (SD = 5.0). Most participants were non-Hispanic White (96.3%), female (59.3%), married (63.0%), and had up to a high school education (51.9%). Rural older survivors reported a general lack of awareness of survivorship care plans, communication challenges with healthcare team, transportation challenges, financial toxicity, psychological challenges, and diet and physical challenges. Rural older survivors recommend the provision of nutritional advice referral to exercise programs, and social support groups and for their healthcare providers to discuss their survivorship plan with them. CONCLUSIONS: Although study participants reported similar survivorship challenges as urban older adult survivors, additional challenges reported regarding transportation and consideration of farm animals have not been previously reported. Heightened awareness of the survivorship needs of rural older adults may result in better survivorship care for this population.

External Validation of Risk Factors for Unplanned Hospitalization in Older Adults With Advanced Cancer Receiving Chemotherapy.

BACKGROUND: Older adults (age ≥65 years) receiving chemotherapy are at risk for hospitalization. Predictors of unplanned hospitalization among older adults receiving chemotherapy for cancer were recently published using data from a study conducted by the Cancer and Aging Research Group (CARG). Our study aimed to externally validate these predictors in an independent cohort including older adults with advanced cancer receiving chemotherapy. METHODS: This validation cohort included patients (n=369) from the GAP70+ trial usual care arm. Enrolled patients were aged ≥70 years with incurable cancer and were starting a new line of chemotherapy. Previously identified risk factors proposed by the CARG study were ≥3 comorbidities, albumin level <3.5 g/dL, creatinine clearance <60 mL/min, gastrointestinal cancer, ≥5 medications, requiring assistance with activities of daily activities (ADLs), and having someone available to take them to the doctor (ie, presence of social support). The primary outcome was unplanned hospitalization within 3 months of treatment initiation. Multivariable logistic regression was applied including the 7 identified risk factors. Discriminative ability of the fitted model was performed by calculating the area under the receiver operating characteristic (AUC) curve. RESULTS: Mean age of the cohort was 77 years, 45% of patients were women, and 29% experienced unplanned hospitalization within the first 3 months of treatment. The proportions of hospitalized patients with 0-3, 4-5, and 6-7 identified risk factors were 24%, 28%, and 47%, respectively (P=.04). Impaired ADLs (odds ratio, 1.76; 95% CI, 1.04-2.99) and albumin level <3.5 g/dL (odds ratio, 2.23; 95% CI, 1.37-3.62) were significantly associated with increased odds of unplanned hospitalization. The AUC of the model, including the 7 identified risk factors, was 0.65 (95% CI, 0.59-0.71). CONCLUSIONS: The presence of a higher number of risk factors was associated with increased odds of unplanned hospitalization. This association was largely driven by impairment in ADLs and low albumin level. Validated predictors of unplanned hospitalization can help with counseling and shared decision-making with patients and their caregivers. CLINICALTRIALS: gov identifier: NCT02054741.

Evaluating the association of frailty with communication about aging-related concerns between older patients with advanced cancer and their oncologists.

BACKGROUND: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. METHODS: This was a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and impairment on 1 or more GA domains (ClinicalTrials.gov Identifier NCT02107443; principal investigator Supriya G. Mohile). Practice sites were randomized to either the GA-intervention or usual care. Frailty was assessed with a deficit accumulation index (range, 0-1), and patients were stratified as robust (0 to <0.2), prefrail (0.2 to <0.35), or frail (≥0.35). The clinic visit after the GA-intervention was audio-recorded, transcribed, and coded to evaluate the number and quality of conversations about aging-related concerns. Linear mixed models examined differences in the number and quality of conversations within and between arms. All P values were 2-sided. RESULTS: Patients (n = 541) were classified as robust (27%), prefrail (42%), or frail (31%). In the usual care arm, frail patients (vs robust ones) engaged in more aging-related conversations (adjusted mean difference, 1.73; 95% confidence interval [CI], 0.59-2.87), conversations of higher quality (difference, 1.12; 95% CI, 0.24-2.0), and more discussions about evidence-based recommendations (difference, 0.71; 95% CI, 0.04-1.38; all P values ≤ .01). Similarly, in the GA intervention arm, frail patients (vs robust ones) engaged in more aging-related conversations (difference, 2.49; 95% CI, 1.51-3.47), conversations of higher quality (difference, 1.31; 95% CI, 0.56-2.06), and more discussions about evidence-based recommendations (difference, 0.87; 95% CI, 0.32-1.42; all P values ≤ .01). Furthermore, the GA-intervention significantly improved the number and quality of conversations in all patients: robust, prefrail, and frail (all P values ≤ .01). CONCLUSIONS: Patients with higher degrees of frailty and those exposed to the GA-intervention had more and higher quality conversations about aging-related concerns with oncologists. LAY SUMMARY: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. This study conducted a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and 1 or more GA domain impairments. Patients were stratified as robust, prefrail, or frail. The number and quality of conversations about aging-related concerns that occurred during the clinic visit after the GA-intervention were determined. Patients with higher degrees of frailty and those in the GA intervention arm had more and higher quality conversations about aging-related concerns with oncologists.

Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.

BACKGROUND: Older adults with advanced cancer are at a high risk for treatment toxic effects. Geriatric assessment evaluates ageing-related domains and guides management. We examined whether a geriatric assessment intervention can reduce serious toxic effects in older patients with advanced cancer who are receiving high risk treatment (eg, chemotherapy). METHODS: In this cluster-randomised trial, we enrolled patients aged 70 years and older with incurable solid tumours or lymphoma and at least one impaired geriatric assessment domain who were starting a new treatment regimen. 40 community oncology practice clusters across the USA were randomly assigned (1:1) to the intervention (oncologists received a tailored geriatric assessment summary and management recommendations) or usual care (no geriatric assessment summary or management recommendations were provided to oncologists) by means of a computer-generated randomisation table. The primary outcome was the proportion of patients who had any grade 3-5 toxic effect (based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4) over 3 months. Practice staff prospectively captured toxic effects. Masked oncology clinicians reviewed medical records to verify. The study was registered with ClinicalTrials.gov, NCT02054741. FINDINGS: Between July 29, 2014, and March 13, 2019, we enrolled 718 patients. Patients had a mean age of 77·2 years (SD 5·4) and 311 (43%) of 718 participants were female. The mean number of geriatric assessment domain impairments was 4·5 (SD 1·6) and was not significantly different between the study groups. More patients in intervention group compared with the usual care group were Black versus other races (40 [11%] of 349 patients vs 12 [3%] of 369 patients; p<0·0001) and had previous chemotherapy (104 [30%] of 349 patients vs 81 [22%] of 369 patients; p=0·016). A lower proportion of patients in the intervention group had grade 3-5 toxic effects (177 [51%] of 349 patients) compared with the usual care group (263 [71%] of 369 patients; relative risk [RR] 0·74 (95% CI 0·64-0·86; p=0·0001). Patients in the intervention group had fewer falls over 3 months (35 [12%] of 298 patients vs 68 [21%] of 329 patients; adjusted RR 0·58, 95% CI 0·40-0·84; p=0·0035) and had more medications discontinued (mean adjusted difference 0·14, 95% CI 0·03-0·25; p=0·015). INTERPRETATION: A geriatric assessment intervention for older patients with advanced cancer reduced serious toxic effects from cancer treatment. Geriatric assessment with management should be integrated into the clinical care of older patients with advanced cancer and ageing-related conditions. FUNDING: National Cancer Institute.

Risk Factors for Hospitalizations Among Older Adults with Gastrointestinal Cancers.

BACKGROUND: Older adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity-related hospitalization among older adults with GI cancers. PATIENTS AND METHODS: We performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of unplanned hospitalizations during the course of chemotherapy treatment was determined. RESULTS: This analysis included 199 patients aged ≥65 years with a diagnosis of GI cancer (85 colorectal, 51 gastric/esophageal, and 63 pancreatic/hepatobiliary). Sixty-five (32.7%) patients had ≥1 hospitalization. Univariate analysis identified sex (female), cardiac comorbidity, stage IV disease, low serum albumin, cancer type (gastric/esophageal), hearing deficits, and polypharmacy as risk factors for hospitalization. Multivariable analyses found that patients who had cardiac comorbidity (OR 2.48, 95% CI 1.13-5.42) were significantly more likely to be hospitalized. CONCLUSION: Cardiac comorbidity may be a risk factor for hospitalization in older adults with GI cancers receiving chemotherapy. Further studies with larger sample sizes are warranted to examine the relationship between GA measures and hospitalization in this vulnerable population.

Patient, caregiver, and oncologist predictions of quality of life in advanced cancer: Accuracy and associations with end-of-life care and caregiver bereavement.

BACKGROUND: Informed treatment decision-making necessitates accurate prognostication, including predictions about quality of life. AIMS: We examined whether oncologists, patients with advanced cancer, and caregivers accurately predict patients' future quality of life and whether these predictions are prospectively associated with end-of-life care and bereavement. MATERIALS & METHODS: We conducted secondary analyses of clinical trial data. Patients with advanced cancer (n = 156), caregivers (n = 156), and oncologists (n = 38) predicted patient quality of life 3 months into the future. Patients subsequently rated their quality of life 3 months later. Medical record data documented chemotherapy and emergency department (ED)/inpatient visits in the 30 days before death (n = 79 decedents). Caregivers self-reported on depression, anxiety, grief, purpose, and regret 7-months post-mortem. In mixed-effects models, patient, caregiver, and oncologist quality-of-life predictions at study entry were used to predict end-of-life care and caregiver outcomes, controlling for patients' quality of life at 3-month follow-up, demographic and clinical characteristics, and nesting within oncologists. RESULTS: Caregivers (P < 0.0001) and oncologists (P = 0.001) predicted lower quality of life than what patients actually experienced. Among decedents, 24.0% received chemotherapy and 54.5% had an ED/inpatient visit. When caregivers' predictions were more negative, patients were less likely to receive chemotherapy (P = 0.028) or have an ED/inpatient visit (P = 0.033), and caregivers reported worse depression (P = 0.002), anxiety (P = 0.019), and grief (P = 0.028) and less purpose in life (P < 0.001) 7-months post-mortem. CONCLUSION: When caregivers have more negative expectations about patients' quality of life, patients receive less intensive end-of-life care, and caregivers report worse bereavement outcomes.

Patient and caregiver agreement on prognosis estimates for older adults with advanced cancer.

BACKGROUND: Disagreements between patients and caregivers about treatment benefits, care decisions, and patients' health are associated with increased patient depression as well as increased caregiver anxiety, distress, depression, and burden. Understanding the factors associated with disagreement may inform interventions to improve the aforementioned outcomes. METHODS: For this analysis, baseline data were obtained from a cluster-randomized geriatric assessment trial that recruited patients aged ≥70 years who had incurable cancer from community oncology practices (University of Rochester Cancer Center 13070; Supriya G. Mohile, principal investigator). Patient and caregiver dyads were asked to estimate the patient's prognosis. Response options were 0 to 6 months, 7 to 12 months, 1 to 2 years, 2 to 5 years, and >5 years. The dependent variable was categorized as exact agreement (reference), patient-reported longer estimate, or caregiver-reported longer estimate. The authors used generalized estimating equations with multinomial distribution to examine the factors associated with patient-caregiver prognostic estimates. Independent variables were selected using the purposeful selection method. RESULTS: Among 354 dyads (89% of screened patients were enrolled), 26% and 22% of patients and caregivers, respectively, reported a longer estimate. Compared with dyads that were in agreement, patients were more likely to report a longer estimate when they screened positive for polypharmacy (ß = 0.81; P = .001), and caregivers reported greater distress (ß = 0.12; P = .03). Compared with dyads that were in agreement, caregivers were more likely to report a longer estimate when patients screened positive for polypharmacy (ß = 0.82; P = .005) and had lower perceived self-efficacy in interacting with physicians (ß = -0.10; P = .008). CONCLUSIONS: Several patient and caregiver factors were associated with patient-caregiver disagreement about prognostic estimates. Future studies should examine the effects of prognostic disagreement on patient and caregiver outcomes.

Association Between Caregiver-Oncologist Discordance in Patient's Life Expectancy Estimates and Caregiver Perceived Autonomy Support by the Oncologist.

BACKGROUND: Caregiver perceived autonomy support by the oncologist is important for caregiver well-being and may be affected by the patient's survival. We determined the association of caregiver-oncologist discordance in patient's life expectancy estimates with perceived autonomy support over time and whether the association differed by patient survival status. MATERIALS AND METHODS: We used data from a geriatric assessment cluster-randomized trial (URCC 13070) that recruited patients aged at least 70 years with incurable cancer considering or receiving treatment, their caregivers, and their oncologists. At baseline, caregivers and oncologists were asked to estimate patient's life expectancy (0-6 months, 7-12 months, 1-2 years, 2-5 years, and >5 years; any difference in response was considered discordant). At 4-6 weeks, 3 months, and 6 months, caregivers completed the Health Care Climate Questionnaire (HCCQ), which measured perceived autonomy support by the oncologist. Generalized estimating equation modeling was conducted to assess the association of baseline caregiver-oncologist discordance with longitudinal HCCQ scores, stratified by patient 6-month survival status. RESULTS: Discordant life expectancy estimates were present in 72.0% of dyads. In multivariate analyses, caregiver-oncologist discordance in patient's life expectancy estimates was associated with higher caregiver HCCQ scores. In stratified analysis, caregiver-oncologist discordance was associated with lower caregiver HCCQ scores (ß = -3.46; 95% CI, -4.64 to -2.29) among patients who died within 6 months but with higher caregiver HCCQ scores (ß = 1.33; 95% CI, 0.63-2.04) among patients who survived beyond 6 months. CONCLUSION: Interventions aimed at mitigating discordance need to consider its association with caregiver perceived autonomy support and patient's survival in order to better inform caregiver expectations. IMPLICATIONS FOR PRACTICE: Among patients who died within the first 6 months, caregivers who estimated a different length of life for the patient compared with oncologists were more likely to report lower support from the oncologist, whereas the opposite relationship was seen within patients who survived beyond the first 6 months. When designing interventions to improve caregiver understanding of the patient's prognosis, its relationship with caregiver-perceived support and patient's survival needs to be considered.

Caregiver-Oncologist Prognostic Concordance, Caregiver Mastery, and Caregiver Psychological Health and Quality of Life.

BACKGROUND: Caregivers of adults with cancer often report a different understanding of the patient's prognosis than the oncologist. We examine the associations of caregiver-oncologist prognostic concordance with caregiver depressive symptoms, distress, and quality of life (QoL). We also explore whether these relationships differed by caregiver environment mastery, an individual's sense of control, and effectiveness in managing life situations. MATERIALS AND METHODS: We used data from a national geriatric assessment cluster-randomized trial (URCC 13070) that recruited patients aged 70 years and older with incurable cancer considering any line of cancer treatment at community oncology practices, their caregivers, and their oncologists. At enrollment, caregivers and oncologists estimated the patient's prognosis (0-6 months, 7-12 months, 1-2 years, 2-5 years, and >5 years; identical responses were concordant). Caregivers completed the Ryff's environmental mastery at enrollment. At 4-6 weeks, caregivers completed the Patient Health Questionnaire-2 (depressive symptoms), distress thermometer, and 12-Item Short-Form Health Survey (quality of life [QoL]). We used generalized estimating equations in models adjusted for covariates. We then assessed the moderation effect of caregiver mastery. RESULTS: Of 411 caregiver-oncologist dyads (mean age = 66.5 years), 369 provided responses and 28% were concordant. Prognostic concordance was associated with greater caregiver depressive symptoms (ß = 0.30; p = .04) but not distress or QoL. A significant moderation effect for caregiver depressive symptoms was found between concordance and mastery (p = .01). Specifically, among caregivers with low mastery (below median), concordance was associated with greater depressive symptoms (ß = 0.68; p = .003). CONCLUSIONS: Caregiver-oncologist prognostic concordance was associated with caregiver depressive symptoms. We found a novel moderating effect of caregiver mastery on the relationship between concordance and caregiver depressive symptoms. IMPLICATIONS FOR PRACTICE: Caregiver-oncologist prognostic concordance is associated with greater caregiver depressive symptoms, particularly in those with low caregiver mastery. When discussing prognosis with caregivers, physicians should be aware that prognostic understanding may affect caregiver psychological health and should assess their depressive symptoms. In addition, while promoting accurate prognostic understanding, physicians should also identify strengths and build resilience among caregivers.

Association of Polypharmacy and Potentially Inappropriate Medications With Physical Functional Impairments in Older Adults With Cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIMs) are prevalent in older adults with cancer, but their associations with physical function are not often studied. This study examined the associations of polypharmacy and PIMs with physical function in older adults with cancer, and determined the optimal cutoff value for the number of medications most strongly associated with physical functional impairment. METHODS: This cross-sectional analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment. We categorized PIM using 2015 American Geriatrics Society Beers Criteria. Three validated physical function measures were used to assess patient-reported impairments: activities of daily living (ADL) scale, instrumental activities of daily living (IADL) scale, and the Older Americans Resources and Services Physical Health (OARS PH) survey. Optimal cutoff value for number of medications was determined by the Youden index. Separate multivariate logistic regressions were then performed to examine associations of polypharmacy and PIMs with physical function measures. RESULTS: Among 439 patients (mean age, 76.9 years), the Youden index identified ≥8 medications as the optimal cutoff value for polypharmacy; 43% were taking ≥8 medications and 62% were taking ≥1 PIMs. On multivariate analysis, taking ≥8 medications was associated with impairment in ADL (adjusted odds ratio [aOR], 1.64; 95% CI, 1.01-2.58) and OARS PH (aOR, 1.73; 95% CI, 1.01-2.98). PIMs were associated with impairments in IADL (aOR, 1.72; 95% CI, 1.09-2.73) and OARS PH (aOR, 1.97; 95% CI, 1.15-3.37). A cutoff of 5 medications was not associated with any of the physical function measures. CONCLUSIONS: Physical function, an important component of outcomes for older adults with cancer, is cross-sectionally associated with polypharmacy (defined as ≥8 medications) and with PIMs. Future studies should evaluate the association of polypharmacy with functional outcomes in this population in a longitudinal fashion.

Characteristics Associated With Functional Changes During Systemic Cancer Treatments: A Systematic Review Focused on Older Adults.

BACKGROUND: Maintaining functional status is important to older adults with cancer, but data are limited on how systemic treatments affect functional status. We systematically reviewed changes in functional status during systemic cancer treatments and identified characteristics associated with functional decline and improvement. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Register of Controlled Trials for articles examining characteristics associated with functional changes in older adults during systemic cancer treatment published in English between database inception and January 11, 2019 (PROSPERO CRD42019123125). Findings were summarized with descriptive statistics. Study characteristics between older adult-specific and non-older adult-specific studies were compared using the Fisher exact test. RESULTS: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 44 studies, which enrolled >8,400 patients; 39% of studies focused on older adults (1 study enrolled adults aged ≥60 years, 10 enrolled adults aged ≥65 years, and 6 enrolled adults aged ≥70 years). Almost all studies (98%) used patient-reported outcomes to measure functional status; only 20% used physical performance tests. Reporting of functional change was heterogeneous, with 48% reporting change scores. Older adult-specific studies were more likely to analyze functional change dichotomously (29% vs 4%; P=.008). Functional decline ranged widely, from 6% to 90%. The most common patient characteristics associated with functional decline were older age (n=7 studies), worse performance status (n=4), progressive disease status (n=4), pain (n=4), anemia (n=4), and worse nutritional status (n=4). Twelve studies examined functional improvement and identified 11 unique associated characteristics. CONCLUSIONS: Functional decline is increasingly recognized as an important outcome in older adults with cancer, but definitions and analyses are heterogeneous, leading to a wide range of prevalence. To identify patients at highest risk of functional decline during systemic cancer treatments, trials need to routinely analyze functional outcomes and measure characteristics associated with decline (eg, nutrition).

Associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors.

BACKGROUND: Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. METHODS: This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. RESULTS: Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). CONCLUSIONS: Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.

Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Polypharmacy (PP) and potentially inappropriate medications (PIM) are highly prevalent in older adults with cancer. This study systematically reviews the associations of PP and/or PIM with outcomes and, through a meta-analysis, obtains estimates of postoperative outcomes associated with PP in this population. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Register of Clinical Trials using standardized terms for concepts of PP, PIM, and cancer. Eligible studies included cohort studies, cross-sectional studies, meta-analyses, and clinical trials which examined outcomes associated with PP and/or PIM and included older adults with cancer. A random effects model included studies in which definitions of PP were consistent to examine the association of PP with postoperative complications. RESULTS: Forty-seven articles met the inclusion criteria. PP was defined as five or more medications in 57% of the studies. Commonly examined outcomes included chemotherapy toxicities, postoperative complications, functional decline, hospitalization, and overall survival. PP was associated with chemotherapy toxicities (4/9 studies), falls (3/3 studies), functional decline (3/3 studies), and overall survival (2/11 studies). A meta-analysis of four studies indicated an association between PP (≥5 medications) and postoperative complications (overall odds ratio, 1.3; 95% confidence interval [1.3-2.8]). PIM was associated with adverse outcomes in 3 of 11 studies. CONCLUSION: PP is associated with postoperative complications, chemotherapy toxicities, and physical and functional decline. Only three studies showed an association between PIM and outcomes. However, because of inconsistent definitions, heterogeneous populations, and variable study designs, these associations should be further investigated in prospective studies. IMPLICATIONS FOR PRACTICE: Polypharmacy and potentially inappropriate medications (PIM) are prevalent in older adults with cancer. This systematic review summarizes the associations of polypharmacy and PIM with health outcomes in older patients with cancer. Polypharmacy and PIM have been associated with postoperative complications, frailty, falls, medication nonadherence, chemotherapy toxicity, and mortality. These findings emphasize the prognostic importance of careful medication review and identification of PIM by oncology teams. They also underscore the need to develop and test interventions to address polypharmacy and PIM in older patients with cancer, with the goal of improving outcomes in these patients.

Capacity to Provide Geriatric Specialty Care for Older Adults in Community Oncology Practices.

BACKGROUND: American Society of Clinical Oncology guidelines recommend that patients ≥65 years of age starting chemotherapy undergo a geriatric assessment (GA) to inform and guide management; however, little is known about resources available in community oncology practices to implement these guidelines and to facilitate geriatric oncology research. MATERIALS AND METHODS: Oncology practices within the National Cancer Institute Community Oncology Research Program (NCORP) were electronically surveyed in 2017 regarding the availability of specialty providers, supportive services, and practice characteristics, as part of a larger survey of cancer care delivery research capacity. RESULTS: Of the 943 NCORP practices, 504 (54%) responded to the survey, representing 210 practice groups. The median new cancer cases per year ≥65 years of age was 457 (interquartile range 227-939). Of respondents, only 2.0% of practices had a fellowship-trained geriatric oncologist on staff. Geriatricians were available for consultation or comanagement at 37% of sites, and of those, only 13% had availability within the oncology clinic (5% of overall). Practice size of ≥1,000 new adult cancer cases (ages ≥18) per year was associated with higher odds (1.81, confidence interval 1.02-3.23) of geriatrician availability. Other multidisciplinary care professionals that could support GA were variably available onsite: social worker (84%), nurse navigator (81%), pharmacist (77%), dietician (71%), rehabilitative medicine (57%), psychologist (42%), and psychiatrist (37%). CONCLUSION: Only a third of community oncology practices have access to a geriatrician within their group and only 5% of community sites have access within the oncology clinic. Use of primarily self-administered GA tools that direct referrals to available services may be an effective implementation strategy for guideline-based care. IMPLICATIONS FOR PRACTICE: Only a minority of community oncology practices in the U.S. have access to geriatric specialty care. Developing models of care that use patient-reported measures and/or other geriatric screening tools to assess and guide interventions in older adults, rather than geriatric consultations, are likely the most practical methods to improve the care of this vulnerable population.

Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. METHODS: The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2). RESULTS: CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87-2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8-27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2. CONCLUSIONS: These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

Willingness to bear adversity and beliefs about the curability of advanced cancer in older adults.

BACKGROUND: Older patients with advanced cancer who are 100% certain they will be cured pose unique challenges for clinical decision making, but to the authors' knowledge, the prevalence and correlates of absolute certainty about curability (ACC) are unknown. METHODS: Cross-sectional data were collected in a geriatric assessment trial. ACC was assessed by asking patients, "What do you believe are the chances that your cancer will go away and never come back with treatment?" Response options were 100% (coded as ACC), >50%, 50/50, <50%, 0%, and uncertain. The willingness to bear adversity in exchange for longevity was assessed by asking patients to consider trade-offs between survival and 2 clinical outcomes that varied in abstractness: 1) maintaining quality of life (QOL; an abstract outcome); and 2) specific treatment-related toxicities (eg, nausea/vomiting, worsening memory). Logistic regression was used to assess the independent associations between willingness to bear adversity and ACC. RESULTS: Of the 524 patients aged 70 to 96 years, approximately 5.3% reported that there was a 100% chance that their cancer would be cured (ACC). ACC was not found to be significantly associated with willingness to bear treatment-related toxicities, but was more common among patients who were willing to trade QOL for survival (adjusted odds ratio, 4.08; 95% CI, 1.17-14.26). CONCLUSIONS: Patients who were more willing to bear adversity in the form of an abstract state, namely decreased QOL, were more likely to demonstrate ACC. Although conversations regarding prognosis should be conducted with all patients, those who are willing to trade QOL for survival may especially benefit from conversations that focus on values and emotions.

Beliefs About Advanced Cancer Curability in Older Patients, Their Caregivers, and Oncologists.

BACKGROUND: Ensuring older patients with advanced cancer and their oncologists have similar beliefs about curability is important. We investigated discordance in beliefs about curability in patient-oncologist and caregiver-oncologist dyads. MATERIALS AND METHODS: We used baseline data from a cluster randomized trial assessing whether geriatric assessment improves communication and quality of life in older patients with advanced cancer and their caregivers. Patients were aged ≥70 years with incurable cancer from community oncology practices. Patients, caregivers, and oncologists were asked: "What do you believe are the chances the cancer will go away and never come back with treatment?" Options were 100%, >50%, 50/50, <50%, and 0% (5-point scale). Discordance in beliefs about curability was defined as any difference in scale scores (≥3 points were severe). We used multivariate logistic regressions to describe correlates of discordance. RESULTS: Discordance was present in 60% (15% severe) of the 336 patient-oncologist dyads and 52% (16% severe) of the 245 caregiver-oncologist dyads. Discordance was less common in patient-oncologist dyads when oncologists practiced longer (adjusted odds ratio [AOR] 0.90, 95% confidence interval [CI] 0.84-0.97) and more common in non-Hispanic white patients (AOR 5.77, CI 1.90-17.50) and when patients had lung (AOR 1.95, CI 1.29-2.94) or gastrointestinal (AOR 1.55, CI 1.09-2.21) compared with breast cancer. Severe discordance was more common when patients were non-Hispanic white, had lower income, and had impaired social support. Caregiver-oncologist discordance was more common when caregivers were non-Hispanic white (AOR 3.32, CI 1.01-10.94) and reported lower physical health (AOR 0.88, CI 0.78-1.00). Severe discordance was more common when caregivers had lower income and lower anxiety level. CONCLUSION: Discordance in beliefs about curability is common, occasionally severe, and correlated with patient, caregiver, and oncologist characteristics. IMPLICATIONS FOR PRACTICE: Ensuring older patients with advanced cancer and their caregivers have similar beliefs about curability as the oncologist is important. This study investigated discordance in beliefs about curability in patient-oncologist (PO) and caregiver-oncologist (CO) dyads. It found that discordance was present in 60% (15% severe) of PO dyads and 52% (16% severe) of CO dyads, raising serious questions about the process by which patients consent to treatment. This study supports the need for interventions targeted at the oncologist, patient, caregiver, and societal levels to improve the delivery of prognostic information and patients'/caregivers' understanding and acceptance of prognosis.