Geriatric assessment for the practicing clinician: The why, what, and how.

Older adults with cancer heterogeneously experience health care, treatment, and symptoms. Geriatric assessment (GA) offers a comprehensive evaluation of an older individual's health status and can predict cancer-related outcomes in individuals with solid tumors and those with hematologic malignancies. In the last decade, randomized controlled trials have demonstrated the benefits of GA and GA management (GAM), which uses GA information to provide tailored intervention strategies to address GA impairments (e.g., implementing physical therapy for impaired physical function). Multiple phase 3 clinical trials in older adults with solid tumors and hematologic malignancies have demonstrated that GAM improves treatment completion, quality of life, communication, and advance care planning while reducing treatment-related toxicity, falls, and polypharmacy. Nonetheless, implementation and uptake of GAM remain challenging. Various strategies have been proposed, including the use of GA screening tools, to identify patients most likely to benefit from GAM, the systematic engagement of the oncology workforce in the delivery of GAM, and the integration of technologies like telemedicine and mobile health to enhance the availability of GA and GAM interventions. Health inequities in minoritized groups persist, and systematic GA implementation has the potential to capture social determinants of health that are relevant to equitable care. Caregivers play an important role in cancer care and experience burden themselves. GA can guide dyadic supportive care interventions, ultimately helping both patients and caregivers achieve optimal health.

Systemic inflammation and changes in physical well-being in patients with breast cancer: a longitudinal study in community oncology settings.

BACKGROUND: Chemotherapy adversely affects physical well-being and inflammation may be related to changes in physical well-being. We evaluated the association of systemic inflammation with changes in physical well-being. METHODS: In a prospective study of 580 patients with stages I-III breast cancer we assessed immune cell counts, neutrophil:lymphocyte ratio (NLR), lymphocyte:monocyte ratio (LMR), and platelet:lymphocyte ratio (PLR) within 7 days before chemotherapy (pre-chemotherapy). Physical well-being was assessed using the Functional Assessment of Cancer Therapy: General-Physical Well-being subscale (FACT-PWB) pre-chemotherapy and 1 month and 6 months post-chemotherapy. Clinically meaningful decline in physical well-being was determined as decreasing FACT-PWB by more than one point from pre-chemotherapy level, and non-resilience defined as having decline post-chemotherapy and not returning to within one-point of pre-chemotherapy FACT-PWB by 6 months post-chemotherapy. Multivariable logistic regressions examined the association between inflammation and changes in physical well-being, adjusting for sociodemographic and clinical characteristics. RESULTS: Fifty-nine percent (310/529) and 36% (178/501) of participants had physical well-being decline post-chemotherapy and 6 months post-chemotherapy, respectively. Fifty percent (147/294) were non-resilient. Low NLR and PLR were associated with 1.78 (P = .01) and 1.66 (P = .02) fold greater odds of having a decline in physical well-being 6 months post-chemotherapy compared to those with high NLR and PLR, respectively. Low NLR and PLR were associated with 1.92 (P = .02) and 2.09 (P = 0.01) fold greater odds of being non-resilient 6 months post-chemotherapy compared to those with high NLR and PLR, respectively. CONCLUSION: Low NLR and PLR were associated with chemotherapy-induced changes in physical well-being independent of sociodemographic and clinical risk factors.

Recruitment of informal caregivers into community oncology research studies: results from the 2022 Landscape Assessment.

Understanding the experiences of community oncology practices in recruiting informal (unpaid/family) caregivers into research studies can inform strategies to improve caregiver enrollment. We used data from the 2022 National Cancer Institute Community Oncology Research Program (NCORP) Landscape Assessment to describe the experience of recruiting informal caregivers for research studies in community oncology practices. Among 258 practice groups, only one-third (30%, 78/258) reported prior experience recruiting informal caregivers for research studies. In multivariable logistic analyses, having a greater number of oncology providers (increase per 10 providers, adjusted odds ratio [AOR] 1.16, 95% CI 1.03-1.31) and having advanced practice providers (APPs) involved in research (AOR 2.17, 95% CI 1.05-4.48) were significantly associated with prior experience recruiting caregivers. In conclusion, many community oncology practices lack caregiver recruitment experience and may benefit from education, integration of APPs/caregiver stakeholders in research infrastructure, and/or other strategies to improve caregiver recruitment.

Communication between Caregivers of Adults with Cancer and Healthcare Professionals: a Review of Communication Experiences, Associated Factors, Outcomes, and Interventions.

PURPOSE OF REVIEW: Family/unpaid caregivers play an important role in cancer care. This review aims to summarize caregiver communication experiences with healthcare professionals (HCPs). RECENT FINDINGS: The Caregiver-Centered Communication model defines five core functions that HCPs should achieve when interacting with caregivers, including fostering relationships, exchanging information, recognizing and responding to caregiver emotions, aiding in decision making, and assisting in patient care management. The literature shows that caregivers have both positive and negative communication experiences with HCPs with respect to these five core functions. Factors at the caregiver (e.g., demographic characteristics, information sources, caregiving duration, health status), patient (e.g., demographic and clinical characteristics), and HCP levels (e.g., time constraints in clinical settings, communication skills) are associated with caregiver-HCP communication quality. Studies further show that these communication experiences may affect caregiver outcomes, including quality of life, mental health, resilience, and satisfaction with cancer care. Moreover, poor quality caregiver-HCP communication is associated with patient readmission to the hospital and unmet care needs. Interventions for caregivers or patient-caregiver dyads have been shown to enhance caregiver confidence and increase their engagement in communication with HCPs. Interventions for HCPs have shown efficacy in improving their communication skills, particularly in involving caregivers in decision-making discussions. Given time constraints during medical visits, we suggest conducting a caregiver assessment by navigators prior to visits to understand their communication needs. Additionally, reimbursing HCPs for time spent communicating with caregivers during visits could be beneficial. More research is needed to better understand how to enhance caregiver-HCP communication quality.

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

PURPOSE: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. METHODS: Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. RESULTS: The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: - 7.9 ± 5.7, effect size [ES] = - 0.9 at mid-intervention; - 4.8 ± 7.3, ES = - 0.5 at post-intervention), CIPN signs (ES = - 1.0 and - 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2 = 40-60%) and higher functional connectivity within the salience network (R2 = 20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). CONCLUSION: Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. TRIAL REGISTRATION: Registered Jan 2017 on ClinicalTrials.gov as NCT03021174.

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.

A Systematic Review of Decision Aids in Hematologic Malignancies: What Are Currently Available and What Are We Missing?

BACKGROUND: Patient decision aids (PDAs) are tools designed to facilitate decision-making. In this systematic review, we summarized existing studies on the development and evaluation of PDAs for patients with hematologic malignancies. PATIENTS AND METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for articles in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. We included studies, abstracts, and clinical trial protocols available in English involving PDAs for patients age ≥18 diagnosed with a hematologic malignancy and/or their caregivers. Data were summarized using descriptive statistics. RESULTS: Of the 5281 titles/abstracts screened, 15 were included: 1 protocol, 7 abstracts, and 7 full-texts. Six were PDA developmental studies, 6 were pilot studies, and 3 were randomized trials. PDA formats included electronic with web content, videos, and/or audio, questionnaires, bedside instruments, and a combination of various formats. Average participant age ranged from 36.0 to 62.4 years. Patients and caregivers identified efficacy, adverse effects, cost, and quality of life as important decision-making factors. PDAs were associated with increased knowledge and patient satisfaction as well as decreased decisional conflict and attitudinal barriers. Research on PDAs for adult patients with hematologic malignancies and their caregivers is limited. Among the studies, PDAs appear to support patients in shared decision-making. CONCLUSION: While current literature examining the use of PDAs for adults with hematologic malignancies is limited, the positive impact of PDAs on shared decision-making and patient outcomes warrants additional research in this field.

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.

Effect of Yoga and Mediational Influence of Fatigue on Walking, Physical Activity, and Quality of Life Among Cancer Survivors.

BACKGROUND: Cancer-related fatigue (CRF) negatively affects survivors' walking, engagement in physical activity (PA), and quality of life (QoL). Yoga is an effective therapy for treating CRF; however, evidence from large clinical trials regarding how reducing CRF through yoga influences CRF's interference with survivors' walking, engagement in PA, and QoL is not available. We examined the effects of yoga and the mediational influence of CRF on CRF's interference with walking, PA, and QoL among cancer survivors in a multicenter phase III randomized controlled trial. PATIENTS AND METHODS: Cancer survivors (n=410) with insomnia 2 to 24 months posttreatment were randomized to a 4-week yoga intervention-Yoga for Cancer Survivors (YOCAS)-or standard care. A symptom inventory was used to assess how much CRF interfered with survivors' walking, PA, and QoL. The Multidimensional Fatigue Symptom Inventory-Short Form was used to assess CRF. Two-tailed t tests and analyses of covariance were used to examine within-group and between-group differences. Path analysis was used to evaluate mediational relationships between CRF and changes in CRF's interference with walking, PA, and QoL among survivors. RESULTS: Compared with standard care controls, YOCAS participants reported significant improvements in CRF's interference with walking, PA, and QoL at postintervention (all effect size = -0.33; all P≤.05). Improvements in CRF resulting from yoga accounted for significant proportions of the improvements in walking (44%), PA (53%), and QoL (45%; all P≤.05). CONCLUSIONS: A significant proportion (44%-53%) of the YOCAS effect on CRF's interference with walking, PA, and QoL was due to improvements in CRF among cancer survivors. Yoga should be introduced and included as a treatment option for survivors experiencing fatigue. By reducing fatigue, survivors further improve their walking, engagement in PA, and QoL.

Chemotherapy-related symptoms and exercise adherence in older patients with myeloid neoplasms.

PURPOSE: Exercise may ameliorate treatment-related symptoms, but older adults have lower exercise adherence compared to their younger counterparts due to treatment-related symptoms. METHODS: We recruited older patients with myeloid neoplasms receiving chemotherapy to a pilot study of a mobile health exercise intervention. Participants entered their steps and resistance data into the app daily, and symptom data twice a week, over an 8-12 week period. In this proof-of-concept analysis, we used a linear mixed-effects model to assess the association of symptoms from the previous week with exercise adherence in the current week among older adults with myeloid neoplasms. RESULTS: Mean age was 74.3 (SD = 5.0) years (N = 7). At baseline, patients on average walked 2564 daily steps (SD = 1816), which increased to 2967 (SD = 3448) post-intervention. Patients on average performed 3.5 (SD = 2.6) days of resistance training weekly, with mean duration of 21.5 min (SD = 11.6) and rated perceived exertion of 3.68 (SD = 1.78) on a 0-10 scale. Lower average steps in the current week was associated with greater interference with daily activities from pain (ß = - 203.13, p = 0.05), memory (ß = - 492.29, p = 0.09), numbness (ß = - 353.57, p = 0.07), and sadness (ß = - 403.03, p = 0.09) in the previous week. Similarly, lower average resistance minutes in the current week were associated with greater pain, sadness, and anxiety in the previous week. CONCLUSIONS: We found that greater pain, sadness, and anxiety were associated with lower exercise adherence. Symptom monitoring and management in older adults with myeloid neoplasms receiving chemotherapy can promote exercise adherence and in turn improve symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04035499. Registered 7/29/2019.

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.

The shared uncertainty experience of older adults with advanced cancer and their caregivers.

OBJECTIVE: One primary source of psychological distress in patients with cancer and their caregivers is uncertainty. However, the uncertainty trajectory and its relationship between older adults with advanced cancer and their caregivers have rarely been examined. This study describes the uncertainty trajectory in patient-caregiver dyads, explores the effect of geriatric assessment (GA) intervention on trajectory, and examines the interdependent relationship of uncertainty. METHODS: This secondary analysis used longitudinal data from a national cluster-randomized controlled trial examining a GA intervention compared to usual care. Participants completed the modified 9-item Mishel Uncertainty in Illness Scale at enrollment, 4-6 weeks, 3 months, and 6 months. The dyadic growth model and cross-lagged actor-partner interdependence model were used. RESULTS: A total of 397 dyads (patient age M = 76.81 ± SD5.43; caregiver age M = 66.69 ± SD12.52) were included. Both had a trend of decreased uncertainty over time (b = -0.16, p < 0.01). There was a greater decrease in uncertainty among caregivers in the GA group than those in the usual care group (b = -0.46, p = 0.02). For both patients and caregivers, their past uncertainty was a significant predictor of their own current uncertainty (i.e., actor effect, p < 0.01). The individual's past uncertainty was a significant predictor of the other dyad member's current uncertainty (i.e., partner effect, p < 0.05), indicating an interdependent relationship between patient and caregiver uncertainty over time. CONCLUSIONS: Findings suggest patient and caregiver function as a unit with uncertainty levels affecting each other. Future interventions could build on GA to address uncertainty for older patients with advanced cancer and caregivers.

How Genetics Can Drive Initial Therapy Choices for Older Patients with Acute Myeloid Leukemia.

OPINION STATEMENT: Treatment of older adults with acute myeloid leukemia (AML) is challenging. Therapy decisions must be guided by multiple factors including aging-related conditions (e.g., comorbidities, functional impairment), therapy benefits and risks, patient preferences, and disease characteristics. Balancing these factors requires understanding the unique, and frequently higher-risk cytogenetic and molecular characteristics of AML in older adult populations, which should caution providers not to reduce therapy intensity on the basis of age alone. Instead, geriatric assessments should be employed to determine fitness for therapy. Treatment options in AML are increasingly targeted to specific mutations or recognized to have differential benefits on the basis of genomics, and representation of older adults and geriatric outcome reporting in clinical trials is improving. Additionally, newer studies have begun to explore personalized therapy strategies on the basis of initial genetic testing. Review and refinement of practice guidelines for older patients on the basis of these advances is needed and is anticipated to remain an important topic in ongoing hematology/oncology clinical education.

The longitudinal relationship between immune cell profiles and frailty in patients with breast cancer receiving chemotherapy.

BACKGROUND: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood. METHODS: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n = 581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time points. Separate linear regressions were used to evaluate the associations of (1) cell counts at T1 with frailty at T1, T2, and T3 and (2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time point. RESULTS: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p < 0.01) and returned to T1 levels by the T3 time point (1.3 vs 1.3; p = 0.85). At the T1 time point, there was a positive association between cellular markers of inflammation and frailty: WBC (ß = 0.04; p < 0.05), neutrophils (ß = 0.04; p < 0.05), and NLR (ß = 0.04; p < 0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: ß = 0.02, p < 0.05; neutrophils: ß = 0.03, p < 0.05; NLR: ß = 0.03; p < 0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy. CONCLUSIONS: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01382082.

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.

Longitudinal study of inflammatory, behavioral, clinical, and psychosocial risk factors for chemotherapy-induced peripheral neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect of taxane and platinum chemotherapy for breast cancer. Clinicians cannot accurately predict CIPN severity partly because its pathophysiology is poorly understood. Although inflammation may play a role in CIPN, there are limited human studies. Here, we identified the strongest predictors of CIPN using variables measured before taxane- or platinum-based chemotherapy, including serum inflammatory markers. METHODS: 116 sedentary women with breast cancer (mean age 55 years) rated (1) numbness and tingling and (2) hot/coldness in hands/feet on 0-10 scales before and after 6 weeks of taxane- or platinum-based chemotherapy. A sub-study was added to collect cytokine data in the final 55 patients. We examined all linear models to predict CIPN severity at 6 weeks using pre-chemotherapy assessments of inflammatory, behavioral, clinical, and psychosocial factors. The final model was selected via goodness of fit. RESULTS: The strongest pre-chemotherapy predictors of numbness and tingling were worse fatigue/anxiety/depression (explaining 27% of variance), older age (9%), and baseline neuropathy (5%). The strongest predictors of hot/coldness in hands/feet were worse baseline neuropathy (11%) and fatigue/anxiety/depression (6%). Inflammation was a risk for CIPN, per more pro-inflammatory IFN-γ (12%) and IL-1ß (6%) and less anti-inflammatory IL-10 (6%) predicting numbness/tingling and more IFN-γ (17%) and less IL-10 (9%) predicting hot/coldness in hands/feet. CONCLUSIONS: The strongest pre-chemotherapy predictors of CIPN included worse fatigue/anxiety/depression and baseline neuropathy. A pro-inflammatory state also predicted CIPN. Because this is an exploratory study, these results suggest specific outcomes (e.g., IL-1ß) and effect size estimates for designing replication and extension studies. CLINICAL TRIAL REGISTRATION: NCT00924651.

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).