Development and Evaluation of a Multisource Approach to Extend Mortality Follow-Up for Older Adults With Advanced Cancer Enrolled in Randomized Trials.

PURPOSE: Mortality data can complement primary end points from cancer clinical trials. Yet, identifying deaths after trial completion is challenging, as timely and comprehensive vital status data are unavailable in the United States. We developed and evaluated a multisource approach to capture death data after clinical trial completion. METHODS: Individuals age 70 years and older with incurable solid tumors or lymphoma and ≥1 aging-related condition were enrolled from October 2014 to March 2019 (ClinicalTrials.gov identifier: NCT02107443 and NCT02054741). Participants provided consent to link trial information to external sources. We developed a stepped approach for extended death capture using (1) active trial follow-up up to 1 year, (2) linkage to the National Death Index (NDI), and (3) obituary searches, thus generating a 5-year survival curve. In a random sample of 50 participants who died during trial follow-up, we estimated sensitivity of death data using NDI and obituary sources and computed survival times by data source. RESULTS: The two trials enrolled 1,169 participants; mean age was 76 years; 46% were female; and gastrointestinal cancer (30%) and lung cancer (26%) were the most common cancer types. Across data sources, maximum follow-up was >7 years; 5-year survival was 18%. In total, there were 841 deaths: 603 identified during trial follow-up; 199 from the NDI; and 39 from obituary searches. The sensitivity for death capture was 92% for the NDI and 94% for the obituary searches compared with the trial data, and computed survival times were similar across data sources. CONCLUSION: Extending clinical trial mortality follow-up through linkage with external data sources was feasible and accurate. Future cancer clinical trials should collect necessary consent and patient identifiers for vital status linkages that can enhance understanding of longer-term outcomes.

Primary Treatment Modification and Treatment Tolerability Among Older Chemotherapy Recipients With Advanced Cancer.

Importance: Older adults with advanced cancer are less likely to tolerate treatment with cytotoxic chemotherapy compared with younger patients due to their aging-related conditions. Hence, oncologists sometimes opt to employ primary treatment modifications (deviation from standard of care) during the first cycle of chemotherapy. Objective: To examine the association between primary treatment modification and treatment tolerability in older adults with advanced cancer who were starting new palliative chemotherapy regimens. Design, Setting, and Participants: This cohort study was a secondary analysis of the GAP70+ (Geriatric Assessment Intervention for Reducing Toxicity in Older Patients with Advanced Cancer) trial, which was conducted between July 2014 and March 2019. The GAP70+ trial included patients aged 70 years or older who had advanced (ie, incurable) cancer, had 1 or more geriatric assessment domain impairments, and planned to start a new palliative chemotherapy regimen. Data analysis was conducted in November 2022. Exposures: Receipt of standard-of-care chemotherapy regimens vs primary treatment modification defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials (eg, primary dose reduction, schedule change). Main Outcomes and Measures: Tolerability outcomes were assessed within 3 months of treatment. These outcomes included the following: (1) any grade 3 to 5 toxic effect, according to the National Cancer Institute Common Terminology Criteria for Adverse Events; (2) patient-reported functional decline, defined as the development of worse dependency in activities of daily living using scale scores; and (3) a composite adverse outcome (an end point that combined toxic effects, functional decline, and 6-month overall survival). Multivariable cluster-weighted generalized estimating equation models examined the association between primary treatment modification and outcomes adjusting for covariates. Results: This study included 609 patients with a mean (SD) age of 77.2 (5.2) years; more than half (333 [54.7%]) were men. Race and ethnicity was available for 607 patients: 39 (6.4%) were Black, 539 (88.5%) were non-Hispanic White, and 29 (4.8%) were of other race or ethnicity. Nearly half (281 [46.1%]) received a primary modified treatment regimen. The most common cancer types were gastrointestinal cancer (228 [37.4%]) and lung cancer (174 [28.6%]). In multivariable analysis, primary treatment modification was associated with a reduced risk of grade 3 to 5 toxic effects (relative risk [RR], 0.85 [95% CI, 0.77-0.94]) and functional decline (RR, 0.80 [95% CI, 0.67-0.95]). Patients who received primary treatment modification had 32.0% lower odds of having a worse composite adverse outcome (odds ratio, 0.68 [95% CI, 0.48-0.97]). Conclusions and Relevance: In this cohort study, primary treatment modification was associated with improved tolerability of chemotherapeutic regimens among older adults with advanced cancer and aging-related conditions. These findings may help optimize cancer treatment dosing in older adults with advanced cancer and aging-related conditions.

Factors associated with the evaluation of geriatric assessment (GA) domains by oncology specialists in Mexico.

The use of geriatric assessment (GA) by oncology specialists in Mexico is low. We aimed to explore factors associated with the evaluation of individual GA domains by Mexican oncology specialists. We performed an exploratory analysis of a sequential explanatory mixed-methods study consisting of an online cross-sectional survey of Mexican oncology specialists and follow-up interviews on the use of GA in cancer care. For each GA domain, we performed multivariable logistic regression analyses with the frequency of evaluation of the domains as the dependent variable (dichotomised as never/rarely/sometimes versus most of the time/always). A p-value <0.05 was considered significant. Qualitative data from the interviews were analysed inductively. Of 196 respondents, 62% were male, 50% were surgical oncologists, 51% took care of >10 patients per day and 61.7% had access to a geriatrician. Self-perceived confidence in managing common geriatric conditions was associated with the evaluation of specific GA domains. For instance, self-perceived confidence in managing dementia (OR 2.72; 95% CI 1.42-5.51, p = 0.008) was associated with cognition evaluation, while for evaluation of falls, self-perceived confidence in evaluation of falls (OR 6.31; 95% CI 3.19-12.46, p < 0.001) was significantly associated. Follow-up interviews showed quality and appropriateness of evaluations may not be ideal: in many cases, physicians do not use guideline-recommended tools. For example, evaluation of cognition is commonly performed through non-validated methods which may miss the detection of patients with an impairment in this domain, partly due to limitations in knowledge and time to use recommended tools. In conclusion, self-perceived confidence in evaluating and managing common situations in older adults was associated with the evaluation of GA domains as part of everyday practice in a sample of oncology specialists in Mexico. This analysis supports the use of educational interventions to boost knowledge and confidence regarding the proper use of validated GA tools among oncology specialists.

Modifiable fall risk factors among older adults with advanced cancer: Secondary analysis of a cluster-randomized clinical trial.

INTRODUCTION: Older adults with cancer have unique fall risk factors related to their disease and treatment such as polypharmacy and neurotoxic treatments. In this secondary analysis, we identified modifiable risk factors associated with future falls among older adults with advanced cancers. MATERIALS AND METHODS: Data were from the COACH study (ClinicalTrials.gov: NCT02107443; PI: Mohile). Patients were age ≥ 70, had stage III/IV solid tumor or lymphoma, ≥1 geriatric assessment impairment, and were receiving palliative intent treatment. Falls were self-reported at baseline (in the past six months), four to six weeks, three months, and six months. We generated inverse probability weights to account for mortality-related loss to follow-up and applied these in generalized linear mixed models to estimate incidence rate ratios. RESULTS: Of 541 patients (mean age: 77, standard deviation [SD]: 5.27), 140 (26%) reported prior falls at baseline, and 467 (86%) had falls data for ≥1 follow-up timepoint. Of those, 103 (22%) reported at least one fall during the follow-up period, and 112 (24%) had incomplete follow-up due to death. In fully adjusted models, prior falls and impaired Timed Up and Go score were associated with higher incidence of falls over 6 months. DISCUSSION: We identified several potentially modifiable fall risk factors in older adults with advanced cancers. Future studies should consider ways to integrate fall risk assessment into ongoing cancer care and intervene to reduce falls in this population.

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.

Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update.

PURPOSE: To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy. METHODS: An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022. RESULTS: A total of 26 publications met eligibility criteria and form the evidentiary basis for the update. RECOMMENDATIONS: The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.

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.

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.

Effects of a Geriatric Assessment Intervention on Patient-Reported Symptomatic Toxicity in Older Adults With Advanced Cancer.

PURPOSE: Providing a geriatric assessment (GA) summary with management recommendations to oncologists reduces clinician-rated toxicity in older patients with advanced cancer receiving treatment. This secondary analysis of a national cluster randomized clinical trial (ClinicalTrials.gov identifier: NCT02054741) aims to assess the effects of a GA intervention on symptomatic toxicity measured by Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). METHODS: From 2014 to 2019, the study enrolled patients age ≥ 70 years, with advanced solid tumors or lymphoma and ≥ 1 GA domain impairment, who were initiating a regimen with high prevalence of toxicity. Patients completed PRO-CTCAEs, including the severity of 24 symptoms (11 classified as core symptoms) at enrollment, 4-6 weeks, 3 months, and 6 months. Symptoms were scored as grade ≥ 2 (at least moderate) and grade ≥ 3 (severe/very severe). Symptomatic toxicity was determined by an increase in severity during treatment. A generalized estimating equation model was used to assess the effects of the GA intervention on symptomatic toxicity. RESULTS: Mean age was 77 years (range, 70-96 years), 43% were female, and 88% were White, 59% had GI or lung cancers, and 27% received prior chemotherapy. In 706 patients who provided PRO-CTCAEs at baseline, 86.1% reported at least one moderate symptom and 49.7% reported severe/very severe symptoms at regimen initiation. In 623 patients with follow-up PRO-CTCAE data, compared with usual care, fewer patients in the GA intervention arm reported grade ≥ 2 symptomatic toxicity (overall: 88.9% v 94.8%, P = .035; core symptoms: 83.4% v 91.7%, P = .001). The results for grade ≥ 3 toxicity were comparable but not significant (P > .05). CONCLUSION: In the presence of a high baseline symptom burden, a GA intervention for older patients with advanced cancer reduces patient-reported symptomatic toxicity.

Change in four measures of physical function among older adults during lung cancer treatment: A mixed methods cohort study.

INTRODUCTION: Functional outcomes during non-small cell lung cancer (NSCLC) treatment are critically important to older adults. Yet, data on physical function and which measures best capture functional change remain limited. MATERIALS AND METHODS: This multisite, mixed methods cohort study recruited adults ≥65 years with advanced NSCLC starting systemic treatment (i.e., chemotherapy, immunotherapy, and/or targeted therapy) with non-curative intent. Participants underwent serial geriatric assessments prior to starting treatment and at one, two, four, and six months, which included the Karnofsky Performance Scale (KPS, range: 0-100%), instrumental activities of daily living (IADL, range: 0-14), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Physical Functioning subscale (EORTC QLQ-C30 PF, range: 0-100), and Life-Space Assessment (LSA, range: 0-120). For all measures, higher scores represent better functioning. In a qualitative substudy, 20 patients completed semi-structured interviews prior to starting treatment and at two and six months to explore how treatment affected their daily functioning. We created joint displays for each interview participant that integrated their longitudinal KPS, IADL, EORTC QLQ-C30 PF, and LSA scores with patient quotes describing their function. RESULTS: Among 87 patients, median age was 73 years (range 65-96). Mean pretreatment KPS score was 79% (standard deviation [SD] 13), EORTC QLQ-C30 PF was 69 (SD 23), and LSA was 67 (SD 28); median IADL was 13 (interquartile range [IQR] 10-14). At two months after treatment initiation, 70% of patients experienced functional decline on at least one measure, with only 13% of these patients recovering at six months. At two and six months, decline in LSA was the most common (48% and 35%, respectively). Joint displays revealed heterogeneity in how well each quantitative measure of physical function captured the qualitative patient experience. DISCUSSION: Functional decline during NSCLC treatment is common among older adults. LSA is a useful measure to detect subtle functional decline that may be missed by other measures. Given heterogeneity in how well each quantitative measure captures changes in physical function, there is value to including more than one functional measure in geriatric oncology research studies.

Clinical Trial Enrollment, Ineligibility, and Reasons for Decline in Older vs Younger Patients With Cancer in the National Cancer Institute Community Oncology Research Program.

This cross-sectional study assesses differences in clinical trial participation among older vs younger adults with cancer.

Communication About Fall Risk in Community Oncology Practice: The Role of Geriatric Assessment.

PURPOSE: Falls are a modifiable source of morbidity for older adults with cancer, yet are underassessed in oncology practice. In this secondary analysis of a nationwide cluster-randomized controlled trial, we examined characteristics associated with patient-oncologist conversations about falls, and whether oncologist knowledge of geriatric assessment (GA) resulted in more conversations. METHODS: Eligible patients (ClinicalTrials.gov identifier: NCT02107443) were age ≥ 70 years, had stage III/IV solid tumor or lymphoma, were being treated with noncurative treatment intent, and ≥ 1 GA domain impairment. Patients in both arms underwent GA. At practices randomly assigned to the intervention arm, oncologists were provided a GA summary with management recommendations. In both arms, patients had one clinical encounter audio-recorded, transcribed, and coded to categorize whether a conversation about falls occurred. Generalized linear mixed models adjusted for arm, practice site, and other important covariates were used to generate proportions and odds ratios (ORs) from the full sample. RESULTS: Of 541 patients (intervention N = 293 and usual care N = 248, mean age: 77 years, standard deviation: 5.3), 528 had evaluable audio recordings. More patients had conversations about falls in the intervention versus usual care arm (61.3% v 10.3%, P < .001). Controlling for the intervention and practice site, history of falls (OR, 2.1; 95% CI, 1.3 to 3.6; P = .005) and impaired physical performance (OR, 4.7; 95% CI, 1.7 to 12.8; P = .002) were significantly associated with patient-oncologist conversations about falls. CONCLUSION: GA intervention increased conversations about falls. History of falls and impaired physical performance were associated with patient-oncologist conversations about falls in community oncology practice.

Survive and thrive: Personal stories of persistence and resilience in aging research.

An academic career in aging research is filled with the incredible highs of important discoveries that improve the lives of older adults and repeated lows when papers and grants are rejected or studies are negative. To normalize the experience of setbacks and failures in aging research, we invited three senior investigators to share their journeys of persistence and resilience as they have navigated their research careers. This career development symposium was presented at the 2021 Annual Scientific Meeting of the American Geriatrics Society, which was held virtually. We aimed to connect researchers in aging, especially trainees and junior investigators, through personal stories of persistence and shared strategies to build resilience and respond to setbacks with a growth mindset.

A Geriatric Assessment Intervention to Reduce Treatment Toxicity Among Older Adults With Advanced Lung Cancer: A Subgroup Analysis From a Cluster Randomized Controlled Trial.

Introduction: More older adults die from lung cancer worldwide than breast, prostate, and colorectal cancers combined. Current lung cancer treatments may prolong life, but can also cause considerable treatment-related toxicity. Objective: This study is a secondary analysis of a cluster-randomized clinical trial which evaluated whether providing a geriatric assessment (GA) summary and GA-guided management recommendations can improve grade 3-5 toxicity among older adults with advanced lung cancer. Methods: We analyzed participants aged ≥70 years(y) with stage III & IV (advanced) lung cancer and ≥1 GA domain impairment starting a new cancer treatment with high-risk of toxicity within the National Cancer Institute's Community Oncology Research Program. Community practices were randomized to the intervention arm (oncologists received GA summary & recommendations) versus usual care (UC: no summary or recommendations given). The primary outcome was grade 3-5 toxicity through 3 months post-treatment initiation. Secondary outcomes included 6-month (mo) and 1-year overall survival (OS), treatment modifications, and unplanned hospitalizations. Outcomes were analyzed using generalized linear mixed and Cox proportional hazards models with practice site as a random effect. Trial Registration: NCT02054741. Results & Conclusion: Among 180 participants with advanced lung cancer, the mean age was 76.3y (SD 5.1), 39.4% were female and 82.2% had stage IV disease. The proportion of patients who experienced grade 3-5 toxicity was significantly lower in the intervention arm vs UC (53.1% vs 71.6%, P=0.01). More participants in the intervention arm received lower intensity treatment at cycle 1 (56.3% vs 35.3%; P<0.01). Even with a cycle 1 dose reduction, OS at 6mo and 1 year was not significantly different (adjusted hazard ratio [HR] intervention vs. UC: 6mo HR=0.90, 95% CI: 0.52-1.57, P=0.72; 1 year HR=0.89, 95% CI: 0.58-1.36, P=0.57). Frequent toxicity checks, providing education and counseling materials, and initiating direct communication with the patient's primary care physician were among the most common GA-guided management recommendations. Providing a GA summary and management recommendations can significantly improve tolerability of cancer treatment among older adults with advanced lung cancer.