Association between frailty and overall survival among older adults with hepatocellular carcinoma.

INTRODUCTION: Older adults undergoing cancer treatment often experience more treatment-related toxicities and increased risk of mortality compared to younger patients. The role of frailty among older individuals as a predictor of outcomes has gained growing significance. We evaluated the association between frailty and overall survival (OS) in patients with hepatocellular carcinoma (HCC) ≥60 years. MATERIALS AND METHODS: Older adults ≥60 years with HCC enrolled in a prospective single-institution registry underwent a patient-reported geriatric assessment (GA) covering multiple health domains related to prior to their initial medical oncology appointment. Frailty was measured using a 44-item deficit accumulation frailty index. We categorized patients as robust, pre-frail, and frail using standard cutpoints. The primary outcome was overall survival (OS). Univariable and multivariable models were built to evaluate the association between frailty and OS after adjusting for potential confounders. RESULTS: Total of 116 older adults with HCC with a median age of 67 years were enrolled; 82% male, 27% Black, and 78% with stage III/IV disease. Overall, 19 (16.3%) were robust, 39 (33.6%) pre-frail, and 58 (50.1%) frail. There were 76 patients receiving liver directed therapy. Of these, 13 (17%) were robust, 26 (34%) were pre-frail, and 37 (49%) were frail. Over a median follow up of 0.9 years, 53 patients died. After adjusting for age, stage, etiology, and Child-Pugh class, being frail (vs. robust) was associated with worse OS (hazard ratio (HR) 2.6 [95% CI 1.03-6.56]; p = 0.04). DISCUSSION: Half of the participants in this study were frail, which was independently associated with worse survival in adults ≥60 years of age with HCC. Identification of pre-treatment frailty may allow opportunities to guide treatment decisions and prognostication.

Identification of older adults with Alzheimer's and related dementias among patients newly diagnosed with cancer: A comparison of methodological approaches.

INTRODUCTION: Research efforts to characterize and evaluate care delivery and outcomes for older adults with cancer and comorbid dementia are limited by varied methods used to classify Alzheimer's disease and related dementias (ADRD). The purpose of this study is to evaluate differences in demographic, clinical, and cancer characteristics of people newly diagnosed with cancer and concomitant dementia comparing two common methods to identify ADRD using administrative claims data. MATERIALS AND METHODS: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Our sample included adults aged 66 years and older with a first primary diagnosis of lung or colorectal cancer between 2011 and 2017. For each cancer diagnosis, we constructed analytical cohorts using the Center for Medicare and Medicaid Services' Chronic Condition Warehouse (CCW) flag and the Bynum-Standard one- and three-year algorithms to capture diagnosed ADRD. We estimated ADRD prevalence using the algorithms and compared Bynum and CCW cohorts on demographic, clinical, and cancer characteristics at cancer diagnosis and survival for lung and colorectal cancer separately. RESULTS: Among older adults with lung cancer, ADRD prevalence was 4.7% with the one-year Bynum, 6.5% with the three-year Bynum, and 12.5% using the CCW flag. In the colorectal cohort, ADRD prevalence was 5.6% with the one-year Bynum, 7.6% with the three-year Bynum, and 14.1% with the CCW flag. Demographic characteristics were similar across ADRD cohorts. The Bynum cohorts identified higher proportions of individuals with moderate to severe dementia (13.8% and 11.2% versus 7.1% CCW in lung cancer; 13.1% and 10.6% versus 6.8% CCW in colorectal cancer), higher frailty rates (27.4% and 22.7% versus 15.0% CCW in lung cancer; 26.4% and 22.3% versus 14.8% CCW in colorectal cancer). Median survival was lower for the Bynum cohorts compared to the CCW, regardless of cancer type. DISCUSSION: Findings demonstrate that ADRD prevalence and certain clinical characteristics vary based on dementia ascertainment method and observation period used to classify individuals with ADRD. Considering differences in the cohorts of registry cases generated by the identification method used is essential when interpreting findings related to treatment, utilization, and outcomes within and across cancer cohorts.

Health-related quality of life in older hematological cancer survivors (70+) compared to older general population-A German cancer-register-based cross-sectional comparative study.

OBJECTIVES: The extent of health-related quality of life (HRQOL) impairments in older hematological cancer survivors (HCS) has not been sufficiently studied. We therefore examined HRQOL in older HCS compared to a community sample (CS) and investigated sociodemographic, disease- and treatment-specific, geriatric, and psychosocial factors associated with reduced HRQOL. MATERIALS AND METHODS: In this cancer-register-based cross-sectional comparative study 200 HCS, aged ≥70 years, and 252 persons of an age- and gender-matched CS completed validated questionnaires including the EORTC QLQ-C30 and EORTC QLQ-ELD14. RESULTS: Older HCS reported a reduced HRQOL in the dimensions of global QOL, physical, role, and social functioning (small clinical significance) and higher symptom burden of fatigue, nausea and vomiting, appetite loss, and poorer mobility compared to the CS (fatigue and mobility with medium, the others with small clinical significance). Perceived disease burden of comorbidities, functional disabilities, psychological distress, and depression showed statistical significance for reduced HRQOL in older HCS in multiple linear regression analysis (R2 = .602, p < .001). DISCUSSION: The screening and treatment of functional limitations and individual symptoms and the integration of a geriatric assessment into oncological practice can help to identify supportive care needs, to implement individualized, patient-centered cancer survivorship care programs and to improve older HCS's HRQOL.

Health-related quality of life with comprehensive geriatric assessment guided care versus usual care in older adults with cancer: A systematic review and meta-analysis of randomized trials.

BACKGROUND: To evaluate if comprehensive geriatric assessment (CGA)-guided care improves health-related quality of life (HRQL) in older adults with cancer compared to usual care. METHODS: Relevant randomized controlled trials (RCTs) were identified through biomedical databases. Meta-analyses using DerSimonian-Laird model summarized the difference in the mean change of HRQL scores from baseline across various time points, with evidence certainty assessed by the GRADE tool. Logistic regression via generalized estimating equations analyzed predictors of HRQL improvement. RESULTS: Potential improvement in the global HRQL score by CGA-guided care at 3 months (Cohen's d 0.27, 95 % CI -0.03-0.58, moderate certainty), could not be excluded. Larger RCTs or those mandating CGA before initiating anti-cancer treatment were predictors of improved HRQL. CONCLUSION: The effects of CGA-guided care on HRQL were variable. Larger RCTs and those mandating pre-treatment CGA tended to report improved HRQL.

Outcomes in older adults with metastatic esophageal and gastric carcinoma treated with palliative chemotherapy.

BACKGROUND: The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. MATERIALS AND METHODS: A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. RESULTS: One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. CONCLUSION: Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.

Improving Care for Older Adults with Cancer in Canada: A Call to Action.

Most patients diagnosed with and dying from cancer in Canada are older adults, with aging contributing to the large projected growth in cancer incidence. Older adults with cancer have unique needs, and on a global scale increasing efforts have been made to address recognized gaps in their cancer care. However, in Canada, geriatric oncology remains a new and developing field. There is increasing recognition of the value of geriatric oncology and there is a growing number of healthcare providers interested in developing the field. While there is an increasing number of dedicated programs in geriatric oncology, they remain limited overall. Developing novel methods to delivery geriatric care in the oncology setting and improving visibility is important. Formal incorporation of a geriatric oncology curriculum into training is critical to both improve knowledge and demonstrate its value to healthcare providers. Although a robust group of dedicated researchers exist, increased collaboration is needed to capitalize on existing expertise. Dedicated funding is critical to promoting clinical programs, research, and training new clinicians and leaders in the field. By addressing challenges and capitalizing on opportunities for improvement, Canada can better meet the unique needs of its aging population with cancer and ultimately improve their outcomes.

Assessing a Suitable Radiotherapy Utilisation Benchmark for Older Patients With Head and Neck Cancer.

AIMS: To (i) determine the actual radiotherapy utilization (RTU) stratified by age, (ii) develop an age- and co-morbidity adjusted optimal RTU model and (iii) examine the tolerance and toxicity of treatment of older patients with head and neck cancer. MATERIALS AND METHODS: A retrospective cohort study based on New South Wales Cancer Registry records (2010-2014) linked to radiotherapy data (2010-2015) and admitted patient data (2008-2015) for patients diagnosed with head and neck cancer. We calculated the actual RTU, defined as the proportion of patients who received at least one course of radiotherapy within a year of diagnosis, by age group, including patients aged 80+ years. We also calculated the age and comorbidity-adjusted optimal RTU. For treatment tolerance, the radiotherapy dose for each age group and the completion rate for a seven week 70 Gray (Gy) course of curative intent radiotherapy were computed. The number of emergency department (ED) presentations were used as a surrogate measure of acute treatment toxicity for patients receiving 70 Gy. RESULTS: Of the 5966 patients diagnosed with head and neck cancer, 814 (13.6%) were aged 80+ years. For all age groups, the actual RTU was less than the optimal RTU. The age- and comorbidity-adjusted optimal RTU for patients aged 80+ was 52% (95% CI: 51%-53%), and the actual RTU was 40% (95% CI: 37%-44%). Only 4.4% of patients aged 80+ received 70 Gy, and the completion rate for a 70 Gy course of radiotherapy for these patients was 92%. The ED presentation rate was similar for all age groups. CONCLUSION: The actual RTU was less in the 80+ years patients and across all age groups. Fewer patients in the 80+ group received curative intent schedules compared to the actual RTU rate for younger age groups, despite similar rates of completion of curative intent radiotherapy and acute toxicity.

The performance of metabolomics-based prediction scores for mortality in older patients with solid tumors.

Prognostic information is needed to balance benefits and risks of cancer treatment in older patients. Metabolomics-based scores were previously developed to predict 5- and 10-year mortality (MetaboHealth) and biological age (MetaboAge). This study aims to investigate the association of MetaboHealth and MetaboAge with 1-year mortality in older patients with solid tumors, and to study their predictive value for mortality in addition to established clinical predictors. This prospective cohort study included patients aged ≥ 70 years with a solid malignant tumor, who underwent blood sampling and a geriatric assessment before treatment initiation. The outcome was all-cause 1-year mortality. Of the 192 patients, the median age was 77 years. With each SD increase of MetaboHealth, patients had a 2.32 times increased risk of mortality (HR 2.32, 95% CI 1.59-3.39). With each year increase in MetaboAge, there was a 4% increased risk of mortality (HR 1.04, 1.01-1.07). MetaboHealth and MetaboAge showed an AUC of 0.66 (0.56-0.75) and 0.60 (0.51-0.68) for mortality prediction accuracy, respectively. The AUC of a predictive model containing age, primary tumor site, distant metastasis, comorbidity, and malnutrition was 0.76 (0.68-0.83). Addition of MetaboHealth increased AUC to 0.80 (0.74-0.87) (p = 0.09) and AUC did not change with MetaboAge (0.76 (0.69-0.83) (p = 0.89)). Higher MetaboHealth and MetaboAge scores were associated with 1-year mortality. The addition of MetaboHealth to established clinical predictors only marginally improved mortality prediction in this cohort with various types of tumors. MetaboHealth may potentially improve identification of older patients vulnerable for adverse events, but numbers were too small for definitive conclusions. The TENT study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

Integrative Geriatric Oncology: A Review of Current Practices.

PURPOSE OF REVIEW: This article aims to offer a comprehensive review of optimal integrative medicine practices for geriatric oncology patients. Given the aging population and the global rise in cancer incidence, it is crucial to identify evidence-based modalities and employ an integrated approach to enhance cancer outcomes and quality of life in older adults. RECENT FINDINGS: It has been predicted that 20.5% (6.9 million) of new cancer cases in 2050 will occur in adults over 80 years old.1 The increasing focus on lifestyle factors in healthy aging has shed light on various overlooked areas of significance. Notably, anti-inflammatory diets and the promotion of a healthy gut microbiome have demonstrated significant impacts on overall health outcomes, bolstering the body's innate capacity to combat disease. This review delves into further evidence and extrapolation concerning integrative approaches and their influence on cancer outcomes and older adults quality of life. The complexity and unique nature of cancer in older adults requires a wide range of support from medical providers. Incorporating various integrative techniques as part of cancer treatment and side effect support can improve health outcomes and patient's quality of life. Familiarity with the lifestyle interventions and other topics explored in this review equips healthcare providers to offer tailored and holistic care to geriatric patients navigating cancer.

Outcomes from a single institution cohort of 248 patients with stage I-III esophageal cancer treated with radiotherapy: Comparison of younger and older populations.

Outcomes for patients receiving radiotherapy (RT) for non-metastatic esophageal cancer at a single institution were assessed, as well as the impact of factors including age and intensity modulated RT (IMRT) planning on patient outcomes. A retrospective cohort of patients treated with RT for stage I-III esophageal cancer between 2010 and 2018 was identified. Among 248 identified patients, 28 % identified as older (≥75 years of age). Other than histology, there were no other statistically significant differences in patient and tumour characteristics between the younger and older populations. Treatments varied between the two age groups, with significantly less older patients completing trimodality treatments (17 % vs 58 %). Median overall survival (M-OS) and progression-free survival (M-PFS) were 20 months and 12 months for all patients and 40 months and 26 months for trimodality patients, respectively. In the older patients, the M-OS improved from 13 months for all to 34 months for trimodality patients; and M-PFS from 10 months to 16 months. On multivariate analysis, the use of trimodality therapy showed improved OS (HR 0.26, p < 0.001). In the non-surgical older patient group, significantly better survival was seen in patients who had a heart V30Gy under 46 %. There was no significant difference in M-OS in patients planned with IMRT compared with 3D-conformal RT. Clinical outcomes in the treatment of esophageal cancer vary significantly by treatment approach, with the most favourable results in those receiving trimodality therapy. Among older patients deemed fit after assessment by the multidisciplinary team for trimodality treatments, the M-OS is comparable to the younger patient group.

Clinicians' Perspectives on the Telehealth Serious Illness Care Program for Older Adults With Myeloid Malignancies: Single-Arm Pilot Study.

BACKGROUND: Serious illness conversations may help patients avoid unwanted treatments. We previously piloted the telehealth Serious Illness Care Program (SICP) for older adults with acute myeloid leukemia and myelodysplastic syndrome. OBJECTIVE: In this study, we aimed to understand the experience of the telehealth SICP from the clinician's perspective. METHODS: We studied 10 clinicians who delivered the telehealth SICP to 20 older adults with acute myeloid leukemia or myelodysplastic syndrome. Quantitative outcomes included confidence and acceptability. Confidence was measured using a 22-item survey (range 1-7; a higher score is better). Acceptability was measured using an 11-item survey (5-point Likert scale). Hypothesis testing was performed at α=.10 (2-tailed) due to the pilot nature and small sample size. Clinicians participated in audio-recorded qualitative interviews at the end of the study to discuss their experience. RESULTS: A total of 8 clinicians completed the confidence measure and 7 clinicians completed the acceptability measure. We found a statistically significant increase in overall confidence (mean increase of 0.5, SD 0.6; P=.03). The largest increase in confidence was in helping families with reconciliation and goodbye (mean 1.4, SD 1.5; P=.04). The majority of clinicians agreed that the format was simple (6/7, 86%) and easy to use (6/7, 86%). Clinicians felt that the telehealth SICP was effective in understanding their patients' values about end-of-life care (7/7, 100%). A total of three qualitative themes emerged: (1) the telehealth SICP deepened relationships and renewed trust; (2) each telehealth SICP visit felt unique and personal in a positive way; and (3) uninterrupted, unrushed time optimized the visit experience. CONCLUSIONS: The telehealth SICP increased confidence in having serious illness conversations while deepening patient-clinician relationships. TRIAL REGISTRATION: ClinicalTrials.gov NCT04745676; https://www.clinicaltrials.gov/study/NCT04745676.

Challenges and Solutions for Better Management of Side Effects in Geriatric Oncology.

This editorial discusses the difficulties encountered in the management of cancer among the geriatric population. Although cancer research has made substantial advancements, treatments frequently fail to consider the long-lasting consequences and adverse effects on elderly people. We advocate for enhanced geriatric oncology care, embodying enhanced evaluation techniques, the incorporation of complementary therapies, and the utilisation of wearable technologies for remote surveillance. Additionally, we suggest modifying future clinical trials to take into account the cognitive well-being of senior individuals. Implementing these modifications would greatly enhance cancer treatment for geriatric cancer patients.

Evaluating the Effectiveness of Geriatric-Specific Cancer Rehabilitation Programs on Patient Health Outcomes.

OBJECTIVE: This study evaluated a specialized rehabilitation program's impact on senior cancer patients' quality of life. METHODS: one hundred and thirty patients aged ≥65 years with various cancer types undergoing/recovering from treatment were enrolled in oncology clinics in Al-Ahsa, Saudi Arabia. The intervention arm (n=65) participated in a tailored geriatric cancer rehabilitation program. The control group (n=65) received standard oncology care. The Functional Assessment of Cancer Therapy-General (FACT-G) tool assessed the quality of life across physical, social, emotional, and functional domains. T-tests and multivariate regression analyses compared outcomes. RESULT: Total FACT-G scores showed a significantly higher quality of life for the geriatric cancer rehabilitation group versus standard care. Rehabilitation patients also demonstrated meaningful improvements across physical, social, and functional subscales. Rehabilitation involvement was the most predictive factor for optimized outcomes. CONCLUSION: Specialized geriatric cancer rehabilitation meaningfully improved several quality of life domains in older patients over standard care. Despite persistent barriers, rehabilitation programming optimized older cancer patients' physical and psychosocial health. Oncology and geriatrics must collaborate to ensure evidence-based rehabilitation access meets older cohorts' unique needs.

Barriers to participation in clinical trials of rural older adult cancer survivors: A qualitative study.

BACKGROUND: Currently, 64% of cancer survivors are aged 65+. Older cancer survivors have unique complications after chemotherapy and are often excluded from cancer clinical trials. Although there is research on barriers to clinical trial participation of older adult cancer survivors, to date no research has explored barriers to clinical trial participation unique to rural older adult cancer survivors. METHODS: This study is a secondary qualitative analysis from a study exploring survivorship challenges of rural older adults. Eligible participants were rural residents over age 65 who have completed curative-intent chemotherapy in the past 12 months. Participants (n = 27) completed open-ended semi-structured interviews that included questions on barriers to clinical trial participation. Transcripts were coded independently by two coders using thematic analysis. We have adhered to the standards for reporting qualitative research. FINDINGS: Participants reported a variety of barriers that included limited knowledge and fear about clinical trials, transportation challenges, their physicians not informing them of clinical trials, and thinking they are too old to participate in clinical trials. However, participants also reported facilitators to participating in clinical trials, including acknowledging benefits to their own health and society, and understanding the importance of clinical trials. CONCLUSION: Rural older cancer survivors face numerous interpersonal, intrapersonal, and organizational barriers to clinical trial participation. Aging- and location-sensitive interventions that focus on patients, their caregivers, and health care providers may lead to improved participation of rural older adult survivors into clinical trials.

Adoption of robot-assisted radical nephroureterectomy permits a minimally invasive option for management of upper tract urothelial carcinoma in geriatric patients: comparison with non-geriatric patients with intermediate-term oncologic follow-up.

To assess the oncologic efficacy and safety of robot-assisted approach to radical nephroureterectomy (RARNU) in geriatric versus younger patients with upper tract urothelial carcinoma (UTUC). A single-center, retrospective cohort study was conducted from 2009 to 2022 of 145 patients (two cohorts: < 75 and ≥ 75 years old) with non-metastatic UTUC who underwent RARNU. Primary endpoint was UTUC-related recurrence of disease during surveillance (bladder-specific and metastatic). Safety was assessed according to 30-day, modified Clavien-Dindo (CD) classifications (Major: C.D. III-V). Survival estimates were performed using Kaplan-Meier method. There were 89 patients < 75 years (median 65 years) and 56 patients ≥ 75 years (median 81 years). Comparing the young versus geriatric cohorts: median follow-up 38 vs 24 months (p = 0.03, respectively) with similar 3-year bladder-specific recurrence survival (60% vs 67%, HR 0.70, 95% CI [0.35, 1.40], p = 0.31) and metastasis-free survival (79% vs 70%, HR 0.71, 95% CI [0.30, 1.70], p = 0.44). Expectedly, the younger cohort had a significant deviation in overall survival compared to the geriatric cohort at 1-year (89% vs 76%) and 3-years (72% vs 41%; HR 3.29, 95% CI [1.88, 5.78], p < 0.01). The 30-day major (1% vs 0) and minor complications (8% vs 14%, p = 0.87). Limitations include retrospective study design of a high-volume, single-surgeon experience. Compared to younger patients with UTUC, geriatric patients undergoing RARNU have similar oncologic outcomes at intermediate-term follow-up with no increased risk of 30-day perioperative complications. Thus, age alone should not be used to disqualify patients from definitive surgical management of UTUC with RARNU.

CML in the very elderly: the impact of comorbidities and TKI selection in a real-life multicenter study.

Tyrosine kinase inhibitors (TKIs) have greatly improved chronic myeloid leukemia (CML) treatments, with survival rates close to the general population. Yet, for the very elderly, robust data remains limited. This study focused on assessing comorbidities, treatment approaches, responses, and survival for elderly CML patients. Our study was conducted on 123 elderly (≥ 75 years) CML patients across four centers in Israel and Moffitt Cancer Center, USA. The median age at diagnosis was 79.1 years, with 44.7% being octogenarians. Comorbidities were very common; cardiovascular risk factors (60%), cardiovascular diseases (42%), with a median age-adjusted Charlson Comorbidity Index (aaCCI) of 5. Imatinib was the leading first-line therapy (69%), while the use of second-generation TKIs increased post-2010. Most patients achieved a major molecular response (MMR, 66.7%), and half achieved a deep molecular response (DMR, 50.4%). Over half (52.8%) of patients moved to second-line, and nearly a quarter (23.5%) to third-line treatments, primarily due to intolerance. Overall survival (OS) was notably longer in patients with an aaCCI score below 5, and in patients who attained DMR. Contrary to expectations, the Israeli cohort showed a shorter actual life expectancy than projected, suggesting a larger impact of CML on elderly survival. In summary, imatinib remains the main initial treatment, but second-generation TKIs are on the rise among elderly CML patients. Outcomes in elderly CML patients depend on comorbidities, TKI type, response, and age, underscoring the need for personalized therapy and additional research on TKI effectiveness and safety.

Frailty and Cancer Prognosis.

PURPOSE OF REVIEW: This review aims to summarize the current evidence regarding the prognostic role of frailty in older patients diagnosed with cancer and to explore the evidence regarding its prognostic implications in cancer survivors. RECENT FINDINGS: Frailty has been consistently associated with mortality/overall survival, postoperative complications, short- and long-term postoperative mortality, length of stay, among other adverse health-related outcomes in several oncological contexts. The possible association between frailty and treatment toxicity has been less explored, however most studies suggest frailty is a predictor of treatment induced toxicity. In addition, in cancer survivors, frailty is a risk factor for cardiovascular disease, incident type 2 diabetes mellitus, mortality, altered cognitive performance and increased symptom severity. Due to its usefulness in establishing prognosis and informing treatment decision making, it is expected that frailty screening and assessment will continue to gain popularity as part of the pretreatment evaluation of older patients with cancer.

Skeletal muscle density performance for screening frailty in older adults with cancer and the impact of diabetes: The CARE Registry.

INTRODUCTION: Skeletal muscle density (SMD) measurements from imaging scans identify myosteatosis and could screen patients for geriatric assessment. We assessed SMD performance as a screening tool to identify older adults with cancer likely to be frail and who could benefit from in-depth assessment; we compared performance by sex and diabetes status. MATERIALS AND METHODS: We analyzed patients in the Cancer & Aging Resilience Evaluation (CARE) Registry. Frailty and diabetes were captured using a patient-reported geriatric assessment (CARE tool). Frailty was defined using CARE frailty index (CARE-FI) based on principles of deficit accumulation. SMD was calculated from computed tomography scans (L3 vertebrae). Analyses were conducted by sex and diabetes status. Scatterplots and linear regression described crude associations between SMD and frailty score. Classification performance (frail vs. non-frail) was analyzed with (1) area under the receiver operating characteristic curves (AUC) and confidence intervals (CIs); and (2) sensitivity/specificity for sex-specific SMD quartile cut-offs (Q1, median, Q3). Performance was compared between patients with and without diabetes using differences and estimated CIs (2000 bootstrap replicates). We additionally calculated positive and negative likelihood ratios (LR+, LR-). RESULTS: The analytic cohort included 872 patients (39% female, median age 68 years, 27% with diabetes) with predominately stage III/IV gastrointestinal cancer; >60% planning to initiate first-line chemotherapy. SMD was negatively associated with frailty score; models were best fit in male patients with diabetes. AUC estimates for female (range: 0.58-0.62) and male (0.58-0.68) patients were low. Q3 cut-offs had high sensitivity (range: 0.76-0.89), but poor specificity (0.25-0.34). Diabetes did not impact estimates for female patients. Male patients with diabetes had greater sensitivity estimates compared to those without (sensitivity differences: 0.23 [0.07, 0.38], 0.08 [-0.07, 0.24], and 0.11 [0.00, 0.22] for Q1, median, Q3, respectively). LR estimates were most notable for male patients with diabetes (LR+ = 2.92, Q1 cut-off; LR- = 0.46, Q3 cut-off). DISCUSSION: Using SMD alone to screen older patients for geriatric assessment requires improvement. High-sensitivity cut-off points could miss 11-24% of patients with frailty, and many non-frail patients may be flagged. Screening with SMD is practical but work is needed to understand clinical andresource impacts of different cut-off points. Future research should evaluate performance with additional clinical data and in subgroups.