Kirsten A. Nyrop

Geriatric Assessment-Identified Deficits in Older Cancer Patients With Normal Performance Status

BACKGROUND We investigated whether a brief geriatric assessment (GA) would identify important patient deficits that could affect treatment tolerance and care outcomes within a sample of older cancer patients rated as functionally normal (80%-100%) on the Karnofsky performance status (KPS) scale. METHODS Cancer patients aged ≥65 years were assessed using a brief GA that included both professionally and patient-scored KPS and measures of comorbidity, polypharmacy, cognition, function, nutrition, and psychosocial status. Data were analyzed using descriptive statistics and multivariable logistic regression. RESULTS The sample included 984 patients: mean age was 73 years (range: 65-99 years), 74% were female, and 89% were white. GA was conducted before (23%), during (41%), or after (36%) treatment. Overall, 54% had a breast cancer diagnosis (n = 528), and 46% (n = 456) had cancers at other sites. Moreover, 81% of participants (n = 796) had both professionally and self-rated KPS ≥80, defined as functionally normal, and those patients are the focus of analysis. In this subsample, 550 (69%) had at least 1 GA-identified deficit, 222 (28%) had 1 deficit, 140 (18%) had 2 deficits, and 188 (24%) had ≥3 deficits. Specifically, 43% reported taking ≥9 medications daily, 28% had decreased social activity, 25% had ≥4 comorbidities, 23% had ≥1 impairment in instrumental activities of daily living, 18% had a Timed Up and Go time ≥14 seconds, 18% had ≥5% unintentional weight loss, and 12% had a Mental Health Index score ≤76. CONCLUSION Within this sample of older cancer patients who were rated as functionally normal by KPS, GA identified important deficits that could affect treatment tolerance and outcomes.

Skeletal Muscle Measures as Predictors of Toxicity, Hospitalization, and Survival in Patients with Metastatic Breast Cancer Receiving Taxane Based Chemotherapy

Purpose: Severe skeletal muscle (SM) loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased toxicity. This study investigates SM measures in metastatic breast cancer (MBC) patients receiving first-line taxane-based chemotherapy and evaluates associations with treatment toxicity and other outcomes. Experimental Design: Using computerized tomography (CT) images taken for the evaluation of disease burden, skeletal muscle area (SMA), and density (SMD) were measured at the third lumbar vertebrae. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) ≤ 41. Skeletal muscle gauge (SMG) was created by multiplying SMI × SMD. Fisher exact tests, t tests, the Kaplan–Meier method, and Cox regression modeling were used. Results: MBC patients (N = 40), median age 55 (range, 34–80), 58% sarcopenic, median SMG 1296 AU (SD, 522). Grade 3–4 toxicity was found in 57% of sarcopenic versus 18% of non-sarcopenic patients (P = 0.02). Toxicity-related hospitalizations were also higher in sarcopenic patients (39% vs. 0%, P = 0.005) as were any adverse events—defined as any grade 3–4 toxicities, hospitalizations, dose reductions, or dose delay—(74% vs. 35%, P = 0.02). Low SMG was associated with grade 3–4 toxicity (P = 0.04), hospitalization (P = 0.01), and time to treatment failure (for progression or toxicity; P = 0.03). Low SMG had a borderline significant association with any adverse event (P = 0.06) and overall survival (P = 0.07). Conclusions: SM measures are associated with toxicity outcomes and survival in MBC patients receiving first-line taxane-based chemotherapy. Further studies are needed to explore how routinely obtained CT scans can be used to individualize dosing and improve treatment planning. Clin Cancer Res; 23(3); 658–65. ©2016 AACR.

Safety and Tolerability of PD‐1/PD‐L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta‐Analysis

BACKGROUND Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. METHODS PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. RESULTS A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. CONCLUSION PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer.

Feasibility and promise of a 6-week program to encourage physical activity and reduce joint symptoms among elderly breast cancer survivors on aromatase inhibitor therapy.

BACKGROUND National guidelines suggest that women with hormone receptor positive breast cancer be considered for adjuvant endocrine treatment with an aromatase inhibitor (AI). Joint symptoms (arthralgia) are a common AI side-effect. There is a need for effective approaches to arthralgia management that enable survivors to remain on AI therapy while optimizing as pain-free a life as possible. This feasibility study investigates a 6-week self-directed walking program in a sample of elderly female breast cancer survivors on AIs reporting joint pain. METHODS INTERVENTION Walk With Ease (WWE) goal--minimum 30 min of walking 5 days a week (150 min per week). Eligibility: age >65; Stage I-III breast cancer; ≥3 months of AI therapy; self-reported joint pain/stiffness. MEASURES (1) walking--number of days/week and number of minutes/walk, (2) visual analog scales (VAS) for joint pain, fatigue and stiffness, and (3) arthritis self-efficacy (ASE) to manage joint pain and fatigue. STATISTICS t-tests, correlation coefficients and effect sizes. RESULTS Sample target of 20 was achieved--mean age 71 (65-87), 85% Caucasian, mean BMI 29. Proportion walking 150 min/week increased from 21% at baseline to 50% at 6 weeks (p < 0.001). Mean joint pain at baseline (39.7 + 26.9) decreased 10% (p = 0.63), fatigue (37.4+33.3) decreased 19% (p = 0.31), joint stiffness (46.1 + 27.2) decreased 32% (p = 0.07). CONCLUSIONS A self-directed walking program among elderly breast cancer survivors on AI therapy significantly increased total time of walking per week over a 6 week period. Joint pain, stiffness, and fatigue also decreased, although not significantly. Testing within a larger sample is warranted.

Prevalence of sarcopenia in older patients with colorectal cancer

OBJECTIVE Sarcopenia is the age-related loss of muscle mass, strength, and function. It is a common finding in older patients and is associated with decreased life expectancy and potentially higher susceptibility to chemotherapy toxicity. This study describes the prevalence of sarcopenia in older adults with early stage colorectal cancer. MATERIALS AND METHODS Patients ≥70 years old who underwent surgical resection for stage I-III colorectal cancer between 2008 and 2013 were identified from the medical record. Sarcopenia was assessed by measuring the total muscle area on computerized tomography (CT) images obtained prior to surgery. Total muscle area was measured at the level of L3 and normalized using each patients height to produce a skeletal muscle index (SMI). Sarcopenia was defined using sex- and body mass index (BMI)-specific threshold values of SMI. RESULTS Eighty-seven patients were included, with a median age of 77 years (70-96). Twenty-five men (60% of 42) and 25 women (56% of 45) had sarcopenia. Sarcopenic patients had significantly lower BMI (p=0.03) compared to non-sarcopenic patients. There was a positive correlation between BMI and SMI for both men (r=0.44) and women (r=0.16). CONCLUSION Sarcopenia is highly prevalent among older patients with early stage colorectal cancer. BMI alone is a poor indicator of lean body mass and improved methods of screening for sarcopenia are necessary. CT scans are a viable option for identifying sarcopenic patients in whom timely interventions may improve survival, quality of life, and functional outcomes.

Physical activity communication between oncology providers and patients with early-stage breast, colon, or prostate cancer.

National guidelines recommend that patients with a cancer diagnosis engage in regular physical activity to reduce cancer‐related fatigue, maintain quality of life and physical function, and improve overall prognosis and survival. This study investigates oncology provider communications about physical activity during routine clinic visits with patients with early‐stage breast, colon, or prostate cancer.

Body Composition as a Predictor of Toxicity in Patients Receiving Anthracycline and Taxane Based Chemotherapy for Early Stage Breast Cancer.

Purpose: Poor body composition metrics (BCM) are associated with inferior cancer outcomes; however, in early breast cancer (EBC), there is a paucity of evidence regarding the impact of BCM on toxicities. This study investigates associations between BCM and treatment-related toxicity in patients with EBC receiving anthracyclines and taxane–based chemotherapy. Experimental Design: Pretreatment computerized tomographic (CT) images were evaluated for skeletal muscle area (SMA), skeletal muscle density (SMD), and fat tissue at the third lumbar vertebrae. Skeletal muscle index (SMI = SMA/height2) and skeletal muscle gauge (SMG = SMI × SMD) were also calculated. Relative risks (RR) are reported for associations between body composition measures and toxicity outcomes, after adjustment for age and body surface area (BSA). Results: BCM were calculated for 151 patients with EBC (median age, 49 years; range, 23–75 years). Fifty patients (33%) developed grade 3/4 toxicity, which was significantly higher in those with low SMI (RR, 1.29; P = 0.002), low SMG (RR, 1.09; P = 0.01), and low lean body mass (RR, 1.48; P = 0.002). Receiver operating characteristic analysis showed the SMG measure to be the best predictor of grade 3/4 toxicity. Dividing SMG into tertiles showed toxicity rates of 46% and 22% for lowest versus highest tertile, respectively (P = 0.005). After adjusting for age and BSA, low SMG (<1,475 units) was significantly associated with hematologic (RR, 2.12; P = 0.02), gastrointestinal grade 3/4 toxicities (RR, 6.49; P = 0.02), and hospitalizations (RR, 1.91; P = 0.05). Conclusions: Poor BCMs are significantly associated with increased treatment-related toxicities. Further studies are needed to investigate how these metrics can be used to more precisely dose chemotherapy to reduce treatment-related toxicity while maintaining efficacy. Clin Cancer Res; 23(14); 3537–43. ©2017 AACR.

Physician perspectives on fall prevention and monitoring in assisted living: a pilot study.

OBJECTIVE To investigate physician perspectives on their own role and the role of residential care/assisted living (RC/AL) staff in fall prevention and monitoring among RC/AL residents. DESIGN Exploratory cross-sectional study. Mailed questionnaire. SETTING RC/AL communities. PARTICIPANTS Primary physicians (N = 36) for residents of 4 RC/AL communities in North Carolina. MEASUREMENTS Theory of Planned Behavior constructs were used to measure physician attitudes, perceived expectations, and perceived barriers to conducting fall risk assessments, medication reviews for potential side effects related to falls, and working with RC/AL staff to reduce falls and fall risks among RC/AL residents. RESULTS Physicians expressed strong support for conducting fall risk assessment of patients in RC/AL communities, believing that these assessments were likely to uncover risks that might be preventable; however, they reported conducting such assessments for only 47% of their RC/AL patients. They believed RC/AL staff had greater responsibility than they did for conducting these assessments, although they believed the staff had less expertise to do so. Further, they believed they were significantly (P < .05) more likely than RC/AL staff to take specific actions to reduce fall risks among individual patients. Physicians supported working with RC/AL staff to reduce fall risks, but expressed concerns about the usefulness and amount of communications from RC/AL staff about residents identified at high risk for falls. CONCLUSION This study provides the first data on physician perspectives on an important issue of quality care and quality of life in RC/AL communities-fall prevention and monitoring among RC/AL residents. Findings point to the need for greatly improved communications between primary physicians and RC/AL staff about residents at high risk for falls and responsibility for conducting fall risk assessments.

Effect of a six-week walking program on work place activity limitations among adults with arthritis

To conduct an exploratory evaluation of the impact of the Arthritis Foundations evidence‐based Walk With Ease (WWE) program on work place activity limitations of adults with self‐reported or doctor‐diagnosed arthritis.

Skeletal muscle measures and physical function in older adults with cancer: sarcopenia or myopenia?

Background Skeletal muscle loss, commonly known as sarcopenia, is highly prevalent in older adults and linked with adverse outcomes in cancer, yet the definition and role of sarcopenia remains uncertain. The aim of this study was to examine the association of Computerized Tomography (CT) assessed skeletal muscle measures with physical function in older adults with cancer. Results CTs for 185 patients were available. Median age 73 (IQR 68–76) and 56.5% female. After controlling for sex and BMI, we found no evidence that SMI was associated with physical function impairments. Both SMD and SMG were associated physical function impairments and higher values were associated with decreased limitations in instrumental activities of daily living (RR 0.84 [CI 0.73–0.96] and 0.94 [CI 0.89–0.99], respectively), climbing stairs (RR 0.84 [CI 0.76–0.94] and 0.91 [CI 0.87–0.96]), walking 1 block (RR 0.77 [CI 0.67–0.90] and 0.91 [CI 0.85–0.97]), and prolonged Timed Up and Go (RR 0.83 [CI 0.75–0.92] and 0.92 [CI 0.88–0.96]). Materials and Methods Using the Carolina Senior Registry, we identified patients with CT imaging performed within 60 days +/− of baseline geriatric assessment (GA). Skeletal muscle area and density (SMD) were analyzed from L3 lumbar segments. Muscle area and height (m2) were used to calculate skeletal muscle index (SMI). Skeletal Muscle Gauge (SMG) was created by multiplying SMI x SMD. Conclusions Skeletal muscle mass as assessed from CT imaging was not associated with physical function impairments. Skeletal muscle radiodensity was more associated with physical function and may aid in identifying older adults at risk for functional impairments.