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Anemia and Functional Disability in Older Adults With Cancer

Cynthia Owusu, Harvey Jay Cohen, Tao Feng, William Tew, Supriya G. Mohile, Heidi D. Klepin, Cary P. Gross, Ajeet Gajra, Stuart M. Lichtman, Arti Hurria, and on behalf of the Cancer and Aging Research Group (CARG)

Objectives: Anemia is associated with functional disability among older adults in general. However, the relationship between anemia and functional disability has not been well characterized among older adults with cancer. Therefore, we examined the association between anemia and functional disability in patients with cancer aged 65 years or older. Patients and Methods: We conducted cross-sectional analysis of data derived from a multicenter prospective study of 500 patients with cancer aged 65 years or older. The primary outcome was functional disability at chemotherapy initiation, defined as the need for assistance with at least one instrumental activity of daily living. Anemia (using WHO criteria) was defined as a hemoglobin (Hb) level of less than 12 g/dL in women and less than 13 g/dL in men. Multivariable logistic regression was used to examine the association between anemia and functional disability. Results: Among 491 evaluable patients (median age, 73.1 years [range, 65–91 years]), the prevalence of functional disability and anemia was 43% and 51%, respectively. Compared with patients without anemia, patients with anemia were more likely to report functional disability. On multivariable analysis, adjusting for sex, stage, and unintentional weight loss, patients with anemia were more likely to have functional disability (odds ratio, 2.40; 95% CI, 1.61–3.59). Conclusions: Anemia was highly prevalent and independently associated with functional disability in this cohort of older adults with cancer. Given the importance of functional status in cancer treatment decision-making, longitudinal studies evaluating the causal relation between anemia and functional status among older patients with cancer are warranted to evaluate causality.

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Use of Inpatient Palliative Care Services in Patients With Advanced Cancer Receiving Critical Care Therapies

Kah Poh Loh, Maya Abdallah, Meng-Shiou Shieh, Mihaela S. Stefan, Penelope S. Pekow, Peter K. Lindenauer, Supriya G. Mohile, Dilip Babu, and Tara Lagu

Background: Invasive mechanical ventilation (IMV), dialysis for acute kidney failure, and other critical care therapies (CCTs) are associated with a high risk for complications in patients with metastatic cancer. Inpatient palliative care (IPC) can assist in assessing patients' preferences for life-prolonging treatment at the end of life. This study investigated the use pattern of IPC, outcomes (in-hospital mortality, length of stay [LOS], discharge destination, and cost of care), and predictors of IPC use in patients with metastatic cancer who received CCTs. We hypothesized that IPC services are underused in this cohort. Methods: In this retrospective cohort study, we used the 2010 California State Inpatient Databases to identify adults with metastatic cancer who received CCTs that are common and reliably coded (IMV, tracheostomy, percutaneous endoscopic gastrostomy tube, dialysis for acute kidney failure, and total parenteral nutrition). We determined IPC use in all patients, in those who received IMV, and across 4 cancer subtypes (lung, breast, colorectal, and genitourinary). Outcomes were assessed based on IPC use. Multivariable analyses were used to investigate factors associated with IPC use. Results: We identified 5,862 hospitalizations, 19.8% of which used IPC services. IPC use varied across cancer subtypes (lung, 28.3%; breast, 22.4%; colorectal, 12.8%; genitourinary, 16.1%; P<.01). Patients who received and did not receive IPC services had high in-hospital mortality rates (63.9% and 29.8%, respectively), and costs of care and LOS were lower in survivors who received IPC compared with those who did not. Predictors of IPC use were lung cancer (vs colorectal or genitourinary cancer), higher comorbidity score, do-not-resuscitate status on admission or within 24 hours of admission, infections (vs cancer-related diagnoses), and higher hospital bed count. Conclusions: Use of IPC was low in the cohort who received CCTs with poor outcomes, although data on outpatient palliative care services is lacking. Predictors of IPC use may be used to identify patients who may benefit from these services.

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

Mostafa R. Mohamed, Kah Poh Loh, Supriya G. Mohile, Michael Sohn, Tracy Webb, Megan Wells, Sule Yilmaz, Rachael Tylock, Eva Culakova, Allison Magnuson, Can-Lan Sun, James Bearden, Judith O. Hopkins, Bryan A. Faller, and Heidi D. Klepin

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

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

Mostafa R. Mohamed, Erika Ramsdale, Kah Poh Loh, Huiwen Xu, Amita Patil, Nikesha Gilmore, Spencer Obrecht, Megan Wells, Ginah Nightingale, Katherine M. Juba, Bryan Faller, Adedayo Onitilo, Thomas Bradley, Eva Culakova, Holly Holmes, and Supriya G. Mohile

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

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Community Oncologists' Decision-Making for Treatment of Older Patients With Cancer

Supriya G. Mohile, Allison Magnuson, Chintan Pandya, Carla Velarde, Paul Duberstein, Arti Hurria, Kah Poh Loh, Megan Wells, Sandy Plumb, Nikesha Gilmore, Marie Flannery, Marsha Wittink, Ronald Epstein, Charles E. Heckler, Michelle Janelsins, Karen Mustian, Judith O. Hopkins, Jane Liu, Srihari Peri, and William Dale

Background: This study's objectives were to describe community oncologists' beliefs about and confidence with geriatric care and to determine whether geriatric-relevant information influences cancer treatment decisions. Methods: Community oncologists were recruited to participate in 2 multisite geriatric oncology trials. Participants shared their beliefs about and confidence in caring for older adults. They were also asked to make a first-line chemotherapy recommendation (combination vs single-agent vs no chemotherapy) for a hypothetical vignette of an older patient with advanced pancreatic cancer. Each oncologist received one randomly chosen vignette that varied on 3 variables: age (72/84 years), impaired function (yes/no), and cognitive impairment (yes/no). Other patient characteristics were held constant. Logistic regression models were used to identify associations between oncologist/vignette-patient characteristics and treatment decisions. Results: Oncologist response rate was 61% (n=305/498). Most oncologists agreed that “the care of older adults with cancer needs to be improved” (89%) and that “geriatrics training is essential” (72%). However, <25% were “very confident” in recognizing dementia or conducting a fall risk or functional assessment, and only 23% reported using the geriatric assessment in clinic. Each randomly varied patient characteristic was independently associated with the decision to treat: younger age (adjusted odds ratio [aOR], 5.01; 95% CI, 2.73–9.20), normal cognition (aOR, 5.42; 95% CI, 3.01–9.76), and being functionally intact (aOR, 3.85; 95% CI, 2.12–7.00). Accounting for all vignettes across all scenarios, 161 oncologists (52%) said they would offer chemotherapy. All variables were independently associated with prescribing single-agent over combination chemotherapy (older age: aOR, 3.22; 95% CI 1.43–7.25, impaired cognition: aOR, 3.13; 95% CI, 1.36–7.20, impaired function: aOR, 2.48; 95% CI, 1.12–5.72). Oncologists' characteristics were not associated with decisions about providing chemotherapy. Conclusion: Geriatric-relevant information, when available, strongly influences community oncologists' treatment decisions.

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

Kah Poh Loh, Vivian Lam, Katey Webber, Simran Padam, Mina S. Sedrak, Vivek Musinipally, Madison Grogan, Carolyn J. Presley, Janice Grandi, Chandrika Sanapala, Daniel A. Castillo, Grace DiGiovanni, Supriya G. Mohile, Louise C. Walter, and Melisa L. Wong

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).