Most cases of breast cancer are diagnosed in older adults. Older women have an increased risk for breast cancer–specific mortality and are at higher risk for treatment-associated morbidity than younger women. However, they are also less likely to be offered preventive care or adjuvant therapy for this disease. Major gaps in evidence exist regarding the optimal evaluation and treatment of older women with breast cancer because of significant underrepresentation in clinical trials. Chronologic age alone is an inadequate predictor of treatment tolerance and benefit in this heterogeneous population. Multiple issues uniquely associated with aging impact cancer care, including functional impairment, comorbidity, social support, cognitive function, psychological state, and financial stress. Applying geriatric principles and assessment to this older adult population would inform decision making by providing estimates of life expectancy and identifying individuals most vulnerable to morbidity. Ongoing research is seeking to identify which assessment tools can best predict outcomes in this population, and thus guide experts in tailoring treatments to maximize benefits in older adults with breast cancer.
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Heidi Klepin, Supriya Mohile, and Arti Hurria
Arti Hurria, Supriya Gupta Mohile, and William Dale
Supriya Gupta Mohile, Carla Velarde, Arti Hurria, Allison Magnuson, Lisa Lowenstein, Chintan Pandya, Anita O'Donovan, Rita Gorawara-Bhat, and William Dale
Background: Structured care processes that provide a framework for how oncologists can incorporate geriatric assessment (GA) into clinical practice could improve outcomes for vulnerable older adults with cancer, a growing population at high risk of toxicity from cancer treatment. We sought to obtain consensus from an expert panel on the use of GA in clinical practice and to develop algorithms of GA-guided care processes. Methods: The Delphi technique, a well-recognized structured and reiterative process to reach consensus, was used. Participants were geriatric oncology experts who attended NIH-funded U13 or Cancer and Aging Research Group conferences. Consensus was defined as an interquartile range of 2 or more units, or 66.7% or greater, selecting a utility/helpfulness rating of 7 or greater on a 10-point Likert scale. For nominal data, consensus was defined as agreement among 66.7% or more of the group. Results: From 33 invited, 30 participants completed all 3 rounds. Most experts (75%) used GA in clinical care, and the remainder were involved in geriatric oncology research. The panel met consensus that “all patients aged 75 years or older and those who are younger with age-related health concerns” should undergo GA and that all domains (function, physical performance, comorbidity/polypharmacy, cognition, nutrition, psychological status, and social support) should be included. Consensus was met for how GA could guide nononcologic interventions and cancer treatment decisions. Algorithms for GA-guided care processes were developed. Conclusions: This Delphi investigation of geriatric oncology experts demonstrated that GA should be performed for older patients with cancer to guide care processes.
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.
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.
Kerry Schaffer, Narmadha Panneerselvam, Kah Poh Loh, Rachel Herrmann, Ian R. Kleckner, Richard Francis Dunne, Po-Ju Lin, Charles E. Heckler, Nicholas Gerbino, Lauren B. Bruckner, Eugene Storozynsky, Bonnie Ky, Andrea Baran, Supriya Gupta Mohile, Karen Michelle Mustian, and Chunkit Fung
Background: Exercise can ameliorate cancer- and treatment-related toxicities, but poor adherence to exercise regimens is a barrier. Exercise interventions using digital activity trackers (E-DATs) may improve exercise adherence, but data are limited for patients with cancer. We conducted a systematic review examining the feasibility of E-DATs in cancer survivors and effects on activity level, body composition, objective fitness outcomes, health-related quality of life (HRQoL), self-reported symptoms, and biomarkers. Methods: We identified randomized controlled trials (RCTs) of E-DATs in adult cancer survivors published in English between January 1, 2008, and July 27, 2017. Two authors independently reviewed article titles (n=160), removed duplicates (n=50), and reviewed the remaining 110 articles for eligibility. Results: A total of 12 RCTs met eligibility criteria, including 1,450 patients (mean age, 50–70 years) with the following cancers: breast (n=5), colon or breast (n=2), prostate (n=1), acute leukemia (n=1), or others (n=3). Duration of E-DATs ranged from 4 to 24 weeks, and the follow-up period ranged from 4 to 52 weeks, with retention rates of 54% to 95%. The technology component of E-DATs included pedometers (n=8); pedometers with smartphone application (n=1), Wii Fit (n=1), heart rate monitor (n=1); and a wireless sensor with accelerometer, gyroscope, and magnetometer (n=1). Adherence by at least one measure to E-DATs was >70% in 8 of 8 RCTs. Compared with controls, E-DATs significantly improved patients' step count in 3 of 5 RCTs, activity level in 6 of 9 RCTs, and HRQoL in 7 of 9 RCTs (all P≤.05), with no significant changes in biomarkers (eg, interleukin 6, tumor necrosis factor α, C-reactive protein, c-peptide, lipid panel) in 3 RCTs. Duration of E-DAT was not significantly correlated with adherence or study retention. Conclusions: This systematic review shows that E-DATs are feasible to implement in cancer survivors. Future research should examine the optimal type, dose, and schedule of E-DATs for cancer survivors.
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).
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.
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
Ryan D. Nipp, Brandon Temel, Charn-Xin Fuh, Paul Kay, Sophia Landay, Daniel Lage, Esteban Franco-Garcia, Erin Scott, Erin Stevens, Terrence O’Malley, Supriya Mohile, William Dale, Lara Traeger, Ardeshir Z. Hashmi, Vicki Jackson, Joseph A. Greer, Areej El-Jawahri, and Jennifer S. Temel
Background: Oncologists often struggle with managing the unique care needs of older adults with cancer. This study sought to determine the feasibility of delivering a transdisciplinary intervention targeting the geriatric-specific (physical function and comorbidity) and palliative care (symptoms and prognostic understanding) needs of older adults with advanced cancer. Methods: Patients aged ≥65 years with incurable gastrointestinal or lung cancer were randomly assigned to a transdisciplinary intervention or usual care. Those in the intervention arm received 2 visits with a geriatrician, who addressed patients’ palliative care needs and conducted a geriatric assessment. We predefined the intervention as feasible if >70% of eligible patients enrolled in the study and >75% of eligible patients completed study visits and surveys. At baseline and week 12, we assessed patients’ quality of life (QoL), symptoms, and communication confidence. We calculated mean change scores in outcomes and estimated intervention effect sizes (ES; Cohen’s d) for changes from baseline to week 12, with 0.2 indicating a small effect, 0.5 a medium effect, and 0.8 a large effect. Results: From February 2017 through June 2018, we randomized 62 patients (55.9% enrollment rate [most common reason for refusal was feeling too ill]; median age, 72.3 years; cancer types: 56.5% gastrointestinal, 43.5% lung). Among intervention patients, 82.1% attended the first visit and 79.6% attended both. Overall, 89.7% completed all study surveys. Compared with usual care, intervention patients had less QoL decrement (–0.77 vs –3.84; ES = 0.21), reduced number of moderate/severe symptoms (–0.69 vs +1.04; ES = 0.58), and improved communication confidence (+1.06 vs –0.80; ES = 0.38). Conclusions: In this pilot trial, enrollment exceeded 55%, and >75% of enrollees completed all study visits and surveys. The transdisciplinary intervention targeting older patients’ unique care needs showed encouraging ES estimates for enhancing patients’ QoL, symptom burden, and communication confidence.