Cohort Of Older Patients Research Articles

The comparative effectiveness of biologic agents among non-hispanic black (NHB) patients with metastatic colorectal cancer (mCRC): Preliminary results of a SEER-medicare analysis.

e19059 Background: Biologic agents (bevacizumab, cetuximab, panitumumab) have improved the overall survival (OS) of patients with mCRC. However, clinical trials are plagued by low representation of NHB patients, and a disproportionately high (>90%) accrual of non-Hispanic whites (NHW). As a result, the real world benefit among NHB patients in unknown. Comparative effectiveness research is an approach for effectively addressing this drawback. Methods: Utilizing the SEER-Medicare linked database, we identified 5,728 patients with mCRC diagnosed between 2004 and 2011 who received chemotherapy (CT; oxaliplatin, irinotecan, 5-FU, capecitabine) alone or chemotherapy with a biologic agent (CBT). OS was examined using the Kaplan-Meier method and a weighted semi-parametric accelerated failure time model. A propensity score model approach was undertaken to further account for potential treatment selection bias. Results: Overall, 88% were NHW and 12% NHB patients. The median age at diagnosis was 73 and 70 years and exposure to biologics was 71.2% and 71.4%, respectively. NHB patients had more women, were single, had lower median incomes, better differentiated tumors, less rectal primary cancers, more right sided tumors, and a worse Charleson co morbidity index. There was no difference in the receipt of 1 (72%) vs > 2 (28%) lines of therapy. The median OS was 11 and 12 months (m) in the CT-alone group, and 21 and 22 m in CBT group, among NHW and NHB, respectively. Based on an unadjusted analysis, receipt of biologics, younger age, left sided primary, well/moderate differentiation, being married, more lines of CT, and lower prevalence of co-morbidity were associated with improved OS. We also performed multiple imputations to properly account for the missing data. Among NHW, median OS was 21 vs 11 m in the CBT and CT groups, respectively (effect 1.47, 95% CI 1.36-1.60, p = 0.0000). Among NHB, median OS was 22 vs 12 m in the CBT and CT groups, respectively (effect 1.48, 95% CI 1.23-1.88, p = 0.0000). All comparisons maintained significance when adjusted for multiple comparisons. We found no interaction between biologics and race (p = 0.8743). On subgroup analysis, those patients receiving both classes of biologics (anti EGFR and anti VEGF) had the best outcome. Conclusions: In this cohort of older patients, CBT was associated with longer survival, regardless of race. Clinicians should offer CBT therapy to all patients to maximize their clinical benefit, factoring in clinical variables, but not their race.

Frailty assessment and risk prediction by GRACE score in older patients with acute myocardial infarction

BackgroundRisk prediction after myocardial infarction is often complex in older patients. The Global Registry of Acute Coronary Events (GRACE) model includes clinical parameters and age, but not frailty. We hypothesised that frailty would enhance the prognostic properties of GRACE.MethodsWe performed a prospective observational cohort study in two independent cardiology units: the Royal Infirmary of Edinburgh, UK (primary cohort) and the South Yorkshire Cardiothoracic Centre, Sheffield, UK (external validation). The study sample included 198 patients ≥65 years old hospitalised with type 1 myocardial infarction (primary cohort) and 96 patients ≥65 years old undergoing cardiac catheterisation for myocardial infarction (external validation). Frailty was assessed using the Clinical Frailty Scale (CFS). The GRACE 2.0 estimated risk of 12-month mortality, Charlson comorbidity index and Karnofsky disability scale were also determined for each patient.ResultsForty (20%) patients were frail (CFS ≥5). These individuals had greater comorbidity, functional impairment and a higher risk of death at 12 months (49% vs. 9% in non-frail patients, p < 0.001). The hazard of 12-month all-cause mortality nearly doubled per point increase in CFS after adjustment for age, sex and comorbidity (Hazard Ratio [HR] 1.90, 95% CI 1.47–2.44, p < 0.001). The CFS had good discrimination for mortality by Receiver Operating Characteristic (ROC) curve analysis (Area Under the Curve [AUC] 0.81, 95% CI 0.72–0.89) and enhanced the GRACE estimate (AUC 0.86 vs. 0.80 without CFS, p = 0.04). At existing GRACE thresholds, the CFS resulted in a Net Reclassification Improvement (NRI) of 0.44 (95% CI 0.28–0.60, p < 0.001), largely through reductions in risk estimates amongst non-frail patients. Similar findings were observed in the external validation cohort (NRI 0.46, 95% CI 0.23–0.69, p < 0.001).ConclusionsThe GRACE score overestimated mortality risk after myocardial infarction in these cohorts of older patients. The CFS is a simple guided frailty tool that may enhance prediction in this setting. These findings merit evaluation in larger cohorts of unselected patients.Trial registrationClinicaltrials.gov; NCT02302014 (November 26th 2014, retrospectively registered).

Leveraging emergency department visits to connect older adults at risk for malnutrition and food insecurity to community resources: design and protocol development for the BRIDGE study

BackgroundMalnutrition is a complex and costly condition that is common among older adults in the United States (US), with up to half at risk for malnutrition. Malnutrition is associated with several non-medical (i.e., social) factors, including food insecurity. Being at risk for both malnutrition and food insecurity likely identifies a subset of older adults with complex care needs and a high burden of social vulnerability (e.g., difficulty accessing or preparing meals, lack of transportation, and social isolation). US emergency departments (EDs) are a unique and important setting for identifying older patients who may benefit from the provision of health-related social services. This paper describes the protocol development for the Building Resilience and InDependence for Geriatric Patients in the Emergency Department (BRIDGE) study. BRIDGE was designed to assess the feasibility of an ED-based screening process to systematically identify older patients who are at risk for malnutrition and food insecurity and link them to health-related social services to address unmet social needs and support their health and well-being.MethodsPhase 1 efforts will be formative and focused on identifying screening tools, establishing screening and referral workflows, and conducting initial feasibility testing with a cohort of older patients and ED staff. In phase 2, which includes process and outcome evaluation, the screening and referral process will be piloted in the ED. A partnership will be formed with an Area Agency on Aging (AAA) identified in phase 1, to assess resource needs and identify community-based social services for older ED patients who screen positive for both malnutrition risk and food insecurity. Data on screening, referrals, linkage to community-based social services, and patient-reported quality of life and healthcare utilization will be used to assess feasibility.DiscussionThe tools and workflows developed and tested in this study, as well as learnings related to forming and maintaining cross-sector partnerships, may serve as a model for future efforts to utilize EDs as a setting for bridging the gap between healthcare and social services for vulnerable patients.

Genetic and Genomic Characterisation of Older Adults with Acute Lymphoblastic Leukemia Treated on the UKALL14 and UKALL60+ Clinical Trials

Genetic and Genomic Characterisation of Older Adults with Acute Lymphoblastic Leukemia Treated on the UKALL14 and UKALL60+ Clinical Trials

Undertreatment of Older Patients with Newly-Diagnosed Multiple Myeloma: Real World Evidence from a Canadian Registry Cohort

Introduction Multiple myeloma (MM) is a malignant plasma cell disease and is considered a disease of older patients as the median age at diagnosis is 70 years. In recent years, the overall survival of patients with MM has improved due to the increasing number of treatment options and better supportive care. However, older patients (age &amp;gt;65) have not benefitted equally from the same gains. There is a paucity of information regarding clinical outcomes in this age cohort given that older patients are often under-represented in clinical trials and prospective studies. Real-world data may allows us to examine the trends in practice patterns over time and help us understand disparities in treatment options and overall patient outcomes in older patients with MM at a population level. Methods We conducted a retrospective population-based study using administrative data from the Institute of Clinical Evaluative Sciences (ICES), which maintains a central database of health records for all patients in the publicly funded health care system for the province of Ontario, Canada. All patients with newly-diagnosed multiple myeloma, identified using the ICD-O-3 code 9732/3 (Multiple Myeloma) between the years 2007-2017, were included to form the cohort. Autologous transplant within one year of diagnosis was captured in the database using a combination of physician billing codes and hospital procedure/discharge codes. Novel drugs usage for transplant ineligible patients was defined as the receipt of thalidomide, lenalidomide and bortezomib in any combination within one year of diagnosis. No treatment was defined as patients that did not receive a transplant, novel drugs or non-novel drugs (melphalan and cyclophosphamide) within one year following diagnosis. Results A total of 11,875 patients with newly-diagnosed myeloma were identified between the years 2007-2017. The proportion of newly-diagnosed MM patients who were older (age &amp;gt;65 years) increased from 60% of those diagnosed in 2007 to 68% of those diagnosed in 2017. The rates of autologous transplantation in older patients with MM increased from 4 to 10%. Overall those who underwent transplant had improved outcomes with decreasing one-year mortality from nearly 24% in 2007 down to 3% in 2017. Novel drugs were increasingly being used in older patients that were transplant ineligible with up to 42% receiving it within one year of diagnosis in 2017. In transplant ineligible older adults using novel drugs, one- year mortality ranged from 15% to 24%. The rates of older adults with newly-diagnosed MM not treated within one year of diagnosis was on average 49% although that number marginally declined from 54% in 2007 to 47% in 2017. Among those that did not receive treatment, 48% of individuals on average (range 40-57%) were not alive at one-year following diagnosis. Conclusion Our results demonstrate that although gains are being made in older adults with newly-diagnosed MM with increasing rates of transplantation and novel-drug usage over the last decade, there remains a sizeable cohort of older patients that do not receive any treatment within one year of diagnosis. While a limitation of our study may be the inclusion of some smouldering cases of myeloma, the mortality for older patients not treated continues to remain high with approximately half the patients not alive at one year following diagnosis. This study represents one of the largest cohort studies done to date over a decade demonstrating the ongoing low rates of no treatment and high rates of one-year mortality for older patients with MM. Further identification of factors associated with no treatment, transplantation and novel drug usage in older patients with MM are currently being explored. Table. Disclosures Mian: Amgen: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pond:Roche Canada: Employment, Other: Stock; Takeda (DSMC membership): Other: Honorarium.

30-Day Potentially Preventable Hospital Readmissions In Older Patients: Clinical Phenotype And Health Care Related Risk Factors.

PurposeEarly readmission rate has been regarded as an indicator of in-hospital and post-discharge quality of care. Evaluating the contributing factors is crucial to optimize the healthcare and target the intervention. In this study we evaluated the potential for preventing 30-day hospital readmission in a cohort of older patients and identified possible risk factors for readmission.Patients and methodsDiagnosis-Related Group (DRG) codes of patients consecutively hospitalized for acute disease in the Geriatrics Unit of the University Hospital of Pisa within a 1-year window were recorded. All the patients had received a comprehensive geriatric assessment. Crossing and elaboration of the DRG codes was performed by the Potentially Preventable Readmission Grouping software (3M™ Corporation). DRG codes were classified as stand-alone admissions (SA), index admissions (IA) and potentially preventable readmissions (PPR) within a time window of 30 days after discharge.ResultsIn total, 1263 SA and 171 IA were identified, with an overall PPR rate of 11.9%. Hospitalizations were significantly longer in IA and PPR than SA (p<0.05). The more frequent readmission causes were acute heart failure, pulmonary edema, sepsis, pneumonia and stroke. In acute heart failure a nonlinear U-shaped readmission trend (with nadir at 5 days of hospitalization) was observed while, in all the other DRG codes, the PPR rate increased with increasing length of hospitalization. Comprehensive geriatric assessment showed a significantly lower degree of disability and comorbidity in SA than IA patients. At stepwise regression analysis, a high degree of disability and comorbidity as well as the diagnosis of sepsis emerged as independent risk factors for PPR.ConclusionAddressing PPR is crucial, especially in older patients. The adequacy of treatment during hospitalization (especially in cases of sepsis) as well as the setting of a comprehensive discharge plan, accounting for comorbidity and disability of the patients, are essential to reduce PPR.

250 Delirium, Common but Forgotten

Abstract Background Delirium is a medical emergency prevalent amongst hospitalised older patients and associated with prolonged hospital stay, functional and cognitive decline, institutionalisation and increased mortality. In Irish hospitals, multiple strategies, e-learning courses, delirium guidelines and prevention programs have aimed to improve delirium care with better diagnosis and prevention. With the increasing awareness campaigns, we aimed to review the prevalence, screening and management of delirium in our cohort of older patients. Methods A review of medical notes of all patients admitted under medical teams to an acute geriatric ward was carried out. Data was collected over a 3 week period in an Irish model 3 hospital. The following information was obtained from medical records: 1) Previous diagnosis of delirium/dementia 2) Documentation of a diagnosis of delirium 3) Features of delirium 4) Development of delirium as an inpatient 5) Formal screening for delirium 6) Cause and management of delirium 7) Length of stay. Results Of 79 consecutive admissions to an acute geriatric ward (mean age 81.4, 57% female, 30% previous history of delirium or dementia), 25% (n=20) had a diagnosis of delirium documented. 22% (n=18) of patients had confusion and features of delirium highlighted but no formal diagnosis of delirium made during their inpatient stay. A further 20% (n=16) developed delirium on admission. Only 2.5% (n=2) of admissions had formal screening for delirium with the 4AT. 27.5% (n=11) of patients with delirium had a cause and management plan recorded. 70% (n=28) of patients with delirium had a length of stay of over 15 days. Conclusion This review showed delirium recognition, screening, prevention and management were overlooked to an alarming extent in our cohort of older patients. The next step is introduction of the 4AT screening tool and regular education sessions to increase the awareness of delirium amongst medical teams looking after older patients and improve care and outcomes.

IMAGE-Guided Brachytherapy for Primary Vaginal Cancers

To evaluate disease control and toxicities of primary vaginal cancer treated with image-guided brachytherapy. A retrospective study was performed on 26 consecutive patients treated for vaginal cancer with brachytherapy (BT) between 2010 and 2018, all treated after the introduction of ultrasound-based catheter guidance and modified dose optimization to reduce vaginal toxicities. External beam radiation therapy (EBRT) was used in 25/26 patients, with a median dose of 45 Gy in 25 fractions. 16/25 patients had concomitant chemotherapy with EBRT. Endocavitary BT alone was used in 3/26 patients. Interstitial BT was used in 23/26 patients. Standard procedure involved the use of a cylinder and interstitial catheters. They were usually inserted under Transrectal Ultrasound (TRUS) and/or TransVaginal Ultrasound (TVUS) guidance. Inverse Planning Simulated Annealing (IPSA) was used for dose optimization and a class solution was developed to reduce high-dose points in the vaginal mucosa by keeping most of the high dose inside the cylinder. Acute (<6 months) and late genitourinary (GU), gastrointestinal (GI), and vaginal toxicities were reported using the Common Terminology Criteria for Adverse Events version 5 (CTCAE v5). Local control (LC), metastatic disease-free survival (mDFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves. Mean age was 69,7 years old. Median follow-up was 35,5 months (range 0-85months). 18/26 patients had Squamous Cell Carcinoma (SCC), 5/26 Adenocarcinoma, 1/26 Clear Cell Carcinoma, 1/26 Melanoma and 1/26 Squamous Transitional Carcinoma. 13%, 71%, 8%, and 8% of patients had FIGO stages I, II, III, and IV respectively. LC of 83% and 83%, mDFS of 91 % and 91%, and OS of 80% and 66 %, were respectively achieved at 3 and 5 years. When limited to SCC only, LC of 88% and 88%, mDFS of 94 % and 94%, and OS of 87% and 70 %, were respectively achieved at 3 and 5 years. There were only 4 local relapses, which all occurred within 8 months after treatment. One was a stage IV SCC at diagnosis, one had a squamous transitional carcinoma, one was a clear cell carcinoma, and the last one had concomitant multiple distant metastasis at time of local relapse. There were no late G3-4 GU/GI toxicity. Acute and late G3 vaginal toxicity (stenosis) occurred in 19% and 42% of patients, respectively. 3 cases of vaginal necrosis and 1 suspicion of fistula were reported, all associated with a local progression of the disease except for one case where necrosis was limited and healed spontaneously. No patient needed Hyperbaric Oxygen Therapy (HBOT). Excellent local control can be achieved with the use of TRUS/TVUS-guided vaginal brachytherapy in primary vaginal cancer, especially for Squamous Cell Carcinoma, with a favorable toxicity profile. GU and GI toxicities are mild, but there is a significant number of G3 vaginal stenosis in this cohort of older patients. This might be reduced with the regular use of a vaginal dilator.

Patients younger than 45 years of age have superior 5-year survival in advanced esophageal cancer

Background: Esophageal cancer is an aggressive malignancy that most commonly presents in the sixth and seventh decade of life. However, there are a subset of patients that present with esophageal cancer at a very young age ( Methods: This study was performed through a retrospective review of patients who underwent esophageal resection performed at our institution from 1985 to 2014 identified 82 patients who were under the age of 45 when they underwent surgical resection for esophageal cancer. This cohort of patients were matched to a cohort of patients who had the same stage, sex, neoadjuvant therapy, pathology, and year of diagnosis within 5 years but were older than 45 years old when they underwent esophageal resection. Results: There was no significant difference in survival between the younger and older cohort of patients with stage I or II disease. Patients with stage III/IV esophageal cancer under the age of 45 had 1-, 3-, and 5-year survival of 88.6%, 31.8% and 24.2%, while in the older matched cohort 1-, 3-, and 5-year survival was 58.3%, 20.6%, 8.8% [P=0.04, hazard ratio (HR) 1.72]. Conclusions: While age doesn’t affect overall survival of early-stage esophageal cancer, patients under the age of 45 with advanced esophageal cancer have superior overall survival compared to older patients.

Hypofractionated radiation in older women with breast cancer.

American Society of Radiation Oncology Choosing Wisely campaign recommends hypofractionated radiation and against routine use of intensity-modulated radiation therapy (IMRT) in early-stage estrogen receptor-positive breast cancer. We analyzed guideline recommendation adherence and financial implications in a modern Medicare cohort of women treated across the southeastern United States. Our study population comprised Medicare patients over 65years of age with breast cancer diagnosis from 12 cancer centers in the Southeast United States with stage 0-II breast treated with lumpectomy from 2012 to 2015. Hypofractionation was defined as 4 or fewer weeks of radiation treatments. Factors associated with utilization of hypofractionation and IMRT were identified using Poisson regression. Median costs during radiation treatments were compared for hypofractionation and IMRT. In older women (median age 71), 75% were treated with conventional fractionation, and 20% received IMRT. Hypofractionated women were more likely to have a positive estrogen(ER) or progestorone(PR) receptor status, lower comorbidity scores, and be treated at a high volume center (all P<0.05). IMRT was utilized in 20% of patients and was more common in women treated with conventional fractionation (P<0.001). Positive ER/PR status (P<0.001) and utilization of hormonal blockade (P=0.02) were associated with increased utilization of IMRT. In an older cohort of patients with early-stage breast cancer, a majority were treated with conventional fractionated radiation, while approximately 20% were treated with IMRT. Both of which were associated with increased cost relative to hypofractionation.

Moderate hypofractionated helical tomotherapy for prostate cancer in a cohort of older patients: a mono-institutional report of toxicity and clinical outcomes

To evaluate toxicity and outcomes of moderately hypofractionated helical tomotherapy for the curative treatment of a cohort of patients aged ≥ 75years with localized prostate cancer (PC). From January 2013 to February 2017, 95 patients with median age 77years (range 75-88) were treated for PC. 39% were low risk, 33% intermediate risk (IR), 28% high risk (HR). Median iPSA was 9.42ng/ml (1.6-107). Androgen deprivation was prescribed according to NCCN recommendations. All patients received 70Gy in 28 fractions to theprostate; 61.6Gy were delivered to the seminal vesicles for IR; whole pelvis irradiation with a total dose of 50.4Gy was added in the HR group.Toxicity evaluation was based on CTCAE V4.0 criteria, biochemical failure was defined following Phoenix criteria. Quality of Life was assessed with the EPIC-26 index. Overall survival and biochemical failure-free survival were analysed with Kaplan-Meier method. With a median follow-up of 36months (range 24-73), acute and late toxicity were acceptable. No correlation between toxicity patterns and clinical or dosimetric parameter was registered. EPIC-26 showed a negligible difference in urinary and bowel function post-treatment that did not reach statistical significance. The 2- and 3-years OS were 93% and 87% with cancer specific survival of 97.9% and 96.2%. Moderate hypofractionated RT reported excellent outcomes in our cohort of older patients. Shorter schedules may be proposed regardless of chronological age facilitating the treatment compliance in the older population.

A single center experience of the impact of treatment-related toxicity in the clinical outcomes of elderly patients with metastatic germ cell tumors.

e16048 Background: Germ cell tumours (GCT) are predominantly a disease of the young, with &lt; 10% of cases being diagnosed at ≥45 years. Platinum based chemotherapy is the gold standard in treating these patients. Data regarding outcomes and treatment toxicities in elderly patients is lacking. We studied the efficacy, toxicities and survival rates in a cohort of men diagnosed with GCT aged ≥45 years receiving chemotherapy in a metastatic setting. Methods: Data was collected retrospectively from 48 patient’s ≥45 years with GCT’s identified at Mount Vernon Cancer Centre, London. The histology, stage and international germ cell consensus (IGCC) risk classification was identified in all patients. Data was collected regarding chemotherapy regimens, number of cycles completed, toxicities and complications that led to treatment modifications or early cessation. Treatment toxicities were evaluated using the common terminology criteria for adverse events (ctCAE) grading. We then assessed progression free survival, relapse rates and overall survival (OS). Results: We identified 48 patients diagnosed with GCTs aged ≥45 years. The median age at diagnosis was 52 (range 45-70) and 75% of patients were aged ≥50. Classic seminoma and nonseminomatous GCTs were seen in 65% and 35% of patients, respectively. 75% of patients were ≥stage II at diagnosis. In total 29 patients received BEP, 4 EP, 7 Carboplatin AUC10, 2 Carboplatin AUC7 and 5 received POMBACE. 73 % (35/48) of patients experienced one or more complication/s from chemotherapy (15/48 ctCAE grade ≥3), of which the most common were neuropathies (27%), thromboembolism (10%) and tinnitus (10%). In 8 cases omissions or dose reductions had to be made and treatment delays occurred in 3 cases. Only 2 patients did not complete all intended cycles. Over 70% (35/48) of patients had an OS of &gt; 5 years. One patient died during chemotherapy due to gastro-intestinal bleed. Conclusions: Survival rates in patients with GCTs aged ≥45 treated with chemotherapy are good with the majority achieving a &gt; 5 year OS. Although age is not a prognostic factor, these patients are more prone to toxicities and have underlying comorbidities. This data will be of value to oncologists weighing up the risks versus benefits of treatment in this older cohort of patients in combination with similar studies.

Prognostic value of two geriatric screening tools in a cohort of older patients with early stage Non-Small Cell Lung Cancer treated with hypofractionated stereotactic radiotherapy

ObjectivesTo investigate whether assessment with two geriatric screening tools shows a correlation with clinical outcomes of patients aged 65 years or more, with early-stage Non-Small Cell Lung Cancer (es-NSCLC) treated with hypofractionated stereotactic radiotherapy. MethodsFrom March 2014 to June 2018 we retrospectively evaluated 42 patients with stage I and II lung tumors. Patients were assessed with Charlson Comorbidity Index (CCI) and G8 screening tool. Median age was 74 years (range, 65–91). Stereotactic radiotherapy was performed with Helical Tomotherapy delivering 50–70 Gray (Gy) in 8–10 fractions. Toxicity was evaluated using Common Terminology Criteria for Adverse Events v4.0 criteria. ResultsMedian CCI and G8 scores were 6 (4–11) and 14 (12–17), respectively. With a median follow-up of 14 months (3–37), we observed: 3 cases of acute Grade 2 (G2) radiation pneumonitis, 1 late G2 non-cardiac chest pain, 1 late G2 dysphagia and 1 case of late G2 radiation pneumonitis. At statistical analysis, G8 scores ≤14 were significantly associated with late toxicity rates (p = .0073). Local failure was predictive of disease free survival and Overall Survival (p < .001 and p = .001). Death occurred in 12 patients, 6 for non-cancer related causes, with 1- and 2-yrs cancer specific survival rates of 94.8% and 90%, 1- and 2-yrs OS rates of 93% and 80%, respectively. ConclusionsOur experience shows a correlation between G8 scores and late toxicity in older patients treated with stereotactic radiotherapy for lung cancer, suggesting the need for prospective studies evaluating its use for the identification of patients at higher risk of adverse events.

Older-Patient-Specific Cancer Trials: A Pooled Analysis of 2,277 Patients (A151715).

Less than 3% of older patients with cancer are enrolled in clinical trials. To reverse this underrepresentation, we compared older patients enrolled with older-patient-specific trials, defined as those designed for older patients with cancer, with those enrolled in age-unspecified trials. We focused on individual patient data from those ≥65 years (younger patients excluded) and included all Alliance phase III adjuvant breast cancer trials from 1985-2012. Among 2,277 patients, 1,014 had been enrolled to older-patient-specific and 1,263 to age-unspecified trials. The median age (range) in the older-patient-specific trials was 72 (65-89) years compared with 68 (65-84) years in the cohort of older patients in age-unspecified trials; p < .0001. A greater percentage of patients 75 years or older had enrolled in older-patient-specific trials compared with the cohort of age-unspecified trials: 26% versus 6% (p < .0001). Median overall survival (OS) was 12.8 years (95% confidence interval [CI], 11.9-13.7) and 13.5 years (95% CI, 12.9-14.1) for older-patient-specific and age-unspecified trials, respectively. OS was comparable (hazard ratio [HR], 1.08; 95% CI, 0.92-1.28; p = .34; referent: age-unspecified trials), after adjusting for age, estrogen receptor status, tumor size, and lymph node status. Similar findings were reached for recurrence-free survival. A lower rate of grade 3-5 adverse events (hematologic and nonhematologic) was reported in older-patient-specific trials (43% vs. 58%; p < .0001). Sensitivity analysis with chemotherapy only trials and subset analysis, adjusted for performance score, yielded similar OS results. Older-patient-specific trials appear to address this underrepresentation of older patients with ostensibly comparable outcomes. Clinical trial identification numbers. NCT00003088 (CALGB 9741); NCT00024102 (CALGB 49907); NCT00068601 (CALGB 40401); NCT00005970 (NCCTG N9831) IMPLICATIONS FOR PRACTICE: This work underscores the importance of clinical trials that focus on the recruitment of older patients with cancer.

Abstract 209: Sex Differences in Characteristics, Symptoms, and Management of Geriatric Patients with Atrial Fibrillation: Insights from the SAGE-AF Study

Background: Data from previous studies that examined sex differences in the characteristics, clinical presentation, and management of patients with atrial fibrillation (AF) have been inconsistent. Objective: To use data from a large contemporary cohort of older patients with AF to examine sex specific differences in baseline characteristics, symptoms, and management practices. Methods: We used data from baseline interviews and the review of medical records of participants in the Systematic Assessment of Geriatric Elements in AF (SAGE-AF) study. Participants were ≥ 65 years old with AF and a CHA2DS2-VASc≥ 2. Results: Of the 1244 participants, 49% were female. Women on average were slightly older (76.3 (7.4) vs. 74.8 (6.7) years, p&lt;0.01), and less often had a history of coronary heart disease, diabetes, renal disease, dyslipidemia, smoking, or alcohol abuse, in comparison with men. Women reported higher rates of anxiety, depression, and frailty (27% vs. 20%, 34% vs. 23%, and 18% vs. 10%, respectively, p&lt;0.01) when compared with men. Women had higher average CHA2DS2-VASc (4.9 (1.6) vs. 4.0 (1.5), p&lt;0.01) but lower HAS-BLED (2.7 (1.0) vs. 3.0 (1.0), p&lt;0.01) scores compared with men. Women more frequently reported AF-related symptoms of palpitations, irregular heartbeat, pause in heart activity, and dizziness (29% vs. 16%, 22% vs. 15%, 11% vs. 6%, and 25% vs. 19%, respectively, p&lt;0.05) than men. Women were more likely to have paroxysmal AF (54% vs. 65%, p&lt;0.01) than persistent AF (30% vs. 20%, p&lt;0.01) than men. Approximately 85% of study participants received oral anticoagulants (OACs). There were no significant differences in either the rates of prescription of OACs or their classes between men and women. There were no sex differences in the choice of rate or rhythm control treatments by sex. Multivariable adjusted models showed that women were less frequently treated with cardioversion (OR=0.69, 95% CI: 0.54-0.90), pacemaker (OR= 0.73, 95% CI: 0.56-0.96), or an implanted defibrillator (OR= 0.32, 95% CI: 0.21-0.50) compared with men. Conclusion: Women with AF were older, had more psychosocial but less comorbidities, and were more symptomatic than men. While no differences in the receipt of OACs were detected, women continue to be treated more conservatively with lower rates of receipt of interventions than men.

Is there a potential association between spironolactone and the risk of new-onset diabetes in a cohort of older patients with heart failure?

Some evidence suggests that spironolactone may have a deleterious effect on glucose homeostasis. The objective of this study was to assess whether spironolactone use is associated with a higher risk of developing diabetes in a large cohort of patients with heart failure (HF). Two Quebec government administrative databases were used to identify a cohort of hospitalized patients discharged between January 1995 and December 2009 with a primary discharge diagnosis of HF and without secondary discharge diagnosis of diabetes. Patients were categorized as new users of spironolactone and non-users. The primary outcome was defined as new-onset diabetes (NOD) during 5years of follow-up and was ascertained using ICD codes for diabetes or use of hypoglycemic agents. Among the 2974 patients that were included in the cohort analysis, 769 were given a new prescription of spironolactone. The incidence rate of NOD was similar among spironolactone users (5.0 per 100 person-years) and non-users (4.9 per 100 person-years). There was no significant association between the use of spironolactone and NOD in the crude, unadjusted model (hazard ratio (HR) 1.01; 95% confidence interval (CI) 0.80-1.28; p = 0.9217), and it remained unchanged in the adjusted Cox proportional hazard model (HR = 0.92; 95% CI = 0.72-1.18; p = 0.5227). The results were consistent with those observed in sensitivity analyses of a 1:3 propensity score-matched cohort (HR = 0.97; CI = 0.76-1.25; p = 0.8169). We found no evidence supporting the claim that use of spironolactone is associated with a higher risk of diabetes among patients hospitalized for HF.

Prevalence and Characteristics of Caregiver Distress One-Year after Allogeneic Hematopoietic Cell Transplant in an Older Cohort of Patients - a Single Institution Experience

Introduction Older patients with hematologic malignancies are increasingly considered for allogeneic hematopoietic cell transplant (allo-HCT). However, older patients may require increased level of post-transplant care than younger allo-HCT patients given their comorbidities. Moreover, older patients commonly have older caregivers and together, these factors contribute to increased caregiver distress, which has been shown to be associated with worsened health outcomes. Objectives To identify predictors of caregiver distress and examine the prevalence of caregiver distress in the older allo-HCT patient population. Methods We examined caregiver distress retrospectively for all patients aged 60 years and older who underwent first allo-HCT at our institution from 2015 to 2016. We systemically identified the incidence and characterized caregiver distress and attendance in a caregiver support group from the start of conditioning up to 1-year post allo-HCT. Caregiver distress was defined in this setting as any social work documentation of evidence of caregiver distress, including burnout, fatigue, burden, or difficulty coping. No standardized instruments were used given the nature of this study. Results 144 patients were included. Table 1 depicts the baseline caregiver characteristics, prevalence of caregiver distress, and attendance at the caregiver groups within one-year post allo-HCT. Caregivers of 15 patients (10%) had developed distress at a median of 14 days post-transplant (range day -5 to day +335). Caregivers of 29 patients (20%) had attended a caregiver support group meeting at least once. Caregiver distress was reported in multiple settings including early in hospitalization, during worsening of patient symptoms (pain, GVHD, pre-engraftment syndrome), critical illness, disease relapse, and readmission for complications. Caregiver distress was also noted when caregivers had documented health issues, difficulty coping with patient illness, or lack of social support. We examined independent association of pre-transplant variables with caregiver distress and caregiver support group participation and did not identify any significant association by univariate logistic regression. Conclusions While limited by the retrospective nature and likely underreporting, this study reveals areas of caregiver distress following allo-HCT for older patients. Future studies will attempt to better identify caregivers experiencing caregiver distress through a larger sample size and through inclusion of standardized assessments of caregiver distress, such as the caregiver reaction assessment, in social work meetings with caregivers. We will continue to examine patient records and to extend follow-ups to identify predictors of caregiver distress to improve outcomes for at-risk older patients and their caregivers.

Managing Challenges in an Aging Vestibular System: Rehabilitation Strategies Normalize Balance Function in a Cohort of Patients Up to 99 Years.

Imbalance is a major health problem affecting 90 million Americans and is the primary risk factor in falls, which consume $50 billion annually in medical costs (US). A person is often unaware of their balance challenge and its potential impact on fall risk and subsequent injury. Even when balance deficits and fall risk are realized, older patients may not pursue intervention for their disorder due to a fatalistic view of their advanced age. In this retrospective study, a cohort of older patients who had completed a course of vestibular rehabilitation therapy was studied for extent of recovery using computerized dynamic posturography (CDP) as the outcomes measure. The study group was comprised of sequential outpatients from a community-based balance treatment facility for whom pre- and posttherapy CDPs were available for analyses (N = 76). Patients had been referred for imbalance, vertigo, unsteadiness, and falls-age range 66 to 99 years (mean 80.5 years). Balance function, measured by composite sensory organization test (SOT) CDP scores, improved on average 35% ( P < .0001). Average posttherapy SOT score was 72.8, equivalent to the oldest SOT normative scores available (70 to 79 year age bracket; SOT Norm = 72.9). A subset 10 years above this eldest norm, mean age 89.4 years (N = 25, range 85 to 99 years), was then analyzed. Results revealed an improvement in balance function of 42.1% ( P < .0001), with average posttherapy SOT score of 74.2. Data confirm that vestibular therapy programs can significantly recover, if not normalize imbalance even to age 99. Given that the eldest participants were well above average life expectancy in the United States (78.9 years), this study could be used by allied health professionals to encourage older patients to engage in balance and falls prevention programs.

The Relationship between Age and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in a Cohort of Older Patients with Acute Myeloid Leukemia (AML)

Introduction: The use of allogeneic HSCT is considered a potential cure for AML but its use is limited in older patients because of significant comorbidities and increased transplant-related morbidity and mortality. However, there is evidence to suggest that older patients up to 80 years old may tolerate and benefit from intensive treatment, despite deteriorating organ function. This real-world analysis compared outcomes of Medicare-aged, chemotherapy-treated AML patients with or without HSCT.Methods: We performed a retrospective cohort analysis of 4,772 patients with a first primary AML in the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were diagnosed between January 1, 2000 and December 31, 2013, were aged > 66 years, continuously enrolled in Medicare Part A and B with no health maintenance organization (HMO) coverage in the year prior to diagnosis, and had received chemotherapy treatment within 3 months of diagnosis. Demographic and clinical characteristics were compared between patients who received HSCT and those who did not, using chi-square test for categorical variables and analysis of variance (ANOVA) or t-test for continuous variables. Unadjusted Kaplan-Meier survival plots were used to assess overall survival. Cox proportional hazards regression modeling evaluated the independent effects of covariates on overall survival, including receipt of HSCT, age, sex, race, prior myelodysplastic syndromes (MDS), poor performance indicators (PPIs), comorbidity burden, income, education, marital status, year of diagnosis, and geographic region. Date of last follow-up was December 31, 2015, permitting a minimum 2-year follow-up.Results: Of 4,772 patients with a first primary AML in the linked SEER-Medicare database, 403 (8%) underwent HSCT therapy after chemotherapy and 4,369 (92%) did not. Rates of HSCT increased over the study time period from 7% in 2000 to 12% in 2012 (P = 0.0033). Of the 403 patients who underwent HSCT, the majority (82%) were aged ≤ 75 years. Overall, patients in the HSCT group were younger at diagnosis (71 vs 75 years), more likely to be male (63% vs 54%), be married (66% vs 60%), less likely to have high-risk disease (11% vs 15% with prior MDS) or PPIs (4% vs 8%), and had lower comorbidity burden (59% vs 53% with a comorbidity score of 0) versus patients treated with chemotherapy only. In a subset analysis stratified by age, the relationships observed between patient characteristics and HSCT receipt persisted in the younger cohort of patients (≤ 75 years) but not in the older cohort (> 75 years). The unadjusted median overall survival was higher for the HSCT group (14.2 months) versus the non-HSCT group (4.8 months; log-rank P < 0.0001). In multivariate survival analysis, patients who underwent HSCT had a 40% lower risk of death versus those who did not undergo HSCT (hazard ratio [HR] 0.60; 95% CI 0.53-0.67). Advanced age, male sex, higher comorbidity score, prior MDS, and PPIs were significantly associated with higher risk of mortality. Stratifying by age, the survival benefit with HSCT was only demonstrated in the younger cohort aged ≤ 75 years (HR 0.53; 95% CI 0.46-0.60); no difference in mortality risk was noted in the older cohort aged > 75 years (HR 0.85; 95% CI 0.67-1.08).Conclusions: Overall, only 8% of patients receiving antileukemic therapy underwent subsequent HSCT therapy, and 82% of patients who did undergo HSCT were aged ≤ 75 years. HSCT was associated with a 40% reduction in mortality risk versus patients receiving chemotherapy only, and the survival benefit was more pronounced among the younger cohort aged ≤ 75 years, with a 47% reduction in mortality risk. Chronologic age appears to be the driving factor in HSCT receipt and prognosis, and these findings provide important new information on real-world outcomes on the benefit of HSCT in an elderly population. DisclosuresSatram-Hoang:Celgene Corp.: Research Funding; Genentech: Research Funding. Parisi:Celgene Corp.: Employment, Equity Ownership.

BIOMARKERS OF LEAKY GUT ARE RELATED TO INFLAMMATION AND REDUCED PHYSICAL FUNCTION IN UNHEALTHY OLDER ADULTS

Age-related leaky gut is hypothesized to be causative for the inflammatory burden of older adults. A relationship between the leaky gut biomarkers and physical function has been observed in healthy older adults, however it is not known whether co-morbid conditions alters this connection. Therefore, we measured biomarkers of inflammation and leaky gut within a cohort of older patients (60–79 years of age; n=288) enrolled into a weight loss and lifestyle intervention study (CLIP-1). Circulatory lipopolysaccharide binding protein 1 (LBP-1), soluble cluster of differentiation (sCD)14, pro-inflammatory cytokines were measured along with a panel of physical function measures. LBP-1 was strongly associated with increases in inflammatory cytokines interleukin (IL)-6, IL-6 soluble receptor, and IL-8 levels in the unadjusted correlation analysis. sCD14 associations were not as strong thus we chose LBP-1 in regression analyses. LBP-1 and inflammatory outcomes remained significantly associated even after adjustment for age, gender, and body mass index (BMI). LBP-1 was also significantly related to physical functional measures after adjusting for age, gender, and BMI. Log transformed 400m walk time (p=0.003) and log transformed IL-8 levels (p<0.001) were positively associated with LBP-1 even when adjusted for baseline IL-6 levels. The lifestyle interventions resulted in improved BMI and some physical function measures, however biomarkers of leaky gut and inflammation did not change. Leaky gut remains an important factor in inflammatory burdens and physical function in older adults with comorbid conditions. Strategies other than weight loss and exercise are needed to improve gut barrier function and limit inflammation in older persons.