Carolyn J. Presley

Patterns of Use and Short-Term Complications of Breast Brachytherapy in the National Medicare Population From 2008-2009

PURPOSE Brachytherapy has disseminated into clinical practice as an alternative to whole-breast irradiation (WBI) for early-stage breast cancer; however, current national treatment patterns and associated complications remain unknown. PATIENTS AND METHODS We constructed a national sample of Medicare beneficiaries ages 66 to 94 years who underwent breast-conserving surgery from 2008 to 2009 and were treated with brachytherapy or WBI. We used hospital referral regions (HRRs) to assess national treatment variation and an instrumental variable analysis to compare complication rates between treatment groups, adjusting for patient and clinical characteristics. We compared overall, wound and skin, and deep-tissue and bone complications between brachytherapy and WBI at 1 year of follow-up. RESULTS Of 29,648 women in our sample, 4,671 (15.8%) received brachytherapy. The percent of patients receiving brachytherapy varied substantially across HRRs, ranging from 0% to over 70% (interquartile range, 7.5% to 23.3%). Of women treated with brachytherapy, 34.3% had a complication compared with 27.3% of women undergoing WBI (P < .001). After adjusting for patient and clinical characteristics, 35.2% of women treated with brachytherapy (95% CI, 28.6 to 41.9) had a complication compared with 18.4% treated with WBI (95% CI, 15.5 to 21.3; P value for difference, <.001). Brachytherapy was associated with a 16.9% higher rate of wound and skin complications compared with WBI (95% CI, 10.0 to 23.9; P < .001), but there was no difference in deep-tissue and bone complications. CONCLUSION Brachytherapy is commonly used among Medicare beneficiaries and varies substantially across regions. After 1 year, wound and skin complications were significantly higher among women receiving brachytherapy compared with those receiving WBI.

The Relationship Between Clinical Benefit and Receipt of Curative Therapy for Prostate Cancer

Ann C. Raldow, MD1,2, Carolyn J. Presley, MD1,3, James B. Yu, MD1,4, Richa Sharma, MPH1, Laura D. Cramer, PhD1, Pamela R. Soulos, MPH1,3, Jessica B. Long, MPH1,3, Danil V. Makarov, MD, MHS1,5, and Cary P. Gross, MD1,3 1Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale Comprehensive Cancer Center and Yale University School of Medicine 2Department of Medicine, Memorial Sloan Kettering Cancer Center 3Section of General Internal Medicine, Department of Internal Medicine, Yale University School of Medicine 4Department of Therapeutic Radiology, Yale University School of Medicine 5Department of Urology, New York University School of Medicine and United States, Department of Veterans Affairs

Designing exercise clinical trials for older adults with cancer: Recommendations from 2015 Cancer and Aging Research Group NCI U13 Meeting

Cancer and its treatment can lead to a myriad of adverse events and negatively impact quality of life of older cancer patients and survivors. Unmet physical activity needs vary across the cancer continuum and remain an important yet understudied area of research in this population. Exercise interventions have been shown to be effective in treating both the physical and psychological declines associated with cancer and its treatment, with a potential to improve cancer-related outcomes. Despite the current evidence, exercise is clearly underutilized due to several barriers and knowledge gaps in existing trials that include appropriate population identification, design, and outcome measures selection. The benefits of regular exercise in both the primary and secondary prevention of chronic conditions are well established in the non-cancer population. In older cancer patients and survivors, further research is needed before exercise gains widespread acceptance. The Cancer and Aging Research Group convened experts in exercise, aging and cancer to evaluate current scientific evidence and knowledge gaps in geriatric exercise oncology. This report summarizes these findings and provides future research directions.

The Treatment of Advanced Lung Cancer in the Elderly: The Role of a Comprehensive Geriatric Assessment and Doublet Chemotherapy.

AbstractThe US lung cancer population is aging, the majority of which receive a diagnosis of incurable advanced non–small cell lung cancer (NSCLC). In US clinical oncology practice, elderly is defined as patients older than 70 years. Treatment of elderly patients with advanced NSCLC is complex. Choosing appropriate chemotherapy in this setting is complicated by multiple chronic conditions in addition to geriatric syndromes, challenging the traditional oncology practice. Although promising new options are on the horizon, the standard of care remains either platinum-based doublet or single-agent chemotherapy. Clinical trials have determined doublet therapy is appropriate for elderly patients; however, out of concern for excessive toxicity, many elderly patients do not receive appropriate treatment. Determining which patients are most likely to benefit from doublet chemotherapy versus monotherapy is a difficult challenge. Researchers have started to implement geriatric assessment and predictive chemotherapy toxicity tools in prospective clinical trials; however, knowledge gaps remain on how to appropriately select and treat elderly patients with advanced NSCLC in efforts to improve disease management and symptoms, maintain functional status, and minimize toxicity.

Gaps in nutritional research among older adults with cancer.

Nutritional issues among older adults with cancer are an understudied area of research despite significant prognostic implications for treatment side effects, cancer-specific mortality, and overall survival. In May of 2015, the National Cancer Institute and the National Institute on Aging co-sponsored a conference focused on future directions in geriatric oncology research. Nutritional research among older adults with cancer was highlighted as a major area of concern as most nutritional cancer research has been conducted among younger adults, with limited evidence to guide the care of nutritional issues among older adults with cancer. Cancer diagnoses among older adults are increasing, and the care of the older adult with cancer is complicated due to multimorbidity, heterogeneous functional status, polypharmacy, deficits in cognitive and mental health, and several other non-cancer factors. Due to this complexity, nutritional needs are dynamic, multifaceted, and dependent on the clinical scenario. This manuscript outlines the proceedings of this conference including knowledge gaps and recommendations for future nutritional research among older adults with cancer. Three common clinical scenarios encountered by oncologists include (1) weight loss during anti-cancer therapy, (2) malnutrition during advanced disease, and (3) obesity during survivorship. In this manuscript, we provide a brief overview of relevant cancer literature within these three areas, knowledge gaps that exist, and recommendations for future research.

Association of Broad-Based Genomic Sequencing With Survival Among Patients With Advanced Non–Small Cell Lung Cancer in the Community Oncology Setting

Importance Broad-based genomic sequencing is being used more frequently for patients with advanced non–small cell lung cancer (NSCLC). However, little is known about the association between broad-based genomic sequencing and treatment selection or survival among patients with advanced NSCLC in a community oncology setting. Objective To compare clinical outcomes between patients with advanced NSCLC who received broad-based genomic sequencing vs a control group of patients who received routine testing for EGFR mutations and/or ALK rearrangements alone. Design, Setting, and Participants Retrospective cohort study of patients with chart-confirmed advanced NSCLC between January 1, 2011, and July 31, 2016, and who received care at 1 of 191 oncology practices across the United States using the Flatiron Health Database. Patients were diagnosed with stage IIIB/IV or unresectable nonsquamous NSCLC who received at least 1 line of antineoplastic treatment. Exposures Receipt of either broad-based genomic sequencing or routine testing (EGFR and/or ALK only). Broad-based genomic sequencing included any multigene panel sequencing assay examining more than 30 genes prior to third-line treatment. Main Outcomes and Measures Primary outcomes were 12-month mortality and overall survival from the start of first-line treatment. Secondary outcomes included frequency of genetic alterations and treatments received. Results Among 5688 individuals with advanced NSCLC (median age, 67 years [interquartile range, 41-85], 63.6% white, 80% with a history of smoking); 875 (15.4%) received broad-based genomic sequencing and 4813 (84.6%) received routine testing. Among patients who received broad-based genomic sequencing, 4.5% received targeted treatment based on testing results, 9.8% received routine EGFR/ALK targeted treatment, and 85.1% received no targeted treatment. Unadjusted mortality rates at 12 months were 49.2% for patients undergoing broad-based genomic sequencing and 35.9% for patients undergoing routine testing. Using an instrumental variable analysis, there was no significant association between broad-based genomic sequencing and 12-month mortality (predicted probability of death at 12 months, 41.1% for broad-based genomic sequencing vs 44.4% for routine testing; difference −3.6% [95% CI, −18.4% to 11.1%]; P = .63). The results were consistent in the propensity score–matched survival analysis (42.0% vs 45.1%; hazard ratio, 0.92 [95% CI, 0.73 to 1.11]; P = .40) vs unmatched cohort (hazard ratio, 0.69 [95% CI, 0.62 to 0.77]; log-rank P < .001). Conclusions and Relevance Among patients with advanced non–small cell lung cancer receiving care in the community oncology setting, broad-based genomic sequencing directly informed treatment in a minority of patients and was not independently associated with better survival.

Treatment Burden of Medicare Beneficiaries With Stage I Non–Small-Cell Lung Cancer

PURPOSE To quantify the burden and complexity associated with treatment of Medicare beneficiaries with stage I non-small-cell lung cancer (NSCLC). METHODS Using the SEER-Medicare database, we conducted a retrospective cohort study of Medicare beneficiaries who were diagnosed with stage I NSCLC from 2007 to 2011 and who were treated with surgery, stereotactic body radiation therapy, or external beam radiation therapy. Main outcome measures were the number of days a patient was in contact with the health care system (encounter days), the number of physicians involved in a patients care, and the number of medications prescribed. Logistic regression modeled the association between patient characteristics, treatment type, and high treatment burden (defined as ≥ 66 encounter days). RESULTS On average, 7,955 patients spent 1 in 3 days interacting with the health care system during the initial 60 days of treatment. Patients experienced a median of 44 encounter days with high variability (interquartile range [IQR], 29 to 66) in the 12 months after treatment initiation. The median number of physicians involved was 20 (IQR, 14 to 28), and the median number of medications prescribed was 12 (IQR, 8 to 17). Patients who were treated with surgery had high treatment burden (predicted probability, 21.6%; 95% CI, 20.2 to 23.1) compared with patients who were treated with stereotactic body radiation therapy (predicted probability, 16.1%; 95% CI, 12.9 to 19.3), whereas patients who were treated with external beam radiation therapy had the highest burden (predicted probability, 46.8%; 95% CI, 43.3 to 50.2). CONCLUSION The treatment burden imposed on patients with early-stage NSCLC was substantial in terms of the number of encounters, physicians involved, and medications prescribed. Because treatment burden varied markedly across patients and treatment types, future work should identify opportunities to understand and ameliorate this burden.

Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials

Importance The US Food and Drug Administration (FDA) is increasing its pace of approvals for novel cancer therapeutics, including for immune checkpoint inhibitors of programmed cell death 1 protein (anti–PD-1 agents). However, little is known about how quickly anti–PD-1 agents agents reach eligible patients in practice or whether such patients differ from those studied in clinical trials that lead to FDA approval (pivotal clinical trials). Objectives To assess the speed with which anti–PD-1 agents agents reached eligible patients in practice and to compare the ages of patients treated in clinical practice with the ages of those treated in pivotal clinical trials. Design, Setting, and Participants This retrospective cohort study, performed from January 1, 2011, through August 31, 2016, included patients from the Flatiron Health Network who were eligible for anti–PD-1 agents treatment of selected cancer types, which included melanoma, non–small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Main Outcomes and Measures Cumulative proportions of eligible patients receiving anti–PD-1 agents treatment and their age distributions. Results The study identified 3089 patients who were eligible for anti–PD-1 agents treatment (median age, 66 [interquartile range, 56-75] years for patients with melanoma, 66 [interquartile range, 58-72] years for patients with RCC, and 67 [interquartile range, 59-74] years for patients with NSCLC; 1742 male [56.4%] and 1347 [43.6%] female; 2066 [66.9%] white). Of these patients, 2123 (68.7%) received anti–PD-1 agents treatment, including 439 eligible patients with melanoma (79.1%), 1417 eligible patients with NSCLC (65.6%), and 267 eligible patients with RCC (71.2%). Within 4 months after FDA approval, greater than 60% of eligible patients in each cohort had received anti–PD-1 agents treatment. Overall, similar proportions of older and younger patients received anti–PD-1 agents treatment during the first 9 months after FDA approval. However, there were significant differences in age between clinical trial participants and patients receiving anti–PD-1 agents treatment in clinical practice, with more patients being older than 65 years in clinical practice (range, 327 of 1365 [60.6%] to 46 of 72 [63.9%]) than in pivotal clinical trials (range, 38 of 120 [31.7%] to 223 of 544 [41.0%]; all P < .001). Conclusions and Relevance Anti-PD-1 agents rapidly reached patients in clinical practice, and patients treated in clinical practice differed significantly from patients treated in pivotal clinical trials. Future actions are needed to ensure that rapid adoption occurs on the basis of representative trial evidence.

Functional trajectories before and after a new cancer diagnosis among community-dwelling older adults

BACKGROUND To characterize functional trajectories in the year before and after a new cancer diagnosis among older adults and to identify risk factors for worsening disability post-diagnosis. METHODS We identified 170 participants 70+ years with monthly assessments of thirteen basic, instrumental, and mobility activities and with a new cancer diagnosis from 1998 to 2014. A group-based trajectory model identified distinct functional trajectories based on a total disability score during the twelve months pre- and post-diagnosis. We evaluated associations between potential risk factors at the time of cancer diagnosis and worsening disability post-diagnosis, explored functional transitions from pre- to post-diagnosis and identified participants whose functional trajectories worsened. RESULTS Three pre-diagnosis functional trajectories were identified among 170 participants (mean age at diagnosis: 83 years (range: 73-105 years): mild, moderate, and severe disability. Three post-diagnosis functional trajectories were identified among 158 non-decedents: mild, moderate, and severe disability. Most participants (93.9%) with severe disability pre-diagnosis had severe disability post-diagnosis. Risk factors independently associated with worsening disability post-diagnosis included moderate or severe disability pre-diagnosis (adjusted risk ratio, aRR: moderate: 2.96; 95%CI: 2.11-4.16; severe: 5.11; 95%CI: 3.07-8.52) vs. mild (reference), poor physical capability (aRR: 1.57; 95%CI: 1.07-2.30), and incurable stage (aRR:1.99; 95%CI: 1.41-2.80). 40% of participants with a mild or moderate disability trajectory pre-diagnosis transitioned to a worse functional trajectory post-diagnosis. CONCLUSION Older adults followed distinct functional trajectories in the twelve months before and after cancer diagnosis. Functional trajectory pre-diagnosis, poor physical capability, and incurable stage were independent risk factors for worsening disability post-diagnosis.