bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a programming algorithm for deep brain stimulation in dystonia used in a double-blind, sham-controlled multicenter study
Authors:   for the DBS study group for dystonia, Steigerwald Frank , Kirsch Anna Dalal , Kühn Andrea A. , Kupsch Andreas , Mueller Joerg , Eisner Wilhelm , Deuschl Günther , Falk Daniela , Schnitzler Alfons , Skogseid Inger Marie , Vollmer-Haase Juliane , Ip Chi W. , Tronnier Volker , Vesper Jan , Naumann Markus , Volkmann Jens
Published: October 2019

Background

Programming deep brain stimulation in dystonia is difficult because of the delayed benefits and absence of evidence-based guidelines. Therefore, we evaluated the efficacy of a programming algorithm applied in a double-blind, sham-controlled multicenter study of pallidal deep brain stimulation in dystonia.

Methods

A standardized monopolar review to identify the contact with the best acute antidystonic effect was applied in 40 patients, who were then programmed 0.5 V below the adverse effect threshold and maintained on these settings for at least 3 months, if tolerated. If no acute effects were observed, contact selection was based on adverse effects or anatomical criteria. Three-year follow-up data was available for 31 patients, and five-year data for 32 patients. The efficacy of the algorithm was based on changes in motor scores, adverse events, and the need for reprogramming.

Results

The mean (±standard deviation) dystonia motor score decreased by 73 ± 24% at 3 years and 63 ± 38% at 5 years for contacts that exhibited acute improvement of dystonia (n = 17) during the monopolar review. Contacts without acute benefit improved by 58 ± 30% at 3 years (n = 63) and 53 ± 31% at 5 years (n = 59). Interestingly, acute worsening or induction of dystonia/dyskinesia (n = 9) correlated significantly with improvement after 3 years, but not 5 years.

Conclusions

Monopolar review helped to detect the best therapeutic contact in approximately 30% of patients exhibiting acute modulation of dystonic symptoms. Acute improvement, as well as worsening of dystonia, predicted a good long-term outcome, while induction of phosphenes did not correlate with outcome.

Trial registration

ClinicalTrials.gov NCT00142259.
An automatic nuclei segmentation method based on deep convolutional neural networks for histopathology images
Authors: Jung Hwejin , Lodhi Bilal , Kang Jaewoo
Published: October 2019

Background

Since nuclei segmentation in histopathology images can provide key information for identifying the presence or stage of a disease, the images need to be assessed carefully. However, color variation in histopathology images, and various structures of nuclei are two major obstacles in accurately segmenting and analyzing histopathology images. Several machine learning methods heavily rely on hand-crafted features which have limitations due to manual thresholding.

Results

To obtain robust results, deep learning based methods have been proposed. Deep convolutional neural networks (DCNN) used for automatically extracting features from raw image data have been proven to achieve great performance. Inspired by such achievements, we propose a nuclei segmentation method based on DCNNs. To normalize the color of histopathology images, we use a deep convolutional Gaussian mixture color normalization model which is able to cluster pixels while considering the structures of nuclei. To segment nuclei, we use Mask R-CNN which achieves state-of-the-art object segmentation performance in the field of computer vision. In addition, we perform multiple inference as a post-processing step to boost segmentation performance. We evaluate our segmentation method on two different datasets. The first dataset consists of histopathology images of various organ while the other consists histopathology images of the same organ. Performance of our segmentation method is measured in various experimental setups at the object-level and the pixel-level. In addition, we compare the performance of our method with that of existing state-of-the-art methods. The experimental results show that our nuclei segmentation method outperforms the existing methods.

Conclusions

We propose a nuclei segmentation method based on DCNNs for histopathology images. The proposed method which uses Mask R-CNN with color normalization and multiple inference post-processing provides robust nuclei segmentation results. Our method also can facilitate downstream nuclei morphological analyses as it provides high-quality features extracted from histopathology images.
Lipopolysaccharide induces neuroglia activation and NF-κB activation in cerebral cortex of adult mice
Authors: Kang Ju-Bin , Park Dong-Ju , Shah Murad-Ali , Kim Myeong-Ok , Koh Phil-Ok
Published: October 2019

Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 μg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.
The effect of duration of dependence and daily dose of tramadol in tramadol dependent patients on cognitive performance
Authors: Ahmad Hossam Eddin Khalifa , Darweesh Alaa Eldin Mohamed , Hassaan Shehab Hassan Mahmoud , Nooman Mostafa , Shaaban Islam , Sayed Sayed Mostafa
Published: October 2019

Background

Tramadol dependence represents a major medical and legal hazardous phenomenon in the last decade. It is a synthetic opiate analgesic which exerts its therapeutic effect by its action on μ opioid receptors. It has a weak dependence ability. The present study investigated the effect of duration of dependence and daily dose of tramadol on cognitive performance. Cognitive functions were assessed using the following: the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) test, Brief Visuospatial Memory Test–Revised (BVMT-R), Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the P300 (ERP), and conventional electroencephalogram.

Results

There was a non-significant negative correlation between the daily dose of tramadol and cognitive performance as regards IQ, Mini-Mental State Examination, MoCA score, P300 reaction time (μs), and deterioration index (r = − 0.08, P = 0.689; r = − 0.02, P = 0.896; r = − 0.11, P = 0.554; r = − 0.11, P = 0.581, r = − 0.17; P = 0.368, respectively). Additionally, the results showed non-significant negative correlation between the duration of dependence and the cognitive performance (r = − 0.19, P = 0.325; r = − 0.15, P = 0.424; r = − 0.30, P = 0.108; r = − 0.02, P = 0.909; r = − 0.02, P = 0.937, respectively).

Conclusion

Daily dose and duration of tramadol dependence have a negative but non-significant effect on cognitive performance.
Improving Adjuvant Endocrine Treatment Tailoring in Premenopausal Women With Hormone Receptor–Positive Breast Cancer
Authors: Lambertini Matteo , Blondeaux Eva , Perrone Francesco , Del Mastro Lucia
Published: October 2019

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Changes in employment and insurance for patients with cancer receiving safety net services.
Authors: Caston Nicole , Williams Courtney , Balch Alan James , Gallagher Kathleen D. , Rocque Gabrielle Betty
Published: October 2019

104

Background: Under-resourced patients with cancer often face financial burdens due, not only to costs of treatment, but also from side effects that prevent individuals’ ability to work, which impact employment status and may cause insurance coverage loss. Financial assistance may be sought from safety net programs, which provide both material support and financial counseling. However, knowledge of the impact of cancer on employment and insurance in a population seeking safety net services is limited. Methods: This observational, cross-sectional study uses data on safety net services from a nationwide survey conducted in July 2017 and distributed by the Patient Advocate Foundation (PAF). The survey respondents included patients with cancer who received services from PAF from July 2016 to June 2017. Descriptive statistics were calculated using frequencies for categorical variables. Results: A total of 508 patients with cancer completed the survey. Most patients had a diagnosis of breast cancer (47%), followed by myeloma (13%), and prostate cancer (8%). The majority of patients reported that their illness affected their employment (67%); by either job loss (13%), income loss (24%), or inability to work as usual (27%). Of these patients, 27% lost their insurance coverage. Those able to enroll in a new insurance plan reported having more expensive rates (40%) and fewer covered services (36%) compared to their previous coverage. The most commonly utilized governmental safety net services were Social Security Disability Insurance (19%) and Medicaid (12%). Non-governmental safety net services such as financial assistance from non-profits (27%) and free medication from drug companies (13%) were also frequently used. Beyond their insurance coverage, cancer patients still needed assistance paying for diagnostic tests (18%), clinic visit fees (23%), and prescription drugs (15%) from the safety net program. Conclusions: Cancer patients commonly experience financial burden due to losses in employment and insurance, resulting in need for safety net programs. Further work is needed to identify approaches to reducing the adverse financial impact of cancer care.
Risk factors for healthcare utilization in patients with newly diagnosed advanced lung cancer.
Authors: Ray Emily Miller , Hinton Sharon Peacock , Reeder-Hayes Katherine Elizabeth
Published: October 2019

111

Background: Advanced lung cancer (ALC) is a symptomatic disease often diagnosed in the context of hospitalization. The index hospitalization may be a window of opportunity to improve care delivery. We aimed to identify newly diagnosed ALC patients at highest risk for subsequent healthcare utilization. Methods: We identified patients in SEER-Medicare with: ALC (stage IIIB-IV SCLC or NSCLC), diagnosed 2007-13; continuous enrollment -6 months from diagnosis through death or 12/2014; and an index hospitalization within 7 days of ALC diagnosis. Our primary outcomes were 30-day re-hospitalization and emergency department (ED) use. We used a time-to-event model with multivariate regression to identify risk factors. Results: Of ALC patients in SEER-Medicare, 54% (n=28,976) had an index hospitalization. Of those who survived to discharge, by 6 months, 47% had been re-hospitalized, and 50% had enrolled in hospice. Only 37% of patients ever received systemic treatment for their cancer, and the median time to treatment was 46 days. The 30-day ED visit and readmission rates were 13% and 35%, respectively. Pre-cancer ED use or hospitalization, SCLC, and prolonged length of stay were associated with higher risk of 30-day utilization. Palliative care consultation and discharge to hospice were associated with substantially lower risk of 30-day readmission. Conclusions: Many newly diagnosed ALC patients experience an early return to the hospital. These patients may benefit from increased access to palliative and other supportive care during index hospitalization to prevent subsequent healthcare utilization.

[Table: see text]
Value appraisal of FDA approved cancer drugs over the past decade.
Authors: Huey Ryan , Anand Seerat , Rogers Jane Elizabeth , Dasari Arvind , Varadhachary Gauri Rajani , Gothwal Anirudh , Loree Jonathan M. , Ellis Lee M. , Overman Michael J. , Raghav Kanwal Pratap Singh
Published: October 2019

115

Background: Value based drug pricing is emerging as an imperative health care precept in recognition of the ever-increasing drug costs, especially in oncology. Though novel therapies are regularly approved based on benefit, they are often associated with physical and financial toxicities to patients. We aimed to assess the value of FDA approved oncology drugs defined as their expected clinical benefit compared to their toxicities and costs. Methods: We reviewed all new cancer drug approvals by the FDA from 7/2008-6/2018. Current analysis was restricted to approvals based on overall survival (OS) and progression-free survival (PFS). Data regarding approval indication, effect size, and toxicity were collected from FDA website and publications. Toxicity was estimated as adverse events ≥ grade 3 (or serious adverse events) as reported. Micromedex RED BOOK was used to estimate the total drug price using 2018 average wholesale prices. Price was estimated over 3 months to account for difference in drug regimens. Results: Among the 231 trials used by FDA for approvals in oncology, 115 had OS or PFS as their primary endpoint. Median patients per trial was 539. Of 79 trials with a PFS endpoint, the median HR was 0.50 (range: 0.15 - 0.91); median 3-month drug price was $45,903.72. Compared to the control arm, median toxicity for new drugs was 7% higher (range: -34.4 - 55%). Correlation of HR benefit to 3-month price was 0.06 (95% CI: -0.17 - 0.28, P = 0.61). Correlation of net toxicities to 3-month price was 0.01 (95% CI: -0.25 - 0.26, P = 0.94). Of 43 trials with an OS endpoint, the median HR was 0.72 (range: 0.37 - 0.94); median 3-month price was $43,523.46. Relative to control arm, median toxicity for new drugs was 4% higher (range: -34.4 - 45.8%). Correlation of HR benefit to 3-month price was 0.38 (95% CI: 0.08 - 0.62, P = 0.012). Correlation of net toxicities to 3-month price was -0.12 (95% CI: -0.45 - 0.24, P = 0.50). Conclusions: Drug approvals in oncology come with a high cost and drug prices have very little correlation with estimated benefit in outcomes and toxicities. As policies evolve to promote higher value in health care, attention should be paid to benefits of drugs in relation to pricing and using biomarker-based patient selection to maximize benefits and minimize toxicities.
Capturing discrete complete staging elements in EPIC for new and progressing breast (B) and prostate (P) cancer patients: A quality training program pilot.
Authors: Bosserman Linda D. , Morse Denise , McNeese Kathleen , Atcha Ridaa , Patel Niki Himat
Published: October 2019

117

Background: Staging is a fundamental quality metric. Entry of discrete elements of staging in the EHR supports & improves efficiencies for clinical notes, therapy summaries, survivorship plans, clinical decision making, pathway use, timely authorizations, clinical trial eligibility evaluations, as well as clinical, financial & quality outcomes. Staging of all new & progressing patients in our EPIC EHR was set as a priority in 2018 but baseline entry through 2018 was below target goals. Methods: A Staging QTP project group was formed & participated in the COH-ASCO QTP Fall training. Baseline capture of staging data in EPIC for campus and community (enterprise) sites for Breast (B) & Prostate (P) patients was collected. QTP processes were used to develop and implement a 12-week pilot with PDSA cycles at weeks 8 and 12. B & P cancer patients seen by 3 B & 2 P medical oncologists (MO), 5B surgeons (S) & 3P urologists (U) agreed to participate in a pilot study. Disease leads determined the elements of complete staging: 9-10 for B & 8 for P. Training was done for all campus APPs & for doctors in the pilot. Follow up by the QTP team was done at clinics during the pilot. Reports were built to capture specific staging elements for B & P patients by doctor. Reports were sent out starting week 9 indicating patients without complete staging with missing elements. A survey about the process was done by participant MDs & APPS weeks 8 & 12. Results: Baseline enterprise wide complete staging in Epic was 6% for B cancer & 3% for P cancer. 6 week PDSA showed capture of complete staging for B-MO & S was 20% and for P-MO & U was 12%. QTP Pilot ends 6/19 & abstract data will be updated for the staging & survey results. Additional results on complete staging for progressing patients is being captured. Conclusions: Complete staging in the EHR requires definition, training, resourcing, leadership support and feedback. Initial results show all new patients had initial staging data entered and complete staging rates increased significantly for new B & P cancer patients before weekly feedback was sent. Analysis of survey results will inform future PDSA cycles & plans for complete staging enterprise wide.
Changing treatment patterns in patients with stage IV non-small cell lung cancer (NSCLC) from United States community-based oncology practices.
Authors: Yong Candice , Seal Brian , Coutinho Anna D. , Lunacsek Orsolya , Dean Bonnie B. , Willey Joanne P. , Eaddy Michael , Cotarla Ion , Mehra Ranee
Published: October 2019

13

Background: This study evaluated the shift in treatment patterns in Stage IV NSCLC following the approval of immune-oncology (IO) agents in the US. Methods: A retrospective cohort study was performed using structured data from a US community-based oncology electronic medical record (EMR) database for care received from Jan 2015-May 2018. The study sample included patients with Stage IV NSCLC, ≥18 years of age initiating first-line (1L) treatment with chemotherapy (chemo) or IO agents and classified into 3 groups: chemo alone, IO alone, or chemo+IO. Treatment patterns in 1L and treatment switch patterns in second-line (2L) are reported. A sub-group analysis of patients initiating 1L therapy during the last 6 months of the study period (Dec 2017-May 2018) was conducted to explore changes in 1L treatment patterns in the post-IO approval setting. Chart reviews were done for a subset of patients initiating 1L from Jan 2017-May 2018 to extract information on programmed cell death ligand 1 (PD-L1) testing and evaluate the association of PD-L1 expression levels with receipt of IO therapy. Results: Between Jan 2015-May 2018, 1,969 patients received 1L therapy with a chemo or IO agent. Mean age (SD) was 69.0 (10.1) years, with 44.7% female. The majority of patients (79%, n = 1570) initiated 1L therapy with chemo alone and 21% initiated IO (alone [14%, n = 271] or in combination with chemo [7%, n = 128]). Of 1L patients, 41% (n = 809) were treated with 2L therapy. Of the 1L chemo alone group, 37% (n = 580) received IO in 2L. The use of IO agents in 1L increased from 21% to 48% (n = 147) in the sub-group analysis of 305 patients initiating therapy Dec 2017-May 2018. In the subset of 62 patients whose charts were reviewed, 87% (n = 54) had their tumor tested for PD-L1, of which 37% (n = 20) had high (≥50%) expression values. The majority of high-PD-L1 patients were treated in 1L with IO alone (80%, n = 16), followed by chemo+IO (15%; n = 3), and only 5% (n = 1) received chemo alone. Conclusions: Initially, IO was used as 2L treatment for Stage IV NSCLC, but IO use shifted to 1L setting in the US by the end of 2017. The use of IO therapy alone or with chemotherapy in 1L was more likely in patients with ≥50% PD-L1 expression level.
Potential impact of clinical trial (CT) participation on survival of patients with metastatic non-small cell lung cancer (NSCLC).
Authors: Merkhofer Cristina , Eaton Keith D. , Martins Renato G. , Ramsey Scott David , Goulart Bernardo H. L.
Published: October 2019

137

Background: Evidence is conflicting as to whether enrollment in therapeutic drug trials confers a survival benefit for NSCLC patients. We assessed the effect of CT participation on overall survival in a cohort of metastatic NSCLC patients treated at a single large academic center. Methods: We retrospectively revised medical records of patients with metastatic NSCLC diagnosed between 1/1/2007 and 12/31/2015 that received treatment at the Seattle Cancer Care Alliance. Eligibility criteria included receipt of ≥ 1 anti-cancer drug within 180 days of M1 diagnosis, no active second malignancy, and 60 day minimum survival. We abstracted patient sociodemographic characteristics, smoking history, ECOG score, tumor histology, EGFR and ALK status, presence of brain metastases, systemic treatment history up to 5 lines, drug trial enrollment, and trial characteristics. We obtained death dates from the Washington State cancer registry complemented by medical records, censoring patients that were alive at end of follow-up (3/7/2019). We used multivariate Cox regression to test whether enrollment in ≥ 1 CT was associated with overall survival. Results: Of 371 eligible patients (median age 63.9 years, 47% male, 94% non-squamous histology, 30% never-smokers, 58% ECOG 0-1, 20% EGFR positive and 8% ALK positive, and 27% brain metastases), 118 (32%) enrolled in ≥ 1 CT. Of CT enrollees: 19% enrolled in > 1 CT, 89% in phase I/II trials, 15% in phase III trials, 26% in randomized trials, and 51% in trials of drugs later approved by the FDA. Median survival in CT enrollees was 838 days (95% CI 688, 1,021), as compared to 454 days in non-enrollees (95% CI 378, 511). After adjusting for sex, ECOG score, smoking, histology, EGFR and ALK status, and presence of brain metastases, CT enrollees had a 47% lower risk of death relative to non-enrollees (HR 0.53; 95% CI 0.13, 0.92; P = 0.002). Conclusions: Participation in therapeutic drug trials is associated with longer overall survival in advanced NSCLC. Besides supporting drug development, CT participation may directly benefit NSCLC patients by providing access to promising agents and/or enhanced supportive care.
Level of scientific evidence supporting NCCN guidelines: Is there evidence of progress?
Authors: Desai Aakash , Go Ronald S. , Poonacha Thejaswi
Published: October 2019

14

Background: National Comprehensive Cancer Network (NCCN) guidelines are the most comprehensive and widely used standard for clinical care in oncology by clinicians and payors in the US. The level of scientific evidence in NCCN guidelines has not been studied since it’s last review in 2010. We describe the categories of evidence and consensus (EC) among the 10 most common cancers in the US as of 2019 and compare them with 2010 guidelines. Methods: We obtained the 2019 version of NCCN guidelines. The definitions for various categories of EC used were: Category 1 (high level evidence such as randomized controlled trials with uniform consensus), 2A (lower level of evidence with uniform consensus), 2B (lower level of evidence without a uniform consensus but with no major disagreement) and 3 (any level of evidence but with major disagreement). We compared our results with previously published results from 2010 guidelines. Results: Total recommendations increased by 77% from 1023 (2010) to 1818 (2019). Of the 1818 recommendations, Category 1, 2A, 2B and 3 EC were 7%, 87%, 6% and 0% while in 2010 they were 5%, 85%, 9% and 1% respectively. Recommendations with category 1 EC were found in lung (13%), prostate (11%), melanoma (8%), breast (7%), NHL (5%), kidney (2%), bladder (2%) and colorectal (2%) guidelines. Pancreatic and uterine cancer guidelines had no recommendations with category 1 EC. 19% of therapeutic recommendations were category 1 EC with the majority (65%) pertaining to initial therapy. Guidelines with highest proportions of therapeutic recommendations with category 1 EC were breast (30%), lung (10%), and kidney (10%) cancers. No category 1 EC recommendations existed in screening or surveillance. Although we found an increase in the total number of recommendations, the distribution of different types of categories of EC are largely similar to 2010. Conclusions: Recommendations in 2019 NCCN guidelines are largely derived from lower levels of evidence with uniform expert opinion. Despite the major advances in oncology in the past decade, this is largely unchanged. Our study underscores the urgent need and available opportunities to expand the current evidence base in oncology which forms the platform for clinical practice guidelines.
Racial/ethnic disparities in childhood cancer survival in the United States: Mediation effects of health insurance coverage and area-level social deprivation.
Authors: Zhao Jingxuan , Han Xuesong , Zheng Zhiyuan , Nogueira Leticia Maciel , Nathan Paul C. , Lu Amy , Yabroff K Robin
Published: October 2019

143

Background: Childhood cancer survival varies by race/ethnicity in the United States. This study evaluated the impact of potentially modifiable characteristics - health insurance and area-level social deprivation - on racial/ethnic disparities in childhood cancer survival nationwide. Methods: We identified 65,113 childhood cancer patients aged < 18 years newly diagnosed with any of 10 common cancer types (e.g. central nervous system (CNS) neoplasms, acute lymphoblastic leukemia (ALL), Hodgkin lymphoma) from the 2004-2014 National Cancer Database. Cox proportional hazard models were used to compare survival probabilities by race and ethnicity (non-Hispanic white (NHW) vs non-Hispanic black (NHB), Hispanic, and non-Hispanic other (NH other)) for each cancer type. We conducted mediation analyses by the mma R package to evaluate the racial/ethnic survival disparities mediated by health insurance (private, Medicaid, and uninsured) and social deprivation index (SDI) quartile. SDI is a composite measure of deprivation based on seven characteristics (e.g. income, education, employment). Results: Compared to NHW, worse survival were observed for NHB (HR (hazard ratio): 1.4, 95% CI: 1.3-1.5), Hispanic (HR: 1.2, 95% CI: 1.1-1.2), and NH other (HR: 1.2, 95% CI: 1.1-1.3) for all cancer sites combined after adjusting for sociodemographic characteristics other than health insurance and SDI. Health insurance explained 20% of the survival disparities and SDI explained 19% of the disparity between NHB vs NHW; health insurance explained 48% of the survival disparities and SDI explained 45% of the disparity between Hispanic vs NHW. For ALL, health insurance significantly explained 15% and 18% of the survival disparities between NHB and Hispanic vs NHW, respectively. SDI significantly explained 19% and 31% of the disparities, respectively. Conclusions: Health insurance and SDI mediated racial/ethnic survival disparities for several childhood cancers. Expanding insurance coverage and improving healthcare access in disadvantaged areas may effectively reduce disparities for these cancer sites.
Barriers to minority recruitment in a multicenter clinical trial (PRO-TECT [AFT-39]): Research staff insights.
Authors: Charlot Marjory , Henson Sydney , Spears Patty , Schrag Deborah , Stover Angela M. , Basch Ethan M.
Published: October 2019

145

Background: Rates of minority enrollment in U.S. cancer clinical trials, including supportive care trials, are disproportionately low. Clinical research associates (CRAs) are the linchpin for successful accrual and often help screen and approach patients to discuss research studies. We sought to understand clinic-level factors that influence recruitment of African American patients (AA) in an ongoing U.S. multicenter, cluster- randomized controlled trial (PRO-TECT: Patient-Reported Outcomes to Enhance Cancer Treatment; NCT03249090 AFT-39]). Notably, partway through this trial, a purposeful enrollment strategy was initiated where sites were asked to focus on minority recruitment. Methods: A subset of community oncology practices participating in PRO-TECT was identified with: 1) overall patient populations ≥20% AA; or 2) <20% AA but trial enrollment ≥20% AA. Semi-structured phone interviews were conducted with CRAs at each site to elicit perceived barriers and facilitators in identifying and approaching AA patients for this trial. Results: Among 13 identified community practices out of a potential 50 randomized sites, 3 had populations <20% AA but enrollment >20% AA; 3 had populations ≥20% AA but enrollment <20% AA; and 7 had populations ≥20% AA and enrollment >20% AA. All sites identified participants through review of clinic visit lists with clinicians. Eleven out of 13 sites felt they experienced no barriers to identifying, approaching, or enrolling minority patients. One site CRA felt minority patients are often “too sick to participate”. One CRA felt awkward about the request to purposefully approach minority patients. Conclusions: Site CRAs generally did not perceive barriers to minority recruitment, even when their population demographics were underrepresented in accrual. Results of efforts in this trial to increase minority participation through a purposeful enrollment strategy will be reported elsewhere.
Bias and stereotyping among research and clinical professionals: Perspectives on minority recruitment for oncology clinical trials.
Authors: Niranjan Soumya J. , Martin Michelle Y. , Fouad Mona N , Vickers Selwyn M. , Wenzel Jennifer , Cook Elise D. , Konety Badrinath R. , Durant Raegan W
Published: October 2019

152

Background: Extensive attention has been paid in recent years to the possibility that bias among health care professionals contributes to health disparities. In its 2003 report, Unequal Treatment, the Institute of Medicine concluded that bias against racial minorities may affect communication or care offered. However, the role of bias in the context of recruitment of racial minorities in cancer clinical trials has not been explored. Therefore, we assessed clinical and research personnel’s experiences related to factors influencing recruitment of racial and ethnic minorities for cancer clinical trials. Methods: Ninety-one qualitative interviews were conducted at 5 U.S. cancer centers among 4 stakeholder groups: cancer center leaders, principal investigators, referring clinicians and research staff. Data analysis was conducted using a content analysis approach to generate themes from the transcribed interviews. Results: Five prominent themes emerged. 1) Recruitment interactions with potential minority participants were perceived to be challenging. 2) Potential minority participants were not perceived to be ideal study candidates. 3) A combination of clinic level barriers and negative perceptions of minority study participants led to providers withholding clinical trial opportunities from potential minority participants. 4) When clinical trial recruitment practices were tailored to minority patients, addressing research misconceptions to build trust was a common strategy. 5) For some respondents, race was perceived as irrelevant when screening and recruiting potential minority participants for clinical trials. Conclusions: Not only did some respondents view racial and ethnic minorities as less promising participants, some respondents reported withholding trial opportunities to minorities based on these perceptions. Some providers endorsed using tailored recruitment strategies while others eschewed race as a factor in trial recruitment. The presence of bias and stereotyping among clinical and research professionals recruiting for cancer clinical trials, should be considered when designing interventions to increase minority enrollment.
ENRICH: Validating a multidimensional patient-reported financial toxicity measure.
Authors: Smith Grace L. , Volk Robert Joseph , Lowenstein Lisa M , Peterson Susan K. , Rieber Alyssa G. , Checka Cristina , Christopherson Kaitlin M. , Jagsi Reshma , Giordano Sharon H. , Mendoza Tito R.
Published: October 2019

153

Background: Financial toxicity is a patient-reported outcome reflecting burdens of cancer treatment costs. There is a need to assess financial toxicity in cancer care, as its unique domains—upstream factors like direct medical costs or downstream economic impact like bankruptcy—predict worse QOL, adherence, and mortality. Socioeconomically disadvantaged patients bear disparate financial toxicity burdens. We thus developed and report performance of a new measure, the Economic StraiN and Resilience in Cancer (ENRICh), to assess all financial toxicity domains in economically diverse patients. Methods: We studied 238 patients with Stage I-IV cancer from a tertiary academic comprehensive cancer center (MDA) and county safety-net hospital serving socioeconomically disadvantaged patients (LBJ). Financial toxicity domains and corresponding subscales were developed from qualitative/cognitive (n = 104) interviews. ENRICh and Comprehensive Score for Financial Toxicity (COST) questions were administered (n = 127; MDA = 71, LBJ = 56). To demonstrate known-group validity, we compared ENRICh scores between centers; for concurrent validity, we correlated ENRICh and COST; for reliability, we calculated Cronbach's coefficient α for ENRICh subscales (range 0, none, to 10, high burden). Results: There were 4 distinct, valid financial toxicity domains/subscales: 1) Burden of cost; 2) Disruption of financial stability; 3) Depletion of financial coping; 4) Depletion of instrumental coping. Patients from the 2 centers significantly differed in subscale and overall ENRICh scores. Socioeconomically disadvantaged patients had worse mean scores (4.9 vs 2.1, 95%CI -3.6,-2.1, effect size 1.4, P < .001). ENRICh significantly correlated with COST (r = -0.82, 95%CI -0.87,-0.77, P < .001). Subscales were reliable with excellent internal consistency (Cronbach α = 0.78 to 0.94). The 4 ENRICh domains collectively had synergistic impact on overall financial toxicity burden. Conclusions: ENRICh is valid, reliable, and identifies and 4 novel domains of financial toxicity. Future utility of this tool is to guide assessment/interventions targeting financial toxicity domains affecting diverse cancer patients, to mitigate disparities.
Examining Oncotype DX testing among a diverse patient population in North Carolina.
Authors: Marsh Katie , Benefield Thad , Lee Sheila , Henderson Louise
Published: October 2019

154

Background: The Oncotype DX (ODX) is a 21-gene assay that quantifies the risk of breast cancer recurrence and predicts chemotherapy benefit among early stage, hormone-receptor positive patients. Most major insurance carriers now cover testing. We sought to determine factors associated with ODX testing in a diverse patient population. Methods: Data from the Carolina Mammography Registry (CMR), a breast imaging registry in North Carolina (NC) was used for this analysis. We included women ages 18 and over diagnosed with breast cancer from 2010-2017 who had a breast imaging exam at a CMR facility with no personal history of breast cancer. ODX testing was obtained through linkage with the NC Central Cancer Registry. Using a backwards elimination selection strategy, we explored the association of patient residence (urban versus rural), age, race, breast density, and family history of breast cancer on receipt of ODX testing. Results: Our population included 12,329 breast cancers among women that were 24.2% non-white with a median age of 64 years (11.2% < 50 years at time of diagnosis). The majority of our sample had dense breasts (52.0%), no family history of breast cancer (80.9%), and lived in urban areas (66.3%). Use of ODX testing increased from 15.7% in 2010 to 24.8% in 2017 (p-value for time trend < 0.00001). Compared with white women, black women were less likely to receive ODX testing (aOR = 0.57; 95% CI: 0.51-0.65), as were women of other races (aOR = 0.68; 95% CI: 0.51-0.90). We found that for every year age increased, the likelihood of receiving ODX testing decreased (aOR = 0.98, 95% CI: 0.97-0.98). Patient residence and breast density influenced the association of ODX testing. Among women in urban areas, women with dense versus non-dense breasts were more likely to receive ODX testing (aOR = 1.13; 95% CI: 1.01-1.27). Among women in rural areas, density was not associated with ODX testing (aOR = 0.91; 95% CI: 0.78-1.06). Conclusions: In our cohort, ODX testing was more common among younger white women with dense breast tissue living in urban areas of NC. Additional research to understand differences in testing by rural/urban areas are warranted to ensure that all appropriate patients receive this genetic assay.
Assessing time to treatment initiation and care delivery among patients with cancer and co-occurring Alzheimer's disease and related dementia using claims data.
Authors: Schiaffino Melody K
Published: October 2019

161

Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in Americans. Prognosis for survival is better if cancer is detected at an early stage, the patient is from a majority racial/ethnic group, and not a member of an older age cohort ( > 65). Risk is also exacerbated when a patient is dealing with concurring condition such as Alzheimer's Disease or dementia (ADRD)which affects approximately 10% of older adults. Methods: A SEER-Medicare cohort of patient with CRC from 2004-2013 was obtained from the NCI. After appropriate criteria were applied, only cases with all data for cancer and ADRD and first cancer-related treatment were included for an analysis sample of N = 54, 357. Results: The prevalence of concurrent ADRD and CRC in our sample was 3.1%. Mean time to treatment initiation (TTI) was 34.99 days for all patients, and 35.19 days for patients in the CRC-only group vs ~ 27 days in the CRC+ADRD group. Most patients in either group were Stage II though TTI decreased as patient stage at diagnosis increased. Conclusions: Using claims data to assess TTI in cancer patients suggests that TTI is shorter for patients with concurrent ADRD. While this may be attributable to ADRD patients existing interactions with the care delivery systems and the role of caregivers it is evident that additional contextual research is necessary to consider these systems and non-clinical factors.
Do rural cancer patients receive lower quality cancer care? Assessing the impact of rurality on oncology practice performance measures.
Authors: Fedorenko Catherine R. , Panattoni Laura Elizabeth , Sun Qin , Li Li , Kreizenbeck Karma L. , Ramsey Scott David
Published: October 2019

166

Background: Rural residents are diagnosed at later stages of cancer compared to urban residents, have poorer survival, and face distinct barriers to receiving quality cancer care. ASCO has developed policy initiatives to address rural cancer care; however, little is known about quality of cancer care among patients residing in rural areas. This study examined the impact of rurality on performance metrics, controlling for socioeconomic status and insurance type. Methods: We linked Washington state cancer registry records from 2015-2017 with claims records for two large commercial insurers, Medicare, and Medicaid. Using claims from this database, we generated eight nationally recognized quality measures. Rurality was measured by the Rural-Urban Commuting Area Codes (RUCAs) categorized into 4 levels (Metro, Metro with commute, Micropolitan, Small Town/Rural). Process and outcome measures were adjusted for age, sex, race, comorbidity score, stage, cancer type, marital status, the Area Deprivation Index, and treatment factors where appropriate. Results were stratified by payer type. Results: The table below lists the effect of a patient’s rurality on the quality metric where significant (p<0.05). Where rurality did not impact the performance measure, results are left blank. Conclusions: After controlling for socioeconomic status and payer type, quality of cancer care for rural cancer patients was not consistently poorer compared to urban patients. These results suggest that lower survival among rural patients may be due to factors beyond quality of care.[Table: see text]
The cancer care network clinical trials program: Rising from the camp fire ashes.
Authors: Vigil Ofilio Ramon , Little Dana Ann , Mensonides Kristin J. , Bold Richard J.
Published: October 2019

168

Background: The UC Davis Health Cancer Care Network (CCN) in Sacramento improves quality through partnerships with community cancer centers and the UC Davis Comprehensive Cancer Center (UCDCCC). The UCDCCC, as an NCI Lead Academic Participating Site (LAPS) grant recipient, lists Adventist Health Rideout Cancer Center (RCC) in Marysville (42 miles north of Sacramento) as a component. The Adventist Health Feather River Cancer Center (FRCC) and the town of Paradise were devastated by the 2018 Camp Fire, forcing FRCC’s relocation to the city of Chico (49 miles north of Marysville). FRCC was forced to disband its local IRB and unable to continue clinical trials research operations during the aftermath of this natural disaster. The CCN established an affiliation with the FRCC in April 2019. Future plans include establishing an IRB agreement and adding FRCC as a LAPS component. The CCN identified strategies to facilitate the participation of FRCC patients in clinical trials. Methods: The CCN identified 13 NCTN clinical trials with 34 enrolled patients that were in need of appropriate research oversight. Four of these trials were previously never activated at the UCDCCC or its affiliates. CCN staff engaged leaders at the various institutions involved: Quality Assurance (QA) Managers at each NCTN research base, the CIRB, the local IRB, the CTSU, and other leaders within UC Davis and Adventist Health. Results: Stakeholders acknowledged the unusual and urgent nature of our requests and questions, while contributing to the development of a plan allowing patients to continue clinical trial participation. QA managers approved a plan transferring patients to the RCC, allowing research staff to collect and submit data while patients continue receiving care closer to home. Together we developed a notification letter to inform patients of this plan. Conclusions: The relocation of facilities and patients brought rare challenges while conducting clinical research in rural communities. We learned that the cooperation and flexibility of all parties involved was crucial in supporting the continued care for FRCC's clinical trial patients and research contributions.
Development and testing of patient-reported outcome performance measures (PRO-PMs) for oncology practice.
Authors: Stover Angela M. , Urick Ben , Deal Allison Mary , Jansen Jennifer , Henson Sydney , Miller Robert S. , Smith Tenbroeck , Scholle Sarah Hudson , Chiang Anne C. , Cleeland Charles S. , Deutsch Yehuda Ethan , Zylla Dylan M. , Pitzen Collette , Snyder Claire Frances , McNiff Kristen K. , Krzyzanowska Monika K. , Spears Patricia , Smith Mary Lou , Geoghegan Cindy , Basch Ethan M.
Published: October 2019

173

Background: Symptom management is a cornerstone of quality oncology practice. ASCO established a Working Group to develop patient-reported outcome performance measures (PRO-PMs) for assessing symptom management. We describe multi-center testing funded by PCORI. Methods: Multi-stakeholder consensus and literature review identified 11 symptoms for testing as potential PRO-PMs. For these symptoms, questions from the NCI’s PRO-CTCAE tool were administered at 6 US academic and community oncology practices. Patients across cancer types completed questions electronically on days 5-15 of chemotherapy cycles. PRO-CTCAE mapped scores were dichotomized to delineate clinically meaningful thresholds (0-1 vs ≥2), and rates were tabulated between practices. Symptoms were selected to become PRO-PMs if clinically actionable and with prevalence ≥20%; between-practice variation was evaluated using χ2. Twelve candidate sociodemographic and clinical risk adjustment (RA) variables were evaluated via Akaike information criterion testing. Risk-adjusted PRO-PM rates were calculated using observed:expected ratios via generalized linear mixed modeling. Results: Among 653 enrolled patients, 607 (93%) completed questionnaires. Four of 11 symptoms met criteria for PRO-PM development: nausea, constipation, insomnia, pain. Four RA variables met inclusion criteria: age, gender, cancer type, insurance type. The Table shows raw and risk-adjusted rates of symptom burden (scores ≥2) for each PRO-PM across practices. Risk-adjustment yielded a modest impact on scores. Conclusions: Oncology PRO-PMs have been developed to quantify the burden of actionable symptoms at the practice level. Collection from patients is feasible. Further refinement is underway prior to submission for endorsement by the National Quality Forum.

[Table: see text]
Exploring and supporting older women’s chemotherapy decision-making in early-stage breast cancer.
Authors: Karuturi Meghan Sri , Housten Ashley , Giordano Sharon H. , Hoover Diana , Volk Robert Joseph
Published: October 2019

181

Background: Few studies have focused on the therapeutic decision-making process in older adults with cancer. This study sought to address this gap by exploring older adult breast cancer patients’ (pts) perspectives on neo/adjuvant chemotherapy, thereby identifying informational needs as they navigate the decision-making process. Methods: Women ≥65 years diagnosed with early stage (I-III) breast cancer were recruited from an academic center following their decision on whether to receive neo/adjuvant chemotherapy. Pts took part in individual semi-structured interviews to explore their perspectives, knowledge, and values. They also completed surveys assessing sociodemographics, health literacy/numeracy, and shared decision-making (SDM-Q-9). Interviews were audio-recorded and transcribed, and analyzed using the Sort and Sift, Think and Shift qualitative approach. Quantitative data was summarized using descriptive statistics. Results: 26 pts completed interviews (age range 65-92; 81% non-Hispanic White; 81% ≥ college degree; 70% single). 14 pts elected to undergo chemotherapy and 11 declined. Most pts had adequate health literacy (mean = 4.31; SD = 1.1 on Single Item Literacy Scale) and numeracy (mean = 4.4; SD = 1.0 on Single Item Numeracy Scale). Pts scored high on the shared decision-making questionnaires (SDM-Q-9, mean = 5.3, SD = 0.7). Thematic analysis uncovered several commonalities regardless of the decision. Pts sought information regarding their disease/treatment, but in some instances were confused regarding the objective of chemotherapy. They often chose treatment outside of the physician’s recommendation, and referenced the subjective experience of friends/family members with cancer. Self-perception of health and the side-effects of chemotherapy were also key factors. Pts also placed importance on the maintenance of quality of life throughout the treatment trajectory. Conclusions: Decision-making strategies in older patients were shaped by knowledge, values and the anectodal experience of others. These discussions will subsequently shape the creation of a decision support tool for older pts and physicians to better facilitate the shared-decision making process.