bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of precision oncology in the Veterans Health Administration (VHA).
Authors: Kelley Michael J. , Duffy Jill , Hintze Bradley J , Williams Christina D. , Spector Neil L
Published: September 2018

6507

Background: VHA is the US’s largest integrated healthcare system providing care to over 6 million Veterans (~40% in rural areas). Precision Oncology offers the promise of effective, low-toxicity targeted therapies tailored to individual tumor genomics but is unequally available to patients in the US. As part of the Cancer Moonshot, VHA is implementing a system-wide Precision Oncology Program (POP) including patients in rural areas, where specialty oncology care has historically had limited availability. Methods: Patients tested with multigene NGS tumor sequencing through 1 of 2 contracted vendors were identified from POP records and cancer characteristics were extracted from POP and medical records. Drug use data was obtained from the VA Corporate Data Warehouse. NGS testing results and annotations were extracted from POP records. Results: A total of 978 tumor samples were sent for NGS testing since program inception in 2015. The most common diagnoses are lung (464: adeno 314, squamous 107), GI (87), LN (75), liver (56), H&N (52), and prostate (43). The rate of sample test requests increased rapidly after national implementation in July 2016 (mean 23 samples/month prior to implementation to mean 126 samples/month 3 months later) as did the number of participating facilities (mean 8/month to 27/month). Sequencing success rate increased from 68% to 71% over the same interval while mean turn around time remained similar at 19.7 and 19.1 d, respectively. NGS results are available for a cohort of 344 patients including: lung 200 (adeno 138, squamous 51), skin 28, LN 20, liver 19, GI 16. 979 variants were found including TP53 278, KRAS 106, STK11, APC 38, PIK3CA 38, and CDKN2A 37. 228 patients had actionable results (on-label drug 24, off-label drug 165, clinical trial 213). To date, 8 patients received a recommended drug outside a clinical trial between 11 and 288 d after testing (median 82 d); 4 additional patients had received an NGS-recommended drug prior to testing. Conclusions: Implementation of tumor NGS testing as part of Precision Oncology Program in a US distributed healthcare system is feasible. Further program implementation and provision of appropriate targeted drugs both on and off study will be necessary to impact patient outcomes.
Pharmaceutical industry payments and oncologist drug selection.
Authors: Mitchell Aaron Philip , Winn Aaron , Dusetzina Stacie
Published: September 2018

6510

Background: Financial relationships between physicians and the pharmaceutical industry are common, and have the potential to influence clinical practice in potentially inappropriate ways. Oncology may be an ideal setting to study the influence of industry payments on physician drug choice given the high levels of competition for market share and high prices commanded by orally administered oncologic drugs. Methods: We linked the Open Payments database of industry-physician financial transactions with the Medicare Part D Prescriber file by physician name and practice location. We used McFadden’s conditional logit model to determine whether receipt of industry payments was associated with higher odds of using a drug manufactured by the same company. We applied this model to clinical scenarios in which oncologists may choose between multiple, on-patent drugs: metastatic renal cell cancer (mRCC) (sunitinib, sorafenib, and pazopanib) and chronic myeloid leukemia (CML) (imatinib, dasatinib, and nilotinib). The primary, binary independent variable was receipt of payments from a manufacturer of one of these drugs in 2013; the primary dependent variable was choosing that manufacturer’s drug in 2014. We divided industry payments into two categories, research payments and non-research “general” payments (including meals, travel, lodging, and speaking/consulting fees), and analyzed each payment type separately. Results: Physicians who received general payments from a manufacturer had increased odds of prescribing that manufacturer’s drug for both mRCC (OR: 1.78, 95%CI 1.23-2.57, mean payments $566) and CML (OR: 1.29, 95%CI 1.13-1.48, mean payments $166). Research payments were associated with an increased odds of manufacturer drug use for mRCC (OR: 2.13, 95%CI 1.13-4.00, mean payments $33,391) but not CML (OR: 1.10, 95%CI 0.83-1.45, mean payments $185,763). Conclusions: Receipt of general payments from pharmaceutical companies is associated with increased prescribing of those companies’ drugs. An association between research payments and prescribing was less consistent. This study suggests that conflicts of interest with the pharmaceutical industry may influence oncologists in high-stakes treatment decisions for patients with cancer.
Oncologists’ perceptions of affordability in the NCCN evidence block value frameworks.
Authors: Wong William Bruce , Ravelo Arliene , DiBonaventura Marco , Shah-Manek Bijal
Published: September 2018

6511

Background: The increasing prevalence of cancer coupled with approvals of new drugs and technologies used in therapy have brought increased scrutiny to the cost and value of treatments in oncology. To address the rising concern about oncology drug costs, NCCN has developed the Evidence Blocks (EB) framework to help assess the value of oncology regimens. The objective of this study was to assess and understand oncologist’s perceptions of affordability in the context of the NCCN EB framework. Methods: Data were collected from an electronic cross-sectional survey of 200 US-based oncologists recruited from an online panel. Using the NCCN EB framework, oncologists were asked to rate a variety of hypothetical cancer therapies and assign costs (in US dollars) to the five levels of affordability. Additional questions assessing perceived patient out-of-pocket costs and comfort level in assessing affordability were also included in the survey. Results: Oncologists’ ratings for an existing cancer immunotherapy were generally similar across the EBs (ratings of 4), however oncologists rated affordability higher (3: Moderately Expensive) vs. the actual NCCN panel affordability rating (1: Very Expensive). The affordability rating was similar across a variety of hypothetical cancer therapies and tumor types (rating of 3). Oncologists estimated the costs for this rating of 3 to range from $4600-$6000 per month, which was inconsistent with actual drug costs. Oncologists estimated the mean monthly out-of-pocket costs for patients with insurance to range from $1260 for a new oral medication to $1700 for a new infused medication. Only 26% of oncologists were comfortable or very comfortable with rating costs associated with affordability levels. Conclusions: Surveyed oncologists rated cancer therapies as more affordable than NCCN panel ratings. Costs associated with affordability were not consistent with actual treatment costs; however, most oncologists were not comfortable with rating affordability.
How costs get discussed (or not) in routine oncology practice.
Authors: Warsame Rahma M. , Jatoi Aminah , Kimball Brittany , Fernandez Cara , Leppin Aaron L , Kumbamu Ashok , Tilburt Jon Charles
Published: September 2018

6512

Background: Cancer patients are nearly 3x more likely to declare bankruptcy than people without cancer. However, little is known about the dynamics of the healthcare provider/patient (pt) conversations around cost issues, the range of topics explored, and the factors that may influence them. We reviewed audio recordings of a cross-section of medical oncology conversations to determine frequency, patterns and attitudes of pts and providers on cost. Methods: We audio recorded conversations between 5/3/2012 & 11/20/2013 for adult patients with any solid tumor malignancy seen in an outpatient medical oncology clinic at one of three sites in the Upper Midwest and Southern California. Basic demographic variables were abstracted from chart review. Recordings were de-identified, reviewed and flagged for any mention of cost. We used descriptive statistics and inductive qualitative content coding methods to further characterize conversation themes. Results: Among 525 recordings, 151 (28%) contained any mention of cost. Median age (range) of pts was 58 years (22-93), and 75% Caucasian, 18% Hispanic, 5% Asian, and 1% Black. Average length of cost discussions was < 2 minutes, and pts usually initiated the discussion (106 /151). Among the 151 conversations, social service referrals were mentioned only 6 times (4%). Through qualitative analysis we identified several key topics: insurance coverage, disability, drug copays, and transportation. The recording dynamics most frequently displayed acknowledging but not taking action on the part of clinicians. Only 25% of clinicians behave confidently in how to address a patients cost concerns. Conclusions: In a diverse cross-section of oncology visits, cost comes up only 1/4 to 1/3 of the time and focuses on insurance coverage, disability and out of pocket drug costs. However clinicians often leave these issues unaddressed. Discussing financial burdens and identifying way to improve existing conversations will be important to mitigate additional financial distress. [Table: see text]
Closure of Medicare Part D coverage gap by the Affordable Care Act (ACA) and use of oral anti-myeloma agents.
Authors: Olszewski Adam J. , Dusetzina Stacie , Davidoff Amy J. , Trivedi Amal N
Published: September 2018

6522

Background: Medicare Part D pays for oral anti-myeloma immunomodulatory drugs (IMiDs, lenalidomide and thalidomide), but has a coverage gap resulting in an out-of-pocket (OOP) expense of > $ 3000 for the 1st prescription (Rx). Patients (pts) eligible for Low Income Subsidies (LIS) are exempt from cost sharing, and LIS is associated with IMiD receipt ( Olszewski, ASH 2016). In 2011, the ACA partly closed the coverage gap with a 50% manufacturer discount on the price of brand-name drugs within the gap. We examined effects of this policy on IMiD use. Methods: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we selected Part D enrollees who started anti-myeloma chemotherapy in 2008-2012. We identified IMiD use in periods pre-ACA (2008-10) and post-ACA (2011-12), among pts with or without LIS. After confirming parallel trends in IMiD use before the ACA, we examined the effect of ACA discount on IMiD use in a difference-in-differences (DiD) model, using LIS recipients as controls whose OOP costs were not influenced by the ACA. Results: Among 3,313 Part D enrollees (of whom 31% received LIS), 41% received IMiDs as part of their anti-myeloma regimen. Compared with the pre-ACA period, in the post-ACA period the median gross IMiD cost of the 1st Rx increased for all pts (Table). OOP costs for the 1st Rx, and for the 1st year of IMiD therapy, decreased for LIS non-recipients. Proportion of pts entering catastrophic coverage with their 1st IMiD Rx decreased from 71% to 49%. However, there was no statistically significant effect of the ACA discount on the proportion of pts treated with IMiDs (DiD estimator, 3% [95%CI, -4 to 10]; P=.40), or on the time from diagnosis to 1st Rx (median 1.5 mo. in all groups). Conclusions: The ACA-mandated partial closure of coverage gap lowered the OOP costs for Part D enrollees treated with IMiDs. As the median OOP cost remains > $2400 for the 1st Rx, and > $4900 for the 1st year of therapy, the policy may be insufficient to overcome the financial barrier for beneficiaries who do not receive the LIS. [Table: see text]
Disrupting end-of-life cancer care delivery: Results from the engagment of patients with advanced cancer trial.
Authors: Patel Manali I. , Sundaram Vandana , Desai Manisha , Periyakoil VJ , Kahn James , Asch Steven M , Milstein Arnold , Bundorf Kate
Published: September 2018

6525

Background: Sustainable approaches to improve quality and safety of care of patients with advanced cancer while concurrently reducing costs is a growing national need. As part of the Veterans Administration Engagement of Patients with Advanced Cancer (EPAC) trial, we trained a lay health worker (LHW) to engage patients with stage 3 and 4 cancer in early advance care planning (ACP). The goal of this follow-up study was to examine the effect of the LHW intervention on patient-reported care experiences, healthcare utilization, and costs in the last 30 days of life for patients who died within 15 months of enrollment. Methods: We evaluated patient-reported experiences with decision-making, healthcare utilization, and total healthcare costs 30 days prior to death. A T-test was used to compare patient experiences with decision-making. To compare ED use and hospitalizations, we utilized an exact Poisson regression. A generalized linear model with gamma link-log function was used to compare total costs. The latter methods adjusted for length of follow-up. Results: In the 30 days prior to death, 60 patients died in each arm within 15 months of enrollment (difference not statistically significant). Patients in the intervention had significantly improved rates of ACP documentation (98% versus 18% p < 0.001), improved experiences with decision-making as measured by an index ranging from 0-5 with higher values representing more favorable experience (4.73 (SD 0.61) vs 4.15 (SD 1.02)) p < 0.001), higher utilization of hospice (77% vs 52%, p < 0.005), lower rates of any emergency department use (5% versus 45% p < 0.001) and any hospitalization (5% versus 43% p < 0.001), and significantly lower total costs of care ($1,048 versus $23,482 p < 0.001) compared to the patients randomized to the usual care arm. Conclusions: Integrating a LHW into oncology care to engage patients in early advance care planning resulted in significantly improved patient experience, decreased utilization and decreased total costs in the last month of life. LHWs may represent a sustainable resource to facilitate optimal patient-centered cancer care at the end-of-life. Clinical trial information: NCT02966509.
Telehospice: Implementation lessons from rural hospice care with mobile tablets.
Authors: Doolittle Gary C. , Nelson Eve-Lynn , Spaulding Ashley , Kuhlman Sandy
Published: September 2018

6546

Background: In underserved rural communities, hospice personnel often travel great distances to reach patients, resulting in challenges to maintain access, quality, cost-effectiveness and safety. To address these disparities, the University of Kansas Medical Center piloted the country’s first TeleHospice (TH) service in 1998. Barriers such as technology limitations, costs and attitudes towards technology limited adoption (Cook et al., 2001). An updated academic-community project utilizes secure mobile videoconferencing to support TH services in Kansas’ frontier communities. Methods: Leveraging lessons learned from the early work, a secure cloud-based videoconferencing solution was chosen for ease of use. To maximize limited resources, the selection of hospice partners was guided by Gustafson et al.’s (2003) Organizational Change Manager, which also informed implementation gaps. The academic team partnered with Hospice Services, Inc., a leader in rural hospice care, providing services to 16 Kansas counties. Results: From February 2016 through January 2017, 116 TH encounters occurred, encompassing 707 attendees over 7,462 minutes. The most common TH uses to date have been: administrative (e.g., connecting hospice staff across 16 counties); professional-to-professional (e.g., connecting hospice nurses at homes to additional TH professionals); and family support (e.g., connecting adult children with loved ones). Initial use of videoconferencing for administrative purposes developed a comfort level in using it for clinical and family support purposes. For staff meetings alone, the hospice has saved approximately $2,500/month in travel, with TH staff noting increased morale driven by increased team communication. Conclusions: Compared with early work, technology advances and a community-centered approach have increased TH adoption. With decreasing budgets as well as rural hospice closures, innovative, cost-effective and community-driven approaches such as TH are needed to decrease disparities. As dissemination occurs in national hospice organizations, continued research is needed to understand best fit within frontier hospices, to inform future urban applications and to address reimbursement.
Themes and costs underlying avoidable terminal oncology ICU hospitalizations.
Authors: Daly Robert Michael , Hantel Andrew , Polite Blase N. , Prigerson Holly Gwen
Published: September 2018

6548

Background: ICU admissions in the last 30 days of life are an indicator of poor care. Our prior research found nearly half of terminal oncology ICU hospitalizations are potentially avoidable. Methods: Data were derived from 72 patients consecutively cared for in an academic medical center’s oncology practice who died in an ICU between July 1, 2012 and June 30, 2013. Oncologists, intensivists, and hospitalists used a standardized assessment tool to review each patient’s electronic health record from 3 months prior to hospitalization until death; they made a clinical determination of avoidability. Two investigators, blinded to the specialty, used a grounded theory approach to extract clinical themes associated with the reviewer’s determination of avoidability. Total, direct, and indirect costs were abstracted for each avoidable hospitalization. Results: Thirty-four (47%) of the examined hospitalizations were deemed avoidable. The primary themes associated with avoidability, and the percentage by specialty, were as follows: 1) failure to initiate appropriate advance care planning in the outpatient setting (68% oncologists, 55% intensivists, 65% hospitalists), 2) failure to integrate understanding of limited prognosis (23% oncologists, 24% intensivists, 26% hospitalists), and 3) failure of clinical management (6% oncologists, 21% intensivists, 6% hospitalists). A failure to educate and integrate surrogates into timely medical decision-making was a prominent secondary theme for oncologists (22%), intensivists (18%), and hospitalists (29%). The total cost per patient averaged $44,532 with direct and indirect costs averaging $25,215 and $19,317, respectively. High cost areas were ICU level care (35%) and pharmaceuticals (16%). Conclusions: The themes identified suggest potential preventative interventions, including higher rates of outpatient advance care planning, oncology inpatient communication to promote patient’s prognostic understanding, prevention of failures in clinical management, and better education and integration of surrogates. Given 8% of oncology patients expire in the ICU and 47% were identified as avoidable, the potential national annual cost of these avoidable hospitalizations is $997MM.
Are physicians social networks linked to breast cancer screening recommendations for older adults?
Authors: Pollack Craig Evan , Radhakrishnan Archana , Parker Andrew M , Visvanathan Kala , Nowak Sarah A
Published: September 2018

6550

Background: Physicians’ prior experiences caring for patients with breast cancer along with experiences in their social networks including family members and friends may be a key and understudied driver of recommendations for cancer screening. Methods: The Breast Cancer Social Networks study (CanSNET) is a national, mailed survey of 2,000 primary care providers (PCPs) randomly selected from the American Medical Association Masterfile. PCPs were asked to provide detailed characteristics on up to 2 women they know who have been diagnosed with breast cancer and “whose cancer, broadly speaking, had the greatest impact” on them, including friends, family members and patients. Each woman was categorized as being diagnosed (a) through screening with a good prognosis, (b) not through screening with a good prognosis, (c) through screening with a poor prognosis or (d) not through screening with a poor prognosis. We used a logistic regression model to assess the association between the network member and recommendations for routine screening mammograms to average-risk women ages 75+, adjusting for provider and practice characteristics. Results: Overall 871 physicians responded to the survey yielding an adjusted response rate of 52.3% (out of 1665 eligible). We found that 67% of physicians recommended screening for women 75+. The sample reported on 762 patients, 378 family members and 476 other network members who had been diagnosed with breast cancer. Ten percent of patients and 25.1% of family members reported on died of their disease. In adjusted models, we found that physicians who reported on family members who did not receive a mammogram and had a poor prognosis were significantly more likely to recommend screening compared to those who did not (Odds Ratio 1.22, 95% Confidence Interval 1.03, 1.43). Conclusions: Physicians’ experiences with their social networks was linked to their breast cancer screening recommendations, underscoring the potential for information that is learned from social networks to differ from clinical guidelines and highlighting the need to address a broad array of influences in trying to reduce potential over-screening in cancer.
The association between employment changes and healthcare use in the year after cancer diagnosis.
Authors: Dickerson John F. , Chubak Jessica , Rabin Borsika , Nekhlyudov Larissa , Varga Alexandra M , Fujii Monica , Ziebell Rebecca , Banegas Matthew P.
Published: September 2018

6551

Background: Employed adults diagnosed with cancer face difficult decisions about continuing/returning to work and intensity of work following diagnosis. We examined the association between employment changes and healthcare use among cancer survivors. Methods: Data on adults enrolled at two health plans (Kaiser Permanente (KP) Colorado and KP Washington), diagnosed with breast, colorectal, lung, melanoma, and prostate cancers between 2003-2008, who responded to a 2013 survey with items on employment patterns following diagnosis were used. Survey data were linked to electronic health record (EHR) data on healthcare use, demographics, and cancer characteristics. Employment status and changes following diagnosis were measured. Multivariable logistic and negative binomial regression models were used to assess associations between employment changes and healthcare use in the year after diagnosis, adjusting for demographic and cancer characteristics. Results: Among 465 cancer survivors with complete survey and EHR data, 225 (48.4%) reported being employed since diagnosis. Among employed survivors, 126 (56.0%) reported making an employment change. Those who made a change were more likely to be female, diagnosed with AJCC stage 3 or 4 cancer, have received chemotherapy or hormone therapy, and had a caregiver (all p < 0.01). The most common employment changes were taking extended paid time off (53.2%), unpaid time off (39.7%), and switching to a flexible schedule (29.4%). Employment changes were made at initial diagnosis (18.3%), during treatment (70.6%), and ≤12 months post-treatment (26.2%); 28.6% made more than one change. Survivors who made an employment change had significantly more oncology visits (IRR = 1.85 [95% CI: 1.14-3.00]) and higher odds of hospitalization (OR = 5.18 [95% CI: 2.50-10.8]), but not primary care visits (IRR = 1.19 [95% CI: 0.94-1.50]) in the year after diagnosis, compared to those who did not make a change. Conclusions: Employment changes among cancer survivors are common and may be associated with treatment intensity and other healthcare use in the year after diagnosis. Prospective studies are needed to assess the impact of employment and healthcare use patterns on health outcomes.
Self-reported financial stress among patients evaluated at a community cancer program.
Authors: Lathan Christopher S. , Akindele Ruth N. , Svoboda Ludmila , Gundersen Daniel A.
Published: September 2018

6553

Background: Cancer related financial stress has been linked to a multitude of factors including socio-economic status, but its impact on the quality of life (QOL) for underserved populations is less well characterized. We evaluated patient reported financial stress, QOL, and quality of health (QOH) at an outreach cancer program located in a federally qualified health center. Methods: Study participants were interviewed at initial clinic visit for financial stress, QOH and QOL between January 2012 and December 2016. Demographic information, insurance coverage, clinical parameters, and comorbidities were abstracted from participants’ medical records. Responses to the financial stress index question “how difficult is it for you or your family to meet monthly payment of your/your family bills?” and overall QOL and QOH of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 were analyzed. Proportional odds logistic regression models were constructed for 5-point quality of life measures and three levels of financial toxicity. Results: Of the 288 participants analyzed, 52% and 12% reported somewhat and extreme financial stress. In an adjusted analysis, patients who reported financial stress were more likely to be younger in age (OR = 4.03, p < 0.001) unemployed (OR = 3.24, p = 0.002), have less than bachelor’s degree (OR = 0.035, p = 0.018), insured by Medicaid (OR = 3.22, p < 0.011), and were more likely to rate their QOL (OR = 3.76, p = 0.031) as poor, compared to those without financial stress. Race, gender, presence of cancer diagnosis and comorbidities were not associated with financial distress. Independent predictors of poor QOL were disability (OR = 3.12, p = 0.005), depression (OR = 2.12, p = 0.007) and extreme financial difficulty (OR = 2.57, p = 0.011). There was a nearly perfect positive correlation between overall QOL and QOH (r = 0.984, p < 0.001). Conclusions: There is a high prevalence of financial burden among underserved minority patients seeking cancer related care, and this is closely associated with poor quality of life. Interventions targeting cancer disparities need to assess financial stress in order to address this issue.
Inpatient hematology and oncology rehabilitation.
Authors: Blankenship Leann , Foluso Ogunleye , Lanni Thomas B. , Hakmeh Basil , Akhtar Adil Jamal , Riutta Justin , Gaikazian Susanna S. , Anderson Joseph M , Stender Michael J. , Jaiyesimi Ishmael A.
Published: September 2018

6580

Background: Functional decline in cancer patients impacts quality of life and overall survival. Increasing attention has been focused on cancer rehabilitation in survivors, largely in the outpatient setting. Beaumont Health System has shifted its focus to include the acute setting by developing an inpatient cancer rehabilitation unit (IPCR) to improve the comprehensive care of patients. Methods: We retrospectively reviewed the patients admitted to IPCR from January 1 - December 31, 2016 for the following: demographics, length of stay (LOS), function independence measure (FIM) gain and efficiency, discharge location, and primary tumor type. Results: IPCR had 117 inpatient admissions; 98 (83.7%) were solid malignancies while 19 (16.3%) were benign hematological disorders and hematological malignancies. Of the 98 patients with solid malignancies, 22 (22.4%) patients had breast cancer, 22 (22.4%) had gastrointestinal cancers, 5 (5.1%) had gynecological cancers, 23 (23.5%) had lung cancer, 8 (8.2%) had CNS malignancies, 11 (11.2%) had other cancers, and 7 (7.2%) had prostate cancer with 81.6% of patients having metastatic disease. Among the hematological malignancies, lymphoma was diagnosed in 11 (57.9%) patients while 3 (15.9%) each had multiple myeloma and leukemia. The mean age of the patients was 68 years and 59% were female. The average LOS was 8.6 days. The mean admission total FIM was 66.7 ±12.8 and discharge total FIM was 87.3 ±16.1. The total improvement in FIM was 20.6 ±13.8 with FIM efficiency of 2.9. There were 21 (18%) patients transferred back to acute care units for decompensation, 7 (6%) went to subacute rehabilitation, 1 (0.85%) went to hospice while 87 (74.3%) were discharge to their homes upon completion of IPCR. Conclusions: Our focused rehabilitation was able to decrease the LOS, well above the 90th percentile Center for Medicare and Medicaid Services (CMS) benchmark and other prior studies, as well as enable patients to safely return home with improved FIM. Creating an IPCR unit proved to be beneficial, allowing for more comprehensive and individualized care, even in the setting of advanced malignancies.
Value frameworks for cancer care: Do they account for potential durable survival with immunotherapies?
Authors: Goldstein Daniel A. , Magnezi Racheli , Leshno Moshe , Ben-Aharon Omer
Published: September 2018

6601

Background: Modern immuno-oncologic agents may have the potential to provide durable survival for some patients. Simultaneously, there is growing concern regarding the cost of cancer care, and multiple frameworks have been developed to assess value. The points based framework created by the American Society of Clinical Oncology (ASCO) has a specific threshold, and more points are awarded if substantial durable survival is demonstrated. The objective of this study was to assess if modern immuno-oncologic agents reach defined efficacy thresholds in this framework. Methods: We reviewedall FDA approvals for immuno-oncologic agents since the first approval in 2011. We collected data regarding study endpoints, specifically the parameters defined in the updated ASCO value framework: improvement in proportion of patients alive with the test regimen, and survival rate with standard. We assessed whether bonus points would be rewarded as per the updated ASCO value framework for durable responses demonstrated on the tails of the Kaplan-Meier curves. These parameters were used as an input to check whether each drug reaches the required achievement defined in the framework. Results: 17 indications for four immunotherapy active ingredients were approved by FDA between 2011-2016: ipilimumab, pembrolizumab, nivolumab and atezolizumab. 59% of the approvals rely on survival endpoints such as overall, progression-free, or relapse-free survival. 41% are based on objective response rates. Only one drug (nivolumab indicated for melanoma first-line treatment) was found to fulfill the threshold defined for the survival rate of standard care (above 20%). Six drugs achieved the required level of improvement in proportion of patients alive in the test regimen compared to the standard (above 50%). As there was no overlap between these two groups of drugs, no drug was found to gain the durable survival bonus points defined by the ASCO framework. Conclusions: Durable survival and responses of modern immuno-oncology agents are currently not recognized to be significant by the ASCO value framework. This may be due to insufficient demonstration of efficacy of such agents, or may be due to an inappropriately calibrated value framework.
Challenges of diagnostic concordance of lung cancer cases in Qualified Clinical Data Registry (QCDR) measure collection by CMS in calculating MACRA's rewards and penalties.
Authors: Glisson Shawn Dana , Goede Patricia Anne , Allen Timothy Craig
Published: September 2018

6604

Background: QCDR was introduced for the Physician Quality Reporting System (PQRS) beginning in 2014. A QCDR is a CMS-approved entity that collects medical and/or clinical data for the purpose of patient and disease tracking to foster improvement in the quality of care provided to patients. Those who satisfactorily participate in PQRS through a QCDR may avoid the 2018 negative payment adjustment -2.0% of total Medicare payments. PQRS #396 is an example of a measurement by which oncologists may be evaluated. A physician’s QCDR score is determined by his/her numerator and denominator per patient based on total data submitted by various healthcare providers. Methods: IRB approval was obtained for a retrospective review of 60 randomly selected NSCLC pathology reports that were diagnosed at UTMB. The Denominator was determined by CMS to be: The patients were between the ages of 18-75; the diagnosis of NSCLC was coded by the appropriate ICD and CPT codes. The Numerator was determined by CMS to be: Pathology reports with a diagnosis that included pT pN for NSCLC with histologic type vs those not documented for medical reasons vs those specimens that were not of lung origin, or were classified as NSCLC-NOS. Results: The study consisted of 60 NSCLC pathology reports of which 2 were determined in retrospect not to have been lung cancer cases. Another 10 were considered to be incomplete. A final 2 were diagnosed as a different histological lung cancer type. As [60 - (2+10+2)]/60 = 76.67%, adherence to the quality standard was less than perfect even though excellent medical care was delivered. This score puts the institution at risk of a 2% Medicare Payment Reduction in 2018 if a majority of other institutions score even slightly higher. Conclusions: Physician remuneration will be reduced by current information submitted to CMS. As the quality scores will be made public, reputations may be negatively impacted. Coding and billing operations may be hindered in their attempt to accurately submit data to CMS. Healthcare Systems may be less inclined to request outside consults (including NGS) that may provide a different diagnosis that could confuse the QCDR.
Can we satisfactorily measure the clinical value of new oncology agents with a single summary measure?
Authors: Jones Clare Frances , Monnickendam Giles , Zhu Mingshu , McKendrick Jan
Published: September 2018

6606

Background: Current value frameworks (VFs) assess clinical value primarily through using clinical trial endpoints as survival metrics (e.g., median and hazard ratio (HR)). But, if key assumptions do not hold, the interpretation of these summary statistics can become problematic and fail to adequately capture the expected benefit to a patient. This has been observed with innovative oncology treatments. As a proof of concept analysis, we reviewed how two VFs (ASCO and ESMO) dealt with cases where the assumption of proportional hazards (PH) does not hold. Methods: Oncology agents approved by the FDA since 2011 were reviewed and three agents were identified with survival profiles where the assumption of PH was found not to hold because, on visual inspection, the survival curves displayed non-standard patterns: Divergence followed by convergence – panobinostat OS in RRMM; Curves initially track together then diverge – nivolumab OS in NSCLC; Curves diverge steadily then a plateau emerged in the active treatment curve – pembrolizumab PFS in refractory melanoma. We evaluated these agents to assess which measures of clinical benefit were most valued under each VF and how the issue of non-PH influenced the outcome. Results: Clinical benefit/value scores varied: ASCO: 14-27 (maximum 100), ESMO: grade 1-3. The ASCO VF uses a hierarchical approach (incorporating HR and median survival benefit, always prioritising the former) adding a bonus for survival benefit in the tail of the distribution. The combination of HR, median survival benefit 2 and 3 year survival rates in the ESMO non-curative VF can potentially capture aspects of clinical benefit in some cases of non-PH. Overall, the ASCO VF appears less flexible to accommodate non-PH than the ESMO VF. Conclusions: Despite VFs using summary statistics which cannot be easily interpreted under conditions of non-PH, the case of non-PH is not explicitly catered for. Additionally, both VFs may miss important interpretation where value is differentiated across patients groups with different response profiles which may underlie non-standard survival curves. In these situations, a more flexible approach to assessing clinical value may render VFs more relevant for clinical decision making.
Barriers to MACRA among a cohort of community oncologists.
Authors: Nabhan Chadi , Smith Yolaine , Ernst Frank R , Fillman Jennifer , Feinberg Bruce A.
Published: September 2018

6613

Background: Value Based Care (VBC) initiatives specifically the Medicare and CHIP Reauthorization Act (MACRA), which includes Medicare Incentive Payment System (MIPS) and Alternative Payment Models (APMs), present challenges for community oncologists. Understanding barriers associated with implementation and compliance are essential for optimal execution. Methods: Using audience response technology, 52 community oncologists and 26 practice managers (PMs) of diverse geography, practice type and affiliations were surveyed in November 2016. Results: Of the attendees, 43% were participating in commercial payer VBC while 33% were participating in the Oncology Care Model (OCM), an APM. Reasons for non-participation: Cost of drugs 58%; data transparency 42%; human resources 33%; technology 29%. The majority of attendees stated limited awareness of MACRA reporting requirements. Once reporting was explained, the stated challenges to MACRA implementation included: inability to measure and track costs 76%; problematic quality improvement activities 56%; lack of patient engagement tools 52%; concern about interpreting CMS reports 52%; meeting meaningful use requirements 33%. In regard to preparation: 52% had survivorship or palliative care plans, 39% made infrastructure investments, and 23% were utilizing clinical pathways. Although 54% stated use of data analytics to maximize efficiency and profitability, half of these were not satisfied with ease of data extraction or output. One third opined that patient satisfaction was irrelevant to quality of care. In the end, nearly half stated reporting requirements could be managed; but 98% stated they were unwilling to assume downside financial risks for hospital and emergency room visits. Conclusions: Identifying and eliminating barriers to MACRA (MIPS/APMs) implementation may be critical to program success. The main reasons for OCM non-participation were costs of drugs and data transparency. There is significant dissatisfaction with available reporting and data extraction tools. Willingness to assume 2-sided risk for total cost of care was identified as the greatest risk to APM adoption.
Spending on antineoplastic agents in the United States: 2011-2016.
Authors: Li Edward C. , Schumock Glen , Hong Samuel
Published: September 2018

6618

Background: Novel antineoplastic therapies confer advantages in efficacy and safety over traditional cytotoxic agents, but they are costly. There is little information on recent trends in actual antineoplastic expenditures representative of the overall U.S. health care system or by healthcare sector. The objective of this study was to describe antineoplastic expenditures by year and healthcare sector in the U.S. Methods: Quintiles IMS National Sales Perspective data for the period of Jan 1, 2011, to Dec 31, 2016, were evaluated to describe antineoplastic agent expenditures. Actual expenditures were totaled by health care sector and calendar year, and then adjusted for U.S. medical-cost inflation (part of the overall consumer price index) to 2016 dollars. Growth was calculated as the percentage increase from previous years. Descriptive statistical analysis was used. Results: Total antineoplastic expenditures increased from $26.8 billion in 2011 to $38.9 billion in 2016. Compared to the previous year, spending increased by 13.7%, 15.6%, 13.4%, 6.3%, and 0.4% in 2016, 2015, 2014, 2013, and 2012, respectively. In hospitals and clinics, spending on biologics grew by 80% from 2011 to 2016. Rituximab, bevacizumab, and trastuzumab expenditures continue to be high ($3.7, $3.0, and $2.6 billion in 2016, respectively) while nivolumab spending increased from $765 million in 2015 to $2.6 billion in 2016. Cytotoxic drug spending remained flat during the study period due to the availability of multiple generic products. Large percentage decreases in spending were seen for oxaliplatin (-97%), docetaxel (-98%), gemcitabine (-92%), bendamustine (-56%) and decitabine (-94%) in 2016 compared to 2011. Conclusions: Antineoplastic expenditures increased significantly since 2011 and are expected to continue to do so with the anticipated approval of additional novel but costly cancer therapies, and because of an aging population. [Table: see text]
Durable long-term survival of adult patients with relapsed B-ALL after CD19 CAR (19-28z) T-cell therapy.
Authors: Park Jae Hong , Riviere Isabelle , Wang Xiuyan , Senechal Brigitte , Wang Yongzeng , Mead Elena , Santomasso Bianca , Halton Elizabeth , Diamonte Claudia , Bernal Yvette , Li Daniel , Sadelain Michel , Brentjens Renier J.
Published: September 2018

7008

Background: CD19-specific chimeric antigen receptor (CAR) T cells have demonstrated high initial responses in patients with relapsed B-ALL. However, clinical characteristics associated with the durability of response remain undefined. Herein, we report the results from analysis of our phase I clinical trial of 19-28z CAR T cells in adult patients with relapsed B-ALL (NCT01044069) with a focus to identify those patients who optimally benefit from 19-28z CAR T cell therapy with durable long-term survival and reduced toxicities. Methods: Adults with relapsed B-ALL were infused with autologous T cells expressing the 19-28z CAR following conditioning chemotherapy. Disease burden was assessed by bone marrow biopsy immediately prior to T cell infusion; patients with < 5% blasts were classified as minimal residual disease (MRD) cohort vs. patients ≥5% blasts as morphologic disease cohort. Response assessment occurred at 4 weeks. Median follow-up duration was 18 months (range, 0.2-57.3). Results: 51 adults received 19-28z CAR T cells; 20 in the MRD and 31 in the morphologic cohort. Complete remission (CR) rates were comparable (95% and 77%, respectively). However, median event-free and overall survivals widely diverged among the 42 patients who achieved MRD-negative CR: not reached (NR) (95% confidence interval [CI]: 4.2-NR) vs. 6.3 months (95% CI, 4.8-9.0) (p = 0.0005), and NR (95% CI, 15.3-NR) vs. 17 months (95% CI, 8.5 – 36.2) (p = 0.0189), in the MRD and morphologic cohorts, respectively. Subsequent allogeneic HSCT in either cohort did not improve survival (p = 0.8). MRD cohort patients developed substantially less severe cytokine release syndrome (CRS) and neurotoxicity, both correlating with peak CAR T cell expansion (p = 0.0326 and p = 0.0001, respectively). Conclusions: Despite comparable initial CR rates regardless of pre-treatment disease burden, durability of 19-28z CAR T cell mediated remissions and survival in adult patients with relapsed B-ALL positively correlated to a low disease burden and do not appear to be enhanced by allogeneic transplant. Our findings strongly support the early incorporation of CD19 CAR therapy before morphologic relapse in B-ALL. Clinical trial information: NCT01044069.
Immune-related gene expression deficit of leukemia stem cells (LSC) in AML.
Authors: Chamoun Kamal , Benton Christopher Brent , AlRawi Ahmed , Jacamo Rodrigo , Williams Patrick , Wang Feng , Zhang Jianhua , Daver Naval Guastad , Garcia-Manero Guillermo , Kantarjian Hagop M. , Futreal Andrew , Andreeff Michael
Published: September 2018

7011

Background: AML LSC are believed to be responsible for residual and resistant leukemic disease leading to relapse. Understanding differences between bulk AML and the LSC subpopulation may allow the identification of novel LSC targets, especially for the most adverse risk AML where few patients are cured. Targeting LSC may be needed to eradicate AML, and immune-based therapies provide an approach for eliminating LSC. The transcriptional landscape of immune-related genes in LSC is not well understood. Methods: Samples were collected at diagnosis from 12 patients with high-risk AML prior to therapy. Bulk (CD45-dim blasts) and LSC (Lin-CD34+CD38-CD123+) AML marrow cells were FACS-sorted and analyzed using whole genome RNA-sequencing. Transcriptomes were analyzed using AltAnalyze software to identify differentially expressed genes in bulk AML cells and in AML LSC populations. These genes were further assessed by gene enrichment analysis using data from Gene Ontology (GO) and the Cancer Genome Atlas Project (CGAP). Results: Sixty-eight genes were identified with greater than 3-fold differential expression between bulk AML and LSC. GO enrichment analysis demonstrated more than 10-fold enrichment of genes involved in the molecular functions, biologic processes, and cell components related to the antigen presentation pathway, with the comparative down-regulation occurring in LSC. Among the top differentially expressed gene clusters, both the MHC class II and interferon-gamma signaling/response pathway gene expression was blunted in LSC. Additional expression analysis revealed that 42% of a CGAP-curated list of 201 antigen-processing and -presentation genes had significantly decreased expression in the LSC subpopulation compared to bulk AML. Conclusions: LSC from primary AML patient samples are characterized by reduction in expression of MHC class II receptor and antigen presentation genes compared to bulk AML. These results suggest that impairment in the presentation and/or processing of tumor associated antigens by MHC class II on LSC, along with tonic sponging of immune response cells and diversion away from LSC by bulk AML, may contribute to LSC evasion of immune surveillance and response.
Five-year results of the ponatinib phase II PACE trial in heavily pretreated CP-CML patients (pts).
Authors: Kantarjian Hagop M. , Pinilla-Ibarz Javier , Le Coutre Philipp D. , Paquette Ronald , Chuah Charles , Nicolini Franck E. , Apperley Jane , Khoury Hanna Jean , Talpaz Moshe , Baccarani Michele , Lustgarten Stephanie , Santillana Sergio , Guilhot Francois , Deininger Michael W.N. , Hochhaus Andreas , Hughes Timothy P. , Shah Neil P. , Cortes Jorge E.
Published: September 2018

7012

Background: The tyrosine kinase inhibitor (TKI) ponatinib has potent activity against native and mutant BCR-ABL1 and is approved for use in pts with relapsed/intolerant CML or Ph+ ALL, or with BCR-ABL1/T315I. Methods: In the pivotal PACE study (NCT01207440), ponatinib (starting dose 45 mg/d) was assessed in pts with CML or Ph+ ALL resistant/intolerant to dasatinib or nilotinib, or with T315I. In Oct ’13, dose reductions were implemented due to observed arterial occlusive events (AOEs). Efficacy and safety at 5 yrs (data as of 3 Oct ’16) for CP-CML pts are reported. Results: Of 270 CP-CML pts in the safety population, 60% received ≥3 prior TKIs. At initiation of study closure, 99 pts were ongoing; among these pts, minimum follow-up was 52 months, and most (78%) had 15 mg/d as their last dose. In all CP-CML pts (n = 267, efficacy evaluable), cumulative response rates were: MCyR, 60%; CCyR, 54%; MMR, 40%; and MR4.5, 24%. Among pts who achieved MCyR (n = 148) or MMR (n = 108), the Kaplan-Meier (KM) estimated probability of remaining in response at 5 yrs was 74% (95% CI, 62 – 83) and 61% (95% CI, 51 – 70), respectively. Regardless of dose reduction in Oct ’13, maintenance of response was high (Table). KM estimated 5-yr rate for PFS/OS was 49%/77%. TEAEs in ≥45% of CP-CML pts were rash 47%, abdominal pain 46%, and thrombocytopenia 46%. Most newly occurring AEs were observed within the first year. The incidence of any AOEs/serious AOEs for CP-CML pts was 29%/23%. Among CP-CML pts with no prior AOEs who had a prospective dose reduction, 17% (11/63) had a first AOE occurring after Oct ‘13. Conclusions: Long-term (5-yr) results from PACE demonstrate that ponatinib continues to show clinical benefit, irrespective of dose reductions, with deep and lasting responses in heavily pretreated CP-CML pts. Safety results were consistent with the safety profile across the ponatinib clinical program. Clinical trial information: NCT01207440. [Table: see text]