bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized phase II study with or without induction chemotherapy combined with accelerated high dose radiotherapy and cetuximab in locally advanced unresectable HPV positive squamous cell carcinoma of the head and neck.
Authors: Friesland Signe , Mercke Clas , Sjödin Helena , von Dobeln Gabriella , Carstens Hanna , Margolin Gregory , Bjorgvinsson Einar , Lax Ingmar , Gubanski Michael , Embring Anna , Farrajota Neves Da Silva Pedro , Nilsson Josef , Wickart-Johansson Gun
Published: May 2019

6077

Background: Concomitant chemoradiotherapy (CT/RT) is the standard treatment for locally advanced non- resectable squamous cell carcinoma of the head and neck. Acute side effects can be serious and late effects important. Patients with HPV+ tumors carry a better prognosis than other patients. De-escalation studies are explored with respect to RT, dose, fractionation, target volumes, adjuvant pharmacotherapy, with encouraging results. However, several patients still recur locoregionally, also in high dose RT volumes. Some patients have distant metastases, often with massive tumor burden and late during follow up (FU). Purpose of the study: 1.To evaluate the effect of induction chemotherapy (IC) on (a) progression free survival (b) distant metastases as first site of failure (c) locoregional failure (d) pattern of tumor response, spatial and timely, exploring the possibility to reduce RT dose and/or target volume(s) in future protocols. 2. to address the impact of high dose RT for bulky disease, T3/T4 given concurrent with cetuximab (E). Methods: Patients had previously untreated stage III/IV (>80 % st IV; TNM 7th), M0 disease, WHO 0-1, unresectable squamous cell carcinoma of the head and neck, HPV positive as evaluated with p16 and/or PCR. Pts were randomised between 2 arms. Pts in arm A were scheduled for 2 cycles of TPF : T (docetaxel) 75 mg/m2 day 1, P (cisplatin) 75 mg/m2 day 1 and F (fluorouracil) 1000 mg/m2 over 24 hours day 1-4. RT was delivered with IMRT to all pts : 68 Gy in 6 weeks for T1/T2 tumors, 76 Gy in 6.5 weeks for T3/T4 tumors with E given one week before and weekly during RT. Tumor response was evaluated according to RECIST with CT, MRI or PET/CT after IC, at 6-8 weeks, 1 and 2 years FU. Results: From january 2011 to february 2016, 152 consecutive pts were enrolled, 77 in arm A. All pts had oropharyngeal cancer. In arm A, 7 pts had CR after TPF, 19 had PR out of 36 evaluable pts. At 2 years FU 70/77 pts (91%) were alive in arm A, 69/75 (92%) in arm B. Distant metastases as first site of failure was 3 (3.9%) in arm A and 7 (9.3%) in arm B. Adverse events grade 3-4, ever registered, were seen in 71 pts in arm A and 63 in arm B, were transient, most often related to RT. Conclusions: Survival and locoregional control at 2 years was high and similar in both arms. Distant metastases as first site of failure was more than doubled in arm B, not having induction chemotherapy (IC). Clinical trial information: EudraCT number: 2009-013438-26.
Influence of tumor size and Eastern Cooperative Oncology Group performance status (ECOG PS) at baseline on patient (pt) outcomes in lenvatinib-treated radioiodine-refractory differentiated thyroid cancer (RR-DTC).
Authors: Wirth Lori J. , Leboulleux Sophie , Kiyota Naomi , Tahara Makoto , Muro Kei , Ahn Myung-Ju , Ando Yuichi , Taylor Matthew H. , Takahashi Shunji , Kim Sung-Bae , Misir Soamnauth , Dutcus Corina E. , Xie Ran , Joshi Prashant Ramesh , Hughes Brett Gordon Maxwell , Aller Javier , Krzyzanowska Monika K. , Capdevila Jaume
Published: May 2019

6081

Background: In SELECT, lenvatinib significantly improved progression-free survival (PFS) of pts with RR-DTC versus placebo (18.3 v 3.6 months; hazard ratio [HR]: 0.21 [99% CI: 0.14, 0.31]; P<0.001). Here we examine the treatment of RR-DTC with lenvatinib in relation to tumor size (sum of all targeted lesions) and ECOG PS. Methods: In this post hoc analysis of SELECT with pts randomized to receive lenvatinib, Kaplan-Meier estimates of time to ECOG PS ≥2 were calculated for subgroups of pts according to baseline ECOG PS or tumor size. Objective response rate (ORR) and Kaplan-Meier estimates of overall survival (OS) and PFS according to ECOG PS (0 or 1) at baseline were calculated. Correlations between ECOG PS at baseline (0 or 1) and maximum tumor shrinkage were calculated using one-way analysis of variance. Results: Pts with ECOG PS 0 or 1 at baseline had similar demographic and disease characteristics. ORR was 78.5% and 51.0% for pts with ECOG PS 0 and 1 at baseline, respectively (odds ratio [95% CI]: 3.508 [2.018, 6.097]). Mean maximum percent decrease in tumor size was significantly greater in pts with baseline ECOG PS 0 (-46.13%) versus pts with ECOG PS 1 (-37.16%; P=0.0017). For pts with ECOG PS 1 at baseline, time to ECOG PS ≥2 was numerically shorter with tumor size >60 mm versus tumor size ≤60 mm (HR [95% CI]: 1.450 [0.708, 2.967]). Additional results are summarized in the table. Conclusions: Among pts with RR-DTC, PFS, OS, ORR, and time to ECOG ≥2 were generally better for patients with lower ECOG PS or smaller tumor size at baseline. These results may indicate that it is beneficial to start lenvatinib in pts with RR-DTC early, before ECOG PS worsens and tumor size increases. Clinical trial information: NCT01321554. [Table: see text]
A randomized phase II study of pembrolizumab with or without radiation in patients with recurrent or metastatic adenoid cystic carcinoma.
Authors: Schoenfeld Jonathan Daniel , Mahmood Umair , Chen Yu-Hui , Mak Raymond H. , Lorch Jochen H. , Hanna Glenn J. , Sridharan Vishwajith , Bang Andrew , Busse Paul Martin , Willers Henning , Mamon Harvey J. , Yoo Hyung-Jin , Pai Sara I. , Wirth Lori J. , Haddad Robert I. , Chau Nicole Grace
Published: May 2019

6082

Background: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy characterized by a high rate of distant recurrence. Systemic therapy has generally failed to produce durable benefit. Radiation (RT) is used for localized disease and as directed treatment for metastases. Here, we report the safety and efficacy of pembrolizumab (pembro) administered with or without hypofractionated RT in a phase II randomized study. Methods: Eligible patients (pts) had recurrent or metastatic ACC with evidence of progressive disease (PD) within the last 12 mos and >=1 measurable non-CNS lesion, along with 1-5 additional lesions deemed appropriate for RT to 30 Gy in 5 fractions. Pts were randomized to pembro alone (200 mg IV q3 weeks) or in combination with RT given within 7 days of cycle 1, day 1. The primary endpoint was objective response rate (ORR) outside the RT field by RECIST 1.1. Using a parallel two-stage design, if >=1 response out of 10 was observed in either arm, 10 more pts would be enrolled to that arm. If >=3 responded, the null hypothesis (ORR=5%) would be rejected in favor of a 25% ORR. Predefined secondary endpoints included progression free survival (PFS) and toxicity. Analyses of tumor growth rate (TGR) excluding RT lesions and immune biomarkers were exploratory. Results: Ten pts per arm were randomized into the trial’s first stage with median age 65 (45-79). No objective responses were seen. Stable disease (SD) was observed in 13 pts; 6 had PD as best response, 1 was unevaluable. Median PFS was 7 mos 95% CI (3 - 13 mos), with 9 pts without progression at 6 mos. 3 pts remain on study treatment (range 8-11 mos). In pts with SD, TGR decreased by >25% in 7 of 12 pts and by >75% in 4 pts. There was no difference in likelihood of SD or PFS between arms. Treatment related AEs (TRAEs) occurred in 18 pts but there were no G3-5 TRAEs. Among 8 biopsies analyzed, PD-L1+ tumor/immune cells ranged from 12-52%. Conclusions: Pembro alone or with hypofractionated RT was well tolerated. We observed no objective responses, but 65% of pts with PD prior to study entry achieved SD, the majority with decreased TGR, and 15% had prolonged SD. Additional strategies are needed to further delay progression and effect response. Clinical trial information: NCT03087019.
Economic analysis of alternative pembrolizumab and nivolumab dosing strategies at an academic cancer center.
Authors: Hall Evan Thomas , Zhang Jenny , Kim Eun-Jeong , Hwang Grace , Bhatia Shailender , Reddy Sunil A.
Published: May 2019

6504

Background: Pembrolizumab (P) and nivolumab (N) were initially investigated and FDA-approved with weight-based dosing strategies, but later the approval label was amended to a fixed dose administration. Given increasing concerns about financial toxicity of cancer therapies, we hypothesize that weight-based dosing of P and N and allowing vial sharing among patients will result in substantial cost savings. Methods: We obtained IRB approval to retrospectively examine all outpatient doses of P and N given at three Stanford Medicine infusion centers between July 1, 2018 and Oct 31, 2018 using the Stanford Medicine Research Data Repository (STARR) database. We performed cost-minimization analysis modeling the impact of dosing strategies based upon patient weight versus fixed dosing (2 mg/kg vs 200 mg q3wks for P; 3 mg/kg vs 240 mg q2wks or 6 mg/kg vs 480 q4wks for N). “Dose-minimization” (DM) was defined as whichever dose was lower (weight-based or fixed dose). The impact of allowing vial sharing (considering commercially available vial sizes) between patients treated at the same site and on the same date was assessed. Average sales price (ASP) from Center for Medicare and Medicaid Services for Part B drugs was used for cost estimates. Results: A total of 1,029 doses of P or N were administered across a variety of cancer types. For most doses (N = 789, 77%), the calculated weight-based dose was less than the fixed dose. DM resulted in decreased usage and expenditures of both P and N, and a further decrease was observed with vial sharing. Total savings estimated with DM and vial sharing strategy were > $1.4 million (Table). This amounted to savings of > 22,000 mg of P (112 fixed doses) and > 11000 mg of N (47 fixed doses). Savings were greatest at the highest volume infusion center. Conclusions: Alternative dosing strategies of P and N would result in significantly less drug utilization and pharmaceutical expenditure without anticipated impact on efficacy. Potential barriers to this approach include existing policies regarding vial sharing and drug vial sizes. [Table: see text]
Deployment and integration of a cognitive technology in China: Experiences and lessons learned.
Authors: Li Tianle , Chen Cheng , Zhang Shan-shan , Dankwa-Mullan Irene , Chen Alan , Preininger Anita , Jackson Gretchen Purcell , Liang Jun
Published: May 2019

6538

Background: Cognitive technologies are rapidly being introduced in oncology for decision-support, prescribing therapy, predicting risk, reducing medical errors and for care management. Few studies have reported on successful approaches for clinical adoption. We report the early adopter experience of BahealIntelligenceTechnologyCo., Ltd. (Baheal), across China within a 2-year period (April 2017-January 2019). We also describe lessons and experiences of oncology users. Methods: Baheal developed collaborative agreements for use of IBM Watson for Oncology (WFO) in 96 hospitals across 8 provinces. Key opinion leaders who saw the potential for AI were recruited as champion advocates. A 29-item survey conducted included usability and integration within clinical workflow. 85 questionnaires were distributed to oncologists who were major WfO users; 51 were completed. All questionnaires were completed anonymously and de-identified prior to analysis. Results: As of January 31, 2019, 866 physicians have entered a total of 52,537 cancer cases into WfO. Most users approved of both the quality (44/51, 86.3%) and comprehensibility (45/51, 88.2%) of treatment options, rationales, and literature references. WfO was most frequently applied in the context of inpatient cases reviewed by a multidisciplinary tumor board (MDT) (44/51, 86.3%). A lack of locally available treatments in WfO was cited as an area for improvement by two-thirds of users (34/51, 66.7%). CDS was rated from 0 (lowest) to 10 (highest) for each of the following uses: EBM medical education (8.1); assistance with literature (7.7); medical care quality control (7.3); second opinion consultations (7.0); case review with tumor board (6.9); and decision support (6.4). Overall, users were willing to recommend CDS to patients and other clinicians (7.3). Conclusions: WfO CDS, employed in a variety of settings, was viewed positively by more than 86% of users, with perceived benefits differing by context. Future incorporation of locally available treatments and understanding reasons for their omission in CDS may increase perceived value, improve standardization, quality of cancer care and equity of care in China.
National lung cancer screening utilization trends in the Veterans Health Administration.
Authors: Lewis Jennifer A. , Denton Jason , Matheny Michael E. , Slatore Christopher G. , Maiga Amelia W , Grogan Eric , Massion Pierre P. , Sherrier Robert H. , Dittus Robert S. , Keohane Laura , Roumie Christianne L. , Nikpay Sayeh
Published: May 2019

6547

Background: Low-dose CT (LDCT) is an effective means for early lung cancer detection, but is often underutilized. An estimated 900,000 Veterans are eligible for lung cancer screening. We are the first to describe national lung cancer screening utilization trends in the Veterans Health Administration (VHA). Methods: We assembled a retrospective cohort of patients within the VHA’s Observational Medical Outcomes Partnership (OMOP) Common Data Model who underwent lung cancer screening. LDCT scans with Common Procedure Terminology (CPT) codes G0297 or 71250 from January 1, 2011 to May 31, 2018 were eligible for inclusion. We further selected exams described as “lung cancer screening,” “screening,” or “LCS.” We used descriptive statistics with frequencies and medians to calculate the total exams per Veteran and evaluate utilization trends over time and by region. Results: At initial screening, Veterans had a median age of 66 (IQR 61, 70), 95% were male, 76% Caucasian. From January 1, 2011 to May 31, 2018, 75 VHA facilities performed 129,363 LDCT exams for lung cancer screening; 87,950 (68%) initial and 41,413 (32%) subsequent exams. Screening has increased over time (226 in 2011-2012; 7848 in 2013-2014; 41,225 in 2015-2016; 80,064 in 2017 until May 31, 2018) in all regions. Providers in primary care/internal medicine (56%), family medicine (16%), pulmonology (6%), oncology (0.3%), other specialties (21%) ordered screening exams. Conclusions: Lung cancer screening with low-dose CT within the VHA increased over time within all geographic regions. Future strategies aimed at the Veteran, provider, and healthcare system levels are needed to increase lung cancer screening utilization among eligible Veterans. [Table: see text]
Use of machine learning to identify relevant research publications in clinical oncology.
Authors: Suarez Saiz Fernando Jose , Sanders Corey , Stevens Rick J , Nielsen Robert , Britt Michael W , Preininger Anita , Jackson Gretchen
Published: May 2019

6558

Background: Finding high-quality science to support decisions for individual patients is challenging. Common approaches to assess clinical literature quality and relevance rely on bibliometrics or expert knowledge. We describe a method to automatically identify clinically relevant, high-quality scientific citations using abstract content. Methods: We used machine learning trained on text from PubMed papers cited in 3 expert resources: NCCN, NCI-PDQ, and Hemonc.org. Balanced training data included text cited in at least two sources to form an “on topic” set (i.e., relevant and high quality), and an “off-topic” set, not cited in any of the above 3 sources. The off-topic set was published in lower ranked journals, using a citation-based score. Articles were part of an Oncology Clinical Trial corpus generated using a standard PubMed query. We used a gradient boosted-tree approach with a binary logistic supervised learning classification. Briefly, 988 texts were processed to produce a term frequency-inverse document frequency (tf-idf) n-gram representation of both the training and the test set (70/30 split). Ideal parameters were determined using 1000-fold cross validation. Results: Our model classified papers in the test set with 0.93 accuracy (95% CI (0.09:0.96) p ≤ 0.0001), with sensitivity 0.95 and specificity 0.91. Some false positives contained language considered clinically relevant that may have been missed or not yet included in expert resources. False negatives revealed a potential bias towards chemotherapy-focused research over radiation therapy or surgical approaches. Conclusions: Machine learning can be used to automatically identify relevant clinical publications from biographic databases, without relying on expert curation or bibliometric methods. The use of machine learning to identify relevant publications may reduce the time clinicians spend finding pertinent evidence for a patient. This approach is generalizable to cases where a corpus of high-quality publications that can serve as a training set exists or cases where document metadata is unreliable, as is the case of “grey” literature within oncology and beyond to other diseases. Future work will extend this approach and may integrate it into oncology clinical decision-support tools.
Impact of travel time on healthcare costs and resource utilization by phase of care for older cancer patients.
Authors: Rocque Gabrielle Betty , Williams Courtney , Miller Harold D. , Azuero Andres , Wheeler Stephanie B. , Pisu Maria , Hull Olivia Margaret , Rocconi Rodney Paul , Kenzik Kelly
Published: May 2019

6560

Background: Closures of hospitals and clinics may have unintended consequences, including increasing patient travel time. Increased patient travel time to healthcare facilities has the potential to adversely impact patient outcomes. Limited data exist on the impact of travel time on healthcare costs and resource utilization. Methods: This retrospective cohort study from 2012-2015 evaluated drive time to cancer care site for Medicare beneficiaries age ≥ 65 in the Southeastern US. The primary outcome was Medicare spending by phase of care (initial, survivorship, end of life [EOL]). Secondary outcomes included resource utilization measured by hospitalization rates, hospitalization sites, intensive care unit (ICU) admissions, and chemotherapy-related hospitalization rates. Hierarchical linear models with patients clustered within cancer care site and adjusted for pertinent covariates were used to determine the effects of drive time on average monthly phase-specific Medicare spending. Results: Median drive time was 32 minutes (IQR 18-59) for the 23,382 included Medicare beneficiaries, with 24% of patients driving > 1 hour to their cancer care site. During the initial phase of care, Medicare spending was 14% higher for patients traveling > 1 hour than those traveling ≤ 30 minutes.Hospitalizationrates were 4-13% higher for patients traveling > 1 hour vs. ≤ 30 minutes in the initial (61 vs. 54), survivorship (27 vs. 26), and EOL (310 vs. 86) phases of care (all p < .05). The majority of patients traveling > 1 hour were hospitalized at a local hospital rather than at their cancer care site, whereas the converse was true for patients traveling ≤ 30 minutes. Conclusions: As healthcare locations close, patients living farther from treatment sites may experience more limited access to care, and healthcare spending could increase for Medicare.
Racial comparisons in receipt of timely guideline-based colon cancer treatment in an equal-access health system.
Authors: Eaglehouse Yvonne L , Georg Matthew W. , Shriver Craig D. , Zhu Kangmin
Published: May 2019

6563

Background: Non-Hispanic Black (NHB) adults with colon cancer may have longer time-to-treatment and be less likely to receive guideline-based therapy than Whites (NHW) in the U.S. This may be largely related to racial differences in access to care and insurance coverage. This study aimed to determine whether there were racial differences in receipt of timely guideline-based colon cancer treatment in the equal-access Military Health System (MHS). Methods: Patients age 18-79 years diagnosed with colon adenocarcinoma between January 1, 1998 and December 31, 2007 were identified in linked databases from the Department of Defense Central Cancer Registry and MHS Data Repository. Odds ratios (ORs) and 95% confidence intervals (CIs) of receiving stage-specific treatment within recommended timeframes [surgery within 6 weeks of diagnosis (stages I-III); adjuvant chemotherapy within 8 weeks of surgery (stages II-III); treatment within 4 weeks of diagnosis (stage IV)] for NHB relative to NHW patients were estimated using multivariable logistic regression. Results: Patients (n = 2,170) had a mean age at diagnosis of 59.6 (SD 11.8) years and the racial distribution was 78.6% NHW and 21.4% NHB. The likelihood of receiving timely surgery between races was similar across the stage groups (I-III). NHB patients were equally likely to receive adjuvant chemotherapy as NHW patients (OR 0.90, 95% CI 0.57, 1.41) and to receive it within 8 weeks of surgery (OR 1.19, 95% CI 0.75, 1.87). The likelihood of receiving timely treatment for patients with stage IV disease was similar between races (OR 0.82, 95% CI 0.39, 1.69). The overall likelihood of receiving treatment adherent to stage-specific guidelines in the study sample was similar between NHB and NHW patients (OR 1.00, 95% CI 0.77 to 1.31). Conclusions: In the MHS population, the likelihood of receiving timely treatment adherent to recommended guidelines was similar between races. Our results support the role of equal access to medical care and insurance coverage in reducing racial disparities in colon cancer treatment.
Development of a financial navigation program to ease the burden of financial toxicity.
Authors: Monak Melissa , Bell Kimberly , Whitt Antoinette
Published: May 2019

6565

Background: Due to the rising cost of cancer care, even well-insured patients are at risk for financial toxicity. Cancer treatment costs can be challenging for patients and families because of increasing deductibles, increasing premiums and frequent co-payments. At Cleveland Clinic Cancer Centers, our goal is to identify patients at risk for financial distress and help ease the financial stress and hardship associated with cancer care. Methods: In 2015 we initiated huddles for all new patients to ensure seven day access for our patients as well as out of network authorizations. During this work we identified the need for a position to help manage the costs of care for our patients. The Financial Navigator (FN) role was created in 2016 to complete benefits investigations to determine covered services and minimize the patient’s out of pocket expenses. We are participants in the Oncology Care Model and are expected to provide and document the estimated out-of-pocket costs in the patient’s medical record. Navigators conduct telephone outreach calls with treatment patients to educate them on their benefits. The FN also assists with applications on copay assistance and free drug options. Finally, the FN will connect patients with resources for premium assistance and household expenses when copay assistance isn’t an option. The FN team has grown to 7 FTE’s since 2016. Results: Since 2016 the dollar amount approved through copay assistance applications has increased by 70%, the free drug value received increased by 55%, and end of year 2018 data shows that we more than doubled what was collected towards patient out of pocket costs from copay assistance programs compared to 2017. We have also been able to comply with the out of pocket expense metric for OCM, not only for our Medicare patients, but for all of our treatment patients and compliance has risen from 44% in December 2017 to 98% in April 2018 and we continued to obtain a goal of 96% or higher throughout 2018. Conclusions: In conclusion our Navigators have built relationships with Social Workers, Care Coordinators, and community services that are available to patients. This added benefit helps patients with non-medical financial stressors. The team can connect patients to organizations that can assist with household utilities, childcare concerns, food concerns, and mortgages. Utilization of the FN role has helped the healthcare team and patients to identify ways to mitigate the costs of care and distress related to financial concerns.
Venous thromboembolism (VTE) in patients with ALK-rearranged non-small cell lung cancer (ALK-LC): A population-based cohort.
Authors: Zer Alona , Joseph Lilach , Battat Erez , Shochat Tzippy , Leader Avi , Goldstein Daniel A. , Hammerman Ariel
Published: May 2019

6608

Background: Advanced NSCLC is associated with an increased risk for VTE, with a reported rate of 8-15%. Clinical observations suggest a higher rate of VTE in patients with ALK-rearranged NSCLC. Clalit Health Services (CHS) is both a healthcare payer and provider, covering over 50% of the population in Israel, with individual patient data recorded in a centralized electronic database. We aimed to determine the incidence of VTE in patients with ALK-LC using a population-based cohort. Methods: We identified all patients diagnosed with NSCLC between 01/2012-12/2017 within CHS. Clinical and demographic data (including VTE risk factors, i.e. components of the Khorana score) were extracted from the CHS registry for all patients. Patients with ALK-LC were identified according to crizotinib prescriptions (dispensed after an approved CHS' pre-authorization for an ALK-LC diagnosis). VTE was identified by ICD diagnosis codes 415.xx, 444.xx, 451.xx and 453.xx. VTE risk factors (Khorana score) were also extracted. Association between ALK-LC and VTE were analyzed using logistic regression, estimating univariate and multivariate Odds Ratios (OR). Results: Overall, 4327 patients with a diagnosis of NSCLC were identified. 149 (3%) had at least one prescription for crizotinib for advanced ALK-LC. The rate of VTE in these patients was 25% (38 of 149 patients), while in the non-ALK-LC the rate was 14% (596/4178), OR = 2.05, p = 0.0004. The association was significant also in a multivariate analysis adjusting for, age, smoking status, BMI, platelet count, hemoglobin and Charlson co-morbidity score (OR 1.66, p = 0.018). Conclusions: This pooled analysis of individual patient data confirms prior data from smaller retrospective studies, suggesting ALK-LC is associated with a high risk of VTE. Randomized trials with prophylactic anti-coagulation are unlikely to be performed in this rare subtype, thus increased awareness and consideration of VTE prophylaxis in high risk patients is warranted.
Impact of an oncology urgent care clinic on emergency department rates.
Authors: Sedghi Tannaz , Canavan Maureen , Gross Cary Philip , Davidoff Amy J. , Gould Rothberg Bonnie Elyssa , Strait Michael , Sinanis Naralys , Adelson Kerin B.
Published: May 2019

6615

Background: Oncology-specific urgent care clinics (UCC) may play a key role in reducing unscheduled emergency department (ED) visits among patients with cancer. We sought to determine if establishment of an Oncology UCC was associated with lower ED utilization among patients receiving cancer care at Yale’s Smilow Cancer Hospital (SCH) and two nearby, integrated community practices. Methods: SCH opened its UCC in April 2017 to provide supportive care and symptom management for patients with cancer who need acute medical attention outside of regular clinic visits. We identified patients who had at least one visit with an oncology provider during the Pre-UCC period (9/1/16 – 12/31/16) or Post-UCC period (9/1/17 – 12/31/17) and received chemotherapy within a year preceding their provider visit. For each patient, we captured all ED visits in a four-month window starting from their last provider visit in each study period. The ED visit rate for both periods was defined as the total number of ED visits divided by the total number of unique patients in the period. To determine the impact of the UCC on ED utilization, we evaluated the absolute difference in the ED visit rate between the Pre- and Post-UCC period using a two-sample t test. Results: There were 3,754 patients in the Pre-UCC period and 4,734 patients in the Post-UCC period. In the full study sample, the mean age was 62.9 and most common cancer types were Hematologic, Gastrointestinal, and Breast. Prior to opening the UCC, the ED visit rate was 0.27 per unique patient. After opening the UCC, we found a 13.9% relative decrease in the overall ED visit rate from 0.27 to 0.23 (p = 0.02). The SCH patient ED visit rate declined by 12.5% (p = 0.03) and the community practice rate declined by 37.1%; however, the latter decline was not statistically significant, potentially due to a small sample size (p = 0.19). Conclusions: Our study found a decrease in the ED visit rate after the opening of an Oncology UCC. An urgent care strategy for cancer centers may serve as an efficient way to manage patients while minimizing ED use. [Table: see text]
Adherence to the guidelines: A comparison of biomarker testing implementation in metastatic non-squamous, non-small cell lung cancer in university versus community institutions.
Authors: Shikdar Sufana , Trisel Zachary Michael , Correa Erika , Vazquez Martinez Mariola A. , Hou Kevin Ye , Hanson Shaun Bryan , Edlukudige Keshava Vinay , Lambert Peter , Thirumaran Rajesh , McCormack Michael Joseph , Ward Kristine Marie , Styler Michael
Published: May 2019

6618

Background: Molecular biomarkers have become essential in determining optimal treatment for patients with advanced non-small-cell-lung cancer (NSCLC). Few studies have evaluated the implementation of biomarker assessment (e.g. EGFR, ALK and ROS1) in routine clinical practice. We endeavored to assess adherence to biomarker testing guidelines in different clinical settings, specifically in a university hospital versus a community hospital in the same region. Methods: A retrospective analysis was conducted in newly diagnosed metastatic non-squamous-NSCLC patients comparing the compliance of biomarker testing based on nationally established guidelines available at the time of diagnosis. De-identified electronic health record (EHR) data were collected from Mercy Catholic Medical Center (MCMC) and Hahnemann University Hospital (HUH) between 1/1/15- 1/30/19. Results were compared in each setting to determine utilization of biomarker testing. Results: 27 patients were identified at MCMC and 41 at HUH. 22 (81%) patients at MCMC and 36 (88%) patients at HUH underwent appropriate molecular testing based on guidelines available at the time of diagnosis. Conclusions: Our data suggests that both university and community institutions have appropriately adapted the evolving guidelines for molecular testing for patients with non-squamous NSCLC. In the rare instances that molecular testing was not performed, the most common reason was inadequate amounts of tissue available. Newer technologies, such as next-gen sequencing and serum based testing, will make compliance with guidelines easier in the future, particularly as increasing numbers of molecular markers will need to be assessed.
Is neratinib following trastuzumab in early-stage HER2-positive breast cancer cost-effective?
Authors: Schwartz Naomi RM , Flanagan Meghan Rose , Babigumira Joseph B , Steuten Lotte Maria Gertruda , Roth Joshua A.
Published: May 2019

6625

Background: Neratinib after adjuvant trastuzumab significantly improves disease-free survival (DFS) in human epidermal growth factor receptor 2-postiive (HER2+) breast cancer, but the median absolute DFS gain is only 1.3 months. There has been much controversy in the clinical and lay media as to whether the substantial cost of neratinib is justified by its effects, including a prominent ASCO Post article from Dr. Vogl about a year ago. We performed a cost-utility analysis to formally assess the value of adding neratinib based on Phase III ExteNET trial results. Methods: We developed a Markov state-transition model to assess the value of neratinib in Stage I-III HER2+ breast cancer. Five-year recurrence rates were derived from ExteNet. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Costs were derived from wholesale acquisition costs and peer-reviewed literature. Health state utilities were derived from ExteNET and prior publications. Outcomes included life years (LY), quality-adjusted life years (QALYs), direct medical expenditures, and cost per QALY gained. The analysis took a payer perspective over a lifetime horizon and results were discounted at 3% per year. One-way and probabilistic analyses were conducted to evaluate uncertainty. As neratinib conferred more clinical benefit in hormone receptor-positive (HR+) disease, we also assessed value in that specific subgroup. Results: Base case results are presented in Table. At typical U.S. willingness to pay thresholds of $100,000 and $150,000 per QALY gained, neratinib had 16.7% and 27.2%, probabilities of cost-effectiveness, respectively. In the HR+ subgroup, neratinib had a cost of $275,311 per QALY gained (19.9% & 31.2% probability of cost-effectiveness at $100,000 & $150,000 per QALY). Conclusions: In the first independent assessment of the value of neratinib after adjuvant trastuzumab, neratinib is not projected to be cost-effective, even among patients who derived the most clinical benefit. Future analyses should reassess the cost-effectiveness of neratinib treatment as trial data mature. Base case results. [Table: see text]
Cost of oral cancer drugs: Trends in the United States Medicare population in 2013 and 2015.
Authors: Seiger Kira Rose-Madison , Ruiz Emily S
Published: May 2019

6631

Background: Rising pharmaceutical costs threaten affordability and access to cancer care. Methods: The 2013 and 2015 Medicare Part D claims databases were queried for CareFirst’s 2017 list of oral cancer drugs. Drugs with on-label indications for conditions other than cancer were excluded. Cost in 2013 were adjusted for inflation to 2015 dollars according to the Bureau of Labor Statistics consumer price index. Results: The total cost of oral cancer drugs paid by Medicare nearly doubled from 2013 to 2015, rising from over $4.8 billion to over $9.1 billion. The number of prescriptions increased by 21.6% from 640,193 to 778,357, suggesting that increased spending is driven more by rising drug prices than by increased utilization. Cost per patient increased for 81% (46) of the 57 drugs prescribed in both years and decreased for the remaining 19% (11). While only seven drugs cost more than $50,000 per patient in 2013, more than fifteen drugs cost more than $50,000 per patient in 2015. The overall average cost per beneficiary increased by 56% from $7,521.64 to $11,734.68, and seven drugs more than doubled in per patient cost. Cost per patient increased by 4.5 times for imbruvica (ibrutinib), 3.5 times for targretin (bexarotene), 3.2 times for soltamox (tamoxifen citrate), 3.1 times for nilandron (nilutamide), 2.6 times for gilotrif (afatinib dimaleate), 2.6 times for cyclophosphamide, and 2.5 times for iclusig (ponatinib hydrochloride). Conclusions: Medicare costs for oral cancer drug nearly doubled from 2013 to 2015, largely due to increased per patient costs. [Table: see text]
Sustaining the gains in cancer care from the oncology care model.
Authors: Csik Valerie P , Minetola Jared , Chapman Andrew E. , Flomenberg Neal
Published: May 2019

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Background: The Oncology Care Model (OCM) is a 5-year demonstration project led by the Centers for Medicare and Medicaid Services (CMS) to create a framework for the future of oncology care in the United States. More than half way through the project, our large, urban NCI-designated cancer center chose to focus on and invest in resources and personnel for patient navigation and the development of clinical pathways. Although navigation has shown to reduce emergency department (ED) visits by as much as 6% per quarter compared to non-navigated patients, sustaining it is a challenge because it is a nonbillable service. Clinical pathways are a tool to reduce care variation by addressing drug expenditures, and represent an opportunity to reduce outpatient costs by as much as 35% when patients are treated on pathway.3 Many OCM practices made similar investments and all are facing the question: How will the infrastructure and efforts developed during OCM be sustainable after the demonstration project ends? Methods: An analysis of average ED cost and utilization as well as drug expenditures was conducted using OCM feedback data (Q1-Q8). Total utilization of ED visits and ED admits were used to determine a projected annualized cost which was compared to a budgeted navigation team. Similarly, projected annualized drug expenditures were compared to the annual cost of the pathways tool. Results: We found that ED visits and ED admits would need to be reduced by 11% to cover navigation costs. Similarly, a 0.7% reduction in total drug expenditures would cover the cost of clinical pathways. The OCM data represents a timeframe prior to implementation of these programs and an average increase of 1.6% per quarter for ED admits, a 0.6% decrease in ED visits and 2.7% increase in drug expenditures. This will serve as a baseline to measure progress towards our sustainability targets. Conclusions: Long term sustainability of the infrastructure developed during OCM to support cancer care transformation will be dependent on reducing high cost and highly utilized services. Aligning impact areas with resources/tools to ensure sustainability is an approach that can help define targets for OCM practices.
Identifying and predicting the most costly patients in oncology.
Authors: Waddle Mark Raymond , Stross William C , Malouff Timothy D , Kaleem Tasneem , Trifiletti Daniel Michael , Vallow Laura , White Launia , Li Zhuo , Naessens James , Spaulding Aaron , Ma Daniel , Keole Sameer R. , Miller Robert Clell
Published: May 2019

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Background: Quality based payment programs in medicine are currently being introduced nationally, aimed to improve care and reduce cost. This study aimed to evaluate the top spenders (TS) after cancer diagnosis and predict TS at two separate time points using predictive analytics. Methods: Patient characteristics, cancer details, treatments, adverse events, and outcomes were collected for patients treated for cancer at Mayo Clinic from 2007 - 2017. Standardized costs over a 2 year period after first treatment were obtained from the Mayo Clinic Cost Data Warehouse with Medicare reimbursements assigned to all services and adjusted to the 2017 GDP Implicit Price Deflator for inflation. TS were identified as those with greater than 93rd percentile costs (≥$113,158) due to a sharp rise in cost at that level. Descriptive statistics and univariate analysis were used for comparison. A prediction model with a training (80%) and validation set (20%) using multivariate selection was used to predict TS and was repeated using information available at 1) the time of consultation and 2) at last follow-up. Results: A total of 80,385 patients were included and 5,626 TS were identified. Mean cost (25th, 75th percentile) overall was $44,953 ($16,776, $51,889). Prediction models at time 1 and 2 had ROC AUC statistics of 0.82 and 0.89 in training and 0.82 and 0.88 in the validation indicating good prediction of high costs. Factors most predictive of TS included need for blood transfusions within 90 days of treatment (OR 5.3), bone marrow transplant (OR 4.0), mild liver disease (OR 3.5), hemiplegia (OR 3.4), weight loss > 10% within 90 days of treatment (OR 3.3), upper GI cancer (OR 3.0), ‘other’ cancer type (OR 2.8), immunotherapy use (OR 2.7), and hospitalizations within 90 days (OR 2.4), all p < 0.001, among others. The largest costs were due to hospital services in the TS and non-TS groups, mean costs $114,258 and $13,185 respectively. Conclusions: This is the first study to predict with high accuracy the top spenders in Oncology. Patient comorbidities and toxicities were among the strongest predictors of high costs, along with certain treatments (bone marrow transplant and immunotherapy). Our findings suggest that quality payment programs should adjust for comorbidities, and that reducing toxicity may be an effective method at reducing costs.
Drug funding price negotiations: Towards achieving a balance between individual and population gains in health benefits.
Authors: Parmar Ambika , Jiao Tina , Chan Kelvin K.
Published: May 2019

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Background: Drug price negotiation to lower cost to a cost-effectiveness threshold (λ) is a recognized approach to improve health care opportunities for the greater benefit of the population. Critics have raised concerns for this approach given the additional time required and speculated loss of quality-adjusted life-years (QALY) for patients. The current study aimed to quantify the incremental net health benefit (INHB) of publicly funded oncology drugs, if funding occurred at list prices without (w/o) negotiations. Methods: Pan-Canadian Oncology Drug Review submissions were reviewed to identify funded drugs with unique indications. For included drug indications economic guidance panel (EGP) reports were reviewed for incremental costs (ΔC) and ΔQALY from manufacturer’s base case cost-effectiveness analyses, EGP lower (LL) and upper limit (UL) re-analyzed estimates (based on list prices). Number of new cases in Ontario (most populous province in Canada) per indication (2017-18) was obtained from provincial databases. Annual QALY gain for each indication was determined by: (ΔQALY×cases). Provincial QALY gain/loss w/o price negotiations to reference λ was estimated by: (INHB= [ΔQALY− (ΔC/λ)] ×cases). Incremental net monetary benefit demonstrated annual monetary gain/loss w/o price negotiations to reference λ: (INMB= [(ΔQALY×λ) −ΔC] ×cases). Results: 34 drug indications including 4,629 new cases were identified. Annual QALY gain for funded indications using manufacturer, LL and UL estimates was 1,851, 1,617 and 1,301, respectively. At reference λ CAD$100,000/QALY, funding w/o negotiations resulted in loss of 2,176, 2,368, 2,451 QALY, representing budgetary diversions away from other health care interventions. This would result in a provincial net annual loss of 325, 751 and 1,150 QALY, respectively. INMB demonstrated provincial net monetary loss of CAD$32,472,389, $75,113,684 and $115,022,331, respectively. Conclusions: Despite an annual gain in QALY for funded drug indications, a net provincial loss in QALY w/o price negotiations was demonstrated. Thus, supportive evidence exists for drug price negotiations towards the promotion of health benefits for the population.
Cost-minimization analysis of using tumor cell-free DNA as monitoring tool in cancer immunotherapy.
Authors: Kuhlmann Alexander , Weiss Glen J. , Beck Julia , Oellerich Michael , Westphal Ronja , Schütz Ekkehard , Graf von der Schulenburg J.-Matthias
Published: May 2019

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Background: Albeit showing great benefit in individual cancer patients, only the minority of patients benefit from checkpoint inhibitor immunotherapies (IMTs). Mutation load and PD-L1 staining are used for response prediction, but are imperfect predictors. A universal method to quantify tumor cell-free DNA (TcfDNA) enables the early and effective evaluation of individual IMT efficacy[1], by comparing TcfDNA to pre-therapeutic values. Here we present a health economic evaluation of test usage. Methods: This cost-minimization study determines the economic efficiency of TcfDNA-test from the perspective of the statutory health insurance in Germany. The assumption is that the effectivity of the intervention (TcfDNA monitoring) and of the comparator (no test), is comparable with regards to the patient-relevant-endpoints (morbidity, mortality, quality of life). The model simulates the course of treatment for each patient with and without TcfDNA testing, calculating the respective cost. Treatment details, outcome (RECIST) and TcfDNA results are derived from an earlier clinical trial.[1] Costs are obtained from publicly accessible data bases. Two testing strategies are explored. Strategy 1: Testing all patients only before the second cycle. Strategy 2: Same as strategy 1 plus a confirmation test before the third cycle, in patients with initial result in a defined grey zone. Results: Both testing strategies correctly classified 68% of progressive disease patients. Testing strategy-1 misclassifies about 8% of disease control patients, which would lead to discontinuation of successful therapies in those. In contrast strategy-2 correctly classifies all patients with disease control, whilst requiring only 24% more tests, since ~50% of patients are undoubtedly classified after one cycle. Assuming six cycles at average costs of 4,781 EUR in the no-test-setting, average costs savings per patient with strategy-1 are 5,735 EUR (20% of treatment costs), with strategy-2 are 2,010 EUR (7%) compared to no testing. Conclusions: TcfDNA monitoring is a cost-saving strategy. However, a confirmatory strategy is desirable to avoid early discontinuation of successful IMT. [1] Weiss GJ et al.: Clin Cancer Res: 2017;5074-81.
Three-year survival outcomes in a prospective cohort evaluating a prognostic 31-gene expression profile (31-GEP) test for cutaneous melanoma (CM).
Authors: Hsueh Eddy C. , DeBloom James R. , Cook Robert W. , McMasters Kelly
Published: May 2019

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Background: A 31-GEP test is a validated prognostic tool for predicting the risk of metastasis in CM, classifying patients (pts) as Class 1 (low risk) or Class 2 (high risk). Here we report updated survival analysis from two clinical registry studies (NCT02355574/NCT02355587) designed to prospectively evaluate outcomes in patients for whom the GEP test was part of their clinical care. Methods: Eleven US dermatologic and surgical centers participated using IRB-approved protocols. Participants were CM pts ≥16 years old who had successful 31-GEP test results. Recurrence-free (RFS), distant metastasis-free (DMFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox regression analysis. Results: At data censoring, 340 pts were accrued who had completed at least one follow-up visit. Median age was 58 years (range 18-87), 53.5% were male, median Breslow thickness was 1.2mm (range 0.2-12mm), 18.2% (62/340) were ulcerated, and 11.2% (38/340) had a positive sentinel lymph node (SLN). Median follow-up was 3.2 years for pts without an event. Six percent (16/265) of Class 1 pts had a recurrence compared to 33% (25/75) of Class 2 pts (p < 0.001). Three-year RFS was 96%, 91%, 80%, and 62% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Three-year DMFS was 97%, 93%, 84%, and 80% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Three-year OS was 98%, 90%, 96%, and 74% for Class 1A, 1B, 2A, and 2B, respectively (p < 0.001). Class 2 was an independent predictor of RFS and OS in multivariate analysis (respective HRs: 2.28 and 3.70, p < 0.05). Conclusions: Consistent with results from previous studies, this analysis demonstrates that the GEP test complements conventional staging and improves the ability to identify high-risk CM pts. These results support use of the test for guiding decisions related to follow-up, surveillance, and treatment in CM pts. Clinical trial information: NCT02355574/NCT02355587.