bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodality risk adapted therapy with induction carboplatin/paclitaxel/lapatinib for SCCHN amenable to transoral surgery.
Authors: Weiss Jared , Hayes David N. , Deal Allison Mary , Zevallos Jose , Chera Bhishamjit S. , Paul Jennifer , Knowles Mary , Usenko Dmitriy , Weissler Mark Christian , Patel Samip , Grilley-Olson Juneko E. , Hackman Trevor 
Published: September 2018

6064 Background: Induction chemotherapy in SCCHN has mostly been studied prior to XRT where proof of improved survival is lacking. Regimens using weekly platinum, taxane and targeted therapy have resulted in high RR. Attempts are frequently made to intensify or de-intensify, but few have adapted therapy by response. Methods: Patients with transorally resectable, treatment naïve SCCHN and node positivity or T > 3 were treated weekly 6 times with Carboplatin AUC 2, paclitaxel 135mg/m2 and daily lapatinib 1000mg followed by transoral resection. Subjects with pN0/1 received no radiation; those with close margins, ECE, pN2a-b, PNI/LVSI were treated with weekly cisplatin 30mg/m2 and XRT with involved-field XRT allowed while those with pN2c/3 were treated with cisplatin 100mg/m2 Q3W and standard XRT. Primary endpoint was clinical RR (cRR) following induction chemotherapy. Results: Primary sites: oropharynx (OP) (30), supraglottic larynx (5), oral cavity (4) and hypophyarnx (1). Of OP patients, 17 were HPV low risk. Grade 3/4 toxicity during induction: decreased WBC (7), fatigue (3), diarrhea (2), febrile neutropenia (2), neuropathy (2), rash (2) and 1 each of ALT and AST increased, hyperglycemia, hypotension, nausea, PPDE. 39/40 proceeded to surgical resection (1 patient refused for non-study reasons). 29/39 subjects who were projected to require XRT were able to avoid it. 8/10 subjects with study-defined indication for adjuvant XRT received it. cRR 37/40, pRR 14/40. Clinical and pathologic responses correlated poorly (see table). With median FU of 1.7 years, there has been no recurrence or death. Mean VRQOL was 91.7 before induction, 92.3 before surgery and 92.3 1 year post surgery. Mean MDADI was 82.8 before induction, 85.9 before surgery and 84.5 1 year post surgery. Conclusions: The regimen led to excellent feasibility of surgical resection, high cRR and a real pCR. cR predicted poorly for pR. Most patients were able to avoid XRT. Speech and swallowing function were preserved. NCT01612351. Clinical trial information: NCT01612351. [Table: see text]
Interim baseline characteristics from RIFTOS MKI, a global non-interventional study assessing the use of multikinase inhibitors (MKIs) in the treatment of patients with asymptomatic radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC).
Authors: Brose Marcia S. , Pitoia Fabian , Smit Johannes WA , Lin Chia-Chi , Fellous Marc Mardoche , De Sanctis Yoriko , Sugitani Iwao , Schlumberger Martin 
Published: September 2018

6084 Background: RIFTOS MKI was designed to compare the time to symptomatic progression from study entry in patients with RAI-R DTC for whom there was a decision to treat or not to treat with an MKI in the real-life setting. Here, we report interim baseline characteristics for the first 274 patients enrolled in the study. Methods: RIFTOS MKI is a non-interventional study enrolling patients with asymptomatic RAI-R DTC. The decision to initiate MKIs at study entry was at the discretion of the treating physician. Final analysis will be performed once 700 patients have been enrolled and the last enrolled patient has been followed for 24 months. Results: Of 274 patients, the median duration of observation was 169.5 days. Patients have been enrolled from USA (n = 74), Japan (n = 55), Europe (n = 80), and rest of the world (n = 65); 54% were female and the median age was 68 years. Most patients had an ECOG performance status of 0 or 1 (97%) and distant metastases (81%). The most frequent histology was papillary (73%). The median time from initial diagnosis of DTC to study entry was 7 years. RAI refractoriness was mainly due to lack of RAI uptake (60%), primarily in Japan (80%). Japan also had the shortest median time from RAI classification to initial visit (2 months) vs other regions, and the average dose per RAI treatment and median cumulative activity of RAI were lower in Japanese patients (3.4 and 3.7 GBq, respectively) (Table). Conclusions: The RIFTOS MKI study is the largest non-interventional study in RAI-R DTC. The regional differences in treatment history observed in the RIFTOS MKI study reflect differences in accessibility and treatment practice. The study is ongoing. Clinical trial information: NCT02303444. [Table: see text]
Combination of dabrafenib (DAB).
Authors: Sherman Eric Jeffrey , Ho Alan Loh , Baxi Shrujal S. , Dunn Lara , Korte Susan H. , Haque Sofia , Ghossein Ronald A. , Chen Helen X. , Pfister David G. 
Published: September 2018

6085 Background: BRAFV600E mutations (BRAFm) are the most common mutations in thyroid cancer. BRAF inhibitors are active in BRAFm melanoma, but there is less activity noted in BRAFm thyroid cancer. Preclinically, BRAF inhibitors inhibit BRAFm thyroid cancers only transiently due to activation of HER2/HER3, driven by a neuregulin-dependent autocrine loop. The addition of LAP, a HER2/HER3 kinase inhibitor, sensitizes the cell to growth suppression by BRAF inhibitors (Cancer Discov 5(3):520, 2013). A phase I study evaluating the combination of DAB, a BRAF inhibitor, and LAP was initiated to evaluate the safety and pharmacodynamic changes the combination. Methods: Eligibility included thyroid cancers with the presence of a BRAFV600E mutation. Any prior treatment was allowed. All patients received DAB 150 mg bid starting 2 weeks prior to LAP. Doses of daily lapatinib were escalated in a standard 3+3 design at (1) 750 mg; (2) 1250 mg; (3) 1500 mg. Toxicities, including Dose Limiting Toxicities (DLT), were noted only after both drugs were started. Patients (pts) removed before the start of LAP were not included in the analysis. Biopsies were done at baseline, after the start of DAB, and after the start of both DAB and LAP. Responses were defined using RECIST 1.1. Results: 15 evaluable pts were enrolled on the phase I portion of the study. Gender – 10/15 (67%) male; median age – 63 years; histology – differentiated thyroid cancer (DTC) 13 (87%), anaplastic thyroid cancer (ATC) 2 (13%); brain metastases – 4/15 (27%); prior tyrosine kinase inhibitor – 9/15 (54%). There was one DLT - Grade 5 event unlikely related to drugs in a pt with ATC. Grade 4 toxicities – 0. Grade 3 toxicities –lymphocytes (1). The partial response rate is 60%. The response rate in the DTC group is 69% (0% in ATC). One other pt came off treatment due to withdrawal of consent. Median progression-free survival is 15 months (range, 2-34+ months). Median follow up is 15 months. Translational studies are pending. Conclusions: The combination of DAB 150 mg bid and LAP 1500 mg daily was safe and well-tolerated. Furthermore, significant activity was noted, especially at the top dose level. Further investigation with this regimen is warranted. Clinical trial information: NCT01947023. [Table: see text]
Global impact of a clinical informatics system: Scalable delivery of on-time access to evidence-based multidisciplinary expert treatment decisions for all cancers.
Authors: Badwe Rajendra A. , CS Pramesh , Gupta Sudeep , Nair Nita S. , Feldman Nancy Renee , D'Cruz Anil 
Published: September 2018

6502 Background: There is a scarcity of expert oncologists in the world. Patients in nonurban areas have poor access to evidence-based treatment decisions and worse outcomes. In India, there are ~1600 experts for 1.8 Million patients. Created in May 2014, “TMC NCG Navya Online” is an expert opinion service based on an informatics system. We prospectively study its real-world impact. Methods: Navya exhaustively searches and outputs evidence and experience based treatment options for an individual patient. Its accuracy was validated in trials at TMC (one of the world’s largest tertiary care centers) and UCLA-OVMC. Navya’s patient data summary and treatment options are rapidly reviewed and vetted (1-2 minutes) on mobile by experts from TMC and NCG, (consortium of 104 cancer centers in India). Expert decisions are converted into a simple language report for patients. System generated evidence based information on diagnostics, regimens, side effects etc are also provided. To prospectively assess impact, from July to December 2016, all patients were asked via phone follow-up: 1. If report was shared with treating provider, 2. Final treatments delivered. Results: 9361patients from 22 developing countries registered with TMC NCG Navya Online. 3402 expert decisions were provided and converted into 2614 simple language reports. 5229 patients received system generated evidence based information. Median time to deliver a report was 24 hours. The prospective sample was 582 decisions with a 75% (n = 436) follow-up rate. 74% of reports were shared with treating providers. 73% of TMC NCG Navya’s decisions, (n = 306), were the final treatments delivered. Common reasons for non-implementation included decline in ECOG status and not testing biomarkers (ER/PR etc). Conclusions: Expert oncologists use Navya to provide rapid online opinions to patients across 22 developing countries. Patients shared the expert opinions with their providers and received evidence-based treatments. Expanding the reach and impact of such a service to nonurban USA and the world, can maximize outcomes for patients without ready access to expertise.
Impact of the timing of hepatitis B virus (HBV) identification and anti-HBV therapy initiation on the risk of adverse liver outcomes in patients receiving cancer therapy.
Authors: Hwang Jessica , Suarez-Almazor Maria E. , Cantor Scott B. , Barbo Andrea G. , Lin Heather Y. , Ahmed Sairah , Chavez-Mac Gregor Mariana , Donato-Santana Christian , Eng Cathy , Ferrajoli Alessandra , Fisch Michael , McLaughlin Peter , Simon George R. , Rondon Gabriela , Shpall Elizabeth J. , Lok Anna S. F. 
Published: September 2018

6503 Background: Patients with cancer and hepatitis B virus (HBV) infection receiving cancer therapy are at risk for HBV reactivation. We aimed to determine the impact of early vs. late HBV identification and early vs. late/no anti-HBV therapy on adverse liver outcomes of patients with cancer with chronic (HBsAg+/anti-HBc+) or past (HBsAg-/anti-HBc+) HBV infection. Methods: We retrospectively studied adult patients with solid or hematologic malignancies who received chemotherapy during 2004-2011. Adverse liver-related events included hepatitis flares, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariable hazard models to determine predictors of outcomes. Early was defined as at the initiation of cancer therapy and late as after therapy initiation. Results: There were 18,688 study patients (80.4% had solid tumors). Among patients with hematologic malignancies, 89.6% had HBV testing of which 90.4% was early. Among patients with solid tumors, 10.8% had HBV testing of which 46.4% was early. Prevalence of chronic HBV was 1.1% (52/4905) and past HBV was 7.1% (350/4905). Among patients with chronic HBV with hematologic or solid malignancy, those identified late had 2.95 times (1.45-6.01) higher risk of liver failure than those identified early. Among chronic HBV patients, 59% (23/39) with early testing had early initiation of anti-HBV therapy, while all of those tested late had late/no initiation of anti-HBV therapy. Predictors of liver failure were male sex, chronic HBV, and late HBV identification for patients with solid tumors, and allogeneic SCT for patients with hematologic malignancies. Conclusions: Early HBV identification correlated with early anti-HBV therapy initiation and reduced risk of liver failure after chemotherapy in chronic HBV patients with solid tumors or hematologic malignancies as well as patients with past HBV and solid tumors.
The role of chronic disease in the costs of potentially preventable emergency department use during treatment: A regional study.
Authors: Panattoni Laura Elizabeth , Fedorenko Catherine R. , Kreizenbeck Karma L. , Greenlee Stuart , Walker Julia Rose , Greenwood-Hickman Mikael Anne , Barger Sarah , Rieke John Whitelaw , Conklin Ted , Brown Thomas D. , Chance Sharon , Eaton Keith D. , Guerrero Rose , Gunkel Mary , Martins Renato G. , Moorhouse Marilyn , Smith Bruce , Lyman Gary H. , Ramsey Scott David 
Published: September 2018

6505 Background: The Centers for Medicare and Medicaid Services (CMS) released a quality metric for potentially preventable chemotherapy-associated emergency department (ED) use, effective in 2020. This metric excludes diagnoses with emerging evidence for outpatient management, such as proactive symptom management (PSM) and those for ambulatory care sensitive chronic conditions. Little is known about the intersection between potentially preventable ED visits due to cancer vs. other chronic disease. This study characterized the number and costs of ED visits during treatment. Methods: Western Washington cancer registry records from 2011- 2015 were linked with claims from two commercial insurers. Patients with newly diagnosed solid tumors undergoing initial treatment with chemotherapy or radiation were eligible. ED use was tracked one year post treatment initiation. ED diagnosis codes for fields 1-10 from the CMS metric and the PSM literature were labeled “Potentially Preventable” (Pp). Codes from the Agency for Healthcare Research and Quality’s Prevention Quality Indicators (PQI) for Chronic Conditions were labeled “Potentially Preventable-Chronic Disease” (PpChronic). Costs were adjusted to $2016. Results: Of the 7,053 eligible patients, 2,543 (36.1%) visited the ED (median # visits [IQR]: 1 [1-2]). The most commonly listed codes included Pain (1,054 visits) and Dyspnea (279 visits) for Pp, Hypertension-PQI (652 visits) and COPD-PQI (206 visits) for PpChronic, and Diabetes (247 visits) and Hyperlipidemia (181 visits) for the other codes. Spending on ED visits including both potentially preventable cancer and chronic disease diagnoses totalled $706,552 (20% of ED costs). Conclusions: One fifth of ED costs potentially resulted from simultaneous poor cancer symptom and chronic disease management. Future research should explore the role of chronic illness in categorizing which ED visits are potentially preventable during cancer treatment. [Table: see text]
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]