bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of HER2 on breast cancer survival.
Authors: Katzorke Nora , Rack Brigitte Kathrin , Haeberle Lothar , Neugebauer Julia Katharina , Melcher Carola Anna , Hagenbeck Carsten , Forstbauer Helmut , Ulmer Hans Ulrich , Soeling Ulrike , Kreienberg Rolf , Fehm Tanja N. , Schneeweiss Andreas , Beckmann Matthias W. , Fasching Peter A. , Janni Wolfgang 
Published: March 2020

640 Background: HER2 overexpression and overamplification have originally been described as a prognostic factor indicating a poor prognosis. However the highly effective anti-HER2 treatment was approved in 2006 after several large randomized trials showing that the prognosis in HER2 positive women could be improved. Few data has been generated comparing HER2 positive patients treated with trastuzumab with comparable HER2 negative patients. Aim of this analysis was to investigate the prognostic relevance of HER2 status in a post trastuzumab approval study. Methods: The SUCCESS trial is an open-label, multicenter, randomized controlled, phase III study comparing FEC-docetaxel (Doc) vs. FEC-Doc-gemcitabine (Doc-G) regime and 2 vs. 5 year treatment with zoledronat in 3754 patients with primary breast cancer (N+ or high risk). All patients were treated per protocol with trastuzumab, if HER2 status was shown to be positive by local pathology. Furthermore HER2 status was a stratification factor. The prognostic value of HER2 status with respect to overall survival (OS) and progression-free survival (PFS), disregarding the above stated treatment arms, was studied with Cox proportional hazards regression models in univariate as well as multivariate analyses adjusted for age, BMI, tumor size, nodal status, grading, estrogen receptor status and progesterone receptor status. Results: 2628 patients were included into this analysis. Median Follow up time was 4.8 years, 221 deaths and 412 recurrences were recorded until data base closure. HER2 was not a prognostic factor in the univariate analysis (OS: HR= 0.86, 95% CI: 0.63 to 1.19; PFS: HR = 0.95, 95% CI: 0.76 to 1.19). In the multivariate analysis all of the above stated prognostic factors were of prognostic relevance. HER2 was of prognostic relevance with a HR of 0.67 (OS, 95% CI: 0.48 to 0.92) and 0.79 (PFS, 95% CI: 0.62 to 0.99) indicating that patients with a positive HER2 status had a better prognosis. Conclusions: Patients treated with trastuzumab showed a more favourable prognosis compared to HER2 negative patients in this prospectively randomized trial, possibly due to the therapeutic effect of HER2-targeted treatment.
Differential expression of microRNAs induced by trastuzumab emtansine (T-DM1) during megakaryocytopoiesis.
Authors: Uppal Hirdesh , Mahapatra Kaushiki , Lewin-Koh Sock-Cheng , Olsen Steven , Sliwkowski Mark X. , Girish Sandhya , Hartley Dylan , Dambach Donna , Ramakrishnan Vanitha 
Published: March 2020

645 Background: Treatment with the HER2-targeted antibody–drug conjugate T-DM1 resulted in significantly longer PFS and OS vs lapatinib + capecitabine in patients previously treated with trastuzumab and a taxane in the phase 3 study EMILIA. Thrombocytopenia (TCP) was the dose-limiting toxicity for patients treated with T-DM1, although platelets do not express HER2. In EMILIA, grade 3/4 TCP was observed in 12.9% of T-DM1-treated patients. We have previously shown that T-DM1 inhibits megakaryocyte (Mk) production and differentiation. Here, we investigated the effect of T-DM1 on microRNAs (miRNAs) associated with megakaryocytopoiesis. Methods: Human stem cells (HSCs; CD133+/CD34+) from 8 donors were differentiated into Mks in the presence of T-DM1, trastuzumab, or vehicle. Total RNA was extracted using the miRNeasy MiniKit. cDNA was prepared using the Taqman miRNA RT Kit, FAM-MGB probes, and stem-loop RT primer pool set. miRNA expression was measured using the 96.96 Dynamic Array Chip on the Biomark HD Reader. Data were analyzed using Fluidigm real-time analysis software Spotfire 5, and SAS 9.2. hsa−let−7g and hsa−miR−671−3p were chosen as reference miRNAs due to their low variation between treatments and time points. Median normalization was also applied. Results: A total of 526 miRNA RT-qPCR assays were used to map miRNA expression during differentiation of HSCs from 8 separate donors to Mks in vitro over 30 days. Several miRNAs demonstrated temporal changes in their expression profiles during maturation, suggesting these miRNAs are potential drivers of Mk differentiation. T-DM1 treatment inhibited Mk production and differentiation. Concomitant modifications in the expression of specific miRNAs were observed. These modifications were not present in trastuzumab- or vehicle-treated cells, suggesting these miRNAs may be involved in the development of T-DM1–induced TCP. Conclusions: These results suggest that the miRNAs have the potential to be used as biomarkers for TCP in patients treated with T-DM1 and possibly other DM1 conjugates. Specific miRNA alterations related to T-DM1 treatment will be discussed following investigations using clinical samples to validate these preliminary data.
Randomized trial of a web-based intervention to address barriers to clinical trials.
Authors: Meropol Neal J. , Albrecht Terrance Lynn , Wong Yu-Ning , Benson Al Bowen , Buzaglo Joanne S. , Collins Michael , Eads Jennifer Rachel , Egleston Brian , Flamm Anne Lederman , Fleisher Linda , Katz Michael S. , Kinzy Tyler G. , Manne Sharon , Margevicius Seunghee , Miller Dawn M. , Miller Suzanne M. , Poole David , Roach Nancy , Ross Eric A , Schluchter Mark D. 
Published: March 2020

6500 Background: Cancer patients (pts) have knowledge and attitudinal barriers to participation in clinical trials (CT). We developed PRE-ACT (Preparatory Education About Clinical Trials), a tailored, interactive, web-based intervention to address these barriers and improve preparation for consideration of CT as a treatment option. Methods: We conducted a prospective, randomized, multicenter, phase III clinical trial of PRE-ACT vs. control (general text about CT excerpted from NCI materials). All assessments and interventions were conducted online. Cancer pts >18 years old were enrolled before initial oncologist consultation. Pts completed a baseline assessment including CT knowledge (19-item); CT attitudes (28-item); preparation for decision making (10-item); and validated measures of preferences for shared decision making and quality/length of life. PRE-ACT pts received a summary of their preferences and a list of their top CT barriers. Based on ranking of individual barriers, pts were presented with a video library of 30-90 second clips addressing their top barriers (10 maximum). After the educational intervention a follow up survey reassessed CT barriers and preparation. Results: 1255 pts were randomized; median age 59 (range 20-88); 58% female; 12% non-white / 2% Hispanic; 76.4% some college education. 1081 pts completed baseline and post-intervention assessments. The control and PRE-ACT groups both had improved knowledge, reduced attitudinal barriers, and improved preparation (p<.0001 for all comparisons). PRE-ACT was more effective than control in improving knowledge (p=.0006) and attitudes (p<.0001). Furthermore, pts in the PRE-ACT arm were more satisfied with the amount (p=.002) and format (<.0001) of information, and felt more prepared to consider CT (p=.0003). Conclusions: This large-scale randomized trial of a tailored, web-based, video intervention demonstrates that educational information delivered online before the oncologist visit can significantly reduce knowledge barriers and attitudinal barriers and improve preparation for consideration of clinical trials. Both text and PRE-ACT are effective, with greater improvements and satisfaction in the PRE-ACT group. Clinical trial information: NCT00750009.
Off-label and compendia use of chemotherapy in patients with metastatic cancer.
Authors: Hershman Dawn L. , Neugut Alfred I. , Buono Donna , Richards Catherine A. , Glied Sherry A. , Wright Jason Dennis 
Published: March 2020

6509 Background: In 2012, ASCO Identified opportunities to improve the quality and value of cancer care by reducing inappropriate and/or prolonged use of chemotherapy The NCCN compendium is recognized as an authoritative reference for insurance coverage for drug indications without FDA approval. We evaluated FDA-approved, compendia and unapproved use of chemotherapy. Methods: We useddata from the SEER-Medicare database to identify patients with metastatic cancer who received chemotherapy. For each tumor, drugs with >3 claims were identified. Each drug was classified as having an FDA-approved indication, an indication based on NCCN compendia guidelines or neither of these. The number of claims for each drug was calculated. Logistic regression was used to assess the factors that Results: Between 1998-2007, 37,351 subjects were identified as having received chemotherapy; of these, 24,876 (66.6%) received only FDA approved drugs, and 12,475 (33.4%) received at least one unapproved drug. Of those who received an unapproved drug, 8,669 (69%) received a drug with a compendia listing. Therefore, of the total population, 10% received a drug that was neither FDA nor compendia approved. The mean number of unapproved claims was 10.3 (SD=15.2) and the mean number of drugs was 1.3. Unapproved use was highest in subjects with prostate and lowest in patients with colon cancer. In a multivariate analysis, unapproved use decreased with increasing age and >2 comorbid conditions. Compared to prostate cancer, the odds of having an unapproved drug was lower for breast (OR=0.27), colon (OR=0.08), lung (OR=0.65), ovary (OR=0.38), uterus (OR=0.49) and myeloma (OR=0.60). No patients with colon or prostate cancer received compendia-approved drugs. Over 90% of unapproved use for breast, ovary and lung cancer were compendia-approved. Costs associated with unapproved/compendia use will be presented. Conclusions: A large fraction of patients who use chemotherapy receive FDA-unapproved drugs; however, the majority of those drugs are acknowledged by NCCN. A better understanding of the costs and benefits of compendia-approved drugs is warranted to reduce the costs of cancer care.
The financial burden of cancer care: Do patients know what to expect?
Authors: Chino Fumiko , Peppercorn Jeffrey M. , Tulsky James A , Ubel Peter A , Schrag Deborah , Rushing Christel , Nicolla Jonathan , Altomare Ivy , Samsa Greg , Abernethy Amy Pickar , Zafar Yousuf 
Published: March 2020

6516 Background: Patients receiving cancer treatment can experience significant financial distress (FD), but little is known about whether patients are adequately informed about costs of care. Methods: This is a planned interim analysis of an ongoing cross-sectional study of insured adults with solid tumors on anticancer therapy for ≥1 month. Consecutive patients were surveyed, in person, at a referral center and 3 rural oncology clinics. Participants were asked about subjective FD (via validated measure), out-of-pocket costs, expected burden, and willingness to accept high out-of-pocket costs. Medical records were reviewed for disease and treatment data. Logistic regression assessed the relationship between FD, expected burden, quality of life (QOL), and willingness to accept high out-of-pocket costs. Results: Among 119 participants (85% response), median age was 60 years (range 27-86), 54% were men, 29% were non-white, 96% had completed high school, and 40% were retired. 81% had incurable cancer. Median income was $50,000/yr. Median out-of-pocket costs were $480/mo. 19% reported high/overwhelming FD. Median time on treatment was 200 days. Compared to anticipated levels of personal financial burden at the start of treatment, 40% were experiencing a higher degree of burden, 24% were experiencing a lower degree of burden, and 32% were experiencing the same degree of burden. In adjusted analyses, both high/overwhelming FD score (OR 4.79; 95% CI 1.64-13.95; p=0.004) and a lower QOL score (OR 0.81; 95% CI 0.67-0.99; p=0.035) were associated with a higher than expected financial burden. The following were not associated with higher than expected financial burden: age, gender, education, cancer stage, cost as a proportion of income, time on treatment, or willingness to accept high out-of-pocket costs. Conclusions: A large portion of insured patients faced out-of-pocket costs that were greater than expected. Those who were least prepared for financial burden reported higher FD and lower QOL. Since patient characteristics could not identify those at highest risk for unexpected cost burden, future research should focus on how to identify patients at risk and better prepare them for potential treatment-related financial burden.
Impact of Medicare Part D on out-of-pocket pharmaceutical costs for patients with cancer.
Authors: Kircher Sheetal Mehta , Johansen Michael , Richardson Caroline , Davis Matthew M 
Published: March 2020

6517 Background: As federal policy, Medicare Part D was designed to reduce OOP costs for Medicare beneficiaries, but the extent to which this occurred for patients with cancer has not been measured. The aim of this study is to quantify the impact of Part D eligibility on out-of-pocket (OOP) cost for prescription drugs for cancer patients. Methods: Differences-in-differences analyses were used to estimate the effects of Medicare Part D eligibility on OOP pharmaceutical costs, by comparing 4-year periods before and after Part D implementation. Analyses were based on data from the publicly available Medical Expenditure Panel Survey, a nationally representative, all-payer sample of the United States non-institutionalized civilian population. Our analysis compared per-capita OOP burden between Medicare beneficiaries (age 65+) with cancer to near-elderly patients age 55-64 years old with cancer. Statistical weights provided with the dataset were used to generate nationally representative estimates. Results: Overall, 2,147 near-elderly individuals with cancer and 5,296 individuals with Medicare and cancer were included in the analysis (total n=7,443), representing over 88 million people with cancer in 8 years of study. As expected, prescription drug coverage more than doubled among individuals with Medicare from before Part D (34.4%) to after (77.8%); in contrast, prescription drug coverage among the near-elderly remained stable before vs. after Part D (72.0% vs. 71.1%). The mean per-capita OOP cost for Medicare beneficiaries with cancer before Part D was $935 (SE ±30) and decreased to $616 (±25) after implementation of Medicare Part D—a decline of 34%. Compared with changes in OOP pharmaceutical costs for non-elderly patients with cancer over the same period, implementation of Medicare Part D was associated with a further reduction of $159 (±73) per person with cancer. Conclusions: The implementation of Medicare D has significantly reduced OOP prescription drug costs for seniors with cancer, beyond trends observed for younger patients. Further analyses will examine OOP cost patterns for patients with cancer with specific sociodemographic and clinical characteristics.
Patient, public, and oncologists’ attitudes toward rationing medical care.
Authors: Gogineni Keerthi , Shuman Katie , Chinn Derek , Cosenza Carol , Colten Mary Ellen , Fowler Floyd Jackson , Emanuel Ezekiel J. 
Published: March 2020

6518 Background: Lowering health care costs is critical. Patients with cancer (PT) and oncologists (MD) regularly make decisions regarding interventions with potentially marginal benefit but substantial expense. What are the attitudes of PT, the public (GP), and MD on ways to control costs? Methods: In 2012, surveys were completed by 326 adult PT (Response Rate (RR)=72%), a random sample of 891 U.S. adults (RR=50%) and 245 MD (RR=55%). Results: A majority thought Medicare spending was a big or moderate problem (76% PT; 75% GP; 97% MD) and that Medicare could spend less without causing harm (66% PT; 70% GP; 74% MD). Respondents attributed rising costs to multiple factors including drug companies charging too much (94% PT; 90% GP; 94% MD) and insurance company profits (88% PT; 88% GP; 83% MD). Many also thought physicians and hospitals provided unnecessary tests and treatments (RX) (69% PT; 81% GP; 70% MD). Regarding solutions, most supported refusing to pay for expensive care if an equally effective, less expensive alternative was available or if therapy did not improve survival or quality of life (QOL). Few respondents were willing to refuse payment for RX that extend life by 4 months. Conclusions: The majority of those sampled view Medicare costs as a substantial problem and pharmaceutical and insurance companies as significant contributors. The GP in particular believe physicians and hospitals add considerably to the cost problem. A majority favor not paying for more expensive RX when cheaper ones are equally effective or if RX do not improve survival or QOL. MD were accepting of an independent oversight panel however this was met with resistance by PT and the GP. Currently, Medicare and other payers do not consistently follow such practices. [Table: see text]
CUSTOM (Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies trial): A radical redesign of clinical trial structure—Use of mass customization and product postponement.
Authors: Lopez-Chavez Ariel , Thomas Anish , Rajan Arun , Steinberg Seth M. , Dilts David M. , Doyle Austin , Giaccone Giuseppe 
Published: March 2020

6524 Background: Traditionally, the structure of clinical trials has relied upon histology as the top eligibility criterion for enrollment. While more modern trial designs (i.e. BATTLE and I-SPY2) have implemented molecular selection for treatment assignment, histology has remained at the top of the clinical trial structure (1. Histology 2. Molecular selection 3. Treatment assignment). CUSTOM is the first completed prospective clinical trial designed by implementing the ideas of mass customization and product postponement into its structure. This report discusses CUSTOM’s innovative clinical trial design strategy. Methods: In CUSTOM, the task of differentiating a particular treatment’s efficacy by statistical analysis based on histology was postponed until the latest possible point in the trial’s structure (1. Molecular selection 2. Treatment assignment 3. Histology). An optimal two-stage phase II design was used to identify compounds with high clinical activity defined by a response rate of more than 40%. Patients were eligible for enrollment regardless of performance status, previous number of therapies or organ function. Results: CUSTOM was able to enroll 668 patients in only 18 months at 2 academic institutions and conduct a parallel and simultaneous evaluation of multiple targeted therapies (5) in molecularly selected patients in 3 cancer histological types. Its design allowed for the inclusion of rare cancers resulting in the largest prospective molecularly based clinical trial in patients with thymic malignancies and small cell lung cancer. Overall, its design resulted in a more rapid, cost-effective and efficient strategy for pharmaceutical development compared to traditional approaches. Conclusions: The traditional methodology used to design and execute clinical trials (i.e., histology-driven, single treatment vs. SOC) is dated, inefficient and expensive. The CUSTOM’s clinical trial design is one approach to increase the efficiency, reduce the cost, and increase the speed of the early phase pharmaceutical development process. Clinical trial information: NCT01306045.
Patient experience and attitudes toward addressing the cost of breast cancer care.
Authors: Irwin Blair Billings , Zafar Yousuf , Altomare Ivy , Kimmick Gretchen Genevieve , Marcom P. Kelly , Houck Kevin , Peppercorn Jeffrey M. 
Published: March 2020

6551 Background: The American Society of Clinical Oncology has suggested that patient-physician discussion of costs is a component of high quality care. Little data exists on patients’ experience confronting costs or attitudes on how cost should be addressed. Methods: We distributed a self-administered anonymous paper survey to consecutive patients with breast cancer presenting for a routine visit within 5 years of diagnosis at an academic center. Survey questions addressed financial distress, experience and preferences concerning discussions of cost, and views on cost control. Results are primarily descriptive, with comparison among patients on the basis of disease stage using Fisher’s exact test. All p-values are 2-sided. Results: We surveyed 134 patients (response rate 86%). Median age was 61. 72% stage I-III disease, and 28% (n=36) had stage IV disease. 44% (n=57) reported at least a moderate level of financial distress. Only 14% (n=18) reported ever discussing costs with their doctor, though 94% (n=121) felt doctors should talk to patients about costs. 53% (n=69) felt doctors should discuss direct costs with patients but only 38% (n=49) felt doctors should consider costs to society or insurance companies in their decision-making. Patients with metastatic disease were significantly less likely than those with earlier stage disease to want doctors to consider societal costs (33% (n=24) vs 6% (n=2), p<0.01). 88% (n=114) reported concern over costs of cancer care, but there was no consensus on how to control costs. Only 3% (n=4) favored greater cost sharing and 9% (n=11) supported greater means testing. A minority (33%, n=43) supported reducing drug costs through government price controls (33% n=43). The majority endorsed generic substitution (59%, n=75) and preferential selection of drugs which prolong survival 53% (n=69). Conclusions: Although many patients with breast cancer want to discuss costs of care with their doctors, there is little consensus on the ideal content of these discussions. Few patients support consideration of societal costs in clinical decision-making. Further research is needed to evaluate the potential for patient-physician discussions of cost to contribute to affordable high quality cancer care.
Should culture affect practice? Prognostic discussions with immigrants.
Authors: Butow Phyllis Noemi , Sze Ming , Eisenbruch Maurice , Bell Melanie , Aldridge Lynley , Vardy Janette L. , Hui Rina , Boyle Frances , Liauw Winston S. , Goldstein David 
Published: March 2020

6556 Background: Poor prognosis is difficult to impart, particularly across a cultural divide. This study is the first to compare prognostic communication with immigrants (with and without interpreters) versus native–born patients in audio-taped oncology consultations. Methods: Ten oncologists, 78 patients (31 Australian-born, 47 immigrants) and 115 family members participated. The first two consultations after diagnosis of incurable disease were audiotaped, transcribed and coded. 142 consultations were included in the analysis. Results: Fifty percent of doctor and 59% of patient prognostic speech units were notinterpreted or interpreted non-equivalently when an interpreter was present. Immigrant status predicted few, and oncologist characteristics no, prognostic facts disclosed. Oncologists were significantly less likely to convey hope to immigrants, and more likely to use medical jargon (p = 0.009) than with Australian-born patients. Incurable disease status and a limited life span were commonly acknowledged, generally with no timeframe provided. Physical issues were discussed more commonly than emotional aspects. Conclusions: While culture did not appear to influence doctor speech, interpreters filtered or blocked much prognostic communication. Initiatives to empower all patients to attain needed information, optimise communication when an interpreter is present and train cancer health professionals in culturally appropriate care, are urgently required.