bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase I pharmacokinetics trial comparing PF-05280014 (a potential biosimilar) and trastuzumab in healthy volunteers (REFLECTIONS B327-01).
Authors: Yin Donghua , Barker Kerry B , Li Ruifeng , Meng Xu , Reich Steven D , Ricart Alejandro D , Rudin Dan , Taylor Carrie T , Zacharchuk Charles M. , Hansson Arne G
Published: March 2020

612

Background: PF-05280014, a proposed biosimilar to trastuzumab, has an identical amino acid sequence and similar physicochemical and in vitro functional properties to trastuzumab. This study was designed to demonstrate PK similarity of PF-05280014 to trastuzumab from the US (trastuzumab-US) and EU (trastuzumab-EU), and between the licensed drugs. Safety and immunogenicity were also evaluated. Methods: In this double-blind trial (NCT01603264), 105 healthy male volunteers, 18-55 years old were randomized 1:1:1 to receive a single 6 mg/kg IV dose of PF-05280014, trastuzumab-US or trastuzumab-EU. All subjects provided informed consent. PK, safety, and immunogenicity assessments were conducted for 70 days. PK similarity for a given test-to-reference comparison was considered to be demonstrated if the 90% CI of the test-to-reference ratio of the AUC from time 0 to the last time point (AUCT) and maximum concentration (Cmax) were within 80% – 125%. Results: The baseline demographics for the 101 subjects evaluable for PK were similar among 3 treatment arms. The 3 study drugs exhibited similar characteristics of target-mediated disposition and similar PK parameters (Table). The 90% CI for the ratios of Cmax, AUCT, and AUC0-∞were within 80% – 125% for the comparisons of PF-05280014 to trastuzumab-EU or trastuzumab-US, and trastuzumab-EU to trastuzumab-US. Adverse events (AE) were similar for the 3 arms with treatment-related AEs reported by 71.4%, 68.6%, and 65.7% subjects in the PF-05280014, trastuzumab-EU and trastuzumab-US, respectively. No serious AEs were reported. Only 4 subjects had treatment interruptions; 2 discontinued. Only 1 subject (trastuzumab-EU) developed anti-drug antibodies after dosing. Conclusions: This study demonstrates PK similarity of PF-05280014 to both trastuzumab-US and trastuzumab-EU and of trastuzumab-EU to trastuzumab-US. The three study drugs also showed similar safety profiles. Clinical trial information: NCT01603264. [Table: see text]
Correlation between poly (ADP-ribose) polymerase (PARP) and phospho-p65 expression in human breast cancer.
Authors: Klepczyk Lisa Caroline , Wei Shi , Brazelton Jason D. , Keene Kimberly Sue , Bonner James A. , LoBuglio Albert F. , Forero Andres , Grizzle William E. , Yang Eddy Shih-Hsin
Published: March 2020

623

Background: Despite the efficacy of targeted agents in patients with HER2+ breast cancer, resistance often develops necessitating novel treatment strategies. Poly (ADP-ribose) polymerase inhibitors (PARPi) are known to target tumors with aberrant DNA repair. We previously reported sensitivity of HER2+ breast cancer cells to PARPi independent of a DNA repair deficiency but rather due to attenuation of NF-kB signaling. In this study, we investigated the expression of PARP and the active NF-kB subunit phospho-p65, indicators of activity for these pathways, in human HER2+ breast tumors and compared to HER2- tumors. Methods: Patients with breast cancer treated at the University of Alabama at Birmingham between the years 1999 and 2012 were identified. Formalin-fixed, paraffin-embedded tissue blocks were stained for PARP and phospho-p65 and evaluated independently by two blinded physicians, including a board-certified pathologist. An H-score was calculated by multiplying the percent of tumor cells with staining intensity of 0, 1, 2, and 3 and subsequently adding these together for a final score of 0-300. Nuclear and cystosolic staining were scored separately for both proteins. Results: Forty-six HER2+ and 38 HER2- patients with available tissue were identified; however, only 41 HER2+ and 32 HER2- cases had tumoral tissue at the time of analysis. PARP and phospho-p65 were found to be almost exclusively nuclear in both groups. The mean nuclear PARP score was 122.3 in HER2+ cases compared to 61.6 in HER2- cases (p value <0.0001). Mean nuclear phospho-p65 scores were 89.0 and 59.4 in HER2+ and HER2- groups, respectively (p value 0.0008). Additionally, a significantly positive correlation was observed between PARP and phospho-p65 levels. Conclusions: Our study suggests that HER2+ breast cancers have elevated PARP and NF-kB activity compared to HER2- cancers. Furthermore, a direct correlation between PARP and phospho-p65 levels was found. When combined with our previously published preclinical findings, the current research supports the potential clinical utility of PARPi in patients with this aggressive form of breast cancer.
Predictive factors for pathologic complete response (pCR) to trastuzumab (T)-based neoadjuvant chemotherapy in HER2+ breast cancer (BC) women treated in the National Cancer Institute (NCI) of Mexico.
Authors: Sifuentes Erika , Chavarri Guerra Yanin , Baez-Revueltas F. Berenice , Soto-Perez-de-Celis Enrique , Lara-Medina Fernando , Ruano Santiago , Villarreal-Garza Cynthia Mayte
Published: March 2020

634

Background: Neoadjuvant treatment identifies subgroups of patients (pts) with different prognosis. In HER2+ BC, some tumors have been reported to be more sensitive to anti-HER2 therapy than others. We conducted an exploratory analysis in HER2+ BC women who received T-based neoadjuvant chemotherapy. Methods: Clinico-pathologic data from HER2+ BC pts who received neoadjuvant chemotherapy and T between January 2007 and May 2012 at the NCI were identified. Estrogen receptor (ER), progesterone receptor (PR) and HER2 expression were determined by immunohistochemistry and/or FISH. pCR was defined as complete absence of invasive tumor in breast and axillary nodes. Proportion differences were tested using the Chi-square test. A generalized linear model was used for multivariate analysis. Results: 243 pts received T-based neoadjuvant chemotherapy for localized HER2+ BC tumors. Median age was 49 (26-72) years. 96% had positive axillary nodes at diagnosis and median tumor size was 5.5 (1.5-20) cm. 49.4% had hormone receptor (HR) + (ER+ and/or PR+) and 50.6% HR negative (ER- and PR-) tumors. 63.4% pts achieved pCR. HR negative tumors reached significantly higher pCR rates than HR + tumors (69.9% vs. 56.7%, p=0.034). Pts with inflammatory BC (n=27) had a trend to achieve pCR less frequently than the non-inflammatory tumors (48.1% vs. 65.3%). Those who received taxane-anthracyline sequence chemotherapy (n=20) achieved pCR in 70% of the cases vs. 62.8% with anthracycline-taxane sequence. Differences among other variables (age, tumor size, nodes and HER2 positivity ++/+++) were not significant. Variables that positively influenced pCR were HR negative status (p=0.015), non-inflammatory BC (p=0.082) and chemotherapy sequence (p=0.086). Conclusions: HR negative HER2+ BC tumors were associated with higher pCR, consistent with neoadjuvant trial reports. Preclinical data suggest bi-directional crosstalk between HER2 and ER pathways, which might influence anti-HER2 agents and chemotherapy sensitivity for tumors co-expressing both receptors. New strategies are needed to overcome resistance for HER2+ HR+ BC tumors.
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.
The potential impact of the Deep South Network for Cancer Control on cervical cancer mortality among black females in historically underserved areas of Alabama.
Authors: Singh Karan P. , Jackson Bradford E , Ojha Rohit P , Wang Chenguang , Uhm Minyong , Fouad Mona , Partridge Edward , Bae Sejong
Published: March 2020

6559

Background: Racial disparities in cervical cancer mortality are well-documented. The Deep South Network for Cancer Control (DSNCC) was implemented in 2000 to address this disparity by targeting blacks for cervical cancer screening in historically underserved areas of Alabama and Mississippi. We aimed to assess whether the implementation of the DSNCC has improved cervical cancer mortality among black females in Alabama. Methods: We used data from the University of Alabama-Birmingham (UAB) Comprehensive Cancer Center Tumor Registry, which comprises all cancer cases treated in the UAB Health system. We selected all black females diagnosed with cervical cancer in the pre-DSNCC (January 1995-December 1999) and post-DSNCC (January 2001-December 2005) periods. Person time was calculated for up to five years post diagnosis. We estimated hazard ratios (HRs) and corresponding 95% confidence limits (CLs) using Cox proportional hazards models. The cervical cancer mortality rate of black females who resided in DSNCC-targeted Alabama counties was compared to non-DSNCC-targeted Alabama counties before and after implementation of the DSNCC. Results: The study population comprised 129 black females diagnosed with cervical cancer pre-DSNCC and 175 diagnosed post-DSNCC. During the pre-intervention period, black females in DSNCC-targeted counties had a two-fold higher cervical cancer mortality rate than black females in non-DSNCC-targeted counties (HR=2.0; 95%CL: 1.10, 3.72). During the post-intervention period, black females in DSNCC-targeted counties had nearly a two-fold lower cervical cancer mortality rate than black females in non-DSNCC-targeted counties (HR=0.54; 95%CL: 0.35, 0.87). Conclusions: Our results suggest that the DSNCC interventions are improving cervical cancer outcomes among black females in historically underserved areas of Alabama. The current analysis was only able to examine the initial 5 years after implementation of the DSNCC; continued assessment of outcomes would be useful for assessing the long-term impact of the DSNCC.
Racial differences in attitudes toward molecular testing for personalized cancer therapy.
Authors: Yusuf Rafeek Adeyemi , Rogith Deevakar , Hovick Shelly Renee Anstey , Peterson Susan K. , Burton-Chase Allison Michelle , Fellman Bryan , Li Yisheng , Urbauer Diana L , McKinney Carolyn , Bernstam Elmer Victor , Meric-Bernstam Funda
Published: March 2020

6566

Background: We assessed attitudes of breast cancer patients regarding molecular testing for personalized therapy and research. Methods: Female breast cancer patients presenting to a cancer center completed a questionnaire. Associations between demographic, clinical variables and attitudes towards molecular testing were evaluated. Results: 308 patients were approached and 100 completed the survey (32% response rate). If covered by insurance, most patients were willing to undergo molecular testing to assist in selection of both approved drugs (81%) and experimental therapy (59%). Even of testing was covered, non-white patients were less willing to undergo molecular testing for selection of approved drugs (nonwhites vs. whites, OR=0.13; p=0.0004) or experimental drugs (OR=0.26; p=0.0072; see table below). Most patients (75%) were willing to undergo a biopsy to guide therapy, and 46% were willing to undergo research biopsies. Non-white patients were less willing to undergo research biopsies (OR=0.17; p=0.0033). Patients desired return of research results when results had implications for treatment (91%), new cancer risk (90%), and other preventable/treatable diseases (87%). Conclusions: Most patients are willing to undergo molecular testing and minimally invasive procedures to guide approved or experimental therapy. There are significant differences in attitudes towards molecular testing between racial groups. Novel approaches may be needed to prevent disparities in delivery of genomically-informed care and to increase minority participation in biomarker-driven trials. [Table: see text]
Social inequality in survival after lung cancer: The attribution of stage at diagnosis, receipt of treatment, and comorbidity in a Danish nationwide clinical database study.
Authors: Dalton Susanne O. , Steding-Jessen Marianne , Jakobsen Erik , Schuz Joachim , Johansen Christoffer
Published: March 2020

6570

Background: Survival after lung cancer depends on stage, treatment, and patient-specific factors as comorbidity. These factors are potentially influenced by social position (SEP). We previously reported a lower risk for advanced-stage lung cancer among persons with higher SEP and we investigate the association between SEP (education, income and cohabiting status) on receipt of 1stline treatment and overall survival in a population-based cohort of lung cancer patients in Denmark. Methods: This registry-based cohort study links data on prognostic factors and treatment from the Danish Lung Cancer Registry to individual socioeconomic information in Statistics Denmark and comorbidity from the National Hospital Discharge Registry for 13,659 persons diagnosed with lung cancer 2004-2011. Results: ORs for receipt of 1stline treatment were higher with longer education and higher income and for patients living with a partner in both men and women with low (T1-3N0M0; T0-3N1M0) and advanced-stage (T0-3N2-3M0; T4N0-3M0; TxNxM1) lung cancer although not statistically significant for all estimates. Among low-stage patients all-cause mortality was 15% higher in patients with short vs higher education, 26% higher for low vs high income and 23% higher for living alone vs living with a partner. In advanced-stage patients, differences in all-cause mortality was 11%, 14% and 8% for education, income and cohabitation status. Stage, treatment, Charlson Comorbidity Score and Performance Score attenuated associations but did not eliminate the association between low income (HR, 1.12; 95% CI, 1.05-1.19) and living alone (HR, 1.15; 95 CI, 1.06-1.25) in low stage lung cancer patients while no social differences in adjusted HR remained in advanced-stage patients. Conclusions: We show that even in a country with free and equal access to health care disparities exist in access to lung cancer treatment both of curative and of palliative intent. Differences in stage, treatment and presence of comorbidity by social position explained most of the social inequality in lung cancer survival although differences remained in the short term for low-stage patients.
Caregiver evaluation of the quality of end-of-life care (CEQUEL) scale: The caregiver’s perception of patient care near death.
Authors: Higgins Philip C , Prigerson Holly Gwen
Published: March 2020

6573

Background: End-of-life (EOL) measures are limited in capturing caregiver assessment of the quality of EOL care. None include caregiver perception of patient suffering and prolongation of death. We developed and validated the Caregiver Evaluation of Quality of End-of-Life Care (CEQUEL) scale, a more comprehensive measure of caregiver-perceived quality of EOL care. Methods: Data were derived from Coping with Cancer (CwC), a multisite, prospective, longitudinal study of advanced cancer patients and their caregivers (N=275 dyads). Caregivers were assessed before and after patient deaths. CEQUEL’s factor structure was examined; reliability was evaluated using Cronbach’s α, and convergent validity by the strength of associations between CEQUEL scores and key EOL outcomes. Results: Factor analysis revealed four distinct factors: Prolongation of Death, Perceived Suffering, Shared Decision-Making, and Preparation for the Death. Each item loaded strongly on only a single factor. The 13-item CEQUEL and its subscales showed moderate to acceptable Cronbach’s α (range: 0.52-0.78). 53% of caregivers reported patients suffering more than expected. Higher CEQUEL scores were positively associated with therapeutic alliance (r=.13; p≤.05) and hospice enrollment (z=-2.09; p≤.05), and negatively associated with bereaved caregiver regret (r=-.36, p≤.001) and trauma symptoms (z=-2.06; p≤.05). Conclusions: CEQUEL is a brief, valid measure of quality of EOL care from the caregiver’s perspective. It is the first scale to include perceived suffering and prolongation of death. If validated in future work, it may prove a useful quality indicator for the delivery of EOL care and a risk indicator for poor bereavement adjustment.
Assessment of the effectiveness of a chemotherapy education program: A Brown University Oncology Research Group study.
Authors: Connell Nathan Theodore , Sikov William M. , Faricy-Anderson Katherine E. , Korber Susan , Thomas Anthony George , Rosati Kayla , Safran Howard , Mega Anthony E.
Published: March 2020

6574

Background: Patients about to begin chemotherapy often have questions about their treatment along with significant anxiety. This study evaluated whether pre-chemotherapy teaching sessions improved patient knowledge and anxiety. Methods: After meeting with their oncologist to discuss planned chemotherapy treatment, subjects completed a 10-question survey which assessed their knowledge of anticipated side effects and treatment schedule on a 1-4 rating scale (1=no knowledge, 2=minimally informed, 3=reasonably informed, 4=well informed) as well as anxiety about initiating chemotherapy (1=no anxiety, 2=minimal anxiety, 3=moderate anxiety, 4=severe anxiety). Subjects then completed a structured nurse-led chemotherapy education session. The survey was repeated on the first day of cycle 1. Mantel-Haentzel Chi-square tests were used to evaluate for changes across the surveys. Subgroup analysis by Wilcoxon signed-rank test was performed to assess differences in anxiety based on age. Results: At the time of analysis, 142 subjects had completed the education session. Improvement was seen in knowledge of treatment schedule (mean score increase from 2.5 to 3.4, p<0.001), side effects (mean score increase from 2.3 to 3.4, p<0.001), and how to use medications designed to prevent and treat nausea (mean score increase from 1.8 to 3.2, p<0.001). There was significant reduction in patient anxiety about starting treatment (mean score decrease from 2.3 to 2, p<0.001) and anxiety related to treatment side effects (mean score decrease from 2.3 to 2, p<0.001). Analysis of anxiety by age showed that those age <65 had higher baseline anxiety scores with a reduction in anxiety after the education session while those age ≥65 had lower baseline anxiety scores with a rise in anxiety after the education session (Table). Conclusions: A pre-chemotherapy teaching session improves patient knowledge about the planned treatment along with reduction in anxiety. Change in anxiety differs between patients 65 years of age and older as compared to those less than 65. [Table: see text]
Are needs of stakeholders in cancer care being met? A novel approch to assessing needs to improve value in cancer care.
Authors: Patel Manali I. , Moore David , Randolph Shannon , Wakelee Heather A. , Blayney Douglas W. , Milstein Arnold
Published: March 2020

6581

Background: Advanced cancer is a leading cause of death in the US. While treatments have improved, patients still report physical, emotional, and financial burdens associated with the disease. In order to improve cancer care, a comprehensive examination of unmet needs among patients, health care professionals, and other stakeholders is required to develop interventions that can improve patient outcomes, experience, and reduce healthcare spending. Methods: A national convenience sample of patients, families, caregivers, healthcare professionals, payer groups, and healthcare delivery systems who have experience with cancer care were selected for participation. A 10-question survey was administered to participants regarding their experiences with current cancer care. A novel combination of Grounded theory, Stanford d.school and bio-design needs-findings methodologies were used to assess and prioritize needs. Results: A total of 273 participants presented 99 unique needs over the study period. Needs were organized into five categories: 1. Monitor/Intervene Patient Clinical and Symptom Data 2. Shared Decision-Making 3. Best Practice Communication 4. Integrated Care Team 5. Patient-Tailored Care. The most common needs of cancer patients were improved symptom control. Needs among providers focused on minimizing tasks that could be performed by others. Payer needs reflected improved value in care. Family and caregiver needs reflected shared decision-making in treatment plans. Healthcare delivery system needs included improved guideline development, evidence-based care, and report of quality metrics. Conclusions: A novel methodology to assess, analyze, and organize unmet needs in cancer care reveals that the top concerns among stakeholders are better symptom control, enhanced efforts to improve patient care commensurate with patients’ values, and a more tailored approach to coordinate care delivery using guideline-based care with attention to quality metrics. Future studies should draw upon these needs to develop targeted interventions for patients with advanced cancer that can improve experience, clinical outcomes, and reduce healthcare spending.
Are oncologists involved in cancer biomarker decisions at their institutions?
Authors: Weldon Christine B. , Trosman Julia R. , Benson Al Bowen , Tsongalis Gregory J. , Siziopikou Kalliopi P. , Gradishar William John , Schink Julian C.
Published: March 2020

6617

Background: Biomarkers play a critical role in oncology, but differences in accuracy and quality exist between different testing methods for specific markers. ASCO/CAP guidelines call for oncologists, on behalf of patients, to seek information on testing quality and to obtain assurance that testing laboratories are appropriately accredited (Wolff et al, JCO, 2007). We surveyed oncologists and pathologists from the NCI designated cancer centers to collect individual perception of their institution’s decision making on biomarkers, and awareness of lab quality accreditation. Methods: We conducted an IRB approved web survey of pathologists and oncologists at the 58 NCI designated cancer centers providing adult breast, gastric, esophageal and non small cell lung cancer care. The survey included 12 questions on institutional decision processes and lab quality accreditation. We analyzed results using simple frequencies and the Fisher's exact test. Results: The study achieved a response rate of 98% (57/58 sites), with survey responses from 115 pathologists and 156 oncologists. The perception that their institution uses a formal organizational review and decision process on new biomarker tests was reported by 47% (54/115) of pathologists and 31% (48/156) of oncologists (p= .0078). 22% (33/153) of oncologists report they are always involved in institutional decision making on biomarker method selection for their specialty. Awareness of CAP certification status for their institutional laboratory was reported by 88% (99/112) of pathologists and 46% (65/142) of oncologists (p <0.0001). Awareness of whether their institutional laboratory underwent CAP HER2 IHC and/or FISH proficiency testing was reported by 70% (53/76) of pathologists and by 21% (13/63) of oncologists who treat breast cancer (p<.0001). Conclusions: Oncologists are typically not actively involved in their institution’s decision making process to select biomarker testing methods, nor are many of them aware of their institutional lab’s quality accreditation. With the ever increasing role of biomarkers in cancer care, oncologists’ awareness of biomarker testing performance and their participation in decision making related to biomarkers will become critical.