bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explorative analysis of expanded access for intermediate-size and larger patient populations.
Authors: Krendyukov Andriy 
Published: May 2020

e19070 Background: Cancer is a major public health problem worldwide and is the second leading cause of death in the USA. While continuous efforts are being made by the US Food and Drug Administration to bring more new oncology products (NOP) to patients, there is a high unmet medical need for oncology patients to get access to care, and in particular access to NOP outside of clinical trials before the NOP is approved or commercialized. To improve access to NOP, several pathways are endorsed by competent authorities including: early dialogue with regulatory agencies; accelerated assessments; conditional marketing authorization; and early access provision, known as expanded access (EA) in the USA and compassionate use (CU) in the EU. Methods: A literature search and explorative analysis of available EA data from Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) relating to submission and approval of existing or investigational new drugs (IND) was performed for individual (single) patient emergency and non-emergency IND (IPIND), intermediate size IND (ISIND), and treatment IND (TIND). The findings were compared to centralized CU programs. The analysis was primarily focused on understanding the current landscape of EA for patient groups compared with individual patient categories. Results: Based on available CDER and CBER data submissions for ISIND and TIND categories were dramatically low compared with IPIND and total applications for EA: 1.25% (ISIND) and 0.13% (TIND) out of 1,598 EA applications received in 2018; and respectively 2.7% and 0.11% out of 1,741 EA applications in 2017; 2.6% and 0.24% out of 1,634 EA applications in 2016; 3.6% and 0.15% out of 1,328 EA applications in 2015; and 2.8% and 0.05% out of 1,886 EA applications in 2014. A high approval rate was reported for all three EA categories, and in particular approval of 95% (174 out 183) for ISIND and 100% (1 application) for TIND by CDER, and approval of 89% (24 out of 27) for ISIND and 80% (8 out of 10) for TIND by CBER. No applications for CU were reported by the European Medicines Agency for the same period of time, however several oncological products have been approved for CU in some European countries. Conclusions: Despite high approval rates, applications for ISIND and TIND remain low, especially in comparison to IPIND. In the absence of, or limited, alternative treatments, access provision to patient groups such as ISIND and TIND in the USA, and CU in the European Union, might represent an underutilized opportunity for oncological patients to obtain early access to care.
Comparison of advanced care discussions between Chinese-American and Caucasian stage IV cancer patients at a single American cancer center.
Authors: Glover Avery , Schroeder Courtney , Ernst Emma , Vesel Tamara 
Published: May 2020

e19081 Background: Timely discussions with cancer patients on prognosis, goals of care (GOC), and end-of-life care (EOLC) are essential components of quality care for diverse populations. Although Chinese-Americans represent one of the fastest growing ethnic groups in the United States, little is known about the utilization of these advanced care discussions with Chinese-American cancer patients. Methods: In this exploratory review, we collected data for 63 Chinese-American and 63 Caucasian stage IV solid cancer patients at a tertiary medical center who died 2013-2018. The following data points were compared: frequency and timing of prognosis, GOC, and EOLC discussions; family inclusion in discussions; healthcare proxy identification; DNR completion. Results: Chinese-American and Caucasian patients had similar frequencies of prognostic (76% vs 71%), GOC (51% vs 56%), and EOLC discussions (89% vs 84%). For all three types of conversations, Chinese-American patients had the discussions earlier on average (days before death: prognosis 86 vs 62; GOC 54 vs 37; EOLC 69 vs 48) and included family members in the discussions more often (30% vs 15%). Chinese-Americans identified healthcare proxies earlier (50 vs 45 days before death). Chinese-Americans had DNR orders placed later (29 vs 33 days before death) and were more likely to have DNR orders placed on the day of death (30% vs 23%). Conclusions: Despite similar frequency of advanced care discussions, earlier conversations, and earlier identification of healthcare proxies in the Chinese-American group, DNR orders were placed later and were often delayed until the day of death for Chinese-American patients. Further studies are needed to better explore the differences indicated in this preliminary study.
Effect of race and insurance status on stage at diagnosis and overall survival of triple-negative breast cancer (TNBC): Analysis of the National Cancer Data Base (NCDB).
Authors: Khan Rafiullah , Abuali Inas , Vick Eric J. , Smart Luke , Xie Changchun , Charif Mahmoud 
Published: May 2020

e19086 Background: TNBC is a heterogeneous sub-type of breast cancer characterized by younger age of onset, more aggressive course, and higher incidence among African Americans who also experience disparities in access to health care including health insurance coverage and cancer screening. Methods: We performed a retrospective analysis of the NCDB to study the impact of race and insurance status on the stage at diagnosis and overall survival of people with TNBC. Chi-square tests analysis was used for univariate analysis. Cox models were used to test for survival differences between race and insurance status adjusted for other covariates such as age at diagnosis, gender. Results: Among 1,148,016 people with TNBC registered in the NCDB from 2010 to 2016, 87.7% were identified as white and 12.3% were identified as black. The majority (99%) were female. Mean age at diagnosis was 62.0 years for females and 65.9 years for males. Among white patients, 1.8% were uninsured while 3.6% of black patients were uninsured. Advanced stage at diagnosis was less common among white people (9.4%, Stage 3; 4.9%, Stage 4) than black people (13.3%, Stage 3; 7.6%, Stage 4). Uninsured patients had more advanced disease at time of diagnosis (16.2%, Stage 3; 14.1%, Stage 4) than insured patients (9.8%, Stage 3; 5.0%, Stage 4). Overall survival after adjustment for age at diagnosis, gender and insurance status was greater for white patients compared to black patients (harm ratio 0.60). Overall survival after adjustment for age at diagnosis, gender and race was lower for uninsured patients than insured patients (harm ratio 2.25). Conclusions: Racial disparities significantly affect TNBC patients, with black women having lower insurance coverage and worse overall survival. [Table: see text]
Factors affecting time to treatment in hepatocellular cancer.
Authors: Seegobin Karan , Majeed Umair , Ritter Ashton , Wylie Natasha , Starr Jason Scott , Jones Jeremy Clifton , Mody Kabir 
Published: May 2020

e19088 Background: Significant disparities in the stage at diagnosis and survival outcomes exist between various groups diagnosed with hepatocellular carcinoma (HCC) based on sex, race, insurance coverage, and marital status. Previously published data shows disparities more in patients who are African-American, Asian and low income. Little data has been published on factors that influence timeliness to treatment initiation in patients diagnosed with HCC. Methods: Retrospective analysis was performed on 96,586 patients diagnosed with HCC from 2004-2014 using data in the National Cancer Database (NCDB). Time to treatment was divided into two categories: ≤40 days (early, n = 66322) and > 40 days (late, n = 30264). We carried out univariate and multivariate analyses to compare demographic, clinical, treatment, and facility-related factors influencing the timeliness of treatment initiation in HCC. Results: Univariate analysis revealed a significant difference in time to treatment initiation based on age, race, income, insurance status, type of area, geographic region, type of facility, and cancer stage (P < 0.001). Multivariate analysis showed that household income < $30,000/year, Pacific region, urban area of residence, black race, age 70-79 years old or ≥80 years old, academic centers, stage II disease and medicaid insurance were all factors with longer time to treatment initiation. Discussion: HCC is the sixth most common cancer and the second leading cause of cancer mortality worldwide. The 5-year relative survival for localized, regional, and distant stages are 32.6%, 10.8% and 2.4% respectively. In our results we noted significant disparities in time to treatment with respect to various socioeconomic factors. These results are comparable to that reported in other cancer types. Further subgroup analysis of our data shows 2581 patients who received their first treatment after 200 days. In a similar study done in Taiwan, those treated more than 181 days and 61–180 days after diagnosis had a 1.68 and a 1.39 increased risk of death respectively, which were statistically significant. Many factors contribute to delayed treatment, some of which are difficult to circumvent, however where possible efforts should be made to overcome these. Conclusions: Various socioeconomic factors were found to affect the time to treatment initiation in HCC patients. The next step would be to strategically implement policies and practices to address these factors.
Cardiotoxicity and heart failure in patients receiving chemotherapy: A nationwide analysis.
Authors: Mariam Roy Arya , Goel Akshay , Konda Manojna , Verma Rashmi 
Published: May 2020

e19097 Background: Cardiotoxicity resulting in heart failure (HF) is one of the most common complications of chemotherapy which significantly impacts patient care and results in poor clinical outcomes. Based on prior clinical studies, cancer patients have multiple cardiovascular comorbidities and higher prevalence of cardiovascular diseases which makes them more vulnerable to cardiovascular injuries during chemotherapy. It may increase their risk of developing cardiomyopathy or worsening of the already existing cardiac conditions which result in HF and death. Methods: We conducted a retrospective analysis of the National Inpatient Sample Database for the year 2017. Patients who were admitted in the hospital for chemotherapy administration and those who have HF were identified using ICD-10 codes. The mortality of patients with HF who receive chemotherapy and the factors affecting the mortality were studied. The two groups that were studied are chemotherapy patients with and without HF. Results: A total of 29,018 admissions for chemotherapy were identified during the year 2017. Out of these, 2.64% of patients were found to have HF (n = 767). The median age for the patients who have an associated diagnosis of HF was 63. The overall mortality of chemotherapy-related admission was 0.80%. The mortality of patients with HF who received chemotherapy was higher than the patients without HF who received chemotherapy (4.3% vs 0.7%, OR = 1.82, p = 0.001). Patients with HF who were admitted for chemotherapy were 82% more likely to die while in hospital than those without HF. Females who have HF had a higher mortality rate and had 64% more odds of dying while admitted for chemotherapy than males with HF (7.92% vs 1.93%, OR = 1.64, P = 0.00, CI = 1.31- 1.82). Also, interestingly Asians who have HF had higher mortality while admitted for chemotherapy than all the other races who had HF who received chemotherapy (Asians vs Caucasians vs African Americans 13.63% vs 4.64% vs 2.85%, p = 0.041). Conclusions: The mortality of patients with heart failure who receives chemotherapy is higher than the overall mortality from chemotherapy-related side effects. Females and Asians who have HF had higher mortality while admitted for chemotherapy. Patients who have prior cardiovascular diseases have to be given diligent care and special attention while we plan for chemotherapy to prevent the development or worsening of heart failure.
The effect of regional anesthesia on cancer related outcomes after oncological surgeries: A systematic review.
Authors: Lin Jun , Jin Zhaosheng , Li Ru 
Published: May 2020

e19099 Background: Surgical resection remains one of the main curative treatment options for most solid-organ malignancies, and oncological surgery caseload has been steadily increasing over the years (1). It has been hypothesized that regional anesthesia may improve cancer related outcome. Both retrospective and prospective studies have been conducted on various cancer types, using different regional anesthesia techniques; and most meta-analyses did not specify the cancer type or regional anesthesia technique as part of their primary outcome (2, 3). In this systematic review, we will review the evidence base of regional anesthesia techniques for each cancer sites. Methods: We systematically reviewed literature from PubMed for studies related to oncological surgery with regional anesthesia, and cancer related outcomes. Main outcomes of interest are recurrence rate or recurrence free survival. The strength of the evidence is reported descriptively. Results: Regional anesthesia techniques most studied in relation to oncological surgery and cancer outcomes are neuraxial (spinal and epidural) anesthesia, and paravertebral block. Neuraxial anesthesia have been shown to improve outcomes in both prostate and ovarian cancer surgeries. On the other hand, current evidence suggest that paravertebral block does not improve breast cancer outcomes, and neuraxial anesthesia does not improve colorectal cancer outcomes. Evidence regarding the use of neuraxial anesthesia in bladder cancer is conflicting. There are also limited evidence suggesting that regional anesthesia may not improve outcomes in lung and upper GI cancers. Conclusions: The protective benefit of regional anesthesia appears to be limited to certain cancer types. More studies are needed in order to determine the effect of regional anesthesia techniques on each cancer types and underlying mechanisms. 1 Vesey SG, McCabe JE, Hounsome L, Fowler S. UK radical prostatectomy outcomes and surgeon case volume: based on an analysis of the British Association of Urological Surgeons Complex Operations Database. BJU Int 2012; 109: 346-54. 2 Sun Y, Li T, Gan TJ. The Effects of Perioperative Regional Anesthesia and Analgesia on Cancer Recurrence and Survival After Oncology Surgery: A Systematic Review and Meta-Analysis. Reg Anesth Pain Med 2015; 40: 589-98. 3 Chen WK, Miao CH. The effect of anesthetic technique on survival in human cancers: a meta-analysis of retrospective and prospective studies. PLoS One 2013; 8: e56540.
National estimates of mental health needs among non-elderly adult cancer survivors.
Authors: Ji Xu , Cummings Janet , Gilleland Marchak Jordan , Han Xuesong , Mertens Ann C. 
Published: May 2020

e19103 Background: As advancements in cancer therapies expand the population of long-term cancer survivors, it is important to understand long-term mental health (MH) outcomes associated with cancer experience. This study used a U.S. nationally-representative sample of adult cancer survivors to assess and compare MH outcomes across age groups. Methods: We used the 2015-2017 National Survey of Drug Use and Health to identify respondents aged 18-64 years who reported a history of cancer (survivors) or never had cancer. MH outcomes were operationalized as events in past year of: major depressive episodes, serious psychological distress, suicidal thoughts, suicidal plans, suicidal attempts, any mental illness, and serious mental illness. We compared these outcomes between survivors and those without cancer in adjusted regression analyses, controlling for respondents’ demographic (gender, race/ethnicity) and socioeconomic (health insurance, employment, education status, marital status) characteristics. All analyses were stratified by age group (18-34, 35-49, and 50-64 years). Results: When comparing 2,656 survivors and 112,952 adults without cancer within each age group, survivors had elevated prevalence of MH problems in in five of the seven domains of adverse MH measures. Among young adults (aged 18-34 years), survivors were more likely than their noncancer counterparts to experience major depressive episodes (18.1% versus 9.6%, p< 0.001), serious psychological distress (34.2% versus 17.9, p< 0.001), suicidal thoughts (10.5% versus 7.0%, p= 0.011), any mental illness (41.1% versus 23.3%, p< 0.001), and serious mental illness (13.2% versus 5.9%, p< 0.001) in the past year. These differences persisted in adjusted analyses ( p-values < 0.01). While similar survivor-comparison differences were observed among older groups, the magnitude of these differences was smaller. When comparing MH outcomes across age groups among survivors, young adult survivors had the highest likelihood of experiencing MH problems across all seven domains of adverse MH measures ( p-values < 0.05). Conclusions: This population-based study shows elevated prevalence of MH problems among adult cancer survivors, as compared to the general noncancer population. We also identified a clear age gradient in the prevalence of MH problems, with young adult survivors exhibiting the highest prevalence of adverse MH outcomes. Our findings highlight the importance of developing strategies to ensure early detection and screening of mental illness and improve access to MH treatment for cancer survivors.
Partner engagement and patients’ receipt of colorectal cancer surveillance.
Authors: Veenstra Christine M , Abrahamse Paul , Morris Arden M. , Hawley Sarah T. 
Published: May 2020

e19106 Background: Over 50% of survivors of colorectal cancer do not receive guideline-concordant surveillance. In light of growing recognition that members of couples influence each other’s health behaviors, we sought to describe partner engagement in surveillance and evaluate associations between partner engagement and patient receipt of surveillance. Methods: In 2019 we surveyed patients who, in 2014-18, underwent resection of Stage III colorectal cancer and were seen at a community oncology practice, an academic cancer center, or reported to Georgia SEER (current RR 46%). Patients gave a separate survey to their partner. 254 partners (68% RR) completed surveys. Using existing measures, we assessed 3 partner-reported elements of engagement: 1) informed about surveillance; 2) involved (extent of and satisfaction with) in surveillance; 3) aware of patients’ values/preferences. Each measure was scored on a continuous scale with higher scores indicating greater engagement. We assessed patient receipt of surveillance by patient-report of receipt of CEA blood test, imaging, and colonoscopy/sigmoidoscopy (all y/n response). We performed multivariable regression analyses to assess associations between each element of partner engagement and patient receipt of surveillance, controlling for important partner- and patient-level variables. Results: Most partners (85%) were > age 50, female (64%), and white (86%). 27% had <high school education. Most patients (60%) had colon primary (vs rectal), received chemotherapy (95%), and were 3-4 years out from diagnosis (62%). Female partners and those with <high school education were more likely to report a greater extent of involvement; Partners < age 50 were more likely to report greater satisfaction with involvement. Female partners, those with <high school education, and partners of patients who received chemotherapy were more likely to report greater awareness (all p < 0.05). Being informed did not vary by partner or patient factors. Having a more aware partner was associated with greater patient receipt of surveillance colonoscopy/sigmoidoscopy (p = 0.01). Receipt of surveillance CEA or imaging did not vary by partner engagement. Conclusions: Partner engagement in patients’ surveillance varied by partner age, gender and education. Partner awareness of patient preferences was associated with patient receipt of surveillance colonoscopy/sigmoidoscopy. Our findings suggest that interventions to engage partners in patients’ surveillance may improve receipt of guideline-concordant care for survivors of colorectal cancer.
Feasibility of randomized controlled trials (RCTs) for drugs approved by the United States Food and Drug Administration (FDA) based on single arm studies.
Authors: Rittberg Rebekah , Czaykowski Piotr , Niraula Saroj 
Published: May 2020

e19115 Background: US FDA introduced an Accelerated Approval (AA) pathway in 1992 to expedite access to promising new drugs, based on the assumption that RCTs would delay introduction or prove unfeasible. One resulting trade-off is an “interim” compromise in acceptable level of evidence: such approvals have increasingly relied on Overall Response Rates (ORR) from Single Arm Studies (SAS). FDA requires confirmation of benefits for such drugs in future RCTs, but that requirement may take years and often never met. Methods: We pooled drugs approved by FDA over 5 years based on ORR observed in SASs for solid tumors. We calculated the differences in ORR between the newly approved drugs and existing standard of care for each cancer sub-type, and designed hypothetical RCTs necessary to detect that difference. RCTs were designed based on power of 0.80, α-error of 5% (two-sided), and 1:1 randomization, using PS software (Vanderbilt University). We estimated accrual time for the RCTs using disease incidence and annual death rates for each cancer subtype in USA using Surveillance, Epidemiology & End Results records. Results: 28 of 129 (22%) FDA approved drugs for solid tumors, from 2015-2019, were based on SAS. Median sample size of 107 patients per approval (range 26-550). Drugs were approved based on median ORR of 38.9% (range 13-78%), compared to median ORR of 24.4% (range 5-62%) for existing standard of care [median difference in ORR 14.9% (range 6-45%)]. Using established statistical standards, median sample size required to conduct RCTs was 206 patients (range 44-1724); based on a conservative accrual rate of 5% of all eligible US patients, for 22 of 24 approvals RCTs with ORR as primary endpoint could have been completed within a timeframe equal to or less than the time used for undertaking the SAS. Drugs for 4 indications of 28 had a lower ORR compared to existing standard of care, while lacking evidence of superiority in any other survival outcome, raising important concerns about the approval process. Conclusions: Feasibility of conducting RCTs with an ORR endpoint within an acceptable time-frame does not appear to be a practical constraint for an overwhelming majority of drugs approved by FDA based on SAS alone. This finding questions the necessity of accepting a lower bar for efficacy and toxicity while approving drugs using the AA pathway, especially when supported by clinical equipoise with existing standards of care. ORR was lower than existing standard of care for 4 indications, putting rationale for these approvals into question.