bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful creation of an outpatient team-based model for traditionally inpatient chemotherapy.
Authors: Kubal Timothy Edward , Salamanca Christopher , Tobon Katherine , Lubas Amber , Frantz Diedra K. , Nelson Rebecca , Smith Melissa , Wartenberg Karen , Lancet Jeffrey E. 
Published: October 2019

86 Background: In 2014, due to increased demand for inpatient hospital beds and subsequent patient dissatisfaction due to delays for patients receiving scheduled chemotherapy, Moffitt Cancer Center created a multi-disciplinary team to transition traditionally inpatient chemotherapy regimens into the outpatient setting. Methods: A Team composed of Physicians, Pharmacists, PA’s/ARNP’s, Social work, Infusion Nursing and IT drove initiation and implementation of new processes from 2014-Current with gradual increases in patient volumes and continued high quality and patient safety. Results: Over the examined 5 year time period, HyperCVAD Arm A, DA-EPOCH, Blinatumomab and Liposomal Daunorubicin and Cytarabine (Vyxeos) were transitioned into the outpatient setting. 667 total cycles of chemotherapy were transitioned into the outpatient setting, saving 4,386 inpatient days over the examined time period. Hospitalization was required in 22 of 667 cycles (3.3%) with no attributable mortality due to outpatient administration. Examination of potential financial impact was consistent with an estimated favorable impact to overall margin of $3,153,534 due to backfill of inpatient beds. Conclusions: Outpatient delivery of traditionally inpatient chemotherapy is safe and effective with the potential for reduction in delays for scheduled chemotherapy patients and favorable financial impact. Critical to success is the creation of an empowered, cross functional leadership team and a gradual and sequential approach to implementation.
Development of a multidisciplinary approach to supportive care for patients with genitourinary cancers.
Authors: Yocavitch Liana , Garber Gregory D. , Petok Alison , Worster Brooke , Handley Nathan 
Published: October 2019

88 Background: Patients with cancer who engage early with palliative care may experience improved quality of life (QOL), increased overall survival (OS), and decreased acute care utilization. The Neu Center for Supportive Medicine and Cancer Survivorship (NCSMC) at Thomas Jefferson University is a program designed to identify patients who would benefit from early intervention palliative and supportive care and deliver appropriate services. After initial experience with the model in patients with gastrointestinal and head and neck malignancies, the NCSMC is expanding to patients with genitourinary cancers. Methods: A multidisciplinary team consisting of palliative care physicians, social work, psychology, and navigation conducts biopsychosocial screening (using the NCCN Distress Thermometer) and initiates a personalized care plan for each patient to clarify treatment goals and offer assistance. Prior to deploying the program, multiple stakeholders were engaged to discuss optimal screening points in the patient journey. Patients with a new cancer diagnosis are approached at a post-operative visit in the urology clinic; patients with high distress or significant barriers are discussed at a weekly interdisciplinary meeting with a team of physicians, nurses, social workers, and psychiatry. Patients are subsequently referred to services identified as potentially beneficial. Results: In the first 10 weeks of the program, 67 patients with new diagnoses of bladder (28, 41.8%), prostate (21, 31.3%), kidney (12, 17.9%), urothelial (5, 7.5%), and testicular (1, 1.5%) cancers were screened. 38 (59.4%) patients were identified as low distress; 24 patients (36%) were identified as high distress and offered NCSMC services. Two patients utilized services. Conclusions: Distress and barriers to care amongst patients with newly diagnosed genitourinary cancers are highly variable. While evaluating all patients in the immediate post-operative period is effective at identifying affected patients, the process is resource intensive. An iterative approach testing the intervention at different points in the patient journey is ongoing. As the program matures, impact on QOL, OS, and utilization will be measured.
Implementing an early discharge initiative for patients receiving high-dose methotrexate.
Authors: Binder Adam , Burdette Samantha , Galanis Patricia , Birchmeier Katlin , Handley Nathan , Piddoubny Maria 
Published: October 2019

90 Background: Over 70% of patients are hospitalized in the first year after a cancer diagnosis. While some admissions are unplanned and potentially preventable, many are planned admissions for intensive chemotherapy. High Dose Methotrexate (HD-MTX) is commonly used for the treatment of osteosarcoma or CNS involvement in lymphoproliferative neoplasms. It is given in the inpatient setting due to monitoring requirements after administration. We postulated that changing discharge criteria for HD-MTX from 0.05 µmol/L to ≤0.1 µmol/L would be feasible and safe, and would reduce length of stay (LOS) for patients receiving HD-MTX. Cost savings were also calculated. Methods: Following an assessment of drivers of LOS amongst patients receiving HD-MTX, we identified discharge criteria as an actionable factor. We developed a workflow to discharge patients with 3 days of oral leucovorin and sodium bicarbonate when MTX level reached ≤0.1 µmol/L. Patient demographics, chemotherapy regimen, cycle, dose, and LOS data were collected for a 7 month period before and a 4 month period after the intervention. Cost savings were estimated based on the daily cost of a hospital bed at the institution. Results: Mean LOS for the pre-intervention and post-intervention group was 4.84 days (n=49) and 3.67 days (n=42), respectively (p=0.007). This resulted in a 24.4% reduction in length of stay. Average reduction in LOS of 1.17 days resulted in a decrease in cost of $1,828.73 per admission, with a 4 months savings of $76, 806.56 and projected annualized savings of $230,419.67. No patient experienced complications because of change in discharge criteria. Conclusions: Liberalizing discharge criteria for HD-MTX is feasible, safe, and cost-effective. Further efforts to reduce LOS for elective chemotherapy admissions or safely transition some of these complex regimens to the home setting are currently underway at our institution.
Health insurance literacy, status, and financial toxicity in women receiving treatment for metastatic breast cancer.
Authors: Williams Courtney , Ingram Stacey A. , Lawhon Valerie , Wan Clara , Kenzik Kelly , Azuero Andres , Pisu Maria , Young Pierce Jennifer , Lowman Janel , Jones Jonathan , Dekle Kendal , Mennemeyer Stephen T. , Nipp Ryan David , Rocque Gabrielle Betty 
Published: October 2019

96 Background: Though uninsurance rates declined after the Affordable Care Act, the number of underinsured, or individuals who spend > 10% of their income on out-of-pocket (OOP) medical costs, continues to rise. In patients with metastatic breast cancer (MBC), underinsurance may lead to financial toxicity (FT), or patient-level financial burden and distress, since diagnosis and treatment is extremely costly. This study explores health insurance literacy and the association between FT and health insurance status in women receiving treatment for MBC. Methods: This cross-sectional study utilized survey data collected from 2017-2019 in women age ≥18 receiving treatment for MBC at two academic medical centers in Alabama. FT was measured by the Comprehensive Score for Financial Toxicity (COST) tool (11-item scale from 0-44, with lower scores indicating worse FT). Health insurance status and OOP costs were self-reported. Effect sizes were calculated using Cohen’s d or Cramer’s V. Mixed and generalized linear models clustered by site and treating medical oncologist estimated the association between FT and health insurance status. Results: In 81 women with MBC, median COST score was 24 (interquartile range [IQR] 17-30), 44% had private insurance, 40% Medicare, and 16% Medicaid. Though 25% and 33% of surveyed patients did not know their health insurance premium or deductible cost, respectively, privately insured patients more often knew the cost of their premiums (97%; V = 0.58) and deductibles (81%; V = 0.33) compared to publicly insured patients. In adjusted models, FT levels did not differ significantly based on health insurance type (private insurance COST 21, 95% confidence interval [CI] 18-25; Medicaid COST 23, 95% CI 17-29; Medicare COST 24, 95% CI 20-27). However, risk of severe FT (COST ≤13) was 147% higher for privately insured patients versus Medicare beneficiaries (risk ratio 2.47, 95% CI 1.44-4.21). Conclusions: Despite higher levels of health insurance literacy, privately insured patients receiving treatment for MBC may be at increased risk of severe FT. Further research is needed to understand causes of underinsurance in patients with MBC, which could lead to cancer-related FT.
Outcomes of immunotherapy administration for hospitalized cancer patients.
Authors: Dougherty David W. , Leblebjian Houry , Duperrault Megan , Awad Mark M. , Bartel Sylvia , McDonnell Anne , Bunnell Craig A. , Wagner Andrew J. , Pandya Chintan , Hamel Lauren M. , Glotzbecker Brett 
Published: October 2019

98 Background: With approvals across multiple cancer types and favorable toxicity profiles, oncologists may consider using immunotherapy (IMT) while their patients are hospitalized. Inpatient IMT may be cost-prohibitive to administer for most institutions due to high cost and inpatient payment structure, but little data are available to evaluate outcomes for IMT in hospitalized patients. We investigated the survival benefit of administering IMT to hospitalized patients with cancer at an NCI-designated cancer center. Methods: We conducted a retrospective chart review of all patients receiving ipilimumab, nivolumab, or pembrolizumab during inpatient admission at Dana-Farber Cancer Institute/Brigham & Women’s Hospital in 2017. For each patient, we assessed: total dose, indication for dosing, cancer type, time between dose and discharge, time between discharge and death, and total cost (average wholesale price). Study follow up was January 1, 2017 to July 1, 2018. Results: Fifty doses of IMT were administered to 44 patients. Most patients (40) received 1 dose, 2 patients received 3 doses, 1 patient received 2 doses, and 1 patient received a combination of ipilimumab/nivolumab. The most common cancer types were lung (41%), gastrointestinal (18%), and head and neck (16%). Indications for IMT administration were: patient due for next dose (48%), disease progression (42%), and new diagnosis (11%). The majority of doses (70%) were received within 7 days prior to discharge, with 32% of doses within 1 day of discharge. The majority of patients (86%) died in the study period; 14% of patients died during admission. Average survival between discharge and death was 54 days (range: 0-444 days). Total cost of inpatient IMT administration was $413,370, an average of $9,395 per patient. Conclusions: To our knowledge, this is the largest analysis of outcomes for patients receiving IMT during a hospitalization. Inpatient use of IMT in cancer patients is associated with high cost and poor clinical outcomes. Dosing within one week prior to hospital discharge was common. Clinical factors such as PD-L1 status, disease status, and reason for admission, which may be important to understand which patients may benefit most from inpatient IMT, should be examined.
Treatment patterns and cost of care in commercially insured relapsed acute myeloid leukemia (AML) patients in the outpatient setting.
Authors: Qian Chunlin , Lin Feng , Kwong Jackie 
Published: October 2019

99 Background: Outpatient administration of cancer therapy has become more common in recent years. The objective of this study was to evaluate treatment patterns and cost of care for relapsed AML patients in the outpatient setting. Methods: A retrospective analysis was performed using the IQVIA Health Plan Claims Data–US database. Patients were eligible if they had at least one outpatient claim associated with relapsed AML diagnosis as identified by ICD-9 (205.02) and ICD-10 (C92.02, C92.42, C92.52, C92.62, C92.A2) codes between 1/1/2009 to 12/31/2017, had no inpatient claim for AML diagnosis within 30 days of index claim, and received treatment for relapsed AML as recommended by NCCN guidelines within 30 days of index outpatient claim. Utilization of high intensity chemotherapy (HIC), hypomethylating agent (HMA), low-dose cytarabine (LoDAC) and sorafenib, duration of treatment and the cost per 28-day treatment cycle were examined. Patients were censored at either treatment switching or end of follow-up. Results: Of the 6,242 patients with relapsed AML diagnosis in the IQVIA™ database, 709 did not have inpatient claim of which only 281 patients [26.0% >65 years; 43.8% females] met inclusion criteria and received a total of 1,336 treatment cycles of NCCN recommended treatment as outpatient. About 75% of patients (n=209) received HMA, 6% (n=17) received HIC and 19.6% (n=55) received LoDAC. Patients >65 years were more likely to receive HMA than HIC and LoDAC (p=0.003). Mean (SD) number of treatment cycles for HMA, high-intensity chemotherapy and LoDAC was 5.7 (5.2), 1.2 (0.4) and 2.2 (1.4), respectively. Sorafenib was used in 4.8%, 17.6% and 3.6% patients treated with HMA, HIC and LoDAC. Mean (SD) cost per cycle was $11,246 (8,895), $10,620 (16,722), $3,254 (2,948), and $10,799 (3,057) for HMA, HIC, LoDAC and sorafenib, respectively. Conclusions: Treatment for relapsed AML in the outpatient setting without hospitalization was uncommon during the study period. Low-intensity regimens remain the mainstay of therapy in the outpatient setting, suggesting that treatment toxicities and monitoring requirement are key determinants for treatment setting for relapsed AML.
Combined PIK3CA and FGFR Inhibition With Alpelisib and Infigratinib in Patients With PIK3CA-Mutant Solid Tumors, With or Without FGFR Alterations
Authors: Hyman David M. , Tran Ben , Paz-Ares Luis , Machiels Jean-Pascal , Schellens Jan H. , Bedard Philippe L. , Campone Mario , Cassier Philippe A. , Sarantopoulos John , Vaishampayan Ulka , Chugh Rashmi , Mahipal Amit , Lockhart A. Craig , Sessa Cristiana , Zander Thomas , Ng Matthew , Curigliano Giuseppe , Bendiske Jennifer , Chen Xueying , Choudhury Somesh , Graus-Porta Diana , Lewis Nancy , Perez Garcia Jose Manuel , de Miguel-Luken María José 
Published: October 2019

PURPOSE Concurrent PIK3CA mutations and fibroblast growth factor receptor (FGFR) alterations occur in multiple cancer types, including estrogen receptor–positive breast cancer, bladder cancer, and endometrial cancer. In this first-in-human combination trial, we explored safety and preliminary efficacy of combining the PI3Kα selective inhibitor alpelisib with the FGFR1-4 selective inhibitor infigratinib. PATIENTS AND METHODS Patients with PIK3CA-mutant advanced solid tumors, with or without FGFR1-3 alterations, were enrolled in the dose escalation or one of three molecular-defined dose-expansion cohorts. The primary end point was the maximum tolerated dose. Secondary end points included safety, pharmacokinetics, and response. Archival tumor samples were sequenced to explore genomic correlates of response. RESULTS In combination, both agents were escalated to full, single-agent recommended doses (alpelisib, 300 mg per day continuously; infigratinib, 125 mg per day 3 weeks on followed by 1 week off). The toxicity profile of the combination was consistent with the established safety profile of each agent, although 71% of all patients required at least one treatment interruption or dose reduction. Molecularly selected dose expansions in breast cancer and other solid tumors harboring PIK3CA mutations, alone or in combination with FGFR alterations, identified sporadic responses, predominately in tumor types and genotypes previously defined to have sensitivity to these agents. CONCLUSION The combination of alpelisib and infigratinib can be administered at full single-agent doses, although the high rate of dose interruption or reduction suggests long-term tolerability may be challenging. In exploratory signal-seeking cohorts of patients harboring dual PIK3CA and FGFR1-3 alterations, no clear evidence of synergistic activity was observed.
Is Testicular Germ Cell Cancer Estrogen Dependent? The Role of Endocrine Disrupting Chemicals
Authors: Fénichel Patrick , Chevalier Nicolas 
Published: October 2019

AbstractTesticular germ cell cancer (TGCC) is the most frequent cancer of the young male, with an increasing incidence worldwide. The pathogenesis and reasons for this increase remain unknown. However, epidemiological and experimental data have suggested that, similar to genital malformations and sperm impairment, it could result from the interaction of genetic and environmental factors including fetal exposure to endocrine-disrupting chemicals (EDCs) with estrogenic effects. In this review, we analyze the expression of classic and nonclassic estrogen receptors by TGCC cells, the way they may influence germ cell proliferation induced by EDCs, and discuss how this estrogen dependency supports the developmental and environmental hypothesis.
Malignant Peritoneal Mesothelioma: Patterns of Care and Survival in the Netherlands: A Population-Based Study
Authors: de Boer Nadine L. , van Kooten Job P. , Damhuis Ronald A. M. , Aerts Joachim G. J. V. , Verhoef Cornelis , Madsen Eva V. E. 
Published: October 2019

Abstract

Background
Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. Recently, focus has shifted toward a more aggressive and multimodal treatment approach. This study aimed to assess the patterns of care and survival for MPM patients in the Netherlands on a nationwide basis.

Methods
The records of patients with a diagnosis of MPM from 1993 to 2016 were retrieved from the Dutch Cancer Registry. Data regarding diagnosis, staging, treatment, and survival were extracted. Cox regression analyses and Kaplan–Meier survival curves were used to study overall survival.

Results
Between 1993 and 2016, MPM was diagnosed for 566 patients. Overall, the prognosis was very poor (24% 1-year survival). The most common morphologic subtype was the epithelioid subtype (88%), followed by the biphasic (8%) and sarcomatoid (4%) subtypes. Surgical treatment has become more common in recent years, which most likely has resulted in improved survival rates. In this study, improved survival was independently associated with hyperthermic intraperitoneal chemotherapy (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.21–0.55) and surgery with adjuvant systemic chemotherapy (HR, 0.33; 95% CI, 0.23–0.48). Nonetheless, most patients (67%) do not receive any form of anti-cancer treatment.

Conclusion
This study indicated that MPM still is a rare and fatal disease. The survival rates in the Netherlands have improved slightly in the past decade, most likely due to more aggressive treatment approaches and increased use of surgery. However, most patients still do not receive cancer-directed treatment. To improve MPM management, and ultimately survival, care should be centralized in expert medical centers.
Gains of Chromosome 1p and 15q are Associated with Poor Survival After Cytoreductive Surgery and HIPEC for Treating Colorectal Peritoneal Metastases
Authors: Enblad Malin , Graf Wilhelm , Terman Alexei , Pucholt Pascal , Viklund Björn , Isaksson Anders , Birgisson Helgi 
Published: October 2019

Abstract

Purpose
Genetic alterations in colorectal peritoneal metastases (PM) are largely unknown. This study was designed to analyze whole-genome copy number alterations (CNA) in colorectal PM and to identify alterations associated with prognosis after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods
All patients with PM, originating from a colorectal adenocarcinoma, who were treated with CRS and HIPEC in Uppsala Sweden, between 2004 and 2015, were included (n = 114). DNA derived from formalin-fixed paraffin-embedded (FFPE) specimens were analyzed for CNA using molecular inversion probe arrays.

Results
There were extensive but varying degrees of CNA, ranging from minimal CNA to total aneuploidy. In particular, gain of parts of chromosome 1p and major parts of 15q were associated with poor survival. A combination of gains of 1p and 15q was associated with poor survival, also after adjustment for differences in peritoneal cancer index and completeness of cytoreduction score [hazard ratio (HR) 5.96; 95% confidence interval (CI) 2.19–16.18]. These patients had a mean copy number (CN) of 3.19 compared with 2.24 in patients without gains. Complete CN analysis was performed in 53 patients. Analysis was unsuccessful for the remaining patients due to insufficient amounts of DNA and signals caused by interstitial components and normal cells. There was no difference in survival between patients with successful and unsuccessful CN analysis.

Conclusions
This study shows that gains of parts of chromosome 1p and of major parts of chromosome 15q were significantly associated with poor survival after CRS and HIPEC, which could represent future prognostic biomarkers.
Evaluation of post-bleaching hypersensitivity using desensitizing agent before and /or after in-office bleaching: A randomized clinical trial.
Authors: Sabry Tawfik Silvia , Khairy Mohamed Adel Ezzat , ElBaz Maha Abd Elsalam , El korashy Maha Ebrahim Mohamed 
Published: October 2019

Background: Dental bleaching has become one of the most demanded aesthetic procedures as it is very simple and gives fast results that satisfy the patient’s wishes. However, unfortunately, it has the annoying side effect of tooth sensitivity. This clinical trial was designed to evaluate the efficacy of using a desensitizing agent, which was applied during in-office bleaching with 30% HP (hydrogen peroxide). Methods: 36 participants were divided into four groups (N = 9). According to the intended intervention as follows: Group I:—Application of Relief ®Amorphous Calcium Phosphate (ACP) before in-office bleaching; Group II—Application of Relief ®ACP before and after in-office bleaching; Group III—Application of Relief ®ACP after in-office bleaching; and Group IV: placebo was applied before and after in-office bleaching. Then, three hydrogen peroxide bleaching applications for a total of 45 minutes were performed. The primary outcome variable was hypersensitivity, assessed with (VAS) scale immediately and 24h, 1 week and 1 month after the procedure; while the secondary outcome was teeth shade assessed using the VITAPAN ® classical shade guide. Results: Statistical analysis was done using Kolmogorov-Smirnov, Shapiro-Wilk tests, Kruskal-Wallis test and Dunn’s test. Immediately after bleaching, there was statistically significant distinction in the median pain score between the groups. After 1 day, the ACP gel before and after bleaching group showed the lowest median score, while, the control group confirmed the highest median score. After 2 days, no statistically sizable difference was observed between all groups. The group receiving ACP gel before and after showed the highest change in median of classical shade guide scores while, (ACP gel after) and control group; showed the lowest change. Conclusion: The application of the desensitizing agent prior to and after in–office bleaching was successful in lowering post-bleaching hypersensitivity. Trail Registration: Clinical trial.gov NCT02942082 21/10/2016