bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aggressiveness of cancer-care near the end of life
Authors: Keam B. , Kim J. , Hong Y. , Lee S. , Kim D. , Im S. , Kim T. , Heo D. , Bang Y. , Kim N. 
Published: March 2020

6103 Background: The objective of this study were to observe the markers of aggressive care in cancer patients including appropriateness of chemotherapy and to evaluate the trends in cancer-care and to assess their association with the availability of related health care resources. Methods: We designed restrospective cohort composed of patients who diagnosed as metastatic cancer and received palliative chemotherapy at Seoul National University Hospital in 2002. Hematologic malignancy and hepatocellular carcinoma with local treatment alone were excluded. Two hundreds ninety eight patients who died of cancer were finally evaluated the appropriateness of cancer-care including chemotherapy. Results: The median duration of chemotherapy was 6.02 months (mo) compared to 8.67 mo of median overall survival. Median periods between last chemotherapy and death were 2.02 mo. Among the 298 patients, 50.3% of the patients received chemotherapy in the last two months of life. Furthermore, 17 patients (5.7%) died within 2 weeks after receiving chemotherapy. It seemed that the patients had not enough time to prepare the death with dignity. The mean number of regimens and cycles the patients had received were 1.83 and 5.52, respectively. However, timing of discontinuance chemotherapy did not affect use of chemotherapy that there was no difference in numbers of regimens and cycles according to months between last chemotherapy and death. The proportion with >1 ER visit in the last months of life were 33.6% and average numbers of ER visits after cancer diagnosed were 1.72. Only 9.1% of patients referred to hospice center and 11.7% of patients agreed with written DNR. The lack of hospice centers and harmony with referring system in Korea might affect to this results. Conclusions: Among the patients who died of cancer, significant portion of patients received chemotherapy till the end of life as well as ER visiting. Relatively, hospice referral and discussions about DNR did not conducted well in end of life care. Not to interfere the dignity of life, the physicians should be concerned whether the patients dying of cancer are overtreated with chemotherapy and receiving the appropriate cancer-care. No significant financial relationships to disclose.
Evaluation of comparative survival based on the AJCC 5th and 6th editions for breast cancer staging: 25 year experience in two southwest Washington state community cancer programs
Authors: Kim E. , Sanghvi P. , Marquez C. , Kim C. R. , Thomas C. R. 
Published: March 2020

6118 Background: The revised American Joint Committee on Cancer (AJCC) sixth edition (6th ed.) cancer staging system increased stratification within breast cancer (BC) stages II and III defined by the AJCC 5th ed. system. The specific aim of this study was to determine and compare disease-free survival (DFS) for stage 0-III breast carcinoma between the 5th and 6th editions using retrospective data gathered from 1980–2004 in southwest Washington state (WA). Methods: 4,810 patients (pts) were identified using cancer registries at Saint John Medical Center in Longview, WA and Southwest Washington Medical Center in Vancouver, WA. Patients were restaged retrospectively using the 5th and 6th ed. systems. DFS was determined using the Kaplan-Meier method and compared using the log-rank test. Results: The age at diagnosis ranged 20–99 yrs, with a mean age = 60. The mean length for disease-free follow-up was 224 mos. Stage 0 and stage 1 criteria were unchanged between editions, and 10-yr DFS was 94% and 87% for stage 0 and stage 1, respectively. In stage II pts, 13% (199/1,519) were upstaged to stage III by the 6th ed. criteria, significantly improving the 10-yr DFS for stage II from 66% (5th ed.) to 72% (6th ed; p = 0.003). The majority, 85% (167/199), of pts upstaged were from the 539 classified as stage IIb disease by the 5th ed. This accompanied an increase in the 10-year DFS for stage IIb from 54% (fifth) to 62% (sixth; p = 0.046). The number of pts with stage III disease increased from 313 to 588 in the 6th ed. 10-year DFS increased from 30% to 36% (p = 0.025), respectively. Most of this increase resulted from changes within stage IIIa, as DFS increased from 32% to 41% (p = 0.046). When compared, DFS outcomes between stage IIIb and IIIc were not found to be statistically significant (p = 0.501). Conclusions: The AJCC 6th ed. system for BC provides greater distinctions between stages compared to the 5th ed., and reclassification results in significant changes in projected outcomes. However, the addition of the IIIc substage does not seem to show the same significant distinction when compared to the existing stage IIIb substage in outcomes. No significant financial relationships to disclose.
A feasibility study of [11C]choline for the molecular imaging of human breast cancer in vivo using positron emission tomography (PET)
Authors: Kenny L. M. , Coombes R. C. , Al-Nahhas A. , Osman S. , Lowdell C. , Aboagye E. 
Published: March 2020

613 Background: [11C]Choline is a novel PET radiotracer. Preclinical studies suggest that it may be promising in breast cancer. [11C]Choline has been recently evaluated as a screening agent in prostate cancer, but no studies have yet investigated its potential in breast cancer. We report a pilot study evaluating the utility and reproducibility of [11C]Choline-PET in breast cancer. Methods: Dynamic imaging was performed on an ECAT962 HR+ PET scanner for 65 min after intravenous injection with 190–369 MBq [11C]choline. Patients with locally advanced and metastatic breast cancer were eligible. All histological subtypes were included (ductal, lobular, and inflammatory). Arterial blood samples were taken continuously for 10 min, with 8 discrete samples up to 60 min to measure [11C]choline and metabolites. Tissue uptake was determined by standardised uptake value at 60 min (SUV, dose and BSA corrected) and Ki (irreversible trapping) calculated using Patlak (corrected for [11C]choline metabolites in plasma) and modified Patlak analysis (corrected for plasma + tissue metabolites). Reproduciblilty scans were performed 2–17 days later in the absence of treatment. Results: Tumour [11C]choline uptake was observed in 10 out of 11 patients (12 out of 13 distinct lesions). There was a significant difference between tumour and normal tissue (breast/lung) in [11C]choline uptake for Ki (p<0.0001) and SUV (p<0.0001). Tissue uptake was of the order lung ≤ normal breast < tumour < liver ≤ spleen. [11C]choline was rapidly metabolised, at 60 min the mean ± S.E. plasma radioactivity due to [11C]choline was 16.4 ± 2.9%. [11C]Choline uptake was found to be reproducible for Ki (modified Patlak: r=0.93, p<0.0001, Patlak: r=0.85, p=0.002) and SUV (r=0.94, p<0.0001) - measured in 8 patients (median of 2 days after the 1st scan). Tumour Patlak Ki was 13.2% > Ki calculated using modified Patlak analysis. Conclusions: [11C]Choline-PET imaging of breast cancer is promising and warrants further evaluation. Tumour [11C]Choline uptake measured by Ki and SUV is reproducible. We plan to study the relationship between choline uptake measured by PET and immunoassays of tumour samples. Functional imaging could have a vital role to determine the efficacy of target-specific agents. No significant financial relationships to disclose.
Characteristics and outcomes of patients receiving chemotherapy in a cancer center ICU: A 5 year retrospective
Authors: Raoof N. D. , Knott M. , Pastores S. M. , Voigt L. P. , Halpern N. A. 
Published: March 2020

6134 Background: Administration of chemotherapy is traditionally guided by functional status, and chemotherapy is commonly withheld from very sick people. In our ICU, we observed that we customarily administered chemotherapy to patients in multisystem organ failure. Very little has been published in the literature on this topic, therefore we sought to characterize patients who received chemotherapy during their intensive care unit (ICU) admission in a cancer hospital over a 5-year period. Methods: We evaluated all ICU admissions receiving chemotherapy between October 1998 and September 2003. If patients had multiple admissions, only the first was included. We analyzed age, gender, MPM-II scores, and ICU and hospital length of stay (LOS). Additionally, we identified patients who were on mechanical ventilation, vasopressors or were treated with renal replacement therapy at the initiation of chemotherapy. Mortality at ICU discharge, hospital discharge, and at 6 months and one year post hospital discharge were also determined. Results: During the study period, 4.2% (111/2,645) of all ICU admissions received chemotherapy, averaging 22.2 administrations per year. Only first admissions (a total of 103 patients; 60 men and 43 women) were analyzed. Average age was 51.4 years, with an MPM-II score of 53%, an ICU LOS of 9.1 days and a hospital LOS of 30.6 days. Although over a third of patients were on mechanical ventilation when chemotherapy was initiated, ICU mortality was only 23%. In contrast, all in hospital mortality was 46%. ( Table ) Conclusions: Most patients were critically ill when chemotherapy was administered but survived to ICU discharge. However, only 24% of patients were alive at one year. Whether chemotherapy should be considered a useful component of ICU care for cancer patients requires further study. [Table: see text] No significant financial relationships to disclose.
Multidisciplinary system for detecting medication errors in antineoplastic chemotherapy
Authors: Almenar-Cubells D. , Jimenez Torres V. , Serrano Fabia A. , Albert Mari A. , Molins Palau C. , Bosch Roig C. , Olmos Anton S. , Jimenez Arenas V. , Muñoz Langa J. , Llorente Domenech R. 
Published: March 2020

6136 Background: The aim of this study is to quantify medication errors (ME) in a multidisciplinary system with a Computerized Pharmacotherapy Process (CPP) in cancer patients. Methods: Longitudinal, prospective, and cohorts study during 2 years (January, 2003-December, 2004) in adult patients who received antineoplastic treatment in Oncology and Haematology services. ME were identified by double cross-validation of every stage of the pharmacotherapy process (prescription, preparation, dispensation, administration and follow-up) carried out by the multidisciplinary team (physician, pharmacist, nurse) with CPP assistance. Variables: number of ME for 1000 patients-day, % according to the stage of the process and severity (scale to 1 -not damage in the patient- to 5 -irreversible damage-) of ME intercepted. Results: 638 patients were on treatment and ME were identified in 225 (35%). On a total of 18,785 preparations and 13,206 patients-day, 276 ME were detected, equivalent to 20.9 ME by 1000 patients-day (95%CI: 18.5–23.5); of these 16.8 ME for 1000 patients-day (80.1%) were intercepted and did not reach a patient (95%CI: 14.6–19.1). ME detected distribution according to the stage were: prescription 75.7% (95%CI: 70.2–80.7), preparation 21.0% (95%CI: 16.4–26.3), dispensation 1.8% (95%CI: 0.6–4.2), administration 1.1% (95%CI: 0.2–3.1), and follow-up 0.4% (95%CI: 0.01–2.0). ME distribution according to the severity were: grade 1: 15.9% (95%CI: 11.8–20.8), grade 2: 49.6% (95%CI: 43.6–55.7), grade 3: 33.7% (95%CI: 28.1–39.6), grade 4: 0.7% (95%CI: 0.1–1.6) and none of grade 5. The system intercepted 98.9% (95%CI: 94.3–99.9) of ME with severity equal or greater than 3 -ME with potential to damage the patient- and 70.2% (95%CI: 62.9–76.7) of severity equal or minor to 2, ME without clinical significance. Conclusions: The multidisciplinary system with well-established CPP detects 20.9 ME for 1,000 patients-day and intercepts 98.8% of ME with potential to damage the oncology patient. No significant financial relationships to disclose.
Trastuzumab in adjuvant breast cancer therapy: A model based cost-effectiveness analysis
Authors: Norum J. , Olsen J. A. 
Published: March 2020

628 Background: Trastuzumab has shown activity in patients with early breast cancer that overexpress HER2. However, significant resources have to be allocated to finance this therapy, therefore its cost-effectiveness is called for and treatment’s value for money should be calculated. We aimed to evaluate the marginal cost effectiveness of trastuzumab in adjuvant treatment of HER2 positive early breast cancer in a model based cost-effectiveness-analysis (CEA). Methods: A breast cancer treatment model was set up. Societal costs were calculated according to Norwegian prices as in September 2005 and converted to Euros at the rate of 1Euro = 7.81 NOK. Life expectancy data were based on the literature and prolonged according to qualified guess (10% and 20% improved overall survival (OS). The comparator was the present practice, the FEC100 regimen alone. The human capital approach was employed and a sensitivity analysis was added. Results: The median raised cost per patient treated was calculated at Euro16,713 - 35,714. The yielding cost per life year saved was in the range between Euro 5,571 and 32,616, depending on survival gain (10% or 20% improved OS) and discount rate (0% or 3%) employed. The sensitivity analyses documented survival gain, discount rate and price of trastuzumab the major factors influencing cost-effectiveness ratio. Conclusion: The economic evaluation indicates trastuzumab cost effective in adjuvant breast cancer treatment. No significant financial relationships to disclose.
Long term cardiac tolerability of trastuzumab in HER-2-overexpressing metastatic breast cancer (MBC)
Authors: Guarneri V. , Lenihan D. J. , Valero V. , Durand J. , Broglio K. , Boehnke-Michaud L. , Gonzalez-Angulo A. M. , Hortobagyi G. N. , Esteva F. J. 
Published: March 2020

629 Background: The use of trastuzumab is associated with an increased risk of cardiotoxic events such as congestive hearth failure (CHF) and decline in the left ventricular ejection fraction (LVEF). Our objectives were to evaluate the incidence of cardiac dysfunction, to identify risk factors and to evaluate the outcome of patients with MBC treated with trastuzumab for one year or longer. Methods: Among 218 MBC patients treated with trastuzumab-based therapy for at least one year, 173 patients were evaluable for cardiac toxicity. Cardiac events (CE) were defined as follows: 1) asymptomatic drop of LVEF below 50%; 2) drop of 20 percentage points in LVEF compared to the baseline; 3) signs or symptoms of CHF. The cardiac toxicity was graded according the NCI-CTCAE, version 3.0. Results: Median age at the start of trastuzumab therapy was 50 years (range, 26–79), median cumulative time on trastuzumab was 21.3 months (range, 11.6–77.6), and median follow-up was 32.2 months (range, 9.7–79.0). Eighty-five percent of patients received prior anthracyclines (median cumulative doxorubicin dose: 300 mg/m2). Forty-nine patients (28%) experienced a CE: 3 patients (1.7%) had an asymptomatic drop in the LVEF of 20 percentage points; 27 patients (15.6%) experienced grade 2 cardiac toxicity; and 18 patients (10.4%) experienced grade 3 cardiac toxicity. There was one cardiac related death (0.5%). Cardiac event-free survival was 87.3% at 1 year. All but four patients had improved LVEF or symptoms of CHF after stopping trastuzumab or with appropriate therapy. After complete recovery, 26 patients were re treated with trastuzumab; 16 patients did not experience further CE. Concomitant taxane use was the only factor significantly associated with a CE (HR: 4.37, 95%CI 1.06–17.98, p:0.04).Prior anthracycline exposure was not associated with increased risk of CE. Conclusions: The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function. The increased risk of cardiotoxicity associated with taxane administration needs to be further investigated. No significant financial relationships to disclose.
Improved antitumor therapy by dual targeting of estrogen and growth factor receptor signaling in human breast cancer cells
Authors: Pietras R. J. , Marquez D. C. , Chen H. , Sliwkowski M. X. , Slamon D. J. 
Published: March 2020

637 Background: Breast cancer growth is tightly regulated by interactions between growth factor and estrogen receptors. Dimerization is crucial for activation of HER receptors (EGFR, HER2, HER3, HER4) that contribute to modulation of tumor progression and the failure of antiestrogen therapy. HER2 is the preferred dimerization partner in a process stimulated by the several HER receptor ligands. HER2 antibody (trastuzumab) shows antitumor efficacy in HER2-overexpressing cancers. New antibodies that disrupt HER2 dimerization (pertuzumab) may be useful in treating cancers with normal HER2 levels. Methods: Estrogen receptor (ER)-positive tumor cells with normal HER levels (MCF-7, ZR75), as well as cells engineered for HER2-overexpression (MCF-7/HER2, ZR75/HER2) or tamoxifen resistance (MCF-7/TAM), were grown in vitro and as xenografts in nude mice and treated with tamoxifen, fulvestrant (Faslodex), trastuzumab or pertuzumab, alone or combined. Effects of agents on phosphorylation of ER and coactivator AIB1, ER-dependent transcripts, p27 and VEGF secretion were assessed. Results: Growth of ER-positive tumors with low HER is reduced by tamoxifen and fulvestrant. In contrast, HER2-overexpressing tumors are tamoxifen-resistant but retain sensitivity to fulvestrant and show greater, synergistic antitumor effects with trastuzumab-fulvestrant combined. Similarly, non-HER2-overexpressing tumors with or without tamoxifen resistance are sensitive to fulvestrant, but fulvestrant-pertuzumab elicits more profound antitumor effects (P<0.001). Enhanced inhibitory action of fulvestrant-pertuzumab is related, in part, to changes in phosphorylation of ER and AIB1, leading to blockade of ER-induced transcripts, as well as nuclear localization of p27, a CDK-inhibitor that downregulates cell proliferation. Further, enhanced tumor secretion of VEGF after estrogen and HER signaling is markedly reduced by fulvestrant-pertuzumab as compared with either agent alone (P<0.001). Conclusions: Pertuzumab promotes antitumor efficacy of the pure antiestrogen, fulvestrant, and dual disruption of ER and HER signaling may be a new way to optimize hormonal therapy and overcome antiestrogen resistance. Supported by US Army BCRP and Stiles Program. [Table: see text]
Association between breast cancer and estrogen receptor gene polymorphism PVU II
Authors: Neuss K. , Elling D. , Cascorbi I. , Lueftner D. 
Published: March 2020

643 Background: The estrogen receptor (ER) is well acknowledged as a prognostic factor in breast cancer, and it is a prerequisite to use the predictive information for hormonal therapy. We investigated whether that the different polymorphisms of the estrogen receptor could influence its expression or functionality. Methods: DNA was extracted from white blood cells of 236 breast cancer patients and 236 healthy, matched controls. The ER genotypes were determined by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion of the PCR product. Results were shown by electrophoreses. Clinical data such as histologic types, pTNM stage and patients age were available for statistical analyses. Results: We found a statistically significant correlation between the estrogen receptor polymorphism pattern and breast cancer. The receptor type PP was detected statistically significantly more often in postmenopausal breast cancer patients (PP vs pp+Pp, p =0.03). However, there was no correlation to the histobiochemical receptor status or UICC-Stadium. Conclusions: These results show an association between the estrogen receptor polymorphism and breast cancer. It seems to be that a complete lack of the p-allel is a risk factor to develop breast cancer at postmenopausal age. There was no influence on estrogen receptor expression or clinical tumor stage. Thus, we propose that there is no clinical use for estrogen receptor polymorphism analyses at this stage. No significant financial relationships to disclose.
Clinical outcomes and rates of molecular remission with all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) combination therapy in newly diagnosed acute promyelocytic leukemia (APL)
Authors: Tsimberidou A. M. , Kantarjian H. M. , Garcia-Manero G. , Koller C. , Jones D. M. , Keating M. J. , Estey E. 
Published: March 2020

6503 Background: ATRA and anthracyclines provide durable remissions in patients with untreated APL. As2O 3 has improved outcomes in untreated and relapsed/refractory APL. The aim of this study was to determine the rates of complete response (CR) and molecular remission with ATRA and As2O 3 combination therapy in untreated APL. Methods: From 2/02 to 1/06, 53 patients with untreated APL received ATRA 45 mg/m2 daily and As2O 3 0.15 mg/kg IV 1-hr infusion daily starting on day 10. Patients with WBC>10×109/L also received gemtuzumab ozogamicin (GO) 9 mg/m2 on day 1 and/or idarubicin 12 mg/m2 on days 1–4. Patients in CR received As2O 3 0.15 mg/kg IV on days 1–5 weekly for 4 weeks on and 4 weeks off and ATRA 45 mg/m2 daily for 2 weeks on and 2 weeks off (for 28 weeks). Polymerase chain reaction (PCR) testing for PML-RARα (sensitivity level, 10−4) was performed every 3 months from CR for 2 years. Patients with molecular relapse received GO 9 mg/m2 once monthly for 3 months in addition to ATRA and As2O 3 as in postremission therapy. If PCR became negative, only the single dose of GO was given. Results: The median age was 46 years; and 20% of patients were Sanz low risk, 40% intermediate, and 40% high risk. The CR rate was 91% (low risk 91%, intermediate 95%, high risk 86%). The median follow-up in surviving patients was 1.6 years. Six patients died during induction, and 2 died in CR from other cancers. The 1-yr survival rate was 88%. Three patients relapsed (at 9, 9, and 16 months). The 1-yr failure-free survival (FFS) rate in responding patients was 94% (high risk 86%, other risk 100%). Molecular remission rates are shown in the Table . Grade 3–4 nonhematologic toxicities were infections (n=16), neurologic (n=4), cardiac arrhythmias (n=4), APL differentiation syndrome (n=4), and headache (n=2). Conclusions: ATRA plus As2O 3 results in high rates of CR, molecular remission, FFS, and survival and is an alternative to ATRA and idarubicin combination therapy in low-risk APL. [Table: see text] No significant financial relationships to disclose.