bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceptability of the NCI patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) in women with metastatic breast cancer (MBC).
Authors: Nichols Christine , Mitchell Sandra A. , Lang Kathy , Federico Victoria , Castro Kathleen M. , Rogak Lauren J. , Lalla Deepa , Clauser Steven B. , Reeve Bryce B. , Denicoff Andrea , Chen Alice P. , Piekarz Richard , Atkinson Thomas Michael , Mayer Musa , Brammer Melissa G. , Sit Laura , O'Mara Ann M. , Minasian Lori M. , Basch Ethan M. 
Published: March 2020

e19633 Background: NCI PRO-CTCAE is a new patient-reported outcome measure designed to enhance adverse event (AE) reporting in clinical trials by integrating the patient experience. The PRO-CTCAE item bank includes items representing the frequency (F), severity (S) and interference (I) with usual activities of 78 symptomatic AEs. The aim of this study was to examine the acceptability of a subset of PRO-CTCAE items to women receiving treatment for HER2+ MBC. Methods: 207 women on active treatment for HER2+ MBC (median 47 months since MBC diagnosis) were recruited from 6 U.S. breast cancer support groups and completed a web survey that included 18 PRO-CTCAE symptoms. Respondents were aged 45-64 years (71%), white (94%), college-educated (72%), with health-related quality of life rated good to excellent (61%) and median EQ5D utility score of 0.8. To explore PRO-CTCAE acceptability and data quality, we examined item level missingness, endorsement frequencies and binary and free-text responses about the comprehensibility of PRO-CTCAE items. Results: Item level missingness across all symptoms for each PRO-CTCAE dimension (F, S and I) ranged from 1.0% to 5.3%, with a median of 2.9%; interference associated with decreased appetite had the greatest missingness (5.3%). Excluding this outlier, maximum missingness was 3.9%. Endorsement frequencies of response choices for S of insomnia, constipation, fatigue, pain, anxiety/worry and sad/unhappy feelings support acceptable instrument sensitivity (all adjacent response points endorsed by >7% of respondents). Most respondents (92%) thought the items were easy to understand; a few were uncertain about how to rate symptoms such as anxiety, depression, insomnia and nausea if they were present but partially controlled with medication. Conclusions: These findings confirm and extend those of other studies demonstrating the acceptability of PRO-CTCAE. Evaluation in a more heterogeneous sample, particularly with respect to education and cancer site, is underway.
Impact of racial and marital status on health services utilization among veterans with terminal cancer.
Authors: Lu Zhiqiang Kevin , Qureshi Zaina P. , Cho Michael , Wang Trent P , Yan Houling , Bennett Charles L. , Chang Victor Tsu-Shih 
Published: March 2020

e19639 Background: Little is known about the association of socio-demographic factors with health services utilization (HSU) for patients with terminal cancer receiving palliative care. The objectives of this study were to evaluate for race or marital status associated variations in HSU among Veterans with terminal cancer. Methods: In an IRB approved protocol, 103 advanced cancer patients receiving palliative care in the Section of Hematology Oncology at a VA Medical Center, but not hospice, were followed every 4-6 weeks from the start of palliative care to death from 2000-2002. This study sample consisted of a subset of 39 pts who received palliative care for at least 24 weeks. Their charts were retrospectively reviewed for measures of health system utilization (HSU), including total length of hospital days, number of admissions, number of clinic visits and emergency room (ER) visits. ANOVA and Chi-square tests were used to explore for potential disparities of HSU across race or marital status. Results: Overall, the subset consisted of 17 Caucasians, 21 African American (AA), and 1 “other” by race. Among them, 21 were married, 7 were divorced, 6 were widowed, 4 never married and 1 had unknown marital status. The majority of patients had prostate cancer (39.47%) or lung cancer (28.95%). Mean total number of inpatient days was 23.6 days (SD=23), mean number of admissions was 2.9(SD=2.5), mean number of clinic visits was 27 (SD=25), and ER visits was 1.3(SD=1.8) per patient. Mean total hospital days were the longer for AA (25) compared to Caucasian (17.7) (p<0.01); the one pt from “other” had a total of 94 hospital days. The average number of ER visits was 0.48 for Caucasian, 2.0 for AA and 0 for other (p<0.05). Total number of inpatient days was longest for those who were never married (33.8 days), less for those who were married (26.0), divorced (12.7) or widowed (9.3) (p>0.05). A similar trend was found for clinic visits (NS). Conclusions: The pilot study identified racial but not marital status-associated variations in HSU among terminally ill cancer patients. These findings have implications for cost of care and should be confirmed in larger studies in our Veterans including caregivers. Funded in part by Project Death in America
Use and perceptions of complementary and alternative medicine in a community cancer center.
Authors: Cusnir Mike , Pozo-Kaderman Christina , Sullivan Irene , Vinas Elaine 
Published: March 2020

e19646 Background: Studies over the past 10 years in the general population showed use of complementary and alternative medicine (CAM) to no more than 42% with the largest study reporting only 28% use in adults. In the cancer population one of the largest studies showed that 83.3% had used at least one CAM approach. After excluding spiritual practices and psychotherapy, 95.8% of participants were aware of CAM and 68.7% of those had used CAM. However most of this information has been obtained in academic medical centers that would be biased since the use of CAM has also been reported to vary by location, education and socio-economic status. Methods: We evaluated with a questionnaire similar to the one use by Richardson et al, in 2000 looking for prevalence and predictors of CAM use in a south Florida community cancer center with a culturally diverse patient population, many of Hispanic descent, we also evaluated the opinion about participating in CAM clinical trials.150 consecutive patients coming to the cancer center were given a questionnaire of which 112 are evaluable at the time of this report. Results: Average age was 66 years, 50 % of the patients were males, 56% of the patients were actively on chemotherapy, 10% on hormonal manipulations and 33% were not actively on treatment. 52% had heard of the term CAM, 34 % had heard the term integrative medicine, 18% had use CAM for their cancer treatment. Only 27% of the patients had discussed the use or interest in use of CAM with one of the health care providers. 59% expressed interest in participating in CAM clinical trials. Regarding specific therapies that the patients had used to “treat cancer” 8% had used dietary interventions, 15% had used movement therapies (TaiChi, yoga, etc.), 12% use of mind-body practices, 25% had used herbal and vitamin supplements and 25 % had used spiritual practices. Conclusions: Our study population had slightly lower use of CAM than in academic centers however the type of practices used appears to be different with increased use of mind/body and movement techniques over spiritual practices which might be a cultural effect. We also found a strong interest and will to participate in clinical trials that should be a window of opportunity to test these therapies in community settings.
Identifying resistance biomarkers against five clinically approved tyrosine kinase inhibitors in 45 cell lines.
Authors: Pénzváltó Zsófia , Tegze Bálint , Szasz Attila Marcell , Schäfer Reinhold , Gyorffy Balazs 
Published: March 2020

e21005 Background: Clinical studies show low overall response rates of 10-47% to targeted cancer therapeutics. Our aim was to identify new biomarkers for predicting sensitivity against five already approved tyrosine kinase inhibitors. Methods: Sensitivity to sunitinib, erlotinib, lapatinib, sorafenib and gefitinib were tested in 45 cancer cell lines, and a resistance index was calculated for each cell line. The gene expression profiles (data were obtained by interrogating the raw microarray data of the caArray database) in the subset of resistant vs. sensitive cell lines were compared for each drug. Feature selection was carried out using significance analysis of microarrays and rank products. The results were validated by qPCR in the cell lines and - in case of four sunitinib resistance associated genes - in clinical samples by immunohistochemistry. Results: A set of 63 genes was identified as associated with resistance against the examined drugs. Overall classification accuracy of the prediction was 92.8% in a leave-one-out cross validation using prediction analysis of microarrays. The expression of the genes was validated by qPCR in the cell lines. The results confirmed 45/63 of the microarray-based resistance associated genes and 7/32 of literature based genes. All together 48 sunitinib-treated metastatic renal cell carcinomas were collected. The immunohistochemical analysis in these confirmed the correlation of the expression of RAB17, LGALS8, and EPCAM with overall survival. Conclusions: We identified new predictive biomarker candidates for five tyrosine kinase inhibitors, and validated a set of sunitinib resistance associated genes in an independent patient cohort.
Correlation of increased tumor expression of estrogen receptor alpha mRNA and low aromatase protein ratio with prognosis in resected non-small cell lung cancer (NSCLC).
Authors: Aresti Unai , Carrera Sergio , Rubio Itziar , Sancho Aintzane , Marrodan Ines , Muñoz Alberto , Martinez Mireia , Calvo Begoña , Buque Aitziber , Azkona Eider , Ruiz de Lobera Abigail , Lopez-Vivanco Guillermo 
Published: March 2020

e21009 Background: Although several studies have shown the presence of estrogen receptors (ERs) in lung tumors, published reports show inconsistent conclusions. Biological role of ER-α, ER-β and aromatase in the development of NSCLC is unclear. Aim of this study was to investigate the prognostic value of ERs and aromatase mRNA-protein concentration in resected NSCLC. Methods: Lung tumor and normal lung were analyzed for expression of ER-α, ER-β and aromatase using a 7900HT Applied Biosystem Fast PCR System. Reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed for the detection of ER and aromatase expression using RNA from lung cancer tissues immediately submerged in RNA Later (Qiagen) after surgery. Aromatase protein was detected with an enzyme-linked immunosorbent assay kit for human aromatase (USCN Life Science). Results: We included 96 patients (80 male/16 female) with resected NSCLC; 51% adenocarcinoma, 43% squamous, 6% others. Pathological stages: 43% I, 33% II, 22% III and 2% IV. Mean expression of ER-α in normal lung was significantly higher than in lung tumor (0.1554 vs. 0.1182, p < 0.0001). Tumoral expression of ER-β inversely correlated with cigarette consumption in current smokers (p=0.046). Patients with the highest values of tumoral ER-α mRNA had better overall survival than those with the lowest values (< p50 =107 weeks >p50 = 139 weeks; p= 0.037). Aromatase protein mean concentration in tumor lung was significantly higher than in normal lung (10.411 vs. 2.125, p<0.0001). Aromatase protein ratio, tumoral concentration/normal tissue concentration, was significantly linked to overall survival (p=0.024; Exp (B) =1.010; 95% CI Exp (B) = 1.001-1.020), showing that a lower aromatase protein ratio is associated with better overall survival. Conclusions: We report a significant association between quantitative expression of mRNA ER-α and overall survival in tumor of resected NSCLC. We define the relationship between tumoral/ normal tissue aromatase protein ratio and overall survival. A better understanding of estrogen action in lung cancer could provide the basis for future targeted therapies.
Analysis of BRAF mutations in circulating tumor cells selected by size from patients with melanoma and comparision to the primary tumor.
Authors: Wechsler Janine , Benali-Furet Naoual , Ye Fei , Avril Marie-Françoise , Boitier Francoise , Carlotti Agnes , Clauser Eric , North Marie- Odile , Paraiso Isbou , Cayre Yvon E 
Published: March 2020

e21014 Background: The efficacy of anti-BRAF therapies in patients with melanoma has emphasized the need to identify BRAF mutations in the tumour. As circulating tumour cells (CTC) derive from the primary tumour (PT), their analysis may represent a non-invasive tool to follow the molecular-target in blood after tumour removal. Methods: This prospective study included 26 patients: 24 patients had confirmed melanoma, 2 patients had benign lesions (1 naevus and 1 pyogenic granuloma). Blood samples were taken at time of the PT surgical excision; 12 healthy donors were included as controls. The 24 patients, 13 females and 11 males, had invasive melanoma (13 superficial spreading melanoma, 7 nodular melanoma, 1 lentigo malignant melanoma, 1 desmoplastic melanoma, 2 unclassified melanoma.). The mean thickness was 7.8 mm. Cytology, immunophenotyping and analysis of BRAF mutations on exon 15 were performed comparatively in primary tumour and CTC from the same patient. CTC were selected by the ScreenCell method, a single-use innovative system to isolate rare tumour cells through a filter-membrane on the basis of their size. Nucleic acids DNA/RNA were extracted from live CTC after filtration. Results: Isolated CTC and microemboli were found in 21/24 patients and were found comparable to the primary melanoma cells. No CTC was found in 10 healthy donors and 2 patients with benign lesions. The mean number of CTC was 2 CTC per ml, the maximum was 4 CTC and 7 microemboli per ml. Malignancy of CTC was assessed on classic criteria: cell size larger than 15 microns, nucleo-cytoplasmic ratio > 0.5, presence of clusters composed of pleomorphic cells. CTC were positively immunostained either by S-100 or MART1/melanA or HMB45 antibodies; 4 patients were studied for BRAF mutations in both melanoma and CTC. The results (2 negative and 2 positive) were concordant in primary melanoma cells and CTC. The V600E-BRAF mutation was found in the 2 positive cases. Conclusions: The ScreenCell method of CTC selection by size allows to detect BRAF mutations in CTC of patients with melanoma. This simple method could be proposed to follow the molecular-target during the course of evolution and treatment after tumour removal.
Blinded comparator study of immunohistochemistry (IHC) versus a 92-gene cancer classifier in the diagnosis of primary site in metastatic tumors.
Authors: Weiss Lawrence M. , Chu Peiguo , Schroeder Brock , Singh Veena , Zhang Yi , Erlander Mark G. , Schnabel Catherine A. 
Published: March 2020

e21019 Background: Metastatic tumors of uncertain or unknown origin pose diagnostic and therapeutic challenges. Accurate tumor classification is fundamental to inform predictive biomarker testing and optimize therapy. Standard of care employs IHC analysis for tumor classification that is varied in approach and interpretation. More recently, gene expression-based tests have been proposed as diagnostic aids. This study directly compared the diagnostic accuracy of IHC vs molecular classification with a 92-gene RT-PCR assay (CancerTYPE ID) for determination of primary tumor site. Methods: In this prospectively-defined, blinded study, 132 high grade, metastatic cases were selected by City of Hope (COH). Cases were reviewed and reference diagnoses established by clinical correlation (eg, patient history, imaging). Blinded FFPE sections were evaluated by either IHC or the 92-gene RT-PCR assay. Results were scored within a clinically-relevant categorization system designated by COH for main tumor type and subtype. The primary endpoint was concordance with the reference diagnosis. Study unblinding and data analysis were conducted by an independent third party. Results: Final analysis included 123 cases (mean age±SD: 61.2±14.4y, 52% female; grades 3/4; 90% metastatic); 9 cases were excluded (8: RNA quality; 1: insufficient tumor tissue). The 92-gene assay demonstrated an overall accuracy of 78% for tumor classification vs 68% for IHC (P = 0.017). For tumor subclassification, the 92-gene assay correctly identified 72% of tumors compared to 61% with IHC (P=0.029). Sensitivities were similar for GI (77%) and kidney (77%). The 92-gene assay demonstrated higher sensitivities for lung (75% vs 67%), urinary bladder (75% vs 42%), and breast (73% vs 55%). Mean IHC use was 7.8 stains per case (median: 8, range: 2-15). Conclusions: This is the first study to directly compare the diagnostic accuracy of IHC vs molecular classification. Results from this blinded series of high grade metastatic cases demonstrate superior accuracy with the 92-gene assay vs standard of care IHC, and strongly support the diagnostic utility of molecular classification in difficult to diagnose metastatic cancer.
Antibody-independent ApoStream technology isolates folate receptor alpha (FRA)–positive circulating tumor cells from blood of non-small cell lung adenocarcinoma patients.
Authors: Davis Darren W. , Neal Christopher , Gupta Vishal , Melnikova Vladislava O. , Woo Jacky , Somers Elizabeth Brooke , O'Shannessy Daniel 
Published: March 2020

e21028 Background: The ability to enrich and interrogate circulating tumor cells (CTCs) from blood may allow for the analysis of metastatic dissemination and potential use of CTCs as surrogates for monitoring drug efficacy. We developed ApoStream, a dieletrophoresis field-flow fractionation based platform, for antibody-independent CTC isolation. We demonstrated that ApoStream successfully isolates non-small cell lung adenocarcinoma (NSCLC) CTCs that express Folate Receptor alpha (FRA), a GPI-anchored receptor, which has emerged as a cancer biomarker and potential therapeutic target in multiple cancer types. Methods: ApoStream technology was used to enrich CTCs from NSCLC patients’ blood. CTC enrichment by ApoStream was compared to that of the FDA cleared CellSearch CTC kit. A multiplexed immunofluorescent assay was developed to enable CTC enumeration (Cytokeratin+/CD45-/DAPI+ cells) and analysis of FRA expression (detection by murine antibody clone 26B3) using single cell quantitative laser scanning cytometry (LSC). Results: In a side-by-side comparison with the CellSearch CTC kit, ApoStream isolated significantly higher numbers of CTCs in 9 metastatic adenocarcinoma NSCLC patients (Apostream: mean =139, range 3-487 per 7.5 mL of blood, versus CellSearch kit: mean =2, range 0-8 per 7.5 mL of blood, n= 9, p=0.041). All patients were found to be CTC-positive by ApoStream, while only 3 of 9 (33%) patients were CTC-positive based on the CellSearch kit. LSC analysis demonstrated that 8-33% of all CTCs isolated expressed FRA and that FRA expression was confined to CTCs only. No false positive CTCs and no FRA-expressing cells were isolated by ApoStream from normal donor blood (n=15). Conclusions: All NSCLC adenocarcinoma patients analyzed had FRA-positive CTCs, suggesting that FRA may play a key role in metastasis and that screening of patients with the ApoStream CTC isolation system may identify patients who could benefit from FRA-targeted therapy.
Comprehensive analysis of serum N-glycans as a biomarker for breast cancer.
Authors: Ueno Takayuki , Sato Fumiaki , Shinkura Nobuhiko , Aihara Taichi , Fukushima Masao , Sekijima Masaru , Toi Masakazu 
Published: March 2020

e21031 Background: Early detection of breast cancer is an important aspect to improve therapeutic outcome. Serum biomarkers have a number of advantages including less invasiveness and possible application for monitoring. Glycans are involved in many biological processes including cancer progression and promising candidates for cancer biomarker. Methods: Sera were collected from 54 patients with operable breast cancer and 118 healthy volunteers. N-glycans were isolated by BlotGlyco (Sumitomo Bakelite Co., LTD, Japan) and N-glycan profile was obtained by MALDI-TOF MS. The principal component analysis (PCA) was performed by SIMCA-P+ ver.12 (Umetrics). N-glycan compositions were estimated from mass spectra using 'GlycoMod' database. Results: Fifty-four pts (age: 31-78) and 118 healthy females (age: 29-73) were enrolled. The tumor size was between 9 and 107mm (median 29mm). Twenty six pts (48%) had lymph node involvement. Fifty three peaks of N-glycans were observed in more than 95% of the samples and utilized for the analyses. By PCA, no distinction was observed in sera form breast cancer pts in terms of the tumor size, hormone receptor status and HER2 status. The N-glycan signature to identify cancer pts was created based on the PCA. The signature categorized samples into three groups: cancer, healthy and border groups. Half of the samples (even registration number) were used for training and the rest for validation. In the validation cohort, 18 (66.7%) of 27 pts were categorized into the cancer group and 9 were into the border group. Forty-seven (79.7%) of 59 volunteers were categorized into the healthy group and 11 were into the border group. When the border group was included in the cancer group, the sensitivity was 100% (27 of 27 pts in the cancer group) and the specificity was 79.7% (47 of 59 volunteers in the healthy group). Conclusions: The comprehensive analysis of N-glycans in sera enabled the creation of the N-glycan signature to distinguish between breast cancer pts and healthy females with high sensitivity and high specificity. Confirmative studies are warranted.
PTHrP(12-48) for the diagnosis of breast cancer bone metastasis.
Authors: Washam Charity L. , Byrum Stephanie D. , Leitzel Kim , Suhail Ali M. , Lipton Allan , Suva Larry J. 
Published: March 2020

e21039 Background: Bone metastasis of breast cancer significantly compromises patient morbidity and mortality. Currently, no reliable methods detect or predict patients at increased risk for developing bone metastasis. We utilized 3 independent cohorts of breast cancer patients to validate a highly discriminatory plasma-based proteomic profile that identifies breast cancer bone metastasis. The identity of the most discriminatory protein component identified was a parathyroid hormone-related protein fragment, PTHrP(12-48). Methods: Plasma samples collected from 21 breast cancer patients with clinical evidence of a bone metastasis and 21 patients with no evidence of bone metastasis from time of diagnosis to clinical outcome were evaluated. A novel mass spectrometry-based assay using human serum spiked with synthetic PTHrP(12-48) was used to measure PTHrP(12-48) concentrations (pg/μl). Statistical significance was assessed by one-way ANOVA. ROC curves evaluated the diagnostic potential of PTHrP(12-48) and a simple logistic regression derived from the combined measurement of PTHrP(12-48) and NTx. Results: PTHrP(12-48) concentrations ranged between 11.6 and 92.1 pg/μl in bone metastasis patients and between 4.5 and 34.2 pg/μl in patients without bone metastases. PTHrP(12-48) was significantly increased in bone metastasis plasma (p < 0.05). No significant correlation was identified between PTHrP(12-48) and NTx. ROC analysis of PTHrP(12-48), threshold 18 pg/μl, classified the two groups with high accuracy. Class prediction by the PTHrP(12-48)/NTx logistic regression model increased diagnostic specificity. Conclusions: The measurement of PTHrP(12-48) in patient plasma has potential as a viable clinical measure of bone metastasis. In combination with serum NTx, PTHrP(12-48) may assist in identifying bone metastases in patients presenting with low to normal bone turnover markers.