bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic predisposition to childhood cancer: A retrospective cohort analysis in a multidisciplinary genetic cancer counseling Unit.
Authors: Rodriguez Salas Nuria , Escudero Adela , Blanco Naiara , Corral Dolores , Higuera Oliver , Ruiz Gimenez Leticia , Gallego Alejandro , Sánchez Cabrero Darío , Rodriguez Laura , Perez Martinez Antonio 
Published: May 2020

e13643 Background: The incidence of childhood cancer in Spain is 18, 2 cases per 100.000 inhabitants per year. The presence of predisposing genetic factors has been revealed in approximately 10% of patients, in them the detection of genetic mutations associated is essential in order to establish the correct clinical management of patients and their relatives. However, genetic counseling in this population is currently underestimated since, not all patients with pediatric malignancies have a family history of cancer or other clinical signs to suspect and inheritance syndrome. Methods: The Unit for Predisposition to Child and Adolescent Cancer of the University Hospital La Paz in Madrid, Spain, is composed by the Units of Clinical Oncology, Pediatric Hemathology-Oncology, and Genetics. Inclusion criteria are based on the characteristics of the individual's neoplasia, family characteristics and other phenotypic characteristics.The molecular study is carried out through Next Generation Sequencing, Direct Sequencing and / or MLPA. In the present study, a retrospective and descriptive analysis of the cases studied from September 2018 to December 2019 was carried out. Results: The Pediatric Cancer Predisposition Functional Unit of the La Paz University Hospital attended during the years 2018 and 2019 a 58 patients with suspected predisposition syndromes to childhood cancer belonging to 41 families. The following inheritance syndromes have been identified: hereditary retinoblastoma in 14 families with mutation in the RB1 gene, Li Fraumeni syndrome in 1 family with mutation in the TP53 gene, multiple endocrine neoplasia type 2A by RET gene mutation in 1 family, 1 hereditary melanoma syndrome with a CDKN2A mutation, and inheritance family leukemia in 1 family with a PAX5 gene mutation. Other cases studied have been negative-non informative, with the following neoplasms of the index cases: unilateral retinoblastoma, hepatoblastoma, hamartomatous colon polyposis, lymphoma, leukemia and soft tissue sarcoma. In addition to the molecular diagnosis of the index case, both cases and family members received genetic counseling and adequate clinical management, adapted to each syndrome. Conclusions: The multidisciplinary and specialized approach improves the diagnosis and monitoring of patients with suspected syndromes of predisposition to childhood cancer and allows the establishment of prevention strategies and early diagnosis individualized to each family.
An ultra-sensitive multiplexed enrichment of rare DNA variants via toehold exchange principle.
Authors: Pu Yue , Wang Qianwen , Lin Rui , Wang Tao 
Published: May 2020

e13658 Background: As a major type of liquid biopsy, circulating tumor DNA (ctDNA) provides important somatic mutation information, but the feature of rare allele frequency of mutation in ctDNA hampers its wide application. Methodology with high sensitivity, cost effectiveness, and multiplexing capability is needed for analyzing ctDNA samples. Methods: We have developed a novel methodology, termed MTEA (Multiplexed Toehold Exchange Amplification), which selectively amplifies and enriches all sequence variants (including SNV and deletion) 1000-fold over the wild-type sequence within ~20-nucleotide window. The amplified products are detected by Sanger sequencing or next-generation sequencing (NGS). This novel approach takes advantage of toehold exchange principle in which PCR amplification of wild-type rather than mutants would be greatly reduced due to the formation of a duplex of wild-type sequence with a blocker targeting to the wild-type rather than the mutant alleles. Results: Using circulating cell-free DNA (cfDNA) reference standards, we demonstrated that the major driver mutations of lung adenocarcinomas, including EGFR L858R and exon 19 deletion, KRAS G12X, and BRAF V600E, were enriched and detected simultaneously with MTEA technology at abundance as low as 0.01-0.05%. The clinical implications of MTEA technology were further validated using ctDNA from liquid biopsy specimens of 29 non-small cell lung cancer patients, and results were compared with those collected from the NGS and ddPCR analysis. Consistent results were obtained from all of the three platforms, which indicated 100% accuracy. The MTEA method has advantages over ddPCR since the later lacks the multiplexing detection ability. The MTEA technology can also save cost compared with NGS method. Conclusions: MTEA technology can enrich ctDNA from cancer patients to detect ultra-low abundance of clinically relevant mutations. Upon validation using a larger cohort, the technology may have wide application in precision medicine and guide clinicians for therapeutic decisions.
Circulating exosome DANCR correlated to the recurrence of hepatitis C virus-related hepatocellular carcinoma.
Authors: Wang Shu-Chi , Huang Jee-Fu , Dai Chia-Yen , Chuang Wan-Long , Yu Ming-Lung 
Published: May 2020

e13688 Background: Long non-coding RNAs (lncRNAs) have been associated with various types of neoplasms. Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) has high risk of recurrence. Methods: Differentially-expressed candidate lncRNAs relevant to HCV-HCC were identified by RNA-seq in Screening set, validated by qPCR in Validation set, and confirmed in external Test cohort. Target lncRNAs in tissue and serum exosome were applied to predict HCC recurrence of HCV-HCC after curative surgical resection in a large Application cohort. Pathogenetic mechanisms of target lncRNA were explored by using JFH1-infectious cells. Results: Of the top ten differentially-expressed lncRNAs relevant to HCV-related HCC identified in Screening set, differentiation antagonizing non-protein coding RNA (DANCR), which was upregulated by HCV infection and identified as the most relevant lncRNA to HCV-HCC, was overexpressed in tumor than in adjacent non-tumor (ANT) tissues. Of 183 HCV-HCC patients followed for 10 years after curative HCC resection, tumor DANCR, tumor/ANT DANCR ratio and circulating exosome DANCR levels were positively associated with HCC recurrence. Circulating exosome DANCR levels by droplet digital PCR provided the best predictive power of HCC recurrence with area under the curve of 0.88, when compared to tumor DANCR levels, tumor/ANT DANCR ratio, and alfa-fetoprotein. Exosome DANCR > 50 copies/ml was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively, Cox regression model). Cell experiments showed that DANCR, positively associated with mesenchymal-associated β-catenin expression, promoted cell migration and invasion ability. Conclusions: lncRNA-DANCR was highly relevant to disease progression of HCV-HCC. Circulating exosome DANCR could serve as a non-invasive prognostic biomarker for HCV-HCC.
The multi-disciplinary meeting as a tool to identify patients for clinical trials and translational research.
Authors: Winter H , Rea David 
Published: May 2020

e14001 Background: Cancer multi-disciplinary team meetings (MDTs) were established with one of the core aims to increase participation in clinical research. However, a recent Cancer Research UK study observing 624 patient MDT discussions revealed only 8 (1.3%) patients included a discussion on clinical trials. Current work in the UK looking at MDT effectiveness has explored the quality of discussions and team dynamics. However, recruitment to clinical trials has not been promoted as an indicator of an effective MDT. This study explored the role of MDTs in identifying patients for research across all solid tumour MDTs in a tertiary cancer centre. Methods: This study explored the outcome data from solid tumour MDTS; reports on the observation of solid tumour MDTs and completion of a trials and translational proforma about patient discussions on research; exploration of MDT members views on the role of MDTS in identifying opportunities for patients to participate in clinical trials and translational research. Results: MDT outcomes from all solid tumour MDTs were reviewed. Out of 7000 local MDT outcomes from Avon Cancer Registry April 2019- Set 2019. Only 409 discussions included an outcome registered with “Clinical Trial y/n” (5%). In the majority there was no mention of any consideration of clinical trial or an explicit trial documented. Conclusions: We report on the exploration of the MDT as integral to identifying patients for clinical trials and translational research. This requires input and buy in from MDT members and the identification of research champions attending MDTs. The integration of genomics data into MDTs will require a proactive approach to access clinical trials for patients with identified potential actionable targets.
Utilization of imaging and outcomes of care among metastatic colorectal cancer (mCRC) patients (pts) receiving bevacizumab containing regimens.
Authors: Barzi Afsaneh , Zheng Hanke , McCombs Jeffrey 
Published: May 2020

e14011 Background: Chemotherapy combined with bevacizumab is the most commonly used treatment first line therapy in pts with mCRC. Decisions for continuation or change of chemotherapy are based on the findings of CT scan, the most commonly used from of imaging in this population. Modeled after clinical trials, CT scan every 2 months is adopted as a standard of care. Yet, patterns of utilization of CT scan in general population is unknown. We set to explore CT scan utilization and associated outcomes among pts with mCRC. Methods: The De-identified Clinformatics Data Mart (OptumInsight, Eden Prairie, MN) covering January 2008 to December 2016 was used for this analysis. Pts with two out-patient and/or one in-patient ICD codes for colorectal cancer were identified. Pts with at least 180 days of enrollment, no chemotherapy within 120 days prior to chemotherapy, and at least one claim for CT scan were eligible for analysis. Recipients of FOLFOX (CAPOX) or FOLFIRI (XILIRI) +bevacizumab were identified using HCPCS codes and the data of their 1sttreatment was registered as index date. The primary endpoint of the analysis was exposure to both FOLFIRI and FOLFOX, secondary endpoint was survival. SAS software was used for data processing and analysis. Results: A total of 3261 pts met the inclusion criteria 78% with oxaliplatin based regimens and 22% with irinotecan regimens. The median age of the population is 66 (19-89), and 58.3% of the identified pts were male. The median duration of first line therapy was 119 days. Median number of CT scan during first line was 2.3. The median and mean number of CT scan per 2 months were 0.82 and 0.94. There was no difference in age, gender, and comorbidities in those with less than 2 vs. 2 or more CT scans. Exposure to both regimens (measured with switching from one regimen to another) was 35% in pts with less than 2 CT scans and 44% in those with 2 or more CT scan (p-value < 0.0001). Probability of survival at 12 months was 83% for all patients regardless of the frequency of scans. Conclusions: In patients with mCRC more frequent scans is associated with higher probability of access to active agents. However, survival probability at 12 months was not different between the two groups.
Systematic analysis of chemotherapy agents for home-based administration.
Authors: Xiangyun Ye George , Binder Adam , Handley Nathan , Piddoubny Maria , Espinosa Gloria , Chung Justine , Alberto Judith 
Published: May 2020

e14012 Background: Improvement in supportive care medications, feasibility of outpatient management, and regulatory changes have led to a dramatic shift in the primary location of chemotherapy delivery from the inpatient setting to outpatient infusion centers. Over the last decade, centers in Europe and Canada have taken the next logical step – home based chemotherapy infusion. To our knowledge there is no systematic large scale initiative that has transitioned chemotherapy to the home in the United States. In order to implement a home based chemotherapy infusion program, we systematically scored anti-neoplastic agents for ease of administration. Methods: We reviewed all anti-neoplastic agents administered at our infusion center. Characteristics of each medication that could be a barrier to home infusion were identified. These included route and duration of administration, vesicant status, emetogenic potential, and duration of stability at room temperature. Scoring was determined by a multi-disciplinary team of pharmacists and oncologists (see Table). Higher scores indicated greater potential for home administration. Results: We reviewed 100 medications. The highest possible score was 8; the lowest possible score was -4. Agents ranged with scores from 8 (fulvestrant) to -1 (dactinomycin), with a median score of 4. The mode score was 3 (24 medications). The largest factor lowering the ease of administration score was stability at room temperature; score of -2 and -1 in 19 and 18 medications respectively. Conclusions: It is feasible to administer the majority of our chemotherapeutic agents in the home setting. The biggest barrier to administration at home is stability of medications at room temperature. This issue can be addressed by transporting and storing the medication in a refrigerated container. Expectedly, injectable drugs and medications with short infusion times that are stable at room temperature would be the easiest to administer in the home. Further analysis in ongoing to assess the financial feasibility and establishment of our home based program. [Table: see text]
First validation of the supportive care score (SCC) scale: Alert scale for referral of solid cancer patients to supportive oncology team.
Authors: Chastenet Mathilde , Laurain Pierre-Antoine , Maupoint Typhaine , Legeay Karine , Salleron Julia , Baumard Florian , Scotte Florian 
Published: May 2020

e14025 Background: Patients’ needs are still underestimated during cancer course. The development of a simple and accessible screening tool to identify supportive care needs is an innovative approach to improve the cancer care pathway. Supportive Scale sCore (SCC) is a new tool developed to trigger alert in main need of supportive care such as social, nutritional, physical, pain or psychological disorders. This study aimed to develop and validate the SCC tool for detecting supportive care needs. Methods: The SCC, the Edmonton Symptom Assessment System (ESAS), a symptom scale and the EQ-5D (for Quality Of Life) was distributed to cancer patients over a week, in an ambulatory hospital of oncology department. The acceptability was assessed by the fill rate. The validity of alerts generated by the SCC scale was assessed by their consistency with ESAS and EQ-5D scores. Results: Hundred patients were included with an average age of 67,2 years. Acceptability was good with a fill rate of over 90%. For a-priori defined risk groups by SCC with alert or not, ESAS symptom score and QOL differed significantly (p < 0,05) between groups. We observed higher ESAS symptom scores in the alert group [nutritional alert: appetite: 4 (Standard Deviation SD 2,4) vs 0 (SD 1,6), p < 0,001; physical alert: fatigue: 4 (SD 1,7) vs 2 (SD 2,2) p < 0,001; psychological alert: depressed: 3,5 (SD 2,7) vs 0 (SD 1,5), p < 0,001; anxiety: 4 (SD 2,9) vs 0 (SD 1,5), p < 0,001; unwell-being: 4,5 (SD 2,7) vs. 0 (SD 1,5), p < 0,001]. Moreover, the QOL was poorer in each domain of EQ-5D in the alert group. [Social alert, self-care: 9,3% vs 0%, p = 0,02; usual activities: 25% vs 5,4%, p = 0,005. Physical alert, usual activities: 21,3% vs 2,6%, p = 0,008; mobility 29,5% vs 2,6%, p = 0,01. Pain alert, pain: 81,8% vs 11,9%, p < 0,001. Psychological alert, psychological: 56,3% vs 11,9%, p < 0,001]. Conclusions: The SCC seems to be a reliable instrument to detect cancer patients’ supportive care needs.
Interdisciplinary risk assessment and delay of chemotherapy.
Authors: Souza Juliana , Santos Monica , Coutinho Ana Paula , Gil Natalia , Silva Alessandra , Fernandes Maria Carolina , Souza Larissa , Souza Vilceia , Neves Daniele Ferreira 
Published: May 2020

e14033 Background: In 2015, in our outpatient clinic, we implemented a breast cancer interdisciplinary team with the goal of identifying risk factors for chemotherapy delay. Evaluation of individual cases and care plans were made by a medical oncologist, clinical pharmacologist, psychologist, dietician and oncology nurse. Methods: 81 patients with breast cancer in neoadjuvant/adjuvant chemotherapy were prospectively evaluated from July 2018 until July 2019 for clinical risk: age, anthracyckine use, presence of symptoms grade >3, ASGPPP questionnaire for nutritional risk, psychological risk for pre existent issues or induce by treatment and IRPO questionnaire for screening, nursing evaluation for comunication, organization and understanding issues, and pharmacologist evaluation of polypharmacy and unknown drugs or routine use. Results: Of 81 patients evaluated and had finish treatment, 55 pts (67.9%) received adjuvant chemotherapy. Median age was 57.9 years (range:29-90.6y). We defined as risk factors for delay chemotherapy treatment: anthracycline-based chemotherapy (9.34 vs 2.58 d p:0.002), psychological risk (both risks combined) (8.1 vs 4.7 p:0.047), comunication, organization and understanding issues (15.25 vs 5.83 d p: 0.004), and unknown drugs that routinely uses (11 vs 5.34d p:0.012). Patients who needed extra nutritional and psychological appointment had greater delay in chemotherapy (Dietician: 9.636 vs 4.7 d P:0.01; Psyc: 9.1 vs 4.2d p:0.008). Conclusions: The chemotherapy scheme, psychological risk, difficulty in understanding and organizing, and unaware of the drugs used routinely uses were high risk factors for delayed chemotherapy and these patients should be handled more carefully.
Optimizing the febrile neutropenia care process in cancer patients in a third level Spanish hospital.
Authors: Solis-Hernandez Maria Pilar , Mihic Góngora Luka , Contreras Toledo Debora Corina , Iglesias Gomez Clara , Fernandez Arrojo Sara , Alvarez Fernandez Carlos , Jiménez Fonseca Paula , Izquierdo Manuel Marta , Revuelta Alfonso , Gómez David , del Río Fernández Jorge , Valcárcel González Sena , Muniz Castrillo Maria , Castillo Trujillo Oscar Alfredo , Villanueva Noemí , Garcia Llano Juan Luis , Palacio Vázquez Isabel , Fernandez Perez Yolanda , Esteban Emilio ,   Hospital Universitario Central de Asturias
Published: May 2020

e14034 Background: Cancer patients under cytotoxic treatment with fever used to have an average time of antibiotics administration of 11h (median 3h43min) when admitted and identified at the Emergency Room Service in the third level Central University Hospital of Asturias. International guidelines recommend antibiotic administration in the first hour: the so called “Golden Hour”. This delay implies an increase in patient morbidity as well as the cost of managing this complication. Methods: Data was collected from our electronic registry after proper authorization and corresponding anonymization. Pareto and fishbone diagrams were built to point out the possible causes and to stratify them in related subgroups. We measured: Number of visits to ER with fever and Number of inpatients with Febrile Neutropenia diagnosis, Time from the admission to antibiotic administration, Average stay of inpatients with Febrile Neutropenia diagnosis. A protocol associated to electronic tools and validated international scores was designed for patients at Febrile Neutropenia risk and launched on March 2019. Results: 66 patients were included since January 2018. Baseline data showed that the median time to antibiotics indication was 3h50min (average 4h38min) with a median delay of 18min to the administration (average 1h06min), a median of 3h54min (average 10h09min) time to antibiotic administration. When the protocol was activated, median time to antibiotic indication was 30min (average (1h08min) with a median 41min (average 40min) delay in administration, and a median of 1h30min (average 1h42min) time to antibiotic administration. Those with activation of the protocol had average length of stay of 1d13h40min vs. 5d11h18min in those to whom this protocol was not applied. Conclusions: A continuous evaluation effort and the design of appropriate protocols and interventions will increase the efficiency of the oncology patient care process with febrile neutropenia, by reducing unnecessary variability and costs.
Lenalidomide use in multiple myeloma.
Authors: Meade Denise , Ng Marie , Alford S 
Published: May 2020

e14045 Background: For patients with multiple myeloma (MM), lenalidomide’s (LEN) received its first FDA approval for use in combination with dexamethasone (DEX) for second-line treatment in 2006, and was expanded to first-line treatment in 2015 for patients not eligible for autologous stem cell transplant, and was further expanded for use as monotherapy for maintenance treatment following a transplant in 2017. We aimed to characterize the treatment patterns of LEN and analyze the impact of the expanded approval on the MM treatment. Methods: A MM disease model was built in IBM Access and Value Connect to interrogate patient demographics, payer types, clinical characteristics, clinical outcomes, utilization, costs, and treatment sequencing, informed by United States Food and Drug Administration (FDA) labels for approvals, professional society guidelines, clinical and economic literature review, and subject matter expertise. Patients were selected from IBM Marketscan Commercial and Medicare Claims database and have an approved MM treatment, at least one diagnosis claim for MM within 30 days of treatment, and a minimum of treatment period of 90 days, but do not have claims for other cancers or pregnancy during the study period. Using advanced visual analytics, we identified trends and outcomes in the treatment and performance of MM patients with LEN to evaluate the impact of LEN’s expanded approval. Results: From October 2017 to September 2018, a total of 1,422 MM patients in the database received treatment with LEN, representing 61% of all MM patients for the same period. Of the patients receiving LEN, 38% of patients were being treated with LEN on monotherapy. In comparison, for the same time period only 1% of patients were on LEN-DEX. Patients receiving LEN as a monotherapy had mean monthly all-cause costs of $15,590 vs $32,352 for the same costs for patients receiving LEN as a combination therapy. Conclusions: The expanded indication of LEN in 2017 has likely increased the population of MM patients receiving LEN as a monotherapy. Further analyses to determine whether clinical outcomes have improved for patients on LEN maintenance therapy should be completed given the increased financial costs of combination therapy.