bluuebunny/crossref_metadata_2025_split huggingface dataset:
A transcriptomic landscape of cancer and TME in early-stage lungadenocarcinomaby single-cell sequencing.
Authors: Wang Siwei , Zhou Yiqi , Fan Jue , Yin Rong 
Published: October 2019

33 Background: Immuno-checkpoint inhibition therapies has been revolutionizing cancer treatment. Yet only a fraction of patients show durable responses , whereas the majority of treated patients show relatively low clinical response. This difference is likely to be caused by the heterogeneity of both cancer cells and cells involved in the tumor microenvironment (TME). However, the extent of this heterogeneity, how it is shaped by other factors in the tumor and vice versa, remains poorly understood. Methods: To explore the heterogeneity of lung adenocarcinoma, we obtained tumor tissuesand peripheral blood froma cohort of 30 treatment-naive patients. For each sample, single-cell RNA sequencingand whole exome sequencing(WES) wereperformed. A graph-based unsupervised clusteringmethod was usedand cell types were assignedto clusters based on marker gene expression. The sub-types of both cancer cells and TME cells along with their gene expression patterns were comparedbetween different cancer stages and mutation status. Results: we presented a landscape of cancer and TME transcriptome in human lung adenocarcinoma at single-cell resolution. We found the expression of cancer cells exhibits distinct characteristics with different TNM stages. For instance, the tumor cells of a patient classified as T1aN2M0 highly express genes enriched in the cell migration pathway. By comparing TME cells among patients with different mutation status, we identified changes in various T cell subtypes and tumor-infiltrating myeloid cells. Conclusions: This study provided a detailed cell atlas of lung adenocarcinoma and identified gene expression patterns that are unique to specific TNM stages. Moreover, single-cell analyses offer valuable knowledgeof immune changes for each patient subgroup, providing ausefultool for the rational design of immunetherapies.
Budget poor, but outcomes rich: How to set up tele-assisted systems in a regional and rural cancer center.
Authors: Poprawski Dagmara Magdalena 
Published: October 2019

4 Background: Tyranny of distance in Australia has motivated oncologists to try innovations in oncology care to improve cost efficiency, access, and compliance. This is often done with little budget availability as health funds are metrocentric. The aim is to bring novel approaches to utilisation of oncology care and show its applicability to most countries even with financial constraints. Methods: Mt Gambier Hospital is a regional hospital in South Eastern South Australia (SE SA). The data collected from clinics was commenced in January 2016, to gain knowledge of epidemiology of cancer in the region, and numbers of patients seen. Despite gold standard cancer care being performed in consultations which are face-to-face, we rolled out telemedicine consultations. We also, implemented a Survivorship Care Model, and entered into a Teletrials Project which sets up a regional trials centre with support from a tertiary hospital, Flinders Medical Centre. Results: Telemedicine has been made in Mt Gambier Hospital’s cancer service a part of every day practice to save patients from unnecessary travel. From January 2016, until May 2019, there were 812 consultations with nurse practitioner, 2542 consultations with consultant in clinic, and 246 telemedicine consultations. Survivorship clinic has been implemented according to South Australian Framework for Survivorship with no extra funding. Since 2017, 49 patients were seen with curative therapy. A re-alignment of appointment scheduling will see 6 patients in the next 2 months, thus increasing clinic potential. Teletrials Project was born from collaboration with Flinders Medical Centre, and gained funding by Beat Cancer South Australia. We are now entering into final stages of Governance agreement for our 1st trial, 18 months from commencing the project. Since then, we also got 2 more collaboration grants from Beat Cancer SA. Conclusions: With limited resources, regional cancer centres are able to maximise their patient outcomes by applying novel strategies. These novel ways of doing things, may be able to be implemented on either existing budgets or through collaboration with metropolitan cancer centres to attract financial grants to improve patient outcomes.
Development of a blood-based cancer screening assay with a novel multivariate cancer risk score (MCRS) model by integrating shallow WGS data and plasma protein markers.
Authors: Mao Mao , Li Shiyong , Ren Qingqi , Zhong Guolin , Li Ruizhen , Chen Yan , Jin Xin , Li Jia , Ju Jia , Long Guanghui 
Published: October 2019

45 Background: Despite the increase of our knowledge about carcinogenesis and recent successful development of innovative cancer drugs, cancer mortality has only slightly decreased in the past decades. Cancer early detection is probably the most cost-effective means to reduce cancer mortality as prognosis is much better when cancer is detected and treated at the early stage. Recently studies have demonstrated that blood-based mutation detection approaches may be effective to identify asymptomatic cancer patients from general population. Methods: Here we reported a novel multivariate cancer risk score (MCRS) model that interrogates shallow whole genome sequencing (WGS) data from cell-free DNA (cfDNA) and protein markers results in a single blood draw. Results: In a prospective clinical study consisting of 76 stage I-IV cancer patients and 152 normal individuals, the MCRS model demonstrated 60% sensitivity at 98.5% specificity. In order to validate clinical utility of the MCRS model in detection of cancer patients, we collated the data from a previous study of occult maternal malignancies from 1.93 million pregnant women undergoing NIPT test between 2016 and 2017. 466 out of the 639 pregnant women who tested positive for multiple chromosomal aneuploidies (MCAs) in the initial NIPTs (i.e. 0.06 - 0.1x WGS), have also underwent the protein markers test. Out of the 466 subjects, 39 maternal malignant cancer cases were diagnosed with a median follow-up of 399 days (IR, 303 - 487 days) by imaging and histology. The cancer patients presented a wide spectrum of cancer types, the most frequent being breast cancer (10 cases), liver cancer (8) and lymphoma (8), at stage II to IV. This subgroup of 466 subjects was selected as an independent validation cohort for our study. Through our new method, we analyzed shallow WGS and proteins data. The MCRS model allowed 28 of the 39 (71.8%) cancer cases to be identified with a positive predictive value of 73.7% and specificity of 97.7%. Conclusions: Taken together, these data demonstrate the MCRS model holds promise for detecting cancer in asymptomatic individuals, particularly in the populations at high risk of cancer.
Mutation spectrum of major cancer driver genes in Vietnamese NSCLC patients.
Authors: Tran Uyen Vu , Pham Hong-Anh Thi , Tran Thanh-Truong , Dang Anh-Thu Huynh , Le Dinh-Thong Vu , Nguyen Son-Lam Vu , Nguyen Ngoc-Vu Vu , Nguyen Vu Trieu , Vo Binh Thanh , Nguyen Nguyen Huu , Nguyen Chu Van , Pham Cam Phuong , Do Thuy Thanh , Dinh Kiet Truong , Do Han Ngoc , Phan Minh-Duy , Nguyen Hoai-Nghia , Tran Le Son , Giang Hoa 
Published: October 2019

54 Background: Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and leading cause of cancer related death worldwide. Acquired genetic alterations in major driver genes including EGFR, KRAS, NRAS, BRAF, ALK and ROS1 are the most common mutations in NSCLC and certain mutations are associated with drug sensitivity or resistance. Hence, the mutation profiles of NSCLC patients are vital to guide targeted therapy and monitor the tumor recurrence, thereby improving the survival rate. The latest Globocan data showed that lung cancer ranks as the second most common cancer in Vietnam with high incidence and mortality rate. Nonetheless, the mutation spectrum of Vietnamese NSCLC patients has not been profiled thoroughly and current views on mutation testing largely rely on data obtained from previous prospective studies in Caucasian or East Asian cohorts. Methods: Massive parallel sequencing was employed to detect both somatic point mutations and rearrangement in six major driver genes in tissue biopsies from 350 NSCLC patients in Vietnam. The χ2/Fisher’s exact test was performed to compare mutation frequency between different cohorts. Additionally, both univariate and multivariate tests were used to identify clinical factors associated with mutation prevalence. Results: EGFR (32.3%) and KRAS (20%) accounted for the most frequently mutated genes, followed by ALK (5.4%), ROS1 (2.9%), BRAF (1.1%) and NRAS (0.6%). Our data showed a unique pattern of mutation profiles in Vietnamese NSCLC patients, with significant enrichment of KRAS mutation as compared to reported East Asian cohorts (20% versus 8%-10%, p < 0.05). Furthermore, EGFR and KRAS mutation frequencies were significantly associated with patients’ gender, with EGFR mutations more commonly detected in female than in male (48.1% versus 26.9%, p < 0.00001) while higher KRAS mutation frequency in male than in female (30.7% versus 9.2%, p < 0.0001). Young patients aged below the median age of 61 years had significantly higher tendency to acquire rearrangements in ALK (p = 0.02) and ROS1 (p = 0.03) than elderly patients. Conclusions: To our knowledge, our study is the first to reveal the mutation profiles of major druggable genes in a large cohort of Vietnamese NSCLC patients.
CancerScreen: A novel ultrasensitive liquid biopsy for early-stage cancer detection by ctDNA Duplex Sequencing and Tissue of Origin identification with supervised machine learning.
Authors: Ding Elizabeth , Zhao Zhilong , Xue Hongsheng , Li Jianxin , Lei Ting , Ma Xuezhen , Wu Jianlin , Huang Qin 
Published: October 2019

60 Background: Circulating tumor DNA (ctDNA) in blood holds promise as a cancer-specific biomarker for early-stage cancer diagnosis. However, detection of ultra-low mutation allelic frequency (MAF) of ctDNA at early stages of cancer is infeasible by conventional next generation sequencing (NGS). Using duplex sequencing with unique molecular identifiers (UMIs) and custom-designed probes, we tested the hypothesis that ctDNA duplex sequencing with UMIs was able to detect ultra-low MAF of ctDNA in patients with early-stage cancers. Methods: A 128-gene panel that contains probes targeted to clinical relevant genome variations in cancers of the lung, stomach, and esophagus was designed and validated with reference DNA and controls using ctDNA duplex sequencing with UMIs. A data analysis pipeline was implemented withimproved algorithms for variant calling, blood tumor mutational burden (bTMB) calculation, and supervised machine learning for tissue-of-origin primary cancer identification. Results: We designed and validated a ctDNA duplex sequencing with UMIs assay that enables simultaneous detection of 128 clinical relevant geneswith SNPs, indels, amplifications, and fusions in a single blood test. Compared to conventional ctDNA NGS, our assay achieved high sensitivity (over 82%) and specificity (over 96%) with LOD at 0.1% MAF for stage I lung, gastric and esophageal cancers with the sequencing depth at 30,000x from a cohort of 136 clinical samples. Results also showed significant concordance of MAF and TMB between DNA from tumor tissues and plasma ctDNA. Our deep learning predictive model with novel algorithms and features for tumor tissue-of-origin classification achieved an overall 85% accuracy. Conclusions: In this study, a novel ultrasensitive assay was designed and validated for accurate detection of MAF at 0.1% from plasma ctDNA of multiple tumors, and accurate classification on tissue-of-origin for major primary cancers using supervised deep learning. The results of this liquid biopsy study from initial clinical testing showed its promise on clinical applications for early-stage cancer diagnosis.
New platform for collecting real-world data on directing clinical trial optimization, especially for rare mutations in lung cancer.
Authors: Qiu Weini , Wu Fengying , Yang Yan , Dong Jie , Wei Xiaoqi , Xie Xingyi , Duan Meiling , Li Yapin , Ou Sai-Hong Ignatius 
Published: October 2019

74 Background: In China, lung cancer pts see different hospitals in various places, but medical info is not shared among different medical centers. It is difficult to obtain complete medical info to evaluate the quality of drug treatment & prognosis of lung cancer pts. Methods: We created a pt’s self-submitted data interactive platform to record and store pt’s info such as locations, gender, diagnosis, treatment etc., & to follow up on pt’s real-world medical info in real time. Based these records, a scientific method was used to establish a real medical treatment data set for lung cancer pts to reflect actual medical treatment process. Results: Between 9/13/2018 - 5/30/2019, 5 rare mutation projects (ROS1, RET, EGFR exon20, HER2, EGFR resistance) were initiated. Data cutoff is 6/15/2019. In all 5 projects, we collected by far the largest number of real-world pt’s self-submitted data reported in China. All cases were confirmed by commercial NGS or PCR. In all 5 projects, there were significant differences in regional distributions of patients. The median age for all 5 projects are: 50, 55, 57, 56 and 55, respectively. A total of 95.6% of pts submitted their 1st-line treatment info & 93.8% received 1st-line treatment. Conclusions: Pts self-submitted interactive platform provides valuable insights for trial design to reconsider site selection, & pts’ criteria selection for the success of the trial in rare mutations lung cancer. [Table: see text]
Prognostic significance of cyclin B1 expression plus clinicopathologic features in hormonal positive, HER2 negative early breast cancer in King Chulalongkorn Memorial Hospital During 2010-2015.
Authors: Takonkitsakul Kanchanaporn , Thanakit Voranuch , Poovorawan Nattaya , Uttamapinan Suleepon , Sriuranpong Virote , Parinyanitikul Napa 
Published: October 2019

75 Background: Approximately one third of hormonal receptor (HR) positive, HER2 negative early breast cancer reported disease relapse after adjuvant treatments. Both clinicopathologic features and multigene assays consider to be predicting factor of relapse. Cyclin B1, one of proliferative markers used in OncotypeDx has been explored previously for predicting recurrence in this subgroup of breast cancers. Our study aims to determine the prognostic significance of cyclin B1 in combination with clinicopathologic factors in recurrent HR positive, HER2 negative breast cancer. Methods: Two-hundred and forty-five HR positive, HER2 negative early breast cancers who were diagnosed during 2010 to 2015 in King Chulalongkorn Memorial Hospital were retrospectively reviewed. All clinicopathologic factors and level of cyclin B1 expression were evaluated. Correlation of cyclin B1 expression with clinicopathologic features was also compared in recurrence and non-recurrence group. Results: In 245 patients, 65 patients were recurrence group while 180 patients were non-recurrence group. Mean age at breast cancer diagnosis were 53 years. Recurrence group had high pathological staging, tumor grade, LVI, Ki-67 and lymph node involvement compared to non-recurrence group ( p < 0.05). Mean cyclin B1 expression was 9.61% (19.62 % in recurrence group and 5.88 % in non-recurrence group; p< 0.001). We have used cut-off of cyclin B1 expression at ≥ 10 % (7th decile) to classify high and low of expression. Cyclin B1 high expression were demonstrated in 53.4% of recurrence group compared to 22.4% of non-recurrence group. In multivariate analysis, tumor grade (OR 8.42, 95%CI 1.04-67.98; p = 0.046), receiving neoadjuvant chemotherapy (NAC) (OR 4.27, 95%CI 1.41-12.87; p = 0.010) and % cyclin B1 expression (OR 1.04, 95%CI 1.00-1.07; p = 0.013) were associated with recurrent disease. Five-year relapse free survival for cyclin B1 low and high expression were 84.9% and 60.1%, respectively. Conclusions: Tumor grade, receiving NAC and % cyclin B1 expression were associated with risk of recurrence in HR positive and HER2 negative early breast cancer.
Not preoperative but prechemotherapy lymphocyte count predicts outcome of non-small cell lung cancer patients treated with adjuvant chemotherapy.
Authors: Lee Hyun Woo , Kang Seok Yun , Han Jae Ho , Yoo Byoung Moo 
Published: October 2019

76 Background: Several systemic inflammatory markers in blood have been suggested as prognostic factors in various cancers. We investigated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) in patients (pts) with non-small cell lung cancer (NSCLC) treated with adjuvant chemotherapy. Methods: A retrospective review was conducted on 108 pts who received adjuvant chemotherapy after surgical resection of NSCLC. Disease-free survival (DFS) and overall survival (OS) of pts with high NLR and ALC ( > median value) before surgery or chemotherapy were compared to those of pts with low NLR and ALC (≤median value). Results: The number of pts at AJCC stage IB, IIA, IIB, IIIA, and IIIB were 1, 38, 9, 58, and 2, respectively. Adenocarcinoma,squamous cell carcinoma, and other histologic types were present in 66 (61.1%), 32 (29.6%), and 10 (9.3%) patients, respectively. The most frequently used chemotherapy regimen was vinorelbine/cisplatin (81 pts), followed by paclitaxel/carboplatin (22 pts), and others (5 pts). A total of 61 (56.5%) pts received adjuvant radiotherapy (before adjuvant chemotherapy: 53 pts). Preoperative NLR and ALC were not associated with clinicopathologic characteristics including stage and histologic types. High prechemotherapy NLR and low ALC were more frequently observed in pts who underwent radiotherapy before chemotherapy (p < 0.0001). The median follow-up duration was 61 (29-153) months for survivors. The longer median DFS was observed in pts with stage IB or II (65 vs. 22 months, p = 0.025) and high prechemotherapyALC (65 vs. 20 months, p = 0.036), without significant difference in OS. On the other hand, NLR and preoperative ALC were not associated with outcome of pts. Conclusions: The present study suggests that high prechemotherapyALC is associated with favorable outcome in stage IB-III NSCLC pts who received adjuvant chemotherapy after surgical resection.
Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) hyperthermia for primary rectal cancer: A virtual feasibility analysis.
Authors: Perry Kaitlyn , Staruch Robert , Pichardo Samuel , Huang Yuexi , McGuffin Merrylee , Partanen Ari , Wong Shun , Czarnota Gregory J. , Hynynen Kullervo , Chan Kelvin K. , Chu William 
Published: October 2019

77 Background: MR-HIFU Hyperthermia (HT) is a non-invasive treatment modality with real-time thermometry that ensures accurate and precise heating of a target with minimal effect on adjacent tissue. This energy deposition within a tumour can produce local bioeffects resulting in thermal chemo- and radiosensitization. MR-HIFU has been shown to be safe and feasible in a companion phase I study for recurrent rectal cancer. The purpose of this study is to determine the feasibility of MR-HIFU in treating primary rectal tumours. Methods: With ethics approval, the anatomic characteristics and surrounding structures of rectal tumours diagnosed at Sunnybrook from 2014-2019 were retrospectively analyzed. Three orthogonal views of MR images were used to determine the potential ultrasound (US) beam path and organs at risk (OAR). In part 2 of the study, the gross tumour volume was delineated for 30 rectal tumours (10 low, mid &high). Image datasets were imported into the Sonalleve MR-HIFU workstation for virtual treatment simulation and planning to determine tumour targetability, coverage, optimal patient set-up, and transducer positioning. Results: Of the 105 tumours analyzed, 36, 52, and 17 were low, mid, and high, respectively. The average width of the acoustic window (sciatic notch) for the US beam path was 5.8 ± 1.4cm, average tumour length was 5.24 ± 2.0cm, and average beam path (skin to tumour edge) was 7.3 ± 1.9cm. Eighty one percent of tumours were ≤ 0.3cm from an OAR. Of the 24 virtually simulated tumours to date, 6/8 lower, 6/8 mid, and 1/8 upper rectal tumours were targetable by MR-HIFU. Conclusions: This is the first virtual analysis to evaluate MR-HIFU HT targetability in primary rectal cancer. Results from this study will support MR-HIFU HT as an option to enhance the treatment of primary rectal cancer. Acknowledgments: This study has been funded by the Canadian Cancer Society. Patient & tumour characteristics. [Table: see text]
Fear of receiving less effective care: A barrier to effective cancer care cost communication.
Authors: Kang Sokbom , Yu Ye Lee 
Published: October 2019

8 Background: Increasing financial burden in cancer care promoted cost communication as an intervention to the problem. We explored patients’ attitudes and concerns for the physician-patient communication of the costs of cancer care. Methods: From an oncology outpatient clinic, patients were recruited and interviewed using a 29-item questionnaire. The questionnaire includes basic and financial characteristics, attitudes toward cost-communication, and experience of cost-communication with oncologists. Results: Among 292 patients with gynecologic cancer, 68% were found to have an income below the nation’s average households income. Although the majority (81%) of patients have a positive attitude toward patient-physician cancer care cost-communication, however, only 19% of them wanted to discuss the cost with their physicians - 33% of them did not want to disclose their financial status to health care providers and 48% wanted to discuss the cost with other providers than their physicians. In addition, while 87% preferred to be informed about costs for various treatment options, 86% of them did not want to receive cost-effective treatment and preferred to receive the most effective treatment regardless of their financial status. Compared with non-cancer patients (n = 83), significantly more patients had a negative attitude to disclosing their financial status especially to their physician (22% vs. 11%, P = 0.024). Conclusions: A considerable proportion of cancer patients had concerns that cost communication with their physician may interfere with their opportunity to access the best care options. To facilitate cost communication, oncologists should understand such concerns and making a thoughtful effort to relieve the concern during cost communication.