bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apatinib to prolong overall survival from recurrence to death in metastatic breast cancer: A single-center experience from east China.
Authors: Shi Lei , Chen Zhanhong , Wang Xiaojia 
Published: May 2020

e13090 Background: To observe the efficacy and side effects of apatinib in patients with metastatic breast cancer in non-clinical trial setting. Methods: Patients with metastatic breast cancer who were treated in Zhejiang Cancer Hospital from January 2014 to September 2019 were collected from the hospital information system. According to whether patients were treated with apatinib, they were divided into apatinib group and control group. There were significant differences in baseline data such as the age of onset between the two groups, and the propensity score match was used to ensure balance. The survival time from the first recurrence to death was compared between the two groups. The progression-free survival, the incidence of side effects and the types of side effects of apatinib were observed. The prognostic factors of apatinib were also analyzed. Results: There were 297 patients who met the criteria, of whom 40 received apatinib treatment. After propensity score match, the balance of the two groups was guaranteed. Compared with the control group, the hazard ratio of apatinib group was 0.111 from first recurrence to death (95% confidence interval: 0.022 to 0.556, p = 0.007). The median progression-free survival of apatinib was 8 months. Patients often received apatinib at the end of the disease. And 67.5% (27/40) of patients received apatinib at the end line. 52.5% (21/40) of patients had adverse reactions, and common adverse reactions included myelosuppression (7/40), fatigue (6/40), hypertension (6/40), proteinuria (5/40), skin and mucosal reactions (5/40) and so on. Three of them had grade Ⅲ to Ⅳ adverse reactions, including hypertension, myelosuppression and skin ulceration. Severe adverse reactions increased the risk of progression-free survival with apatinib. Its hazard ratio is 10.103 (95% confidence interval: 1.149 to 88.825, p = 0.037). Conclusions: As the choice of multi-line therapy for metastatic breast cancer, apatinib can prolong the survival time after recurrence. The adverse reactions are common, so it is necessary to guard against the severe adverse reactions that lead to poor prognosis.
Depressive factors associated with breast cancer.
Authors: Tostes Alexandre Alberto Mendes , Freitas Carla Simone Moreira de , Soares Aleida Nazareth 
Published: May 2020

e13091 Background: In Brazil, the estimated cancer for the 2019 was approximately 420 thousand new cases. In Minas Gerais, the estimate was 5,360 new cases. Objective is to relate comorbid humor disorders with breast cancer in patients treated at a cancer hospital. Methods: Cross-sectional and descriptive study with a sample of 100 patients with Breast Cancer (BC), chosen at random. Data were collected at a Muriaé cancer hospital in, from January to June 2019. Semi-structured sociodemographic and clinical suervey and the Beck Depression Inventory (BDI-II) to check for signs and symptoms of depression. Data analysis was performed using the statistical packages SPSS. To check if there was a difference between groups in continuous variables, Shapiro-Wilk test; the data considered normal the Student's t test (parametric test) and the data considered non-normal the Mann Whitney test (non-parametric test). For categorical variables, the chi-square test, Fisher's exact test or Monte Carlo simulation. As for the interpretation of Beck's inventory, the scores were analyzed and demonstrated according to the standardized by the inventory, that is, the result obtained was the sum of the individual items, reaching a maximum score of 63 points. The classification of the levels of depression varies between minimum, mild, moderate and severe, thus indicating the intensity of the depression. The study was developed according to Resol. 466/12, of the National Health Council. Results: Average age of women with BC in both groups was 55 years, with low education (43%), married (48%), and, 50% of them have one or more children and, 70% do not work. Regarding the use of drugs and/or medication and smoking, it was higher in group B (with depression) (64.6%). In the other variables (family relationship, self-preservation of health, affected daily life, family/social isolation, living with other women with BC, perspective of life after treatment, type of follow-up), the proportion was always higher in group B compared to group A (without depression). The time of diagnosis, staging, type of surgery and edema in the upper limb did not show significant difference between the two groups analyzed. Regarding the type of treatment, there was a significant difference, mainly showing that proportionally the Surgery + Chemotherapy treatment is higher in the group without depression while the and Surgery + Chemotherapy + Radiotherapy + Hormone therapy are proportionally higher in the group with depression. Conclusions: Women with BC have depressive symptoms frequently and should be investigated and treated so that the negative impacts can be minimized.
Very long term follow-up of high dose chemotherapy followed by autologous stem cell transplantation in high risk locally advanced triple negative breast cancer.
Authors: Al-Share Bayan A , Assad Hadeel , Abrams Judith , Deol Abhinav , Alavi Asif , Ratanatharathorn Voravit , Uberti Joseph P. , Ayash Lois Jeanne 
Published: May 2020

e13094 Background: The role of High Dose Chemotherapy (HDC) with Autologous Stem Cell Transplantation (ASCT) in treatment of high risk locally advanced breast cancer remains unclear. This modality stopped being used for breast cancer treatment when trials in early 2000s reported Disease Free Survival (DFS) benefit but no Overall survival (OS) benefit. However, subgroup analyses of these studies reported OS benefit in young and Triple Negative Breast Cancer (TNBC). We report very long-term outcomes of high risk locally advanced TNBC treated with HDC-ASCT at our institution between 1995 and 2001. Methods: We reviewed our BMT database for women with stage IIB or III TNBC treated with HDC-ASCT. We excluded women with hormone positive, Her2/Neu positive/Unknown and metastatic disease prior to transplant per updated AJCC 7th edition. The majority of patients underwent surgery followed by adjuvant Anthracycline and Taxane based induction chemotherapy followed by HDC-ASCT for consolidation. The HDC regimen consisted of Carmustine 600 mg/m2, Cyclophosphamide 5.6gm/ m2 and Cisplatin 165mg/ m2 (STAMP 1 regimen). Four patients received induction regimen as neoadjuvant and HDC-ASCT as adjuvant treatment per the same protocol. All patients received loco-regional radiation after ASCT. Results: 29 patients had locally advanced TNBC treated with HDC-ASCT. Median age at diagnosis was 43 years (IQR 40-51). 28 had at least 4 positive lymph nodes. Median time from diagnosis to ASCT was 5 months. Median overall survival was 17 years (95% CI, 3-19 years), and median DFS was 14 years (95% CI, 1-19). There was no treatment related mortality (TRM) at 30- and 100-days post ASCT. 12 patients (41%) were alive at median of 16 years (95% CI, 12-19) post ASCT. Conclusions: This single institution study of locally advanced high risk TNBC patients who received HDC-ASCT as part of treatment demonstrates a high long term OS exceeded historical controls. This supports a potential role for HDC-ASCT in this cohort of high risk TNBC. Considering the low TRM associated with this approach, prospective evaluation of this strategy is warranted.
Outcomes of transarterial chemoembolization (TACE) of the liver in patients with metastatic triple-negative breast cancer (TNBC).
Authors: Storozhakova Anna E. , Vladimirova Liubov Yu , Kit Oleg I. , Kolesnikov Evgeniy N. , Snezhko Aleksandr V. , Chernyak Maksim N. , Snezhko Tatiana A. , Samaneva Natalia Yu. , Svetitskaya Yana V. , Kalabanova Elena A. , Kabanov Sergey N. , Tishina Anna V. , Teplyakova Maria A. , Lisutin Aleksandr E. 
Published: May 2020

e13107 Background: TACE is widely used in oncology in patients with metastasis in liver from GI tumors, meanwhile its opportunities in management pts with TNBC are unknown. The purpose of the study was to analyze the results of TACE of the liver metastases from TNBC. Methods: The study included 60 TNBC pts with unresectable liver metastases. 34 pts of the main group underwent chemotherapy including taxanes in standard regimens. After 6-12 chemotherapy cycles, the main group received 1-2 TACE procedures (doxorubicin 30 mg/m², 5-fluorouracil 600 mg/m², 10 ml of lipiodol and 1-2 ml of 300-500 µm HepaSphere microspheres). The control group (n = 32) received only 6-12 cycles of taxane-containing chemotherapy. Pts were aged 32-66 years, mean age in the main group 49.4, in controls 55 years. Primarily advanced breast cancer with unresectable liver metastases was diagnosed in 6 (17.6%) pts of the main group and in 5 (15.6%) controls. Progression after previous treatment was observed in 91.2% (31) main group and 90.6% (29) controls. Sizes of metastatic foci were 2.7-7.3 cm, average number 7.5. Bilobar metastases were most common. Liver metastases were own accompanied by metastases to the bones, intrathoracic lymph nodes, lungs and pleura. Obtained data were processed with software package “Statistica 7.0”. Results: Main group received a total of 46 TACE procedures performed for a maximal number of metastatic lesions, especially for those progressing after systemic therapy and the largest ones, when possible. Post-embolization syndrome after performing TACE, was observed in 60.86% (28) of cases, managed with conservative therapy for 2-7 days. Icterus was not observed. The tumor response rate was 94.1% in the main group vs. 80.6% in controls, with significant differences in PR (44.1% and 15.3% respectively, p < 0.05). Median of duration treatment response was 13.4 months in the main group and 9.3 months in control group (p < 0.05). CR was not achieved. Median follow-up was 17 months. 3-year disease-free survival was 63.2% in the main group and 43.8% in controls (p = 0.039). Conclusions: TACE resulted in better response to the therapy as well as improved disease-free survival in pts with TNBC. TACE is possible to be used to consolidate the achieved effect of the chemotherapy.
Staging the cancer ecosystem: Survival data from a registry study of patients with active cancer.
Authors: Cunningham James R. , Rittenbach Jon , Dodd Cheryl , Clemens Mitch 
Published: May 2020

e13505 Background: Predicting cancer evolutionary trajectories remains an unmet goal for current cancer staging systems. Understanding the influence of selection pressures operating in the host-cancer environment and capable of effecting neoplastic evolution may be a means of informing such predictions. Methods: An IRB-approved cancer ecology registry study was begun, recruiting subjects whose cancer required active treatment. A set of 22 clinical and laboratory parameters obtained at time of entry onto the registry were compiled into eight separate profiles ( tumor microenvironment, inflammation, energy balance, psychosocial stress, GI microbiome, endocrine, skeletal remodeling, mutagenic) to help define a subjects’ ecological landscape. Parameters were chosen based on previous evidence of selection influence and scored using a trichotimzation of data (0, 1, 2). Resulting quantitative profiles from each subject were then aggregated using a geometric figure, an octomer, (an ‘ecogram’), length of vertices representing individual profile scores and whose net area, bounded by the ecogram, it is hypothesized will reflect strength of net selection pressure occurring at the level of the whole-patient. Survival data from the enrolled registry subjects was then correlated with ecogram area. Results: Complete ecological assessments were obtained in 15 subjects participating in the registry. Resulting ecograms demonstrated considerable variation among participants both in derived ecogram area of over 12-fold (range 0-12.7 arbitrary units, mean 4.7±2.9) as well as in morphologic appearance suggesting sensitivity and specificity for strength and character of active selection pressures. Overall survival for registry participants ranged from 14-198 months (median 47 mos.). For 12 subjects with advanced stage disease, survival from time of initial cancer diagnosis demonstrated a moderate degree of inverse correlation with ecogram area (r = -.38, R2= 0.144). Conclusions: A method for making a quantitative ecological assessment of patients with active cancer demonstrated both sensitivity and specificity for differences among participants in a cancer ecology registry study. Overall survival among subjects with advanced disease demonstrated inverse correlation with ecogram area supporting further study to predict cancer evolutionary tendency.
Towards cancer mega-cohorts: A novel homogenization algorithm applied to diverse breast cancer RNA-Seq datasets.
Authors: Ahmed Talal , Carty Mark , Wenric Stephane , Pelossof Raphael 
Published: May 2020

e13507 Background: Recent advances in transcriptomics have resulted in the emergence of several publicly available breast cancer RNA-Seq datasets, such as TCGA, SCAN-B, and METABRIC. However, molecular predictors cannot be applied across datasets without the correction of batch differences. In this study, we demonstrate a homogenization algorithm that allows the transfer of molecular subtype predictors from one RNA-Seq cohort to another. The algorithm only uses cohort-level RNA-Seq summary statistics, and therefore, does not require joint normalization of both datasets nor the transfer of patient information. Using this approach, we transferred a breast cancer subtype (Luminal A, Luminal B, HER2+, Basal) predictor trained on SCAN-B data to accurately predict subtypes from TCGA. Methods: First, we randomly split the TCGA cohort (n = 481 Luminal A, n = 189 Luminal B, n = 73 Her2+, n = 168 Basal) into two sets: TCGA-train and held-out TCGA-test (n = 455 and n = 456, respectively). Second, the SCAN-B cohort (n = 837) was homogenized with the TCGA-train set. Third, a molecular subtype predictor, based on a logistic regression model, was trained on homogenized SCAN-B RNA-Seq samples and used to predict the subtypes of TCGA-test RNA-Seq samples. For baseline comparison, a similar predictor trained on the non-homogenized SCAN-B cohort was tested on the TCGA-test set. The experimental framework was iterated 250 times. Reported P-values reflect a paired one-sided t-test. Results: To quantify model performance, we measured the average F1 score for each tumor subtype prediction from the held-out TCGA test set with and without cohort homogenization. The average F1 scores with vs. without homogenization were: Luminal A, 0.88 vs. 0.85 ( P< 1e-69); Luminal B, 0.74 vs. 0.51 ( P< 1e-183); Her2+, 0.73 vs. 0.53 ( P< 1e-99); Basal, 0.98 vs. 0.97 ( P< 1e-53). Overall, homogenization significantly outperformed no homogenization. Conclusions: We developed a novel homogenization algorithm that accurately transfers subtype predictors across diverse, independent breast cancer cohorts.
Family aggregation of pulmonary ground-glass nodules: Identification of multiple candidate risk loci.
Authors: Fu Rui , Zhang Jia-Tao , Chen Rongrong , Tai Zai-Xian , Lin Hao-Xiang , Su Jian , Chu Xiang-Peng , Zhang Chao , Tang Wen-Fang , Lin Jun-Tao , Nie Qiang , Yang Xue-Ning , Wu Yi-Long , Zhong Wenzhao 
Published: May 2020

e13512 Background: Lung cancer with family history have been emerging gradually of late years in East Asian, especially those presenting as pulmonary ground-glass nodules (GGNs). The predisposition of GGNs with lung cancer family history remains baffling. Methods: This prospective study was registered at clinicaltrials.gov (number NCT04220268) and enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, especially presenting as GGNs. We collected blood and tumor samples from 29 GGNs patients with family history to investigated germline and somatic mutations by whole exome sequencing (WES). As the first part of our study, we focused on 107 nonoverlapping susceptibility loci for lung carcinogenesis identified by recent genome-wide association studies (GWAS) to identify novel rare causal variants. Potential causal variants were further verified in other patients from the families when possible. Results: A total of 461267 single neocleotide variants (SNVs) and 132268 insertion-deletions (InDels) were detected from the 29 index patients. By focusing on exome profiles of the 107 target loci, we identified three key rare mutations, namely MSH5 p.Ala702Thr, ADGRG6 p.Asn338Ile and CCDC147 p.Arg619Trp in two index patients respectively. The minor allele frequency (MAF) of these three variants was extremely low in the general population, which is 1/5008, 2/5008 and 6/5008 respectively in the 1000 Genomes database, and 2/31406, 5/31346, and 5/31394 respectively in the GnomAD database. There three mutations were predicted as probably damaging or disease-causing variations by SIFT or Polyphen. Mutations of MSH5 and CCDC147 were also detected in other patients from the two families. Conclusions: With the identification of highly disruptive risk-conferring MSH5, ADGRG6 and CCDC147 mutations, we confirmed the probably heritable and risk loci exists in the GGNs patients with lung cancer family history in East Asians. Exome sequencing has great potential to identify novel rare causal variants, and more analyses on more patients are still ongoing.
Incidence of mutated DNA damage response pathway and clinically actionable alterations in Chinese patients with unknown primary tumor revealed by comprehensive genomic profiling.
Authors: Wang Shibao , Yu Ruoying , Ou Qiuxiang , Wu Xue , Bao Hua , Shao Yang , Wei Suju 
Published: May 2020

e13523 Background: Carcinoma of unknown primary(CUP) is a clinically aggressive disorder with early tumor dissemination. Without drugs specifically approved for CUP, the outcome of standard chemotherapy is generally poor. Identifying molecular traits of CUP can be beneficial not only for better therapy approach but also potentially for all patients with metastatic dissemination. Methods: From January 2015 to July 2019, 36 unique cases were diagnosed as CUP. DNA was extracted with formalin-fixed paraffin-embedded specimens(FFPEs) or plasma samples and sequenced with 400+ gene panels. Results: In this cohort, identified sites of tumor dissemination included lymph node(36%), bone(19%), liver(8%), lung(5%), gut(5%). More than half of patients were male(65%) with a median age of 62 years old(range:42-82). 83% of CUP patients harboured at least one altered DNA damage repair(DDR) gene including TP53(74%), ATM(19%), ARID1A(11%), ATR(11%). Patients with altered homologous recombination repair (HRR) pathway(42%) showed significantly increased tumor mutational burden(TMB) compared to patients with intact HRR(p = 0.025). MYC gene displayed the most copy number variation (gain, 22%) followed by CDKN2A(loss, 15%) and ZNF217(gain, 15%). Clinically actionable mutations were identified in ten patients including KRAS G12C(3), PIK3CA E545K(2), PIK3CA E542K(1), BRAF V600L(1), EGFR L861Q(1), EML4- ALK(1), ALK L1196M(1). One SCC patient with lymph node metastasis had a PIK3CA mutation E545K and a resistant ALK mutation L1196M without prior ALK TKI treatment, suggesting this patient might benefit from PI3K inhibitors. Unfortunately, He progressed on paclitaxel and cisplatin and died in 2019. The other ADC patient with lymph node metastasis achieved SD on pemetrexed disodium and oxaliplatin. He harboured a KRAS G12C mutation (allele frequency 77.75%), indicating target therapy with KRAS inhibitor might be a better treatment option. Conclusions: Majority of CUP patients showed impaired DDR pathway. TMB of CUP patients with altered HRR pathway is significantly higher than ones with intact HRR. Comprehensive genomic profiling revealed the potentiality of target therapy in CUP patients with clinically actionable mutations.
Distinct genomic and immune microenvironment between thymomas and thymic carcinomas.
Authors: Wang Kaicheng , Lin Suxia , Hou Xue , Liu Yongdong , Li Meichen , Chen Jing , Wang Na , Wang Fang , Bai Jing , Xu Yaping , Chen Likun 
Published: May 2020

e13529 Background: Thymomas and thymic carcinomas which uniformly known as thymic epithelial tumors (TETs) are rare intrathoracic malignancies and a limited studies have been reported addressing the molecular biology and immune discrepancy. The main purpose of this study was to depict the genomic and transcriptomic landscape of thymomas and thymic carcinomas, as well as elucidate the differentiated immune microenvironment. Methods: Totally 15 thymomas and 7 thymic carcinomas patients were enrolled from January 2014 to July 2018. Treatment-naïve tissue samples were collected, and we also obtained matched peripheral blood mononucleocytes as negative control. DNA and RNA were co-extracted and performed with whole exon and transcriptome sequencing. The immune cell infiltration scores were estimated using ssGSEA algorithm. Results: Exome sequencing revealed that GTF2I mutation occurred in all of type A thymomas but was absent in the aggressive subtypes. The median tumor mutation burden of thymomas was 0.12/Mb, significantly lower than thymic carcinomas (median: 1.02/Mb, p = 0.001). Copy number variation was more common in thymic carcinomas than thymomas (83.3% vs 9.1%, p = 0.005). Top mutational signatures enriched in both thymomas and thymic carcinomas included age and Aristolochic acid exposure, while the APOBEC signature was more common in thymomas than thymic carcinomas (81.8% vs 16.7%, p = 0.03). As a confirmed immune escape event, loss of heterozygosity of human leukocyte antigen was identified in 9.1% of thymomas and 50% of thymic carcinomas. Via unsupervised clustering of immune infiltration, all tissue samples were classified into high- and low-infiltration subgroups. Remarkably, up to 71.4% of samples from thymic carcinomas and only 6.7% of samples from thymomas were defined as low immune cell infiltration. In consideration of specific immune cell types, macrophage ( p = 0.01) and neutrophil ( p = 0.02) were enriched in thymic carcinomas while CD56+ NK cell ( p = 0.005) was enriched in thymomas, indicating the evidential discrepancy about immune cell infiltration between two subtypes of TETs. Conclusions: This study elucidated the molecular and immune microenvironment discrepancy between two subtypes of TETs. From molecular perspective, thymomas and thymic carcinomas are entirely different diseases with different etiology and characterized by distinct immune infiltration, and thus should be managed with disparate therapeutic strategies. Findings in this study may also be useful in future targets development and exploration of immunotherapies in TETs.