tbuckley/cabot-search huggingface dataset:
Chemotherapy-induced-fatigue and gene expression profile in peripheral blood mononuclear cells of breast cancer patients receiving adjuvant or neoadjuvant chemotherapy.
Authors: Auro Del Giglio, Fernando Fonseca, Beatriz da Costa Aguiar Alves, Daniel de Iracema Gomes Cubero, Felipe Melo Cruz, Claudia Vaz De Melo Sette, Barbara Bonaparte Ribas de Alcântara, Matheus M Perez
Journal: Journal of Clinical Oncology (2018)

e22168 Background: Chemotherapy-Induced-Fatigue (CIF) is a frequent symptom that impairs patient functioning during chemotherapy for neoplastic disease. We aimed at evaluating if CIF can induce a specific gene expression profile in peripheral blood mononuclear cells (PBMNC) of patients with locoregional breast cancer (LRBC) receiving chemotherapy. Methods: Initially, we sequenced the total transcriptome of the PBMNC of 3 patients who developed CIF collected before and after their initial chemotherapy first cycle. We employed the Ion Torrent™ System (Life Technologies) using the Ion AmpliSeq™ Transcriptome Human Gene Expression Kit (ThermoFisher Scientific). We sequenced a total of 12.345 transcripts from which we selected 26 out of 137 that had significant differential expression before and after chemotherapy. We then validated these results by RT-PCR in a different group of 28 patients with LRBC who developed CIF after their first cycle of chemotherapy and in 6 patients who also received chemotherapy but did not develop CIF (controls). We assessed CIF by the BFI and Chalder Questionnaires. Results: : We noted a significant increase in expression of DUSP18 and RHOBTB1 and a decreased expression of NCAN and RAET1G in patients who developed CIF after Chemotherapy. Control patients only had a significant decreased expression of NCAN. Conclusions: CIF may induce specific changes in gene expression in PBMC of LRBC patients. Some of these changes such as decreased NCAN expression may reflect direct effects of chemotherapy as its also shared by controls. Since NCAN deficiency is involved cognitive and psychiatric illnesses, its significant decrease induced by chemotherapy may underlie cognitive alterations such as chemobrain. Furthermore, CIF may involve gene deregulation of Skeletal muscular (RHOBT1, DUSP18) and immune (RAETG1) systems.
TCT-438 Telemedicine Increases the Access to Primary Percutaneous Coronary Intervention Saving Costs and Lives in ST-Elevation Myocardial Infarction (STEMI). Three-year Analysis of the Latin America Telemedicine Network (LATIN) Program in Sao Paulo East Zone.
Authors: Jamil Cade, Marco Aurelio Pereira, Bruno Janella, Sameer Mehta, Roberto Botelho, Dyonne Costa Neto, Edmar Carvalho, Andre Soares, Carlos Opazo, Monique Bourget, Marco Perin
Journal: Journal of the American College of Cardiology (2018)
Canadian experience managing dose intensity of regorafenib in relation to safety and clinical outcome in metastatic colorectal cancer patients.
Authors: Tasnia Hasan, Aline Mamo, Tomas Kavan, Young soo Rho, Petr Kavan
Journal: Journal of Clinical Oncology (2016)

e15154 Background: Phase III trials CORRECT and CONCUR have shown that Regorafenib confers survival advantage in metastatic colorectal (mCRC) patients. Unfortunately, toxicity often limits its full use. Therefore, upfront priori dose reduction (PDR) is often performed. Its clinical implications and outcomes were reviewed. Methods: A chart review was conducted on 50 mCRC patients who failed standard chemotherapy and received Regorafenib as a 3rd or 4th line of treatment at the Jewish General Hospital, McGill University between 2013-2015. The primary endpoints examined treatment patterns and adverse events (AEs) as per CTCAE v 4.0. A secondary endpoint examined progression free survival (PFS) as estimated by the Kaplan Meier method. Results: Among the 50 patients were 44 males with a median age of 61 (42-82), 24 KRAS mutated (47%) and 19 (KRAS) wild type (38%). All patients had either ECOG 0 or 1 (32% ECOG 0,68% ECOG 1). Upfront PDR of 25% (120 mg) was performed in 26/50 patients (52%). The median duration of treatment was 2.7 months (2-11 months). In most cases, PDR lowered Aes: fatigue (58% vs 73%); diarrhea (5% vs 27%) and hepatotoxicity (11% vs 82%) (p < 0.05). However, the occurrence of skin reactions (47% vs 46%) did not fluctuate much. Throughout the course of treatment, 24/50 patients (48%) receiving a full dose (160 mg) required dose modification, including 8/24 (33%) while 45% required dose interruption or delays secondary to AEs respectively. The median PFS was 3.7 months (95% CI: 3.4 – 7.5 months) with no statistically significant difference in PFS between patients receiving a full dose, compared to those who received PDR upfront.Conclusions: Our findings suggest that patients treated with upfront PDR (120 mg) of Regorafenib had a better tolerance for treatment than those treated with the recommended dose of 160 mg. No further statistically significant differences were observed between the two cohorts in clinical outcomes.
Antitumor effect of a whole tumor cell vaccine expressing human fibroblast activation protein in murine tumor models.
Authors: Meihua Chen, Jin Yi Lang, Tao Li, Qifeng Wang, Guangchao Xu, Shun Lu
Journal: Journal of Clinical Oncology (2017)

e14542 Background: Immunosuppressive factors in the tumor microenvironment reduce the therapeutic efficacy of cancer vaccines; therefore, dampening the tumor immunosuppressive environment while activating antitumor immunity should be a useful approach for cancer therapy. Cancer-associated fibroblasts (CAFs) are among the most important cellular components of the tumor microenvironment and play an important role in the development and progression of tumors. Fibroblast activation protein α (FAPα) is a type II transmembrane protein specifically expressed by CAFs in most epithelial cancers. Gene sequence homology between human and murine FAPα is 90%. Heterogeneity of genes in the evolution of the formation of such nuances can be utilized to break immune tolerance, enhance immunogenicity, induce tumour cell autoimmune responses and thus inhibit tumor growth. Methods: Tumor cells were transfected with human FAPα plasmids employing the cationic lipid DOTAP. Its antitumor effects were investigated in three established tumor models. The potential immune mechanisms were investigated through adoptive immunotherapy and 51 Cr release assay. The distributions of the immune cells in the tumor microenvironment were detected by immunohistochemical staining and flow cytometry. Results: Our results shown that whole tumor cell vaccine expressing human FAPα significantly inhibit tumor growth and prolong the survival of tumor bearing mice. This antitumor immune response was involved both of cellular and humoral immune responses. FAPα specific neutralizing antibodies were found in the serum of vaccinated mice and CAFs were significantly reduced within the tumors. Furthermore, this vaccine enhanced the infiltration of CD4+ T cells and CD8+ T cells, and suppressed the accumulation of immunosuppressive cells in the tumor microenvironment. Conclusions: These findings suggest that whole tumor cell vaccine expressing human FAPα inhibit tumor growth by producing FAPα specific neutralizing antibodies and CTLs, and targeting tumor cells and CAFs. These observations provide a new strategy for the clinical use of genetically modified tumor cells as cancer vaccines.
Skin type differences in solar‐simulated radiation‐induced oxidative stress
Authors: S. Albrecht, S. Jung, R. Müller, J. Lademann, T. Zuberbier, L. Zastrow, C. Reble, I. Beckers, M.C. Meinke
Journal: British Journal of Dermatology (2018)

Human skin protects the body from external damage, pathogens and oxidative stress factors such as ultraviolet (UV) radiation. Excessive exposure to UV radiation can lead to increased production of free radicals and hence to skin damage such as inflammation, premature skin ageing and skin cancer. Besides UV, the visible and near infrared (NIR) regions are also a source of radical production. Half of all free radicals are induced by the visible + NIR region of the solar spectrum in people with skin types I–III, but data on the effects in people with skin types IV–VI are missing. This in vivo pilot study addressed the distribution of radical production in skin types IV and V during irradiation in the UV, visible and NIR spectral regions, comparing the first results with those of skin type II. The measurements were performed in vivo using L‐band electron paramagnetic resonance spectroscopy and the spin probe PCA. In skin types IV–V most radicals were induced in the visible + NIR region, followed by the NIR and UV regions of the sun spectrum. Significantly (P ≤0·05) more radicals were induced in skin types IV–V than in type II during NIR irradiation, whereas skin types IV–V exhibited significantly less UV‐induced radicals (P ≤0·01) than skin type II. All spectral regions (UV, visible and NIR) cause free radical formation in skin types II and IV–V. After 4 min of solar‐simulated exposure (UV‐NIR), the radical formation in skin types IV–V is 60% of that in skin type II. Therefore people with darker skin types also need solar protection.
Local interventions for actinic keratosis in organ transplant recipients: a systematic review
Authors: M.V. Heppt, T. Steeb, A.C. Niesert, M. Zacher, U. Leiter, C. Garbe, C. Berking
Journal: British Journal of Dermatology (2018)

BackgroundActinic keratosis (AK) in organ transplant recipients (OTRs) has a high risk of progressing to invasive squamous cell carcinoma of the skin. Thus, early and consequent treatment of AKs is warranted in OTRs.
Comparative analysis of cell cycle parameters in primary and recurrent soft tissue sarcomas.
Authors: Inna Arnoldovna Novikova, Evgeniya M. Nepomnyashchaya, Timur Aliev, Elena Yurievna Zlatnik, Olesya N. Selyutina, Elena Petrovna Ulianova, Larisa Nikolaevna Vashchenko, Tatiana Valeryevna Ausheva Ausheva, Elena A. Andreyko
Journal: Journal of Clinical Oncology (2017)

e22538 Background: The purpose of the study was to determine DNA content and distribution of cells in cell cycle phases by flow cytometry in patients with primary and recurrent soft tissue sarcomas. Methods: 60 patients with soft tissue sarcomas (STS) were recruited: 30 with primary tumors and 30 with recurrent ones. Mean age of patients with primary STS was 56±5.4 years, with recurrent STS – 55±6.7 years. DNA content was determined using the BD Facs Cantoo II flow cytometer with CycleTEST PLUS DNA Reagent Kit (Becton Dickinson). The data were processed using ModFit LT program. Results: Comparative analysis of the cell cycle kinetics showed an increase in the percentage of cells in G2+M phase by 2 times in diploid and by 2.1 times in aneuploid recurrent tumors in comparison with primary ones (1.8±0.5% vs. 0.9±0.1% for diploid tumors; 5.4±2.2% vs. 2.6±0.7% for aneuploid tumors). An increase in the percentage of aneuploid tumors was found in recurrent G2 and G3 tumors (from 50% in primary to 66.7% in recurrent G2 tumors and from 63.25% in primary to 85% in recurrent G3 tumors). Mean content of aneuploid cells in recurrent G2 tumors was 2.2 times higher (p≤0.05), while the differences in primary and recurrent G3 tumors were not significant. The percentage of aneuploid tumors depended on the disease stage and increased in stages IIb and III in recurrent tumors, compared to primary ones (from 37.5% to 71.4% in recurrent st. IIb; and from 65% in primary st. III to 72.7% in recurrences) (p≤0.05). Conclusions: DNA analysis by flow cytometry demonstrated a high biologic potential of both primary and recurrent tumors. Some values in the mitotic cycle in recurrent tumors were probably associated with adjuvant therapy, as well as influenced by the coefficient of two parameters – the percentage of cells in G2+M phase and the cell loss factor determining a high malignant potential of these tumors.
A meta-analysis on ABVD administration in HIV+ patients with advanced stage Hodgkin’s lymphoma (HL).
Authors: Kritika Subramanian, Jeffrey M. Switchenko, Christopher Flowers, Mohammad Khurram Khan
Journal: Journal of Clinical Oncology (2018)

e19522 Background: HIV+ patients have approximately 15% higher risk of developing Hodgkin lymphoma (HL) than the general population, and the 5-year overall survival (OS) from HIV+ patients with HL was 14% less than that of non-HIV HL patients2,3. Limited data exist on the value of standard therapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in HIV+ patients with advanced stage HL. We combined our own, institutional data with others, to produce a meta-analysis examining the effectiveness of ABVD in HIV+ patients. Methods: After obtaining institutional board (IRB) approval we examined 340 HL charts and identified 7 HIV+ patients who received ABVD and compared their outcome against 180 HIV negative patients. We further pooled our data with two other published, non-overlapping HIV+ and advanced stage Hodgkin’s lymphoma cohorts with an n = 229 (Olszewski 2016) and n = 71 (Hentrich 2012) to examine OS and progression-free survival (PFS). Two HIV- advanced stage HL cohorts were also included with n = 275 and n = 48 (Sorigué 2017; Carde 2016). Results: In the Emory cohort of HIV+ patients, the 2-year PFS was 80.0%, and a 2-year OS was 85.7%. The 2-yr PFS and OS for the HIV+ meta-analysis (n = 307) was 74.5% [0.69, 0.80] and 85.7% [0.78, 0.87] respectively. The 2-yr PFS and OS for the HIV- meta-analysis (n = 503) was 74.0% [0.46, 0.86] and 86.7% [0.68, 0.99] respectively. We did not find any difference in PFS (p = 0.98) and OS (p = 0.98) when comparing the HIV- and HIV+ cohorts. Conclusions: ABVD appears to be a reasonable strategy for HIV+ patients with advanced stage HL. Further trials, are needed to validate these findings.
Correlation between natural killer cell activity and treatment effect in patients with disseminated cancer.
Authors: Torben Hansen, Line Nederby, Ahmed Hussien Zedan, Inge Mejlholm, Jon Henriksen, Karina Dahl Steffensen, Caroline Brenner Thomsen, Louise Raunkilde, Lars Henrik Jensen, Anders Kristian Moeller Jakobsen
Journal: Journal of Clinical Oncology (2018)

12029 Background: Prediction of treatment effect remains an unsolved problem in patients with malignant tumors. The aim of the present study was to analyze the possible correlation between Natural Killer (NK) cell activity as measured by the NK Vue assay and treatment effect in patients with different tumors. Methods: The study included four different trials encompassing palliative treatment to patients with prostate, ovarian and colorectal cancer. The current results are based on 93 patients with mature data on treatment effect. Blood samples were collected at baseline and prior to each treatment cycle into NK Vue Promoca tubes and placed in an incubator at 37°C within 15 minutes of sampling. Following 24 hours of stimulation the level of interferon-gamma (IFNγ) in the plasma was measured by ELISA (NK Vue Gold) as a surrogate for NK cell activity. Response rates (RR) and progression free survival (PFS) were endpoints. Results: The relationship between NK cell activity and treatment response was similar across tumor types and treatment, and data were consequently pooled for analyses. The outcome suggested a classification into three groups. During the first two months of treatment the IFNγ dropped to an abnormal level ( < 200 pg/mL) in group 1 or remained at an abnormal level (n = 35). In group 2 (n = 30) the level remained within a normal range ( > 500 pg/mL), while in group 3 (n = 28) it increased from an abnormal to a normal level. The RR were 29%, 47%, and 82%, respectively, p = 0.0001. The median PFS was 2.6 months (95% confidence interval (CI) 2.1-3.9), 10.0 months (95% CI 6.5-11.1), and 8.3 months (95% CI 6.5-8.7), respectively, p < 0.0001 (log-rank). Conclusions: The results suggest a correlation between NK cell activity and treatment effect across different tumor types and treatments. Patients lacking the ability to mount an immune response during the first two months of treatment have a very poor prognosis and clinical benefit of the treatment is questionable.
The association of <i>BRCA1</i> and <i>BRCA2</i> mutations on prostate cancer risk, frequency, and mortality: Systematic review and meta-analysis.
Authors: Mok Oh, Rana Aljadeed, Nasser Mubarak Al Khushaym, Abdulhamid Althagafi, Saad Fallatah, Hani M. Babiker, Ali McBride, Ivo Abraham
Journal: Journal of Clinical Oncology (2018)

5060 Background: A prior meta-analysis (Fachal, Prostate, 2011) suggested no association between BRCA1 mutation and prostate cancer (PCa). Several additional BRCA2 studies have shown an association with PCa risk and mortality. We conducted a systematic review and meta-analysis of BRCA1 and BRCA2 studies to estimate PCa risk in BRCA mutation carriers, evaluate the frequency of BRCA mutation carriers in PCa patients (pts) and compare survival rate among BRCA mutation carriers and non-carriers. Methods: PubMed/MEDLINE, Embase and Cochrane databases were searched for relevant studies for the above objectives. Meta-analyses were conducted using unadjusted odds ratio (OR) with 95% confidence interval (95%CI) for PCa incidence; frequency (%) of BRCA mutation in PCa pts; and hazard ratio (HR) with 95%CI for cancer-specific survival (CSS) and overall survival (OS). Random effects analyses were performed for overall BRCA (BRCA1 or BRCA2), with subgroup analyses for BRCA1 and BRCA2 separately. Results: 10 cohort, 10 case-control, 38 frequency and 11 survival studies were included. Being a BRCA carrier was associated with a significant increase in PCa risk (OR 1.97, 95%CI 1.60-2.42), with BRCA2 mutation being associated with a greater risk of PCa (OR 2.72, 95%CI 2.10-3.54) than BRCA1 (OR 1.39, 95%CI 1.07-1.81). The frequency of BRCA1 and BRCA2 carriers in PCa patients was 1.8% and 2.7% respectively. OS (HR 2.21, 95%CI 1.64-2.30) and CSS (HR 2.63, 95%CI 2.00-3.45) were significantly worse among BRCA2 carriers compared to non-carriers, whereas OS (HR 0.47, 95%CI 0.11-1.99) and CSS (HR 1.07, 95%CI 0.38-2.96) were not statistically significant when comparing BRCA1 carriers and non-carriers. Conclusions: Meta-analyses revealed a 1.97-fold greater risk of prostate cancer in overall BRCA mutation carriers. This elevated PCa risk was attributable largely to a 2.72-fold greater risk of PCa in BRCA2 carriers and a moderate 1.39-fold greater risk in BRCA1 carrier. BRCA2, but not BRCA1, mutations were associated with higher PCa mortality. BRCA mutation may be a clinical factor to stratify high-risk patients and provide clinical strategies for more effective targeted treatments for patients with PCa.
Genomic profiling of Chinese pancreatic adenocarcinoma and the implications for therapy.
Authors: Songzhu Yang, Linlin Qu, Yujie Feng, Jun Guo, William Lewis, Jicheng Yao, Yue Che, Weifeng Wang, Ming Yao
Journal: Journal of Clinical Oncology (2018)

e13515 Background: Pancreatic adenocarcinoma (PAC) remains one of the most deadly diseases with short-lived treatment responses. KRAS is the dominant driver gene in PAC, contributing to approximately 90% of PAC. Studies had revealed molecular profiles of Western population, but the mutational signatures of Chinese PAC need to be further investigated. Methods: FFPE tumor and matched blood samples of 81 Chinese PAC patients (pts) including 52 males (64.2%) and 29 females (35.8%) with a median age of 60 (range: 37-86) were collected for next-generation sequencing (NGS)-based multi genes panel assay. Genomic alterations including single base substitutions, short and long insertions/deletions, copy number variations, and gene rearrangement and fusions in selected genes were assessed. Results: In Chinese PAC pts, the top 10 mutated genes were: KRAS (95.1%), TP53 (81.5%), CDKN2A (25.9%), SMAD4 (22.2%), ARID1A (17.3%), GATA6 (8.6%), FGFR1 (8.6%), ATM (7.4%), CDK6 (6.2%) and STK11 (6.2%). In total, 51.9% of the pts harbored at least one actionable genomic alterations. We compared our Chinese cohort with TCGA data, which were mainly composed of Western population. DNA damage repair related genes including BRCA1/2, PALB2 and ATM accounted for approximately 10% in both Chinese and Western populations (9.9% vs. 9.4%). However, we observed a higher percentage of FGFR1 alteration in Chinese pts (8.6% vs. 4.7%). The median TMB value of Chinese PAC pts was 4.8 muts/Mb (range: 0-24.8), and 8.8% of the pts had TMB value greater than 10 muts/Mb. In addition, loss of function mutation of PBRM1 was found in 2.5% of the pts. Conclusions: Our study revealed the mutational signatures of Chinese PAC pts, and found that the genomic alteration frequency of the potential therapy target FGFR1 was higher than its TCGA counterpart. Moreover, approximately 10% of the pts harbored mutations in DNA damage repair genes, suggesting potential therapy options using PARP inhibitors. Further analyses of these genomic alterations associated with clinical features in PAC are still needed.
Clinical significance of relative dose intensity during pazopanib treatment to advanced/metastatic soft tissue sarcoma (STS) patients.
Authors: Kenji Nakano, Yoshiya Sugiura, Shinichiro Taira, Junichi Tomomatsu, Keiko Hayakawa, Yuki Funauchi, Tabu Gokita, Taisuke Tanizawa, Keisuke Ae, Seiichi Matsumoto, Shunji Takahashi
Journal: Journal of Clinical Oncology (2016)

e22541 Background: The correlation between relative dose intensity (RDI) and clinical outcome of pazopanib therapy to STS patients in real-world clinical practice has not been established. Methods: We retrospective reviewed medical records of STS patients treated with pazopanib between November 2012 and December 2015 in our institute. Based on clinical courses of pazopanib treatment, RDI for 12 weeks (12W-RDI) of each patient was estimated, and the relationship of 12W-RDI and prognoses and predictive factors of keeping high RDI were evaluated. Results: Total of 78 STS patients were enrolled. Median age was 51.9 years old (range 19-75, and distributions of pathological diagnoses were as follows; Leiomyosarcoma (n = 17), synovial sarcoma (n = 11), liposarcoma (n = 13), and other STS types (n = 37). Median follow-up time was 8.0 months (range: 0.9-33.4). All patients except for one started pazopanib at 800 mg daily and treatment interruption and dose reduction due to adverse events were observed in 44 (56 %) and 21 (27 %) patients, respectively. 43 (55 %) patients achieved 12W-RDI≧75% and they had significantly longer progression-free survival (4.2 months vs 1.6 months, p < 0.001) and overall survival (10.8 months vs 7.4 months, p = 0.009) than those who did not achieve 12W-RDI≧75% by log-rank test. In logistic regression analysis, baseline status of high serum albumin (≧4 g/dL) and high creatinine clearance (≧100 mL/min) were predictive for the achievement of RDI≧75 during 12 weeks (odds ratio: 4.9, p = 0.003, and odds ratio: 4.0, p = 0.009, respectively). Conclusions: Treatment interruptions and dose reductions of pazopanib were modestly observed in pazopanib treatment. Maintaining 12W-RDI≧75% of pazopanib was related to longer prognoses to STS patients, and the baseline serum albumin and creatinine clearance could be predictive factors for achieving high RDI.