tbuckley/cabot-search huggingface dataset:
Systemic therapy in patients with advanced cutaneous squamous cell carcinoma of the head and neck.
Authors: Samantha Tam, Mona Gajera, Xiaoning Luo, Bonnie S. Glisson, Renata Ferrarotto, David Ira Rosenthal, Randal S. Weber, Jeffrey Myers, Neil D. Gross
Journal: Journal of Clinical Oncology (2018)

e21550 Background: Treatment of advanced cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is complex. Radiotherapy is often recommended after surgery for high-risk cancers but the role of systemic therapy is less well defined. This study aims to help define the impact of systemic therapy on survival in patients with advanced cSCCHN. Methods: Patients with advanced cSCCHN treated with systemic therapy at MD Anderson Cancer Center from 1995 through 2015 were included in this retrospective cohort study. Patients treated with immunotherapy were excluded. Patients were divided into two groups by the presence of distant metastasis (DM) at presentation. The primary outcome measure was overall survival. A proportional hazards model was used to assess for independent predictors of survival. Results: Of 130 cSCCHN included patients, 21 (16%) were DM-positive and 109 (84%) were DM-negative. Treatment regimens are detailed in Table 1. In DM-positive patients, 12 (57%) received single agent therapy, compared to 69 (68%) in DM-negative patients (p = 0.59). Independent predictors of improved survival were absence of DM at presentation, treatment of locally advanced disease with radiotherapy, and increased ECOG score (Table 1). Conclusions: Survival after treatment with systemic therapy was worse in patients with DM at presentation and poor baseline performance status but improved in those receiving radiotherapy. These data can serve as a historical control for future trials using systemic therapies, including immunotherapy, in advanced cSCCHN. Table 1. Multivariate Proportional Hazards Model for Overall Survival Characteristic N (%) Hazard Ratio 95% Confidence Interval Agea 66 (38-90)b 1.01 0.99-1.03 M Classification 0 109 (84) 1 21 (16) 2.40 1.24-4.66 Radiotherapy No 62 (48) Yes 68 (52) 0.31 0.19-0.51 Chemotherapy Regimen Cisplatin Based 31 (24) Carboplatin Based 40 (31) 0.94 0.47-1.85 EGFR Inhibitor Only 48 (37) 1.40 0.72-2.71 Other 11 (8) 1.31 0.56-3.08 ECOG Performance Status 0 22 (17) 1 69 (53) 1.40 0.72-2.71 2 20 (15) 4.61 2.02-10.49 3 3 (2) 13.73 3.81-49.4 Unknown 16 (12) 2.70 1.16-6.32 a Per year b Median (Range) Abbreviations: EGFR = epithelial growth factor receptor; ECOG = European Cooperative Oncology Group
Viability of tumor cells of breast carcinoma incubated with carbon nanostructures.
Authors: Irena Netikova, Jan Hartinger, Lubos B. Petruzelka, Jakub Tolasz, Petr Vomacka, Vaclav Stengl
Journal: Journal of Clinical Oncology (2016)

e23185 Background: The study results show that surfaces treated with carbon nanostructures such as fullerenes, carbon nanotubes, graphene and graphene oxide in themselves exhibit antibacterial properties. Suitably functionalized carbon nanotubes, graphene and graphene oxide mainly may be used as carriers for cytostatic agents in the targeted treatment of oncological diseases. Methods: Cells from the breast cancer cell line and lung epithelial cells were exposed to aqueous colloidal solutions of graphene oxide and single walled carbon nanotubes (SWCN), then incubated and examined the effect of graphene oxide and carbon nanotubes on viability and structural changes in cells. The graphene oxide we prepared direct from graphene using sulphuric acid, pottasium permanganate and phosphoric acid, The bio-distribution of nanoparticles into the cell body to the subcellular level was monitored by Raman spectroscopy and high resolution transmission electron microscopy. As a model cell population for our study a clonal cell line, EM-G3 and A549 lung epithelial cells (ATCC CCL-185; American Type Culture Collection) was used. The EM-G3 line was derived from a primary lesion of human infiltrating ductal breast carcinoma. Cells were cultured in RPMI-1640 supplemented with 10% fetal calf serum and gentamicin at 37°C in a humidified atmosphere with 5% CO2 . Results: Nanoparticles are unlike other particles able to enter biological membranes into cells, tissues and organs. They penetrate into mitochondria and cell nuclei and influenced the tumor cell viability. Cell viability is significantly decreased with incubation with single- walled carbon nanotubes and multiwalled carbon nanotubes. Incubation with graphene and graphene oxide respectively increase the cell viability and proliferation. Conclusions: Studies have proven the possibility of carbon nanotubes to induce DNA mutations and structural changes, even leading to cell death. In opposite graphene and graphene oxide don’t casue serious DNA damage and increase cell viabillity in vitro. Using phosphoric acid instead toxic chlorates and nitrates at graphene oxyide synthsis enable prepare biologically adaptable graphene oxide.
TCT-559 Prevalence of eye lesions in interventional cardiology staff in Mexico: Estudio iCataratas
Authors: Jose Azpir-Lopez, Jesus Vidaurry-Leal, Adolfo Morales, Francisco Torres-Quintanilla, Ray Ramos-Cazares, Aldo Valdovinos-Bañuelos, Aline Meza-Ramos, Jose Arenas-Diaz
Journal: Journal of the American College of Cardiology (2018)
Genomic subtypes of angiosarcoma: A comprehensive genomic profiling (CGP) study.
Authors: Vinod Ravi, Sally E. Trabucco, Mrinal M. Gounder, Ethan Sokol, Umut Disel, Garrett Michael Frampton, Sherri Z. Millis, Alexa Betzig Schrock, Jon Chung, Vincent A. Miller, Jeffrey S. Ross, Siraj Mahamed Ali
Journal: Journal of Clinical Oncology (2018)

11576 Background: Angiosarcomas (AS) arise from the vascular endothelium of skin and other visceral organs and from such diverse etiologies as exposure to carcinogenic agents or therapeutic radiation. We used CGP to sub-classify AS and to identify genomic alterations (GA) linked to responsiveness to targeted therapy and immune checkpoint inhibitor (ICPI) therapies. Median overall survival of metastatic AS is only 13.1 months. Methods: Hybrid capture based CGP including RNA-seq in a subset of cases was performed on 278 cases of AS including 53 breast angiosarcomas (BA) and 207 soft tissue (STA). Tumor mutational burden (TMB), was calculated from 1.1Mb of sequenced DNA and UV exposure signature was determined. Results: For all AS, the most commonly altered genes were TP53 (38%), MYC amplification (22%), CDKN2A (17%), KDR (12%) and PIK3CA (8.6%). 4q12 (KIT/KDR/PDGFRA) amplifications were increased in STA relative to BA (p = 0.18). MYC amplifications were more frequent in BA than STA (p < 0.001) likely due to radiation associated BA. Three genomic subsets were identified within BA: MYC amplified (mean 60 copies, range 16-277) with increased age (p < 0.0001), KDR altered mutually exclusive to MYC amplified (p < 0.05) and MYC/KDR wildtype, 42% of which have PI3K pathway alterations. A subset (19%) of STA had a UV signature (UV-STA) with a median TMB of 21. We identified 14 AS cases (5%) with KDR T771R none of which harbor other KDR, MYC or tyrosine kinase mutations. Conclusions: Broadly assessing GA in AS has potential benefit from matched therapy and correlates with anatomic and etiologic origin. AS patients may benefit from matched TKIs to kinase fusions, 4q12amp and KDR GAs. KDR T771R defines a new class of AS which should be investigated for a unique non-radiation etiology. The high TMB UV-STA cases suggest potential benefit from ICPI and indicates cutaneous non-melanocytic, non-squamous neoplasms can arise from UV damage. Type (n) Median age Median TMB 4q12 amplified (%) MYC amplified (%) AS (278) 64 (5-88) 2.5 (0-151) 4 22 STA (207) 64 (10-88) 3.2 (0-151) 4.8 18 UV-STA (39) 72 (33-86) 21 (2.4-151) 5.1 2.6 BA (54) 61 (19-88) 2.4 (0-8.9) 0 46 BA-MYC (25) 72 (19-88) 3.2 (0.8-8.9) 0 100 BA-KDR (10) 36 (22-66) 2.4 (0.8-6.45) 0 0 BA-KDR/MYCwt (19) 49 (23-71) 1.6 (0-8.1) 0 0
Generational Differences in Mentoring Relationships—Reply
Authors: Jennifer F. Waljee, Vineet Chopra, Sanjay Saint
Journal: JAMA (2018)

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TCT-728 Long-term Medication Adherence and Prognosis after Successful Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction: Experiences from the Korean Multicenter Registry
Authors: Min Chul Kim, Doo Sun Sim, Young Joon Hong, None Juhan Kim, Youngkeun Ahn, Myung Ho Jeong
Journal: Journal of the American College of Cardiology (2018)
The impact of race and insurance status on survival of patients with non-small cell lung cancer.
Authors: Vinay Nikhil Minocha, Carmen Smotherman, Jason Desmond Hew, Dat C. Pham
Journal: Journal of Clinical Oncology (2017)

e18064 Background: Previous studies have demonstrated disparities in survival outcomes between black and white patients with lung cancer. Black patients are more likely than white patients to have no health insurance or insufficient coverage which may limit their access to treatment. The purpose of this study was to determine the impact of race and insurance status of patients with non-small cell lung cancer on survival outcomes at our institution. Methods: Our study included patients diagnosed and treated for non-small cell lung cancer from 2005 through 2015 at University of Florida hospital in Jacksonville. Cox proportional hazard models were used to study the effect of race (black vs white), insurance, age, tobacco use, family history of cancer and stage on hazard rates for mortality. Time to treatment was compared between blacks and whites using the non-parametric Wilcoxon rank sum test. Results: Of the 1301 patients in our study, 445 (34%) were black. More black patients had Medicaid (24% vs 18%, p = 0.01), and were diagnosed at stage III or IV (81% vs 75%, p = 0.01) compared to white patients. Black patients had higher death rates compared to white patients (80% vs. 71%, p &lt; .0004). Adjusting for stage and insurance, black patients had higher hazard rates for mortality than white patients (HR = 1.18, 95%CI 1.03, 1.35, p = 0.02). Patients with Medicaid and Medicare without supplement had higher hazard rates for mortality compared to other insurance categories (Table). There was no significant difference in time to treatment amongst patients of different races (p = 0.38) and insurance types (p = 0.54). Conclusions: Our study reveals worse survival outcomes in black patients compared to white patients with non-small cell lung cancer, controlling for insurance status and stage at presentation. Future research is needed to determine whether other factors may explain these racial disparities. [Table: see text]
P01.007 Absence of Correlation between Necrosis Volume and Overall Survival in Glioblastoma
Authors: G Hallaert, H Pinson, C Vandenbroecke, D Vanhauwaert, D van Roost, T Boterberg
Journal: Neuro-Oncology (2018)

Necrosis is an important feature of glioblastoma. It is commonly accepted that it reflects the malignancy of the tumor and correlates with survival. We tested this assumption. 140 patients were included in a retrospective study of histologically confirmed glioblastoma patients. All patients were treated according to the “Stupp” protocol, after biopsy or resection. Volumetric analysis was performed using semi-automated segmentation with the S7 StealthStation software (Medtronic) on MPRAGE (Magnetization Prepared-Rapid Echo Gradient) images with 0.9mm thickness (1.5T). MGMT-promotor-gene methylation status was determined. Statistical analyses were performed with SAS software (version 9.4, basic edition, 2012–2016, SAS Institute Inc., Cary, NC, USA). Two-sided Mann-Whitney U test was used to compare mean ranks of tumor necrosis volume between MGMT groups. Separate Cox proportional hazard models were fitted, each adjusted for the type of procedure, to assess the lineair relationship of tumor necrosis volume with mortality hazard. Mean overall survival was 19,3 months. In 107 patients, volumetric analysis could be performed. There was no difference in mean necrosis volume between the MGMT-methylated group and non-methylated group. There was no difference in OS between the group with (n= 93) and without necrosis (p = 0.195). Necrosis volume at diagnosis was not correlated with mortality hazard (p = 0.484) nor when adjusted for surgical procedure (p = 0.473). In this retrospective study using semi-automated volumetric analysis, there is no correlation between necrosis volume at diagnosis of glioblastoma and mortality hazard.
Genomic profiling of primary prostate tumors from patients who develop metastatic castration-resistant prostate cancer (mCRPC).
Authors: Joaquin Mateo, Suzanne Carreira, George Seed, Robert Chandler, David Dolling, Ines Figueiredo, Susana Miranda, Daniel Nava Rodrigues, Claudia Bertan, Diletta Bianchini, Christy Ralph, Robert J Jones, Ursula Brigid McGovern, Mohini Anna Varughese, Omni Parikh, Suneil Jain, Tony Elliott, Nuria Porta, Emma Hall, Johann S. De Bono
Journal: Journal of Clinical Oncology (2018)

5013 Background: mCRPC is enriched for genomic aberrations in TP53, RB1, AR, PTEN and DNA damage repair (DDR) compared to localized prostate cancer. Here we pursued NGS of 470 primary prostate tumors from patients who all later developed mCRPC to evaluate this enrichment in this poor prognosis population. We also compared 49 pairs of same patient primary tumor and mCRPC biopsies. Methods: Libraries for targeted DNA NGS were built using a customized amplicon-based panel (Generead v2 DNAseq, Qiagen) and read in a MiSeq (Illumina). Copy number aberrations (CNA) were assessed using a previously described bioinformatics pipeline (Seed, CCR 2017) for 98 genes. We compared gene aberration frequencies with previously reported cohorts. Results: A total of 470 treatment naïve primary prostate biopsies were sequenced and passed QC filters for mutation and CNA calling. Frequencies for TP53 (27%) and RB1 (5%) aberrations were higher than previously reported for localized prostate cancer (TCGA, p<0.01 each) but lower than for mCRPC (SU2C/PCF, TP53 p = 0.001, RB1 p = 0.07). Conversely DDR gene defects were more common: BRCA2 5% (p = 0.004); CDK12 5% (including 7 cases with two mutations; p = 0.06); ATM 4% (p = 0.2), and PALB2, BRCA1, RAD50, FANCA 1% each. Overall, 2% of primary tumors had detectable mutations in MMR genes. PTEN genomic loss was detected in 12% of primary tumors; 5% had activating mutations of PIK3CA or AKT. Other genes recurrently mutated were SPOP (7%) and CTNNB1 (3%). Surprisingly, in 5 cases (1%) AR mutations at low allele frequencies were detectable prior to ADT. Among the 49 patient matched sample pairs, mutations detectable only in mCRPC were identified in AR (n = 4), TP53 (4), RB1 (3) and CTNNB1 (1). All 9 truncating mutations in BRCA2, ATM, CDK12, PALB2 were shared between treatment naïve and mCRPC samples. Conclusions: TP53 and RB1 aberrations are more common in poor prognosis primary prostate cancer than in localized, more curable, disease (TCGA) but lower than in mCRPC (SU2C/PCF). Aberrations detected only at mCRPC in patient-matched samples support the evolution of these mutations under treatment selection pressures. Poorer prognosis prostate cancers are enriched for BRCA2 aberrations.
Abstract P305: Obesity is Associated with Differentiated Methylation in Glucose Tolerance-related Genes in Adolescents
Authors: Fan He, Arthur Berg, Yuka Imamura Kawasawa, Anna C Salzberg, Edward O Bixler, Alexandros N Vgontzas, Duanping Liao
Journal: Circulation (2016)

Background: Childhood obesity is related to increased cardiometabolic risk in adulthood. Insulin resistance is an established underlying mechanism between obesity and CVD risk. However, the role of epigenetic profiles in this mechanistic link is less investigated, especially in adolescents. Hypothesis: We assessed the hypothesis that obesity is associated with differentiated methylation profiles in genes related to glucose tolerance and its downstream functions in adolescents. Methods: We used data from a sample of 116 adolescents from the population-based Penn State Child Cohort follow-up exam (N=421). Among which, 22 were obese (BMI percentile ≥ 95) and 94 were normal weight (BMI percentile &lt; 85). Peripheral leukocytes DNA was extracted and subject to enhanced reduced representation bisulfite sequencing. The high-throughput assay provided single nucleotide resolution of DNA methylation in CpG sites and surrounding regions. The R package methylKit was used in the post-processing and analysis. Bases with &lt; 10x coverage were excluded in the assay, resulting in a total of 634,418 methylation sites with a minimum of 10 samples per group. Logistic regression was used in the differential methylation calculation. We decided a priori to choose the sites with ≥ 25% difference in methylation with a q value &lt;0.01 for the enrichment analysis. We used Ingenuity Pathway Analysis (IPA) to perform gene-set enrichment analysis for downstream function and effects on the differentially methylated genes. Results: The mean (SD) age of the study sample was 16.3 (2.2) years. The sample consisted of 52% male and 79% white. No significant difference was observed between obese and normal weight groups with respect to demographic characteristics. We identified a total of 2349 bases with statistically significant (q&lt;0.01) differentiated methylation with a difference of 25% or more. IPA revealed 38 sites related to glucose tolerance function, and this function is significantly enriched (p=1.51E-4). Highlighting some individual genes, obese adolescents showed 26.4% higher methylation at a site on the insulin (INS) gene compared to normal weight adolescents, and a site on the gastric inhibitory polypeptide receptor (GIPR) gene had 47.3% differential methylation. Other major significantly differentially methylated glucose tolerance-related genes included interleukin 6 (IL6), and tumor necrosis factor (TNF), and low density lipoprotein receptor (LDLR) genes. Conclusion: Obesity in adolescents is significantly associated with substantially differentiated methylation in glucose tolerance-related genes. It indicated that obesity is related to alternations in the epigenetic profiles related to impaired glucose tolerance, and potentially through which associated with elevated risk of its downstream diseases, such as diabetes and CVD.
Influence of patient characteristics on provider surveillance for colorectal cancer.
Authors: Joanna M. Brell, Debora S. Bruno, Steven A Lewis, John Daryl Thornton
Journal: Journal of Clinical Oncology (2017)

10071 Background: The majority of colorectal cancer (CRC) patients present with resectable disease and benefit from future resection of second primary CRC, local recurrence, and oligometastases. Therefore, in addition to colonoscopy one year after diagnosis, American Society of Clinical Oncology (ASCO) offers consensus recommendations to monitor serum CEA and CT scans for early detection. Limited adherence to guidelines has been reported; we explore the impact of specific patient factors related to CRC on provider prescribing in the first year. Methods: At a single urban safety-net hospital, electronic medical records of patients diagnosed with stages I-III CRC from 2002-2014 were reviewed with IRB approval. Chi-square tests determined extent of associations between categorical variables. Two sample t-tests compared means for continuous outcomes across groups. Cut-off for Type 1 error was alpha = 0.05. Due to minimal change in surveillance guidelines, we applied ASCO 2005 recommendations. Results: Records for 357 patients included 52% females and 40% African-Americans. Median age was 63 years, ever tobacco abuse was 69%. BMI &gt; 30 found in 38%, median weight at diagnosis was 79 kg. Incidence of surveillance and associated variables are in the Table. Conclusions: The providers of this young, urban, almost 40% obese population were &lt; 50% compliant with first year colonoscopy and &lt; 60% compliant with CEA tests. Providers did significantly survey patients with co-morbidities, such as higher weight at diagnosis, in this small study. Most patients complied with orders and primary care providers were least compliant (data not shown). The data supports verification in larger study of safety-net hospitals and future comparison regarding influence of new Survivorship Care Plans on guideline adherence. To improve provider compliance, etiology of nonadherence must be addressed. [Table: see text]
Risk-adapted therapy utilizing upfront brentuximab vedotin (Bv) and rituximab (R) with reduced toxicity chemotherapy in children, adolescents, and young adults with Hodgkin lymphoma.
Authors: Jessica Hochberg, Liana Klejmont, Lauren Harrison, Allyson Flower, Quihu Shi, Jaclyn Basso, Mitchell S. Cairo
Journal: Journal of Clinical Oncology (2017)

10532 Background: Cure rates for CAYA patients with Hodgkin Lymphoma remain high, however are limited by significant toxicity of chemoradiotherapy. Brentuximab Vedotin and Rituximab have shown efficacy in relapsed HL. We hypothesize that the addition of both to combination chemotherapy will be safe in newly diagnosed HL preserving current EFS with elimination of more toxic chemoradiotherapy. Objective: To evaluate the safety and overall response and EFS of Brentuximab and Rituximab in combination with risk adapted chemotherapy in CAYA with newly diagnosed HL. Methods: Age 1-30 yrs with newly diagnosed classical HL given 3 to 6 cycles of chemoimmunotherapy: Brentuximab vedotin with Doxorubicin, Vincristine, Prednisone and Darcarbazine (Bv-AVPD) for Low risk patients or Doxorubicin, Vinblastine, Darcarbazine and Rituximab (Bv-AVD-R) for Intermediate/High risk. Early response measured by PET/CT scan following 2 cycles. Slow responders received an additional 2 cycles of Bv-AVD-R for Intermediate Risk or Ifosfamide/Vinorelbine for High Risk patients. Radiation therapy was given ONLY to those patients not in CR. Results: Total = 19 patients. Median age = 15yr (range 4-23yr). Risk = 2 low, 13 intermediate, 4 high. Toxcity = 1 episode of GrIII mucositis, 1 episode of GrIII infusion reaction to Brentuximab. 17 patients have completed therapy. All 17 patients achieved a complete response to therapy for a CR = 100%. Eleven (58%) have achieved a rapid early response. No patient has required radiation therapy. For 17 patients who have completed therapy, the EFS and OS is 100% with a median follow up time of 915 days (30 months). Conclusions: The addition of Brentuximab vedotin and Rituximab to combination chemotherapy for newly diagnosed Hodgkin Lymphoma appears to be safe. Our early results show significant promise with a CR rate of 100% and 58% rapid early response. We have successfully deleted toxic alkylator, topoisomerase inhibitor, bleomycin and radiation from this treatment regimen. The EFS/OS to date is 100% with a median follow up time of 2.5 years. Further follow up and a larger cohort is needed to determine long term outcomes of this approach. Clinical trial information: NCT02398240.