tbuckley/cabot-search huggingface dataset:
Association of CD49d expression with small lymphocytic lymphoma (SLL) presentation of chronic lymphocytic leukemia (CLL).
Authors: Paolo Strati, Kari G. Chaffee, Sara J Achenbach, Susan L. Slager, Timothy Call, Neil E. Kay, Wei Ding, Sameer Ashok Parikh, Diane F Jelinek, Curtis A Hanson, Tait D. Shanafelt
Journal: Journal of Clinical Oncology (2016)

e19008 Background: CD49d is a surface integrin expressed on CLL lymphocytes that facilitates interactions between CLL B-cells and stromal cells in the microenvironment. CD49d has been shown to have robust prognostic value, with shorter time to treatment and overall survival among patients with higher CD49d expression. Some case series suggest high expression of CD49d in CLL patients may also be associated with lymphadenopathy or presentation as SLL. Methods: We used the Mayo Clinic CLL database to evaluate the association between CD49d expression and the presence/absence of nodal disease at the time of diagnosis in a cohort of patients with newly diagnosed early stage CLL/SLL. All patients seen at our center between 08/2001 and 12/2015 and who had pre-treatment CD49d testing available within 1 year of the date of diagnosis were included in the study. The percent of clonal B-cells expressing CD49d was summarized as a continuous variable. Consistent with previous publications, for dichotomous classification, CD49d was considered positive if > 45% of cells expressed CD49d. Results: The study included 704 patients. At diagnosis, 389 patients had Rai stage 0 CLL, 136 had Rai stage I CLL, and 179 had SLL. At the time of diagnosis, CD49d was positive in 17.0% of patients with CLL Rai stage 0, 30.1% of patients with CLL Rai I (p = 0.726 vs CLL Rai 0), and 51.4% of patients with SLL (p < 0.001 vs CLL Rai 0). The median % of leukemic cells expressing CD49d at diagnosis was 3.7% (IQR, 2%-14%) in patients with Rai stage 0, 7% (IQR, 1%-71%) in patients with CLL Rai stage I (p = 0.096 vs CLL Rai 0), and 49% (IQR, 13%-92%) in patients presenting as SLL (p < 0.001 vs CLL Rai 0). Similar results were observed if employing a 30% cut-off for CD49d positivity. Conclusions: CD49d is associated with SLL presentation of CLL. These observations suggest CD49d expression may identify a cohort of CLL patients whose clinical course will be dominated by lymphadenopathy as opposed to bone marrow infiltration and cytopenias. Our study has implications that a high or elevating CD49d should be studied further to ascertain its relationship to nodal progressive disease for a given patient. Additional analysis is ongoing and data will be presented at the meeting.
What is the impact of treatments received for MBC on the ability to perform activities of daily living, symptom burden, and productivity?
Authors: Amye Tevaarwerk, Carolina M. Reyes, Hans-Peter Goertz, Mary Lou Smith, Preeti S. Bajaj, Elda Railey, Deepa Lalla
Journal: Journal of Clinical Oncology (2016)

e18118 Background: A greater proportion of women diagnosed with MBC are working at the time of diagnosis and through their treatment. We surveyed women with MBC to understand the impact of treatments on symptom burden, ability to perform activities of daily living (ADL), and productivity. Methods: We invited members of three advocacy groups currently living with MBC to participate in a cross-sectional, web-based survey. Respondents completed the MD Anderson Symptom Inventory (MDASI), Rotterdam Symptom Checklist-ADL (R-ADL) and the Work Productivity and Activity Impairment (WPAI) questionnaires. Adjusting for age, race, education, US region, health insurance, and work status, we evaluated outcomes for respondents if they received one of the following agent classes at any time since the diagnosis of MBC: Biologics+Hormonals(BH), Chemo+Biologics(CB), Chemo+Hormonal agents(CH). We also evaluated relationships between symptom burden, ability to perform ADLs, and level of impairment at work. Results: We received 1,169 responses from US residents with complete covariate information. 545 respondents received all 3 agent classes and 116 received only one agent class. Adjusted means for agent classes are reported in the table. Patients receiving BH reported significant differences compared to CB and CH across all measures evaluated. Ability to perform ADLs and symptom burden score were negatively correlated (Pearson r=-0.58, p<0.001). In adjusted analyses, as symptom burden increased, respondents also reported a greater degree of impairment at work (p<0.0001), and level of impairment at work decreased with an increase in the respondent’s ability to perform their ADLs (p<0.0001). Conclusions: These results show that treatments received can affect a number of outcomes including the severity/intensity of symptom burden, the ability to perform ADLs and productivity at work. Agent Class received N MDASI SS MDASI SI R-ADL % impairment WPAI BH 121 3.64* 3.95* 26.2* 36.1* CB 275 4.8 5.1 20.6 60.7 CH 109 4.7 5.0 21.6 56.5 * statistically significant vs. CB, CH (p<0.001). For the MDASI and the WPAI, lower is better. For R-ADL, higher is better.
The psychosomatic state of patients with differences in the prevalence of cancer process in biliopancreatic duodenal zone and in the volume of a surgical intervention.
Authors: Galina Vitalyevna Zhukova, Oleg Ivanovich Kit, Umar Muhmadovich Gaziev, Elena Alekseevna Shirnina, Alla Ivanovna Shikhlyarova, Alexander V. Snezhko, Izabella Torpudzhyan, Stanislav Stanislavovich Mezentsev
Journal: Journal of Clinical Oncology (2017)

e15619 Background: Associations between the psychosomatic state of cancer patients and the disease course, treatment and complications are poorly studied. Our purpose was to study adaptation and mental statuses of patients with biliopancreatoduodenal cancer (BPDC) at different disease stages with various volumes of surgical intervention. Methods: Parameters of the psychosomatic state of 32 patients with BPDC were studied before treatment, 1 day after surgery and at the dismissal from hospital. Adaptation statuses were assessed by a character and intensity of the general nonspecific adaptation reactions (AR) with scoring by the Antistress program. Mental statuses were evaluated by the levels of personal (PA) and situational anxiety (SA) by the Spielberger-Khanin method. Patients with pancreatoduodenectomy (PDE, 19 patients) and those with palliative intervention for a bypass anastomosis (BA, 13 patients) were compared. Patients with stage II disease prevailed in the PDE group and stage III-IV – in the BA group. Results: Patients with PDE had a higher adaptation status than patients with BA (p &lt; 0.05). It resulted in lower rates of most adverse AR prior to the surgery (21% vs. 61%, respectively) and a higher AR score 1 day after the surgery (187±39 and 80±24, respectively). The AR score of 18 and lower 1 day after PDE was associated with postoperative complications. A tendency to a higher number of patients with a high PA was found in the PDE group compared to the BA group (58 and 31%, respectively) which could affect the time of pathology detection in patients of different groups. Patients of the two groups showed differences in the SA dynamics determined by the volume of surgical intervention. Conclusions: The association between the psychosomatic state of BPDC patients and the disease stage and volume of surgical intervention was demonstrated. The AR scoring 1 day after the surgery allows prognosis of postoperative complications.
Association of baseline body mass index (BMI) with overall survival (OS) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) treated with nivolumab (N) and pembrolizumab (P).
Authors: Jizu Zhi, Sean Khozin, Deborah Kuk, Aracelis Z. Torres, Rachael Sorg, Shannon E. Lee, Rebecca A. Miksad, Richard Pazdur, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2018)

6553 Background: Poor performance status (PS) is associated with worse clinical outcomes for pts with mNSCLC. However, in the real-world PS is not routinely captured in electronic health records (EHRs). Pts with poor PS may also have cachexia and low BMI. As such, underweight BMI may be a proxy for deteriorated real-world PS when PS score is missing. We have shown that female gender and positive EGFR/ALK mutation status predict longer OS, but not age or other factors. We explore the association of baseline BMI with OS in real world mNSCLC pts treated with N or P. Methods: We conducted a retrospective analysis of mNSCLC pts treated with N or P using de-identified real-world data (RWD) from the Flatiron Health network. Index date was start of first single agent N or P. Baseline BMI (kg/m2) was calculated from the most recent weight and height recorded within 30 days prior to index date and categorized as: Underweight ( < 18.5), Normal (18.5 – 24.99), Overweight (25 – 29.99), and Obese (30+). Association of baseline BMI with OS was assessed using multivariate Cox proportional hazards model adjusted for gender, age, and EGFR/ALK status prior to N or P start. Eligible pts had valid values for all parameters. Results: 703 pts met inclusion criteria (Table). For OS, gender was significant overall, EGFR/ALK mutation was significant overall and for women. Conclusions: We observed BMI-based differences in OS for real world mNSCLC pts treated with N or P. Underweight BMI is associated with shorter OS and obese BMI is associated with longer OS. In pts with cancer, declining BMI and PS may signal biologic processes indicative of progressive disease that negatively affect OS. Since PS data is commonly missing in EHRs, our results suggest that BMI can potentially be used as a proxy for poor PS in RWD studies. Investigating the impact of changes in BMI on OS and correlation of BMI with PS would further verify this assumption. BMI N (%) All Male Female aHR p aHR p aHR p Normal 326 (46) - - - - - - UnderWeight 59 (8) 1.66 0.002 2.09 0.004 1.4 0.111 OverWeight 207 (29) 0.82 0.071 0.9 0.503 0.71 0.048 Obese 111 (16) 0.75 0.039 0.74 0.131 0.75 0.145 - = Reference, aHR = adjusted Hazard Ratio
Comprehensive analysis of genomic alterations in Chinese high-grade serous ovarian carcinoma patients.
Authors: Fangfang Zhong, Yu Wang, Rong Shen, Li Zhou, XiaoWei Dong, Xuedong Pan, Lei Mei, Jinwei Hu, Donglin Chen, Weiwei Shi, Xianrong Zhou, Kai Wang
Journal: Journal of Clinical Oncology (2018)

e17535 Background: High-grade serous ovarian carcinoma (HSOC) is a major subtype of ovarian epithelial carcinoma with poor overall survival. It has been previously documented that HSOC has prevalent TP53 mutations and deleterious BRCA1/2 germline mutations. Understanding genomic alterations is critical to improving current therapeutic strategies for HSOC patients (pts). Methods: FFPE and matched normal tissue (26 blood and 20 paracancerous tissue) were collected from 46 Chinese HSOC pts with a median age of 53 years (range 36-82). All cases were reviewed and confirmed by two experienced pathologists. DNA was extracted and ultra-deep NGS was performed on hybridization captured libraries of 450 cancer genes to detect all classes of genomic alterations including substitutions, short and long indels, copy number alterations, and gene rearrangements. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were calculated based on the NGS data. Results: A total of 330 genomic alterations were identified in the 46 HSOC pts, with an average of 7.2 alterations per individual. The top altered genes were TP53 (98%) and BRCA1 (24%), followed by a long tail of genes altered in less than 13% of pts. Five pts (11%) harbored both TP53 and KRAS mutations (two had KRAS G12V, one G12D, one A59G and one D57N). BRCA1/2 mutations were observed in 33% (15/46) pts. Other common altered genes included APC, ERBB2, FAM135B, NF1, PTK2, and RB1. The median TMB was 8.0 mut/Mb (range 0.8-283). Five out of 46 pts were identified as MSI-H (11%). Conclusions: Surprisingly, 5 Chinese HSOC cases (11%) were detected to have both TP53 and KRAS mutations, a much higher percentage than that of TCGA (less than 1%). This might indicate a unique molecular subtype of Chinese HSOC. We also identified a higher proportion of BRCA1/2 mutation carriers (33%) compared with TCGA (22%), suggesting a higher percentage of Chinese HSOC pts might benefit from PARP inhibitors. With the ability to detect all types of genomic alterations, TMB, and MSI at once, NGS-based DNA testing offers a comprehensive understanding of the potential treatment options for ovarian cancer, including targeted therapies and/or immunotherapy such as checkpoint inhibitors.
Targeting EZH2 in acral lentiginous melanoma (ALM).
Authors: Allison Izsak, Keith Michael Giles, Kevin Paul Lui, Sarah A. Weiss, Una Moran, Eleazar Vega-Saenz de Miera, Jennifer Stein, Ann Yeelin Lee, Farbod Darvishian, Richard L. Shapiro, Russell S. Berman, Anna C. Pavlick, Melissa Wilson, Iman Osman
Journal: Journal of Clinical Oncology (2017)

9534 Background: Efforts to identify targeted therapies that can improve treatment outcome in metastatic ALM have been unsuccessful. In a previous genomic screening, we identified copy number amplification of the histone methyltransferase EZH2 in 47% of ALM cases, a higher frequency than previously reported in cutaneous melanomas (CM) (5%). Here, we tested the hypothesis that increased EZH2 expression contributes to ALM progression and may confer selective sensitivity to EZH2 inhibition. Methods: EZH2 expression was examined by immunohistochemistry (IHC) in 51 primary (21 stage I, 13 Stage II and 17 Stage III) and 23 metastatic (11 in transit, 8 nodal and 4 visceral) ALM cases with extensive clinicopathological data and protocol-driven follow up. Colony formation and cell proliferation was assessed following treatment of ALM and CM cell lines with three EZH2 inhibitors, including GSK126, currently in clinical trials. The effect of GSK126 on H3K27me3 and downstream EZH2 targets was analyzed by western blotting. Results: EZH2 is commonly overexpressed in both primary (30/51; 65%) and metastatic (20/23; 87%) ALM cases, with a significant increase in mean IHC score between primary and metastatic tumors (1.9 vs. 2.7, respectively, p = 0.047). EZH2 expression increased in 6/10 metastatic ALM tumors compared to their matched primary tumors. ALM tumors with EZH2 gene amplification showed increased EZH2 protein expression; however more cases showed overexpression with no amplification suggesting a potential epigenetic component of EZH2 regulation. GSK126 significantly suppressed ALM colony formation at lower doses compared to CM (1 µM vs. 5 µM, respectively). EZH2 inhibition also increased expression of the downstream tumor suppressor E-cadherin in ALM but not in CM cell lines. Finally, ALM cell lines had significantly lower basal H3K27me3 levels than CM cell lines, suggesting an additional, histone methyltransferase-independent function of EZH2 in ALM. Conclusions: Our data demonstrate thatEZH2 upregulation is common in ALM, and suggest that it may play a role in ALM’s metastatic progression that requires further investigation. Selective sensitivity of ALM cell lines to EZH2 inhibitors supports the therapeutic potential of EZH2-targeted therapy in ALM.
Modifiable risk behaviors in adolescents and young adults (AYA) with cancer.
Authors: Lia J. Smith, Andrea C. King, Xiaolei Lin, Donald Hedeker, Tara O. Henderson
Journal: Journal of Clinical Oncology (2017)

e18095 Background: A cancer diagnosis in adolescents and young adults (AYA) comes at a complex developmental interval that often coincides with risky behaviors, such as substance use. Modifiable risk behaviors are an important area of research to minimize morbidity for AYA. Our goal was to examine substance use, affect, and other health indicators in a diverse AYA cancer patient sample. Methods: We identified patients between the ages of 18-39 years and 6 or more months from date of cancer diagnosis. Measures included demographic, general health and substance use variables, the Center for Epidemiologic Studies Depression Scale (CES-D), and the State-Trait Anxiety Inventory (STAI-T). Linear trend analyses were performed to examine group differences. Backward-selection ordinal regression analyses identified specific factors associated with risky health behaviors. Results: Participants (60% male; Mage = 27; 70% White; 14% Black) included 100 patients with primary diagnoses of lymphoma (N = 45); leukemia (N = 37); sarcoma (N = 10); other (N = 8). Median time from cancer diagnosis was 2 years (range 6 months - 20 years). Past year alcohol, cigarette, and marijuana use was reported in 80% ,15%, and 33% of participants, respectively. We classified three subgroups based on past year alcohol and smoking, including non-smoker/non-drinker (n = 20), non-smoker/drinker (n = 65), and smoker/drinker (n = 15). Linear trend analyses indicated that the groups did not differ on time since diagnosis, but the smoker/drinker group initiated drinking younger ( p&lt; 0.01), were more likely to use marijuana in the past year ( p&lt; 0.01), and had increased depressive symptoms (CES-D; p&lt; 0.01), anxiety (STAI-T; p&lt; 0.05), body pain ( p&lt; 0.05), and poorer sleep quality ( p&lt; 0.05). Backward model selection treating outcome categories as ordinal indicated that frequent marijuana use and poor sleep quality were associated with being a past year smoker/drinker. Conclusions: A sizeable portion of AYA cancer patients engage in drinking and smoking, which is associated with negative affect and poorer self-reported health. Targeted interventions should be considered to reduce risky behaviors in this population.
Correlation of tumor enhancement and imaging features on multiphasic multidetector CT with microvessel density as a step toward a minimally invasive method to predict Fuhrman nuclear grade in patients with clear cell renal cell carcinoma.
Authors: Heidi Coy, Jonathan Young, Michael Douek, Clara Magyar, Anthony Sisk, Matthew S. Brown, James Sayre, Steven Raman
Journal: Journal of Clinical Oncology (2017)

e16049 Background: Clear cell renal cell carcinoma (ccRCC) is the most common tumor of the kidney. Up to 70% are incidentally detected on multiphasic CT. The prognosis for patients with ccRCC is related to Fuhrman grade (FG) and is diagnosed by biopsy or excision. There is a great need for a non-invasive method to assess tumor grade which may help inform clinical decision-making. The purpose of our study is to determine if contrast enhancement on CT predicts FG and microvessel density (MVD) of ccRCC lesions and to assess which combination of quantitative and qualitative radiological features and clinical features predict high FG ccRCC lesions. Methods: With IRB approval for this HIPAA-compliant retrospective study, our pathology and imaging databases were queried to obtain a cohort of ccRCC with a preoperative multiphasic (unenhanced (U), corticomedullary (C), nephrographic (N), and excretory (E)) CT scan. Tumors were stained with CD4 to quantify % MVD. Spearman’s rank correlation was calculated to test the strength of the association between CT enhancement, %MVD and FG. Stepwise logistic regression analysis was performed to determine the quantitative and/or qualitative feature with the highest performance in predicting high FG tumor. The multivariate logistic regression analysis was evaluated using ROC curves and AUCs. Results: Our cohort had 127 patients with 89 low-grade tumors and 43 high-grade tumors. The %wash-in of enhancement from the U to the C phase showed a significant correlation with %MVD of the tumor (R 2 = 0.181,p &lt; . 001) as did enhancement of the tumor in the early C phase with %MVD (R 2 = 0.159,p &lt; . 001). There was a significant inverse correlation with %MVD and FG (R 2 = 0.137,p &lt; . 001). T-stage, tumor size, %MVD and presence of renal vein invasion were determined to be significant independent predictors of high grade lesions with an AUC of .838 (95% CI .748-.927). Conclusions: Lower grade ccRCC tumors have a higher MVD. Therefore, contrast material washes in at a faster rate from the UN to the CM phase, enabling low grade to be discriminated from high-grade tumors on CT.
Biomarkers and response to pembrolizumab (pembro) in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Authors: Laura Quan Man Chow, Ranee Mehra, Robert I. Haddad, Amit Mahipal, Jared Weiss, Raanan Berger, Joseph Paul Eder, Barbara Burtness, Makoto Tahara, Bhumsuk Keam, Dung T. Le, Kei Muro, Ravit Geva, Hyun Cheol Chung, Chia-Chi Lin, Mark Ayers, Deepti Aurora-Garg, Jared K. Lunceford, Jonathan D. Cheng, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2016)

6010 Background: Pembro shows promising efficacy in R/M HNSCC in the phase 1 KEYNOTE-012 (NCT01848834) study. We present the first analyses of potential immune correlative biomarkers (PD-L1, PD-L2, IFN-γ signature) associated with response in the total R/M HNSCC population. Methods: Initial cohort (I) enrolled PD-L1+ pts; expansion cohort (E) enrolled PD-L1+ and PD-L1- pts. Pts received pembro 10 mg/kg Q2W (I, n = 60) or 200 mg Q3W (E, n = 132). FFPE baseline tissue was used for PD-L1 and PD-L2 scoring (positive or negative) per immunohistochemistry (IHC) in tumor and inflammatory cells. The 6-gene IFN-γ signature (IDO1, CXCL10, CXCL9, HLA-DRA, STAT1, IFNG) was assessed on the Nanostring nCounter platform using FFPE-extracted RNA. Results: When tumor and inflammatory cells were used to score PD-L1 status, an increase in ORR was observed between PD-L1+ vs PD-L1- tumors (P = 0.023); when scoring was restricted to tumor cells only, this increase was not seen (Table). Improved PFS (P = 0.026) and OS (P = 0.008) were also observed in PD-L1+ vs PD-L1- tumors when scoring was conducted in tumor and inflammatory cells, but not tumor cells alone. An increase in ORR was seen for PD-L2+ vs PD-L2- tumors (P = 0.022) (Table), with a trend towards higher ORR in PD-L1+/PD-L2+ vs PD-L1+/PD-L2- tumors. The IFN-γ signature score was significantly associated with ORR, PFS, and OS (all, P < 0.001). Area under the ROC curves were 0.74 (gene signature) and 0.65 (PD-L1 expression). HPV status did not predict PD-L1 positivity or expression of the IFN-γ signature. Conclusions: Inclusion of inflammatory cells in IHC scoring improves the ability to predict response based on PD-L1 status compared to tumor cells alone in pts with R/M HNSCC. Exploratory analyses suggest that PD-L2 and IFN-γ signature may be associated with clinical response to pembro and may offer additional strategies to improve prediction of response. Clinical trial information: NCT01848834.Response based on PD-L1 and PD-L2 status. Status Nonresponders Responders Response, % (95% CI) Tumor cells only PD-L1- 53 12 18.5 (9.9-30.0) PD-L1+ 101 22 17.9 (11.6-25.8) Tumor and inflammatory cells PD-L1- 34 2 5.6 (0.7-18.7) PD-L1+ 120 32 21.1 (14.9-28.4) PD-L2- 55 6 9.8 (3.7-20.2) PD-L2+ 86 25 22.5 (15.1-31.4)
TCT-842 Patterns of Proton Pump Inhibitor Use in Patients Post Coronary Revascularization: Impact of Bleeding Risk on Prescription Patterns
Authors: Kiran Sarathy, Richard Jung, Alisha Labinaz, Rebecca Rochman, Ian Pitcher, Pouya Motazedian, Francisco Ramirez, Pietro Di Santo, Rebecca Rochman, Jeffrey Marbach, Paul Boland, Benjamin Hibbert, Trevor Simard, Saleh Alghofaili, Juan Russo, Etienne Couture, Chris Glover, Marino Labinaz
Journal: Journal of the American College of Cardiology (2018)