tbuckley/cabot-search huggingface dataset:
Abstract P389: Smoking, Biomarkers and Ischemic Stroke Risk: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
Authors: Juan Conde, Maxwell Pistilli, Timothy Plante, Neil Zakai, Leslie McClure, Nels Olson, George Howard, Mary Cushman
Journal: Circulation (2019)

Introduction: Identifying biological pathways that mediate the increased stroke risk in smokers may allow study of novel strategies to reduce risk. In the REGARDS study, we evaluated the association of smoking status with incident stroke and assessed biomarkers as mediators of smoking related stroke. Methods: 30,239 black and white adults aged 45 and older were enrolled in 2003-7, and followed for incident stroke. Biomarkers were measured in a case cohort substudy and compared across groups of smoking status (never, former or current). Hazard ratios (HRs) of stroke by smoking status and by pack years were calculated using Cox proportional hazards models. Results: Among 1,224 participants with biomarker data (mean age 62, 50% male, 50% black) there were 531 incident stroke cases over 12.9 yrs maximal follow up. Compared to never smokers, the multivariable (age, race, sex and Framingham risk factors) adjusted HR of stroke in current smokers was 1.30 (95% CI 1.11, 1.53) and in former smokers was 1.18 (95% CI 1.05, 1.32). The association of pack years with stroke was substantial in current smokers and weak in former smokers in the adjusted model (Table). Among 7 biomarkers, white blood count, interleukin-6 (IL-6) and fibrinogen were higher in former and current smokers, and with increasing pack years in both groups (data not shown). The association of pack years with stroke in current smokers was partly attenuated with adjustment for IL-6, but not white count or fibrinogen. Among former smokers, white count fully attenuated the weak association. Conclusions: Former and current smoking, and pack years (primarily among current smokers) were stroke risk factors in a contemporary biracial cohort. Among both current and former smokers, smoking-related stroke risk was attenuated after adjustment for IL-6 and white count respectively, suggesting biological pathways for intervention.
Radiomic correlates of molecular and clinicopathological characteristics in clear cell renal cell carcinoma.
Authors: Heidi Coy, Jonathan R Young, Allan J. Pantuck, Michael Douek, Anthony Sisk, Clara Magyar, Matthew S. Brown, James Sayre, Steven Raman
Journal: Journal of Clinical Oncology (2019)

625 Background: Clear cell renal cell carcinoma (ccRCC) is a highly vascularized tumor and has a heterogeneous molecular profile, but the correlation between its tumor biology and radiomic features have only recently been investigated. As 70% of ccRCCs are detected incidentally at imaging, and tumor phenotypes are only available after surgery, a non-invasive biomarker to predict ccRCC phenotypes and aggressiveness on imaging may be clinically valuable, as low grade lesions may undergo active surveillance. Methods: With IRB approval and HIPAA compliance, our study cohort comprised 92 consecutive patients with 102 ccRCCs (mean age, 62 years (SD ± 14.2) with histopathology and molecular endpoints imaged preoperatively on CT with a four-phase renal protocol [unenhanced (U), corticomedullary (C), nephrographic (N), excretory (E)]. Radiomic data was obtained by contouring the entire ccRCC in each phase to obtain a 3D tumor volume of interest (VOI). The mean enhancement in each phase the and wash-in and wash-out of enhancement was calculated for each ccRCC. Molecular data was obtained through immunohistochemistry of resected ccRCCs to assess carbonic anhydrase-IX (CAIX), microvessel density (MVD), phosphatase and tension homolog (PTEN), and tumor grade (TG). Categorical variables were analyzed with logistic regression and odds ratio (OR) was reported. Continuous variables were analyzed with linear regression and Pearson correlation coefficient (r 2 ) was reported. P-values &lt; .05 were considered significant. Results: Significant radiomic associations included TG and 3D tumor enhancement in the C (OR = 4.72, p = .030), N (OR = 17.71, p &lt; .0001), and E phases (OR = 17.10, p &lt; .0001), and wash-in from U to C (OR = 8.27, p = .004). MVD had a significant positive association with 3D tumor enhancement in the C phase (r 2 = 0.410, p &lt; .0001), wash-in from U to C (r 2 = 0.435, p &lt; .0001) and wash-out from the C to N (r 2 = 0.435, p = .001). There were no significant radiomic correlates with CAIX or PTEN expression. Conclusions: A 3D ccRCC VOI on multiphasic CT had significant correlations with TG and MVD, independent of clinical features, potentially becoming a predictive imaging biomarker of ccRCC aggressiveness and clinical outcome.
Safety and Efficacy of Idelalisib Treatment of Chronic Lymphocytic Leukemia (CLL) or Lymphoma Relapsing after Allogeneic Hematopoietic Cell Transplantation (alloHCT): A Survey By the EBMT Chronic Malignancies and Lymphoma Working Parties
Authors: Peter Dreger, Linda Koster, Jakob R. Passweg, Matthew Collin, Christof Scheid, Amandine Charbonnier, Fabio Ciceri, Catherine Thieblemont, Daniel Wolff, Joerg Bittenbring, John Gribben, Rocio Parody Porras, Cecilia Isaksson, Mathilde Hunault, Paolo Corradini, Michael Doubek, Guido Kobbe, Ali Bazarbachi, Keith Wilson, Jean Yves Cahn, Veronique Leblond, Nicolaus Kröger, Silvia Montoto, Johannes Schetelig
Journal: Blood (2017)
Mutational patterns of HPV+ and HPV- squamous cell carcinomas of the head and neck (SCCHN) and their interference with outcome after adjuvant chemoradiation: A multicenter biomarker study of the German Cancer Consortium Radiation Oncology Group.
Authors: Inge Tinhofer, Volker Budach, Annett Linge, Fabian Lohaus, Eleni Gkika, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Melanie Avlar, Anca Grosu, Amir Abdollahi, Juergen Debus, Claus Belka, Steffi Pigorsch, Stephanie E. Combs, David Mönnich, Daniel Zips, Wilko Weichert, Mechthild Krause, Michael Baumann
Journal: Journal of Clinical Oncology (2015)

6006 Background: The genetic landscape of SCCHN is currently being unravelled, but the role of distinct mutations for treatment outcome remains largely unknown. We compared mutational patterns of HPV+ and HPV- tumors with outcome after uniform chemoradiation. Methods: Archival tumor specimens from 208 patients with carcinomas of the hypopharynx, oropharynx or oral cavity, all uniformly treated with surgery and adjuvant cisplatin-based radiochemotherapy, were included in this study. An in-house gene panel for semiconductor-based next-generation ultra-deep sequencing, covering 211 exons from 45 genes frequently altered in SCCHN was used for mutational analysis. Genetic alterations were correlated with HPV status and patient outcome. Results: Mutational profiles were successfully established for 185 SCCHN cases. Interestingly, HPV+ carcinomas were significantly enriched for activating mutations in driver genes (PIK3CA 27%, KRAS 8%, NRAS 4%, HRAS 2%) compared to HPV- cases (P = 0.002). Conversely, HPV- tumors showed an increased frequency of loss-of-function alterations in tumor suppressor genes (TP53 67%, CDKN2A 30%, PTEN 4%, SMAD4 3%) compared to HPV+ cases (P < 0.001). After a median follow-up of 55 months, alterations in tumor suppressor genes significantly increased the risk of death (HR 2.9, 95% CI 1.5-5.8, P = 0.001), locoregional recurrence (HR 5.4, 95% CI 1.6-18.1, P = 0.006) and distant metastasis (HR 2.3, 95% CI 1.0-5.1, P = 0.04). The occurrence of activating driver gene mutations did not influence outcome in the total cohort of patients; however, they were associated per trend with increased risk of locoregional recurrence and death (HR 3.7, 95% CI 0.7-20.6, P = 0.12) in HPV+ oropharyngeal carcinomas. Conclusions: Overall, loss-of-function tumor suppressor gene mutations negatively interfere with efficacy of adjuvant cisplatin-based chemoradiation, whereas activating driver gene mutations define poor risk specifically in HPV-driven SCCHN. These genes and their signalling pathways might represent therapeutic targets for improving cure rates of SCCHN.
Early Interim PET in Patients with Advanced-Stage Hodgkin's Lymphoma Treated within the Phase 3 GHSG HD18 Study
Authors: Peter Borchmann, Helen Goergen, Carsten Kobe, Andreas Lohri, Richard Greil, Dennis A. Eichenauer, Josée M Zijlstra, Jana Markova, Julia Meissner, Michaela Feuring-Buske, Andreas Hüttmann, Judith Dierlamm, Martin Sökler, Stefan W. Krause, Hans Eich, Christian Baues, Stefanie Kreissl, Michael Fuchs, Markus Dietlein, Andreas Engert
Journal: Blood (2017)
Retrospective analysis of benefit from concurrent chemoradiotherapy (CRT) in high-risk squamous cell carcinoma of the oral cavity (SCC-OC).
Authors: Leticia Brasiliense Fusco Varella, Anisha R. Noble, Shlomo A. Koyfman, Chandana A. Reddy, John Greskovich, Tobenna Igweonu Nwizu, Brian Burkey, Joseph Scharpf, Mumtaz Khan, Robert Lorenz, Eric Lamarre, David J. Adelstein
Journal: Journal of Clinical Oncology (2015)

e17091 Background: The RTOG and EORTC have reported benefit from adding chemotherapy to post-operative radiation therapy (PORT) in high-risk patients (pts) with squamous cell head and neck cancer, particularly those with positive surgical margins (PSM) or extracapsular nodal extension (ECE). We reviewed our results in a population restricted to SCC-OC to confirm these results. Methods: An IRB-approved review of all pts with stage III-IVB SCC-OC treated with surgery and PORT at the Cleveland Clinic from 1995-2013 was performed. Pts with PSM or ECE were identified and results compared between those treated with CRT, or with PORT alone. Results: Of the 191 identified pts with SCC-OC, 91 had either PSM or ECE; 39 had PSM, 64 had ECE, and 12 had both. PORT alone was given to 56 pts and CRT was given to 35 pts. The CRT and RT cohorts were statistically similar in gender, tumor stage, T classification, tobacco and alcohol use, primary tumor site, tumor differentiation, and incidence of PSM or ECE. CRT pts were younger (median 55 vs. 67 years, p < 0.0001), had a better mean Karnofsky performance status (KPS 89 vs. 84, p = 0.004) and were more likely to have N2-3 disease (80% vs. 43%, p < 0.001). With a median follow-up of 21 (range 3–194) months, the Kaplan-Meier projected 3-year freedom from progression was significantly longer for the CRT pts (79% vs. 43%, p = 0.02); a benefit most apparent in those CRT pts with ECE (3 year projection 80% vs. 42%, p = 0.02) and not seen in pts with PSM alone. CRT pts experienced a reduction in locoregional (LR) recurrence rate (11% vs. 36%, p = 0.02), but no difference in distant recurrence rate (14% vs. 21%, p = 0.4). Over time there was a significantly increased likelihood that pts with PSM or ECE would be treated with adjuvant CRT (p = 0.045). A multivariate analysis controlling for age, KPS, and nodal extent confirmed the progression-free benefit seen for the CRT pts (HR 0.37, 95% CI 0.14-0.93, p = 0.03). Conclusions: This retrospective analysis confirms the benefit of adding chemotherapy to PORT in high-risk SCC-OC pts. This was most apparent in those with ECE, and appeared to reflect an improvement in LR control. The use of adjuvant CRT has appropriately increased at our institution over time.
Response to PARP inhibitor therapy in metastatic castrate-resistant prostate cancer (mCRPC) patients with <i>BRCA1/2</i> versus <i>ATM</i> mutations.
Authors: Catherine Handy Marshall, Andrea McNatty, Mario A. Eisenberger, Alan Haruo Bryce, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2019)

154 Background: Poly ADP-ribose polymerase inhibitors (PARPi) are being studied as a treatment option for men with mCRPC and deficient homologous recombination DNA repair. While the FDA has granted “breakthrough” designation status to olaparib for use in mCRPC patients with either BRCA1/2 or ATM mutations, it is not known if responsiveness to PARPi may be influenced by the mutation type. Because ATM functions as a sensor of DNA damage rather than a mediator of DNA repair, we hypothesized that patients with ATM mutations may not show robust responses to PARPi therapy compared to those with BRCA1/2 mutations. Methods: We conducted a retrospective analysis of mCRPC patients treated with off-label olaparib at Johns Hopkins Hospital and Mayo Clinic Scottsdale who had somatic or germline mutations in BRCA1/ 2 or ATM. The primary endpoint was PSA 50 response. Secondary endpoints included overall survival (OS) and radiographic/clinical progression-free survival (PFS). Results: 40 men received olaparib for mCRPC of which 17 had pathogenic mutations (5 ATM-mutant, 12 BRCA1/2-mutant). Eleven (65%) had germline and 6 (35%) had somatic alterations. Five (29%) had Gleason sum ≤7 at diagnosis, 4 (24%) had Gleason sum 8, and 8 (47%) had Gleason sum ≥9. Three (18%) had metastatic disease at diagnosis. Mean age at start of olaparib therapy was 65.6 (range, 52-76) years. Prior chemotherapy was received by 59% of men, and prior abiraterone/enzalutamide by 88% of men. Eleven (65%) had extra-osseous metastases at start of therapy. PSA 50 responses were achieved by 10/12 men (83%) with BRCA1/2 mutations and 0/5 men (0%) with ATM mutations (Fisher’s exact test, P= 0.003). Men with BRCA1/2 mutations had a median PFS of 12.3 mo versus 3.3 mo for those with ATM mutations (HR 0.14, 95%CI 0.03-0.60; P= 0.008). There was no difference in OS (HR 0.24, 95%CI 0.03-1.173; P= 0.16). Conclusions: Men with mCRPC harboring mutations in BRCA1/2 appear to have better PSA responses and longer PFS with olaparib compared to men with ATM mutations. ATM-mutant mCRPC patients may require alternative therapies ( e.g. chemotherapy, ATR inhibitors). Larger prospective studies are needed to confirm or refute these preliminary findings.
Communication with children and adolescents about the diagnosis of their own life-threatening condition
Authors: Alan Stein, Louise Dalton, Elizabeth Rapa, Myra Bluebond-Langner, Lucy Hanington, Kim Fredman Stein, Sue Ziebland, Tamsen Rochat, Emily Harrop, Brenda Kelly, Ruth Bland, Theresa Betancourt, Catherine D'Souza, Mina Fazel, Daniel Hochhauser, Barbara Kolucki, Aoife C Lowney, Elena Netsi, Linda Richter, Aisha Yousafzai
Journal: The Lancet (2019)
Assessing correlation between LINE-1 methylation and MGMT promoter methylation in glioblastomas.
Authors: Jarin Chindaprasirt, Piyamai Chankate, Mathawee Aumchaaumchaya, Chinachote Teerapakpinyo, Iyavut Thaipisuttikul, Shanop Shuangshoti, Virote Sriuranpong
Journal: Journal of Clinical Oncology (2015)

e13048 Background: Genome-wide hypomethylation is one of the cancer characteristics. In malignant gliomas, hypermethylation of MGMT promoter serves as an important prognostic factor and a predictive factor for response to alkylating agents. Recently, level of LINE-1 methylation has been used as a surrogate for global DNA methylation. LINE-1 methylation level in GBMs has been shown to be lower compared with low-grade gliomas. We hypothesized that there may be a certain correlation between MGMT promoter methylation and global DNA methylation in GBMs. Methods: We collected 25 formalin-fixed, paraffin-embedded GBM tissues derived from patients treated at the King Chulalongkorn Memorial Hospital during 2008-2013. We used pyrosequencing technique to determine the percentage of methylation of both LINE-1 promoter and MGMT promoter methylations. Results: There were 25 GBMs included in this study. There was a trend toward direct correlation between LINE-1 methylation and MGMT promoter methylation, however such correlation was not statistically significant (r = 0.177, p = 0.397). In only tissues with low LINE-1 methylation, there was a trend toward favorable survival outcomes in high MGMT methylation compared with low MGMT methylation; 9.2 mo vs. 4.5 mo (HR 0.51, p = 0.16). Conclusions: In GBMs, there may be a direct correlation between genome-wide methylation and MGMT promoter methylation status. In GBMs with low Line-1 methylation, high MGMT methylation was associated with a trend for better survival. Further studies in larger population are warranted.
Abstract P134: Greater Burden of Cardiovascular Disease Among Incarcerated Women of Color Compared to Whites
Authors: Monik C Jimenez, Lenny Lopez, Kathryn M Rexrode
Journal: Circulation (2019)

Background: Although non-institutionalized black American and Latino adults exhibit a disproportionate burden of cardiovascular disease (CVD) compared to US whites, racial/ethnic disparities are not consistently observed among those incarcerated. Importantly, it is uncertain whether the burden of multiple cardiovascular conditions varies by race/ethnicity among incarcerated individuals. Hypothesis: We assessed the hypothesis that the burden of multiple CVD conditions would be higher among incarcerated non-Hispanic blacks (black) and Latinos compared to non-Hispanic whites (white). Methods: Data from a sample of 14,499 men and women (weighted N=689,161) from the 2004 Survey of Inmates in State Correctional Facilities, a nationally representative sample of adults incarcerated in state facilities, were analyzed. Computer-assisted personal interviews were utilized to collect information on medical history, demographic and socioeconomic factors, prison activities and various offense related factors. Race/ethnicity was defined as self-reported white, black, Spanish/Latino/Hispanic (Latino), or Other. Prior or current CVD conditions (hypertension, diabetes, BMI≥30 kg/m 2 , heart problems, or stroke) were obtained by self-report. Body mass index (BMI, kg/m 2 ) was based on self-reported height and weight. Three separate outcomes were defined based on the cumulative number of CVD conditions (≥1, ≥2 or ≥3 CVD conditions). Age-adjusted survey weighted multivariable logistic regression was used to estimate racial/ethnic disparities in the burden of CVD conditions separately by sex. Results: The median age was 34 years (IQR: 26-42) among men and 35 years (IQR: 27-41) among women. A history of ≥1 CVD condition was reported by 41% of men and 51% of women, while 26% of men and 37% of women reported ≥2 CVD conditions and 10% and 15% of men and women, respectively, reported ≥3. In age adjusted models, among women, significant racial/ethnic disparities were observed among both black and Latina women across all three definitions of CVD burden. The greatest disparities were observed among black women with ≥2 CVD conditions (OR=1.94, 95% CI: 1.62-2.33) followed by Latinas (OR=1.67, 95% CI: 1.32-2.13) compared to whites. Among men in age-adjusted analyses, black men exhibited a similarly greater odds of ≥2 or ≥3 CVD conditions (OR=1.31, 95% CI: 1.18-1.45 and OR=1.36, 95% CI: 1.17-1.57, respectively) compared to white men. Among Latino men compared to whites, modest disparities were only observed for ≥2 CVD conditions (OR=1.17, 95%CI: 1.03-1.33). Conclusions: Black and Latina women and black men exhibited a significantly greater burden of CVD conditions compared to white women and men, respectively. These data highlight the prominent racial/ethnic disparities among incarcerated populations of color and the need for tailored interventions to reduce cardiovascular risk in these populations.
Manageable treatment with lapatinib and continuous metronomic capecitabine in HER2 positive advanced breast cancer (ABC): Efficacy and safety data.
Authors: Laura Orlando, Stefania Eufemia Lutrino, Caterina Fontanella, Annamaria Quaranta, Chiara Caliolo, Margherita Cinefra, Paola Schiavone, Palma Fedele, Nicola Calvani, Enrica Mazzoni, Antonella Marino, Pietro Rizzo, Angelo Nacci, Maria D'amico, Francesco Sponziello, Pasqualinda Ferrara, Manuela Caloro, Cosimo Caforio, Emiliano Sordi, Saverio Cinieri
Journal: Journal of Clinical Oncology (2015)

e11571 Background: Clinical activity of lapatinib-capecitabine has been well documented in advanced breast cancer (ABC). However, cutaneous and gastro-intestinal toxicity may interfere with the optimal treatment delivery. We report efficacy and safety data of the combination of lapatinib and metronomic capecitabine in a retrospective cohort of HER-2 positive ABC patients (pts). Methods: Pts treated with lapatinib (Lap, 1250 mg/daily) plus capecitabine (Cap, 1500 mg/daily) were included. Data on overall response rate (ORR), progression free survival (PFS), clinical benefit rate (CBR = partial response PR+ complete response CR + prolonged stable disease SD ≥ 24 weeks), overall survival (OS) and tolerability were reported. Results: In this observational cohort study 24 pts with ABC from a single Institutionwho received Lap/Cap modified schedule from November 2009 to December 2014were enrolled. Twenty pts were evaluable for response and 23 for toxicity. In our analysis 52.5% pts received ≥ 3 previous lines for advanced disease. Median age was 51 years (range 34-70), PS was 0-1 in 100%, visceral metastases were present in most patients (84%). Median follow-up was 25 months (range 1-53). The ORR was 40% (95% CI, 19-64%), with 2 CR and 6 PR. Four patients had prolonged SD (21%). The CBR was achieved in 60% (95% CI , 36%-80%). Four progressions disease (PD) were observed (20%). Median PFS was 4.8 months (range 1.4- 28.7+), median OS 27 months (range 3.0-52.3+). Four-year OS was 75%. Main toxicities were grade 2 hand-foot syndrome (HFS) in 7 pts (30%), grade 2 diarrhea in 5 pts (21%), ungueal alterations G2 in 3 pts (13%), grade 2 rash in 2 pts (8%). No grade 3 or 4 specific Lap/Cap induced toxicities were reported, mainly in terms of photosensitivity reaction during sun exposure. Three pts had dose reduction for gastrointestinal toxicity and 2 treatment discontinuation for persistent diarrhea G2. Conclusions: Efficacy and tolerabilityof Lap/Cap modified schedule are encouraging. This combination might be considered when low toxicity burden is advisable and could allow sun exposure contrary to literature data.