tbuckley/cabot-search huggingface dataset:
Risk of second primary HPV-associated cancers after index HPV-associated cancers.
Authors: Ryan Suk, Parag Mahale, Kalyani Sonawane, Andrew G. Sikora, Jagpreet Chhatwal, Kathleen M. Schmeler, Keith Sigel, Scott B. Cantor, Elizabeth Chiao, Ashish A Deshmukh
Journal: Journal of Clinical Oncology (2018)

1520 Background: For the HPV-associated index cancer survivors, persistent HPV infection may remain a risk factor for preventable HPV-associated second primary cancer (HPV-SPC). However, the risk of HPV-SPCs among HPV-associated index cancer patients has not been well documented. Methods: Longitudinal data from 9 cancer registries of the Surveillance, Epidemiology, and End Results (SEER) database were used to identify cases of HPV-associated cancers diagnosed from 1973 to 2014. The HPV-SPC risk was quantified using standard incidence ratios (SIRs) and excess absolute risk (EAR) per 10,000 person-years at risk (PYR). Results: The SIRs for second primary HPV-related cancers after index HPV-related cancers among women and men were 3.3 (95% CI 3.2 to 3.4) and 15.8 (95% CI, 15.0 to 16.7), respectively; the EAR was 6.0 and 51.4 for women and men, respectively. When the same site second primary cancers were excluded, the risk remain significant both among women (SIR = 2.7) and men (SIR = 2.3). The risk of HPV-SPC was highest for oropharyngeal cancer both among women (SIR = 20.6; EAR = 83.8) and men (SIR = 18.8; EAR = 64.3), and lowest for cervical (SIR = 2.0; EAR = 2.4) and penile (SIR = 7.0; EAR = 20.7) cancer. Conclusions: The risk of developing HPV-SPC among HPV-related cancer survivors is significant, implying that HPV might be a cause for developing HPV-SPC. Our findings have the potential to inform surveillance recommendations among HPV-related cancer survivors. SIRs for HPV-SPCs after index HPV-related cancers. Index HPV Cancers Women Men All HPV-SPC All HPV-SPC (same site excluded) All HPV-SPC All HPV-SPC (same site excluded) SIR (95% CI) EAR SIR (95% CI) EAR SIR (95% CI) EAR SIR (95% CI) EAR All HPV-related cancers 3.3 (3.2-3.4) 6.0 2.7 (2.5-2.8) 2.3 15.8 (15.0-16.7) 51.4 2.3 (1.8-2.9) 1.6 Cervical 2.0 (1.9-2.1) 2.4 2.5 (2.3-2.7) 1.8 NA NA NA NA Vaginal 6.6 (5.2-8.3) 20.5 3.9 (2.8-5.3) 10.0 NA NA NA NA Vulvar 9.5 (8.7-10.3) 28.0 4.1 (3.6-4.7) 8.5 NA NA NA NA Oropharyngeal 20.6 (19.1-22.2) 83.8 1.7 (1.2-2.3) 1.9 18.8 (17.7-19.9) 64.3 1.7 (0.9-2.7) 0.4 Anal 6.1 (5.0-7.4) 20.8 3.5 (2.6-4.6) 9.0 10.4 (8.5-12.5) 26.6 2.1 (1.3-3.3) 2.9 Penile NA NA NA NA 7.0 (5.7-8.7) 20.7 2.9 (2.0-4.0) 5.8
TCT-21 Prognostic impact of SYNTAX II score in patients with ST-elevation myocardial infarction undergoing Primary Percutaneous Coronary Intervention: analysis of an 8-year all-comers registry
Authors: Fernando Gómez Peña, Ana Belen Cid Alvarez, Alejandro Avila Carrillo, Alfredo Redondo Dieguez, Diego Lopez Otero
Journal: Journal of the American College of Cardiology (2018)
Abstract 14695: Identification of Emetine as a Novel Therapeutic Agent for Pulmonary Hypertension in Rats -High-throughput Screening of 5,562 Compounds
Authors: Mohammad Abdul Hai Siddique, Kimio Satoh, Ryo Kurosawa, Md. Elias Al-Mamun, Nobuhiro Kikuchi, Junichi Omura, Taijyu Satoh, Masamichi Nogi, Shinichiro Sunamura, Hiroaki Shimokawa
Journal: Circulation (2016)

Background: Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary arterial smooth muscle cells (PASMCs). Emetine, a natural alkaloid ex...
Population based analysis of male patients with breast cancer.
Authors: Osama Ahmed, Winson Y. Cheung, Gloria Roldan Urgoiti
Journal: Journal of Clinical Oncology (2018)

e18715 Background: We aimed to evaluate the clinical and pathological characteristics, management and outcomes of male patients with breast cancer (BC) in a large Canadian province. Methods: We identified and reviewed all male patients diagnosed with BC between 2004 and 2016.The provincial cancer registry was merged with electronic medical records to compare aggregated data of this male cohort with contemporary female patients with BC. Results: We included 31,228 patients; 180 (0.6 %) were men (M). Median age was 66 years in M and 61 years in women (W) (P < 0,001).18 (10%) of M vs 1643 (5%) of W presented as stage IV (p≤ 0.001).84% of male patients had a modified radical mastectomy. The most frequent pathology was invasive ductal carcinoma (89% in M and 77% in W; p≤ 0.001). Tumors were estrogen receptor positive in 92% of M and 81% of W (p = 0.001); progesterone receptor positive in 83% and 70%, respectively (p = 0.003) and Her2 positive in 22% and 31%, respectively (p < 0.001). Tamoxifen was the preferred hormonal therapy in both the adjuvant (89.6 %) and palliative settings (83%). Sites of metastases were bone (66%), visceral (57%), skin (16%) and brain (14%). Median overall survival (OS) for M was significantly shorter than for W (7.6 years vs not reached at 12.5 years; p < 0.001). When analyzed by stage, there was no difference in survival by sex in patients with advanced BC (Stage III p = 0.203; Stage IV p = 0.255). In patients with Stage I and II, however, male patients had significantly shorter survival (p = 0.006 and p < 0.001, respectively) (Table). Sex was associated with worse OS even when after adjusting for confounders (p = 0.001). Conclusions: In this population-based study, sex-based differences in outcomes were limited to early stage BC where surgery is the main treatment modality. These variations in outcomes may be driven by differences in access, delivery, or quality of surgical care, which should be the focus of further studies. Table. Median OS in Male BC vs. Female BC Stratified by Stage. Median OS, years Male BC patients Female BC patients P value Stage I 8.67 (95%CI 7.88 to 11.13) not reached 0.006 Stage II 9.08 (95%CI 5.39 to 12.78) not reached < 0.001 Stage III 7.08 (95%CI 2.86 to 11.30) 10.42 (95%CI 9.58 to 11.25) 0.203 Stage IV 1.58 (95%CI 0.90 to 2.27) 2.17 (95%CI 2.01 to 2.32) 0.255
Ewing sarcoma Family of Tumors in Older Patients (EFyTOP): Management and outcome of Ewing sarcoma family of tumors (EFTs) in patients older than 50 years.
Authors: Pauline Rochefort, Antoine Italiano, Valerie Laurence, Nicolas Penel, Audrey Lardy-Cleaud, Olivier Mir, Christine Chevreau, Francois Bertucci, Emmanuelle Bompas, Loic Chaigneau, Dominique Levy, Thomas Ryckewaert, Sarah Naomie Dumont, Pierre Meeus, Dominique Ranchere, Jean-Yves Blay, Philippe Alexandre Cassier
Journal: Journal of Clinical Oncology (2016)

11023 Background: Ewing’s sarcoma family of tumorsis a group of rare and aggressive tumors. Data on tumor, clinical presentation and treatment in patients (pts) older than 50 years are limited. Outcomes of older pts with EFTs have been reported to be worse than in pediatric population in some studies but with discordant results. Methods: We conducted a retrospective analysis among centers of affiliated with the French Sarcoma Group (GSF-GETO) focusing on pts diagnosed with EFTs at age ≥ 50 between 2000 and 2012. Clinical features, treatment modality and outcomes were recorded and analyzed. Results: 77 pts were identified. There were 36 females (47%) and themedian age at diagnosis was 56 years (range: 50-86). The primary tumor was located in the soft tissue in 59 pts (76.6%) and in the bone in 18 (23.4%). 56 pts (72.8%) had localized disease whereas 21 (27.2%) presented with metastases at diagnosis. Median follow-up was 71 months (m) and median overall survival (OS) was 92.8 m for the whole cohort. Among 56 pts with localized disease, 50 (87.7%) received chemotherapy (CT) in addition to local therapy (surgery in 19 pts, surgery and RT in 37 pts and RT only in 7 pts), and among these, CT was considered intensive in 36 pts (63%). For patients with localized disease, the estimated 3-year OS and relapse free survival (RFS) rates were respectively 73.3% and 62.2%. Recurrence occurred in 43 pts, with a median time to recurrence of 18.2 m. Recurrences were most often metastatic only (62.7%), followed by local only (23%). Recurrence site was lung for 16 pts (37.2%) and bone for 9 pts (20.9%). Median post-recurrence survival was 9.5 m. In univariate analysis only high LDH were marginally associated with worse overall survival in patient with localized disease. All pts with metastatic disease at presentation received CT, their estimated 3-year OS rate was 37%. Conclusions: EFTs characteristics in patients ≥ 50 years differ from the pediatric population: they had more likely soft tissue primary tumor and metastatic disease. The outcomes were worse than in younger pts but could be partially explained by less intensive therapy. The management of Ewing sarcoma in adult pts remains to be defined.
Abstract 14785: Oral Administration of Eicosapentaenoic Acid Ameliorates Anti-inflammatory Functions of High-Density Lipoprotein in Dyslipidemic Patients
Authors: Nobuaki Tanaka, Tatsuro Ishida, Manabu Nagao, Takeshige Mori, Tomoko Monguchi, Maki Sasaki, Kenta Mori, Kensuke Kondo, Hideto Nakajima, Tomoyuki Honjo, Ryuji Toh, Ken-ichi Hirata
Journal: Circulation (2014)

Objective: Previous studies have reported that inflammation converts high-density lipoprotein (HDL) to dysfunctional form lacking its anti-inflammatory properties. However, little is known about pharmacological therapy to improve HDL function. It has been recently postulated that fatty acid component in HDL-phospholipids modulates HDL functions. We investigated the effect of oral administration of high dose eicosapentaenoic acid (EPA) on HDL functions. Methods: Patients with dyslipidemia were treated with 1800 mg/day EPA for 4 weeks, and HDL fractions were isolated by ultracentrifuge before and after the EPA treatment. HDL functions were evaluated by multiple in vitro cell-based assays. Results: The EPA treatment did not affect the quantity in the serum lipid profile including serum cholesterol, triglyceride and apolipoprotein levels, but significantly increased EPA concentrations both in the serum and HDL fraction. The EPA/arachidonic acid ratio in the HDL was in proportion to that in the serum, suggesting that EPA was incorporated in HDL particles. The HDL after EPA treatment possessed high activity of paraoxonase-1, an HDL-associated anti-oxidative enzyme, compared to HDL before EPA treatment. In addition, the EPA-rich HDL significantly improved endothelial cell migration, and markedly inhibited cytokine-induced expression of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells, compared to HDL before the EPA treatment. Moreover, the EPA-rich HDL had high capacity of cholesterol efflux capacity from macrophages. Conclusion: Administration of high dose EPA improves anti-inflammatory, anti-oxidative, and cholesterol efflux capacity of HDL in dyslipidemic patients. Thus, EPA may transform “dysfunctional HDL” to “functional”, in patients with coronary risk factors.
Acute kidney injury in head and neck cancer patients treated with chemoradiation with cisplatin: A single-center cohort study.
Authors: Esther Van Meerten, Catherine Owusuaa, Ewout Hoorn, Esther Oomen De Hoop
Journal: Journal of Clinical Oncology (2017)

e17559 Background: Patients with advanced head and neck cancer (HNC) are commonly treated with chemoradiation with concomitant cisplatin. Acute kidney injury (AKI) is considered a dose-limiting toxicity of cisplatin. We aim to describe the incidence and risk factors of AKI. Methods: In our tertiary center, we retrospectively identified 261 patients with advanced HNC and adequate renal function who were treated curatively from 2008 to 2015 using radiotherapy and concurrent three-weekly cisplatin. Outcome was the first AKI episode, defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a ≥50% rise in serum creatinine compared to baseline. Several potential predictors were investigated by means of logistic regression analyses. Results: In our cohort (mean age 58 ± 8 years, 74.3% male), a total of 102 (39.1%) patients developed AKI. Factors significantly associated with AKI in the univariate analysis were: age, alcohol consumption, excessive smoking, diabetes, hypertension, diuretic use, renin-angiotensin-aldosterone-system blockers, and administration of furosemide when indicated during first cisplatin cycle. In the multivariable model smoking 6-25 and &gt; 25 cigarettes per day (OR 1.85; 95% CI 1.01-3.39 and OR 3.22; 95% CI 1.34-7.70, respectively), diabetes (OR 2.58; 95% CI, 1.01-6.61), furosemide (OR 2.39; 95% CI, 1.36-4.18) , and hypertension (OR 2.79; 95% CI, 1.52-5.12) remained independent risk factors for AKI. Conclusions: The identified risk factors smoking, diabetes, and hypertension may have caused pre-existing kidney damage and therefore have predisposed to AKI. Co-administration of furosemide with cisplatin is a potentially reversible risk factor for AKI.
P04.19 Detailed analysis of mutation change after treatment in glioblastoma
Authors: M Nagane, K Saito, S Shimizu, E Nozaki, K Kobayashi, S Kume, T Chiba, J Shibahara, Y Shiokawa
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is poor-prognosis cancer and tumor recurrence is inevitable despite intensive chemoradiotherapy. Thus, insights into the mechanism of tumor recurrence are critical for improved patient treatment. Here, we describe our integrated genomic analyses using next-generation sequencing of the paired samples from initial and recurrent tumors. We collected paired GBM samples in patients who recurred after temozolomide (TMZ) treatment. Mutation analysis of the cancer-related genes was performed using Ion Ampliseq Cancer Hotspot Panel v2. In addition, MGMT promoter methylation and expression of mismatch repair (MMR) protein such as MLH1, MSH2, MSH6, and PMS2 were analyzed by pyrosequencing and Western blotting, respectively. Sixty tumor samples from 29 patients were included in this study. Mutation acquisition of cancer-related genes was observed only in 12 (41%) patients while remaining 17 (59%) patients were mutationally stable even after TMZ treatment. Mutations were gained in 5 MGMT methylated tumors and 7 unmethylated. Remarkably, 70% of acquired mutations in MGMT methylated tumor were G:C>A:T at non-CpG sites whereas only 8% in MGMT unmethylated tumors. In mutation gain group, MMR expression decreased significantly after treatment (p=0.012~0.048). Furthermore, in contrast to MGMT unmethylated tumors, MGMT methylated tumors showed marked MMR inactivation (40% vs. 7.5%, p=0.078). We showed different types of the mutation acquisition after TMZ treatment according to MGMT status, providing further insights into the mechanism of TMZ resistance to improve treatment of the patients with GBM.
BI 1482694 (HM61713), an EGFR mutant-specific inhibitor, in T790M+ NSCLC: Efficacy and safety at the RP2D.
Authors: Keunchil Park, Jong-Seok Lee, Ki Hyeong Lee, Joo-Hang Kim, Byoung Chul Cho, Young Joo Min, Jae Yong Cho, Ji-Youn Han, Bong-Seog Kim, Jin-Soo Kim, Dae Ho Lee, Jin Hyoung Kang, Eun Kyung Cho, Hoon-Gu Kim, Kyung Hee Lee, Hoon Kyo Kim, In-Jin Jang, Hyo-Yeon Kim, Jeewoong Son, Dong-Wan Kim
Journal: Journal of Clinical Oncology (2016)

9055 Background: T790M mediates acquired resistance to 1st/2nd generation EGFR-TKIs. BI 1482694 is a 3rd generation TKI active against mutant EGFR, including T790M. This Phase I/II trial is evaluating BI 1482694 in Korean patients (pts) with EGFR-TKI pre-treated NSCLC (NCT01588145). Preliminary data in T790M+ pts treated at the RP2D (800 mg/d) were reported previously (Lee et al. ESMO Asia 2015); as of 30 Jun 2015, ORR by independent review was 62% (confirmed ORR 46%). Here we present updated efficacy and safety findings as of 30 Nov 2015. Methods: Pts with locally advanced or metastatic EGFR mutant NSCLC who previously received an EGFR-TKI and had centrally confirmed T790M+ tumors were recruited in Phase II. Pts received BI 1482694 800 mg/d until disease progression, unacceptable toxicity, or other stopping criteria. Tumors were assessed every 6 wks by investigator and independent review. Pts were evaluable for response if they had at least one tumor assessment post baseline; PFS and safety were evaluated in all treated pts. Results: Among 76 T790M+ pts who received BI 1482694 800 mg in Phase II, median age was 60 yrs, 58% were female, 80% had ECOG PS ≤ 1, and 75% had ≥ 2 prior lines of systemic therapy, including EGFR-TKI. Median treatment duration was 7.0 mos (range 0.3–13.8); 26 (34%) pts remain on treatment at data cut-off. Most common drug-related (DR) AEs (all/grade ≥ 3) were diarrhea (55%/0), rash (39%/5%), pruritus (39%/1%), and nausea (38%/0). 3 (4%) pts discontinued due to DR AEs (abdominal pain upper and vomiting [n = 1], interstitial lung disease [n = 1], neuropathy peripheral [n = 1]). 9 (12%) pts had serious DR AEs. There were no AEs of QT prolongation or hyperglycemia and no DR deaths. Of 71 pts evaluable for response, 40 (56%) had an objective response by investigator review (31 [44%] confirmed) with median duration of response 8.3 mos (range 5.6–NE). Disease control rate was 90%. Median PFS by investigator review was 7.0 mos (95% CI 5.5–8.3). Updated efficacy data by independent review will be presented at the meeting. Conclusions: BI 1482694 showed meaningful clinical activity with favorable tolerability in Korean pts with EGFR-TKI-resistant T790M+ NSCLC, and is being further evaluated in the global Phase II ELUXA 1 trial. Clinical trial information: NCT01588145.
Palliative care interventions and EOL care outcomes for hepatocellular patients (pts) at 2 VA medical centers.
Authors: Zhen Wang, Sarah Lee, Sejal Kothadia, Yucai Wang, Victor Tsu-Shih Chang, Yeun-Hee Anna Park, Ellen Olson, David Klein, Fengming Zhong
Journal: Journal of Clinical Oncology (2016)

e21514 Background: Palliative care interventions and their effect on EOL outcomes for liver cancer pts have not been described. We investigated the association between palliative care intervention and EOL care outcomes. Methods: We reviewed the charts of pts with hepatocellular carcinoma and who were seen by palliative care at 2 VA medical centers from 2006 to 2012. We investigated the association between EOL outcomes (number of ER visits, ICU visits, chemotherapy, place of death, number of hospitalizations during their last 30 days), and interventions such as early referral (within 30 days of diagnosis), defined goals of care, holding a family meeting, and symptom assessment and management. The protocol was reviewed by the IRB of both VAs and analyses were done with SAS Studio v3.4. Results: 82 charts were reviewed (30 from EOVA and 52 from BVA). All Pts were men; 30 (39%) were white and 47(61%) African American. Interval from diagnosis to palliative care consult was 68 days (median). 72 (90%) pts were not aware of their diagnosis. 48 (65%) were not aware of prognosis. 65 (88%) had decision making capacity. 32 (39%) pts were DNR/DNI. 60 (86%) pts chose symptom management and 10 (14%) life prolongation. 47 pts (50%) had family meeting. In the last month, 35 pts (48%) had ER visit. 9 pts (12%) had ICU visits, 4 pts (5%) had chemotherapy and 48 pts (71%) had at least 1 hospitalization. 68 (85%) underwent symptom assessment. Most frequently treated symptoms were pain (78%), nausea (27%), constipation (46%), dyspnea (34%). Significant associations were found for early referral and ER admissions (OR = 3.2, p = 0.0178), family meeting and site of death (OR = 0.136 p = 0.0037), family meeting and number of hospitalizations (OR = 0.2652, p = 0.0169). Pts choosing symptom management and who had family meetings associated with hospice/home as place of death (chisq = 5.7368, p = 0.016). Knowledge of prognosis was not associated with site of death. Conclusions: In this population, many palliative care interventions were performed. Early referral, family meetings were significantly associated with site of death, ER admissions, and number of hospitalizations. These results should be replicated in larger studies.
Inhibition of Acetyl-CoA Carboxylase by Phosphorylation or the Inhibitor ND-654 Suppresses Lipogenesis and Hepatocellular Carcinoma
Authors: James S.V. Lally, Sarani Ghoshal, Danielle K. DePeralta, Omeed Moaven, Lan Wei, Ricard Masia, Derek J. Erstad, Naoto Fujiwara, Vivian Leong, Vanessa P. Houde, Alexander E. Anagnostopoulos, Alice Wang, Lindsay A. Broadfield, Rebecca J. Ford, Robert A. Foster, Jamie Bates, Hailing Sun, Ting Wang, Henry Liu, Adrian S. Ray, Asish K. Saha, Jeremy Greenwood, Sathesh Bhat, Geraldine Harriman, Wenyan Miao, Jennifer L. Rocnik, William F. Westlin, Paola Muti, Theodoros Tsakiridis, H. James Harwood, Rosana Kapeller, Yujin Hoshida, Kenneth K. Tanabe, Gregory R. Steinberg, Bryan C. Fuchs
Journal: Cell Metabolism (2018)
A phase I molecular adaptive clinical study to evaluate safety and tolerability of BPM31510-IV in advanced solid tumors: Final study results.
Authors: Niven R. Narain, Vivek Subbiah, David S. Hong, David Lucius, Viatcheslav R Akmaev, Michael A Kiebish, Gregory M Miller, Eric Milliman, Leonardo O Rodrigues, Lixia Zhang, Rangaprasad Sarangarajan
Journal: Journal of Clinical Oncology (2018)

2541 Background: BPM31510-IV is an Ubidecarenone (CoQ10) containing IV nanodispersion targeting metabolic machinery in cancer, shifting bioenergetics from lactate dependency towards mitochondrial OxPhos and reversing the Warburg effect. This study evaluated the safety & tolerability of BPM 31510-IV alone or in combination with chemotherapy. The study design included PD sampling for multi-omic analysis to identify predictive markers of clinical benefit and patient stratification. Methods: Eligible patients were relapsed/refractory to standard therapy. The monotherapy arm received IV BPM 31510 for 6 d in continuous infusion in 28-d cycles, and combination arms (gemcitabine, 5-FU or docetaxel) were primed for 3 wks with BPM31510 prior to chemotherapy regimen followed by weekly dosing in a 6 wk cycle. Endpoints were safety, pharmacokinetics (PK) and pharmacodynamics (PD). Tumor response was evaluated at cycle 1 and then after every 2 cycles. Results: A total of 98 pts were enrolled. Thirty of 66 evaluable pts (45%) achieved stable Disease, for ≥ 2 cycles and 16/66 (24%) maintained a minimum of SD for ≥ 4 cycles. 99% patients receiving ≥ 1 treatments with BPM31510 experienced a TEAE. The most frequently experienced TEAEs were asymptomatic elevated APTT in 80% of pts, INR increased in 74%, PTT prolonged 64%, Anemia in 41%, fatigue in 24% and both AST increase & platelet decrease in 16% of pts. Molecular predictors of coagulation-related events prior to and 24h after 1st treatment with IP were identified. Biomarker candidates correlating with favorable clinical response & safety identified were independent of tumor type and prior therapy, suggesting a broad anti-tumor effect. Novel multi-omic panels with potential to stratify response before and 24h post treatment with AUC > 0.85 were identified. Conclusions: BPM31510-IV is well tolerated as monotherapy and in combination with several standard chemotherapeutic agents. Molecular signatures with predictive potential of the safety and clinical response have been identified that will guide Phase 2/3 clinical development. Clinical trial information: NCT01957735.