tbuckley/cabot-search huggingface dataset:
Effect of minocycline on symptom burden and inflammation markers in patients with colorectal cancer: A randomized phase II trial.
Authors: Xin Shelley Wang, Qiuling Shi, Nishin Bhadkamkar, Cobi Heijnen, Charles S. Cleeland, Cathy Eng
Journal: Journal of Clinical Oncology (2018)

e22176 Background: Colorectal cancer (CRC) may experience substantial symptom burden that is often exacerbated by standard chemotherapy. It’s a high price to pay for cure and persists into survivorship. Minocycline is a readily available, low-cost antibiotic with anti-inflammatory properties. This ACS-funded proof-of-concept study investigated minocycline’s ability to reduce symptoms during chemotherapy in a phase II randomized, double-blinded, placebo-controlled clinical trial. Methods: Patients with CRC scheduled for oxaliplatin-based chemotherapy at MD Anderson Cancer Center or Lyndon B. Johnson General Hospital (LBJ), a city public hospital, were randomized to receive either minocycline (100 mg twice daily) or placebo over 4 months of therapy. Toxicities, blood samples, and patient-reported symptoms were prospectively collected. The MD Anderson Symptom Inventory gastrointestinal module (MDASI-GI) was used to assess symptoms weekly. Longitudinal results from the minocycline and placebo groups were compared. Results: From Apr 2013–Aug 2016, 69 patients (33 minocycline, 36 placebo; 78% of 88 enrolled patients) were evaluable (ie, completed ≥2 MDASI-GI assessments); 43 were from MD Anderson (75% white-non Hispanic) and 44 were from LBJ (73% Hispanic/Latino). No grade ≥3 minocycline-related adverse events were observed. The 5 worst symptoms longitudinally were fatigue, pain, numbness/tingling, drowsiness, and disturbed sleep. No significant differences were found between the minocycline and placebo groups in terms of symptom severity or serum and leukocyte-derived proinflammatory and anti-inflammatory markers. Major symptom burden was significantly more severe in patients at MD Anderson than at LBJ, possibly due to a higher frequency of treatment discontinuation at LBJ. Conclusions: Minocycline treatment is feasible with a low toxicity profile. However, the use of minocycline yielded no statistically significant positive signal to reduce symptoms that attributed to oxaliplatin-based chemotherapy or on inflammatory biomarkers. Our results cannot encourage continued exploration of minocycline for mechanism-driven symptom intervention in CRC patients. Clinical trial information: NCT01906008.
Brachyury, a driver of epithelial mesenchymal transition, as an independent prognostic factor in high-grade testicular germ cell tumors.
Authors: Flavio Mavignier Carcano, Filipe Pinto, Eduardo CA da Silva, Daniel Onofre Vidal, Cristovam Scapulatempo Neto, Luiz Fernando Lopes, Rui Manuel Reis
Journal: Journal of Clinical Oncology (2017)

e16039 Background: The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis and poor prognosis. However, its clinical association with testicular germ cell tumor (TGCT) is unknown. Methods: We analyzed the expression of Brachyury both at protein and transcript levels in a series of 96 TGCT samples and by in silico analysis, respectively. Additionally, we investigated the clinical significance of Brachyury in TGCT. Results: Brachyury protein showed to be over-represented in 89.6% (86/96) of TGCT cases with nuclear staining in 24% (23/96) of them. Microarray expression analysis in two independent cohorts of TGCTs showed similar results with increased levels of Brachyury in TGCTs and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk TGCTs. Multivariate analysis showed that Brachyury nuclear subcellular localization was an independent predictor of poor prognosis (HR: 3.56, p = 0.06). Conclusions: These results indicate that Brachyury plays an oncogenic role in TGCTs and its subcellular localization in the nucleus is a potential novel biomarker of poor prognosis and an oncotarget for intermediate/high-risk TGCTs treatment.
Real-world benefits of allergen immunotherapy for birch pollen-associated allergic rhinitis and asthma
Authors: Ulrich Wahn, Claus Bachert, Joachim Heinrich, Hartmut Richter, Stefan Zielen
Journal: Allergy (2018)

Real-world evidence is sparse on the benefits of allergen immunotherapy [AIT; subcutaneous/sublingual immunotherapy (SCIT/SLIT)], the only disease-modifying intervention for allergic rhinitis (AR) with long-term efficacy. This real-life study evaluated the effect of six AITs (native pollen SLIT/SCIT, four allergoid SCITs) vs symptomatic medication use, on AR symptoms and asthma symptoms/onset, in patients with birch pollen-associated AR and/or asthma.
TCT-419 Effects of Body Mass Index on the Comparative Effectiveness of PCI Versus CABG for Left Main Coronary Artery Disease: Insights From the EXCEL Trial
Authors: Sabato Sorrentino, Gennaro Giustino, Roxana Mehran, David Kandzari, Marie-Claude Morice, Anthony Gershlick, Ovidiu Dressler, Joseph Sabik, A. Pieter Kappetein, Patrick Serruys, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
DNA methyltransferase 1 (DNMT1) polymorphism and chemotherapy-associated cognitive impairment in early-stage breast cancer patients (ESBC): A prospective, longitudinal study.
Authors: Terence NG, Ming Tjong Chian, Hui Ling Angie Yeo, Maung Shwe, Yan Xiang Gan, Wei-Jen Kiley Loh, Si-Lin Koo, Amit Jain, Guek Eng Lee, Rebecca Alexandra Dent, Yoon Sim Yap, Raymond C.H. Ng, Mooi Tai Cham, Jung Ah Lee, Pak Yan Pa Chu, Chiea Chuen Khor, Han Kiat Ho, Alexandre Chan
Journal: Journal of Clinical Oncology (2016)

10014 Background: Epigenetic regulation via methylation plays a crucial role for the functioning and survival of neuronal cells. DNA methyltransferase 1 (DNMT1) is an enzyme to maintain methylation during cells division. In this study, we aimed to evaluate the impact of DNMT1 polymorphisms, rs2162560 (G>A) and rs759920 (G>A), on a patient’s susceptibility to chemotherapy-associated cognitive impairment. Methods: 220 chemotherapy-receiving ESBC patients (mean age: 51.0 ± 9.2 years; 80.5% Chinese) were recruited. Patients’ self-perceived cognitive function were assessed longitudinally over three time points using the validated FACT-Cog (v.3). Six cognitive domains were examined: concentration, functional interference, memory, mental acuity, multitasking ability, and verbal fluency. Genotyping was performed using Sanger sequencing. Logistic regression was used to evaluate the association between the genetic polymorphisms and cognition, adjusting for ethnicity and clinically important covariates. After adjustment for multiple testing, p<0.0045 was considered as statistically significant. Results: For rs2162560, 130 (59.1%) patients were homozygous for GG, 81 (36.8%) were heterozygous for GA, and 9 (4.1%) were homozygous for AA without deviation from the Hardy-Weinberg equilibrium (HWE). The genotype distribution of rs759920 deviated from the HWE. Within a recessive model, carriers of the DNMT1 rs2162560 A allele were less likely to experience impairment in the concentration domain (OR= 0.31, 95% CI 0.14 - 0.69, p = 0.004). In particular, the AG genotype was associated with lower odds (OR = 0.28, 95% CI 0.12 – 0.64, p= 0.003) of cognitive decline in the concentration domain. Conclusions: Carriers of DNMT1 rs2162560 polymorphism were protected from cognitive decline during chemotherapy. This suggests that alterations in normal epigenetic patterns via DNMT1 gene polymorphisms are implicated in chemotherapy-associated cognitive impairment.
Risk of second malignancies in breast cancer patients who received chemotherapy: A SEER analysis.
Authors: Snigdha Nutalapati, Sanjay R. Jain
Journal: Journal of Clinical Oncology (2018)

1565 Background: Chemotherapy agents used in breast cancer have carcinogenic potential and can cause malignancies. Patients with breast cancer could also be at risk for a second malignancy as well. We aimed at determining the risk of after adjuvant chemotherapy for breast cancer. Methods: We did an observational study of women who received a diagnosis of breast cancer from 1990 to 2009 using Surveillance, Epidemiology, and End Results (SEER) registries database 9 registries. Second malignancy(SM) was defined as any malignancy diagnosed 6 months after initial diagnosis of breast cancer (includes both chemotherapy-related malignancies and second primary malignancies). hormone receptor (HR) status into estrogen receptor (ER) and progesterone receptor (PR), positive (+) and negative (-). Standardized incidence ratios(SIR) were calculated based on United States population in 2000. p-value of < 0.05 is considered statistically significant. Results: Total of 245,235 cases (2,409,502 person-years) were identified, 36.3% received chemotherapy. 66.2% were ER+PR+, 11.9% were ER+PR-, 2.5% ER-PR+ and 19.5% were ER-PR-. Median follow up was 11.3 years (range 1-22.9 years), 36,005 (14.7%) cases eventually developed SM. In patients who received radiotherapy (RT), risk of developing SM was increased by 43% (SIR 1.43 [95%CI 1.39-1.46] in those who received chemotherapy (CT) compared to only 22% (SIR 1.22 [95%CI 1.20-1.24]) in those who did not receive chemotherapy (non-CT). In patients who were not treated with radiotherapy, those who got chemotherapy (CT) had an increased risk of developing SM: SIR 1.27 [95%CI 1.23-1.31]. Breast cancers represented 37% of all SM followed by digestive system (16.6%), uterine (14.3%), bronchopulmonary (12.7%), colorectal (9.4%), urinary system (4.6%), lymphoma (3.4%) and ovarian cancers (3.0%). Acute myeloid leukemia (AML) and salivary gland tumors represented only 1.3% and 0.3% of all SM. Conclusions: Risk of secondary malignancies, which includes second primary cancers is significantly higher for cases that received chemotherapy and the risk is increased irrespective of radiation status. Radiation therapy increases the risk for secondary malignancies.
TCT-204 Role of Different Antithrombotic Regimens After Percutaneous Left Atrial Appendage Occlusion: A Large Single-Center Experience
Authors: Alessandra Laricchia, Patrizio Mazzone, Damiano Regazzoli, Giuseppe D'Angelo, Satoru Mitomo, Lorenzo Azzalini, Antonio Colombo, Matteo Montorfano
Journal: Journal of the American College of Cardiology (2018)
Effect of weight loss during concurrent chemoradiation on outcomes of oropharyngeal cancer.
Authors: Timothy Hancock Dorius, Nathan Ronald Bennion, Lynette Smith, Brett Van Briggle, Weining Zhen, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2016)

e17541 Background: Concurrent chemoradiation improves outcomes in patients with locoregionally advanced oropharyngeal cancer (LA-OPC). Weight loss during treatment affects optimal delivery of treatment, but its effects on overall outcomes are unknown. We review our data to determine factors that predict for outcomes in LA-OPC. Methods: This is a retrospective analysis of patients treated with concurrent chemoradiation for LA-OPC at a single center from 2007-2014. Patient data were abstracted from medical records. Overall survival (OS) and event-free survival (EFS) were compared using Kaplan-Meier curves. The log-rank test was used to determine statistical significance. Results: Seventy-four patients with Stage III (n = 3) or Stage IV (n = 71) LA-OPC were analyzed. These included 65 males and 9 females. Of the 55 patients with known HPV status, 47 (85.5%) were positive. The median age at diagnosis was 58.5 years. The planned chemotherapy regimen was high dose cisplatin in 58 patients (78.4%) and cetuximab in 15 (20.3%). Of the 74 patients, 72 (97.3%) completed the planned radiation while 39 (53.4%) completed the planned chemotherapy. Two (2.7%) patients had a local recurrence while 4 (5.4%), and 9 (12.3%) patients had regional or distant recurrence respectively. Eleven patients had a feeding tube placed before treatment, while another 32 had one placed during treatment. Fifty-two (70.3%) patients were alive at a median follow-up of 3.4 years. Receipt of less than planned chemotherapy was significantly associated with worsened OS (p = 0.0032) and EFS (p = 0.01). On multivariate analysis, increased age, pre-treatment weight, and pre-treatment placement of a feeding tube were associated with inferior OS and DFS. Increased percentage weight loss (HR-0.82 per 1% increase in weight loss; 95% CI, 0.72 - 0.94; p = 0.005 for OS; HR-0.88; 95% CI, 0.79-0.98; p = 0.03 for EFS) and absolute weight loss (HR-0.81 per 1 kg decrease in weight; 95% CI, 0.70-0.94; p = 0.005 for OS; HR-0.87; 95% CI, 0.77-0.98; p = 0.02 for EFS) were associated with better outcomes. Conclusions: Weight loss during concurrent chemoradiation seems to be associated with improved outcomes. The mechanisms behind this phenomenon need to be investigated further.
Baseline plasma matrix metalloproteinase 9 (MMP9) to predict overall survival (OS) benefit from bevacizumab (BEV) in newly diagnosed glioblastoma (GBM): Retrospective analysis of AVAglio.
Authors: Olivier L. Chinot, Josep Garcia, Sylvie Romain, Cedric Revil, Timothy Cloughesy, Warren P. Mason, Ryo Nishikawa, Roger Henriksson, Frank Saran, Antoine F. Carpentier, Khe Hoang-Xuan, Petr Kavan, Dana Cernea, Alba Ariela Brandes, Yannick Kerloeguen, Christoph Mancao, L'Houcine Ouafik, Lauren E. Abrey, Wolfgang Wick, Emeline Tabouret
Journal: Journal of Clinical Oncology (2016)

2020 Background: BEV + radiotherapy/temozolomide (RT/TMZ) improves progression-free survival (PFS) (vs placebo [PBO] + RT/TMZ) in newly diagnosedGBM, but this does not translate into an OS benefit (AVAglio/NCT00943826). Data from recurrent GBM (Tabouret, Neuro Oncol 2014, 2015) suggest that MMP9 and MMP2 plasma levels may predict BEV-related tumor response and correlate with improved OS. Evaluation of MMP9 and MMP2 as potential biomarkers for patients likely to derive OS benefit from BEV is needed. We present data from a retrospective analysis of AVAglio, which assessed whether MMP9 baseline levels predicted OS benefit from BEV in newly diagnosed GBM. Methods: MMP9 and MMP2 levels were assessed (ELISA; R&D Systems) in baselineplasma samples (after surgery/before treatment) from 577/921 patients enrolled in AVAglio (PBO n=294; BEV n=283). Post-hoc analysis and PFS/OS multivariate models including MMP9–treatment interactions were carried out. Results: MMP9 distribution at baseline was comparable between arms (median [Quartile1–3]: PBO 82.4ng/mL [44.8–160.3]; BEV 83.6ng/mL [43.8–133.8]). Patient characteristics were generally balanced between MMP9 subgroups (per quartile), including for known prognostic factors. Patients with low MMP9 (<Quartile1) derived significant OS benefit from BEV, which translated into a median 5.2-month OS increase (HR 0.51, 95% CI 0.34−0.76, p=0.0009; median 13.6 [PBO] vs 18.8 [BEV] months); a consistent PFS benefit was seen (HR 0.36, 95% CI 0.24−0.54, p<0.0001). In patients with high MMP9, there was a trend for the HR to favor the PBO arm for OS (>Quartile 3 HR 1.21, 95% CI 0.80−1.81). No clear prognostic value of MMP9 was shown, although an interaction was seen between treatment and MMP9 (p=0.03) for OS. MMP2 (by quartile) did not exhibit prognostic or predictive value. Conclusions: A post-hoc analysis of AVAglio suggested that baselineplasma MMP9 levels were predictive of OS benefit from the addition of BEV to RT/TMZ in newly diagnosed GBM. Clinical trial information: NCT00943826.
Analysis of patient related and trial related factors leading to non-participation of patients with advanced cancer in immunotherapy clinical trials: Implications for modifying eligibility criteria.
Authors: Ishwaria Mohan Subbiah, Le Huang, Mary Jane Schneck, Anna Lui, Vivek Subbiah, David S. Hong
Journal: Journal of Clinical Oncology (2018)

e15066 Background: Patients with advanced cancers are referred to early phase clinical trials after progression on standard-of-care regimens. However early phase I/II trials tend to have stringent eligibility criteria not only regarding performance status and organ function but also on wash-out periods from prior therapies. In this study, we sought to better characterize the clinical circumstances and outcomes of patients who signed consent to participate in a phase I trial but ultimately did not receive any study drug/therapy on that trial. Methods: We identified 650 consecutive pts w advanced cancer who consented to participate on a immunotherapy-based phase I trials bw 12/2015-12/2017, and collected patient and disease characteristics as well as clinical outcomes, in particular if they in fact did proceed to receive therapy. Results: Among the 650 pts who initially consented to participate on immunotherapy based phase I trials, 178 (27%) were never treated. Reasons for non-participation in trial were included: 33 (19%) pursued alternate therapies (of whom 13 elected to receive therapy at home), 28 (16%) had an unfavorable result on a pre-trial screening test, 22 (12%) had systemic disease progression, 9 (5%) developed new brain mets. 18 (10%) pts died prior to start of trial, 16 (9%) developed a new lab abnormality (hepatic, renal dysfunction), 14 (8%) had a decline in performance status, 12 (7%) withdrew consent for reasons not provided, 12 (7%) did not have enough biopsy or archival tissue for correlative studies as directed by the protocol, 8 (4%) had no reason documented, 7 (4%) reported other reasons [ prohibited concomitant medications, no measureable disease on imaging,]. Six (3%) pts were denied by insurance, to participate on trial & 2 (1%) did not start bc that protocol was on an administrative hold. Conclusions: Almost a third of patients who signed consent on a trial were unable to start on study, for the reasons above. In-depth analysis into these reasons can identify potentially modifiable factors that can streamline the pretrial period to ensure this vulnerable population has maximum access to initiate the study.
Psychosocial impact of skin biopsies in the setting of melanoma screening: a cross‐sectional survey
Authors: N.H. Matthews, P.M. Risica, L.K. Ferris, M. Beatson, M. Saul, A.C. Geller, F. Solano, J.M. Kirkwood, M.A. Weinstock
Journal: British Journal of Dermatology (2018)
TCT-222 Safety and Feasibility of an Early Ambulation Protocol after Transfemoral Transcatheter Aortic Valve Implantation: Results of the Early Mobilisation after TF-TAVI (MobiTAVI) Trial
Authors: Jeroen Vendrik, Martijn van Mourik, Wieneke Vlastra, Ronak Delewi, Jan Piek, Marije Vis, Karel Koch, Jan Baan
Journal: Journal of the American College of Cardiology (2018)
Prognostic value of pretreatment <sup>18</sup>F-FDG PET-CT for nasopharyngeal carcinoma patients.
Authors: Yecai Huang, Mei Feng, Qiao He, Peng Xu, Jinyi Lang
Journal: Journal of Clinical Oncology (2017)

e17521 Background: Nasopharyngeal carcinoma (NPC) is a special subtype of head and neck cancer (HNC), there is no highly specific prognostic parameters for NPC. Prognostic value of pretreatment 18 F-PET-CT in NPC patient has controversial conclusion. Methods: The prospective and retrospective observational trails which used the 18 F-FDG PET to predict the prognosis of the NPC patients were searched in MEDLINE, EMBASE, Cochrane library, CBM, CNKI and VIP (inception to July 2016). Two authors independently assessed study quality and extracted data. Event-free survival (EFS) was considered as the primary endpoint and overall survival rate (OS) was considered as the secondary endpoint. Results: 14 studies and 1,134 patients were included in our analysis. The HR (Hazard ratio) of SUVmax-T, MTV-T and TLG-T for EFS was 1.71 (95% CI, 1.02-2.86, p= 0.04), 2.38 (95%CI 1.53-3.70, p= 0.0001) and 1.65 (95%CI 0.76-3.59, p= 0.21) respectively. Among studies including TLG-T, those with a fixed SUV of 2.5 had an HR 3.55 (95% CI, 1.42–8.84, p= 0.007). The HR of SUVmax-T and MTV-T for OS was 2.19 (95%CI, 1.47-3.27, p= 0.0001) and 2.69 (95% CI, 1.01-7.17, p =0.05). Among studies including MTV-T, those with a fixed SUV of 2.5 had an HR of 4.07 (95% CI, 2.22–7.46, p&lt; 0.00001). Test for predictive value of pretreatment SUVmax-LN, MTV-LN and TLG-LN for EFS and OS showed no significant results ( p&gt; 0.05). Conclusions: We suggested thatSUVmax, MTV and TLG (with a fixed SUV of 2.5) of primary tumor before treatment may be the independent prognostic factors for NPC patients, while SUVmax, MTV and TLG of metastatic lymph node are not.
Abstract 18812: Myocardial Senescence Induced by Inactivation Aldh2-SIRT1-GATA4 Pathway Involves in Heart Remolding After Acute Infarction
Authors: Li Xue, Sumei Cui, Feihong Yang, Baoshan Liu, Qiuhuan Yuan, Jiaojiao Pang, Shujian Wei, Jiali Wang, Feng Xu, Yuguo Chen
Journal: Circulation (2016)

Introduction: It is well known that there exist myocardial apoptosis and necrosis after acute myocardial infarction (AMI). Moreover, our previous study has found cellular senescence occurs after cardiac hypoxia. Compared with cellular apoptosis and necrosis, senescent cells can secrete soluble factors continuously, termed as the senescence-associated secretory phenotype (SASP), by which to influence the local microenvironment. Hypothesis: Myocardial senescence may play an important pathological role in the process of heart remolding after AMI, and the underlying mechanisms may be due to the accumulation of GATA4 resulted from ALDH2 inactivation-inhibited autophagy. Methods: Myocardial senescence in myocardium after AMI was assessed by immunohistochemistry (p16Ink4a, p21CDKN1A and p53) and senescence- associated β-galactosidase (SA-β-gal) staining. And the abundance of mRNA relevant with SASP was quantified by RT-qPCR. To identify the molecular targets regulating cellular senescence, siRNAs were used to de...