tbuckley/cabot-search huggingface dataset:
Genomic landscape of pineoblastoma.
Authors: Bryan Kincheon Li, Alexandre Vasiljevic, Ben Ho, Anne Jouvet, Eugene I. Hwang, Jordan R. Hansford, Annie Laquerriere, Marie-Bernadette Delisle, Sridharan Gururangan, Jason R. Fangusaro, Fabien Forest, Nobusawa Sumihito, Helen Toledano, Maryam Fouladi, Guillaume Gauchotte, David Simon Ziegler, Eric Bouffet, Richard G Grundy, Christelle Dufour, Annie A Huang
Journal: Journal of Clinical Oncology (2018)

2028 Background: Pineoblastoma (PB) is a rare but aggressive pediatric brain tumour arising from the pineal gland. Overall survival rates are estimated at 50-60%, with younger patients ( < 5 years old) faring much worse (15-40%) despite intensive treatment regimens. Although germline RB1 and DICER1 alterations have been reported in a small proportion of PB, the clinical significance of such alterations and the biology of sporadic cases remains unknown. Methods: We collected tumor tissue from 75 cases of PB diagnosed at their local centres from across five continents. We undertook global DNA methylation profiling and performed multiple orthogonal consensus clustering analyses to elucidate PB subgroups. Chromosomal copy number alterations were determined using Conumee then GISTIC 2.0. Mutational analysis was conducted by whole exome and RNA sequencing. Clinical data was analyzed with correlative statistical methods and outcomes were measured by Kaplan-Meier survival estimates. Results: We discovered that PBs comprise four molecular sub-types, designated groups 1 to 4, with characteristic copy number alterations and mutational patterns. These molecular sub-groups exhibit distinct clinical features and survival outcomes. While PB groups 1-3 arose in older children (median ages 5.2-12.6 years), group 4 PB was restricted to much younger children (median age 1.4 years). Group 4 PB exhibited the highest incidence of metastases (53%) and had the worst 5-year event-free survival (EFS) and overall survival (OS) at 7.7% and 16.7%, respectively. In contrast, group 2 patients had a 5-year EFS and OS of 100%, while groups 1 and 3 had intermediate outcomes (5-year EFS 36.1% and 53.3%, 5-year OS 68.1% and 53.3%, respectively). Conclusions: PBs divide into four groups, each with a distinct genetic and clinical profile. These findings will have important implications for precise patient stratification and form the foundation for preclinical studies of biology-informed therapies.
Biomarker to cost-effectively harness the technical prowess of palliative radiation: Neutrophil lymphocyte ratio (NLR) and overall survival following palliative radiotherapy in an unselected real-world population of all tumor sites.
Authors: Santhanam Sundar, James Price, Kirsty Clarke, Thomas Wolfe, D Thurairasa, Ewan Shawcroft
Journal: Journal of Clinical Oncology (2017)

10111 Background: Single fraction radiotherapy (RT) is standard of care for palliation of pain from bone metastases (ASTRO IJROBP 2011 79:965). But costly, complex, multi-fraction RT is quite often used for palliation of symptoms from various organs. Health care costs are burgeoning (ASCO JCO 2012 30: 1715). Costs can be constrained by judiciously reducing use of unnecessary multi-fraction RT in pts with limited life expectancy. But radiation oncologists’ ability to predict survival is inaccurate. (Chow IJROBP 2005 61:870). Hence we assessed clinical utility of Neutrophil Lymphocyte ratio (NLR) - a routinely available biomarker. Methods: 233 patients (pts) undergoing palliative RT over a 3 month at Nottingham University Hospital. Predominant Tumour SITES: Lung 28% Breast 13% Prostate 13% Colorectal 9% Gastro-Oesophageal 5% Myeloma 5% Bladder 5%. Predominant HISTOLOGY: Adenocarcinoma 61% Squamous Cell 14%. NLR available for 158 pts. Results: A NLR of 4.5 was highly predictive of 90-day mortality &amp; overall survival in an unselected real world population. (Table). No survival benefit seen for multi-fraction RT over single fraction RT across all tumour sites. On survival analysis by Cox regression, increased NLR was significant with a hazard ratio of 2.2 (95% CI 1.3 to 3.7) whereas total radiation dose, use of multiple fractions , age, serum haemoglobin, serum albumin &amp; histology were not significant. Conclusions: In palliative care of advanced cancer, for pts with high NLR (&gt;4.5), Single fraction RT should be the standard of care for palliation of symptoms. [Table: see text]
Genetic variations associated with cancer cachexia pathways to predict survival in metastatic colorectal cancer (mCRC): Results from FIRE-3 and TRIBE.
Authors: Yuji Miyamoto, Sebastian Stintzing, Fotios Loupakis, Wu Zhang, Shu Cao, Yan Ning, Satoshi Okazaki, Martin D. Berger, Mitsukuni Suenaga, Marta Schirripa, Satoshi Matsusaka, Dongyun Yang, Jordan David West, Roel Gopez, Diana L. Hanna, Afsaneh Barzi, Hideo Baba, Volker Heinemann, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2016)

3590 Background: Cancer cachexia is a multifactorial syndrome that commonly affects mCRC patients (pts) leading to progressive functional impairment. Cachexia occurs in 70% of pts with advanced cancer. The Activin/TGF-beta/SMAD pathway, known as cachexia pathway, plays a critical role in development and progression of CRC. We aimed to evaluate whether single nucleotide polymorphisms (SNPs) of genes involved in the cachexia pathway predict clinical outcomes in bevacizumab (BV) treated mCRC pts. Methods: Genomic DNA was obtained from mCRC pts receiving bevacizumab plus FOLFIRI as first-line treatment and analyzed by using PCR-based direct sequencing. Nine functional SNPs in 5 genes (INHBA, MSTN, ACVR2B, SMAD2 and FOXO3) were tested in a discovery cohort of 294 pts in FIRE3 trial (NCT00433927), then validated in 230 pts in TRIBE trial (NCT00719797). Results: In FIRE3 BV arm, main characteristics were the following: male/female = 194/100; median age = 65; RAS-wildtype/mutant = 198/83; median PFS = 10.2 months; median OS = 24.2 months, median follow-up time = 40.8 months. Among RAS-wildtype pts, SMAD2 rs1792689 A/- (N = 34) achieved a significantly worse PFS compared to G/G variant carriers (N = 157) in the univariate (median PFS 9.2 vs 10.8 months respectively, HR = 1.50 [95%CI 1.02-2.22], p = 0.037) and in the multivariate analysis (HR = 1.58 [95%CI 1.06-2.34], p = 0.023). Among RAS-mutant pts, ACVR2B rs2268753 T/T (N = 30) showed a significant worse OS compared to C/- variant carriers (N = 46) in the univariate (median OS 8.8 vs 11.2 months respectively, HR = 1.81 [95%CI 1.06-3.09], p = 0.029) and in the multivariate analysis (HR = 2.13 [95%CI 1.19-3.81], p = 0.011). Among female pts, INHBA rs17776182 A/- (N = 31) showed a significant worse PFS compared to G/G variant carriers (N = 59) in the univariate (median PFS 8.8 vs 10.1 months respectively, HR = 1.61 [95%CI 1.01-2.57], p = 0.045) and in the multivariate analysis (HR = 1.75 [95%CI 1.08-2.85], p = 0.024). The validation analyses using TRIBE cohort are ongoing. Conclusions: Our study showed for the first time that variations in genes regulating cancer cachexia may be affect prognosis of mCRC pts treated with BV based chemotherapy.
Patient safety: A progressive deprescribing model in patients with advanced solid tumors assisted at Instituto Oncológico Henry Moore (IOHM).
Authors: Ernesto Gil Deza, Eduardo L. Morgenfeld, Edgardo G. J. Rivarola, Marcelo Muino, Carlos Fernando Garcia Gerardi, Flavio Tognelli, Mariana Abal, Sandra L. Ares, Monica Montiel, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2017)

6594 Background: "Deprescribing is the process of withdrawal of an inappropriate medication, supervised by a health care professional with the goal of managing polypharmacy and improving outcomes" ( Br J Clin Pharmacol 80:6, 1254. 2015). The aim of this paper is to present a model for deprescribing used at IOHM. Methods: Between 09/26/2012 and 09/26/2016, 10,053 pt filled out a Past Medical History Form, listing all the medications they were taking regularly. We selected all the pt. with advanced solid tumors (AST). In each pt the expected survival was established in order to evaluate the usefulness of the Tx. The drugs were classified in three groups: A) Green: Adequate (must be maintained); B) Yellow: Questionable (could be maintained or removed) or C) Red: Avoidable (must be removed). Results: We registered 2,103 pt who met the inclusion criteria. Sex F/M: 905 /1198. Median age 63 y (r = 19-99). A total of 1,629 pt. (77%) were taking medications on a regular basis. The total amount of medications was 5,679 . Median medications per patient: 3 (range: 1-14). Eighty percent of the pt (1,298 pt) were receiving questionable of avoidable medications. The following table shows the distribution of medications per group. Conclusions: A) In this cohort of 2,103 pt with AST, half of them had an average life expectancy of less than one year. B) 1,298 out of 1,629 pt (80%) were receiving a questionable medication C) 596/5,769 (10%) of the registered drugs, had to be suspended immediately and at least a thousand more could be eliminated. d) Obstacles to deprescribing were essentially medical ignorance, fear and inexperience. [Table: see text]
PD-L1 expression and its significance in Chinese patients with non-small cell lung cancer.
Authors: Susmita Sharma, Xiubao Ren
Journal: Journal of Clinical Oncology (2016)

e20013 Background: Over the past few years PD-1-PD-L1 pathway has received a considerable amount of interest from the researchers working in the field of cancer immunotherapy,Expression of PD-L1, a ligand for PD-1 has been described in many tumor types including NSCLC and considered as poor prognostic factor for survival. Lung cancer is one of the major cause of mortality in many countries including china where every year 130,000 deaths occur because of it. However, very few researches have been done regarding the role of PD-L1 in NSCLC and even among these the results of various studies are still conflicting. The main objective of this study was to examine the expression and significance of PD-L1 in chinese patients with NSCLC . Methods: A retrospective analysis was conducted on 195 NSCLC patients who had undergone diagnostic surgery as well as treatment and follow up for NSCLC in TJMUCIH. Immunohistochemistry technique was utilized to examine the expression of PD-L1 in FFPE tissue samples of NSCLC, collected from these patients during diagnostic/therapeutic surgery. Immunohistochemistry staining was analyzed to examine the difference in PD-L1 expression among various clinicopathological variables as well as the prognostic significance and independent predictive value of PD-L1 in NSCLC Results: Significant difference in PD-L1 expression was observed in between two histological subtypes (Adenocarcinoma and Squamous cell carcinoma) of NSCLC.PD-L1 expression by NSCLC tumor tissue was found be a good prognostic marker in NSCLC patients with better overall survival in those with higher expression than those with negative or low PD-L1 expression.PD-L1 was also identified as an independent predictor of outcome in NSCLC patients. Conclusions: PD-L1 can be considered as an important and independent marker in predicting the outcome of NSCLC patients as well as their response to treatment. A powerful and reliable tool to measure its expression should be devised in future in an attempt to finding a cure for this otherwise resilient tumor which is responsible for high mortality and morbidity among modern human population
Prospective phase II trial of neoadjuvant chemotherapy with gemcitabine and S-1 (GS) for borderline resectable (BR)/unresectable (UR) pancreatic cancer (CAP-003 study).
Authors: Hideyuki Yoshitomi, Shigetsugu Takano, Shingo Kagawa, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Masaru Miyazaki, Masayuki Ohtsuka
Journal: Journal of Clinical Oncology (2018)

e16225 Background: Recently, neoadjuvant therapy for BR/UR pancreatic cancer is widely performed. However, no standard regimen has been established so far. GS showed favorable response rate in unresectable pancreatic cancer. Methods: Patients with BR or UR pancreatic cancer without distant metastasis were enrolled. Patients received GS (S-1 60/80/100mg/day based on BSA po, d1-14 plus GEM 1g/ m2,iv, d8, 15, q3w X 3). Thereafter, staging was re-estimated and patients underwent surgery, if possible. After surgery, patients received adjuvant therapy with S-1 (60/80/100mg/day based on BSA po, d1-14 q3 X8). Primary endpoint was R0 resection rate and secondary endpoints included R0+R1 resection rate, overall survival, and safety. Results: Between April 2011 and October 2014, 46 patients were enrolled in this study. One patient was excluded due to the accompanied breast cancer which was found just after enrollment. GS therapy was discontinued in 3 patients due to adverse events (AE) in 2 and tumor progression in 1. Grade 3 or more hematologic AE was occurred in 21 patients (46.7%) and non-hematologic AE in 3 patients (6.7%). No treatment related death was occurred. Thirty six patients underwent surgical resection and R0 and R0+R1 resection was achieved in 17 (37.8%) and 33 patients (73.3%), respectively. Median overall survival and 2 year survival rate were 18.9m and 47.6%, respectively, with 18.7m of median observation period. Those of resected patients were 28.8m and 59.8%, respectively. Conclusions: GS is well tolerated as neoadjuvant therapy. The favorable overall survival, especially for patients with resection, indicates the usefulness of this regimen for BR/UR locally advanced pancreatic cancer patients. Clinical trial information: UMIN000005578.
Immunohistochemical evaluation of p53, Ki67, ERG, MYC and PTEN in Gleason pattern 3 prostate cancer: Implication in active surveillance.
Authors: Arie Carneiro, Paulo Priante Kayano, Adam G. Sowalsky, Tercia Jovino Neves Santos, Paolo Dell'oglio, Natasha Kouvaleski Saviano Moran, Lucila Heloisa Simardi Santiago, Gustavo Caserta Lemos, Marcos Tobias Machado, Rafael Sanchez-Salas, Andrew Wagner, Bianca Bianco
Journal: Journal of Clinical Oncology (2018)

e17068 Background: The presence of prostate cancer (PCa) Gleason pattern 4 or 5 on biopsy is a major contraindication for active surveillance (AS). Limitations of anatomopathological morphological analysis, can severely compromise the accuracy of PCa risk stratification. In this study, expression of recurrent oncogenes (MYC and ERG), tumor suppressors (PTEN and p53) and a marker of proliferation (Ki67) were evaluated as biomarkers in order to predict whether histologically indolent Gleason pattern 3 co-occurs with unsampled higher grade disease warranting further biopsy, which may in turn inform more intensive treatment. Methods: This cross-sectional study involved 37 patients diagnosed with localized PCa and very low risk who underwent radical prostatectomy. The patients were divided into two groups according to the final pathology: Group 1, Gleason score 6 (ISUP 1, n = 17) and Group 2, Gleason score 7 (ISUP 2 or 3, n = 20). The expression of proteins p53, Ki67, ERG, MYC and PTEN in FFPE samples of neoplastic and adjacent benign prostatic tissue were evaluated by digital image immunohistochemistry. Results: The expression of ERG, Ki67, and MYC was significantly higher in neoplastic tissue when compared to benign in both groups, while expression of PTEN was significantly lower. Strong p53 staining, which is enriched for gain-of-function missense alleles, did not present a significant statistical difference. When the Gleason 3 and Gleason 4 areas of group 2 were compared, no difference was observed in the expression of any of the markers studied. In the univariate analysis, comparing the absolute expression of the biomarkers in Gleason 3 PCa samples from both groups, Ki67 was the only independent predictor of adjacent Gleason 4 (ISUP 2 or 3). In the multivariate analysis, including the relative expression of the biomarkers in the Gleason 3 PCa of the two groups, age and PSA; it was observed that only PTEN (OR = 1, CI = 1.03-1.31) presented as an independent factor of adjacent Gleason 4 (ISUP 2 or 3). Conclusions: An increase in absolute Ki67 expression and loss PTEN protein expression, associated with age and PSA, were predictors of adjacent Gleason pattern 4.
TCT-67 Post-Stent OCT vs IVUS Predictors of 2-Year Outcomes
Authors: Xiao Wang, Yongqing Lin, Mitsuaki Matsumura, Eisuke Usui, Tetsumin Lee, Wenbin Zhang, Yang Cao, Mengdan Liu, Masahiro Hoshino, Taishi Yonetsu, Gary Mintz, Tsunekazu Kakuta, Akiko Maehara
Journal: Journal of the American College of Cardiology (2018)
De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation
Authors: M. Felicia Basilicata, Ange-Line Bruel, Giuseppe Semplicio, Claudia Isabelle Keller Valsecchi, Tuğçe Aktaş, Yannis Duffourd, Tobias Rumpf, Jenny Morton, Iben Bache, Witold G. Szymanski, Christian Gilissen, Olivier Vanakker, Katrin Õunap, Gerhard Mittler, Ineke van der Burgt, Salima El Chehadeh, Megan T. Cho, Rolph Pfundt, Tiong Yang Tan, Maria Kirchhoff, Björn Menten, Sarah Vergult, Kristin Lindstrom, André Reis, Diana S. Johnson, Alan Fryer, Victoria McKay, Richard B. Fisher, Christel Thauvin-Robinet, David Francis, Tony Roscioli, Sander Pajusalu, Kelly Radtke, Jaya Ganesh, Han G. Brunner, Meredith Wilson, Laurence Faivre, Vera M. Kalscheuer, Julien Thevenon, Asifa Akhtar
Journal: Nature Genetics (2018)
Prognostic impact of BRAF V600E mutation in patients with non-metastatic colorectal cancer with microsatellite instability: A systematic review and meta-analysis.
Authors: Sashidhar Manthravadi, Weijing Sun, Anwaar Saeed
Journal: Journal of Clinical Oncology (2018)

3597 Background: Colorectal cancer (CRC) displaying high levels of microsatellite instability (MSI-H) has been associated with improved survival in colorectal cancer. MSI-H CRC is also known to be enriched in V600E mutations in the BRAF gene (BRAF-Mut). BRAF-Mut is a known adverse prognostic factor in patients with non-metastatic MSI-low CRC. However, the prognostic role of BRAF V600E mutations in non-metastatic MSI-H CRC remains unclear. Methods: Following PRISMA guidelines, a systematic review of PubMed and Embase was performed from inception through January 2018 to identify studies which described the impact of BRAF-Mut on outcomes in patients with non-metastatic MSI-H CRC. Summary hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS) were estimated using a random effects model and heterogeneity was estimated using the inconsistency index (I2). Results: After reviewing 988 reports, 8 studies which described the association between BRAF status and outcomes in non-metastatic MSI-H CRC were selected for inclusion. These were reported from Europe, North America and Asia. A total of 1164 patients with MSI-H CRC were included of whom 553 were found to carry BRAF V600E mutation. Data regarding RFS and OS for BRAF-Mut vs BRAF-Wild type was provided in 5 and 8 studies respectively. No association was found between BRAF-Mut and RFS in patients with non-metastatic MSI-H CRC (HR 1.13; 95% CI 0.77- 1.67, I2= 0%). In contrast to these findings, BRAF-Mut had an adverse impact on OS in patients with non-metastatic MSI-H CRC (OS = HR 1.53; 95% CI 1.15- 2.03, I2= 0%). Conclusions: BRAF V600E mutation appears to have no association with disease recurrence but does correlate with adverse overall survival in patients with non-metastatic colorectal cancer with high levels of microsatellite instability. Clinical trials planned in the future must therefore consider adding BRAF status as a stratification factor.
Role of hematologic markers as prognostic factors in head and neck squamous cell carcinoma: Experience of a Brazilian Public Hospital.
Authors: Tiago Costa de Padua, Hakaru Tadokoro, Otavio Baiocchi
Journal: Journal of Clinical Oncology (2018)

e18041 Background: HNSCC has a high incidence around the world and in Brazil it is one of the most common malignancies. Hematologic markers represent a measurable parameter of host inflammation with known prognostic value in several malignancies. Our objective was to investigate the prognostic role of pretreatment neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in patients with HNSCC treated with chemoradiotherapy (CRT) at our institution. Methods: We retrospectively analyzed medical records of 52 HNSCC patients treated with definitive CRT between 2007 and 2015. Baseline complete blood count, demographic and clinica data were collected. Pretreatment NLR and PLR were retrospectively calculated and investigated for correlation with OS using Kaplan-Meier method and ROC analysis. Results: A total of 52 patients with oral cavity (n = 3, 5.8%), oropharyngeal (n = 25, 48.1%), laryngeal (n = 23, 44.2%), and hypopharingeal (n = 1, 1.9%) cancer were included. The mean age was 61.5 ± 9.1 years and the population was predominately male (82.7%). The median interval from diagnosis to beginning of treatment was 94 days (29-234). In the overall population, median OS (mOS) were 28 months. The median value of NLR was 3.239 (0.92 – 23.51) and PLR was 129.56 (51.42 – 817.93). Using median value as cut-off, NLR and PLR were significantly associated with OS. Patient with NLR > 3.239 had a mOS of 16 months, whereas the mOS for NLR ≤ 3.239 was 84 months (Log-rank p = 0.050). Patient with PLR > 129.56 had a mOS of 13 months, whereas the mOS for PLR ≤ 129.56 was 84 months (Log-rank p = 0.050). Using ROC curves, NLR and PLR were also associated with OS. PLR had the greatest area under the curve (AUC) of 0.739 (0.595 – 0.883; p = 0.004), and NLR had the AUC of 0.672 (0.506 – 0.838; p = 0.039). Conclusions: Our results indicate that pretreatment hematologic markers (NLR and PLR) provide important prognostic information in HNSCC patients treated with CRT and represent a cost-effective and easily measured marker for patient stratification. When possible, these parameters should be integrated into clinical decision-making. A second study o is ongoing analyzing these markers in HNSCC patients treated with immunotherapy.
TCT-396 Association of Peripheral Artery Disease with In-hospital Outcomes after Endovascular Transcatheter Aortic Valve Replacement
Authors: Divyanshu Mohananey, Pedro Villablanca, Sagar Ranka, Tanush Gupta, Nirmanmoh Bhatia, Oluwole Adegbala, Tomo Ando, Adam Greenbaum, Dee Dee Wang, Jose Wiley, Marvin Eng, Ankur Kalra, Harish Ramakrishna, Binita Shah, William O'Neill, Deepak Bhatt
Journal: Journal of the American College of Cardiology (2018)
TCT-469 One-year clinical outcome of biodegradable polymer sirolimus-eluting stent in patients with acute coronary syndrome. Insight from the ULISSE registry.
Authors: Elisabetta Moscarella, Alfonso Ielasi, Cosmo Godino, Giuseppe Ferrante, Carlo Andrea Pivato, Mauro Chiarito, Alberto Cappelletti, Giulia Perfetti, Valeria Magni, Eugenio Prati, Stefania Falcone, Adele Pierri, Stefano De Martini, Matteo Montorfano, None rosario parisi, Nicola Locuratolo, Angelo Anzuini, Alberto Margonato, Alberto Benassi, Paolo Calabro', Carlo Briguori, Franco Fabbiocchi, Bernhard Reimers, Antonio Bartorelli, Antonio Colombo
Journal: Journal of the American College of Cardiology (2018)