tbuckley/cabot-search huggingface dataset:
Comparison between lobaplatin and cisplatin plus 5-fluorouracil combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: A multicenter randomized phase III clinical trial.
Authors: Kuiyuan Liu, Wei-Xiong Xia, Wen-Ze Qiu, Ya-Hui Yu, Guo-Ying Liu, Hu Liang, Wang-Zhong Li, Shu-Hui Lv, Liang-Ru Ke, Hao-Yuan Mo, Guo Ling, Ming-Yuan Chen, Ka-Jia Cao, Chong Zhao, Chao-Nan Qian, Xing Lv, Xiang Yanqun, Xiang Guo, Xin-Jun Huang
Journal: Journal of Clinical Oncology (2018)

6029 Background: Cisplatin-based chemoradiotherapy(CRT) has been widely applied as a first-line regimen in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). However, cisplatin can induce severe side effects .Our previous phase II trial revealed that lobaplatin combined with 5-fluorouracil (5-FU) followed by concurrent chemoradiotherapy (CCRT) showed encouraging anti-tumor effects with tolerable toxicities for LA-NPC. Here, we assess the efficacy and toxicities of a regimen of lobaplatin versus cisplatin plus 5-FU as induction chemotherapy (ICT) followed by concomitant lobaplatin versus cisplatin with intensity-modulated radiotherapy (IMRT). Methods: Stage III-IVB NPC patients were randomly assigned to receive lobaplatin or cisplatin plus 5-FU as ICT followed by CCRT. In the lobaplatin arm, patients received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-FU at a dose of 4 g/m2 followed by lobaplatin at a dose of 30 mg/m2 on days 43 and 64 concomitant with IMRT. Lobaplatin was replaced by cisplatin (100mg/m2) in the cisplatin arm. The primary end-point was progression-free survival (PFS). Results: Of the 494 eligible patients, 250 were assigned to lobaplatin arm and 244 to cisplatin arm. No difference was observed in overall tumor response between two arms (98.6% vs. 97.7%, P= 0.459). After a median follow-up of 42.6 months, no statistically significant differences in 3-year PFS rate was observed between two arms (PFS: 78.9% vs. 82.0%, P= 0.985). During ICT, more patients suffered grade 3-4 leucopenia, neutropenia, nausea and vomiting in cisplatin arm (all P< 0.001). During CCRT, grade 3-4 anemia, nausea and vomiting were more common in cisplatin arm (all P< 0.001). Conclusions: The regimen of ICT with lobaplatin plus 5-FU followed by concomitant lobaplatin and IMRT achieved similar survival outcomes with less acute toxicity compared to cisplatin-based CRT in LA-NPC. Long-term follow up is required to determine whether lobaplatin-based systemic chemotherapy should be the first line of therapy for LA-NPC. Clinical trial information: ChiCTR-TRC-13003285.
Differences in systemic and surgical therapy between right (R) and left (L) sided metastatic colorectal cancer (mCRC).
Authors: Hagen F. Kennecke, Yaling Yin, Jonathan M. Loree, Rachel Leung, Sharlene Gill
Journal: Journal of Clinical Oncology (2017)

3602 Background: Patients (pts) with L sided primary tumors and mCRC have a significantly longer overall survival (mOS) than R sided tumors. Reasons for this remain unclear. The objective of this study was to compare systemic and surgical therapy received by tumor side and correlate this with mOS. Methods: Sequential pts with mCRC referred to the British Columbia Cancer Agency in 4 treatment eras were included. Pts with unresected primary tumors were excluded to ensure accurate ascertainment of tumor location. Receipt of systemic therapy includes Òall 3 drugsÓ (irinotecan, oxaliplatin, fluouracil), bevacizumab and epidermal growth factor receptor inhibitors (EGFRi). Cox-regression survival analysis for sidedness was performed controlling for age, sex, tumor grade, lymphovascular/perineural invasion, nodes removed and metastatectomy. Results: Among 3242 pts, a progressive improvement in mOS is documented in both L and R sided tumors since 1995. L and R tumors received Òall 3 drugsÓ, bevacizumab and EGFRi therapy with similar frequency which plateaued after the introduction of EGFRiÕs in 2009. Patients with L sided tumors were significantly more likely to have a hepatic or pulmonary resection. In Cox regression analysis, the mOS difference between L and R sided tumors was more pronounced in more recent eras. Conclusions: Patients with R sided tumors receive similar systemic therapy compared to L sided tumors, but are significantly less likely to undergo resection of distant disease. Resection of distant metastases may be an important consideration to understand the survival differences between R vs L mCRC. [Table: see text]
I accuse NHS England of a lack of transparency
Authors: Hendrik J Beerstecher
Journal: BMJ (2018)

Robinson says, of plans to restrict access to 17 interventions, “You can’t accuse NHS England of a lack of transparency.”1 But elusive phrases like “not routinely funded” or “not to commission them routinely” are used by policy makers. My interpretation is: “not available on the NHS.” The distinction is important as the NHS constitution gives the population the right to “a …
Febrile neutropenia in the nationwide inpatient sample: In-hospital outcomes and impact of cormobidities in 2007-2012.
Authors: Saqib Abbasi, Bassel Nazha, Elias Moussaly, Monika Manchanda, Jean Paul Atallah
Journal: Journal of Clinical Oncology (2017)

e18103 Background: Febrile Neutropenia (FN) is associated with significant in-patient morbidity and mortality. The goal of this study is to describe the in-patient outcomes of febrile neutropenia as well as the impact of comorbid conditions through a large national dataset. Methods: Using the Nationwide Inpatient Sample (NIS) for years 2007-2012, FN was defined as ICD-9 codes 288.0x for a primary discharge diagnosis of neutropenia in conjunction with 780.61 and 780.6 for fever in cancer patients. Linear regression analysis assessed for annual trends in in-hospital mortality, length of stay (LOS), and cost of stay (COS). Seasonal variations in admission rates were evaluated using ANOVA. We employed univariate and multivariate logistic regression analysis to elucidate the relationship between common comorbid conditions and mortality. Results: Among 55,253 cancer patients (weighted N = 264,384) admitted with FN between 2007 and 2012, there is a mean decrease in LOS from 5.78 to 5.47 days (p &lt; 0.0001), an increase in COS from $33,939 to $41,395 (p &lt; 0.0001), and a 12-15% drop in hospital admissions in winter months. Mortality rate is unchanged annually (1.06-1.28%). Univariate analysis identified an increased risk of mortality associated with atrial fibrillation (OR = 4.06), coronary artery disease (OR = 2.09), congestive heart failure (OR 4.39), hypertension (1.20), COPD (OR 2.33) pancytopenia (OR 1.81), and adrenal insufficiency (OR 5.32). All remained significant on multivariate analysis, except hypertension and diabetes mellitus. Conclusions: Between 2007-2012, FN had a slight decrease in length of stay, unchanged in-patient mortality and a 22% increase in hospitalization costs. Our results are in line with recently presented analyses of the same database (Blood 2016 128:4762, Blood 2016 128:5904). Comorbid conditions are associated with higher in-patient mortality, with up to 5-fold increase for those with atrial fibrillation, congestive heart failure and adrenal insufficiency. Clinicians should consider the significant impact of such comorbidities. Additional vigilance and potentially prophylactic antibiotics following treatment should be considered in affected patients.
Abstract 15259: The Prognosis of Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Naokata Sumitomo, Wataru Shimizu, Masao Yoshinaga, Hitoshi Horigome, Takeshi Aiba, Tsugutoshi Suzuki, Yoshihide Nakamura, Yoshio Aragaki, Kenichi Kurosaki, Masaru Miura, Hiroya Ushinohama, Hideto Takahashi, Minoru Horie
Journal: Circulation (2017)

Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is reported to have one of the worst prognoses among inherited arrhythmias. Methods: This study aimed to investigate the c...
Genomic landscape of diverse rare tumors: Next-generation sequencing of paired DNA and RNA analysis.
Authors: Ryosuke Okamura, Shumei Kato, Rahul Parulkar, Christopher Szeto, Sandip Reddy, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2018)

12114 Background: Patients (pts) with rare tumors (defined as incidence of < 15/100,000 per year) and ultra-rare tumors (prevalence < 2,000 in the U.S.) may lack standard or investigational therapeutic options. We have recently shown that matched targeted therapy approach based on the molecular profiling may result in responses in these cancers. Herein, we interrogated paired DNA/RNA among rare tumors using next-generation sequencing (NGS). Methods: A total of 286 pts with a rare tumor diagnoses were available for this analysis from NantHealth database. Somatic-specific variants were identified using paired tumor/normal comprehensive NGS. Analysis was focused on the 200 most frequently mutated genes in this cohort. Deep whole transcriptomic sequencing (RNA-Seq) (∼200x106 reads per tumor) was used to determine expression of observed somatic variants. Results: Median age was 57.8 (range 0.60 – 87.7 yo), 48.6% (139/286) were women. The most common diagnoses were bone and soft tissue sarcomas (39.5%, N = 113) followed by oral and throat cancers (9.4%, N = 27) and cholangiocarcinoma (7.3%, N = 21). Ultra-rare tumors such as carcinoma of thymus (N = 10), adrenal (N = 5) and ampulla of Vater (N = 1) were included. All 286 pts had at least one alteration (including characterized alterations and variant of unknown significance). 79.0% (226/286) had ≥ 1 characterized alteration, with median number of alteration = 1 (range: 0-42). Among pts with characterized alterations, 74.3% (168/226) had ≥ 1 potentially actionable target (median: 1, range: 0-12) (with FDA-approved [on- or off-label] or investigational drug). Paired DNA/RNA sequencing revealed 44.1% (126/286) of pts had ≥1 DNA alteration that was not seen at the RNA level. Conclusions: Most pts with rare and ultra-rare cancers had theoretically tractable alteration. Interestingly, not all the DNA alterations were seen in RNA level, indicating potential silencing at the RNA level.
Abstract 20675: Utility of End-Systolic Ventricular Elastance for Predicting Post-Operative Left Ventricular Dysfunction in Patients With Severe Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction
Authors: Junichi Ooka, Hidekazu Tanaka, Kensuke Matsumoto, Hiroki Takada, Fumitaka Soga, Yutaka Hatani, Keiko Hatazawa, Hiroki Matsuzoe, Hiroyuki Shimoura, Hiroyuki Sano, Yasuhide Mochizuki, Keiko Ryo-Koriyama, Ken-ichi Hirata
Journal: Circulation (2016)

Background: Patients with chronic aortic regurgitation (AR) suffer from volume and pressure overload. Post-operative left ventricular (LV) systolic function is an important determinant of post-oper...
Clinical implications of cell free DNA concentration in patients with small cell lung cancer.
Authors: Wade Thomas Iams, Karinna Almodovar, Catherine Meador, Zhiguo Zhao, Sally York, Leora Horn, Chris Raymond, Jennifer Hernandez, Lee Lim, Christine Marie Lovly
Journal: Journal of Clinical Oncology (2018)

e20563Background: Detecting hallmark genomic changes in peripheral blood circulating, cell-free DNA (cfDNA) in patients with small cell lung cancer (SCLC) has been increasingly validated. While the...
TCT-857 A 75% Stenosis Created Turbulent FLow, Ruptured Bubbles (Cavitation Phenomenon), Eroded the Vulnerable Cap and Triggered Acute Myocardial Infarction
Authors: Marco Zuin, Thach Nguyen, Hoa Bui, Thao Dang, Ai Vu, Tarneem Darwish, Thy Dang, Khoi Che, QUoc Bui, Ngoc Hoang, Tuan Nguyen, Gianluca Rigatelli, Ernest Talarico
Journal: Journal of the American College of Cardiology (2018)
CD8+ TILs in early stage epithelial ovarian cancer: A GEICO study.
Authors: Ignacio Romero, Susanna Leskella, Andres Redondo, Ana Gutierrez-Pecharroman, Ana Santaballa, Eva Maria Cristobal Lana, Elisa Calvo, Juan Manuel Rosa-Rosa, Ana Oaknin, Isabel Bover, Ana Herrero, Ana Beatriz Sanchez-Heras, Cristina Maria Churruca, Ana De Juan, Cesar Mendiola, Margarita Romeo, Belen Ojeda, Jose Antonio Lopez-Guerrero, José Palacios, Andres Poveda
Journal: Journal of Clinical Oncology (2017)

5543 Background: The extent of tumor infiltrating lymphocytes (TILs) has emerged as a potential clinical useful biomarker in epithelial ovarian cancer (OC); however differences in TILs among OC histological types have not been extensively analysed. Methods: From a prospective early stage (I-II) GEICO registry of 1151 cases, 573 were sent for central pathology review. Complete analysis for classification of OC correctly identified 488 cases. Histological typing was performed according to morphological features and the expression of WT1, p53, p16, estrogen receptor (ER), progesterone receptor, and napsin A. The expression of mismatch repair (MMR) proteins MLH1, PMS2, MSH2 and MSH6 was performed in all tumors. The absolute number of stromal and intraepithelial CD8 + TILs per 0.6 mm 2 TMA core was quantified and correlated with pathological features. Results: The series included 127 high-grade serous carcinomas (HGSC) (26%), 22 low-grade serous carcinomas (LGSOC) (4.5%), 165 endometrioid carcinomas (EC) (33.8%), 124 clear cell carcinomas (CCC) (2.4%), and 50 mucinous carcinomas (MC) (10.2%). The mean of intraepithelial CD8 + TILs was higher in HGSG (48.7) than in all other histological types (LGSG: 16.3; EC: 27.1; MC: 7.0; and CCC 10.3; p&lt;0.0001). In the stromal component, the mean of CD8 + TILs was also higher in HGSG (31.1) than in EC, MC and CCC (15.8, 8.0 and 12.7, respectively; p&lt;0.0001). The mean of intraepithelial CD8 + TILs was significantly higher in RE-positive (71.9) than in RE-negative (34.8) HGSC ( p=0.002). In the complete series, 33 (6.6%) OCs showed absent expression of at least 1 MMR protein, and the mean of intraepithelial CD8 + TILs was significantly higher in these OCs (57.0) than in those with preserved expression of all MMR proteins (23.6; p=0.0035). MMR protein deficiency was observed in 27 (16%) ECs, and these tumours had significantly higher mean of both intraepithelial (60.4 vs. 20.7 p=0.003) and stromal CD8+ TILs (26.6 vs. 13.8, p= 0.046). No significant differences in TILs were observed among EC of different histological grades. Conclusions: The extent of CD8 + TILs significantly correlates with the histological type and MMR status in OCs, being HGSCs and EC with MMR deficiency those OCs with higher CD8 + TILs.
Is chemical/surgical castration necessary during docetaxel chemotherapy for castration-resistant prostate cancer?
Authors: Masahito Watanabe, Kent Kanao, Hiroyuki Muramatsu, Shingo Morinaga, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Yoshiharu Kato, Kogenta Nakamura, Makoto Sumitomo
Journal: Journal of Clinical Oncology (2017)

e16530 Background: Docetaxel is the standard treatment for castration-resistant prostate cancer (CRPC). However, the role of chemical/surgical castration during docetaxel chemotherapy is unclear. The purpose of this study was to analyze the impact of castration during docetaxel chemotherapy. Methods: Data from 43 patients diagnosed with CRPC and treated at our institute with docetaxel chemotherapy, from January 2007 to September 2016, were analyzed retrospectively. They were divided into two groups according to the continuation of chemical castration during docetaxel chemotherapy: a continuation group and a discontinued group. Patients’ background data (age and serum prostate-specific antigen [PSA] level), PSA decline, progression-free survival, and overall survival were compared between the two groups. Results: The continuation group included 19 patients, and the discontinued group included 24 patients. Castration included surgical castration (15.8%), use of a luteinizing hormone-releasing hormone (LH-RH) agonist (68.4%), and use of an LH-RH antagonist (15.8%). There were no significant differences in patient age (73.5 years vs. 73.5 years; p = 0.878) and baseline serum PSA levels (14.25 ng/ml vs. 31.1 ng/ml, p = 0.745) between the two groups at the start of chemotherapy. PSA declines of ≥50% were observed in 7/14 patients and in 9/20 patients, respectively. There were no significant differences between the two groups with respect to the median progression-free survival (5.7 months vs. 9.9 months, p = 0.406) and overall survival. (52.1 months vs. 44.1 months, p = 0.776). Conclusions: Continuing chemical/surgical castration during docetaxel chemotherapy did not affect progression and prognosis of CRPC. Our results might suggest that chemical castration is not necessary during docetaxel chemotherapy.
A cell cycle-related RNA expression signature of neoantigen burden in lung adenocarcinoma.
Authors: Michael F Sharpnack, Travis Johnson, Gregory Alan Otterson, David Paul Carbone, Kun Huang, Kai He
Journal: Journal of Clinical Oncology (2018)

12072 Background: Tumor somatic mutation burden (TMB) and neoantigen burden (NB), are emerging therapeutic biomarkers for immune checkpoint blockade in NSCLC; however, these biomarkers are costly and require extensive expertise to measure. Cheaper, simpler surrogate biomarkers are necessary to keep up with current translational research findings. Methods: We curated RNAseq, NB, and clinical data from The Cancer Genome Atlas (TCGA) for lung adenocarcinoma (LUAD, n = 461) tumors. Gene-level RNAseq data was correlated with TMB and NB, and ontological enrichment of genes associated with these quantities are discovered using the enrichR tool. In addition, RNA expression and TMB data from lung adenocarcinoma cell lines were curated from the Cancer Cell Line Encyclopedia. Neural network and penalized linear regression methods were used to create and test RNA expression signatures of somatic mutation and neoantigen burden. The code for these methods was implemented in R. Results: 5199 genes' RNA expression are significantly correlated with NB (Spearman correlation, Benjamin hochberg q-value < 0.01). Genes positively associated with NB are highly enriched in cell cycle related genes (pathway database, corrected p-value < 0.01). Further, we correlated RNA expression with mutation burden in lung adenocarcinoma cell lines and found a similar enrichment of cell cycle related genes. We created RNA expression signatures of NB using two separate methods and tested their performance on TCGA LUAD tumors using a random cross validation approach. Neural network and penalized linear regression cross-validation experiments had mean AUCs of 0.74 and 0.68, respectively. The final signatures were selected based on consistent and accurate performance on LUAD tumors. 50 genes were selected for the final signature, including YBX2, TDRKH, HDGF and others. Conclusions: Cell cycle-related RNA abundances are strongly associated with NB in LUAD. We show that these genes can be incorporated into a biomarker of NB. We are in the process of validating this RNA signature's ability to predict NB with a NanoString RNA panel on a separate LUAD cohort and investigating its implication in lung cancer immunotherapy.
Specific needs of non-visceral sarcoma patients: Evidence from an early multidisciplinary intervention.
Authors: Pascaline Boudou-Rouquette, Ariane de Buyer, Camille Tlemsani, Sophie Chauffour, Camille Le Bris, Nathalie Lhuillier, Florence Astorg, Catherine du Mortier, Béatrice Mushenghesi, Lucie Prin, Camille Lambert, Audrey Bellesoeur, Isabelle Colombet, Francois Goldwasser
Journal: Journal of Clinical Oncology (2018)

e22133 Background: sarcoma are rare tumors, with an incidence < 1% of all neoplasms. Supportive care of pts with advanced sarcomas is an underestimated aspect in oncology practice. Methods: in our university hospital, a systematic outpatient multidisciplinary needs and risks assessment including psychological and nutritional evaluation and intervention of a social worker was made prior to initiate therapy. All bone (41%) and non visceral soft-tissue sarcoma pts consecutively referred between 01/2013 and 12/2016 were included. We collected data from retrospective chart review and described their clinical characteristics and needs for supportive care during the first 3 months. We report here data from the first 115 consecutive pts. Results: Results: The median age was 45 years (range: 16-88), 54% of the pts were male, 45% had metastases and 52% a performance status ≥ 2. A large majority of the patients (85%) could have the multidisciplinary assessement. During the first 3 months, 74/115 (63%) had uncontrolled symptoms (i.e pain, anxiety or disability). Social evaluation reveals that 51/105 (47%) of pts presented at least one factor of vulnerability (e.g no health insurance, no income, social isolation, unemployment, no personal accommodation) and 10% had a low education/comprehension level. 30/85 (35%) presented with malnutrition. Prior depression was found in 12/103 (12%) pts and biography revealed a previous stressful life-event in 21/80 (26%) pts within 10 years of diagnosis. During psychologists-led clinical interviews, multiple concerns were detected, the most frequent being loss of autonomy (68%), change in body image (39%), social consequences (work 35%, dependents 34%), fear of death (19%) fertility issues (15%), and financial limitations (12%). Importantly, 78/104 (75%) pts mentioned at least two simultaneous issues. Conclusions: patients with sarcoma of bone and soft-tissues have a high symptom burden. They have multiple and specific needs. A specific multidisciplinary team is necessary to provide a rapid and adjusted supportive care.
The impact of BMI on post-operative survival in bladder cancer patients.
Authors: Gray Jodon, Elizabeth Riley Kessler, Derek Smith, Shandra Wilson
Journal: Journal of Clinical Oncology (2018)

e16501 Background: A known risk factor for developing bladder cancer is a patient’s body mass index (BMI). Recent studies have shown that increased BMI is associated with higher mortality and disease recurrence in patients undergoing cystectomy who did not receive neoadjuvant chemotherapy or radiation therapy. The impact on survival of BMI in patients undergoing cystectomy who received perioperative chemotherapy is less known. Methods: This was a retrospective cohort study that included bladder cancer patients who underwent cystectomy at a single academic institution between the years 2008-2016. Patients were stage II, IIIA, and IIIB based on cystectomy staging. Modeling was conducted using a cox proportional hazards model stratified by cancer stage to assess whether survival differed between patients receiving neoadjuvant chemotherapy and adjuvant chemotherapy. This analysis also explored the impact of BMI as determined at the time of cystectomy and evaluated as a continuous variable. Kaplan Meier estimates were used to display overall survival among those with chemotherapy treatment as well as survival stratified by pre- and post-surgery treatment groups. Results: A total of 101 patients with surgical pathologic stage II, IIIA, and IIIB bladder cancer treated with neoadjuvant or adjuvant chemotherapy were included in the analysis. Median BMI for the neoadjuvant group was 26.4 with an interquartile range (IQR) of 23.1-31.8. The adjuvant group had a median BMI of 27.4 and IQR of 24.25-30.7. The impact of BMI on survival was a hazard ratio of 1.026 (confidence interval (CI) 0.979-1.076, p = 0.285). The median survival for patients receiving neoadjuvant chemotherapy was 30.35 months compared to 29.03 months in patients receiving adjuvant chemotherapy, with a hazard ratio of 0.970 (CI 0.553-1.701, p = 0.915). Conclusions: In patients with stage II, IIIA, and IIIB bladder cancer that have been treated with cystectomy and chemotherapy, no significant association between BMI and survival was found. Stage seems a primary driver of outcome in this group. Also, survival was not found to significantly differ between individuals that received neoadjuvant and adjuvant chemotherapy. This was a variable population with high risk disease overall.