tbuckley/cabot-search huggingface dataset:
Effect of target lesions selection on between-reader variability of response assessment according to RECIST 1.1.
Authors: Christiane K. Kuhl, Yunus Alparslan, Bruno Sequeira, Jonas Schmoe, Hannah Engelke, Annika Keulers, Tim Bruemmendorf, Sebastian Keil
Journal: Journal of Clinical Oncology (2017)

2528 Background: Response-classification-systems, e.g. RECIST1.1, and dedicated oncology software-tools (DOST) are used to standardize response assessment. Expectation is that different readers should yield the same response-classification for any given patient. We investigated real-life variability between readers who, as in clinical practice, were free to select target-lesions (TL). Methods: Prospective study on 316 patients with metastatic disease who underwent 932 CT-studies, yielding a total 616 follow-up occasions (baseline vs. follow-up) for analysis. All CT-studies were independently evaluated by 3 radiologists who used state-of-the-art DOST (MintLesion). Readers were free to select TL in the respective baseline study, and did so independently. Kappa-statistics were used to analyse agreement for RECIST1.1 response-class-assignment depending on whether readers had selected the same or different TL.To investigate possible impact on treatment decisions, agreement was also determined after aggregating response classes into progressive (PD) vs. non-progressive (CR/PR/SD). Results: Readers used the same TL in 38.6 (238/616), different in 61.4% (378/616). Where readers happened to select the same TL, agreement was “almost perfect” (κ = 0.966 [96%-CI: 0.912–1.00] for assignment of individual response-classes, and 0.977 [0.898–1.0] for the distinction progressive-vs-non-progressive). Where readers had selected different TL, agreement was only “moderate” (0.583 [0.541–0.624] for individual response-class-assignment, and 0.644 [0.587 to 0.701] for distinction progressive-vs.-non-progressive). Choice of the same TL was associated with agreement for distinction between progressive-vs.-non-progressive-disease in 97.7 % [95.4%–100.0%] of patients; choice of different TL was associated with disagreement in 44.7% [37.6%–51.8%]. Conclusions: If different radiologists use RECIST1.1 and DOST for response assessment, they will select different TL more often than not. Just depending on whether TL selection was concordant or not, radiologists will exhibit perfect agreement, or substantial disagreement, even for distinguishing progressive vs non-progressive disease.
Phase 1 study of ARQ 761, a β-lapachone analog that promotes NQO1-mediated programmed cancer cell necrosis.
Authors: David E. Gerber, Ajit Kumar Bisen, Muhammad Shaalan Beg, Arthur E. Frankel, Oluwatomilade Fatunde, Farjana Fattah, Yull Edwin Arriaga, Jonathan Dowell, Claudia Meek, Joyce D. Bolluyt, Venetia Sarode, Xin Luo, Yang Xie, Brian E. Schwartz, David A. Boothman, Richard Leff
Journal: Journal of Clinical Oncology (2017)

2517 Background: NAD(P)H:quinone oxidoreductase 1 (NQO1) is a two-electron oxidoreductase expressed in multiple tumor types at levels 5- to 200-fold above normal tissue. ARQ761 is a β-lapachone hydroquinone analog that exploits the unique elevation of NQO1 found in solid tumors to cause tumor-specific cell death by eliciting a futile redox cycle generating high levels of reactive oxygen species and ultimately PARP1 hyperactivation-dependent cell death. Methods: 3+3 dose escalation study of 3 schedules (weekly, every other week, 2/3 weeks) of ARQ 761 as a 1-hr or 2-hr infusion. Eligible patients had refractory advanced solid tumors, ECOG 0-1, adequate organ function, and central venous access. Blood samples were analyzed for ARQ761 levels and NQO1 polymorphisms. Archival tumor tissue was analyzed for NQO1 staining intensity and prevalence. After 18 patients were analyzed, enrollment was restricted to patients with NQO1-positive tumors (defined as Histo-score ≥200). Results: A total of 42 patients were treated. Median number of prior lines of therapy was 4. For all schedules, the maximum tolerated dose (MTD) was 390 mg/m 2 as a 2-hr infusion. DLT was hemolytic anemia. The most common treatment-related adverse events were anemia (79%), fatigue (45%), hypoxia (33%), hemolysis (17%), nausea (17%) and vomiting (17%). Transient grade 3 hypoxia, due to methemoglobinemia, occurred in 26% of patients. Among 31 evaluable patients, the best response was stable disease (n = 11) and progressive disease (n = 19). For the 18 analyzed cases analyzed prior to NQO1 enrollment biomarker, clinical benefit appeared associated with tissue NQO1 expression: disease control rate was 65% in NQO1-positive tumors and 18% in NQO1-negative tumors ( P=0.06). Analysis of all 31 evaluable patients did not show a significant difference in progression-free survival (PFS) according to NQO1 status ( P=0.26), but 3-mo PFS rate was numerically greater among NQO1-positive cases (40% versus 20%). Conclusions: ARQ 761 has clinical activity in NQO1-positive tumors. Principal toxicities include hemolytic anemia and methemoglobinemia. Combination studies are underway.
Sustained intensive transmission of Q fever in the south of the Netherlands, 2009
Authors: B Schimmer, F Dijkstra, P Vellema, P M Schneeberger, V Hackert, R ter Schegget, C Wijkmans, Y van Duynhoven, W van der Hoek
Journal: Eurosurveillance (2009)

The Netherlands is again facing a sharp increase in Q fever notifications, after the unprecedented outbreaks of 2007 and 2008. The most affected province of Noord Brabant has a high density of large dairy goat farms, and farms with abortion waves have been incriminated. Mandatory vaccination of small ruminants has started and should have an effect in 2010. A large multidisciplinary research portfolio is expected to generate better knowledge about transmission and additional control measures.
SOLAR-1: A phase III study of alpelisib + fulvestrant in men and postmenopausal women with HR+/HER2– advanced breast cancer (BC) progressing on or after prior aromatase inhibitor therapy.
Authors: Fabrice Andre, Mario Campone, Eva M. Ciruelos, Hiroji Iwata, Sibylle Loibl, Hope S. Rugo, Celine Wilke, David Mills, Marie Chol, Anne-Sophie Longin, Dejan Juric
Journal: Journal of Clinical Oncology (2016)

TPS618 Background: The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in hormone receptor-positive (HR+) BC and is associated with resistance to endocrine therapy. The combination of the PI3Kα-specific inhibitor alpelisib (BYL719) and fulvestrant showed promising activity in a phase I study of HR+/human epidermal growth factor 2-negative (HER2–) BC, with the strongest treatment benefit in patients (pts) with PIK3CA-mutant tumors (Janku et al. SABCS 2014, Abstract PD5-5). Further data are required to confirm these observations. Methods: In the phase III, randomized, double-blind SOLAR-1 study (NCT02437318), men and postmenopausal women with HR+/HER2– advanced BC are randomized (1:1) to alpelisib or placebo (300 mg once daily) + fulvestrant (500 mg intramuscularly on Days 1 and 15 of Cycle 1 [28 days], and Day 1 of Cycles ≥ 2) until disease progression or discontinuation for other reason. Pts are assigned to 2 cohorts (PIK3CAmutant vs non-mutant status in tumor tissue) prior to randomization, and stratified by presence of liver and/or lung metastases, and prior CDK4/6 inhibitor treatment. Key inclusion criteria include disease progression/recurrence on or after prior aromatase inhibitor therapy, and Eastern Cooperative Oncology Group performance status ≤ 1. Exclusion criteria include symptomatic visceral disease, or disease burden precluding endocrine therapy, and prior therapy with fulvestrant, chemotherapy, ([neo] adjuvant permitted) or PI3K/mTOR/AKT inhibitors. The primary and key secondary endpoints are progression-free survival (PFS; local assessment, RECIST v1.1) and overall survival, respectively. Other secondary endpoints include PFS, as per blinded independent review, PFS based on PIK3CA status in circulating tumor DNA, overall response rate, clinical benefit rate, safety, pharmacokinetics, and global health status/quality of life. Analysis of the primary endpoint will be performed with a stratified log-rank test (95% confidence interval). Global recruitment of the planned 820 pts is ongoing. Clinical trial information: NCT02437318.
Cbcsg-10: Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple negative breast cancer.
Authors: Shao Zhimin, Junjie Li, Da Pang, Changqing Wang, Jun Jiang, Suisheng Yang, Yunjiang Liu, Pei Fen Fu, Yuan Sheng, Guojun Zhang, Liya Cao, Qi He, Shude Cui, Xijing Wang, Guosheng Ren, Xinzheng Li, Shiyou Yu, Pengxi Liu, Binghe Xu, Xi-Chun Hu
Journal: Journal of Clinical Oncology (2016)

1012 Background: Standard adjuvant chemotherapy regimens for triple-negative breast cancer (TNBC) contain taxane and anthracycline. We aimed to investigate the efficacy and safety of integrate capecitabine in the adjuvant treatment of triple-negative patients. Methods: For this randomized, open-label, phase 3 trial undertaken at 35 institutions or hospitals in China, we recruited women with early TNBC after surgery. Eligible patients were randomly assigned (1:1) using a central patient screening and randomization system to either three cycles of capecitabine and docetaxel (TX) followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (XEC), or to three cycles of docetaxel (T) followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (FEC). The primary endpoint was disease-free survival (DFS). This trial is registered with ClinicalTrials.gov, number NCT01642771. Results: Between Jun, 2012, and Nov, 2013, 585 patients were assessed for eligibility and randomized. 288 patients in capecitabine group and 273 in control group were included in the intention-to-treat analysis for efficacy and safety. The clinical and pathological features were well balanced in two groups. Both regimen were well tolerated, the most common toxicities were neutropenia, alopecia, neuropathy and hand-foot-syndrome, 87.15% patients in the capecitabine group and 89.75% patients in the control group completed 6 cycles of chemotherapy. 38.89% patients had capecitabine dose reduction. After a median follow-up of 30 months, disease-free survival was not significantly different between the groups, (90.58% vs 86.8%; p=0∙23). However, capecitabine regimen showed better recurrence-free survival (92.73% vs 87.84%, p=0.049), distant-disease free survival (94.29% vs 89.27%, p=0.019) and overall survival (97.4% vs 95.61%, p=0.063). Conclusions: Integration of capecitabine into standard chemotherapy regimen reduced recurrence in TNBC. Clinical trial information: NCT01642771. T--FEC TX--XEC Any event 32 25 Second primary 0 3 Contralateral breast 1 3 Recurrence or death 31 19 Local 9 6 Ipsilateral breast 3 4 Chest 5 1 Regional nodes 1 1 Distant 26 16 Liver 3 3 Lung 11 7 Bone 4 3 Other 15 5 Death 11 5
Outcomes of primary central nervous system lymphoma in the era of immunotherapy: Cleveland Clinic experience.
Authors: Suresh Kumar Balasubramanian, Philipp Schmitt, Meena Sadaps, Vidhya Karivedu, Debra Kangisser, Samuel T. Chao, Erin Sennett Murphy, John H. Suh, Manmeet Singh Ahluwalia, Arun D Singh, David M. Peereboom
Journal: Journal of Clinical Oncology (2017)

e13516 Background: Primary central nervous system lymphoma (PCNSL), a form of extranodal non-Hodgkin lymphoma represents 3% of primary CNS tumors. It is aggressive but typically confined to the CNS. Despite improvements in the management of PCNSL, more than 50% of patients eventually relapse. There are limited data on PCNSL from larger cohort studies. Methods: With IRB approval, the Cleveland Clinic Neuro-Oncology Center database was used to identify patients treated between 2006-2015 for PCNSL. Overall survival (OS) from the diagnosis of PCNSL and progression free survival (PFS) were the primary and secondary end points respectively. Cox proportional hazards models were used for data analysis. Results: 86 PCNSL patients were included in the analysis. Only 5% (4/76) were HIV positive. The median age of diagnosis was 63 (range 15 - 86) and 50% were males. 88% of patients presented only with brain lesion, 8% only in eye and 4% had both brain and eye involvement. 15% of patients (12/81) had positive CSF findings. Treatment included: chemotherapy (CT) alone (39% of patients); chemoimmunotherapy (CIT) (32%); CIT with radiotherapy (RT) (13%); RT alone (11%); CT with RT (4%); and immunotherapy (IT) alone (1%). Among 23 patients (31%) who received RT upfront, 74% had WBRT (n = 17). The most common upfront therapy was high dose methotrexate (HD MTX) (44%), followed by HD MTX with rituximab (23%), RTOG 0227 (12%), RTOG 1114 (11%) and rest 14% included rituximab or temozolomide or other cytotoxic chemotherapy alone or in combinations. The most common relapse site was brain (72%), followed by eyes (12%) and spine (8%). The median follow-up was 26 months. At last follow up, 41% had died and 93% of which were PCNSL-related. The median PFS and OS were 17.7 months and 84 months, respectively. There was a trend towards superior PFS in upfront IT vs. no IT (20 vs. 14 months, p 0.08). Better performance status (KPS &gt; 80 vs. &lt; 80, HR 0.42 (p = 0.033)) and PFS ≥ 24 months compared to ≤ 24 months (p = 0.0012) were associated with improved OS. Conclusions: We report a large single institution cohort of PCNSL patients treated in the era of immunotherapy. In our cohort, better KPS (≥80) and PFS ≥ 24 months had improved OS. Upfront IT showed a trend towards improved PFS.
Epidemiologic study of risk factors for meningioma in the Mayo Clinic Study of Aging.
Authors: Alissa Butts, Jeremy A. Syrjanen, Jeremiah Aakre, Paul D. Brown, Clifford R. Jack, Ronald C. Petersen, Rosebud O. Roberts, Jane H Cerhan
Journal: Journal of Clinical Oncology (2017)

2067 Background: An estimated 2% of the general population has a meningioma (Vernooij et al. 2007), which accounts for about 36% of all primary intracranial tumors (Ostrom et al. 2015). The most established risk factors are older age and female gender. One small study identified gender but no other risk factors with meningioma (Krampla et al 2004). A larger study using the Iowa Women’s Health study data found lower levels of physical activity, greater body mass index (BMI), greater height and uterine fibroids were associated with meningioma (Johnson et al. 2011). We sought to replicate these findings and to identify additional risk factors related to meningioma in a large population-based sample. Methods: Study participants were enrolled in the Mayo Clinic Study of Aging (MCSA), a population-based sample of Olmsted County, Minnesota residents used to study prevalence, incidence, and risk-factors for Mild Cognitive Impairment and dementia and includes a variety of medical factors. Using a text search of radiologists’ notes of 2,402 MCSA individuals, mean age 77±8 years and scanned between 2004-2014.We identified 52 subjects who had at least one meningioma. We estimated the association of selected potential risk factors with presence of meningioma using odds ratios and 95% confidence intervals from logistic regression models adjusted for age and gender, which informed the multivariable models. Results: In the initial models, significant risk factors identified included BMI (as a continuous variable) (OR = 1.06 95%CI 1.01 to 1.12), taking NSAIDS (OR = 2.11, 95%CI 1.13 to 3.95), aspirin (OR = 1.90, 95%CI 1.04 to 3.46), and blood pressure lowering medication (OR = 2.06, 95%CI 1.07 to 3.99). Protective factors included male gender (OR = 0.51, 95%CI 0.29 to 0.90), coronary artery disease (CAD; OR = 0.46, 95%CI 0.22 to 0.97) and higher Beck Anxiety Inventory (BAI) total score (OR = 0.88, 95%CI 0.78 to 0.98). Simultaneous adjustment for these factors in a multivariable model did not attenuate these associations. Conclusions: Findings reveal gender and BMI as risk factors for meningioma. Additionally, certain medications such as NSAIDS and BP lowering medications warrant follow up as potential factors related to development of meningioma.
Early-onset neutropenia-related events in eribulin monotherapy: A possible biomarker in the real world?
Authors: Junichiro Watanabe, Yusuke Onozawa
Journal: Journal of Clinical Oncology (2017)

e12529 Background: Eribulin mesylate (eribulin) showed antitumor activity via the anti-tubulin effect, and improved overall survival (OS) in HER2-negative (HER2-) metastatic breast cancer (MBC) patients without extending progression-free survival (PFS) in a phase 3 trial. On the other hand, according to the published data (Watanabe J, Springerplus, 2015), eribulin monotherapy improved OS in the clinical setting, and PFS is a possible surrogate for OS in HER2-, hormone receptor-positive (HR+) MBC patients. However, there is no practical biomarker for PFS in relation to eribulin monotherapy in patients with HER2-HR+MBC. Methods: Eribulin was administered according to the instructions in the package insert (1.4mg/m 2 on days [D] 1 and 8, and a 21-day cycle [C]). The medical records of the patients who received eribulin monotherapy were reviewed. Results: From August 2011 to December 2016, 90 HER2-HR+MBC patients received eribulin monotherapy as daily practice at our institution, and 84 (93.3%) patients terminated their therapy. Lung and/or liver metastasis was observed at the induction of the therapy in 68 (86.7%) of the patients. The median relative dose of eribulin on C1D1 was 95.3% (1.33mg/body). Fever was observed during C1 in 23 (25.6%) patients, and grade (G) 3/4 neutropenia was observed on C1D8 in 28 (31.1%) patients. In contrast, only 4 (4.4%) patients developed febrile neutropenia within C1. Due to the delayed recovery of neutrophils, the second cycle of treatment was suspended in 8 (8.9%) patients. With regard to liver test abnormalities, an elevation of one grade in comparison to baseline, which resolved afterward without specific treatment, was observed during C1 in 24 (26.7%) patients. A multivariate Cox regression analysis revealed that G3/4 neutropenia on C1D8 and a delay of C2D1 were strong predictors of PFS (hazard ratio [HR] 0.53; p &lt; 0.05, HR 0.42; p &lt; 0.05, respectively). A chi-squared test revealed no statistically significant differences between the two subgroups in the relative dose on C1D1. Conclusions: This retrospective, observational study revealed that early-onset neutropenia-related events may be a biomarker for eribulin therapy that can be applied in the clinical setting.
Abstract 4116: Electrocardiographic Markers of Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: A reappraisal
Authors: Rahul Jain, Darshan Dalal, Ariana Evenson, Rohit Jain, Amy Daly, Crystal Tichnell, Cynthia James, Stephen Plantholt, Hugh Calkins
Journal: Circulation (2008)

Background: The Task Force criteria for diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) rely on depolarization and repolarization abnormalities detected on a surface ECG. Terminal activation delay (TAD) has recently been presented as specific and sensitive marker of ARVD/C. The purpose of this study was to evaluate the sensitivity and specificity of TAD in patients with ARVD/C. Methods : In a cohort of 74 patients with definite ARVD/C (51% male); age 36 ± 12 years) and 48 phenotypically normal non cardiac patients (35% male); age 35 ± 14 years) we studied the ECG criteria used to diagnose ARVD/C with specific a focus on TAD. The parameters analyzed were: T wave inversion (TWI) in ≥ V2, TWI ≥ V3, epsilon wave, QRS ≥ 110ms in V1 to V3, parietal block defined as QRSd V1–V6 or V2–V6 or V3–V6 &gt;25 ms in the presence of QRS ≥ 100ms in at least 2 right precordial leads, TAD in V1-V3 and QRSd in V1+V2+V3/V4+V5+V6 ≥ 1.2. Sigma scan software was used for the ECG analysis. Results : In the ARVD/C group, the prevalence of TWI ≥ V2 was 82%, TWI ≥ V3 was 66%, epsilon wave: 1%, QRSd ≥ 110ms V1-V3: 39%, parietal block: 16%, TAD: 46 %, QRSd ratio ≥ 1.2: 19%. In the non cardiac group the prevalence of TWI ≥ V2 was 6 %, TWI ≥ V3: 6%, epsilon wave: 0%, QRSd ≥ 110ms V1–V3: 4%, parietal block: 2%, TAD: 12%, and QRSd ratio ≥ 1.2: 4% (Figure). Conclusion : The results of this study reveal that terminal activation delay has only moderate sensitivity and specificity for the diagnosis of ARVD/C. Our results also reveal that T wave inversion in the right precordial leads is a very sensitive marker of ARVD/C.
Turmoil in the Individual Insurance Market — Where It Came From and How to Fix It
Authors: Henry J. Aaron, Matthew Fiedler, Paul B. Ginsburg, Loren Adler, Alice M. Rivlin
Journal: New England Journal of Medicine (2017)

Claims that the Affordable Care Act's individual insurance market is in a death spiral reflecting design flaws are misdiagnoses. The market structure is sound and has greatly expanded coverage; the President and Congress have created needless turmoil.
Robotic gastrectomy for gastric cancer: Subgroup analysis of a multicenter prospective comparative study of robotic versus laparoscopic gastrectomy.
Authors: Joong-Min Park, Hyoung-Il Kim, Sang Uk Han, Han-Kwang Yang, Young Woo Kim, Hyuk-Joon Lee, Ji Yeong An, Min-Chan Kim, Sungsoo Park, Kyo Young Song, Sung Jin Oh, Seong-Ho Kong, Byoung Jo Suh, Dae Hyun Yang, Tae Kyung Ha, Woo Jin Hyung, Keun Won Ryu
Journal: Journal of Clinical Oncology (2016)

4025 Background: Robotic gastrectomy for gastric cancer has been proven to be a feasible and safe minimally invasive procedure. However, our previous multicenter prospective study indicated that robotic gastrectomy is not superior to laparoscopic gastrectomy. This study aimed to identify which subgroups of patients would benefit from robotic gastrectomy over conventional laparoscopic gastrectomy. Methods: A prospective multicenter comparative study was conducted. Surgical outcomes were compared between the robotic and laparoscopic groups. The analysis was conducted in each subgroup according to the patients’ obesity status, the type of gastrectomy, and the extent of lymph node dissection. Results: A total of 434 patients were enrolled for the robotic (n = 223) and laparoscopic (n = 211) groups. According to obesity and gastrectomy type, there was no difference in the estimated blood loss (EBL), number of retrieved lymph nodes (RLN), complication rate, open conversion rate, and the length of hospital stay between the robotic and laparoscopic groups. According to the extent of lymph node dissection, the robotic group showed a significantly lower EBL than the laparoscopic group after D2 dissection (98.9 ml in the robotic group and 140.5 ml in the laparoscopic group, p = 0.021), while there was no difference in EBL in patients that did not undergo D2 dissection (96.5 ml in the robotic group and 82.6 ml in the laparoscopic group, p = 0.365). Further subgroup analysis showed that non-obese patients who underwent D2 lymph node dissection benefited from less blood loss with robotic gastrectomy (83.5 ml in the robotic group and 146.4 ml in the laparoscopic group, p = 0.002). Conclusions: Non-obese patients undergoing D2 lymph node dissection can benefit from less blood loss with a robotic surgery system. Clinical trial information: NCT01309256.
Alcohol consumption and risk of coronary heart disease
Authors: M. Gronbaek, T. I A Sorensen
Journal: BMJ (1996)

injection of the suspect ampicillin.This batch of ampicillin was taken out of circulation immediately, and samples were sent for analysis in Europe.Chemical analysis confirmed the presence of ampicillin but also of high concentrations of N, N-dimethylanalin, a degradation product, and of another, unknown, substance.Culture showed Pseudomonas spp and an unknown organism in the first two phials and Bacillus spp and an unknown organism in the second two phials.The laboratory suggested
Effect of dose timing on the blood concentration of lapatinib in patients with breast cancer
Authors: M. Ohgami, H. Bando, H. Ishiguro, M. Tsuda, N. Toriguchi, K. Aogi, M. Toi, N. Masuda, S. Mitsuhashi, A. Kurosawa, M. Homma
Journal: Annals of Oncology (2017)