tbuckley/cabot-search huggingface dataset:
Biconcave Carbon Nanodisks for Enhanced Drug Accumulation and Chemo‐Photothermal Tumor Therapy
Authors: Qingxin Mu, Hui Wang, Xinyu Gu, Zachary R. Stephen, Charles Yen, Fei‐Chien Chang, Christopher J. Dayringer, Miqin Zhang
Journal: Advanced Healthcare Materials (2019)

It is considered a significant challenge to construct nanocarriers that have high drug loading capacity and can overcome physiological barriers to deliver efficacious amounts of drugs to solid tumors. Here, the development of a safe, biconcave carbon nanodisk to address this challenge for treating breast cancer is reported. The nanodisk demonstrates fluorescent imaging capability, an exceedingly high loading capacity (947.8 mg g
Analysis of toxicity and clinical outcomes (CO) in full versus reduced dose cabozantinib (cabo) in metastatic renal cell carcinoma (mRCC) patients (pts).
Authors: Dylan J Martini, Julie M. Shabto, Yuan Liu, Bradley Curtis Carthon, Alexandra Speak, Elise Hitron, Greta Russler, Sarah Caulfield, Kenneth Ogan, Wayne Harris, Viraj A. Master, Omer Kucuk, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2019)

671 Background: The full dose of cabo is 60 mg, but some pts are treated with a reduced dose with the clinical anticipation of adverse events (AEs). We compared AEs and CO in mRCC pts treated with full versus reduced dose cabo. Methods: We performed a retrospective analysis of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016-2018. CO were measured by overall survival (OS), progression-free survival (PFS), and objective response (OR). OS and PFS were measured from first dose of cabo to date of death and clinical or radiographic progression, respectively. OR was defined as partial response (PR) or complete response (CR) per RECISTv1.1. AEs were collected from clinic notes. Univariate analysis (UVA) of association between AEs and CO was performed using logistic regression model. Results: Most pts were males (68%) and the median age was 63 years. Most (79%) had clear cell RCC (ccRCC) and the majority were IMDC intermediate (59%) or poor (39%) risk. Most pts (68%) received 60 mg and 48% of these pts underwent a dose reduction for AEs. Nearly all pts (95%) who started on a reduced dose experienced AEs, compared to 66% for pts treated with 60 mg. OR rate was similar for pts on 60 mg (18%) and pts on a reduced dose (19%). The median survival was comparable in pts treated with 60 mg and pts treated with a reduced dose (10.9 vs. 8.8 months, p=0.92 for OS and 5.6 vs. 5.1 months, p=0.23 for PFS) per Kaplan Meier estimation. AEs, particularly gastrointestinal (GI) AEs, were associated with significantly lower chance of OR (Table). Conclusions: CO may be comparable in mRCC pts treated with full versus reduced dose of cabo, but a reduced dose of cabo may not be associated with decreased AEs. GI side effects may be a poor prognostic factor in mRCC pts treated with cabo. Larger studies are warranted to validate these findings. [Table: see text]
A open label phase II trial of cetuximab plus cisplatin in patients with recurrent or metastatic undifferentiated carcinoma of nasopharyngeal type: Results after three years.
Authors: Esma Kerboua, Amina Tahrat, Kamel Bouzid
Journal: Journal of Clinical Oncology (2015)

e17021 Background: To evaluate efficacy and toxicity of cetuximab plus cisplatin in recurrent or metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT) after previous platinum based chemotherapy Methods: An open-label, single-arm in patients with UCNT who progressed on or within 12 months after termination of platinum-based chemotherapy for recurrent or metastatic disease. Cetuximab was administered at an initial dose of 400 mg/m2 followed by every two weeks doses of 500 mg/m2 as maintenance therapy until progression or unacceptable toxicity. Cisplatin70 mg/m2day 1 was administered every 3 weeks up to a maximum of 04 cycles. Results: Fifty- four patients were enrolled (40 males, 14 females; median age 40 years ( range 18 to 64 years), All patients were included in the intent-to-treat and safety analyses. Response was assessed every 6 weeks,according to RECIST .The primary end point was objective response rate (ORR) at 12 weeks. Secondary endpoints were safety, progression free survival and overall survival .Of the 50 patients (pts) assessable for efficacy, ten pts had partial responses (20%), twenty five pts (50%) with stable disease, and eleven pts (22%) with progressive disease, Four pts with complete response (8%) for locoregional reccurence and cervical nodes, giving an overall response rate of 78%. The time to progression is between 03 months to 25 months with a median at 19,5 months. The median overall survival time was 22 months. Grade 3 cutaneous toxicities occurred in 5 patients. No death was related to study treatment. Conclusions: Cetuximab in combination with cisplatin demonstrates clinical activity and an acceptable safety profile in heavily pretreated patients with recurrent or metastatic UCNT who had previously experienced treatment failure with platinum-based therapy.
Inflammatory macrophage dependence on NAD+ salvage is a consequence of reactive oxygen species–mediated DNA damage
Authors: Alanna M. Cameron, Angela Castoldi, David E. Sanin, Lea J. Flachsmann, Cameron S. Field, Daniel. J. Puleston, Ryan L. Kyle, Annette E. Patterson, Fabian Hässler, Joerg M. Buescher, Beth Kelly, Erika L. Pearce, Edward J. Pearce
Journal: Nature Immunology (2019)
Novel chromosome copy number changes to predict clinical response to sunitinib in patients with advanced renal cell carcinoma.
Authors: Chung-Han Lee, Robert Motzer, Andreas Hoetker, Oguz Akin, Ana M. Molina, Theresa Margaret Gold, Sujata Patil, Banumathy Gowrishankar, Jane Houldsworth
Journal: Journal of Clinical Oncology (2015)

4552 Background: Sunitinib is a 1st-line therapy for clear cell Renal Cell Carcinoma (ccRCC); however, 20-30% of tumors show primary resistant disease (PRD) with progression as the best response. This study identifies the chromosomal copy number changes that are associated with sunitinib clinical response. Methods: Whole genome comparative genomic hybridization (aCGH) was performed on pretreatment tumor derived DNA from 76 sunitinib treated patients. Differential copy number alterations (CNAs) were identified using Fisher’s exact test with p-values < 0.05 and a 15% minimum threshold difference. Identified CNAs were univariately tested for association with PFS, and compared to two publically available ccRCC SNP datasets, TCGA-436 (N = 436, TCGA, Nature, 2013, 499: 43) and University of Tokyo-240 (N = 240, Nature Genetics, 2013, 45: 860). Results: In patients with PRD gains of 22q and 6p were more common, and univariate PFS analysis for these CNAs showed a worse PFS (table). In patients with objective radiographic response (CR/PR), losses of 4q, 8p, and 10q were more common, and univariate PFS analysis identified loss of 4q and 8p trended toward improved PFS (table). Using databases comprising of largely sunitinib naïve patients (TCGA-436 and University of Tokyo-240), these CNAs were not correlated with overall survival, suggesting that these CNAs reflect sunitinib response, and not sunitinib-independent tumor biology. Conclusions: aCGH analysis of sunitinib treated ccRCC patients reveal multiple novel CNAs associated with clinical response. These CNAs warrant further investigation and may provide insight into mechanisms of sunitinib resistance. Chromosome copy number changes. Worse Prognosis Improved Prognosis PD as best response Worse PFS CR/PR as best response Improved PFS Gain 22q (P = 0.03) Gain 6p21.1 (P = 0.03) Gain 22q (p = 0.06) Gain 6p21.2 (p < 0.001) Loss 4q25 (P = 0.03) Loss 4q28.1-q28.2 (P = 0.03) 8p21.1 (P = 0.03) 10q21.3-q22.1 (P = 0.03) 10q23.32-23.33 (P = 0.03) Loss 4q13.1-q13.3 (P = 0.07) Loss 8p21.1 (P = 0.06)
Evaluation of Phenotype-Genotype Correlation in Two Common PIEZO1 Mutations p.R2456H and p.L2495_E2495dup
Authors: Mary Risinger, Vandy Black, Loan Hsieh, Renee C. Prins, Jill Menell, Mohamad Badawi, Cynthia Rutherford, Karen L. Bride, Omar Niss, Charles T. Quinn, Katie Giger Seu, Wenying Zhang, Theodosia A. Kalfa
Journal: Blood (2018)
A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy
Authors: Hee-Gyeong Yi, Young Hun Jeong, Yona Kim, Yeong-Jin Choi, Hyo Eun Moon, Sung Hye Park, Kyung Shin Kang, Mihyeon Bae, Jinah Jang, Hyewon Youn, Sun Ha Paek, Dong-Woo Cho
Journal: Nature Biomedical Engineering (2019)
Efficacy and Safety of Ibrutinib (IBR) after Venetoclax (VEN) Treatment in IBR-Naïve Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Follow-up of Patients from the MURANO Study
Authors: Richard Greil, Graeme Fraser, Brian Leber, Reinhard Marks, Giulia Quaresmini, Jan Moritz Middeke, Gianpietro Semenzato, William Schary, Michelle Boyer, Madlaina Breuleux, Noelle Crompton, Kathryn Humphrey, Paula Marlton
Journal: Blood (2018)
Hematopoietic Recovery and Transfusion Needs after Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide in Adult Patients with Hematologic Malignancies
Authors: Razan Mohty, Florent Malard, Annalisa Ruggeri, Eolia Brissot, Remy Dulery, Giorgia Battipaglia, Frederica Giannotti, Simona Sestili, Clemence Mediavilla, Mohamad Mohty
Journal: Blood (2018)
Abstract MP69: The Weight Loss by Using the Smartphone Application for People with Metabolic Abnormalities: A Randomized Controlled Trial
Authors: Jung Hyun Lee, Jee-Seon Shim, Hyungseon Yeom, Su Jin Lee, Hyeon Chang Kim
Journal: Circulation (2019)

Introduction: Obesity has been an important issue for global health. The use of the smartphone application might contribute to weight loss. However, there is still little evidence for the effectiveness among people without overt metabolic disorder. Hypothesis: We assessed the weight loss for people who used the smartphone application with and without personal coaching, with respect to people who did not use any. Methods: A total of 129 participants (aged 30-59 years; 63 men; 66 women) were recruited from the community-based cohort study in Korea during 2017-18. The inclusion criteria were as follows. 1) no cardiovascular disease; 2) no medication for hypertension, diabetes and dyslipidemia; 3) no current use of the application for behavior modification; 4) at least two components of metabolic syndrome (waist circumference ≥ 90/80 cm (men/women), SBP/DBP ≥ 135/85 mmHg, triglyceride ≥ 150 mg/dL, HDL cholesterol &lt; 40/50 mg/dL (men/women), and fasting glucose ≥ 100 mg/dL). Participants were educated for behavior modification and randomly assigned to three groups; CO (control, no use of the application), AO (the application only; without personal coaching) and APC (the application with personal coaching). The weight was measured during a screening examination and follow-up examinations at 1.5, 3 and 6 months from a start date. A linear mixed model including the data from participants who attended the follow-up examination at least once was used to assess the weight loss. Results: A total of 111 participants attended the follow-up examination at least once. The mean (±SD) weight of those at screening was 71.6±12.2 kg. The mean weight loss of participants after 6 months was 0.11±1.6 kg (p = 0.67) in CO, 0.34±2.8 kg (p = 0.45) in AO, and 0.96±2.2 kg (p =0.02) in APC. Compared with the weight loss in CO, there was no significant additional weight loss in AO (0.35 kg; p = 0.41, 0.60 kg after 3 months; p = 0.16 and 0.24 kg after 6 months; p = 0.58), however, there was significant additional weight loss in APC for 3 and 6 months later (0.51 kg after 1.5 months; p = 0.23, 0.93 kg after 3 months; p = 0.03 and 0.87 kg after 6 months; p = 0.04). Conclusions: The use of the application with personal coaching had the effect of losing weight. These results support that the use of the application can be useful for people with metabolic abnormalities that require weight loss.
Prevalence, disease-free (DFS) and overall (OS) survival of contemporary high-risk renal cell carcinoma (RCC) patients eligible for adjuvant checkpoint inhibitor trials: A RECUR database analysis.
Authors: Saeed Dabestani, Christian Beisland, Grant Stewart, Umberto Capitanio, Petrus Jarvinen, Harry Nisen, Karim Bensalah, Eirikur Guðmundsson, Thomas B Lam, Lorenzo Marconi, Sergio Fernandèz-Pello, Serenella Monagas, Thomas Powles, Richard Paul Meijer, Alessandro Volpe, Michael D. Staehler, Borje Ljungberg, Axel Bex
Journal: Journal of Clinical Oncology (2019)

636 Background: Designing adjuvant trials is challenging because of uncertainties of prevalence and outcome of high-risk RCC despite use of validated risk scores. Methods: RECUR is a European multicenter database capturing patient and tumour characteristics, recurrence patterns and survival of all patients treated with (partial) nephrectomy for non-metastatic RCC from 2006 to 2011 at each participating center. We evaluated prevalence, DFS and OS of RCC according to eligibility criteria of adjuvant trials IMMotion 010 (NCT03024996, IM), Checkmate 914 (NCT03138512, CM), Keynote-564 (NCT03142334, KN) and RAMPART (NCT03288532, RP), which all predominantly recruited high-risk clear cell RCC patients. Results: Of 2669 relevant patients in RECUR, 424(15.9%), 681(25.5%), 579(21.7%) and 1221(45.7%) met eligibility criteria for IM, CM, KN and RP respectively (p &lt; 0.001). Median DFS and OS estimates (Kaplan-Meier) in RECUR corresponding to each trial placebo arm were 37.5 (95%CI 30.4–44.6) and 89.6 (95%CI 76.1–103.0) months for IM, 89.4 (95%CI 66.1–112.7) and 96.2 (95%CI 79.8–112.6) months for CM, 62.6 (95% CI39.6–85.6) and 86.6 (95%CI 74.3–98.9) months for KN and finally at 144 months (DFS not reached) and 123.8 (95% CI 110.1 – 137.4) months for RP. Additionally, at pairwise analysis of evaluated trials, DFS estimates were significantly different between all trials (p &lt; 0.001) except between CM and KN (p = 0.125), while OS estimates did not differ significantly between all trials except between RP and the other three trials (p = 0.002). Conclusions: Percentages of eligible high-risk RCC patients in RECUR were low to moderate and, together with estimated placebo arm DFS and OS, varied due to differences in trial eligibility criteria. These differences may impact on the results and interpretation of the trials.
Efficacy and toxicity from phase II study of dose escalation to intraprostatic tumor nodule in localized prostate cancer.
Authors: Julia Murray, Emma Alexander, Alison Tree, Helen McNair, Vibeke Hansen, Annie Gao, Karen Thomas, Nandita M DeSouza, David P. Dearnaley
Journal: Journal of Clinical Oncology (2019)

102 Background: Intra-prostatic boost to dominant nodule is an attractive method for biological dose augmentation. Aim of study was to assess clinical feasibility of radiation boost to mp-MRI visible tumour using external beam radiotherapy. We report a planned analysis of toxicity and efficacy in the first two dose cohorts in this study. Methods: DELINEATE (ISRCTN04483921) was a single centre prospective phase 2 multi-cohort study including standard (Cohort A (A): 74Gy/37F) and moderately hypofractionated (Cohort B (B): 60Gy/20F) prostate image-guided IMRT regimens. Patients treated in A and B received integrated boost of 82Gy and 67Gy to mp-MRI-visible lesions. 55 patients were recruited to A and 158 patients recruited to B; the first 50 sequentially treated patients in B were included in analysis. Duration of androgen deprivation therapy was at clinician discretion. Primary endpoint was RTOG late toxicity at 1 year. Secondary endpoints included acute and late toxicity timepoints and biochemical relapse (BCR) free survival, using Phoenix definition. Treatment related toxicity was measured by RTOG, CTCAE v4 scales, IPSS and EPIC-26. Results: Between July 2011 and January 2015, 105 patients were treated within A&amp;B. Median follow up for A was 74.5 months and 52 months for B. Median age was 71 years (range 57-80). In A and B, there were 27% and 40% of patients respectively classified with NCCN high risk disease. Cumulative RTOG toxicity in Table. 6 patients had BCR (5 patients: A and 1 patient: B). Within A, 1 patient had pelvic nodal progression and 1 local progression; patient in B had local progression. Conclusions: Delivery of intra-prostatic boost to dominant nodule is feasible with acceptable toxicity and good efficacy. Intra-prostatic boost is now part of the randomised phase 3 PIVOTALboost trial (ISRCTN80146950). Clinical trial information: 04483921. [Table: see text]
Abstract MP29: Body Fat and Cardiovascular Disease Risk in Postmenopausal Women With Normal Body Mass Index: the Women’s Health Initiative
Authors: Guo-Chong Chen, Rhonda Arthur, Neil M Iyengar, Victor Kamensky, Xiaonan Xue, Sylvia Wassertheil-Smoller, Matthew A Allison, Aladdin H Shadyab, Robert A Wild, Yangbo Sun, Hailey R Banack, Jean Wactawski-Wende, JoAnn E Manson, Marcia L Stefanick, Andrew J Dannenberg, Thomas E Rohan, Qibin Qi
Journal: Circulation (2019)

Introduction: Excess body weight characterized by higher BMI is associated with increased risk of cardiovascular disease (CVD). In individuals with normal BMI, the extent to which body fat distribution may impact CVD risk is unclear, particularly in postmenopausal women who often experience fat redistribution. Hypothesis: We hypothesized a detrimental impact of trunk fat and a favorable impact of leg fat on risk of CVD risk among postmenopausal women with normal BMI. Methods: We analyzed data from 2683 normal-weight (BMI: 18.5-24.9 kg/m 2 ) women in the Women’s Health Initiative study without known CVD at baseline (1993-1998). Body composition including whole body and regional fat mass (FM) were determined by dual-energy X-ray absorptiometry. Incident CVD events including coronary heart disease (coronary death, nonfatal myocardial infarction, or coronary revascularization) and stroke were ascertained through February 2017. Results: There were 291 incident cases of CVD during a median 17.9 years of follow-up. After multivariable adjustment, whole body FM or FM percentage was not significantly associated with CVD risk. Higher trunk FM percentage was associated with increased risk of CVD (HR comparing extreme quartiles = 1.91, 95% CI: 1.33-2.74, P -trend &lt;0.001), while higher leg FM percentage was associated with lower risk of CVD (HR = 0.62, 95% CI: 0.43-0.89, P -trend = 0.008) ( Figure ). These associations were slightly attenuated but remained significant after further adjustment for waist circumference or waist-to-hip ratio. Higher trunk fat combined with lower leg fat was associated with particularly higher risk of CVD (HR comparing extreme groups = 3.33, 95% CI: 1.46-7.62). Similar significant associations of trunk fat and leg fat were observed for coronary heart disease but not for stroke. Conclusions: Among postmenopausal women with normal BMI, higher trunk fat was associated with increased risk of CVD, while higher leg fat was associated with decreased risk of CVD, independently of central adiposity measures.
Doctors have authority to assess injuries from alleged torture, says Supreme Court
Authors: Clare Dyer
Journal: BMJ (2019)

Doctors providing medical reports on asylum seekers who claim they were tortured are entitled to reach conclusions on how consistent the injuries are with the person’s account of what happened, the UK Supreme Court has ruled.1

Such evidence can be of “significant potential value” to decision makers in their “supremely difficult and important task,” the justices added, and is consistent with the Istanbul Protocol, the international agreement on the investigation of torture.

Giving authoritative guidance on the correct approach to medical evidence in asylum claims, the UK’s highest court corrected “controversial” observations by the Court of Appeal accusing a doctor of straying beyond the limit of his role.

The five justices were considering the case of KV, who …
School Mobility and Its Impact on Student Health
Authors: Gage Odom
Journal: JAMA Pediatrics (2019)

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Quantifying the relative value of drug therapy options in HER2+, ER-/PR- breast cancer.
Authors: John Whang, Amy R Steinkellner, Jane M Borne, Elizabeth N Piana, Winston Wong, Ronald E Aubert, Norman C Selby
Journal: Journal of Clinical Oncology (2015)

6602 Background: US health care spending continues to exceed that of other industrialized countries, in part because there is insufficient transparency as to the relative value (benefit-cost) of different treatment options. Comparing drug regimens based on their overall value would help create a common set of metrics to enable better drug therapy decision-making and help improve quality and reduce costs of care. Methods: We developed a methodology to review, synthesize and assess the evidence of a drug's performance across three major domains of clinical efficacy, safety & use and economics, and to combine those assessments to determine overall value of a drug regimen. We then incorporated multi-attribute decision analysis and our evidence methodology into an interactive web-based tool to compare the relative value of all relevant drug regimens in an indication. The tool uses an explicit and transparent methodology and uses a total of 30 elements within the three domains. Results: Using the interactive web-based tool, we compared 3 adjuvant chemotherapy regimens in HER2+, ER-/ PR- breast cancer: 1) doxorubicin + cyclophosphamide then paclitaxel (AC-T), 2) doxorubicin + cyclophosphamide then paclitaxel + trastuzumab (AC-TH), and 3) carboplatin + docetaxel + trastuzumab (TCH). We assessed the relative value of the regimens based on weighted scores within the 3 domains. Higher scores are better. In this case study, AC-TH and TCH had similar efficacy and safety scores; AC-TH scored highest overall because of better economics. (See table.) Scores can be modified by the end user to reflect patient-specific factors such as unique toxicity concerns (e.g., history of heart failure). Conclusions: A transparent, personalizable interactive tool created to compare the relative value of drug regimens can be used to support treatment decisions for HER2+, ER-/PR- breast cancer incorporating clinical and economic considerations. Next steps will include validation using network meta-analysis and extension to other related areas of cancer care. Weighted domain scores by drug regimen. DOMAIN (Weighting) AC-T AC-TH TCH Efficacy (70%) 189 320 320 Safety & Use (20%) 58.1 56.6 58.6 Economic (10%) 70.5 63.2 45.7 TOTAL SCORE 318 440 424