tbuckley/cabot-search huggingface dataset:
Relationship of time to metastasis (TTM) and site of metastases in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Results from the phase 3 SPARTAN trial.
Authors: Matthew Raymond Smith, Fred Saad, Dana E. Rathkopf, Boris A. Hadaschik, Simon Chowdhury, Margaret K. Yu, Angela Lopez-Gitlitz, Oliver Brendan Rooney, Mohamed Darif, Eric Jay Small
Journal: Journal of Clinical Oncology (2018)

5033 Background: SPARTAN, a randomized placebo (PBO)-controlled phase 3 study, evaluated the effect of apalutamide (APA), an orally administered next-generation androgen receptor inhibitor, in men with nmCRPC and a rapidly rising PSA. In SPARTAN, APA was associated with a 73% relative risk reduction of distant metastasis. We assessed the relationship between TTM and site of metastases after androgen deprivation therapy (ADT) plus APA or PBO. Methods: 1207 pts with nmCRPC and PSA doubling time (PSADT) ≤ 10 months were randomized 2:1 to APA (240 mg QD) or PBO, with concurrent ADT (both arms). TTM, defined as time from randomization to first evidence of blinded central review–confirmed radiographically detectable distant metastasis, was assessed by site of metastases, nodal (M1 nodes + soft tissue) vs bone (bone ± M1 nodes) vs visceral (visceral, regardless of other sites). Kaplan-Meier methods were used to analyze TTM. A stratified proportional hazards model with treatment group as a factor, stratified by PSADT, bone-sparing agent use, and loco-regional disease, was used to estimate HR and 95% CI. Results: Of those pts with metastases (APA vs PBO, respectively), 30% (52/175) and 40% (76/191) developed nodal metastases, while 57% (100/175) and 52% (100/191) developed bone metastases, and 13% (23/175) and 8% (15/191) developed visceral metastases. The HRs (APA vs PBO; 95% CI) for TTM for the intent-to-treat population were 0.19 (0.13-0.27) and 0.31 (0.23-0.41) for nodal and bone metastases, respectively (p < 0.0001). Conclusions: Treatment with APA markedly decreased the risk of metastases, regardless of the site of metastasis. The consistency of these results provides further evidence for the clinical benefit of APA in nmCRPC. Clinical trial information: NCT01946204.
The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers
Authors: Pedram Razavi, Matthew T. Chang, Guotai Xu, Chaitanya Bandlamudi, Dara S. Ross, Neil Vasan, Yanyan Cai, Craig M. Bielski, Mark T.A. Donoghue, Philip Jonsson, Alexander Penson, Ronglai Shen, Fresia Pareja, Ritika Kundra, Sumit Middha, Michael L. Cheng, Ahmet Zehir, Cyriac Kandoth, Ruchi Patel, Kety Huberman, Lillian M. Smyth, Komal Jhaveri, Shanu Modi, Tiffany A. Traina, Chau Dang, Wen Zhang, Britta Weigelt, Bob T. Li, Marc Ladanyi, David M. Hyman, Nikolaus Schultz, Mark E. Robson, Clifford Hudis, Edi Brogi, Agnes Viale, Larry Norton, Maura N. Dickler, Michael F. Berger, Christine A. Iacobuzio-Donahue, Sarat Chandarlapaty, Maurizio Scaltriti, Jorge S. Reis-Filho, David B. Solit, Barry S. Taylor, José Baselga
Journal: Cancer Cell (2018)
Relationship between preoperative geriatric frailty and need for postoperative intensive care unit admission and subsequent short- and long-term mortality.
Authors: Armin Shahrokni, Saman Sarraf, Koshy Alexander, Sung W. Sun, Soo Jung Kim, Sincere McMillan, Heidi Yulico, Robert J. Downey, Beatriz Korc-Grodzicki
Journal: Journal of Clinical Oncology (2018)

10011 Background: The relationship between age-related impairments in geriatric surgical patients and the need for postoperative intensive care unit (ICU) admission and subsequent outcomes is largely unknown. Methods: Since 2015, Memorial Hospital surgical services have referred cancer patients age 75+ to the Geriatrics Service for preoperative evaluation including the eRFA (Shahrokni et al., JNCCN, Feb 2017). The eRFA has 13 items: the Karnofsky Performance Scale, basic and instrumental activities of daily living, Timed Up and Go test, history of falls, social activity level, social support, distress level, depression, cognitive impairment, polypharmacy, weight loss, and number of comorbid conditions. In order to develop a scoring system , we performed a univariate & multivariate analysis of the correlation between these variables, the frequency of ICU admission, and the likelihood of 12-month mortality among ICU survivors. Results: 1164 patients (median age 79) were evaluated prior to surgery after which 53 patients (4.6%) were admitted to the ICU. Five eRFA factors were associated with ICU admission: > 4 comorbid conditions, weight loss > 10 pounds, polypharmacy, limited social activity, and high distress level. The median number per patient of these 5 impairments in our cohort was 2. In a univariate analysis, frail patients ( > 2 of 5 impairments) were more likely to be admitted to the ICU than fit patients (≤2 of 5 impairments (OR = 3.42, p < 0.001). The correlation persisted after adjusting for age, gender, ASA performance status, duration of surgery, and preoperative albumin level (OR = 2.87, p = 0.013). The one year mortality of patients not needing ICU care was 1.8% for fit patients and 5.7% for frail patients. The one year mortality of patients needing ICU care was 9.4% for fit patients and 20.4% for frail patients. Conclusions: Frail patients are at higher risk for postoperative ICU stay compared to fit patients. 1 out of 5 frail patients age 75+ dies within 1 year after ICU stay. Future studies should assess the effectiveness of interventions aimed to improve the long-term outcomes of geriatric ICU survivors.
Practice patterns and clinical outcomes of therapy-related acute myeloid leukemia (TAML) in the US.
Authors: Manisha Pant, Smith Giri, Prajwal Dhakal, Vijaya Raj Bhatt
Journal: Journal of Clinical Oncology (2017)

e18139 Background: tAML, compared to de novo AML, has higher adverse features and a shorter overall survival (OS). The use of chemotherapy and hematopoietic cell transplant (HCT), and OS of tAML outside of clinical trials has not been studied well. Current study was designed to identify the treatment patterns and OS of tAML based on a national database. Methods: A total of 1,611 cases of tAML were identified between 2001-2011 using the National Cancer Database (NCDB). Data on age, race, gender, income, insurance and educational status, Charlson comorbidity index (CCI), receipt of chemotherapy and HCT were abstracted. Log-rank test was used to test equality of survivor function among the variables. Factors that attained statistical significance during bivariate analysis were factored into multivariate analysis using Cox Regression model. Results: Median age at diagnosis was 63 years (range 18-90), with 54% &lt; 65 years, 59% females and 80% Caucasians. 67% underwent chemotherapy (20% single agent, 45% multiple agents and 2% unknown). 19% received HCT. Median OS was 6.7 months (m) with 1-year OS of 33%. Median OS was lower among patients ≥65 versus &lt; 65 years (4.1 vs. 9.5 m; p &lt; 0.001), those with higher comorbidity burden (7.8 m for CCI of 0, 6.0 m for CCI of 1, and 3.8 m for CCI of 2; p &lt; 0.001), and diagnosed before versus during/after 2008 (5.6 vs. 7.7 m, p = 0.05). Median OS was higher among patients who received chemotherapy (8.4 vs. 3.7 m; p &lt; 0.001) and HCT (22.6 vs. 4.9 m, p &lt; 0.001), as compared to those who did not. Cox regression model showed the predictors of OS to be: receipt of HCT (hazard ratio, HR 0.36); use of multiagent chemotherapy (HR 0.80); age≥65 years (HR 1.25), higher comorbidities (HR of 1.21 for CCI of 1, and 1.45 for CCI of 2) and diagnosis on or after 2008 (HR of 0.81). Conclusions: Over half of patients with tAML are younger adults ( &lt; 65 years), however, the receipt of chemotherapy and HCT is relatively low. OS is poor in general but improves with the use of multiagent chemotherapy and HCT. OS is worse in older patients and those with comorbidities. Given a dismal prognosis, older patients may be managed by leukemia team with expertise in geriatric oncology and should be encouraged to participate in clinical trials of novel therapies.
A phase II trial of vandetanib (ZD6474) in children and adults with wild-type gastrointestinal stromal tumors.
Authors: John Glod, Fernanda Arnaldez, Lori Wiener, Melissa Amaya, Joanne Derdak, Ramaprasad Srinivasan, W Linehan, Paul S. Meltzer, Markku Miettenen, Seth M. Steinberg, Brigitte C. Widemann
Journal: Journal of Clinical Oncology (2016)

11009 Background: Gastrointestinal stromal tumors (GIST) are resistant to cytotoxic chemotherapy and radiation therapy. The majority of GIST in pediatric patients are wild-type for KIT and PDGFRA (wt-GIST) and are deficient in expression of succinate dehydrogenase (SDH). Vandetanib is an oral small molecule inhibitor of VEGFR2, EGFR, and RET-dependent signaling. There are no wt-GIST preclinical models, but treatment of SDH-deficient renal cell carcinoma cell lines with vandetanib resulted in growth inhibition. Methods: We have conducted a phase II study of vandetanib administered PO once daily on a continuous dosing schedule (1 cycle = 28 days) to assess the clinical activity (partial and complete response rate RECIST v1.1) in patients with wt-GIST. Vandetanib was administered at a dose of 300 mg daily to patients ≥ 18 years. Patients < 18 years of age were dosed at 100mg/m2/dose. Response was evaluated after every 3 cycles x4 and every 6 cycles thereafter. An optimal two-stage design (target response rate 25%, rule out 5%) was used: If ≥ 1/9 patients in stage 1 responded, enrollment would be expanded to 24 patients, and if ≥ 3/24 responded, vandetanib would be considered active. Results: Nine patients (7F:2M), (median age 24 years, range 11-52) with metastatic disease enrolled. Three of five adult patients initially enrolled developed toxicities requiring dose modifications: Grade (gr) 3 hypertension (n = 1), seizure (n = 1), pneumonitis (n = 1), gr 2-3 abdominal pain (n = 2). After a protocol amendment 2 adults received vandetanib at 200 mg/dose with improved tolerability. The 2 children enrolled did not experience toxicities requiring dose changes. No partial or complete responses were observed. The median number of completed cycles was 4 (range 2-15+). Two patients remain on treatment with SD after 14 and 15 cycles. Two patients were taken off study at the request of the patient and five patients were taken off study for progressive disease. Conclusions: Vandetanib was not tolerated by adults at the 300 mg daily dose. Two of 9 patients had prolonged stable disease, but nor partial or complete responses were observed and vandetanib is thus not considered active in wt-GIST. Clinical trial information: NCT02015065.
The Translational Machinery of Human CD4+ T Cells Is Poised for Activation and Controls the Switch from Quiescence to Metabolic Remodeling
Authors: Sara Ricciardi, Nicola Manfrini, Roberta Alfieri, Piera Calamita, Maria Cristina Crosti, Simone Gallo, Rolf Müller, Massimiliano Pagani, Sergio Abrignani, Stefano Biffo
Journal: Cell Metabolism (2018)
Mortality due to low-quality health systems in the universal health coverage era: a systematic analysis of amenable deaths in 137 countries
Authors: Margaret E Kruk, Anna D Gage, Naima T Joseph, Goodarz Danaei, Sebastián García-Saisó, Joshua A Salomon
Journal: The Lancet (2018)

Universal health coverage has been proposed as a strategy to improve health in low-income and middle-income countries (LMICs). However, this is contingent on the provision of good-quality health care. We estimate the excess mortality for conditions targeted in the Sustainable Development Goals (SDG) that are amenable to health care and the portion of this excess mortality due to poor-quality care in 137 LMICs, in which excess mortality refers to deaths that could have been averted in settings with strong health systems.Using data from the 2016 Global Burden of Disease study, we calculated mortality amenable to personal health care for 61 SDG conditions by comparing case fatality between each LMIC with corresponding numbers from 23 high-income reference countries with strong health systems. We used data on health-care utilisation from population surveys to separately estimate the portion of amenable mortality attributable to non-utilisation of health care versus that attributable to receipt of poor-quality care.15·6 million excess deaths from 61 conditions occurred in LMICs in 2016. After excluding deaths that could be prevented through public health measures, 8·6 million excess deaths were amenable to health care of which 5·0 million were estimated to be due to receipt of poor-quality care and 3·6 million were due to non-utilisation of health care. Poor quality of health care was a major driver of excess mortality across conditions, from cardiovascular disease and injuries to neonatal and communicable disorders.Universal health coverage for SDG conditions could avert 8·6 million deaths per year but only if expansion of service coverage is accompanied by investments into high-quality health systems.Bill & Melinda Gates Foundation.
Radiosensitization and micro CT imaging of multifunctional gold nanoparticles in lung adenocarcinoma A549 cell: An in vivo animal study.
Authors: Tao Li, Chuan Yang, Guojun Zhang, Jianming Huang, Jiahua Lv, Sheng Qin
Journal: Journal of Clinical Oncology (2018)

e20557 Background: To investigate the effect of multifunctional gold nanoparticles on radiosensitization and micro CT imaging in lung adenocarcinoma A549 tumor bearing mice. Methods: The tumor-bearing mice were treated with gold nanoparticles and irradiated with different energy levels of 160KV X-ray and 6MV X-ray, respectively. The tumor volume of each group was measured every time of treatment. The tumor-bearing mice were treated with gold nanoparticles via Intra-tumoral injection. The Micro CT scan was carried out at fixed time intervals to observe the imaging and deposition time of nano-gold in the tumor tissue. Results: There were no significant differences between control group and gold nanoparticles group (P = 0.842) in tumor volume. Compared to the 6MV X-ray group, the 6MV X-ray combined with gold nanoparticles group resulted in a smaller tumor volume. But there was no significant difference (P = 0.96) between the groups. The tumor volume of 160kv X-ray combined with gold nanoparticles group was significantly smaller than that of 160kv X-ray group (P = 0.031). The Micro CT scan assay showed that the deposition time of nano-gold in the tumor tissue was 30 days. The effect of imaging was good, and no toxicity of gold nanoparticles was observed in this study. Conclusions: multifunctional gold nanoparticles and 160kv X-ray irradiation exhibited significant radiosensitization effect in A549 cells-bearing mice. The stable CT imaging of the nano-gold in the tumor can be used as a potential method for mapping and delineating the target area of tumor-guided radiotherapy.
P04.29 Modelling delivery of Tumor Treating Fields (TTFields) to the brain using Water-based Electrical Properties Tomography
Authors: Z Bomzon, C Temple-Brami, H S Hershkovich, M Giladi, C Wenger
Journal: Neuro-Oncology (2018)

Tumor Treating Fields are anti-cancer treatment utilizing alternating electric fields in the intermediate frequency range. TTFields (@200 kHz) are approved for the treatment of glioblastoma multiforme. The effect of TTFields is intensity-dependent, suggesting it is important to maximize TTFields dose at the tumor. Hence, it is important to understand how TTFields distribute in the brain. The distribution of TTFields within the brain depends on the electric properties (EPs) of the brain, which are heterogeneous. Therefore, there is a need for methods that map electric properties within tissue with high spatial resolution. Water content based EP tomography (wEPT) is a method that utilizes the ratio of two T1w images with different relaxation times (TRs) to map EPs. wEPT has been applied to map EPs of healthy brain at 128 MHz. Here we attempted to adapt wEPT to map EPs in the 100–1000 kHz. An empirical model connecting T1 images, Water content (WC) and EPs in the 100–1000 kHz range was created using 32 tissue samples derived from three 3 juvenile bovine brains and 1 Porcine CSF sample. For each sample, T1w MRIs with TRs {700, 4000} ms were acquired and the image ratio (Ir) between the images calculated. EPs of samples were measured with a parallel plate setup. The dry and wet mass of the samples was measured for each sample, and the water content estimated from the difference between the two measurements. Curve fitting yielded empirical models connecting Ir, WC and EPs. Next, T1w MRIs of tumor-bearing rat brains in-vivo were acquired, and the empirical curves described above used to map WC and EP within the rat brains. In addition, EPs and WC were measured on 6 samples excised from each imaged brain. The measured values were compared to the median WC and EPs in the voxels of the wEPT map corresponding to the sample. Anatomical structures and the tumor were clearly visible in wEPT maps of the rat brains. WC estimated using wEPT agreed well with measurements on excised sample. The data showed a connection between EPs estimated with wEPT and the measured values. However, in some samples large differences between wEPT-derived EP values and measurements were found. In particular, differences between tumor conductivity and the conductivity of grey and white matter estimated using wEPT was significantly higher than the difference in conductivities measured within the excised samples. wEPT maps WC in healthy and tumor brain tissues and provides information on local electrical properties at frequencies of 100–1000 kHz. Further investigation is needed to clarify the relationship between WC and EP within this frequency range. Clarifying this relationship would enable a robust non-invasive method for tissue electrical properties within the brain, ultimately leading to a better understanding of how TTFields distribute within the brain and influence disease progression.
Prognostic factors and effects of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.
Authors: Zhaohui Jin, Mindy L. Hartgers, Cristobal T. Sanhueza, Benny Johnson, Christopher R. Shubert, David M. Nagorney, Rory L. Smoot, Mark J. Truty, Michael L. Kendrick, Thomas C. Smyrk, Amit Mahipal
Journal: Journal of Clinical Oncology (2017)

e15703 Background: The aim of this study is to identify prognostic factors and effects of adjuvant therapy for patients with ampullary adenocarcinoma who had pancreatoduodenectomy. Methods: A cohort of 123 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from January 1, 2006, through August 31, 2016 at Mayo Clinic in Rochester, MN. Only patients with ampullary carcinoma by pathology review were included and were histologically classified as pancreaticobiliary or intestinal subtypes. Median follow-up duration was 41.0 months. Patient survival and its correlation with patient and tumor variables were tested by univariate and multivariate analysis. Results: Pancreatoduodenectomy was curative-intent in 120 out of 123 patients. All 123 patients underwent radical surgery, 32 patients (26.0%) had laparoscopic pancreatoduodenectomy. Among 123 patients, there were 76 men (61.8%).Median age at diagnosis was 67.2 years. 54 patients (45%) without metastatic disease upon surgery had adjuvant therapy (35 patients had chemotherapy only while 19 patient also had radiation). Median overall survival (OS) was 91.8 months. Poor performance status at disease diagnosis (ECOG &gt; = 1), old age ( &gt; = 70 years), primary tumor infiltration (T), lymph node metastasis (N), and advanced disease stage (TNM) had a significant negative impact on survival (p &lt; 0.05 by univariate analysis). Gender, diabetes at disease diagnosis, laparoscopic surgery approach, number of lymph nodes removed, number of positive lymph nodes, and tumor size did not influence survival. In multivariate analysis, ECOG score &gt; = 1, adjuvant treatment, primary tumor infiltration (T) and lymph node metastasis (N) remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (P = 0.0388) and overall survival (p = 0.030) for patients with advanced disease (stage IIB and above). Conclusions: Poor performance status and advanced disease stage are associated with decreased survival in patients with ampullary adenocarcinoma. Patients with advanced disease should be considered for adjuvant chemotherapy.
Abstract 20148: Noninvasive Quantification of Pressure Difference Across a Coronary Stenosis Using Phase-Contrast (PC)-MRI: Initial Patient study Using Fractional Flow Reserve as Reference
Authors: Zixin Deng, Sang-Eun Lee, Zhaoyang Fan, Christopher Nguyen, Yibin Xie, Jianing Pang, Xiaoming Bi, Qi Yang, Byoung-Wook Choi, Jung-Sun Kim, Berman Daniel, Hyuk-Jae Chang, Debiao Li
Journal: Circulation (2016)

Introduction: In patients suspected of coronary artery disease (CAD) undergoing invasive coronary angiography (ICA), ~50% has nonsignificant stenoses ( 0.80). Recent noninvasive technique, FFRCT (coronary computed tomography angiography, CCTA with computational fluid dynamic simulations), has shown to decrease the number of unnecessary invasive procedures, however, CCTA requires exposure to ionizing radiation and is more prone to artifacts caused by calcification. In this study, we evaluate a noninvasive technique using cross-sectional 2D phase-contrast (PC)-MRI and Navier-Stokes analysis to derive pressure difference (ΔP) across a coronary stenosis, with the ultimate goal of estimating FFR. As FFR requires adenosine, which is technically challenging for PC-MRI due to high heart rates, the proposed technique mimics an instantaneous wave-free ratio (iFR) (ΔP obtained at diastole without adenosine; assuming aortic pressure of 74.2 mmHg), denoted as MR-iF...