tbuckley/cabot-search huggingface dataset:
Continuous low dose temozolamide with or without VT-122 in glioblastoma.
Authors: Tanweer Shahid, Gouri Shankar Bhattacharyya, Hemant Malhotra, Kanaka Setty Govindbabu, Purvish M. Parikh, Anantbhushan Ranade, Ghanashyam Biswas, Shailesh Arjun Bondarde, Amitabha Chanda, Newell F. Bascomb
Journal: Journal of Clinical Oncology (2015)

e13010 Background: Recurrent Glioblastoma is associated with poor prognosis despite treatment.Treatment options are limited. One of the novel methods of delivering Temozolomide is to use metronomic dosing which also has anti angiogenic properties, beside cytotoxic properties. Preclinical and clinical studies of beta-blockers and NSAIDs.Propranolol and etodolac (PE) are well known drugs that function by blocking adrenergic and prostaglandin signaling pathways.Their ability to inhibit cancer progression and metastasis may be through Anti-angiogenesis by inhibiting the expression of HIF-1alpha,iNOS and reducing cytokine—driven induction of immune regulating indoleamine 2,3 dioxygenase (IDO).Propranolol and etodolac induce changes in tumor microenvironment and immune system.The aim of this study was to evaluate the impact of the co-administration of the beta blocker Propranolol (P) and the selective COX-2 inhibitor Etodolac (E) on survival of patients with Recurrent Glioblastoma receiving Continuous low dose Temozolomide in metronomic dosing Methods: Eligible patients who had radio-chemotherapy with or without surgery for glioblastoma. All patients were treated with Temozolomide 20mg in empty stomach twice a day continuously. Patients were randomized to VT-122. All patients continued on standard planned supportive care. Patient who had received Temozolomide were continued either till progression or unacceptable toxicity. Results: 41 patients - 24 men and 16 women with proven advanced Recurrent Glioblastoma. Conclusions: Metronomic dosing of Temozolomide with VT-122 is an effective option in treatment of recurrent glioblastoma. The median survival time is almost doubled. Side-effects are manageable. Metrionomic Temozolomide (n=20) Metrionomic Temozolomide and VT-122 (n=21) Median Karnofsky Score >60 >60 Response Rate 7 (35%) 12 (57%) Complete Response 1 (5%) 5 (24%) Partial Response 4 (20%) 7 (33%) Stable Disease 3 (15%) 3 (14%) 1 year survival rate 6 (30)% 14 (67%) Median Overall Survival 9.2 months 17.6 months Thrombocytopenia Grade III/IV 3 (15%) 5 (24%) Neutropenia Grade III/IV 1 (5%) 2 (10%) Anemia Grade III/IV 3 (15%) 6 (29%)
Abstract MP60: Changes in Gut Microbiota Metabolite TMAO Are Related to Changes in Hepatic and Visceral Fat in Weight-loss Diet Interventions: the POUNDS Lost Trial
Authors: Xiang Li, Dianjianyi Sun, Tao Zhou, Yoriko Heianza, George Bray, Frank Sacks, Lu Qi
Journal: Circulation (2019)

Objective: Gut microbiota metabolite Trimethylamine-N-oxide (TMAO) has been related to obesity and various cardiometabolic disorders. TMAO is involved in lipid metabolism in the liver; however, little is known about whether changes in TMAO affect hepatic fat and abdominal fat distribution, and whether genetic variations modify such effects. Research Design and Methods: The present study included 92 overweight and obese participants from the POUNDS Lost trial having complete data on computed tomography (CT) scans and a genetic risk score (GRS) for nonalcoholic fatty liver disease (NAFLD). We analyzed the associations of changes in plasma TMAO with changes in hepatic fat and fat distribution from baseline to 6 months; we also assessed the interactions between the GRS and changes in TMAO. Results: Larger decreases in TMAO from baseline were significanly associated with a reduction in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and total adipose tissue (TAT) at 6 months, p=0.01, 0.02, and 0.003, respectively. In addition, we found that larger decreases in TMAO were associated with increases in HDL-cholesterol and decreases in triglycerides, p=0.02 and 0.03, respectively. Moreover, we observed significant interactions between 6-month changes in TMAO and the NAFLD GRS on the concurrent changes in liver fat (P interaction =0.007) and VAT (p interaction =0.018). Among individuals whose TMAO decreased, a lower NAFLD GRS tends to predict a greater improvement in hepatic fat and a reduction in VAT; while in those whose TMAO increased, no differences in hepatic fat or VAT were observed across the tertiles of NAFLD GRS. Conclusions: Our data indicate that changes in TMAO are related to changes in hepatic and visceral fat in weight loss diet interventions; and such relations are modified by genetic variation. Trial Registration: ClinicalTrials.gov NCT00072995.
Noninvasive high-resolution electromyometrial imaging of uterine contractions in a translational sheep model
Authors: Wenjie Wu, Hui Wang, Peinan Zhao, Michael Talcott, Shengsheng Lai, Robert C. McKinstry, Pamela K. Woodard, George A. Macones, Alan L. Schwartz, Alison G. Cahill, Phillip S. Cuculich, Yong Wang
Journal: Science Translational Medicine (2019)

Three-dimensional electromyometrial imaging accurately and noninvasively measures the electrical activation pattern of uterine contractions in sheep.
Nano genome altas (NGA) of body wide organ responses
Authors: Bingbing Wu, Yu Li, Nanfang Nie, Jiaqi Xu, Chengrui An, Yixiao Liu, Yafei Wang, Yishan Chen, Lin Gong, Qikai Li, Elena Giusto, Varitsara Bunpetch, Dandan Zhang, HongWei Ouyang, XiaoHui Zou
Journal: Biomaterials (2019)
Development and validation of a novel scoring index (C-reactive protein, age, race, and tumor size) to predict renal functional decline post partial nephrectomy.
Authors: Margaret Frances Meagher, Dattatraya H Patil, Kazutaka Saito, Brittney Cotta, Yosuke Yasuda, Aaron Bradshaw, Ahmed Eldefrawy, Stephen Ryan, Ryan Nasseri, David Anyakora, Juliana Alksne, Fang Wan, Yasuhisa Fujii, Viraj A. Master, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2019)

597 Background: Functional decline is a sequelae of extirpative renal surgery with potential for significant morbidity. We utilized pre-operative patient demographics, C-reactive protein, and tumor size to design and validate a novel scoring index to predict functional decline post partial nephrectomy. Methods: A multi-institutional dataset was utilized for analysis of patients with pre-operative estimated glomerular filtration rate (eGFR) &gt; 60mL/min/1.73m2 by CKD-EPI equation. Multivariable analysis (MVA) was carried out for potential variables associated with development of post-operative chronic kidney disease (CKD) stage IIIB at last follow-up (eGFR &lt; 45 mL/min/1.73m2). Significant variables were included in the predictive model and assigned an index score based on odds ratio. Receiver-operating-characteristic (ROC) analysis was employed to evaluate predictive validity, and bootstrapping technique was utilized to validate the model. Results: 924 patients were analyzed. 826 patients had post-operative eGFR &gt; 45, while 111 patients had eGFR. Factors on MVA independently associated with increased risk of development of eGFR &lt; 45 included age 65+ (OR = 2.6, p &lt; 0.001), African-American race (OR = 2.3, p = 0.006), C-reactive protein level &gt; 0.5mg/dL (OR = 5.3, p &lt; 0.001), and tumor size &gt; 4 cm (OR = 1.458, p = 0.189). For CART (C-reactive protein, Age, Race, Tumor size) score, the following values were assigned: age ( &lt; 65 = 1, age &gt; 65 = 3), race (non-African-American = 1, African-American = 2), tumor size ( &lt; 4 = 1, &gt; 4cm = 2), and CRP ( &lt; 0.5mg/dL = 1, &gt; 0.5mg/dL = 4). Analysis demonstrated 2.6% (12/469) of patients with a low (4-6) score had de novo eGFR &lt; 45 postoperatively, while 35% (41/117) of patients with a high (10-11) score had de novo eGFR &lt; 45. ROC analysis revealed AUC of 0.778, and ROC bootstrapping validation of 95 randomly selected patients revealed an AUC of 0.808. Conclusions: CART score represents a novel composite score that significantly predicts development of eGFR &lt; 45 after surgery. This scoring system may assist in patient counseling and clinical decision making, as well as an impetus to improve outcomes in at-risk patient subgroups.
Impact of a Stage IV NSCLC care pathway on front-line (FL) and maintenance (M) chemotherapy use at the Cleveland Clinic Taussig Cancer Institute (TCI).
Authors: Marc A. Shapiro, James Stevenson, Emily Van Wagoner, Katherine Glass, Chad W Cummings, Nathan A. Pennell, Patrick C. Ma, Vamsidhar Velcheti, Bruno R. Bastos, Brian James Bolwell, Abdo Haddad
Journal: Journal of Clinical Oncology (2015)

6609 Background: Care pathways can reduce cancer care costs and variability in NSCLC. Effective implementation requires measurable outcomes and available data in near real-time. Methods: Between 10/1/13 and 7/7/14, TCI developed an evidence and value-based Stage IV NSCLC pathway. For patients with non-squamous EGFR WT/ALK neg NSCLC, ECOG PS 0-2 and sufficient renal function, FL carboplatin/pemetrexed (pem) followed by M pem is recommended standard care while bevacizumab (bev) is not. The pathway recommends best supportive care for pts with ECOG PS ≥ 3. To test feasibility, 4 academic thoracic and 12 community oncologists implemented the pathway into their practices starting 7/7/14. This analysis studies pathway impact on FL and M treatment decisions and charges in patients with metastatic non-squamous EGFR WT/ALK negative NSCLC. 57 pts meeting pathway criteria initiated care with these oncologists from 7/7/14 to 12/31/14 (Cohort A). A retrospective cohort (Cohort B) of 181 pts meeting similar criteria initiated care from 1/1/12 to 7/1/13. Care patterns were defined by manual chart review through 1/8/15. As only 1 Cohort A pt has progressed on M therapy, charge results assume pts who have initiated M pem will receive the same average of 5.11 doses seen in Cohort B. For Cohort B, actual FL and M therapy charges are reported. 3 Cohort B pts remain on M therapy. Results: Care patterns in Cohorts A and B were compared. 53 (93%) vs 128 (71%) (p = 0.0003) pts received pathway recommended FL care respectively. 42 (74%) vs 110 (61%) received chemotherapy (p = 0.0839). In pts receiving FL platinum-based regimens, 2 (6%) vs 35 (39%) received bev (p < 0.0001) outside of pathway recommendations. In Cohort A, 6 (32%) completing FL therapy initiated M therapy vs 36 (40%) in Cohort B. In pts completing FL therapy, FL and M drug charges per pt were an estimated $107,258 vs $205,431 (48% decrease). Conclusions: Implementation and measurement of adherence to a stage IV NSCLC pathway is feasible at an academic oncology practice with a regional network. This implementation led to a significant improvement in care variation and nearly 50% reduction in chemotherapy charges primarily through decreased bev use.
Abstract MP07: The Association of Optimism, Chronic Kidney Disease and Rapid Kidney Function Decline Among African Americans in the Jackson Heart Study
Authors: La’Shaunta’ Glover, Loretta Cain, Crystal Butler, Allana Forde, Tanjala Purnell, Bessie Young, Mario Sims
Journal: Circulation (2019)

Background: The burden of chronic kidney disease (CKD) and incidence of end-stage renal disease are greater among African Americans than other racial and ethnic groups. A number of studies have attributed the higher prevalence of CKD to traditional risk factors and lower socioeconomic status. However, few studies have examined the association of kidney disease with dispositional optimism, the expectation that positive things will happen. Hypothesis: We hypothesize that there would be an inverse association between optimism and CKD and RKFD. Objective: To examine the association of optimism with CKD at baseline (2000-2004) and rapid kidney function decline (RKFD) between exams 1 and 3 (2000-2013) among African Americans. Methods: We examined 5292 African American participants from the Jackson Heart Study. Optimism was measured using the 6-item Life Orientation Test-Revised (LOT-R) scale and was categorized into tertiles. CKD at baseline was defined as the presence of albuminuria or reduced glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m 2 , or report of dialysis at baseline examination. RKFD was defined as a decline &gt; 4 ml/min/1.73m 2 / year between exams 1 and 3. The associations between optimism and kidney outcomes were tested using multivariable logistic regression to obtain odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, education, income, waist circumference, alcohol intake, physical activity, smoking, diabetes, and hypertension. Results: After exclusion of missing CKD status, there were 682/3422 (19.9%) cases of CKD at exam 1 and 303/3706 (8.2%) who had RKFD at exam 3. Participants with CKD and RKFD were less optimistic ( p &lt;0.05) and were more likely to be older, less educated, have a higher waist circumference, a higher diabetes prevalence. After full adjustment, high (vs. low) optimism was associated with a 32% lower odds of CKD (OR 0.68, 95% CI 0.53-0.85). After 7.21 median years of follow up, high (vs. low) baseline optimism was associated with a 33% lower odds of RKFD after full adjustment (OR 0.67 95% CI 0.48-0.95). Conclusions: Higher optimism was associated with a lower odds of CKD and a lower odds of RKFD over a period of 7 years in this sample of African Americans.
A phase II/III, double-blind, randomized trial comparing maintenance lapatinib versus placebo after first line chemotherapy in HER1/2 positive metastatic bladder cancer patients.
Authors: Thomas Powles, Robert Anthony Huddart, Tony Elliott, Robert Jones, Syed A. Hussain, Simon J. Crabb, Charlotte Ackerman, Satinder Jagdev, John D. Chester, Serena Hilman, Mark Beresford, A. Graham Macdonald, Santhanam Sundar, John A. Frew, Andrew Stockdale, Shah-Jalal Sarker, Daniel Berney, Simon Chowdhury
Journal: Journal of Clinical Oncology (2015)

4505 Background: First-line chemotherapy for metastatic transitional cell carcinoma (TCC) is associated with clinical benefit. Further therapies are largely ineffective. The purpose of this trial was to establish if maintenance lapatinib after first-line chemotherapy was associated with clinical benefit in HER1/HER2 positive TCC patients. Method: During first-line chemotherapy, patients were screened for their HER1/HER2 status by centralised immunohistochemistry (IHC). HER1/2 positive patients with advanced/metastatic TCC who achieved clinical benefit after completing first-line chemotherapy (4-8 cycles) were potentially eligible for randomisation (1:1). The primary endpoint was to compare progression free survival (PFS). Secondary endpoints included adverse events (AE), overall survival (OS) and subset analysis for HER status. Results: Between 2007-2013, 455 patients were screened and 232 HER 1 or 2 positive patients were randomised to lapatinib (L) (n = 116) or placebo (P) (n = 116). 71.2% had visceral metastasis. 64.1% received cisplatin based chemotherapy. The median number of chemotherapy cycles was 6. The progression free survival for L and P was 4.6 months (95% CI: 2.8 – 5.4) and 5.3 months (95% CI: 3.0 – 5.9) respectively [HR: 1.04 (95% CI: 0.79 – 1.39) p = 0.77]. The overall survival for L and P was 12.6 months (95% CI: 9.5 – 16.2) and 11.9 months (95% CI: 10.6 – 15.8) respectively [HR = 0.98 (95% CI: 0.71 – 1.35) p = 0.89). The best response rate for L and P was 13.8% vs 7.8% (p = 0.14). The rate of grade 3-4 AEs for L and P was 24.3% vs. 15.5% (p = 0.09). Subset analysis of i) HER1/HER2 3+ positive patients on IHC ii) HER1 positive patients iii) HER2 positive patients showed no significant benefit in PFS (HR 0.94, 0.99 and 1.19 respectively: p > 0.05 for each) or OS (HR 0.76, 0.92 and 1.03 respectively: p > 0.05 for each) for lapatinib. A model predicting outcomes was constructed. Conclusion: This is the first personalised randomised trial in metastatic TCC. It shows maintenance lapatinib does not improve outcomes in HER1 or HER2 positive individuals. Clinical trial information: NCT00949455.
Mechanisms underlying the association between sarcopenia and poor oncologic outcomes in clear cell renal cell carcinoma.
Authors: Alejandro Sanchez, Fengshen Kuo, Stacey Petruzella, Oguz Akin, Michael Paris, Paul Russo, Timothy An-thy Chan, Marina Mourtzakis, A. Ari Hakimi, Helena Furberg
Journal: Journal of Clinical Oncology (2019)

662 Background: Sarcopenia (low skeletal muscle mass) is associated with poor outcomes in patients with ccRCC. The mechanisms underlying this association are unclear. To understand this association, we examined gene expression differences by sarcopenic status in patients with ccRCC. Methods: The cohort consisted of 62 ccRCC patients treated by nephrectomy and previously transcriptomically-profiled in the Cancer Genome Atlas. Computed tomography scans without contrast performed within two months of surgery were reviewed to determine skeletal muscle cross-sectional area. Sarcopenia (yes/no) was defined according to gender-specific international consensus definitions. Baseline differences in clinicopathologic characteristics were assessed using the Chi-squared test for categorical and t-test for continuous variables. Differential expression analyses were performed using the R package “DESeq2.” Gene set enrichment analyses (GSEA) and single-set GSEA were used to evaluate differences in MSigDB Hallmark gene sets and estimate immune cell infiltration, respectively. P-values were corrected for multiple testing (p-adjust). Results: The cohort was predominantly male (82%), white (97%) and had localized disease (58%). Median age was 58.9 years (SD: 12.1). Sarcopenic (47%) patients were older (p &lt; 0.001), obese (p &lt; 0.001), and presented with higher AJCC stage (p = 0.006). In primary tumor specimens, sarcopenic patients demonstrated increased expression of angiogenic, inflammatory (e.g., IL-6, TNF-alpha), and epithelial mesenchymal transition programs (p-adjust &lt; 0.05). Furthermore, sarcopenic patients had higher macrophage (p = 0.003) and Th17 immune cell infiltration (p = 0.003). Conclusions: Our findings suggest that ccRCC patients who are sarcopenic harbor gene expression programs associated with more aggressive biology. Increased macrophage infiltration and decreased Th17 immune cell infiltration have been previously associated with worse prognosis in ccRCC. It is not clear whether sarcopenia is a cause or consequence of tumor aggressiveness. Validation of these results in a larger cohort of patients and orthogonal validation are ongoing.
Potential use of PEG-HbCO in severe anemia.
Authors: Deven V. Parmar, Hemant K. Misra, John B. Berryman, Abraham Abuchowski
Journal: Journal of Clinical Oncology (2015)

e18086 Background: Patients who cannot receive blood transfusions in the presence of severe anemia can sustain significant morbidity and mortality. Religious beliefs and hemolytic reactions are the most common reasons for not transfusing a patient. Pegylated bovine carboxyhemoglobin (PEG-HbCO) has been used in 5 such patients including a patient who developed a severe hemolytic reaction following stem cell transplantation. Methods: Five patients with hemoglobin (Hb) levels under 3.5 g/dL were treated with repeated doses of PEG-HbCO. Diagnoses included AML, hemolytic reaction, acute chest syndrome and sickle cell crisis. Patients ranged in age from 19 to 61. A unit of PEG-HbCO consists of 500 mL (40 mg/mL). Total doses ranged from 1 unit/day for 2 to 4 days up to 8 units given over 9 days. No adverse events associated with PEG-HbCO were reported. Results: Each investigator reported clinical improvements in their patient following administration of PEG-HbCO, despite continuing low Hb levels. Patient reported well-being was also consistently improved. The number and size of allowed blood draws were restricted; therefore analysis of clinical chemistries was limited. One patient had a significant increase in cerebral oximetry and another showed improvements in cerebral blood flow measured by TCD. Patients with reported extreme fatigue or neurological deficit each demonstrated increases in responsiveness or self-reported comfort within close temporal association with PEG-HbCO treatment. A patient who had undergone a stem cell transplant developed immune hemolytic anemia, with resulting extreme fatigue and tachycardia. He received 4 once-daily units of PEG-HbCO, during which time his heart rate normalized and was reported to be alert and oriented. Conclusions: The improved clinical status in these patients suggests that PEG-HbCO has potential utility in patients with severe anemia who are unable to receive blood transfusions.
Cell-free and Concentrated Ascites Reinfusion Therapy (CART) for management of massive malignant ascites in gastric cancer patients with peritoneal metastasis treated with intravenous and intraperitoneal administration of Paclitaxel with Oral S-1.
Authors: Joji Kitayama, Hironori Ishigami, Hironori Yamaguchi, Norio Hanafusa
Journal: Journal of Clinical Oncology (2015)

e15042 Background: Peritoneal metastasis is the most frequent and life-threatening types of metastasis in gastric cancer (GC). Massive malignant ascites are often associated with peritoneal metastasis of GC and is considered to be difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the variation of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. In this study, we retrospectively studied the safety and efficacy of IP chemotherapy combined with CART in GC patients with massive malignant ascites. Methods: PTX was administered via IP access port implanted in subcutaneous space. If patient had massive ascites at the beginning of treatment, paracentesis was performed through a percutaneous IP catheter and CART was performed. PTX was administered through the catheter until the ascites diminished. PTX was administered IP at 20 mg/m2 as well as IV at 50 mg/m2 on days 1 and 8. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Results: A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increase in the urine volume, serum total protein and albumin level was found after CART procedure. The significant increase in the body temperature (0.3 oC), decrease in platelet count (3.8 × 104/µl), and changes in blood pressure (2 mm Hg) were also found after CART procedure but no clinically significant adverse event was experienced. The MST and 1-year survival of 30 patients who received IP chemotherapy combined with CART procedure was 10.2 months and 43.3% respectively. Two patients received salvage gastrectomy after apparent downstage and survived for 15 and 33 months. Conclusions: IP chemotherapy combined with CART is a promising strategy even for patients with massive malignant ascites originated from peritoneal metastasis of GC.