tbuckley/cabot-search huggingface dataset:
Integration of neuropathy-sparing multimetronomic bevacizumab and multibiochemical modulation followed by regional consolidation and maintenance therapy for refractory ovarian cancer.
Authors: Howard Bruckner, Alison Emily Brandeis, Amir Reza Radjabi, Ruslan Mull, Jeanetta Stega, Azriel Hirschfeld
Journal: Journal of Clinical Oncology (2012)

e15576 Background: In vitro disease models predicted advantages for use of 1/2-1/4 standard cytotoxic doses and selection of drugs each of which simultaneously interact with multiple drugs. Methods: Treatment (rx) combined 10mg/kg bevacizumab (B) q 2 weeks, cyclophosphamide (Cy) 400mg/m 2 modified AC (Garcia Gyn Onc 05) with low dose GFLIP (carboplatin=P) P -/+ docetaxel (D) (Bruckner, ASCO 08). Regional therapy followed: +/- intraperitoneal, target directed or D+cisplatin, +/- or empirical HIPEC. To prevent further neuropathy, present in 8 of 10 pts, D was reserved for late addition (as needed) to create less than 0.5cm or otherwise “eligible for reduction surgery” tumors. Results: Overall S is 8/10 and 4/6 @ 6 and 12 mos. Two lead pts S at 18+ mos. 10/10 tumor marker responses (R); 9/10 objective R all with benefit. Patients (pts) had failed a median of 3 prior regimens and all had large rapidly worsening tumors during prior rx; 6/10 were considered “entirely untreatable.” There were no grade 4 complicated AEs, other than anemia. Epistaxis and HTN were minor, easily controlled AEs. Three deaths due to disease: One pt, PS3, refused surgery for a preexisting bowel obstruction and one, PS3, required weekly paracentesis and had sb obstruction. She relapsed after four mos OR. The third, PS4, pt was paracentesis and thorocentesis dependent and had a 6 mos OR. Median PFS is not yet reached. The lead pt, a 33yo third line, twice operated achieved a pCR in 4 mos, now stoma reversed, unmaintained for 14+ mos, following vaccine rx. Seven had OR without D; brief addition of D; brief addition of D produced 3/3 OR, a pCR, CR and PR. IRB provided prospective oversight of consent. Conclusions: This is an active multi-drug, in theory, anti BRCA rx, for very high risk and some otherwise “untreatable” pts. Simultaneous modulation of multiple drugs, both metronomically, six ways, (Cy-GFIC-D) and biochemically, up to five ways "each," 15 ways (5+4+3+2+1), is safe. Algorithms can offer cost savings (for B) by selecting a finite, short, “best” period for rx and then definitive, B free, consolidation rx. B driven response can create new windows of opportunity for test worthy multidisciplinary rxs.
3T MRI of the prostate correlation to 3D reconstruction of transperineal mapping biopsies.
Authors: Kyle O. Rove, Thomas J. Pshak, Nayana Patel, Colin O'Donnell, E. David Crawford
Journal: Journal of Clinical Oncology (2012)

e15176 Background: MRI is new tool in the diagnosis and surveillance of localized prostate cancer. Studies have examined the sensitivity and specificity of MRI for detecting and localizing prostate cancer as compared to radical prostatectomy specimens. We have previously demonstrated excellent correlation between 3-dimensional transperineal mapping biopsies (3DMB) to radical prostatectomy specimens. We hypothesize that MRI does not perform as well detecting smaller lesions of the prostate as larger ones. In this study, we retrospectively compare the correlation of 3DMB to 3T MRI-positive lesions. Methods: Between 2010 and 2011, 34 men with histologically-proven prostate cancer underwent 3T endorectal coil MRI and subsequent template-guided (5-mm grid) 3DMB. Three-dimensional computer models of the mapping biopsies were created using Proview software to identify clusters of positive biopsies likely belonging to a single lesion. MRIs were read by two trained radiologists blinded to 3DMB results. Disagreement between radiologists was settled by consensus. MRI and 3DMB were then compared in a retrospective fashion. Results: Median age and PSA were 65 years (49-76) and 4.3 ng/mL (0.7-15.0). Median prostate volume was 40 cm 3 (21-105 cm 3 ). Median total biopsy cores on 3DMB was 60 (26-151), and mean positive cores was 3 (0-13). 3D reconstruction of patient biopsy sets resulted in 58 distinct foci of cancer. MRI identified 64 individual lesions suspicious for cancer. Of these, 66% (n=42) could be correlated to a positive area on 3DMB consisting of one or more positive biopsies, and 34% (n=22) corresponded to negative regions on 3DMB. When two or more biopsies represented a positive lesion on 3DMB, the positive-predictive value of MRI was 100% (n=24). Conversely, only 72% (n=42) of positive 3DMB areas could be correlated to a lesion on MRI, and 28% (n=16) were not seen on MRI.. Conclusions: MRI has vast potential as a less-invasive method in the detection and surveillance of prostate cancer. While MRI does appear to have excellent positive predictive value, the number of false negatives and relevance to clinically-significant lesions require further illumination.
Comparison of the Health Benefits of Different Types of Nature
Authors: Sjerp de Vries
Journal: JAMA Network Open (2019)

In their study, Astell-Burt and Feng 1 address 2 important limitations of much of the research on contact with nearby nature and human health and well-being. 2 The first one is its cross-sectional design, preventing the ability to draw firm conclusions regarding the causality of observed associations.The second one is that most studies do not distinguish between different types of green and/or blue space and consequently tell us little about which type of nature is most beneficial.In their study, they begin to address this gap by making efficient use of longitudinal health data already
Conditional survival in gallbladder carcinoma: Results from the SEER 11 dataset
Authors: C. R. Thomas, C. D. Fuller, G. D. Starling, S. J. Wang
Journal: Journal of Clinical Oncology (2006)

4130 Background: Traditionally, survival is reported as 5-or10-yr survival from diagnosis. However, the 5-yr probability of demise changes considerably with each year survived in many cancers. Clinicians may utilize conditional survival to estimate risk over time. Gallbladder cancer is a rare neoplasm with little extant data with regard to risk assessment for patients with one or more years survival post-therapy. The specific aim of this study is to assess the conditional survival of patients with gallbladder adenocarcinoma using data extracted from the Surveillance, Epidemiology, and End Results (SEER 11) Program. Methods: Cumulative observed survival rates were calculated by the life-table method using SEER data for 3744 patients with histologically confirmed gallbladder adenocarcinoma (diagnosed from 1973 to 2001). On the basis of the cumulative survival estimates, we derived the conditional survival, defined as the calculated probability of survival having already survived a specified number of years from diagnosis, with sub-stratification by extent of disease. Results: Conditional survival calculations reveal dismal 5-year survival at diagnosis (Figures 1 and 2), with increasing probability of survival per each year survived. However, conditional survival plateaus at approximately 60–70% at 4 years post-diagnosis, with little change in conditional survival until 10 years. Conclusions: This dataset represents the largest pooled data for gallbladder carcinoma, and is markedly larger than any given institutional series. Consequently, while imperfect, this data represents a useful estimate for patients with considerable post-diagnosis survival. Although the disease-free survival outcomes for patients with gallbladder adenocarcinoma remain low, for those patient surviving even 1 year post-diagnosis, conditional survival estimates increase rapidly. [Table: see text] No significant financial relationships to disclose.
Abstract 20122: HIV Protein Negative Factor (Nef) - Induced Release of Endothelial Monocyte Activating Polypeptide II (EMAPII) Mediates Endothelial Dysfunction in HIV Patients
Authors: Sarvesh Chelvanambi, Samir Gupta, Noelle Dahl, Homer Twigg, Matthias Clauss
Journal: Circulation (2017)

HIV patients have increased risk of vascular pathologies including cardiovascular diseases and pulmonary hypertension. A likely candidate is the endothelial dysfunction causing HIV-Nef protein, whi...
Clinical pharmacokinetics (PK) of BMS-936558, a fully human anti-PD-1 monoclonal antibody.
Authors: Shruti Agrawal, Yan Feng, Georgia Kollia, Sally Saeger, Martin Ullmann, Dan McDonald, Ashok Kumar Gupta, Amit Roy, Eric Masson
Journal: Journal of Clinical Oncology (2012)

TPS2622 Background: BMS-936558 is a fully human IgG4 monoclonal antibody targeted against human Programed Death-1 (PD1) receptor on activated T and B lymphocytes. Blocking of PD-1 prevents these activated cells from becoming anergic, thereby maintaining anti-tumor immunologic activity. Methods: The PK of BMS-936558 was characterized with data from a single ascending dose (SAD) and a multiple ascending dose (MAD) study in subjects with advanced solid malignancies. Subjects received a single IV infusion of 0.3 to 10 mg/kg BMS-936558 in the SAD study (MDX-1106-01 Study) and 0.1 to 10 mg/kg BMS-936558 every two weeks in the MAD study (MDX-1106-03/CA209003 Study). The PK of BMS-936558 was characterized by non-compartmental analysis of intensively sampled PK data from a SAD study, as well as by population PK analysis of available intensive and sparse PK data from the SAD and MAD studies, respectively. Results: The PK of BMS-936558 is linear in the studied dose range with dose-proportional increase in Cmax and AUC with low to moderate (20-44%) inter-subject variability. Geometric mean clearance ranged from 0.13 - 0.19 mL/h/kg, whereas mean volume of distribution ranged from 83 -113 mL/kg. The range of mean terminal elimination half-life of BMS-936558 is 17 to 25 days which is consistent with half-life of endogenous IgG4. BMS-936558 PK was adequately described by a linear two-compartment model, and there was no evidence of a contribution of target mediated drug disposition to drug elimination within tested dose range. Body weight and gender are potentially clinically significant covariate for both clearance and volume of distribution (&gt; 20% effect); and baseline CRP, LDH, and albumin are potentially clinically significant covariates for CL. The body weight normalized dosing employed produces trough concentrations that are approximately constant over a wide range of body weights. Conclusions: The pharmacokinetics of BMS-936558 is dose-proportional and body weight normalized dosing is appropriate to ensure consistent exposure over a wide range of body weights.
Stable Ischemic Heart Disease
Authors: Daniel Katz, Michael C. Gavin
Journal: Annals of Internal Medicine (2019)

Stable ischemic heart disease (SIHD) is a leading cause of death in the United States and many other countries. The defining pathobiology is an imbalance between the metabolic demands of the myocardium and its oxygen supply, which most often results from coronary artery atherosclerosis. The classic presenting symptom of SIHD is angina, but clinical presentation varies greatly among patients. Since the last In the Clinic on SIHD in 2014, several new drugs have been approved to reduce ischemic complications, such as myocardial infarction and congestive heart failure.
Antitumor Activity and Tolerability of hu14.18-IL2 with GMCSF and Isotretinoin in Recurrent or Refractory Neuroblastoma: A Children's Oncology Group Phase II Study
Authors: Suzanne Shusterman, Arlene Naranjo, Collin Van Ryn, Jaquelyn A. Hank, Marguerite T. Parisi, Barry L. Shulkin, Sabah Servaes, Wendy B. London, Hiroyuki Shimada, Jacek Gan, Steven D. Gillies, John M. Maris, Julie R. Park, Paul M. Sondel
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Combining anti-GD2 (disialoganglioside) mAb with GM-CSF, IL2, and isotretinoin is now FDA-approved for high-risk neuroblastoma minimal residual disease (MRD) therapy. The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in neuroblastoma and is more effective in neuroblastoma-bearing mice than antibody and cytokine given separately. We therefore evaluated the safety, tolerability, and antitumor activity of hu14.18-IL2 given with GM-CSF and isotretinoin in a schedule similar to standard MRD therapy. Patients and Methods: Hu14.18-IL2 was given at the recommended phase II dose of 12 mg/m2/day on days 4–6 of a 28-day cycle with GM-CSF (250 mg/m2/dose, days 1–2 and 8–14) and isotretinoin (160 mg/m2/day, days 11–25). Tolerability was determined on the basis of the number of unacceptable toxicities observed. Response was evaluated separately for patients with disease measurable by standard radiologic criteria (stratum 1), and for patients with disease evaluable only by I123-metaiodobenzylguanidine (I123-MIBG) scan and/or bone marrow histology (stratum 2). Results: Fifty-two patients with recurrent or refractory neuroblastoma were enrolled; 51 were evaluable for toxicity and 45 were evaluable for response. Four patients had unacceptable toxicities, well below the protocol-defined rule for tolerability. Other grade 3 and 4 nonhematologic toxicities were expected and reversible. No responses were seen in stratum 1 (n = 14). In stratum 2 (n = 31), 5 objective responses were confirmed by central review (3 complete, 2 partial). Conclusions: Hu14.18-IL2 given in combination with GM-CSF and isotretinoin is safe and tolerable. Patients with MIBG and/or bone marrow–only disease had a 16.1% response rate, confirming activity of the combination.
Association Between Recurrent Febrile Urinary Tract Infections and Renal Scarring
Authors: Kenneth B. Roberts
Journal: JAMA Pediatrics (2019)

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Chemotherapy for patients with brain metastases from melanoma.
Authors: David R. Naskhletashvili, Vera A. Gorbunova, Mark B. Bychkov, Ali H. Bekyashev, Vladislav B. Karahan, Vladimir A. Aloshin, Zoya P. Michina, Ekaterina A. Moskvina
Journal: Journal of Clinical Oncology (2012)

e19012 Background: There have not been standards of chemo- and chemo-radiotherapy for treatment for patients with brain metastases. The patients (pts) with brain metastases (BM) from melanoma have poor prognoses. The main goal of this trial is to assess the efficacy of nitrosoureas (CCNU or FCNU), temozolomide (TMZ) as monotherapy, TMZ combined with whole brain irradiation (WBI), or combined chemotherapy of TMZ and cisplatin in pts with BM from melanoma. Methods: 78 pts were included in this study. 21 pts were treated with WBI (3Gy/30Gy) and concomitant TMZ therapy (75 mg/m 2 /day orally on days 1-14), 19 pts were treated with TMZ (150 mg/m 2 /day orally on days 1-5, every 4 weeks) as monotherapy, 17 pts pts were treated with nitrosoureas (CCNU or FCNU), 21 pts were treated with combined chemotherapy of TMZ (150/mg/m 2 /day orally on days 1-5, every 4 weeks) + cisplatin (20/mg/m 2 /day intravenous on days 1-5, every 4 weeks). The main aims of this study were objective response (OR) – complete response (CR) + partial response (PR) in the brain and in the extracranial sites (ES), median of survival (mOS), 1-year and 2-year survival. Results: Observations were as follows: in the TMZ + WBI treated pts, 4 OR (19,0%) in 21 pts group in the brain and 1 OR (6,7%) in 15 pts group in ES. The mOS was 6.0 months, 1-year survival was 23,8%. In the TMZ monotherapy treated pts there were 5 OR (26,3%) in 19 pts group in the brain and no OR in 13 pts group in ES. The mOS was 6 months, 1-year survival was 21,1%. In the nitrisoureas treated pts we achieved 2 OR (11,8%) in 17 pts group in the brain and 1 OR (9,1%) in 11 pts group in ES. The mOS was 5 months, 1-year survival was 17,6%. In the TMZ + cisplatin treated pts there were 7 OR (33.3%) in 21 pts group in the brain and 7 OR (35,0%) in 20 pts group in ES. The mOS was 8 months, 1-year survival was 33,3%. 2-year survival (19,0%) was achieved only in TMZ and cisplatin group. Conclusions: Previous results of our study showed promising higher efficacy of TMZ and cisplatin, especially in OR in ES (p&lt;0.05) and in 2-year survival (p&lt;0.05), in comparison with TMZ alone, nitrosoureas or TMZ with whole brain irradiation in patients with metastatic melanoma with BM. Control of extracranial lesions is important factor for patients with BM. Further investigation is to be expected.
The effect of copper nanoparticles on the progression of tumor in vivo.
Authors: Polina Sergeevna Kachesova, Irina Aleksandrovna Goroshinskaya, Vladimir Borisovich Borodulin
Journal: Journal of Clinical Oncology (2013)

3084 Background: The study of the anticancer activity of copper nanoparticles (CuNP) measuring 70-75 nm in rats transplantable tumors. Methods: Experiments were carried out on white outbreed male rats with transplanted sarcoma 45 (9.10-dimethyl-1.2-benzanthracene-induced fusiform cell fibrosarcoma, S-45) and Pliss’s lymphosarcoma (Pliss). 0.5 ml of tumor tissue suspension (1x10 6 cells) in saline was inoculated subcutaneously in rat dorsal region for induction of sarcoma 45 or Pliss's lymphosarcoma. 7-8 days after tumors transplantation the animals were divided into three groups. Group 1: control (rats received 0.3 ml of saline only). Group 2: CuNP in 0.9% w/v of NaCl were injected intratumorally (1.25 mg/kg bodyweight). Group 3: The same amount of CuNP was injected intraperitonially. Animals received nanoparticles four times a week for one week, then after a week's break, the procedure was repeated. The associated nanoparticles are spherical in shape and have an oxide film on its surface. CuNP effect on tumor growth was determined by the mass (M) and size (V) of tumors. Results: The analysis of the received data showed that administration of CuNP to rats with S-45 caused reduced growth rates or cases with complete regression (8 of 17 cases) in 67.0% of experimental animals independently of injection way (V=0.81±0.3 cm 3 , M=0.91±0.3 g). The other 33% of rats with S-45 showed tumor growth (V=7.58±1.3 cm 3 , M=9.2±1.6 g). Overall, for the entire group of animals with S-45, nanoparticles inhibited tumor growth of 45%. In the control group there was an increase of tumor growth (V=9.0±1.8 cm 3 , M=10.4±2.5 g). CuNP introduction to animals with Pliss caused a delay in tumor growth and partial or complete regression (12 of 28 eight cases) in 40.0-48.0% of the rats in the route of Cu injection (V=1.4±0.8 cm 3 , M=10.4±2.5g). Observation of the remaining animals revealed tumor growth (V=60.6±5.93 cm 3 , M=67.13±8.7 g). In the whole group tumor growth inhibition was 50.0%. In the control group we observed increase of tumor growth (V=62.1±5.21 cm 3 , M=75.9±8.2 g). Conclusions: Thus the study showed that the copper nanoparticles possess antiproliferative activity, can inhibit the growth of transplanted tumors in rats and may be potentially used in anticancer medical therapy.
Provider Attitudes and Practice Patterns for Direct-Acting Antiviral Therapy for Patients With Hepatocellular Carcinoma
Authors: Nicole E. Rich, Ju Dong Yang, Ponni V. Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D. Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N. Ioannou, Maarouf A. Hoteit, Andrew M. Moon, Amol S. Rangnekar, Sheila L. Eswaran, Elizabeth Zheng, Janice H. Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T. Frenette, Sanjaya K. Satapathy, Parvez Mantry, Prasun Jalal, Binu V. John, Oren K. Fix, Michael Leise, Christina C. Lindenmeyer, Avegail Flores, Nayan Patel, Z. Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A. Marrero, Amit G. Singal
Journal: Clinical Gastroenterology and Hepatology (2019)
Case study of a flexible bayesian design in a phase II study in patients with resected pancreas cancer
Authors: F. E. Harrell, T. Rodell, D. Apelian
Journal: Journal of Clinical Oncology (2009)

e15651 Background: This presentation will describe a Bayesian flexible design for an ongoing randomized, placebo controlled phase II trial in newly diagnosed, resected pancreas cancer comparing gemcitabine plus therapeutic vaccine (GI-4000) vs. gemcitabine alone. The design allows for infinitely many looks at the data, possible study expansion, and conversion to adaptive allocation. Unlike frequentist approaches, the Bayesian procedure does not require penalizing the final analysis for earlier analyses nor does it require down-weighting of data collected before the decision to expand the study. The same analysis procedure is used for final and interim analyses, whereas there is no consensus in the frequentist approach for how to analyze an expanded study. Methods: Our primary analysis is based on a Bayesian Cox proportional hazards model using a skeptical prior distribution. The endpoint is time to recurrence or death. Evidence for efficacy is taken to be a posterior probability of efficacy ≥ 0.95 at any analysis time, where ‘efficacy’ means a true hazard ratio &lt; 1.0. The planned rule for expanding the study is a probability of efficacy ≥ 0.7 prior to the last pre-planned analysis. Results: This ongoing study remains blinded. Results will include statistical methods (including simulations to assess study properties of the design) and experience in collaborating on the design with the FDA. Conclusions: In the frequentist approach, computing the probability of getting a result as or more impressive than that observed if there is truly no treatment effect (the P-value) requires contemplating experiments that were never carried out and analyses that were never done. The Bayesian approach offers the advantage of computing only ‘forward’ probabilities (Bayesian posterior probabilities) and conditioning only on what has been observed up to the time of analysis. There is no requirement to assume unknowable information such as the true population treatment effect. The adaptability afforded by Bayesian trial design can greatly enhance the likelihood of gaining useful clinical data from phase II trials. [Table: see text]