tbuckley/cabot-search huggingface dataset:
Concordance of PD-L1 expression detection in non-small cell lung cancer (NSCLC) tissue biopsies between OncoTect iO single cell PD-L1 quantification assay and immunohistochemistry (IHC).
Authors: Amanda Chargin, Rian Janine Morgan, Bruce Kendrick Patterson
Journal: Journal of Clinical Oncology (2017)

e23172 Background: PD-1/PD-L1 therapy has been shown to be effective in patients with NSCLC, specifically those with 50% PD-L1 expression or greater by IHC. Response rates for those with lower PD-L1 expression do not consistently correlate with PD-L1 amount. The OncoTect iO Lung PD-L1 Assay was designed to provide non-subjective quantification of PD-L1 expression on tumor cells and immune cells from a multitude of tumor types. The objective of this study was to compare OncoTect iO and the current method of PD-L1 testing by immunohistochemistry (IHC) in NSCLC biopsies. Methods: Eleven NSCLC tissues were obtained from two IRB approved sites. Fresh tissues were processed into single cell suspensions using the IVD IncellPREP Kit (IncellDx, Inc). Normal lung tissue adjacent to tumor sites was obtained for 9 of the samples. Cell suspensions were tested with the OncoTect iO Lung Assay which contains antibodies directed against PD-L1 (28-8), CD45, CD3, and CD8. Suspensions are fixed and permeabilized, labeled with the antibodies, and then stained with DAPI to identify intact, single cells, and to analyze cell cycle including aneuploidy.Matched FFPE sections were taken from the tissue biopsies and were tested at BioReference Laboratories with the Dako PD-L1 IHC 28-8 PharmDx Kit. Results: A cut-off of 4% was used for the OncoTect iO Assay and a positive result for the Dako assay is ≥ 5% of the tumor cells (equivalent to 5 cells out of 100). PD-L1 expression ranged from 0% to 75% in the tumor samples which is consistent with reported ranges. Seven samples were positive by OncoTect iO Lung and 6 were positive by IHC. Twelve samples were negative by OncoTect iO Lung and 13 were negative by IHC demonstrating a concordance of 95%. Of note, one tumor that was negative by OncoTect iO and IHC demonstrated 5% of aneuploidy tumor cells that were positive and most likely very rare to be detected in the assays. Conclusions: In this study, the concordance between Oncotect iO and IHC was 95%, however, the Oncotect iO Single Cell PD-L1 Quantification Assay was fast ( &lt; 3 hours), non-subjective, and provided addition expression information for aneuploid tumor cells.
Efficacy of aggressive thoracic therapy (ATT) compared with no ATT for synchronous oligometastatic non-small cell lung cancer (NSCLC): Results of a meta-analysis.
Authors: Xiaoxia Zhu, Dianhe Li, Na Li, Yiyi Li
Journal: Journal of Clinical Oncology (2016)

e20574 Background: A number of literature reported a long-term survival in oligometastatic NSCLC patients cured with a radical approach, however, most studies do not differentiate between synchronous versus metachronous metastases. A meta-analysis of individual patient data showed that patients with synchronous metastases and N1/N2 disease experienced the poorest survival among oligometastatic NSCLC received radical treatment paradigm, leading us to question whether synchronous oligometastatic NSCLC patients might gain survival benefit from ATT. Methods: A systematic review of controlled trials of ATT on survival in synchronous oligometastatic NSCLC was conducted via searching Pubmed, Embase and Cochrane database. Hazard ratio (HR) for the main endpoint overall survival (OS) were pooled using a fixed-effects model. We performed the stratified analysis of single organ metastases, solitary brain metastasis, thoracic primary tumor stagings. Pooled survival curves of OS were constructed. Results: Seven eligible studies were identified including 668 synchronous oligometastatic NSCLC patients, of whom 227 (34.0%) received ATT. Overall, ATT in patients with synchronous oligometastatic NSCLC was associated with a significant benefit of OS (HR 0.48; 95% CI 0.39-0.60; p < 0.00001). The HRs for single organ metastases subgroup, solitary brain metastasis subgroup, and thoracic stage I-II subgroup were 0.42 (95% CI 0.31-0.56; p < 0.00001), 0.49 (95% CI 0.31-0.75; p = 0.001), and 0.38 (95% CI, 0.20-0.73; p = 0.004), respectively. The absolute cumulative survival rate differences were 42.6% at 1 year, 38.4% at 2 years, 19.3% at 3 years, and 10.6% at 4 years. Conclusions: This meta-analysis demonstrated improvement in overall survival benefit with aggressive thoracic management in patients with synchronous oligometastatic NSCLC.
The Promise of Mobile Technologies for the Health Care System in the Developing World: A Systematic Review
Authors: Grigorios Karageorgos, Ioannis Andreadis, Konstantinos Psychas, George Mourkousis, Asimina Kiourti, Gianluca Lazzi, Konstantina S. Nikita
Journal: IEEE Reviews in Biomedical Engineering (2018)

Evolution of mobile technologies and their rapid penetration into people's daily lives, especially in the developing countries, have highlighted mobile health, or m-health, as a promising solution to improve health outcomes. Several studies have been conducted that characterize the impact of m-health solutions in resource-limited settings and assess their potential to improve health care. The aim of this review is twofold: 1) to present an overview of the background and significance of m-health and 2) to summarize and discuss the existing evidence for the effectiveness of m-health in the developing world. A systematic search in the literature was performed in Pubmed, Scopus, as well as reference lists, and a broad sample of 98 relevant articles was identified, which were then categorized into five wider m-health categories. Although statistically significant conclusions cannot be drawn since the majority of studies relied on small-scale trials and limited assessment of long-term effects, this review provides a systematic and extensive analysis of the advantages, disadvantages, and challenges of m-health in developing countries in an attempt to determine future research directions of m-health interventions.
An open-label, single arm, phase IIa study of bortezomib, lenalidomide, dexamethasone, and elotuzumab in newly diagnosed multiple myeloma.
Authors: Jacob Laubach, Ajay K. Nooka, Craig Cole, Elizabeth O'Donnell, Ravi Vij, Saad Zafar Usmani, Gregory Joshua Orloff, Joshua Ryan Richter, Robert Redd, Heidi DiPietro, Kristen Cummings, Joshua Hansen, Patrick M. Henrick, Paul Bassett, Haley Schachter, Paul G. Richardson, Sagar Lonial
Journal: Journal of Clinical Oncology (2017)

8002 Background: Elotuzumab (elo) is approved for use in combination with lenalidomide (len) and dexamethasone (dex) for relapsed and refractory multiple myeloma (MM). This phase 2a study evaluated the efficacy and safety of elo in combination with len, subcutaneous bortezomib (bortez), and dex. Methods: The primary objective of this study was to determine the response rate of newly diagnosed, transplant-eligible MM patients (pts) after four cycles of therapy with elo plus len, bortez, and dex. Pts were newly diagnosed with MM by the revised IMWG criteria. Elo was administered days 1, 8, and 15 of the first two 28 day cycles and days 1 and 11 in cycles 3 and 4. Following cycle 4, pts underwent stem cell mobilization and could then proceed with either autologous stem cell transplant (ASCT) or defer transplant and receive four more cycles of induction therapy with elo plus len, bortez, and dex. Following either ASCT or 8 cycles of induction chemotherapy, pts transitioned to risk-adapted maintenance with elo, len, and dex plus every other week bortez (pts with high-risk cytogenetics, ISS stage II or III) or elo, len, dex (all others). Responses were assessed by the modified Uniform Response Criteria and toxicities graded based on NCI-CTCAE V4. Results: 41 patients with a median age of 60 were enrolled and this analysis encompasses response data from 29 patients. The overall response rate (ORR) after four cycles was 100%, with 24% achieving a complete response (CR), 47% achieving a very good partial response (VGPR), and 29% a partial response (PR). The rate of VGPR or better was 71%. The median number of CD34+ stem cells collected was 10.3 x 10^6. The most frequent grade 3 or higher toxicities included thrombocytopenia (15%) and hypophosphatemia (12%). The rate of grade 3 or higher peripheral neuropathy was 2%. Two pts died while on study, one due to complications of septicemia and the other due to respiratory failure. Conclusions: The combination of elo plus len, bortez, and dex was effective in newly diagnosed, ASCT-eligible patients. The rate of high-grade toxicities was low, although there were two grade 5 events (septicemia and respiratory failure). Clinical trial information: NCT02375555.
Effect of Portable Air Filtration Systems on Personal Exposure to Fine Particulate Matter and Blood Pressure Among Residents in a Low-Income Senior Facility
Authors: Masako Morishita, Sara D. Adar, Jennifer D’Souza, Rosemary A. Ziemba, Robert L. Bard, Catherine Spino, Robert D. Brook
Journal: JAMA Internal Medicine (2018)

Fine particulate matter (smaller than 2.5 μm) (PM2.5) air pollution is a major global risk factor for cardiovascular (CV) morbidity and mortality. Few studies have tested the benefits of portable air filtration systems in urban settings in the United States.To investigate the effectiveness of air filtration at reducing personal exposures to PM2.5 and mitigating related CV health effects among older adults in a typical US urban location.This randomized, double-blind crossover intervention study was conducted from October 21, 2014, through November 4, 2016, in a low-income senior residential building in Detroit, Michigan. Forty nonsmoking older adults were enrolled, with daily CV health outcome and PM2.5 exposure measurements.Participants were exposed to the following three 3-day scenarios separated by 1-week washout periods: unfiltered air (sham filtration), low-efficiency (LE) high-efficiency particulate arrestance (HEPA)-type filtered air, and high-efficiency (HE) true-HEPA filtered air using filtration systems in their bedroom and living room.The primary outcome was brachial blood pressure (BP). Secondary outcomes included aortic hemodynamics, pulse-wave velocity, and heart rate variability. Exposures to PM2.5 were measured in the participants' residences and by personal monitoring.The 40 participants had a mean (SD) age of 67 (8) years (62% men). Personal PM2.5 exposures were significantly reduced by air filtration from a mean (SD) of 15.5 (10.9) μg/m3 with sham filtration to 10.9 (7.4) μg/m3 with LE fitration and 7.4 (3.3) μg/m3 with HE filtration. Compared with sham filtration, any filtration for 3 days decreased brachial systolic and diastolic BP by 3.2 mm Hg (95% CI, -6.1 to -0.2 mm Hg) and 1.5 mm Hg (95% CI, -3.3 to 0.2 mm Hg), respectively. A continuous decrease occurred in systolic and diastolic BP during the 3-day period of LE filtration, with a mean of 3.4 mm Hg (95% CI, -6.8 to -0.1 mm Hg) and 2.2 mm Hg (95% CI, -4.2 to -0.3 mm Hg), respectively. For HE filtration, systolic and diastolic BP decreased by 2.9 mm Hg (95% CI, -6.2 to 0.5 mm Hg) and 0.8 mm Hg (95% CI, -2.8 to 1.2 mm Hg), respectively. Most secondary outcomes were not significantly improved.Results of this study showed that short-term use of portable air filtration systems reduced personal PM2.5 exposures and systolic BP among older adults living in a typical US urban location. The use of these relatively inexpensive systems is potentially cardioprotective against PM2.5 exposures and warrants further research.ClinicalTrials.gov identifier: NCT03334565.
Pharmacodynamic study using FLT PET/CT in advanced solid malignancies treated with a sequential combination of X-82 and docetaxel.
Authors: Murtuza M. Rampurwala, Lakeesha Carmichael, Jens C. Eickhoff, Jill Kolesar, Kimberly Binger, Jennifer Heideman, Scott Perlman, Chris Liang, Robert Jeraj, Glenn Liu, Justine Yang Bruce
Journal: Journal of Clinical Oncology (2015)

TPS2601 Background: Clinical experience has shown that despite resolution of tumor pain while on vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI), pain not only returns, but increases during treatment break. We believe this is due to a withdrawal flare i.e. increased tumor proliferation after VEGFR TKI cessation driven by VEGF. We have previously demonstrated this flare using 18-Fluorothymidine (FLT) PET/CT. ( Liu G et.al. Clin Cancer Res 2011;17:7634-44) A sequential approach synchronizing cell-cycle specific chemotherapy with this withdrawal flare may maximize therapeutic index of chemotherapy. Here we propose a novel sequential study using X-82, a VEGFR TKI with docetaxel using FLT PET/CT to measure change in vascular parameters and proliferation. We plan comparing low and high doses of X-82 to explore if low dose is preferable with chemotherapy. Methods: A phase 1 pharmacodynamic study in advanced solid malignancies is planned. Inclusion criteria include at least one lesion amenable to FLT PET/CT, ECOG performance status of ≤ 1 with normal organ and marrow function. 30 patients will be randomized 1:1 to low dose X-82 (200 mg) or high dose X-82 (400 mg) arm. In Cycle 1, X-82 is administered daily on days 2-15. FLT PET/CT (FLT 1) is obtained on day 1, once on day 12-15 (FLT 2) and day 19-21 (FLT 3). Comparison between FLT 1 and 2 will characterize response to X-82 and FLT 2 and 3 will characterize withdrawal flare. In Cycle 2, docetaxel (75 mg/m2) is administered on day 1, followed by X-82 on days 2-15. FLT PET/CT (FLT 4) once on day 12-15 will characterize response to X-82 and docetaxel. Sequential treatment is continued until progression or unacceptable toxicity. Correlative studies include VEGF levels and X-82 pharmacokinetics. Primary objectives are to evaluate safety, tolerability and FLT PET/CT changes with X-82 alone and with docetaxel. Secondary objectives include evaluating objective response rate to the combination. Toxicities will be monitored based on Pocock stopping boundaries with overall type I error of 0.10. At this time, 2 patients are enrolled on study. After establishing safety, we plan dose expansion cohorts in multiple disease sub-types. Clinical trial information: NCT02146222.
Comparison of cap-assisted endoscopy vs. side-viewing endoscopy for examination of the major duodenal papilla: a randomized, controlled, noninferiority crossover study
Authors: Mohamed Abdelhafez, Veit Phillip, Alexander Hapfelmeier, Veronika Sturm, Mayada Elnegouly, Markus Dollhopf, Abdelmeguid Kassem, Peter Klare, Simon Nennstiel, Roland M. Schmid, Stefan von Delius, Florian Eckel
Journal: Endoscopy (2018)

Abstract Background Use of a side-viewing endoscope is currently mandatory to examine the major duodenal papilla; however, previous studies have used cap-assisted endoscopy for complete examination of the papilla. The aim of this study was to compare cap-assisted endoscopy with side-viewing endoscopy for examination of the major duodenal papilla. Methods This was a prospective, randomized, blinded, controlled, noninferiority crossover study. Patients were randomized to undergo either side-viewing endoscopy followed by cap-assisted endoscopy or cap-assisted endoscopy followed by side-viewing endoscope. Photographs of the major duodenal papilla were digitally edited to mask the cap area before they were evaluated by three blinded external examiners. Our primary end point was complete visualization of the major duodenal papilla. Secondary end points were the ability to examine the mucosal pattern, the overview of the periampullary region, overall satisfaction, and time to locate the papilla. Results 62 patients completed the study. Complete visualization of the major duodenal papilla was achieved in 60 examinations by side-viewing endoscopy and in 59 by cap-assisted endoscopy (97 % vs. 95 %). The difference between the two examinations was 1.6 % with a two-sided 95 % confidence interval of −4.0 % to 7.3 %, which did not exceed the noninferiority margin of 8 %. Cap-assisted endoscopy achieved better scores regarding the examination of mucosal pattern and overall satisfaction, whereas side-viewing endoscopy had a better overview score (P &lt; 0.001, P = 0.004, and P &lt; 0.001, respectively). There was no relevant difference in the median times to locate the major duodenal papilla. Conclusion Cap-assisted endoscopy and side-viewing endoscopy had similar success rates for complete visualization of the major duodenal papilla. Cap-assisted endoscopy is superior to side-viewing endoscopy regarding the mucosal pattern and overall satisfaction. Side-viewing endoscopy gives a better overview of the periampullary region.
ET190L1-ARTEMIS T cell therapy to induce complete remission of relapsed and refractory (r/r) B-cell lymphoma with no cytokine release syndrome in the first-in-human clinical study.
Authors: Zhi Tao Ying, Li Long, Hong Liu, Mei Zhang, Pengcheng He, David Rizzieri, Yuqin Song, Bijan Nejadnik, Jun Zhu, Cheng Liu
Journal: Journal of Clinical Oncology (2018)

3049 Background: To ameliorate CRS commonly associated with CAR T-cell therapy, we developed a novel T cell therapy, the ARTEMIS platform, which functionally matches the potency of CAR-T cells, but triggers significantly less cytokine release upon target engagement. Herein we describe the first-in-human clinical studies of anti-CD19 ET190L1-ARTEMIS™ T cell therapy in r/r B-cell lymphoma at multiple sites. Methods: Patients are assigned to 1 of 3 cohorts: single infusion of ET190L1-ARTEMIS™ T cells at 1, 3 or 6 × 106 cells/kg. The primary objective is to evaluate safety. Additional objectives include assessment of T cell engraftment and tumor response. Results: As of Jan 23, 2018, twelve heavily pretreated adult patients received autologous ET190L1-ARTEMIS T cells, 3 in the 1 × 106/kg cohort and 9 in the 3 × 106/kg cohort. Expansion of ARTEMIS T cells after infusion was observed in all patients. No CRS or neurotoxicity was observed. Plasma levels of IL-2, 4, 6, 8, 10, IFNg, TNFa, and GM-CSF were below detection at most time point post-infusion. Vital signs were normal except for 3 patients in the 3 × 106/kg cohort who had transient fever (37.5-39°C) from day 2 to day 4 post-infusion. One patient from the 1 × 106/kg cohort developed a transient skin rash. The overall response rate is 78% (7/9) (See Table 1). Six month follow-up data for the first 9 patients and early data from additional patients will be presented. Conclusions: In the studies, ET190L1-ARTEMIS T cell therapy demonstrated a favorable safety profile with no observed CRS or neurotoxicity and shows promising efficacy in r/r lymphoma patients. Durability of the responses will be evaluated with longer follow-up. Based on its observed response rate and lack of CRS and neurotoxicity, the ARTEMIS platform is potentially a major improvement over existing CAR-T cell therapy. Tumor response (using Cheson criteria) and treatment-related safety events. Patient Subtype Dose (Cells/kg) Month Post Dosing CRS Neurotoxicity 1 2 3 1 DLBCL 1x106 CR CR CR 0 0 3 DLBCL SD SD SD 0 0 4 FL CR CR CR 0 0 5 DLBCL 3x106 PD 0 0 6 DLBCL PD 0 0 7 FL CR 0 0 8 DLBCL CR 0 0 9 MCL CR 0 0 10 FL PR 0 0
Norethindrone substituted for megestrol in the treatment of metastatic endometrial carcinoma: Three cases.
Authors: Sumita Trivedi, Felicia Williams, William L. Read
Journal: Journal of Clinical Oncology (2017)

e17111 Background: Megestrol (M) is an effective palliative treatment for endometrial carcinoma but causes weight gain via activity at the corticosteroid receptor. Norethindrone (N) is a progestin without corticosteroid activity. We report 3 women with metastatic endometrial cancer responsive to M for whom a switch to N decreased side effects with continued cancer control. Methods: Case-series Results: 1. 62 year old with endometrial adenocarcinoma underwent surgery and chemoradiation. Lung metastases were discovered 31 months later and she began M with complete response at 13 months. She suffered weight gain and lymphedema. M was switched to N and continued for 4 years to date with weight loss and without progression. 2. 54 year old with endometrial adenocarcinoma underwent surgery and radiation. Lung metastases developed 30 months later. Chemotherapy produced response but was complicated by cerebrovascular accident. lung lesions developed 3 years later and slowly grew over the ensuing year. M was started and continued for 8 months. Her lung lesions responded but weight gain impacted her already reduced mobility. She was switched to N which has continued 11 months to date, with stable disease, without further weight gain. 3. 64 year old with a history of metastatic squamous cell carcinoma of the lung developed what was thought to be a second primary endometrial adenocarcinoma. She received surgery and radiation with pelvic recurrence 34 months later. M was started and continued for 17 months with response in pelvic and lung lesions, which proved to be metastatic endometrial carcinoma presenting before her primary. Weight gain resulted in wheelchair dependence. She was switched to N with continuing response over the ensuing 2 years. 28 months after starting N, imaging showed progression and she was switched back to M, her poor performance status precluding other treatments. She died 5 months later. Conclusions: In patients with metastatic endometrial cancer responding to megestrol, switching to norethindrone improved palliative benefit. Prospective clinical trials of norethindrone or similar progestins without corticosteroid activity should be considered for this population.
Trastuzumab plus docetaxel and capecitabine for first-line treatment of Her2-positive advanced gastric cancer: A phase II, multi-center, open-label, single-arm study.
Authors: Feng Wang, Tian Shu Liu, Xianglin Yuan, Kangsheng Gu, Ying Yuan, Yanhong Deng, Jian-Ming Xu, Yu-Xian Bai, Ying Wang, Wangjun Liao, He-Long Zhang, Feng Bi, Bang-Mao Wang, Zhixiang Zhuang, Huiyan Luo, Rui-hua Xu
Journal: Journal of Clinical Oncology (2018)

4045 Background: Gastric cancer (GC) is one of the most common tumors in China. The ToGA study has shown trastuzumab in combination with fluoropyrimidine plus cisplatin prolonged overall survival (OS) in patients with HER2-positive advanced GC (AGC). Although docetaxel plus capecitabine(DX) is a standard regimen for AGC, combination of trastuzumab plus DX has not been studied. In this study, the efficacy and safety of trastuzumab in combination with DX was evaluated in Chinese patients with HER2-positive advanced GC. Methods: This phase II, multi-center, open label, single arm study enrolled patients with HER2-positive metastatic gastric or gastro-esophageal junction adenocarcinoma who have not received prior treatment for metastatic disease. Patients were treated with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg on day 1), capecitabine (1000mg/m2 twice daily, d1-14) and docetaxel (60mg/m2 on day1 for 6 cycles), every 3 weeks. Primary endpoint is progression-free survival (PFS) and secondary endpoints are objective response rate (ORR), OS and toxicity profiles. Results: 67 patients with AGC were enrolled from 14 centers and 64 patients were in Full Analysis Set (median age 58, 73.4% male, 78.1% ECOG PS 1, 79.7% HER2 IHC 3+, 17.2% GE junction). Until November 2017, among 64 patients, the median PFS was 8.1 months (95 % CI: 5.6-12.8) and the median OS was 20.9 months (95 % CI: 15.1-33). Response was evaluated in 59 patients (5 missing in FAS), five patients achieved CR and thirty-five patients achieved PR, the ORR was 67.8%. In 67 patients who received at least one cycle of treatment, the most common adverse events of grade 3 or above were neutropenia (17.9%), leucopenia (19.4%), hand-foot syndrome (9%), febrile neutropenia (4.5%) and anemia (3%). Conclusions: Combination of trastuzumab and docetaxel/capecitabine is a well-tolerated and highly effective regimen in patients with HER2-positive advanced gastric cancer. Clinical trial information: NCT02004769.