tbuckley/cabot-search huggingface dataset:
Abstract OT3-05-01: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze
Authors: CE Geyer, S Loibl, P Rastogi, S Seiler, JP Costantino, VN Nekljudova, P Cortazar, PC Lucas, C Denkert, EP Mamounas, C Jackisch, N Wolmark
Journal: Cancer Research (2019)

Abstract Background: TNBC is associated with higher percentages of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), and women with a pCR have a favorable prognosis. However, Liedtke (2008) and Loibl (2017) found that women with residual disease have a substantially higher risk of recurrence than women with other subtypes of breast cancer. Additionally, Adams (2017) and Schmid (2017) found that therapeutic blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy. Methods: Design This is a phase III, double blind, placebo-control trial evaluating neoadjuvant atezolizumab with NAC followed by adjuvant atezolizumab in TNBC. Pts are stratified by region (North America; Europe), tumor size (1.1-3.0cm; &amp;gt;3.0cm), AC/EC schedule (q2w; q3w), and nodal status (positive; negative), then randomized 1:1 to receive atezolizumab/placebo 1200 mg IV every 3 wks concurrently with both sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses with every 3-wk carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 wks (per investigator discretion) for 4 cycles. Following surgery, pts resume atezolizumab/placebo 1200 mg IV every 3 wks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo. Eligibility criteria Centrally-confirmed ER-neg, PR-neg, HER2-neg invasive breast cancer by ASCO/CAP guidelines. Primary tumor must be stage T2 or T3 if cN0 or cN1 with negative biopsy or T1c, T2, or T3 if cN1 with positive biopsy or cN2 or cN3. LVEF &amp;gt;55% and no significant cardiac history. Statistical methods Co-primary endpoints are event-free survival (EFS) and pCR breast/nodes. Secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. Trial is an academic collaboration between NSABP and GBG with support from Genentech/Roche. NCT03281954 Support: Genentech/Roche Citation Format: Geyer, Jr. CE, Loibl S, Rastogi P, Seiler S, Costantino JP, Nekljudova VN, Cortazar P, Lucas PC, Denkert C, Mamounas EP, Jackisch C, Wolmark N. A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-05-01.
CLO19-050: Risk of Health- Related Quality of Life (HRQOL) Events in Patients With Advanced Solid Tumors Treated With Cabozantinib: A Combined Analysis of Four Phase 3 Randomized Controlled Trials
Authors: Sriman Swarup, Anita Sultan, Nusrat Jahan, Upama Sharma, Nimesh Adhikari, Yin M. Myat, Ye Aung, Myo H. Zaw, Kyaw Z. Thein
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: VEGFR, KIT, RET, and MET pathways are implicated in several solid tumors. Cabozantinib is an oral inhibitor of these kinase pathways, and hence has found its use in treatment of multiple malignancies. However, it has several side effects that can limit tolerance amongst patients. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of health-related quality of life (HRQOL) events in patients with advanced solid tumors treated with cabozantinib. Methods: We systematically conducted a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through September 30, 2018. Phase 3 trials that mention HRQOL events like pain, arthralgia, fatigue, and reduced appetite as adverse effects were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% CI. Random effects model was applied. Results: 4 phase 3 RCTs with a total of 2,703 patients with medullary thyroid cancer, prostate cancer, renal cell carcinoma, and hepatocellular carcinoma were eligible. Studies comparing cabozantinib (C) vs everolimus, C vs placebo, C vs prednisone were included in the analysis. The relative risks of all-grade side effects were as follows: fatigue, 1.378 (95% CI: 1.236–1.536; P &lt;.0001); asthenia, 1.704 (95% CI: 1.190–2.441; P =.004); reduced appetite, 2.088 (95% CI: 1.471–2.964; P &lt;.0001); back pain, 1.047 (95% CI: 0.871–1.259; P =.626); pain in limbs, 1.444 (95% CI: 1.128–1.847; P =.004); arthralgia, 0.982 (95% CI: 0.707–1.363; P =.912). The RR of high-grade side effects were as follows: fatigue, 1.937 (95% CI: 1.483–2.528; P &lt;.0001); asthenia, 2.211 (95% CI: 1.536–3.184; P &lt;.0001); reduced appetite, 4.329 (95% CI: 2.372–7.900; P &lt;.0001); back pain, 1.227 (95% CI: 0.738–2.040; P =.431); pain in limbs, 2.933 (95% CI: 1.127–7.635; P =.028); arthralgia, 0.820 (95% CI: 0.394–1.709; P= .597). Conclusion: Our meta-analysis showed that cabozantinib contributed to significant toxicity of all grades of fatigue, asthenia, pain in limbs, and reduced appetite. Identifying and addressing these toxicities will be important in improving quality of life for these patients.
CLO19-026: Determining the Treatment Decision of Tumors With Mixed Response
Authors: Candice Baldeo, Tasneem Kaleem, Ricardo Paz-Fumagalli, John Copland, Michael Menefee
Journal: Journal of the National Comprehensive Cancer Network (2019)

Introduction: Individuals receiving systemic anticancer therapies for advanced solid tumors routinely undergo imaging studies to assess the efficacy of the treatment. Mixed response (MR) to cancer therapy is a common but poorly described phenomenon. There is a paucity of data regarding both the incidence and possible mechanisms of this clinical quandary. Potential etiologies include tumor heterogeneity, differences in tumor microenvironment, and discrepancies in drug delivery to different tumor deposits. It is also possible that MR simply reflects differences in the rate of resistance emerging. MR represents a therapeutic dilemma for the clinician. Methods: Mixed tumor response was defined as: One tumor decreasing in size; one tumor increasing in size (classified as RECIST response/progressions), One tumor stable; another tumor progressing, One tumor stable; another tumor responding, New tumor; another tumor responding or remaining stable. Between 2015 and 2017, 120 restaging CT scans were reviewed of patients who had received at least 1 line of therapy for advanced cancer diagnosis which showed MR; hematologic malignancies were excluded. Charts were reviewed to determine the clinical decision that was made at the time of the MR. Results: A total of 120 scans with MR were reviewed from various solid tumor diagnoses. 38 scans were excluded due to loss of follow-up or death. Of the remaining 82 scans, therapy was switched in 30, the same therapy was continued in 50, and an additional agent was added to the current treatment in 2 cases (Table). Of the patients in which treatment was switched, 20% (6/30) showed response to treatment on the following scan. Of the cases that were kept on current treatment, none showed response on the following restaging scan which was done 6–8 weeks later. There were 4 (10%) deaths prior to the next scan in the group that had treatment switched and similarly 5 deaths (10%) prior to the next scan in the group in which treatment remained the same. Conclusion: MR is associated with a poor prognosis, irrespective of treatment decisions. These data are retrospective and our sample size is small, so definitive conclusions cannot be drawn. However, changing therapy when a MR is observed may be of benefit to some patients. A prospective evaluation to more accurately describe and understand the MR phenomenon is warranted.
Capita stripped of NHS cervical screening contract
Authors: Matthew Limb
Journal: BMJ (2019)

The NHS is bringing the administration of its cervical screening programme back in-house following blunders by the private sector group Capita, which holds the contract for the service.

On 20 March, NHS England chief executive Simon Stevens told a hearing of the Public Accounts Committee into failings with adult health screening programmes that action was being taken because NHS England “have not been satisfied” with Capita’s performance. This included late notification by Capita of delays in sending out cervical test invitation, reminder, and results letters.

He said that, starting from June, the cervical screening service would be returned to the NHS, with a phased transition through the rest of the year.

The cervical screening system is part of Capita’s contract to deliver primary care …
Induction Toxicities Are More Frequent in Young Adults Compared to Children Treated on the Children's Oncology Group (COG) First Relapse B-Lymphoblastic Leukemia Clinical Trial AALL1331
Authors: Laura Brook Hogan, Teena Bhatla, Sue Rheingold, Lingyun Ji, Xinxin Xu, Elizabeth A. Raetz, Stephen P. Hunger, Mignon L. Loh, Patrick Brown
Journal: Blood (2018)
Monitoring of the Clonal Architecture of B-Cell Precursor ALL during Induction Chemoimmunotherapy
Authors: Michaela Kotrova, Monika Szczepanowski, Henrik Knecht, Christoph Faul, Mustafa Kondakci, Björn Steffen, Andreas Viardot, Michael Kneba, Dieter Hoelzer, Nicola Goekbuget, Nikos Darzentas, Monika Brüggemann
Journal: Blood (2018)
Susceptibility Perturbation MRI Maps Tumor Infiltration into Mesorectal Lymph Nodes
Authors: Inês Santiago, João Santinha, Andrada Ianus, Antonio Galzerano, Rita Theias, Joana Maia, Maria J. Barata, Nuno Loução, Bruno Costa-Silva, Antonio Beltran, Celso Matos, Noam Shemesh
Journal: Cancer Research (2019)

Noninvasive characterization of lymph node involvement in cancer is an enduring onerous challenge. In rectal cancer, pathologic lymph node status constitutes the most important determinant of local recurrence and overall survival, and patients with involved lymph nodes may benefit from preoperative chemo and/or radiotherapy. However, knowledge of lymph node status before surgery is currently hampered by limited imaging accuracy. Here, we introduce Susceptibility-Perturbation MRI (SPI) as a novel source of contrast to map malignant infiltration into mesorectal lymph nodes. SPI involves multigradient echo (MGE) signal decays presenting a nonmonoexponential nature, which we show is sensitive to the underlying microstructure via susceptibility perturbations. Using numerical simulations, we predicted that the large cell morphology and the high cellularity of tumor within affected mesorectal lymph nodes would induce signature SPI decays. We validated this prediction in mesorectal lymph nodes excised from total mesorectal excision specimens of patients with rectal cancer using ultrahigh field (16.4 T) MRI. SPI signals distinguished benign from malignant nodal tissue, both qualitatively and quantitatively, and our histologic analyses confirmed cellularity and cell size were the likely underlying sources for the differences observed. SPI was then adapted to a clinical 1.5 T scanner, added to patients' staging protocol, and compared with conventional assessment by two expert radiologists. Nonmonoexponential decays, similar to those observed in the ex vivo study, were demonstrated, and SPI classified lymph nodes more accurately than standard high-resolution T2-weighted imaging assessment. These findings suggest this simple, yet highly informative, method can improve rectal cancer patient selection for neoadjuvant therapy. SIGNIFICANCE: These findings introduce an MRI methodology tailored to detect magnetic susceptibility perturbations induced by subtle alterations in tissue microstructure.
Differential Uptake of 68Ga-PSMA-HBED-CC (PSMA-11) in Low-Grade Versus High-Grade Gliomas in Treatment-Naive Patients
Authors: Priyanka Verma, Gaurav Malhotra, Atul Goel, Sutapa Rakshit, Ashok Chandak, Rupal Chedda, Sharmila Banerjee, Ramesh V. Asopa
Journal: Clinical Nuclear Medicine (2019)

Purpose of the Report Prostate-specific membrane antigen (PSMA) is a type II membrane glycoprotein, which is not only overexpressed in prostate cancers but also in variety of solid tumors including glioblastoma multiforme. The aim of the present study was to demonstrate PSMA expression in gliomas using 68 Ga-PSMA-HBED-CC(PSMA 11) PET/CT. Patients and Methods Ten patients with initially MRI suspected and eventually histopathologically proven gliomas [8 males (age range 30–73 yr; mean age 51.8 yr); 2 females aged 39 and 55 years] were subjected preoperatively to regional brain PET scan with 68 Ga-PSMA-11 and 18 F-FDG PET/CT. Final histopathology of brain lesions, their MIB-1 proliferation index (MIB-1 PI) were compared with PSMA and FDG PET findings. Results FDG PET/CT showed distinct FDG uptake in high-grade gliomas, whereas low-grade gliomas were non-FDG-avid amidst physiological tracer uptake. In vivo PSMA expression was seen in all patients with glioma. Of these, the 7 patients of glioblastoma harboring 8 lesions showed significantly higher PSMA expression than those with low-grade gliomas, average SUVmax being 16.93 and 2.93, respectively. Similarly, average tumor-to-background ratios (13.95 and 3.42, respectively) and MIB-1 PI (17.31 and 3.3, respectively) were substantially more in high-grade versus low-grade gliomas. Conclusions The results of this pilot study show that 68 Ga-HBED-CC-PSMA PET/CT can be used to characterize the PSMA expression in gliomas, high-grade ones demonstrating higher SUVmax, MIB-1 PI tumor-to-background ratio than the low-grade ones. With these results as basis, certain patients may benefit from potential PSMA-targeted radionuclide therapy.
Experimental and clinical studies on regenerative periodontal therapy
Authors: Enilson A. Sallum, Fernanda V. Ribeiro, Karina S. Ruiz, Antonio W. Sallum
Journal: Periodontology 2000 (2019)

Abstract The recognition of a periodontal therapy as a regenerative procedure requires the demonstration of new cementum, periodontal ligament, and bone coronal to the base of the defect. A diversity of regenerative strategies has been evaluated, including root surface conditioning, bone grafts and bone substitute materials, guided tissue regeneration, enamel matrix proteins, growth/differentiation factors, combined therapies and, more recently, tissue‐engineering approaches. The aim of this chapter of Periodontology 2000 is to review the research carried out in Latin America in the field of periodontal regeneration, focusing mainly on studies using preclinical models (animal models) and randomized controlled clinical trials. This review may help clinicians and researchers to evaluate the current status of the therapies available and to discuss the challenges that must be faced in order to achieve predictable periodontal regeneration in clinical practice.
Maternal and child health and care provision in Palestine: data from the national electronic maternal and child health registry (MCH eRegistry)
Authors: Mervett Isbeih, Mahima Venkateswaran, Tamara Awwad, Buthaina Ghanem, Khadija Abu-Khader, Taghreed Hijaz, Mohammad Baniode, Eatimad Abbas, Rand Salman, Asad Ramlawi, Binyam Bogale, J Frederik Frøen
Journal: The Lancet (2019)
Composition-Tunable Ultrasmall Manganese Ferrite Nanoparticles: Insights into their <i>In Vivo</i> T<sub>1</sub> Contrast Efficacy
Authors: Yuqing Miao, Qian Xie, Huan Zhang, Jing Cai, Xiaoli Liu, Ju Jiao, Shanshuang Hu, Anujit Ghosal, Yu Yang, Haiming Fan
Journal: Theranostics (2019)

The development of a highly efficient, low-toxicity, ultrasmall ferrite nanoparticle-based T1 contrast agent for high-resolution magnetic resonance imaging (MRI) is highly desirable. However, the correlations between the chemical compositions, in vitro T1 relaxivities, in vivo nano-bio interactions and toxicities remain unclear, which has been a challenge in optimizing the in vivo T1 contrast efficacy. Methods: Ultrasmall (3 nm) manganese ferrite nanoparticles (MnxFe3-xO4) with different doping concentrations of the manganese ions (x = 0.32, 0.37, 0.75, 1, 1.23 and 1.57) were used as a model system to investigate the composition-dependence of the in vivo T1 contrast efficacy. The efficacy of liver-specific contrast-enhanced MRI was assessed through systematic multiple factor analysis, which included the in vitro T1 relaxivity, in vivo MRI contrast enhancement, pharmacokinetic profiles (blood half-life time, biodistribution) and biosafety evaluations (in vitro cytotoxicity testing, in vivo blood routine examination, in vivo blood biochemistry testing and H&E staining to examine the liver). Results: With increasing Mn doping, the T1 relaxivities initially increased to their highest value of 10.35 mM-1s-1, which was obtained for Mn0.75Fe2.25O4, and then the values decreased to 7.64 m M-1s-1, which was obtained for the Mn1.57Fe1.43O4 nanoparticles. Nearly linear increases in the in vivo MRI signals (ΔSNR) and biodistributions (accumulation in the liver) of the MnxFe3-xO4 nanoparticles were observed for increasing levels of Mn doping. However, both the in vitro and in vivo biosafety evaluations suggested that MnxFe3-xO4 nanoparticles with high Mn-doping levels (x > 1) can induce significant toxicity. Conclusion: The systematic multiple factor assessment indicated that the MnxFe3-xO4 (x = 0.75-1) nanoparticles were the optimal T1 contrast agents with higher in vivo efficacies for liver-specific MRI than those of the other compositions of the MnxFe3-xO4 nanoparticles. Our work provides insight into the optimization of ultrasmall ferrite nanoparticle-based T1 contrast agents by tuning their compositions and promotes the translation of these ultrasmall ferrite nanoparticles for clinical use of high-performance contrast-enhanced MRI.
Genomic Landscape of Sporadic Retinitis Pigmentosa
Authors: Inmaculada Martin-Merida, Almudena Avila-Fernandez, Marta Del Pozo-Valero, Fiona Blanco-Kelly, Olga Zurita, Raquel Perez-Carro, Domingo Aguilera-Garcia, Rosa Riveiro-Alvarez, Ana Arteche, Maria Jose Trujillo-Tiebas, Saoud Tahsin-Swafiri, Elvira Rodriguez-Pinilla, Isabel Lorda-Sanchez, Blanca Garcia-Sandoval, Marta Corton, Carmen Ayuso
Journal: Ophthalmology (2019)
Extracellular Matrix Protein Tenascin C Increases Phagocytosis Mediated by CD47 Loss of Function in Glioblastoma
Authors: Ding Ma, Senquan Liu, Bachchu Lal, Shuang Wei, Shuyan Wang, Daqian Zhan, Hao Zhang, Richard S. Lee, Peisong Gao, Hernando Lopez-Bertoni, Mingyao Ying, Jian Jian Li, John Laterra, Mary Ann Wilson, Shuli Xia
Journal: Cancer Research (2019)

Abstract Glioblastomas (GBM) are highly infiltrated by myeloid-derived innate immune cells that contribute to the immunosuppressive nature of the brain tumor microenvironment (TME). CD47 has been shown to mediate immune evasion, as the CD47–SIRPα axis prevents phagocytosis of tumor cells by macrophages and other myeloid cells. In this study, we established CD47 homozygous deletion (CD47−/−) in human and mouse GBM cells and investigated the impact of eliminating the "don't eat me" signal on tumor growth and tumor–TME interactions. CD47 knockout (KO) did not significantly alter tumor cell proliferation in vitro but significantly increased phagocytosis of tumor cells by macrophages in cocultures. Compared with CD47 wild-type xenografts, orthotopic xenografts derived from CD47−/− tumor cells grew significantly slower with enhanced tumor cell phagocytosis and increased recruitment of M2-like tumor-associated microglia/macrophages (TAM). CD47 KO increased tumor-associated extracellular matrix protein tenascin C (TNC) in xenografts, which was further examined in vitro. CD47 loss of function upregulated TNC expression in tumor cells via a Notch pathway–mediated mechanism. Depletion of TNC in tumor cells enhanced the growth of CD47−/− xenografts in vivo and decreased the number of TAM. TNC knockdown also inhibited phagocytosis of CD47−/− tumor cells in cocultures. Furthermore, TNC stimulated release of proinflammatory factors including TNFα via a Toll-like receptor 4 and STAT3-dependent mechanism in human macrophage cells. These results reveal a vital role for TNC in immunomodulation in brain tumor biology and demonstrate the prominence of the TME extracellular matrix in affecting the antitumor function of brain innate immune cells. Significance: These findings link TNC to CD47-driven phagocytosis and demonstrate that TNC affects the antitumor function of brain TAM, facilitating the development of novel innate immune system–based therapies for brain tumors.
Ultrasound/Acidity‐Triggered and Nanoparticle‐Enabled Analgesia
Authors: Xiong Gao, Piao Zhu, Luodan Yu, Liqun Yang, Yu Chen
Journal: Advanced Healthcare Materials (2019)

Abstract Local anesthetics have been extensively employed to treat postoperative pain, but they generally suffer from short acting duration and potential neurotoxicity under high local concentrations, which require the controlled and sustained releasing patterns of treatment drugs. In this work, it is reported, for the first time, the construction of hollow mesoporous organosilica nanoparticles (HMONs)‐based nanoplatforms for localized delivery and controlled/sustained release of loaded ropivacaine for local anesthetics, which can be repeatedly triggered by either external ultrasound irradiation or acidity triggering to release the payload, causing on‐demand and long‐lasting analgesia. Based on the in vivo mouse model of incision pain, the controlled and sustained release of ropivacaine achieves more than six hours of continuous analgesia, which is almost three times longer as compared to single free ropivacaine injection. The low neurotoxicity and high biocompatibility of HMONs for nanoparticle‐enabled analgesia are also demonstrated both in vitro and in vivo. This designed/constructed HMONs‐based nanoplatform provides a potential methodology for clinical pain management via on‐demand and long‐lasting pain relief.