tbuckley/cabot-search huggingface dataset:
OS5.3 Imaging comparative analysis of intracranial meningiomas in adult and pediatric NF2 patients
Authors: P Li, Z Yang, Z Wang, X Wang, B Wang, P Liu
Journal: Neuro-Oncology (2018)

Various central nervous system tumors show different clinical behaviors in adult and pediatric patients. Intracranial meningiomas are the main cause of neurofibromatosis type 2 (NF2) patients’ death. It is very important to know well of the detailed clinical behaviors of the death-cause NF2 intracranial meningiomas. It will help us to make up optimal treatment strategy for every single NF2 patient. The aim of this study is to evaluate the differences in the clinical behaviors of intracranial meningiomas in adult and pediatric NF2 patients via analyzing the MR imaging data. The study was a retrospective review of 452 NF2 patients. Their cranial MR imaging data were carefully reviewed. The location patterns of meningiomas in adult and pediatric patients were calculated and compared with each other. The total 452 NF2 patients included 367 adult and 85 pediatric (younger than 18 years old) patients. Twenty five adult NF2 patients had more than 10 intracranial meningiomas, and they were defined as severe-type NF2 in our study. To avoid selection bias, they were excluded from the comparative analysis. None pediatric patients had more than 10 intracranial meningiomas. Of the remaining no-severe-type 342 adult patients, 216 patients had 629 meningiomas and 126 patients had none. Of the total 85 pediatric patients, 50 patients had 81 meningiomas and 35 patients had none. The locations of adult and pediatric meningiomas included parafalcine (28.9% vs. 29.6%), parasagittal (15.4% vs. 6.2%), convex surface (22.3% vs. 14.8%), tentorial (6.0% vs. 7.4%), anterior cranial fossa (4.9% vs. 6.2%), middle cranial fossa (5.7% vs. 11.1%), posterior cranial fossa (9.4% vs. 8.6%), intraorbital (1.4% vs. 3.7%), lateral ventricle (5.9% vs. 12.4%). The 25 severe-type adult patients were analyzed separately. They had 310 intracranial meningiomas. Their locations included parafalcine (25.2%), parasagittal (20.0%), convex surface (31.0%), tentorial (8.4%), anterior cranial fossa (2.9%), middle cranial fossa (4.8%), posterior cranial fossa (2.9%), intraorbital (0.7%), lateral ventricle (4.2%). The location patterns of intracranial meningiomas vary in adult and pediatric NF2 patients. The intracranial meningiomas of adult NF2 patients relatively predominate in the parasagittal and convex surface regions compared with the pediatric patients. The newly developed NF2 meningiomas in adulthood are more likely to occur in the parasagittal and convex surface regions. The location patterns of intracranial meningiomas in severe-type patients are highly compatible with those in no-severe-type adult NF2 patients, showing the severe type of NF2 is most likely caused by the newly developed meningiomas in adulthood.
Platinum based chemotherapy selects for PDGFRα dependent angiogenesis.
Authors: Nuala McCabe, Aya El-Helali, Christopher Steele, Lara Dura Perez, Christina O'neill, Andrena McCavigan, Reinhold Medina, Laura A Knight, Stephen McQuaid, Jacqueline James, Caroline Ogilvie Michie, Charlie Gourley, W. Glenn McCluggage, Denis P Harkin, Richard H. Wilson, Alan Stitt, Richard D. Kennedy
Journal: Journal of Clinical Oncology (2018)

5578 Background: Patients with High Grade Serous Ovarian Cancer (HGSOC) initially respond to SOC platinum based treatment but most will eventually relapse with platinum resistant disease. Angiogenesis is known to be an integral pathological feature of HGSOC and anti-angiogenic agents have been trialed in this population, but have failed to demonstrate a significant impact on overall survival (OS). Here, we asked if platinum resistance could be associated with an improved response to anti-angiogenic therapies. Methods: A meta-analysis of 14 phase II and III clinical trials in EOC were used to investigate the association between platinum resistance and response to anti-angiogenic agents. In addition we analysed gene expression in 12 matched pre-and post-chemotherapy samples. Novel cisplatin-resistant HGSOC cell lines and novel ascites-derived primary cell lines from HGSOC patients with known outcomes following platinum-based chemotherapy were developed to investigate the relationship between angiogenesis and platinum resistance. Results: The meta-analysis revealed an OS benefit for anti-angiogenics in platinum-resistant disease (p = 0.029), whilst platinum-sensitive disease derived only PFS benefit (p = < 0.0001). In the matched pairs of patient samples, post-platinum samples had a higher micro-vessel density (MVD) relative to their paired treatment-naïve sample (p = 0.0001). Additionally, an in vivo angiogenesis matrigel plug assay demonstrated that cisplatin-resistant EOC cell lines were associated with an increase in MVD (p = < 0.0001). MVD was reduced in the platinum-resistant cells following treatment with bevacizumab (p = 0.001). Ascites-derived cells established from platinum-resistant patients demonstrated overexpression of VEGF-A through increased PDGFRa and PDGFRb expression. Conclusions: We have demonstrated that previous platinum therapy for EOC is associated with an increase in tumour PDGFα and VEGF-A expression, correlating with a response to anti-angiogenic therapies. This data suggests that platinum therapy resistance may inform the selection of EOC patients for novel anti-angiogenic therapies in future clinical trials.
Safety and efficacy of direct oral anticoagulants (DOAC) in cancer patients: Meta-analysis of randomized controlled trials (RCT).
Authors: Ali McBride, Chinmayee Katragadda, Ivo Abraham
Journal: Journal of Clinical Oncology (2017)

e18264 Background: The DOACs apixaban, edoxaban, rivaroxaban, dabigatran offer advantageous alternatives for venous thromboembolism (VTE) treatment in cancer patients, however, there lacks a prospective assessment in this population. We conducted a meta-analysis of RCTs comparing these DOACs to controls to evaluate the safety and efficacy of these new agents for patients with active cancer. Methods: We systematically searched PUBMED, EMBASE, Cochrane Reviews, CINAHL and Clinicaltrials.gov. Two authors (CK, IA) screened and reviewed abstracts and full text, with disagreements resolved by third author (AB). Data extracted included major bleeding and clinically relevant nonmajor bleeding for safety; recurrent VTE and VTE death for efficacy. Analyses included Mantel-Haenszel random effects risk ratios (RR); I 2 for heterogeneity; and meta-regression by publication year. Results: Of 2307 records reviewed, 8 RCTs were retained. Pooled analysis yielded safety RR 0.82 (95%CI = 0.56-1.21, I 2 = 44% ) and efficacy RR 0.94 (95%CI = 0.68-1.31; I 2 = 0%). Meta-regression revealed no publication year bias. Conclusions: Current guidelines have not supported the use of DOACs in clinical cancer practice due to the paucity of data in this setting. Our results indicate no differential efficacy and no increased bleeding risk for DOACs in cancer patients. Additional prospective research is required to determine long term effects in subgroups of cancer patientss at higher risk for VTE or bleeding events. [Table: see text]
Hyponatraemia as an unrecognised risk factor in non-small cell lung cancer (NSCLC) treatment with nivolumab.
Authors: Christian Grohe, Simon Gwynn, Richard Evans
Journal: Journal of Clinical Oncology (2017)

e14526 Background: The investigation, diagnosis and management of hyponatraemia is often inadequate in cancer patients. In a retrospective analysis of 3,357 cancer patients hyponatraemia was noted in up to 47%. A strong and independent association between hyponatremia and longer length of stay with higher mortality was highlighted and associated with standard chemotherapy. No pooled data, however are available on the effect of immuno-oncology (IO) treatment options such as nivolumab on HN in lung cancer patients. Methods: Key publications and data registries concerning the incidence, evaluation and management of hyponatraemia in patients with NSCLC and treated with nivolumab were analysed. Our data show that hyponatraemia is a common side effect and around 5.2% of patients treated with nivolumab progressed from baseline to a Grade 3 / 4 adverse event. Results: The aetiology of hyponatraemia in cancer patients is complex, appearing to be a negative prognostic indicator. Existing data show that effective treatment of hyponatraemia in cancer patients may be associated with reduced mortality. In addition, the role of sodium on the cancer cell cycle requires further investigation. It has been shown in vitro that a hypotonic environment is pro-tumorigenic, whereas a slightly hypertonic environment may have a negative impact on clonogenicity in prostate cancer cells. This may suggest a more complex interaction impacting on cancer patients other than a simplistic mortality association with hyponatraemia. Nivolumab treatment is associated with HN and particular attention should be paid to the correction of symptomatic HN in these patients. Conclusions: Hyponatraemia is the most commonly occurring electrolyte disturbance in cancer patients and may represent a modifiable risk factor impacting patient survival. The clinician should be aware of the potential for IO therapies to precipitate hyponatraemia. Consideration of the correct diagnosis and management of hyponatraemia may further enhance the prognosis of NSCLC patients treated with IO agents.
Change in inflammatory status as a prognostic marker of overall survival in colorectal patients undergoing resection.
Authors: Joseph Chan, Connie Irene Diakos, David Chan, Anthony J Gill, Nick Pavlakis, Alexander Engel, Stephen John Clarke
Journal: Journal of Clinical Oncology (2016)

6571 Background: Recent evidence suggests that markers of systemic inflammation such as the pre-operative Neutrophil-to-lymphocyte ratio (NLR) and the Lymphocyte-to-monocyte ratio (LMR) are accurate predictors of survival. However, few studies have examined the impact of changes in systemic inflammation post-operatively on patient survival. Our aims were to investigate whether postoperative change in NLR and LMR (NLR/LMR “conversion”) at 21-56 days compared to pre-operative baseline levels confer a survival benefit in colorectal cancer patients undergoing surgical resection. Methods: Data from the Northern Sydney Local Health District from January 1998 to December 2012 were retrospectively collected. Complete data were available for 594 patients. The prognostic role of LMR, NLR and LMR/NLR conversion on overall survival (OS) was assessed using Cox regression models. Results: Pre and post-operatively, both the NLR and LMR were independently associated with OS. Patients who had high pre-operative LMR and converted post-operatively to low LMR had significantly poorer survival, median OS 142.35 vs 63.64 months, HR 0.411 (95% CI 0.236-0.716, p = 0.002). Those with low pre-operative LMR who converted to high LMR had significantly better survival than those who did not convert, median OS 64.74 vs 38.16 months, HR 1.921 (95% CI 1.329-2.775, p < 0.001). For the NLR, conversion from low NLR to high NLR resulted in significantly poorer outcomes, median OS 51.764 vs 115.696 months, HR 0.434 (95% CI 0.290-0.650, p < 0.001). Conversion from high NLR to low NLR conferred marginal survival benefit, median OS 51.39 vs 47.15 months, HR 1.508 (95% CI 1.054-2.157, p = 0.024). Conclusions: LMR andNLR conversion may be early indicators of prognosis in resected colorectal cancer, further stratifying patients for selection of adjuvant therapy and potentially optimizing use of health care resources.
TCT-98 Early Clinical Impact of Cerebral Embolic Protection With Transcatheter Aortic Valve Replacement, a Multicenter Study in the Netherlands.
Authors: Herbert Kroon, Hindrik van der Werf, Lennart van Gils, F.R. Van Den Berge, Nahid El Faquir, Zouhair Rahhab, Joost Daemen, J.E. Poelman, Remco Schurer, Ad F.M. Van den Heuvel, Peter de Jaegere, Pim van der Harst, Nicolas Van Mieghem
Journal: Journal of the American College of Cardiology (2018)
Antigenic sites in influenza H1 hemagglutinin display species-specific immunodominance
Authors: Sean T. H. Liu, Mohammad Amin Behzadi, Weina Sun, Alec W. Freyn, Wen-Chun Liu, Felix Broecker, Randy A. Albrecht, Nicole M. Bouvier, Viviana Simon, Raffael Nachbagauer, Florian Krammer, Peter Palese
Journal: Journal of Clinical Investigation (2018)

Hemagglutination inhibition (HI) titers are a major correlate of protection for influenza-related illness. The influenza virus hemagglutinin possesses antigenic sites that are the targets of HI active antibodies. Here, a panel of mutant viruses each lacking a classically defined antigenic site was created to compare the species-specific immunodominance of the antigenic sites in a clinically relevant hemagglutinin. HI active antibodies of antisera from influenza virus-infected mice targeted sites Sb and Ca2. HI active antibodies of guinea pigs were not directed against any specific antigenic site, although trends were observed toward Sb, Ca2, and Sa. HI titers of antisera from infected ferrets were significantly affected by site Sa. HI active antibodies of adult humans followed yet another immunodominance pattern, in which sites Sb and Sa were immunodominant. When comparing the HI profiles among different species by antigenic cartography, animals and humans grouped separately. This study provides characterizations of the antibody-mediated immune responses against the head domain of a recent H1 hemagglutinin in animals and humans.
Abstract 17536: Cardiac Macrophage is Required to Avoid Atrioventricular Block After Right Heart Pressure Overload
Authors: Junichi Sugita, Katsuhito Fujiu, Yukiteru Nakayama, Takumi Matsubara, Jun Matsuda, Ichiro Manabe, Issei Komuro
Journal: Circulation (2016)

Right heart dysfunction is of current interest in managing severe heart failure and pulmonary hypertension, and cardiomyocyte-immune cell interactions play an important role after myocardial infarc...
Can duration of response be used as a surrogate endpoint for overall survival in advanced non-small cell lung cancer?
Authors: Boris M Pfeiffer, Margarita Kulakova, Mahmoud Hashim, Bart Heeg
Journal: Journal of Clinical Oncology (2018)

9082 Background: Surrogate endpoints for overall survival (OS) in advanced non-small cell lung cancer (NSCLC), such as overall response rate (ORR) and progression-free survival, are prone to bias due to crossover and unbalanced post-progression therapy or inconsistent response assessment criteria. This study aimed to evaluate the surrogacy of duration of response (DoR) for OS in phase III trials adjusted for crossover, unbalanced post-progression treatment, insufficient information and inconsistent response criteria. Methods: The analysis was based on systematic literature review and data extraction. The relationship between absolute differences in median DoR and in median OS was assessed using the correlation coefficient (R). Additionally, the relationship of the combination of ORR and DoR, which may be a better surrogate for OS because it captures both the frequency and duration of response, with OS was evaluated. The bias arising from different definitions of ORR and DoR was addressed in a subset analysis on RECIST-based trials and WHO-based trials. Further stratification by reported definition of DoR, either from start of treatment (randomization) or onset of response, was performed. Results: ORR, DoR, and OS values were reported in 20 trials (8,382 patients). The correlation coefficient of DoR with OS was 0.356 (95% CI: 0.000-0.690). 8 trials defined response according to RECIST criteria and 11 trials defined DoR from the first documented response. In these subsets, the correlation was 0.630 (95% CI:0.000–0.924) and 0.572 (95% CI:0.000–0.873), respectively. The correlation coefficient of the combination of DoR and ORR with OS was 0.790 (95% CI: 0.535–0.913). In the RECIST-based trials and trials defining DoR from first documented response, the correlation coefficients of the combination of ORR and DoR with OS were 0.742 (95% CI: 0.079–0.950) and 0.887 (95% CI: 0.614–0.971), respectively. Conclusions: Evaluation of DoR as a surrogate for OS should take into consideration both response assessment criteria and ORR. The adjustment with ORR gives a better estimate of the treatment effect and can be used jointly with DoR as a surrogate endpoint to predict OS benefit.
Reduced phenotypic expression in genetic hemochromatosis with time: Role of exposure to non-genetic modifiers
Authors: Yves Deugnier, Jeff Morcet, Fabrice Lainé, Houda Hamdi-Roze, Anne-Sophie Bollard, Dominique Guyader, Romain Moirand, Edouard Bardou-Jacquet
Journal: Journal of Hepatology (2018)
TCT-299 Pulse Wave Velocity and Aortic Distensibility in Patients with Hypertensive Response Post Transcatheter Aortic Valve Replacement
Authors: Eyal Ben Assa, Jose de la Torre Hernandez, Jonathan Brown, Max Olender, Rasha Al-Bawardy, Zahra K. Motamed, Pinak Shah, Jonathan Passeri, Ignacio Inglessis, Sammy Elmariah, Martin Leon, Elazer Edelman
Journal: Journal of the American College of Cardiology (2018)
Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes
Authors: Shu Han, Ruiyang Sun, Hong Su, Jing Lv, Huan Xu, Di Zhang, Yuanshan Fu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate (TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and 1H-NMR. The buffering capacity of polyethylene glycol- distearoyl phosphatidylethanolamine (PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel (DOC) liposomes (TPOS-DOC-L) had a slower drug-release rate at pH 7.4 similar to PEGylated-DOC liposomes (PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes (TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4 (P < 0.01). Conversely, for PEGylated C6 liposomes (PEG-C6-L) and conventional C6 liposomes (C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes (DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-L significantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.
Resminostat plus sorafenib in hepatocellular carcinoma (HCC) as apotential new treatment approach in platelet-driven solid tumors.
Authors: Frank Hermann, Gundula Streubel, Sabine Schrepfer, Ulrike Parnitzke, Rolf Krauss, Matthias Borgmann, Svetlana Hamm
Journal: Journal of Clinical Oncology (2018)

e14571 Background: A phase I/II clinical trial in advanced hepatocellular carcinoma (HCC) conducted by Yakult Honsha (NCT02400788) indicated the combination of the HDAC inhibitor resminostat and sorafenib was beneficial compared to sorafenib for patients with a platelet count ≥150.000/µl at baseline. In line with the role of platelets in tumor progression, in HCC, high platelet count is linked to bad prognosis, increased tumor size and metastasis, e.g. via induction of epithelial-to-mesenchymal transition (EMT), as well as to resistance against sorafenib, the current standard of care first-line treatment in HCC. Methods: To provide a preclinical rationale for the observed benefit, different HCC cell lines were used to investigate the role of platelets and interplay with the compounds. Results: While the potency of sorafenib was counteracted by platelet factors, resminostat´s anti-proliferative activity was not affected by platelets. A key feature of cancer is cellular invasiveness, a prerequisite of metastasis. Using in-vitro invasion assays, we observed that platelets increased the invasive capacity of HCC cells. The combination of resminostat and sorafenib, but not monotherapy treatments, counteracted platelet-induced cell invasion. Conclusions: Resminostat’s anti-proliferative effects, even in sorafenib insensitive cells together with block of platelet-induced invasion of HCC cells by the combination could explain the observed benefit for the combination treatment in advanced HCC patients with a platelet count ≥150.000/µl at baseline. As platelets play a critical role in tumor progression, EMT and metastasis not only in HCC but also in other solid tumor indications, our data suggest the combination of resminostat and multi-kinase inhibitor as a promising regimen for the treatment of solid tumors, especially in platelet-driven extensive disease.
TelePsychiatry for cancer patients undergoing active treatment.
Authors: Christian Otto, Kylie Cotter, Jashonna Harris, William Breitbart
Journal: Journal of Clinical Oncology (2018)

6603 Background: Numerous studies have demonstrated the effectiveness of telepsychiatry in non-cancer related disease; however, there are limited reports of telepsychiatry for cancer patients under active treatment. The MSK Counseling Center initiated a telepsychiatry program for patients residing near MSK regional care sites with limited counseling services. Methods: Patients were identified who lived within the catchment area of two MSK regional sites in Westchester County and Suffolk County, NY. Patients were invited to participate who had previously been seen in-person who were scheduled for psychotherapy follow-up or medication management. Data on telepsychiatry visits performed by 5 psychiatrists was collected over a 2-year period beginning in January 2016. Telepsychiatry sessions took place between the patient at the MSK regional site and the psychiatrist at the Manhattan Counseling Center. Sessions were supported by Cisco Jabber Movi videoconferencing software and high definition videoconferencing equipment. Patients were asked to fill out a technology acceptability questionnaire post-visit. Results: Thirty-eight patients (14 males; 56.3 ±10.8 years) with 19 cancer diagnoses, and 26 psychiatric diagnoses (1.8±0.9/patient) completed 159/187 telepsychiatry visits (cancellation rate 15.0%). Each patient had an average of 4.2±5.8 visits. Anxiety disorder- unspecified, adjustment disorder with mixed anxiety and depressed mood, and major depressive disorder were the three most common diagnoses. Fifty percent (N = 19) of patients completed the questionnaire. Most respondents (96.0%) highly agreed or agreed that telepsychiatry visits made it easier for them to obtain care, and that the quality of care was the same as in-person. The majority of patients who completed the questionnaire underscored the benefits of avoiding lengthy travel to Manhattan for appointments, the ease of scheduling, decreased appointment wait time, and the similarity to in-person visits. Conclusions: Telepsychiatry has high acceptability among cancer patients and offers a means of providing care to established patients who are stable, while decreasing the stress encountered from frequent travel, missed work, and associated caregiver requirements.