tbuckley/cabot-search huggingface dataset:
Prospsective phase II pilot study to evaluate the use of intravenous iron in the treatment of anemia in cancer patients.
Authors: Youjin Kim, Jun Ho Jang, Silvia Park, Jiyun Lee, Sung Won Lim
Journal: Journal of Clinical Oncology (2018)

10113 Background: Iron deficiency anemia (IDA) are common complications in cancer patients. Evidence on intravenous (IV) iron for treatment of chemotherapy-induced anemia (CIA) is emerging. Herein, we evaluated the efficacy of IV iron for improvement of anemia in cancer patients. Methods: This prospective single arm phase II study aims at evaluation of efficacy of IV iron without additional ESA for correction of CIA. Patients received Ferinject® (ferric carboxymaltose) 1000mg injection on the first day of chemotherapy . Thereafter, hemoglobin (Hb) response defined by increase of Hb ≥ 1.0g/dL was assessed at visit 1, visit 2 and visit 3. To identify biochemical parameter predictive for Hb response, TSAT, sTFR, hepcidin, EPO, IL-6, CRP were also assessed at each visit. Results: Between Oct 2010 and Jul 2017, a total of 104 patients were enrolled, and 92 patients were available for for injection. Hemoglobin response was observed in 36, 53 and 61 patients at visit 1 (39.1%), visit 2 (57.6%) and visit 3 (66.3%), respectively. When excluding 19 patients (20.6%) with absolute IDA defined by ferritin < 30ng/mL or TSAT < 20%, Hb response rate was 83.5% (61/73). Of 73 patients without absolute IDA, there were i) 56 patients whose serum ferritin were between 30- 500 ng/ml , ii) 6 patients whose serum ferritin were between 500-800 ng/ml and TSAT < 50 % , and iii) 10 patients whose ferritin levels were > 800ng/mL or TSAT ≥ 50% . In patients groups of i), ii) and iii), Hb response was observed in 60.7% (34/56), 50% (6/6), and 50%(5/10), respectively. Regarding anemia related biochemical parameters, responders had significantly lower levels of hepcidin (13.5 vs. 35.2 ng/mL, p = 0.007), CRP (0.7 vs. 2.5mg/mL, p = 0.044) and ferritin (249.2 vs. 575.3 ng/mL, p = 0.048). When comparing Hb response by baseline hepcidin level, there were significantly more responders in the low hepcidin (58/61, 95.1%) compared to the high hepcidin group (3/61, 4.9%) at the cut-off value of 34.1 ng/mL (p = 0.002). Conclusions: IV iron supplementation alone showed promising result in improving anemia in cancer patients. Hepcidin may predict response to IV iron in cancer and chemotherapy induced anemia, and is superior to TSAT or ferritin for this purpose. Clinical trial information: NCT02599012.
Self-stated and actual practice patterns of general medical oncologists (MO) regarding the use of predictive biomarkers to guide treatment for patients (pts) with chronic lymphocytic leukemia (CLL).
Authors: Maricer P. Escalon, William G. Wierda, Ann S. LaCasce, Dragan Jevremovic, William N. Harwin, Gloria Kelly, Kirsten Miller, Douglas Paley, Joe Nelson, Kathryn Ziel, Neil Love
Journal: Journal of Clinical Oncology (2018)

e19510 Background: Available research and guidelines support the use of a number of genomic biomarkers to determine prognosis in pts with CLL. However, previous surveys of clinical investigators (CIs) by our group have clarified that only 3 of these, IGHV mutation (mut), TP53 mut and del(17p), affect therapeutic selection. This project evaluated how general MO in a regional practice approach biomarker assessment and treatment decision-making for pts with CLL. Methods: In fall 2017, 21 MO provided information on biomarkers assessed and therapies administered for 104 pts with CLL. A survey evaluating self-reported practice patterns was also executed. IRB exemption was obtained and a modest honorarium was provided. Results: All but 1 MO reported testing pts for del(17p) and IGHV mut before first-line therapy, but only 8/20 (40%) reported ordering TP53 mut testing. Analysis of the cases revealed that del(17p) and IGHV mut status were assessed at diagnosis in 77 pts (74%) and 68 pts (65%) respectively, while only 35 pts (34%) underwent testing for TP53 mut. For pts with negative or unknown del(17p) status at diagnosis, 9/20 MO (45%) indicated that they order repeat analysis before treatment of relapsed disease. In terms of biomarker-related decisions, only 8/19 MO (42%) would employ FCR in a young, otherwise healthy pt with mutated IGHV. Conclusions: Many MO may not be assessing TP53 at baseline or requesting repeat FISH testing in pts with relapsed disease requiring re-treatment. In addition, for younger, fit pts with mutated IGHV, MO may generally not be using FCR in the front-line setting. These findings should be confirmed in a larger, more diverse cohort but suggest that MO may approach biomarker assessment and related treatment somewhat differently than their CI colleagues.
Various checkpoint proteins, and tumor infiltrating lymphocytes in common pediatric solid tumors: Possibilities for novel immunotherapy.
Authors: Kazuhiro Mochizuki, Satoshi Kawana, Moe Muramatsu, Hideki Sano, Shogo Kobayashi, Yoshihiro Ohara, Nobuhisa Takahashi, Yuko Hashimoto, Atsushi Kikuta
Journal: Journal of Clinical Oncology (2018)

10544 Background: Despite the significant improvements of long-term survival rates for pediatric cancers, prognosis of refractory/relapsed solid tumors are extremely poor, and novel strategies are desired. Recently, tumor immunotherapies such as anti-PD-1/PD-L1 antibodies have been recognized as an effective option for many intractable cancers. However, there are still a substantial number of patients who do not show objective responses to the PD-1/ PL-L1 blockades. On the other hand, like PD-1/PD-L1, other immune checkpoint pathways such as TIM3/GAL9, LAG3/MHC-II, and BTLA/HVEM have been reported to regulate immune responses in tumor microenvironment. Although these pathways could be alternative targets for novel immune therapies, almost no information is available whether pediatric solid tumors express these molecules. Herein, we characterized the expression of various checkpoint proteins, and tumor infiltrating lymphocytes (TILs) in tumor specimens from untreated children with common pediatric solid tumors. Methods: Sections cut from formalin-fixed, paraffin-embedded tissue blocks were processed and evaluated for GAL9, MHC-II, and HVEM on tumor cells, and TIM3, LAG3, and BTLA on TILs by immunohistochemistry. Results: Specimens from 65 patients, including 16 neuroblastomas, 11 rhabdomyosarcomas, 12 osteosarcomas, 10 hepatoblastomas, 10 Wilms tumors, and 6 Ewing sarcomas were evaluated. Although in neuroblastoma and Ewing sarcoma, checkpoint proteins on the tumor were rarely detected, 64% of the patients with rhabdomyosarcoma and 83% with osteosarcoma expressed moderate to high levels of HVEM. TILs were detected in all tumor types among which CD8 positive T cells were the most dominant population following CD4 positive T cells. Interestingly, in rhabdomyosarcoma, and osteosarcoma, more than 70% of the TILs expressed moderate to high levels of BTLA. Conclusions: A subset of pediatric solid tumors demonstrated tumor associated checkpoint expressions, and TILs also expressed corresponding ligands of the checkpoints, which suggested immunogenic environments may be created, and the checkpoint blockades could induce favorable immune responses.
Safety profile and reduced observation time in outpatients using subcutaneous Herceptin.
Authors: Fabiano Hosken Pombo, Patricia Martins Passos, Nathalia Fonseca Gamboa, Karoline Conceição Alvellos, Marcos Coelho Simões Travassos Soares
Journal: Journal of Clinical Oncology (2018)

e18848 Background: There are new oncology drugs every year. We can see the development of new products that came from another one consolidated in the market for over a decade such as subcutaneous option for Herceptin ™ sc. Adequately managing of the length of stay of the outpatient in use of cancer medication is most important way to guarantee quality of life and adherence to new technologies. Methods: Qualitative and quantitative evaluation score of the late reactions after administration of Herceptin ™ sc were performed using CTCAE in a private oncology outpatient clinic in the city of Rio de Janeiro, in order to evaluate the feasibility of reducing outpatient observation time. Adverse reaction data are entered into the medical records of the institution by the health team, doctors, pharmacists or nurses, and later this information is extracted and analyzed by the clinical pharmacy team. Results: In the past 5 years 508 patients have been treated with Herceptin ™ administered intravenous. All the reactions were scored as: grade 1 (25, 4.92%); 2 (26, 5.12%); 3 (4, 0.79%) and 4 (7, 1.38%) reactions in the first 30 minutes during infusion and no reaction was reported after 30 minutes from the beginning of the infusion. From seven months after incorporation of Herceptin ™ sc, 28 patients received this drug subcutaneously and no reaction of any degree was reported. Conclusions: The long time in the market and the number of patients using Herceptin ™ in the last 10 years show that is possible to study the safety profile of the product, which showed no late reaction of any degree in 508 patients. Observing the patients who are migrating to the infusion of the subcutaneous drug, with the absence of any reaction, it can be suggested that the safety profile is the same as that of the intravenous administration, making it possible to manage patient length of stay in the institution.
Considering cost and value with patients in clinic.
Authors: Jeffrey M. Peppercorn, Katharine M. Quain, Karen Sepucha, Don S. Dizon, Beverly Moy, Laura Spring, Therese Marie Mulvey, Jennifer Adrienne Shin, Giselle Katiria Perez
Journal: Journal of Clinical Oncology (2018)

e18905 Background: In the context of financial burdens that can impact distress and adherence, there is a movement to promote high value care and discussions of value and cost with patients in clinic. The ideal content of such discussions, and patients’ desire to discuss cost and value has not been defined. Methods: We conducted structured interviews regarding care and communication preferences among women with metastatic breast cancer. Interview questions addressed experience with financial barriers to care, desire for discussion of cost, and patient definitions of value in cancer care. Interview transcripts were qualitatively analyzed for thematic content. Results: Among 18 patients interviewed (median age 60 (range 43 – 78), 67% college educated, median income $50,000-100,000), many patients experienced high costs of care, and several identified cost as a potential barrier to treatment. Participants offered diverse perspectives on discussions of cost in clinic. Several patients noted issues of cost should not be raised; as they felt this would lead them to lose trust and question providers’ intentions. Others felt that insurance coverage and out of pocket costs should be disclosed, perhaps by other clinic staff. Notably, none of the patients believed costs of care should influence treatment decisions. When asked about “value”, only one patient associated value with financial costs of care but noted: “Value is not a word that I can associate with cancer care. As far as I'm concerned, cancer care should be the absolute best that it can possibly be.” All other patients defined value in terms of individualized care, having a specialized and compassionate care team, receiving “the best, most recent” treatment that maintains quality of life, or some other non-financial aspect of care. Conclusions: Patients with metastatic breast cancer report financial barriers to care and desire transparency and assistance with costs; however, they do not want discussions of cost to drive decision making. The concept of value, as promoted in recent clinical and policy frameworks, is not familiar to patients who tend to associate this term with compassionate care. Further research is needed to define how clinicians should consider and address cost and value in clinic.
CARING FOR OLDER PEOPLE
Authors: T A Roper, G P Mulley
Journal: BMJ (1996)

Most older people are mobile and able to use public transport without any problems. Those who are hard of hearing of have poor vision and those with mobility problems need not be deterred from using public transport. Although the design and provision of suitable buses, taxis, and trains is not always optimum, many now have imaginative features to help older passengers. Travel by air and sea needs extra planning for disabled elderly people, but helpful advice is available and much can be done to enable even the most disabled traveler to make long journeys confidently and in comfort.
PARP inhibitor combination therapy in desmoplastic small round cell tumors.
Authors: Marcia Mellado-Lagarde, Sara Michele Federico, Christopher Tinkle, Anang Shelat, Elizabeth Stewart
Journal: Journal of Clinical Oncology (2017)

e23212 Background: Desmoplastic small round cell tumor (DSRCT) is a rare but pernicious mesenchymal neoplasm that expresses the EWS-WT1 gene fusion transcript. It has similar histopathology to Ewing sarcoma (EWS). In previous work, we showed that addition of Poly (ADP-ribose) polymerase 1 and 2 inhibitors (PARPi) to the existing standard of care (SOC) therapy of irinotecan (IRN) and temozolomide (TMZ) was remarkably successful at treating mouse models of EWS, resulting in &gt; 80% complete response compared to 100% mortality with SOC alone. EWS has high levels of the protein Schlafen-11 (SLFN11), a putative biomarker for defective DNA damage repair. The goal of this study is to determine whether DSCRT also expresses SLFN11, and whether high levels of the protein sensitize the tumor to PARPi as single-agent or in combination with other drugs and ionizing radiation. Methods: SLFN11 mRNA and protein levels were assessed by immunohistochemistry, quantitative PCR, Western blot, and immunofluorescence microscopy. Viability of the DSRCT cell line, JN-DSCRT-1, was measured using CellTiterGlo and the colony forming assay. Ionizing radiation (IR) was delivered using an orthovoltage irradiator calibrated to deliver graded doses of 0-16 Gy. Results: We found that SLFN11 was detected at high levels in several DSRCT patient tumor samples, and we confirmed that SLFN11 transcript and protein levels in JN-DSCRT-1were comparable to EWS cell lines. JN-DSCRT-1 demonstrated sensitivity to PARPi as single-agent or in combination with either the topoisomerase I inhibitor irinotecan or ionizing radiation comparable to EWS cell lines. To supplement our in vitro studies and to utilize more accurate models of the clinical disease, we developed orthotopic patient derived xenograft models (O-PDX) from three patients with DSCRT. Preliminary findings suggest that these O-PDX models maintain SLFN11 expression and recapitulate important aspects of DSRCT biology, including widespread dissemination of tumor in the abdominal cavity and characteristic cellular phenotype. Preclinical in vivo efficacy studies with PARPi combinations are in progress. Conclusions: Our work suggests that DSCRT expresses the SLFN11 biomarker and is sensitive to PARPi combination therapy.
A new pancreatojejunostomy of duct-to-mucosa combining back-to-back cross horizontal mattress anastomosisin pancreaticoduodenectomy.
Authors: Wenchuan Wu, Lei Zhang, Ning Pu
Journal: Journal of Clinical Oncology (2017)

e18216 Background: Postoperative pancreatic fistula(POPF) is always related to the morbidity and mortality. The objective of our study was to evaluate the safety and efficiency of the novel anastomotic method that termed duct-to-mucosa combining with “back-to-back” cross horizontal mattress inserting pancreatojejunostomy. In this technique, we used 4-0 Coated VICRYL to stitch the posterior of the stump of pancreas into the side of jejunum in the method of horizontal mattress suture. Then, we used 5-0 polypropylene to stitch the posterior of the pancreatic duct into the jejunum interruptedly. After that, a pancreatic duct stent was inputted. The anterior side of the pancreatic duct and the pancreas was stitched the same as the anastomosis of the posterior side. Methods: We investigated the postoperative recovery and complications of 49 patients who underwent pancreaticoduodenectomy from October 2015 to October 2016 retrospectively. The new technique was used in 24 patients, and was compared with the regular interrupted suturing anastomosis technique that was used in 25 patients as controls. We defined, diagnosed and graded POPF accroding to the International Study Group in Pancreatic Surgery criteria. Results: The anastomosis time in the conventional group was less than that in new technique group (21.52±2.26 min vs28.10±6.20 min, P=0.000), but we could find the POPF rate decreased significantly in the new technique group from the following data. There were 2 grade B POPF patients in the new technique group. Meanwhile, there were 8 grade B POPF and 1 grade C POPF patients in the control group (8.3% vs 36.0%, P=0.020). Conclusions: Duct-to-mucosa combining with “back-to-back” cross horizontal mattress inserting pancreatojejunostomy reduced the incidence of POPF effectively in our study. [Table: see text]
100,000 Genomes Project: Cancer programme
Authors: A. Sosinsky, N. Murugaesu, A. Hamblin, J. Ambrose, C. Turnbull, S. Henderson, A. Rueda-Martin, T. Fowler, M. Caulfield, A. Rendon
Journal: Annals of Oncology (2018)

Background: The 100,000 Genomes Project aims to improve cancer care for NHS patients in the UK through personalised medicine. Our target is to return whole genome sequencing (WGS) results to clinicians in a clinically meaningful timescale to help with diagnosis and treatment choices for patient and in parallel to provide a research platform of genomic data linked to longitudinal clinical data. We demonstrate that WGA results for surgical resection or biopsy samples can be returned to clinicians within 2-3 weeks. Methods: Currently our bioinformatics analysis of WGS includes somatic small variants and somatic structural variants, germline pertinent findings, mutational signatures and mutational burden. Work is underway to implement other genomic signatures for predicting therapeutic response for specific tumour types. Results: We present here an overview of clinical utility for reported outcomes. To date, bioinformatics reports for WGS, with links to potentially relevant therapies and UK clinical trials, have been produced for thousands of cancer patients in the UK. Our data suggests that WGS has the potential to affect patient management and facilitate an increase in recruitment to existing clinical trials. To iteratively develop a high-quality bioinformatics pipeline, we are obtaining feedback via the Interpretation Portal for Cancer (within the NHS) from Molecular Tumour Boards to improve our analysis. Further research analysis is being undertaken within the Research Embassy by Genomics England Clinical Interpretation Partnerships (https://www.genomicsengland.co.uk/about-gecip). Conclusions: Future applications will include the utilisation of pan-genomic markers such as tumour mutational burden and genomic signatures to better stratify patients within the context of a clinical study. Legal entity responsible for the study: Genomics England. Funding: Government and NHSE. Disclosure: All authors have declared no conflicts of interest.
How we resect colorectal polyps &lt; 20 mm in size
Authors: Douglas K. Rex, Evelien Dekker
Journal: Endoscopy (2018)

Publication Information This article is being published jointly in Gastrointestinal Endoscopy and Endoscopy.Copyright © 2018 by the American Society for Gastrointestinal Endoscopy and Georg Thieme Verlag KG
TCT-440 Revascularization Outcomes, Financial Impact and Mortality Reduction – Effects of a Telemedicine-guided Strategy on Population-based AMI management
Authors: Sameer Mehta, Carlos Campos, Adam Yoculan, Roberto Botelho, Francisco Fernandez, Mauricio Prudente, Ricardo Cavalcanti, Jamil Cade, Cesar Dusilek, Fausto Feres, Marco Alcocer-Gamba, Alfredo Estrada, Mario Torres, Daniel Rodriguez, Haytham Aboushi, Lucas Lauar Cortizo Vidal
Journal: Journal of the American College of Cardiology (2018)
Association of a novel set of 7 homopolymer indels for detection of MSI with tumor mutation burden and total indel load in endometrial and colorectal cancers.
Authors: Hui Zhao, Bram De Craene, Xavier Sagaert, Frederic Amant, Geert G. Maertens, Diether Lambrechts
Journal: Journal of Clinical Oncology (2018)

e15654 Background: Immune checkpoint blockade was recently approved for the treatment of unresectable or metastatic, microsatellite-instability-high (MSI-H) tumors regardless of site or histology. Observed response rates were ~40%. Currently, there is no FDA-approved test to detect MSI status. MSI-H tumors share histopathological characteristics, such as high lymphocytic infiltration and high tumor mutation burden. Specifically, these tumors have a high number of insertion-deletion (indel) mutations, which are known to be highly immunogenic leading to an abundance of neoantigens. High indel rates in MSI-H tumors may therefore predict response to anti-PD1 therapy. Methods: We previously characterized the mutation landscape of 14 endometrial and colorectal MSI-H tumors by whole-exome sequencing (Zhao et al., Elife 2014), and identified indels in homopolymers that recurrently affect MSI-H tumors (frequency up to 80% per tumor type). We selected 7 of the most robust indels as a set of markers to detect MSI-H and correlated them with mutation burden, as determined by whole-exome sequencing. Results: Another 19 MSI-H tumors were positive for at least 2 out of 7 indels, while MSS tumors were positive for none of them. Additionally, we further correlated the number of positive indels in all available MSI-H tumors (n = 19+14) with mutation load. This revealed a positive correlation for both non-synonymous and indel mutation load (r = 0.56 and r = 0.62, respectively; p < 1e-06). Per additional indel marker that was positive, we observed an increase in indel mutation rate of ~130 indels, starting with a median of ~250 indels as of 2 markers positive. Conclusions: A selection of 7 indels reliably detects MSI-H in endometrial and colorectal cancer, while the number of positive indels serves as a proxy, not only for tumor mutational burden, but also for total indel load, and may thus be used as a test for tumor neoantigen load predictive of response to anti-PD-1 therapy in MSI-H tumors. These 7 markers will be available as a fully automated Idylla™ MSI test to detect MSI status and could be used as a companion diagnostic to predict immunotherapy outcome in MSI-H tumors.