tbuckley/cabot-search huggingface dataset:
Low-grade gastric mucosa-associated lymphoid tissue lymphoma: Clinicopathological factors associated with Helicobacter pylori eradication and tumor regression.
Authors: Hyun Ik Shim, Dong Ho Lee, Jae Ho Cho, Cheol Min Shin, Hyuk Yoon, Young Soo Park, Nayoung Kim
Journal: Journal of Clinical Oncology (2020)

353 Background: Eradication of Helicobacter pylori is widely accepted as the initial therapy for low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The aim of this study was to assess the remission and relapse rates of low-grade gastric MALT lymphoma after H. pylori eradication and to identify the clinical factors affecting remission. Methods: We retrospectively analyzed 151 patients diagnosed with gastric MALT lymphoma from May 2003 to December 2018. Results: Of the 151 patients, 112 (74.2%) had an H. pylori infection. Total regression rates with eradication was 90.2% (101/112) in H. pylori-positive patients and 55% (11/20) in H. pylori-negative patients. Age, sex, tumor location, endoscopic findings, and the severity of mononuclear lymphocytes were not related to achieving successful initial H. pylori eradication and remission. However, patients with a smaller H. pylori burden ( p=0.030) and less neutrophil infiltration ( p=0.003) were more likely to achieve a successful initial H. pylori eradication. H. pylori ( p&lt;0.001) and the burden ( p=0.020) were significantly related to remission of MALT lymphoma. Conclusions: The results show that H. pylori burden and neutrophil infiltration were inversely related to the success of the initial H. pylori eradication procedure and that the H. pylori burden was inversely related to the remission of MALT lymphoma.
Interventions to promote cycling: systematic review
Authors: L. Yang, S. Sahlqvist, A. McMinn, S. J. Griffin, D. Ogilvie
Journal: BMJ (2010)

<b>Objectives</b> To determine what interventions are effective in promoting cycling, the size of the effects of interventions, and evidence of any associated benefits on overall physical activity or anthropometric measures. <b>Design</b> Systematic review. <b>Data sources</b> Published and unpublished reports in any language identified by searching 13 electronic databases, websites, reference lists, and existing systematic reviews, and papers identified by experts in the field. <b>Review methods</b> Controlled "before and after" experimental or observational studies of the effect of any type of intervention on cycling behaviour measured at either individual or population level. <b>Results</b> Twenty five studies (of which two were randomised controlled trials) from seven countries were included. Six studies examined interventions aimed specifically at promoting cycling, of which four (an intensive individual intervention in obese women, high quality improvements to a cycle route network, and two multifaceted cycle promotion initiatives at town or city level) were found to be associated with increases in cycling. Those studies that evaluated interventions at population level reported net increases of up to 3.4 percentage points in the population prevalence of cycling or the proportion of trips made by bicycle. Sixteen studies assessing individualised marketing of "environmentally friendly" modes of transport to interested households reported modest but consistent net effects equating to an average of eight additional cycling trips per person per year in the local population. Other interventions that targeted travel behaviour in general were not associated with a clear increase in cycling. Only two studies assessed effects of interventions on physical activity; one reported a positive shift in the population distribution of overall physical activity during the intervention. <b>Conclusions</b> Community-wide promotional activities and improving infrastructure for cycling have the potential to increase cycling by modest amounts, but further controlled evaluative studies incorporating more precise measures are required, particularly in areas without an established cycling culture. Studies of individualised marketing report consistent positive effects of interventions on cycling behaviour, but these findings should be confirmed using more robust study designs. Future research should also examine how best to promote cycling in children and adolescents and through workplaces. Whether interventions to promote cycling result in an increase in overall physical activity or changes in anthropometric measures is unclear.
Factors associated with effectiveness of trifluridine/tipiracil versus regorafenib in patients with pretreated metastatic colorectal cancer (mCRC).
Authors: Peter Grell, Simona Borilova, Renata Schwanzerova, Sabina Kukolikova, Josef Dvorak, Michal Vocka, Stanislav John, Tomas Buchler, Iveta Selingerova, Lubos B. Petruzelka, Rostislav Vyzula, Igor Kiss, Radka Obermannova
Journal: Journal of Clinical Oncology (2020)

137 Background: Trifluridine/tipiracil (T) and regorafenib (R) are indicated for patients with refractory mCRC. Currently, no biomarkers are used to select which patient will benefit from which treatment. Methods: We retrospectively evaluated 212 patients who received T and/or R. Different factors associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Results: T received 132, R 52, both drugs 28 patients. Median age was 64 (range 28-83), male 64%, PS 0 37%, median line of treatment 3, characteristic was similar between treatment groups. Median follow-up was 16.5 months. Median OS for T was 10.2, for R 6.9 months, P = 0.03. Factors significantly associated with OS were: ≥ 24 months from diagnosis of mCRC (0.49, P &lt; 0.001), PS 0 (HR 1.54, P = 0.007), baseline WBC &lt; 8 × 10 9 /L (HR 0.47, P &lt; 0.001), normal baseline CRP (HR 0.47, P &lt; 0.001), ≥ 3 months from last therapy (fluoropyrimidine for T, anti-VEGF for R) (HR 0.66, P = 0.006). We developed a scoring system TASREG from these factors, 1 point for each factor, the overall score was the sum of these points and patients were divided into 3 groups: high risk group with 0 to 1 point, intermediate with 2 to 3, favorable with 4 or more points. OS for all patients according to risk group was 4.6 for high risk, 7.9 intermediate, 11.8 months favorable risk (P &lt; 0.001). Score was also significant for T and R group evaluated separately. Score was also significant for PFS. Factors associated with OS specific for T were neutropenia G≥2 (HR 0.34, P &lt; 0.001); for R normal baseline LDH (HR 0,40. P &lt; 0.001), no liver metastases (HR 0.45, P = 0.002), non-synchronous disease (HR 0,40, P &lt; 0.001). Conclusions: We could find factors associated with better outcomes for both treatment groups and factors specific for T or R. TASREG is simple prognostic tool for patients with refractory mCRC.
Predictors of outcome following local excision for T1 rectal adenocarcinoma: A contemporary analysis.
Authors: Thejus Thayyil Jayakrishnan, Stephen Abel, Ari Reichstein, Richard Fortunato, Stanislav Nosik, James McCormick, Gene Grant Finley, Dulabh K. Monga, Alexander V. Kirichenko, Rodney E. Wegner
Journal: Journal of Clinical Oncology (2020)

35 Background: Local excision (LE) alone is a standard treatment option for appropriately selected early stage rectal adenocarcinoma patients. Guidelines for this therapeutic approach are based upon retrospective single institution data, some of which dates back 30 years. We thus sought to use the National Cancer Database (NCDB) to examine outcomes in a large cohort of patients with early stage rectal adenocarcinoma treated with LE and to identify/confirm predictors of outcome. Methods: We queried the NCDB for patients with pT1N0M0 rectal adenocarcinoma treated with local excision alone. Baseline characteristics were tabulated and included lymphovascular invasion (LVI), perineural invasion (PNI), grade, and size all of which have been recorded in the NCDB since 2010. Multivariable Cox regression was used to identify predictors of overall survival. Kaplan Meier curves were generated to compare survival based upon significant factors found on multivariable analysis. Results: Using the above criteria, we identified 887 patients eligible for analysis across 2010-2014. The median age was 67 and 57% of patients were male. The median tumor size was 1.5 cm (IQ range: 0.9-2.5 cm). A minority of patients had grade 3 tumors (5%), LVI (8%), or PNI ( &lt; 1%). Median follow up was 36 months (1-83). On multivariable Cox regression, predictors of worse survival included: size &gt; 4 cm, age &gt; 67, higher comorbidity score, and presence of LVI. On Kaplan Meier analysis, 5 year OS was 75% vs. 74% for patients without and with LVI, respectively (p = 0.0115). In terms of size, the 5 year OS was 74% vs. 51%for size &lt; 4cm and size &gt; 4cm (p = 0.0138). Conclusions: Our large contemporary series demonstrates excellent survival outcomes in patients with early stage rectal adenocarcinoma treated with LE alone. LVI remains a predictor of outcome, while grade and perineural invasion were not significant in this analysis. This finding is likely due to a small number of patients with those characteristics.
EORTC 1707 VESTIGE: Adjuvant immunotherapy in patients with resected gastric cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1)—An open-label randomized controlled phase II study.
Authors: Elizabeth Catherine Smyth, Ellen Peeters, Maren Kristina Knoedler, Anne Giraut, Anna Dorothea Wagner, Markus H. Moehler, Nicole C.T. van Grieken, Magnus Nilsson, Murielle E. Mauer, Florian Lordick
Journal: Journal of Clinical Oncology (2021)

TPS4156 Background: Gastroesophageal adenocarcinoma (GEA) patients with metastatic lymph nodes (ypN+) or a microscopically incomplete surgical resection (R1) following neoadjuvant chemotherapy are at high risk of disease recurrence. Current practice is to continue with the same perioperative chemotherapy used prior to surgery, despite these suboptimal outcomes. Adjuvant immunotherapy with nivolumab has shown efficacy in poor risk GEA patients following chemoradiotherapy and surgery in the CheckMate 577 trial, and nivolumab and ipilimumab have demonstrated activity in advanced GEA. We hypothesise that high risk (ypN+ and/or R1) post resection GEA patients who are treated with nivolumab and ipilimumab will have better disease free survival than patients who continue with standard post-operative chemotherapy. Methods: VESTIGE is an ongoing, international, open label randomized phase II study designed to evaluate the efficacy of adjuvant nivolumab plus ipilimumab versus standard post-operative chemotherapy in high risk (ypN+ and/or R1) post resection GEA patients. Eligible patients (n=240) will be randomised 1:1 to receive post-operative adjuvant chemotherapy (identical regimen as pre-operatively) or nivolumab 3mg/kg IV q2w plus ipilimumab 1mg/kg IV q6w x 1 year. Key inclusion criteria include ypN+ and/or R1 status following neoadjuvant chemotherapy plus surgery and an adequate pre-specified surgical resection. The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety, toxicity and quality of life. Since start of recruitment in August 2019, the trial has recruited 85 of 240 patients at 18 sites in the Czech Republic, France, Germany, Israel, Italy, Norway, Poland, Spain, and United Kingdom. The VESTIGE translational research programme includes collection of pre-treatment biopsies, post-chemotherapy resection specimens and serial liquid biopsy on treatment to explore biomarkers predictive of immune checkpoint blockade efficacy. Clinical trial information: NCT03443856.
Long-Term Evolocumab in Patients With Familial Hypercholesterolemia
Authors: Raul D. Santos, Evan A. Stein, G. Kees Hovingh, Dirk J. Blom, Handrean Soran, Gerald F. Watts, J. Antonio G. López, Sarah Bray, Christopher E. Kurtz, Andrew W. Hamer, Frederick J. Raal
Journal: Journal of the American College of Cardiology (2020)

Proprotein convertase subtilisin/kexin type 9 inhibitor therapy is a treatment option for patients with familial hypercholesterolemia (FH) who are unable to reach low-density lipoprotein cholesterol (LDL-C) goals.The aim of this study was to provide long-term safety and efficacy data for evolocumab in patients with homozygous FH (HoFH) and severe heterozygous FH (HeFH).In this open-label, single-arm study, patients with HoFH or severe HeFH ≥12 years of age and on stable lipid-lowering therapy began subcutaneous evolocumab 420 mg monthly or 420 mg every 2 weeks if on lipoprotein apheresis. After 12 weeks, those not on apheresis could be up-titrated to 420 mg every 2 weeks. The primary endpoint was the incidence of treatment-emergent adverse events; secondary endpoints were changes in LDL-C and other lipids.In total, 300 patients (106 with HoFH, including 14 <18 years of age at enrollment) received evolocumab for a median of 4.1 years. Adverse events occurred in 89.3% of patients, the most common of which were nasopharyngitis, influenza, upper respiratory tract infection, and headache. Mean change in LDL-C from baseline to week 12 was -21.2% (-59.8 mg/dl) in patients with HoFH and -54.9% (-104.4 mg/dl) in those with severe HeFH and was sustained over time. Of 48 patients with HoFH who were up-titrated, mean change in LDL-C improved from -19.6% at week 12 to -29.7% after 12 weeks of 420 mg every 2 weeks. The adjudicated cardiovascular event rate was 2.7% per year. Of 61 patients receiving apheresis at enrollment, 16 discontinued apheresis.Evolocumab was well tolerated and effectively reduced plasma LDL-C levels in patients with HoFH and severe HeFH over a median of 4.1 years.
Association of immune microenvironment to response in treatment-naïve non-small cell lung cancer (NSCLC) samples with follow-up second-line immunotherapy data.
Authors: Marie Cumberbatch, Nathan Elliott, Sarah Warren, Woo Ho Kim, Christopher Womack, Milan Bhagat, Lorenzo Colarossi, Lorenzo Memeo
Journal: Journal of Clinical Oncology (2020)

49 Background: Archival specimens collected months or years prior to starting immunotherapy are often used to identify patients for second line immune checkpoint inhibitor (ICI) treatment. PD-L1 expression and the immune microenvironment in these patients may have altered over time following multiple lines of failed standard of care (SOC) treatments. Methods: Formalin fixed paraffin embedded (FFPE) tumor samples, taken during resection performed as first line surgical treatment from a cohort of NSCLC patients (n = 18), were evaluated by Nanostring using the IO360 gene expression panel, and by immunohistochemistry (IHC) for CD3, CD8, PD-L1, CD68 and CD163. The resultant immune profiles were correlated with the clinical follow-up data for radiotherapy, SOC chemotherapy, and second line immunotherapy with the aim of understanding whether immune signatures predictive of response to ICI therapy may be identified in such samples. Results: Of the 18 cases, clinical follow-up data indicated objective response to ICI therapy for 4 patients, with the mean time from initial diagnosis to ICI treatment being 2.8 years (range: 0.4 to 8.5 years). Although pathologist PD-L1 IHC scores were not predictive of response, IHC image analysis data revealed significant increases in CD3 (2.3-fold) and CD8 (2.7-fold) T cell numbers in the responder population. In addition, although CD68+ macrophage frequencies did not differ significantly between responder and non-responder populations, reduced M2-like CD163+ macrophage/monocyte numbers were evident for responders. While the Tumor Inflammation Signature was not predictive of response, several gene expression signatures were significantly associated with response including increased abundance of CD8 T cells, cytotoxic cells, cytotoxicity, MHC class II antigen presentation and Melanoma-Associated Antigens (MAGE). Conclusions: Despite these patients having received various lines of radiotherapy and SOC chemotherapy prior to receiving immunotherapy, immune profiles associated with response to second line immunotherapy were detected in surgical first line resection samples.
Splenomegaly during oxaliplatin-based chemotherapy in colon cancer.
Authors: Ruoyu Ji, Guanghua Huang, Lingshan Liu, Mengyin Chen, Xiaoduo Yu, Aiping Zhou, Chun-Xia Du
Journal: Journal of Clinical Oncology (2020)

88 Background: Splenic enlargement has been reported in patients treated with oxaliplatin. However, the characteristics of oxaliplatin-induced splenomegaly were not well studied. Here we evaluated the change of splenic volume and its clinical significance in patients treated by oxaliplatin-based regimen. Methods: Patients with stage II-IV primary colon cancer treated with oxaliplatin and capecitabine in China National Cancer Center from January 2016 to December 2017 were screened for this retrospective study. Those with complete laboratory tests and computed tomographic data before, during and up to 1.5 years after the chemotherapy were selected. The splenic size was measured by AWVolumeshare5. Splenomegaly was defined as an over 30% increase of splenic size from baseline. Recovery of splenomegaly was defined as the splenic size fell back to a 0.9 to1.1-fold range of baseline. Results: Out of a total of 144 patients, 102 (70.8%) had over 30% increase, 72 (50.0%) had over 50% increase, and 22 (15.3%) had over 100% increase in splenic size after oxaliplatin-based regimen. Among the 102 splenomegaly patients, 5 (4.9%) develop splenomegaly within 3 chemotherapy cycles, 53 (53.0%) within 6 cycles, 73 (71.6%) within 9 cycles, and 102 (100.0%) within 3 months after the last administration of oxaliplatin. Compared to the group without splenomegaly, patients with splenomegaly received more cycles of oxaliplatin administrations (median 8 vs 6, p &lt; 0.001) and greater dose intensity (total dose per square meter) (median 822.8mg/m 2 vs 629.3mg/m 2 , p &lt; 0.001). Patients with splenomegaly had higher incidence of thrombocytopenia (61.7% vs 38.1%, p = 0.009) and are more likely to undergo oxaliplatin dose reduction due to thrombocytopenia (21.6% vs 7.1%, p = 0.038). The recovery rates of splenic size within 0.5, 1 and 1.5 years after the end of oxaliplatin treatment were 23.2%, 50.6% and 74.3%, respectively. Conclusions: Splenomegaly are common in patients treated with oxaliplatin-based chemotherapy, and most would recover in 1.5 years after completion of therapy. Patients with splenomegaly are prone to experience thrombocytopenia and oxaliplatin dose reduction. Further studies are needed to reveal the mechanism how oxaliplatin induce splenomegaly.
CellCoal: Coalescent Simulation of Single-Cell Sequencing Samples
Authors: David Posada
Journal: Molecular Biology and Evolution (2020)

Our capacity to study individual cells has enabled a new level of resolution for understanding complex biological systems such as multicellular organisms or microbial communities. Not surprisingly, several methods have been developed in recent years with a formidable potential to investigate the somatic evolution of single cells in both healthy and pathological tissues. However, single-cell sequencing data can be quite noisy due to different technical biases, so inferences resulting from these new methods need to be carefully contrasted. Here, I introduce CellCoal, a software tool for the coalescent simulation of single-cell sequencing genotypes. CellCoal simulates the history of single-cell samples obtained from somatic cell populations with different demographic histories and produces single-nucleotide variants under a variety of mutation models, sequencing read counts, and genotype likelihoods, considering allelic imbalance, allelic dropout, amplification, and sequencing errors, typical of this type of data. CellCoal is a flexible tool that can be used to understand the implications of different somatic evolutionary processes at the single-cell level, and to benchmark dedicated bioinformatic tools for the analysis of single-cell sequencing data. CellCoal is available at https://github.com/dapogon/cellcoal.
A digital therapeutic for proactive monitoring of patients on immune checkpoint inhibitor therapy for early detection of immune-related adverse events.
Authors: Shyamali Mallick Singhal, Shane Dormady, Jiali Li, Shiva Singhal, Lynda Chin
Journal: Journal of Clinical Oncology (2020)

101 Background: Immune-related adverse events (irAEs) occur frequently in patients receiving immuno-oncology therapy. irAEs are heterogeneous and unpredictable. Experience at academic cancer centers has shown that (1) education of patients and families must be continuous; (2) experience of the care team can improve outcomes; and (3) close monitoring of patients in between visits translate into early detection and timely intervention. Most oncologists in lower volume community practices have not gained the experience nor have the resource for continuous education frequent proactive monitoring. Methods: In addition to self-monitoring by patients on chemotherapy to improve outcome (Basch ref), we hypothesized that adoption of evidence-based management is critical as well. Thus, we have developed ApricityRx, a digital therapeutic (DTx) for end-to-end irAE management, which not only engages patients in frequent self-nonitoring but also activates the oncology team for timely intervention. In brief, ApricityRx (i) enables intelligent monitoring by educating and guiding patients to track specific expert-prioritized symptoms in between clinic visits; (ii) facilitates early recognition by prompting triage at the right time and (iii) recommends evidence-based management based on consensus guidelines. Results: In a community cancer center, 16 patients have been enrolled (44% consent rate) in an IRB approved feasibility trial to evaluate the usability of ApricityRx as a tool for frequent monitoring and timely triage. Over 435 unique longitudinal records containing over 34K data points, including patient-reported outcome (PRO) and clinical care data (EMR), were generated. Interim analyses have shown that primary and secondary endpoints were met. Detailed results will be presented. Conclusions: ApricityRx has shown usability in a low-volume community-based oncology practice to facilitate proactive monitoring and tinely triage by the oncology team. Further, ApricityRx has enabled not only generation of high-resolution patient-reported outcome (PRO) data, but also aggregation of PRO and real-world EHRs data for downstream analyses.