tbuckley/cabot-search huggingface dataset:
CALGB/ECOG 100104 (Alliance) study: Lenalidomide (LEN) vs placebo (PBO) maintenance (maint) after stem cell transplant (SCT) for patients (pts) with multiple myeloma—Overall survival (OS) and progression-free survival (PFS) adjusted for treatment (tx) crossover (XO).
Authors: Philip L. McCarthy, Sarah A. Holstein, Sin-Ho Jung, Miranda Cooper, Craig J Gibson, Edward Allen Stadtmauer, Benjamin Winograd, Paul G. Richardson
Journal: Journal of Clinical Oncology (2017)

8037 Background: At a prespecified interim analysis (Dec 2009), the phase 3 CALGB study results surpassed the prespecified superiority boundary (significantly improved PFS for LEN maint vs PBO after SCT) and the majority of PBO arm pts without progressive disease (PD) crossed over to LEN maint. An updated analysis (cutoff Mar 2015), showed significantly longer OS with LEN maint (HR, 0.56; 95% CI, 0.42-0.76). We examined the effect of LEN vs PBO on OS and PFS from randomization, adjusting for XO effects. Methods: The rank-preserving structural failure time model (RPSFTM; Robins, Commun Stat Theory Methods, 1991) was used for XO adjustment; the iterative parameter estimation (IPE; Branson, Stat Med, 2002) algorithm was used as validation. Survival was portioned assuming a residual LEN effect after discontinuation. A landmark analysis was also performed at the Dec 2009 interim for pts who remained on Tx. Results: Pts were randomized to LEN maint (n = 231) and PBO (n = 229) (intent-to-treat [ITT] population); 76 pts without PD crossed over from PBO to LEN. Median time from randomization to XO was 11.5 mos. The relative Tx effect for OS and PFS increased for LEN vs PBO when adjusting for XO using RPSFTM and IPE (Table). The landmark analysis at the Dec 2009 interim (PBO XO, n = 76; No XO, n = 34) showed the Tx effect is not dissimilar to the ITT analysis (HR 0.53; 95% CI, 0.25-1.13). Sensitivity analyses showed consistent results. Conclusions: Adjusting for the potential diluting effects of XO reduced median OS and PFS with PBO, and improved the Tx effect in the ITT analyses for OS and PFS for LEN vs PBO maint after SCT. The statistical significance of the ITT analyses was maintained throughout. Support: U10CA180821, U10CA180882, CA180820. Clinical trial information: NCT00114101. [Table: see text]
Future Vision for ILCOR and Its Role in the Global Resuscitation Community
Authors: Robert W. Neumar, Gavin D. Perkins
Journal: Circulation (2018)

International Liaison Committee on Resuscitation (ILCOR) was formed in 1992 to work collaboratively across international boundaries to synthesize scientific evidence and develop consensus on optimal resuscitation practice. 1n doing so, ILCOR aimed to reduce variation and ensure that victims of sudden cardiac death receive the most effective, evidence-based treatments.The resulting international consensus on science with treatment recommendations form a common platform for resuscitation councils around the world to develop local treatment guidelines (Figure).Decades since the creation of ILCOR, cardiac arrest remains a major international public health problem accounting for an estimated 15% to 20% of all deaths. 2he incidence of emergency medical services-assessed out-of-hospital cardiac arrest in various continents ranges from 53 to 112 per 100 000/y, with survival rates rarely exceeding 10%. 2 Despite this significant disease burden, only 92 cardiac arrest randomized clinical trials were published in the 20 years between 1995 and 2014. 3However, the pipeline moving forward is more promising with 140 interventional cardiac arrest clinical trials registered in ClinicalTrials.govas of March 1, 2018.To further catalyze resuscitation research, ILCOR has prioritized knowledge gaps in the field. 4ut challenges remain for ILCOR.In parallel with the rapid growth in clinical resuscitation science is the demand for rapid translation of these findings into clinical practice.Social media platforms such as blogs, podcasts, and electronic journal clubs have enabled disruptive innovation in this arena.However, this accelerated method of knowledge translation creates an emerging risk that treatment strategies will be prematurely adopted or discontinued based on the misinterpretation of clinical trial results.A further challenge is that the greatest burden of cardiac arrest is in regions underrepresented in ILCOR's organizational structure.Last, our vision of "saving more lives globally through resuscitation" cannot be realized without measuring the effect of new treatment recommendations and guidelines on patient outcome across the globe.ILCOR is responding to these challenges by: 1. Transitioning from periodic to continuous evidence evaluation: For the past 2 decades, ILCOR has published the Consensus on Science with Treatment Recommendations (CoSTR) in 5-year cycles.After the publication of the 2015 CoSTR, ILCOR transitioned to a continuous evidence evaluation process that will now regularly generate new and updated CoSTRs based on structured PICOST questions (population, intervention, comparison, outcome, situation, and type of evidence).ILCOR Task Forces, supported by domain leads, expert systematic reviewers, and knowledge synthesis units, will prioritize the generation of new or updated CoSTRs based on emerging science and potential effect on patient outcomes.
Transient T-bet expression functionally specifies a distinct T follicular helper subset
Authors: Difeng Fang, Kairong Cui, Kairui Mao, Gangqing Hu, Rao Li, Mingzhu Zheng, Nicolas Riteau, Steven L. Reiner, Alan Sher, Keji Zhao, Jinfang Zhu
Journal: The Journal of Experimental Medicine (2018)

T follicular helper (Tfh) cells express transcription factor BCL-6 and cytokine IL-21. Mature Tfh cells are also capable of producing IFN-γ without expressing the Th1 transcription factor T-bet. Whether this IFN-γ–producing Tfh population represents a unique Tfh subset with a distinct differentiation pathway is poorly understood. By using T-bet fate–mapping mouse strains, we discovered that almost all the IFN-γ–producing Tfh cells have previously expressed T-bet and express high levels of NKG2D. DNase I hypersensitivity analysis indicated that the Ifng gene locus is partially accessible in this “ex–T-bet” population with a history of T-bet expression. Furthermore, multicolor tissue imaging revealed that the ex–T-bet Tfh cells found in germinal centers express IFN-γ in situ. Finally, we found that IFN-γ–expressing Tfh cells are absent in T-bet–deficient mice, but fully present in mice with T-bet deletion at late stages of T cell differentiation. Together, our findings demonstrate that transient expression of T-bet epigenetically imprints the Ifng locus for cytokine production in this Th1-like Tfh cell subset.
Predictive impact of PD-L1-expressing circulating tumor cells in NSCLC patients treated with nivolumab.
Authors: Ryota Shibaki, Yasuhiro Koh, Hiroaki Akamatsu, Kazuki Kurita, Satomi Yagi, Kuninobu Kanai, Atsushi Hayata, Nahomi Tokudome, Masayuki Higuchi, Hisashige Kanbara, Keiichiro Akamatsu, Hiroki Ueda, Masanori Nakanishi, Nobuyuki Yamamoto
Journal: Journal of Clinical Oncology (2017)

11541 Background: PD-L1 expression on tumor tissue is associated with response to PD-1 blockade in NSCLC. Here, we conducted a serial evaluation of PD-1-expressing circulating tumor cells (CTCs) as a potential real-time diagnostic modality in NSCLC patients treated with nivolumab. Methods: Advanced NSCLC patients after failure of at least one prior chemotherapy regimen received nivolumab monotherapy (3mg/kg, q2W) until progressive disease (PD) or unacceptable toxicity. Peripheral whole blood (3 mL) was collected for CTC evaluation at baseline and at week 4. CTCs were detected using microcavity array system (Hitachi Chemical Co., Ltd, Chikusei, Japan). PD-L1 expression was immunohistochemically examined on both tumor tissues and CTCs. This study was registered at UMIN (ID: 000024414). Results: Thirty patients were registered in the study between January 2016 and September 2016 at Wakayama Medical University Hospital and 29 were included in the analysis. Demographics of the patients were as follows: median age 70 (range, 49 to 86); male 73 %; stage IV, 100 %; squamous/non-squamous, 27/73 %. At baseline, CTCs were detected in all patients (median, 15; range, 1 to 90) and PD-L1-expressing CTCs were detected in 87% of patients. Tumor proportion score (TPS) of PD-L1 expression on CTCs ranged from 6% to 100%, indicating intrapatient heterogeneity. Matched tumor tissues were available from 14 patients and 7 showed the PD-L1 TPS ≥ 50%. No positive correlation was observed on PD-L1 expression between tumor tissues and CTCs based on TPS (R2 = 0.0035). Overall response rate was 25% (7/29), and disease control rate was 54% (15/29). Total CTC count was significantly decreased after nivolumab treatment at week 4 (p &lt; 0.05), but no significant change was observed in PD-L1 TPS on CTC. Patients harboring CTCs with PD-L1 TPS 50% or more at baseline were significantly more likely to achieve non-PD than those harboring CTCs with TPS less than 50% (p &lt; 0.05). Conclusions: This is the first report on a serial monitoring of PD-L1 expression on CTCs in patients treated with nivolumab. PD-L1-expressing CTCs are suggested to hold potential for predicting clinical benefit. Clinical trial information: 000024414.
Does the season of diagnosis affect survival of cutaneous melanoma?
Authors: Srinath Sundararajan, Mohammed Nawaf Kanaan, Haiyan Cui, Joanne M. Jeter
Journal: Journal of Clinical Oncology (2016)

e21064 Background: Incidence of cutaneous melanoma (CM) is known to have seasonal variations. We aimed to study the survival pattern of CM in the United States based on the season of diagnosis. Methods: We queried the Surveillance, Epidemiology, and End Result Program (SEER database) for adults with histologically confirmed CM from 2004 to 2007. June-Aug was classified as summer, Sept-Nov was classified as fall, Dec- Feb was classified as winter and Mar-May was classified as spring. The primary end point assessed was 5-year overall survival (OS) based on season of diagnosis. The 5-year OS was estimated using the Kaplan–Meier method. Results: A total of 63,087 cases of CM were identified. Median age at diagnosis was 60 years; 57.3% of patients were men and 42.7% were women. The majority of the patients were Caucasians (95.3%). The most common anatomical site of diagnosis was the extremities or limbs (42.8%), followed by the trunk (33%), the head & neck (20.2%) and other locations (3.8%). Summer to winter CM incidence ratio was 1.32. Overall, patients diagnosed in the summer had significantly better 5-year OS in the unadjusted model; Fall HR = 1.064 (p = 0.005), Spring HR = 1.061 (p = 0.006), Winter HR = 1.0059 (p = 0.01). The 5-year OS for women diagnosed in summer was significantly higher than for those diagnosed in other seasons [87.44% in summer vs. 85.74% in fall (p = 0.01), 85.26% in spring (p = 0.02), and 85.56% in winter (p = 0.02)]. Caucasians diagnosed in summer had better OS rate than those diagnosed in fall, spring and winter (p = 0.02, p = 0.02 and p = 0.03, respectively). However, when adjusted for age, gender, race, stage and site of CM, the difference in OS between the seasons in all patients, women and Caucasians was not statistically significant. There was no difference in 5-year OS based on season of diagnosis when stratified by tumor histology or anatomical site of tumor. Conclusions: A statistically significant improvement in 5-year OS was noted in all patients, women and Caucasians diagnosed in summer. However, the magnitude of this benefit was small and did not persist in the adjusted model, possibly due to slight differences in stage distribution within the summer group as compared to the other groups. Subjects with unreported staging may also have affected the results.
P01 Integrating Liquid Biopsy in Molecular Tumor Board Decision for Lung Cancer Patients
Authors: C. Rolfo, P. Manca, R. Salgado, P. Van Dam, A. Dendooven, A. Coelho, J.F. Gandia, A. Rutten, W. Lybaert, J. Vermeij, T. Gevaert, S. Metsu, S. Van Laeren, M. Peeters, P. Pauwels
Journal: Journal of Thoracic Oncology (2018)
Size and influence of the decision support networks of women newly diagnosed with breast cancer.
Authors: Lauren P. Wallner, Yun Li, Chandler McLeod, Ann S Hamilton, Kevin C. Ward, Christine Marie Veenstra, Lawrence C. An, Nancy K. Janz, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2017)

e18012 Background: Little is known about the size and characteristics of informal decision support networks of women diagnosed with breast cancer and whether involvement of informal decision supporters (DSP) influences breast cancer treatment decisions. Methods: A population-based sample of newly diagnosed breast cancer patients reported to the Georgia and Los Angeles SEER registries in 2014-15 were surveyed approximately 6 months after diagnosis (N = 2,502, 68% response rate). Network size was estimated by asking women to list up to 3 of the most important DSPs who helped them with locoregional therapy decisions. For each individual DSP listed, respondents reported how important each DSP’s opinion was in treatment decision making, and how satisfied they were with their involvement (5 pt. scales, “not at all” to “very”). Decision deliberation was measured using 5-items assessing degree patients thought through the decision, with higher scores reflecting more deliberative treatment decisions. We compared network size (0-3 or more) across patient-level characteristics and estimated the association between network size and deliberation using multivariable linear regression. Results: Of the 2,502 women in this analysis, 51% reported having 3 or more DSPs, 20% reported 2, 18% reported 1, and 11% reported not having any DSPs. Married/partnered women, those younger than 45 years old, and black women were all more likely to report larger networks (all p &lt; 0.001). Partnered women most often reported their partner as their main DSP (37.9%), whereas not partnered/unmarried women most often reported children (38.4%). The majority of women were highly satisfied with their DSP being involved in their decisions (76.5%) and 68.6% felt their DSP was very important in their decision making. Larger support networks were associated with more deliberative surgical treatment decision-making (p &lt; 0.001). Conclusions: Most women engaged multiple DSPs in their treatment decision making, including spouses, children, and friends. Involving more DSPs was associated with more deliberative treatment decisions. Future initiatives to improve breast cancer treatment decision making should acknowledge and engage informal DSPs.
Treatment patterns and characteristics of acute promyelocytic leukemia (APL) patients receiving arsenic trioxide (ATO) therapy in a real-world setting.
Authors: Boxiong Tang, Susan Gabriel, Jifang Zhou, Ashutosh K. Pathak, Debra Irwin, Ellen Riehle, Francesco Lo-Coco, Martin S. Tallman
Journal: Journal of Clinical Oncology (2017)

e18522 Background: Clinical trials have shown that low-risk APL patients had significantly better outcomes when receiving first-line all-trans retinoic acid (ATRA) + ATO compared with standard ATRA + chemotherapy. Few published studies have used real-world data to describe patients using ATO and their current treatment patterns. This study used United States (US) administrative claims data to describe treatment patterns and characteristics of patients receiving first-line ATO. Methods: This retrospective, observational cohort study used claims data from the MarketScan databases. As there is no ICD-9-CM diagnosis code for APL, ATO treatment was used as a surrogate for the diagnosis of APL since ATO is typically used only in APL patients. Patients were selected if they had ≥1 claims for ATO between January 1, 2000, and June 30, 2015. Date of first use was designated the index date. To identify first-line ATO initiation, patients with ATRA or other APL-indicated chemotherapy claims any time before the index date were excluded. Variable baseline and follow-up periods consisting of ≥3 months of pre-index and ≥30 days of post-index continuous enrollment in medical and pharmacy benefit were used. Results: In total, 331 patients were identified with a subset (n = 265) having ≥2 claims for ATO. The analysis focused on these 265 patients, 54% of whom were male. Mean age was 60.6 years; 45% were covered by Medicare. The most common comorbid conditions measured were diabetes (6%), chronic obstructive pulmonary disease (5%), and congestive heart failure (4%). The most commonly selected APL treatments administered during follow-up were ATRA (17%) and daunorubicin (9%) with the use of idarubicin, cytarabine, and mitoxantrone at less than 3%. Maintenance therapy with methotrexate or 6-mercaptopurine was observed in 7% and 6% of patients, respectively. Conclusions: This is one of the first studies to examine patient characteristics and treatment patterns for first-line ATO using real-world data. Further research is needed to evaluate outcomes for patients receiving ATO as first-line therapy and to re-evaluate treatment guidelines in light of these outcomes.
Addition of concurrent chemotherapy to adjuvant radiotherapy versus radiotherapy alone for resected salivary gland cancers: A systematic review and meta-analysis.
Authors: Paolo Generato Sogono, Michael Benedict A. Mejia, Ryan Anthony Francisco Agas
Journal: Journal of Clinical Oncology (2017)

e17563 Background: Surgery remains to be the standard definitive treatment for malignant tumors of the salivary gland. Post-operative radiotherapy (RT) is warranted for high risk individuals having tumors with high grade, advanced disease or inadequate resection, showing local control and survival benefit. Despite lack of evidence, adjuvant chemoradiation (CRT) has been suggested for worse prognosis patients. Two recent population-based studies showed that adding chemotherapy to RT did not demonstrate a survival advantage, and no randomized study answers this question. Our aim is to review current evidence comparing RT with and without concurrent chemotherapy in non-metastatic, resected salivary gland cancer. Methods: Literature was searched using: CINAHL plus, EBSCOhost, Medline Complete, Science Direct, Proquest, Scopus, and Pubmed. Eligible studies were experimental or observational which compare adjuvant radiotherapy alone versus radiotherapy with concurrent chemotherapy after primary surgery. Pooled analysis for eligible studies was conducted utilizing the Mantel-Haenzel model (random effects) for the outcomes of interest. The NHMRC of Australia Body of Evidence Framework was used to provide an overall evidence recommendation. Results: Eight retrospective studies were included in the qualitative analysis and two were cancer database studies. Pooled analysis from 4 studies showed inferior 3-year overall survival in patients receiving adjuvant CRT(RR 2.15, 95% CI 1.23-6.75). There were no significant differences in 3-year LRC, DMFS or PFS between both groups, although a trend for worse 3-year DMFS and PFS was observed in the CRT group. G3 hematologic toxicity was worse in patients receiving adjuvant CRT vs RT alone (RR 8.63, 95% CI 1.69-44). Critical appraisal revealed that more patients with adverse risk features (T3-T4, node positive, LVSI, PNI, close or positive margins) received CRT. Conclusions: The addition of concurrent chemotherapy to RT in resected salivary gland cancer does not improve overall survival is associated with worse outcomes and greater toxicity.
Identification of patient population with longer survival when treated with S-1 plus cisplatin via predictive enrichment strategy analysis of the FLAGS phase III trial.
Authors: Jaffer A. Ajani, Madoka Takeuchi, Masahiro Takeuchi
Journal: Journal of Clinical Oncology (2017)

e15612 Background: FLAGS, a randomized phase III trial, compared S-1, an oral fluoropyrimidine, plus cisplatin (SP) with 5-fluorouracil plus cisplatin (FP) in the first-line treatment for advanced gastric cancer (AGC). The purpose of this analysis was to discover a clinically significant covariate model using the Predictive Enrichment Strategy Analysis (PESA) to identify a patient population most likely to benefit from the treatment. Methods: PESA is a newly introduced concept proposed by the United States Food and Drug Administration and provides robust results. Consensus-based 15 clinical covariates were selected for enrichment analysis and a large cohort with no missing data (889 patients) was analyzed for model development. The models generated were cross-validated 200 times and ROC-AUC for the Cox PH model with the selected variables by the enrichment analysis were computed. Results: ECOGPerformance status (PS = 1) was the strongest covariate and most significant in identifying the enrichment group for SP. In the population with PS = 1, the OS in the SP group was significantly longer than the FP group (Hazard Ratio [HR] = 0.798, 95%CI = (0.66-0.96) p = 0.0166) Other covariates with high potential to be associated with benefit included: diffuse-type histology, presence of peritoneal metastases, and the lack of liver metastases. Various models using different combinations of the covariates were compared using ROC-AUC analysis and found that the model including all four covariates had the best ROC-AUC (0.566, 95%CI = (0.546-0.587)). Conclusions: PESA identified a cross-validated, robust model (PS, diffuse histology, peritoneal mets, and no liver mets). This patient population is associated with improved OS in Advanced Gastric Cancer patients who receive SP. An independent validation of this model will be carried out with data derived from the DIGEST trial. NCT00400179
P02.12 Moringa oleifera, Lam extract as anti tumor through inhibition of ICAM-1 expression in brain tissue of white rat with metabolic syndrome
Authors: M A Fikri, B E Rezkita, R L Putri
Journal: Neuro-Oncology (2018)

High fat diets are related to the incidence of metabolic syndrome. Metabolic syndrome has been associated with chronic inflammation due to the increased production of reactive oxygen radical that impact on the increasing of ICAM-1 expression. The increasing of ICAM-1 state associated with irritation may lead to environments that foster genomic lesion and tumor initiation. Moringa seeds (Moringa oleifera, Lam.) contain plenty of secondary metabolites rich in antioxidants. This study aimed to determine the effect of Moringa seeds ethanolic extract against ICAM-1 expression on and brain tissue of metabolic syndrome rats (Rattus norvegicus). This was laboratory experimental research using posttest only group design held in UGM and pathology anatomy laboratory of UNS. The sample were 28 Rats that divided into 4 groups: K1 (control) were fed with standard pellet, K2 were metabolic syndrome rats model without Moringa seeds extract, K3 were metabolic syndrome rats model and given Moringa seeds extract dose 1 (150mg/kgBW) and K4 were metabolic syndrome rats model and given Moringa oleifera seeds extract dose 2 (200mg/kgBW). Dependent variable was ICAM-1 expression on brain tissue, whereas the independent variable was Moringa seeds extract. ICAM-1 expression was measured with intensity distribution score (IDS). The effect of Moringa seeds extract to ICAM-1 expression on brain tissue was analyzed with one way ANOVA and Tukey HSD posthoc test. One way ANOVA showed that there were differences between 4 groups of brain tissue (p<0.05). Tukey HSD posthoc test showed differences between brain tissue groups except between K3-K4. Moringa oleifera seeds extract at a dose of 150 mg/kgBW and a dose of 200 mg/kgBW potentially lowered ICAM-1 expression on brain tissue in metabolic syndrome Wistar rats (Rattus norvegicus).