tbuckley/cabot-search huggingface dataset:
Insurance disparity and outcomes among younger non-small cell lung cancer (NSCLC) patients: A SEER analysis 2007-2014.
Authors: Qian Wang, Changchuan Jiang, Yaning Zhang, Siddharth Kunte, Lei Deng, Yuzhou Liu, Zhengrui Xiao, Stuthi Perimbeti, Robert Michael Daly
Journal: Journal of Clinical Oncology (2018)

e21049 Background: Lung cancer is the leading cause of cancer-related death in the US. In 2017 there were approximately 222,500 newly diagnosed lung cancer cases with 80-85% being NSCLC. Thirty percent of them was diagnosed before 65 years old. Among elderly lung cancer patients, studies demonstrated that uninsured and Medicaid patients were less likely to receive guideline-concordant therapy and have higher overall mortality. It remains unknown how insurance status influences the treatment and survival of NSCLC patients less than 65 years. Methods: NSCLC patients were identified through Surveillance, Epidemiology, and End Results (SEER) 18 Program from 2007-2014. Baseline patient features including age, gender, race, education, income, insurance, tumor grade, stage and treatment were included. Subjects aged 65 years or older or those who developed secondary cancers were excluded. Logistic regression and Cox proportional hazards modeling were employed using SAS 9.4 to determine the affect of insurance on treatment and survival. Results: A total of 56,743 NSCLC patients were included. Medicaid and uninsured patients were significantly less likely to be treated than privately insured patients across all stages. Medicaid or uninsured status was associated with higher overall and cause-specific mortality compared to insured after controlling for confounding factors regardless of stage and age. However, there was a 14.7% mortality reduction seen among uninsured patient who were diagnosed after 2010 compared to before 2010 (p < 0.05). Conclusions: Medicaid insured NSCLC patients have poorer survival outcome compared to the uninsured and insured, regardless of stage. Despite the passage of the ACA and Medicaid expansion in 2010, the overall mortality among NSCLC patients with Medicaid remained unchanged. However, the uninsured did witness a mortality benefit which could be possibly due to selection bias – among uninsured patients, those with more comorbidities were more likely to be enrolled in expanded Medicaid than relatively younger, healthier uninsured patients and thus left the latter a better survival. The long-term benefit of ACA on NSCLC outcomes warrants further investigation.
Immune response induced by preoperative chemotherapy in breast cancer: Role of peripheral natural killer (pNK) cell activity, tumor-infiltrating lymphocytes (TILs), and tumor microenvironment factors (TMEFs).
Authors: Ryungsa Kim, Ami Kawai, Megumi Wakisaka, Yuri Funaoka, Yui Tasaka, Naomi Yasuda, Masayuki Hidaka, Yukitaka Morita, Shoichiro Ohtani, Mitsuya Ito, Koji Arihiro
Journal: Journal of Clinical Oncology (2018)

e12644 Background: TILs are predictive and prognostic factors in HER2 type and triple negative breast cancer patients undergoing neoadjuvant chemotherapy. NK cells exert innate immunity, a decrease in NK cells is associated with an increased risk of breast cancer recurrence. TMEFs affect tumor immune surveillance. Relationships between immune response and therapeutic effect induced by preoperative chemotherapy were assessed by pNK cell activity, TILs, and TMEFs. Methods: 28 patients with stage II-IV breast cancer underwent preoperative chemotherapy with nab-PTX/FEC, nab-PTX/FEC/trastuzumab (Tz), DTX/FEC, FEC/nab-PTX, FEC/nab-PTX/Tz, FEC/DTX, or FEC/DTX/Tz. pNK cell activity, TILs, and TMEFs were assessed before and after chemotherapy. TILs were evaluated by H&E staining of biopsy samples and surgical specimens, and TMEFs were assessed by NGS for CD4, CD8, NK, FOXP3, CTLA-4, PD-1, PD-L1, IL-2, IL-6, IL-12, IFN-γ, IL-10, TGF-β, and VEGF using the FFPE samples. Results: Pathologic therapeutic effects were: Grade 1a (G1a), 5 cases; G1b, 10 cases; G2a, 5 cases; G2b, 1 case; G3, 7 cases. Increased pNK cell activity was significantly associated with disappearance of axillar lymph node metastasis (Ax+). In multivariate analysis, increased pNK cell activity was significantly associated with disappearance of Ax+ (OR = 8.00, 95% CI = 1.24-51.50, P = 0.028) and HER-2-positive breast cancer (OR = 7.87, 95% CI = 1.10-56.12, P = 0.039). More than 5% TILs prior to chemotherapy tended to be associated with disappearance of Ax+. G2 or higher effect was significantly associated with high level of CTLA-4 prior to chemotherapy, and with increased CD4, NK, and TGF-β after chemotherapy. Disappearance of Ax+ was significantly associated with high level of CTLA-4 prior to chemotherapy, and increased CD4 after chemotherapy. Conclusions: Release from systemic and local immunosuppression and activation of tumor immunity by preoperative chemotherapy define therapeutic effect and prognosis in patients with breast cancer. The immune checkpoint inhibitors targeting PD-L1 and CTLA-4 may be optimal for breast cancer.
Adjuvant therapy in stage II colon cancer: A NCDB analysis.
Authors: Lakshmi Manogna Chintalacheruvu, Mridula Krishnan, Nicholas B George, Carlos J Silva, Smrity Upadhyay, Nabin Khanal, Ryan W Walters, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2016)

e15120 Background: In stage II Colon cancer, QUASSAR trial indicated significant survival benefit with adjuvant therapy, where as analysis of SEER data base indicated no benefit. Now decision making for adjuvant therapy is individualized. Methods: A total of 127,670 patients with Stage II colon cancer were analyzed from the National Cancer Database from year 2004 to 2013. Multivariate analysis was done and Kaplan Meyer curve was used to compare survival rates. Results: Patients receiving adjuvant therapy were older, more likely to have private insurance, had lower Charlson co morbidity scores, and a higher socio-economic status. Kaplan-Meier analysis indicated patients who received adjuvant therapy were less likely to die (p < .05) compared to patients not receiving adjuvant therapy (median survival: 129 months vs. 82 months). Multivariable Cox regression indicated an interaction between therapy and time from diagnosis such that patients receiving adjuvant therapy were initially more likely to die (e.g., 81% more likely to die at 36 months) and became significantly less likely to die if they survived beyond 50 months (e.g., 39% less likely to die at 60 months) Conclusions: Patients receiving adjuvant therapy were more likely to live longer with greater interval from date of diagnosis. Survival was worse with advancing age, male sex, lower income, Medicaid insurance, poor educational status and higher comorbidities. Multivariate Cox proportional hazards analysis. p HR 95% CI Lower Upper Age <0.05 1.056 1.054 1.057 White 0.200 0.977 0.943 1.012 Spanish <0.05 0.804 0.745 0.868 Female <0.05 0.806 0.790 0.823 Income < $48,000 <0.05 1.082 1.053 1.111 Primary Payera Not Insured 0.069 1.159 0.989 1.358 Private <0.05 0.808 0.706 0.925 Medicaid <0.05 1.313 1.135 1.520 Medicare 0.094 0.893 0.782 1.019 Charlston Scoreb 0 <0.05 0.516 0.500 0.532 1 <0.05 0.674 0.651 0.697 High School Diplomac >21% <0.05 1.137 1.089 1.186 13%-20.9% <0.05 1.110 1.072 1.150 7%-12.9% <0.05 1.047 1.016 1.079 Adjuvant Therapy <0.05 1.812 1.746 1.881
Reliability and consistency of three value frameworks for oncology therapeutics.
Authors: Tanya G.K. Bentley, Joshua T Cohen, Elena B. Elkin, Julie Huynh, Arnab Mukherjea, Thanh Neville, Ioana Popescu, Jenelle Zambrano, Eunice Chang, Michael S. Broder
Journal: Journal of Clinical Oncology (2016)

e18250 Background: In response to rising costs in oncology care, several organizations have developed frameworks to systematically assess the value of oncology drugs. The frameworks produce regimen-specific ratings reflecting factors such as efficacy, toxicity, costs, quality of life, and strength of evidence. The reliability and consistency of these frameworks have not been evaluated. Methods: Six raters (3 MDs, 1 DNP, 2 PhDs) all rated 2 oncology products for each of 3 cancers (6 product-cancer combinations in all) using 3 frameworks: ASCO Value Framework, ESMO Magnitude of Clinical Benefit Scale, and Institute for Clinical and Economic Review (ICER) Evidence Rating Matrix. More prevalent and costly cancers and related products were selected to represent a range of indications (curative and palliative), malignancies (solid and hematologic) and mechanisms (cytotoxic, biologic, immunologic). Raters received the published clinical data required to complete the evaluations and detailed instructions for each framework, but were provided no formal training. Intraclass correlation coefficients (ICC) were estimated to measure tool reliability. Drugs indicated for advanced disease (5 of the 6) were rank ordered by mean and individual scores, and Kendall’s Wcoeffecient was calculated to measure agreement among tools. In sensitivity analyses (SA) for ICC, raters were excluded one at a time. Results: There were 6 ratings of 6 products for each of the 3 frameworks (108 ratings total). ICC results (SA range) were: ASCO 0.66 (0.61-0.70); ESMO 0.73 (0.67-0.78); ICER 0.72 (0.65-0.95). Rankings for the 5 advanced disease regimens (A-E) varied by framework: see table. Conclusions: Knowledgable but untrained raters, provided with key data, produced moderately reliable results using 3 recently published frameworks for assessing the value of cancer treatments. The frameworks had fair to good consistency, indicating convergent validity, although they led to significantly different conclusions about the relative value of treatments for advanced disease. ASCO ESMO ICER A B A B D C C A D D C B E E E Kendall’s W across all 3 frameworks was 0.69 (range 0.59-0.85 among individual raters). Pairwise, Kendall’s Wwas 0.75 for ASCO-ESMO, 0.85 ASCO-ICER, and 0.70 ESMO-ICER.
Analysis of prognostic factors of end-stage cancer patients within 6 months prior to death.
Authors: Qiang Fu, Xiaoyun Kang, Shiying Yu, Huayuan Hu, Jie Rao, Jin Tong, Ting Zhou
Journal: Journal of Clinical Oncology (2018)

e22008 Background: Determining prognosis in advanced cancer is of key importance. Various prognostic scores have been developed. However, they are often very complex, and physicians still do not accurately estimate survival time according to these tools. In this study, we dynamically evaluated the feasibility of clinical routine examination including blood cells and biochemistry as indices to estimate survival in end-stage cancer patients. Methods: From January 2016 to December 2017, the clinical data of 556 patients with advanced cancer in Xinfeng County People's Hospital and Tongji Hospital were collected. 201 cases among them died, we retrospectively analyzed clinical data of these 201 patients within 6 months before death, The clinical symptoms and blood biochemical changes in 1 week, 1 month, 3 months and 6 months before the death were observed. Results: 201 cases of death among the 556 cases included 72 cases of liver cancer, 53 cases of lung cancer, 42 cases of digestive system tumor (excluding liver cancer), 18 cases of head and neck squamous cell carcinoma, 11 cases of urogenital tumors, and 5 cases of others. The incidence of symptoms was fatigue (94.5%), pain (90.0%), constipation (89.1%), dysphagia (27.9%) and dyspnea (20.9%) in 1 week prior to death. Multivariate Logistic regression analysis showed that white blood cell count (P= 0.012) and neutrophil count (P= 0.008), alanine aminotransferase (P= 0.003), albumin (P= 0.000), urea nitrogen (P= 0.035), serum sodium (P= 0.002), lactate dehydrogenase (P= 0.038) and C reactive protein (P= 0.000) were independent prognostic factors of end-stage tumor death. The hematological indices of 201 patients in 6 months before death were dynamically analyzed, the results of 1 week before death were compared with those of 1 month, 3 months and 6 months before death (P< 0.03). The trends of these independent prognostic factors were more obvious between 1 week and 6 months before death. Conclusions: Dynamic changes in clinical routine hematological indices of end-stage cancer patients within 6 months prior to death can obviously predict the prognosis, which is helpful for the accurate judgement of patients' survival and palliative care.
Liquid biopsy analysis of ALK alterations from advanced NSCLC patients: The value of exosomal RNA cargo (ExoALK).
Authors: Christian Diego Rolfo, Jean-Francois Laes, Pablo Reclusa, Maxime Lienard, Ignacio Gil-Bazo, Umberto Malapelle, Danilo Rocco, Jan Van Meerbeeck, Patrick Pauwels, Marc Peeters, Marco Giallombardo
Journal: Journal of Clinical Oncology (2017)

e20569 Background: About 5% of NSCLCs present alterations in the ALK gene. Among them the most common is EML4-ALK translocation. The gold standard detection method to treat the patient with ALKi is the tissue, thus, it is mandatory to develop new techniques that allow to detect ALK alterations in liquid biopsy. The purpose of this study is, analyze the feasibility to detect ALK alterations in exosomes (Exo-ALK) derived from NSCLC patients. Methods: We recruit 18 NSCLC patients including EML4-ALK and wild-type patients stage- and time-independent. ALK-positive status is identified by IHQ. The isolation of RNA with the exoRNeasy Kit Serum/Plasma (Qiagen) in UZA and the retrotranscription with ProtoScript II First Strand cDNA Synthesis kit. The ALK alteration present in the exosomes is determined by NGS and bio-informatic analysis in OncoDNA. Samples were provided by the Biobank of the University of Navarra, the UZA Biobank and the University of Naples Federico II. Samples and data were processed following the processes approved by the local Ethical and Scientific Committees. Results: Among analyzed patients, 15 patients were EML4-ALK tissue positive, and 3 were EML4-ALK tissue negative. With our analysis, 9 patients were positive, 7 negative and 2 sample were degraded at the time of analysis. Comparing the results, the 9 positive patients in the exosomes were also positive in the tissue. Moreover, the 2 negative patients were also negative for the translocation in the tissue. However, we were unable to detect 4 positive EML4-ALK patients in the exosomes. Nonetheless, these data show a sensitivity of 69% and a specificity of 100%. No correlation was found comparing treatment-naïve and pretreated patients. Conclusions: Exosomes are raising as a very promising tool to determine the tumor profile due to their stability and their cargo. With further study and a larger number of patients, we demonstrate that exosomes isolation and analysis will be feasible tool, and thus we will reduce the tumor biopsy risks and costs in the clinical practice. Our preliminary results show a good specificity for a proof of concept analysis. These results will be cross-validated and amplified with more patients in the following months.
Identification of leptomeningeal metastasis-specific exosomal miRNA signature in cerebrospinal fluid of non-small-cell lung cancer patients.
Authors: Ben-Yuan Jiang, Yangsi Li, Xue Wu, Hua Bao, Yan Ding, Jinji Yang, Xuchao Zhang, Xuening Yang, Wenzhao Zhong, Qing Zhou, Haiyan Tu, Shuyu Wu, Yang Shao, Cunyi Gao, Yi-Long Wu
Journal: Journal of Clinical Oncology (2018)

e21024 Background: Leptomeningeal metastasis (LM) is a devastating complication with poor prognosis in non-small-cell lung cancer (NSCLC) patients. Exosomes are extracellular vesicles in body fluids enriched with microRNAs (miRNAs), which have been implicated in brain metastasis. Here, we aimed to identify exosomal miRNA signatures in NSCLC patients with LM and elucidate the potential LM mechanism. Methods: We prepared exosomes from cerebrospinal fluid (CSF) samples of 29 advanced NSCLC patients with (n = 22, LM+) or without (n = 7, LM-) LM as well as 4 non-cancer individuals. Exosomal miRNA profiles obtained from next-generation sequencing were subjected for differential expression analysis and signature discovery. Results: Unsupervised hierarchical clustering of the miRNA expression profiles clearly separated CSF samples into LM+ and LM- groups. Interestingly, these samples were stratified based on their LM status only, regardless of their intraparenchymal metastasis status. In total, 181 (129 up and 52 down-regulated) miRNAs were identified differentially presented in the LM+ CSF samples compared to the LM- group. Predicted targets of up and down-regulated miRNAs were significantly enriched in the neurotrophin/MAPK and PI3K-AKT signaling pathway, respectively. Top altered miRNAs include dramatically up-regulated miR-200 family members and down-regulated miR-144/451 cluster, which have been previously reported to be involved in metastasis. Using machine learning, we identified a signature of 8 CSF exosome miRNAs (let-7e-5p, miR-142-5p, miR-148a-3p, miR-200b-3p, miR-451a, miR-483-5p, miR-486-5p, and miR-96-5p) for classification of LM+ patients with 97% sensitivity and 100% specificity. Interestingly, one CSF sample, which was taken 321 days before LM was confirmed in clinic, was predicted as LM+ based on our signature. Conclusions: NSCLC patients with LM present a remarkably distinct CSF exosomal miRNA signature, which may involve in the progression of LM, and can be potentially used as diagnostic biomarkers for LM.
Behavioral and Pharmacotherapy Weight Loss Interventions to Prevent Obesity-Related Morbidity and Mortality in Adults
Authors: Erin S. LeBlanc, Carrie D. Patnode, Elizabeth M. Webber, Nadia Redmond, Megan Rushkin, Elizabeth A. O’Connor
Journal: JAMA (2018)

<h3>Importance</h3> Overweight and obesity have been associated with adverse health effects. <h3>Objective</h3> To systematically review evidence on benefits and harms of behavioral and pharmacotherapy weight loss and weight loss maintenance interventions in adults to inform the US Preventive Services Task Force. <h3>Data Sources</h3> MEDLINE, PubMed Publisher-Supplied Records, PsycINFO, and the Cochrane Central Register of Controlled Trials for studies published through June 6, 2017; ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials through August 2017; and ongoing surveillance in targeted publications through March 23, 2018. Studies from previous reviews were reevaluated for inclusion. <h3>Study Selection</h3> Randomized clinical trials (RCTs) focusing on weight loss or weight loss maintenance in adults. <h3>Data Extraction and Synthesis</h3> Data were abstracted by one reviewer and confirmed by another. Random-effects meta-analyses were conducted for weight loss outcomes in behavior-based interventions. <h3>Main Outcomes and Measures</h3> Health outcomes, weight loss or weight loss maintenance, reduction in obesity-related conditions, and adverse events. <h3>Results</h3> A total of 122 RCTs (N = 62 533) and 2 observational studies (N = 209 993) were identified. Compared with controls, participants in behavior-based interventions had greater mean weight loss at 12 to 18 months (−2.39 kg [95% CI, −2.86 to −1.93]; 67 studies [n = 22065]) and less weight regain (−1.59 kg [95% CI, −2.38 to −0.79]; 8 studies [n = 1408]). Studies of medication-based weight loss and maintenance interventions also reported greater weight loss or less weight regain in intervention compared with placebo groups at 12 to 18 months (range, −0.6 to −5.8 kg; no meta-analysis). Participants with prediabetes in weight loss interventions had a lower risk of developing diabetes compared with controls (relative risk, 0.67 [95% CI, 0.51 to 0.89]). There was no evidence of other benefits, but most health outcomes such as mortality, cardiovascular disease, and cancer were infrequently reported. Small improvements in quality of life in some medication trials were noted but were of unclear clinical significance. There was no evidence of harm such as cardiovascular disease from behavior-based interventions; higher rates of adverse events were associated with higher dropout rates in medication groups than in placebo groups. <h3>Conclusions and Relevance</h3> Behavior-based weight loss interventions with or without weight loss medications were associated with more weight loss and a lower risk of developing diabetes than control conditions. Weight loss medications, but not behavior-based interventions, were associated with higher rates of harms. Long-term weight and health outcomes data, as well as data on important subgroups, were limited.
Interim analysis of a prospective, randomized, double blind, placebo controlled, phase IIb trial of the TLPLDC vaccine to prevent recurrence in resected stage III or IV melanoma patients.
Authors: John William Myers, Guy T Clifton, Diane F Hale, Tommy A Brown, Timothy J Vreeland, Robert Hans Ingemar Andtbacka, Adam C. Berger, James W. Jakub, Jeffrey J. Sussman, Alicia Maria Terando, Mark B. Faries, George Earl Peoples
Journal: Journal of Clinical Oncology (2018)

9525 Background: The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine has been shown to be safe and immunogenic while producing objective tumor responses in a variety of metastatic patients (pts). Here, we present the pre-specified interim results of a randomized, double blind phase IIb trial (NCT02301611) assessing the TLPLDC vaccine to prevent recurrences in high risk melanoma pts. Methods: Stage III & IV resectable melanoma pts were identified prior to definitive surgery and consented for tumor collection. Pts were re-consented for treatment and randomized 2:1 (vaccine (V): placebo (P)). TLPLDC or placebo vaccines were initiated within 3 mos of completion of standard of care (SoC) therapies. Intradermal inoculations were given at 0, 1, 2, 6, 12, and 18 mos. Pts were followed for recurrence per SoC, and the primary endpoint is 2 yr disease-free survival (DFS). The interim was pre-specified at 6 mos from the 120th randomization. Survival analysis was performed on the intention-to-treat (ITT) and per treatment (PT) populations. The latter excludes early recurrences during the primary vaccine series (PVS) (up to 6 mos). Results: The trial randomized 120 patients (V = 83, P = 37). There were no clinicopathologic or treatment-related differences between the groups except for median age (V = 65 yrs, P = 57 yrs, p = 0.02). There were 3:1 stage III:IV in both groups. Study-wide, only 33% of pts experienced treatment-related adverse events (AEs) with 98.6% being grade 1-2. There were no serious AEs or immune-mediated AEs. In the ITT analysis, there was no difference in recurrence (V = 56.6%, P = 54.1%, p = 0.65) at a median f/u of 11.9 mos. In the PT analysis (V = 51, P = 30), there was a trend toward decreased recurrences in the TLPLDC arm (V = 29.4%, P = 43.3%, p = 0.07) at a median f/u of 12.6 mos. Conclusions: The TLPLDC vaccine is safe with minimal toxicity. Among pts completing the PVS period (6 mos), there is a strong trend toward fewer recurrences in the TLPLDC arm. This benefit will be confirmed at the primary analysis of 2 yr DFS; however, these early data provide an encouraging signal that a phase III trial for efficacy may be warranted. Clinical trial information: NCT02301611.