tbuckley/cabot-search huggingface dataset:
Early change in blood-based biomarkers and association with clinical outcome (CO) in advanced stage cancer patients (pts) treated with immunotherapy (IO).
Authors: Dylan J. Martini, Yuan Liu, Colleen Margaret Lewis, Julie M. Shabto, Mehmet Akce, Haydn Kissick, Bradley Curtis Carthon, Walid Labib Shaib, Olatunji B. Alese, Rathi Narayana Pillai, Conor Ernst Steuer, Christina Wu, David H. Lawson, Ragini Reiney Kudchadkar, Bassel F. El-Rayes, Viraj A. Master, Suresh S. Ramalingam, Taofeek Kunle Owonikoko, R. Donald Harvey, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2018)

e15022 Background: Ideal biomarkers for cancer pts receiving IO are currently lacking. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are readily available inflammatory markers and are linked to poor outcomes. We studied the association between these and CO in pts receiving IO. Methods: We conducted a retrospective review of 90 pts treated on IO-based phase I trials at the Winship Cancer Institute between 2009-2017. Baseline (BL) NLR, MLR, and PLR were treated as continuous variables with log transformation. Change from BL to 6 (+/-2) weeks (6W) was dichotomized into increased or decreased. Overall survival (OS) and progression-free survival (PFS) were measured from start of IO to date of death and to clinical/radiographic progression, respectively. Multivariable analysis (MVA) was carried out using Cox proportional hazard model. Results: The median age was 63 years and most pts (53%) were men. The most common histologies were melanoma (33%) and GI cancers (22%). The majority (81%) were Royal Marsden Hospital (RMH) good risk. Increased baseline and 6W increase in NLR, MLR, and PLR were associated with worse OS and PFS (Table 1). NLR, MLR and PLR are correlated to each other (Pearson correlation coefficients ≥ 0.67, all p < 0.0001). Conclusions: Baseline and 6W change in NLR, MLR, and PLR may be useful predictive and prognostic biomarkers of CO in pts treated with IO. Table 1: MVA† of NLR, MLR, and PLR with CO OS PFS HR (CI) p-value HR (CI) p-value Baseline NLR 2.28 (1.50-3.47) < 0.001* 2.00 (1.39-2.89) < 0.001* MLR 2.15(1.25-3.68) 0.005* 2.11 (1.36-3.30) < 0.001* PLR 2.14 (1.29-3.54) 0.003* 2.64 (1.71-4.08) < 0.001* 6W Change Increased NLR 4.11 (1.86-9.11) < 0.001* 2.58 (1.38-4.80) 0.003* Increased MLR 2.26 (1.06-4.79) 0.034* 2.02 (1.09-3.74) 0.026* Increased PLR 3.13 (1.42-6.88) 0.005* 1.84 (0.99-3.41) 0.052 †The multivariable model was built by controlling for age, prior IO, # of prior therapies, RMH risk group, # of metastatic sites, liver metastasis, and # of previous treatment lines. *statistical significance at alpha < 0.05.
Molecular biomarkers in early-stage lung cancer.
Authors: Elena Guerini Rocco, Caterina Fumagalli, Davide Vacirca, Paola Rafaniello Raviele, Giovanni Bertalot, Matteo Lazzeroni, Lorenzo Spaggiari, Filippo De Marinis, Giuseppe Viale, Fabrizio Bianchi, Massimo Barberis
Journal: Journal of Clinical Oncology (2016)

e23082 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide; early diagnosis represents the main approach to reduce disease mortality. Molecular biomarkers coupled with imaging studies are promising tools to improve early detection. We performed a multi-level biological characterization of a unique group of patients with early-stage NSCLCs during long-term follow-up of chemopreventive trial (NCT00321893). Methods: Blood and sputum samples were collected at baseline and 12 months from 202 high-risk asymptomatic individuals with CT-detected stable lung nodules. Real-time PCR was performed on plasma to quantify free circulating DNA. Promoter methylation status of p16, RASSF1a and RARβ2 and telomerase activity were assessed in each sputum sample using quantitative methylation specific PCR and Elisa Telomerase assay, respectively. Clinico-pathologic characteristics of tumors developed during follow-up were analyzed. DNA was extracted from each tumor sample and subjected to a mutation survey using LungCarta panel on Sequenom MassARRAY platform. Baseline serum of these patients were investigated with a previously validated diagnostic test based on 13 circulating miRNAs (miR-Test) which demonstrated high sensitivity and specificity (77.8% and 74.8%, respectively) for early detection of lung cancer in high-risk individuals. Results: Six individuals underwent surgical resection for NSCLC with a median time of disease onset (nodule evolution) of 20.5 months. These tumors were classified as stage I adenocarcinoma. No association was identified between free circulating DNA or sputum biomarkers and disease onset. miR-Test scores were positive (range: 0.14-7.24) in 4 out of 6 baseline pre-disease onset sera. All tumors harbored at least one driver somatic mutation in well-known cancer genes, including KRAS (n = 4), BRAF (n = 1) and TP53 (n = 3). Conclusions: Screening programs are essential for the diagnosis of early-stage highly-curable NSCLCs. Circulating miRNA tests may represent valuable tools to detect clinically-silent tumors. Early-stage lung adenocarcinomas harbor recurrent driver genetic events similar to those described in advanced-stage NSCLCs occurring in high-risk population.
TCT-785 Misclassification of Type 2 Myocardial Infarction and its Implication on Outcomes
Authors: Amer Hawatmeh, Mohammad Thawabi, Rashmi Aggarwal, Ilan Vavilin, Chandra Abirami Balasubramaniapandian, Najam Wasty, Gautam Visveswaran, Marc Cohen
Journal: Journal of the American College of Cardiology (2018)
Analysis of circulating tumor DNA to monitor disease status in colorectal cancer after surgery.
Authors: Liren Li, Wenhao Zhou, Cong Li, Pansong Li, Yuhua Gong, Yan-Fang Guan, Xuefeng Xia, Ling Yang, Xin Yi
Journal: Journal of Clinical Oncology (2018)

e15583 Background: Colorectal cancer (CRC) has high prevalence and mortality worldwide. Surgery is the preferred treatment for CRC. Recurrence occurrs in more than one-third of patients (pts) with stage II and III CRC undergoing radical surgery. Early detection of recurrence or metastasis helps promptly selecting the appropriate treatment. Circulating tumor DNA (ctDNA) in peripheral blood carries tumor-specific somatic alterations. We investigated the potential of ctDNA as a biomarker for prediction of post-operative recurrence or metastasis. Methods: Plasma sample within one week after surgery and matched tissue from surgery were collected from CRC pts. All samples were performed next generation sequencing (NGS) using the targeted panel containing 1021 genes. Tissue-derived mutations were tracked and quantified in post-operative plasma. Pts received adjuvant therapy at clinician discretion. Post-operative follow-up was recorded. Results: 63 CRC pts (47 colon, 14 rectal, and 2 rectosigmoid) were enrolled between Jan-2017 and Jan-2018. Sixty-three tissues and 63 post-operative plasma samples were collected. All 63 pts were detected with at least one mutation in tissues. The mean of tumor mutation burden (TMB) is 19. After surgery, 18/63 (28.6%) pts had detectable ctDNA. Five of these 18 pts (27.8%) have disease progression during a median follow up of 6 months after diagnose. Disease progression occurred in only 2 of 45 (4.4%) with negative ctDNA (Fisher test, OR 7.9, p= 0.0169, 95% CI). Eleven (17.5%) pts were identified TMB-H with at least 35 mutations. Eight pts with mismatch repair defects (dMMR) were found clinically, and 100% of them were confirmed by NGS as high microsatellite instability (MSI-H). Of TMB-H pts, 45.5% (5/11) had detectable ctDNA and all of them were MSI-H. Five of 8 (62.5%) MSI-H pts were detected with post-operative ctDNA, while 13/55 (23.6%) non-MSI-H pts were detected (OR 5.2, p = 0.0365). One MSI-H patient with ctDNA have disease progression. Conclusions: Post-operative ctDNA implies a high risk of recurrence or metastasis. Post-operative ctDNA in MSI-H pts may not be considered as high risk factors. ctDNA analysis offers the biomarker for molecular monitoring of disease in CRC.
A phase I/IIa, open label, clinical trial evaluating the safety and efficacy of autologous T cells expressing enhanced TCRs specific for NY-ESO-1 in patients with recurrent or treatment refractory ovarian cancer (NCT01567891).
Authors: Kunle Odunsi, Mihaela C. Cristea, Oliver Dorigo, Amir A. Jazaeri, Brian M. Slomovitz, Karen Chagin, Erin Van Winkle, Gabor Kari, Malini Iyengar, Elliot Norry, Arundathy N. Bartlett-Pandite, Rafael G. Amado
Journal: Journal of Clinical Oncology (2017)

TPS3094 Background: Epithelial ovarian cancer comprises the majority of malignant ovarian neoplasms (~80%) and is the leading cause of death from gynecologic cancer in the US. Due to lack of effective screening strategies, the majority (63%) of patients are diagnosed with ovarian cancer at advanced stages. New therapies are needed to address the unmet medical need of patients with ovarian cancer. 11-40% of ovarian cancers express NY-ESO-1 cancer testis/antigen. This study is evaluating affinity enhanced autologous NY-ESO-1 c259 T cells recognizing an NY-ESO-1 derived peptide complexed with HLA-A*02 in ovarian cancer. Methods: This single arm, open label clinical trial is evaluating safety and tolerability, antitumor activity (response rate by RECIST v1.1, progression free survival, overall survival, duration of response), and translational research endpoints. The study evaluates two lymphodepleting regimens: cyclophosphamide (enrolment completed; n = 7) and cyclophosphamide plus fludarabine (at least 10 subjects to be enrolled). Subjects must be ≥ 18 years old; HLA-A*02:01, *02:05, or *02:06 positive; have recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum-resistant disease expressing NY-ESO-1 by IHC; have measurable disease; have ECOG status 0 or 1; and have adequate organ function. Following apheresis, the T cells are isolated and expanded with CD3/CD28 beads, transduced with a lentiviral vector containing the NY-ESO-1 c259 TCR, and 1 – 6 × 10 9 transduced T cells are infused intravenously on Day 0 after lymphodepletion with fludarabine 30 mg/m 2 /day and cyclophosphamide 600 mg/m 2 /day on days -7 to -5. Response is assessed at weeks 4, 8, 12 and 24, and then every 3 months until confirmation of disease progression. Clinical trial information: NCT01567891.
Is surgical resection beneficial in recurrent or metastatic gastric cancer?
Authors: Yong Won Choi, Mi Sun Ann, Hyun Woo Lee, Seok Yun Kang, Jin-Hyuk Choi
Journal: Journal of Clinical Oncology (2017)

4043 Background: Although chemotherapy is currently established as a standard treatment in recurrent or metastatic gastric cancer, the role of palliative surgical resection is still controversial. We investigated the survival benefit of surgical resection in patients (pts) with recurrent or metastatic gastric cancer who received systemic chemotherapy. Methods: A retrospective review was conducted on 698 pts who received palliative chemotherapy for recurrent (n = 307) or primary metastatic (n = 391) gastric cancer. Overall survival (OS) of pts who underwent surgical resection followed by chemotherapy was compared to that of pts who received chemotherapy alone. Results: Among 140 pts (primary metastatic: 97, recurrent: 43) with surgical resection, gastrectomy, metastasectomy, and gastrectomy with metastasectomy were performed in 83 (primary metastatic: 81), 44, and 13 pts, respectively. Higher surgical resection rate was observed in pts with young age ( &lt; 70) (p = 0.010), ECOG PS 0 or 1 (p = 0.010), primary metastatic (p &lt; 0.0001), absence of liver metastasis (p = 0.002), and signet ring cell histology (p = 0.002). The median OS of pts who underwent surgical resection before chemotherapy was significantly longer than that of pts who received chemotherapy alone (19 vs. 9 months, p &lt;0.0001). The OS benefit of surgical resection was consistent across subgroups in terms of baseline characteristics including age, ECOG PS, disease status (primary metastatic vs. recurrent), peritoneal metastasis, and first-line chemotherapy regimen (single vs. combination). In multivariate analysis, surgical resection was independently associated with favorable OS (hazard ratio = 0.41, p &lt; 0.0001) along with ≥second-line chemotherapy (p &lt; 0.0001), whereas ECOG PS 2 or 3 (p = 0.013), signet ring cell histology (p &lt; 0.0001), and peritoneal metastasis (p = 0.046) were independent prognostic factors of poor OS. Conclusions: The present study suggests that judicious use of surgical resection before chemotherapy in recurrent or metastatic gastric cancer pts may result in favorable outcome, although large scale phase III trials are essential to establish this treatment approach as a standard practice.
Activated Natural Killer Cells in Combination with Anti-GD2 Antibody Dinutuximab Improve Survival of Mice after Surgical Resection of Primary Neuroblastoma
Authors: Wesley E. Barry, Jeremy R. Jackson, Grace E. Asuelime, Hong-Wei Wu, Jianping Sun, Zesheng Wan, Jemily Malvar, Michael A. Sheard, Larry Wang, Robert C. Seeger, Eugene S. Kim
Journal: Clinical Cancer Research (2018)

Immunotherapy of neuroblastoma that remains after myeloablative chemotherapy with anti-GD2 antibody dinutuximab has increased the two-year event-free and overall survival of high-risk neuroblastoma patients; however, 40% of patients develop recurrent disease during or after this treatment. To determine the potential of such antibody-based immunotherapy earlier in treatment, a mouse model was developed in which surgical resection of the primary tumor was followed by therapy of residual disease with dinutuximab combined with ex vivo-activated human natural killer (aNK) cells.The effect of combining dinutuximab with human aNK cells was determined in vitro with cellular cytotoxicity and Matrigel invasion assays. The in vivo efficacy of dinutuximab and aNK cells against neuroblastoma was assessed following resection of primary tumors formed by two cell lines or a patient-derived xenograft (PDX) in immunodeficient NOD-scid gamma mice.In vitro, the combination of aNK cells and dinutuximab caused cytotoxicity and decreased invasiveness of three human neuroblastoma cell lines. Treatment of mice with dinutuximab combined with aNK cells after surgical resection of primary intrarenal tumors formed by two cell lines or a PDX decreased tumor cells in liver and bone marrow as evaluated by histopathology and bioluminescence imaging. Survival of mice after resection of these tumors was most significantly increased by treatment with dinutuximab combined with aNK cells compared with that of untreated mice.The combination of dinutuximab and adoptively transferred human aNK cells following surgical resection of primary neuroblastomas significantly improves survival of immunodeficient mice.
Nutritional status and quality of life in patients with gastric cancer in China.
Authors: Hongli Li, Shaohua Ge, Yi Ba
Journal: Journal of Clinical Oncology (2017)

e15508 Background: The incidence of gastric cancer is much higher in China than in any other country. Although the overall survival rate of patients with gastric cancer has increased due to the advancements in multimodality management. However, significant morbidity, including loss of appetite, dysphagia, nausea, and vomiting is still associated with gastric cancer patients. These symptoms have a profound impact on nutritional status and quality of life in these patients. The primary objective of the present study was to assess the nutritional status and quality of life in gastric cancer patients. Methods: A preliminary assessment of patients’ nutritional status, quality of life, and medical characteristics was conducted using the Patient Generated Subjective Global Assessment (PG-SGA) and the European Organization for Research and Treatment of Cancer quality of life (QOL-C30, version 3) questionnaires. The PG-SGA is a clinical nutrition assessment tool used to evaluate oncology patients. The nutritional status of the patients fell into three groups by a score of PG-SGA-A, -B, and C. Results: A preliminary assessment of patients’ nutritional status, quality of life, and medical characteristics was conducted using the Patient Generated Subjective Global Assessment (PG-SGA) and the European Organization for Research and Treatment of Cancer quality of life (QOL-C30, version 3) questionnaires. The PG-SGA is a clinical nutrition assessment tool used to evaluate oncology patients. The nutritional status of the patients fell into three groups by a score of PG-SGA-A, -B, and C. Conclusions: These results suggest that the nutritional status of the patients with stomach cancer may impact on their QoL. It is necessary to develop nutritional intervention to improve QoL in gastric cancer patients.
The role of PIDD gene in the radiation-induced brain injury.
Authors: Fan Tong, Xiaorong Dong, Gang Wu, Xican Gao, Lingjuan Chen, Ruiguang Zhang, Chunjin Xiong, Hui Lu, Chunhua Wei
Journal: Journal of Clinical Oncology (2018)

e14008 Background: Radiation-induced brain injury (RIBI) is an unavoidable adverse side-effect for the cranial radiotherapy (CRT), and its underlying mechanisms were poorly understood. Methods: We firstly employed Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales to assess the cognitive function in the patients after CRT, and used ELISA to detect the serum levels of TNF-α and IL-1β. And then we established RIBI models in mice infected respectively by lentiviruses interfering or over-expressing C-terminal fragment of the mouse p53-induced protein with a death domain (PIDD) gene (PIDD-C). Morris water maze test was used to test the cognitive function in mice. Cell scratch and transwell assays were used to examine the migration ability of microglial cells. Ultrastructural observation and cells phalloidin staining were used to detect the microglial activation. The real time PCR, immunofluorescence staining and western blotting were used to examine the expressions of inflammatory factors and the fragments of PIDD, and the activation of NF-κB pathway. Co-Immunoprecipitation was used to explore the interaction between PIDD-C and NF-κB essential modulator (NEMO). Results: A decrease in cognitive ability was found in patients 6 months after CRT and accompanied by increased serum TNF-α and IL-1β, showed by ELISA. Morris water maze test showed that down-regulated PIDD attenuated the learning and memory abilities of RIBI mice, and over-expressed PIDD-C aggravated the deficits. Cell scratch assay and transwell assay showed that down-regulated PIDD enhanced the migration ability of microglial cells. Moreover, the irradiation-induced microglial activation and its release of TNF-α and IL-1β, were inhibited by down-regulated PIDD and enhanced by over-expressed PIDD-C. Co-Immunoprecipitation studies demonstrated that PIDD-C and NEMO were co-localized and bound directly. And the irradiation-induced phosphorylated p65 and IκBα, the down-stream factor of NEMO, were found to be increased by over-expressed PIDD-C and decreased by down-regulated PIDD. Conclusions: RIBI was principally mediated by the PIDD-C-associated microglial activation and neuo-inflammation relied on the interaction of PIDD-C with NEMO/NF-κB pathway.
Abstract 18020: Competitive Athletes With Implantable Cardioverter Defibrillators - How to Program? Data From the ICD Sports Registry
Authors: Brian Olshansky, Gourg Atteya, David Cannom, Hein Heidbuchel, Elizabeth Saarel, Ole-Gunnar Anfinsen, Alan Cheng, Michael R Gold, Andreas Müssigbrodt, Kristen Patton, Leslie Saxon, Bruce Wilkoff, Rik Willems, Rachel Lampert
Journal: Circulation (2017)

Introduction: Athletes, at risk for sudden cardiac death and who have implantable cardioverter defibrillators (ICDs), represent a unique group, for whom, optimal ICD programming remains uncertain. ...
A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell disease: A 2-part phase 2 study
Authors: Lewis L. Hsu, Sharada Sarnaik, Suzan Williams, Carl Amilon, Jenny Wissmar, Anders Berggren
Journal: American Journal of Hematology (2018)

Antiplatelet treatment is a potential therapeutic approach for sickle cell disease (SCD). Ticagrelor inhibits platelet aggregation and is approved for adults with acute coronary syndrome and following myocardial infarction. HESTIA1 (NCT02214121) was a 2-part, phase 2 dose-finding study generating ticagrelor exposure, platelet inhibition, and safety data in children with SCD (3-17 years). In part A (n = 45), patients received 2 ticagrelor single doses, 0.125-2.25 mg/kg (washout ≥7 days), then 7 days of twice-daily (bid) dosing with 0.125, 0.563, or 0.75 mg/kg. In the 4-week blinded Part B extension (optional), patients received ticagrelor (0.125, 0.563, or 0.75 mg/kg bid; n = 16) or placebo (n = 7). Platelet reactivity decreased from baseline to 2 hours postdosing, and returned to near baseline after 6 hours postdosing. Dose-dependent platelet inhibition was seen with ticagrelor; mean relative P2Y12 reaction unit inhibition 2 hours after a single dose ranged from 6% (0.125 mg/kg) to 73% (2.25 mg/kg). Ticagrelor plasma exposure increased approximately dose proportionally. No patients experienced a hemorrhagic event during treatment. No differences were seen between groups in pain ratings and analgesic use during Part B. Ticagrelor was well tolerated with no safety concerns, no discontinuations due to adverse events (AEs), and reported AEs were mainly due to SCD. In conclusion, a dose-exposure-response relationship for ticagrelor was demonstrated in children with SCD for the first time. These data are important for future pediatric studies of the efficacy and safety of ticagrelor in SCD.
TCT-31 Comparison of Standard Renal Denervation Procedure versus Novel Distal and Branch Vessel Procedure with Brachial Arterial Access
Authors: Ivo Petrov, Iveta Tasheva, Iskren Garvanski, Zoran Stankov, Iana Simova, Iskren Garvanski
Journal: Journal of the American College of Cardiology (2018)