tbuckley/cabot-search huggingface dataset:
Prognostic value of dysregulated ErbB signaling network in endometrial cancer.
Authors: Anna Maria Supernat, Sylwia Lapinska-Szumczyk, Hanna Majewska, Jacek Gulczynski, Wojciech Biernat, Dariusz Wydra, Anna Joanna Zaczek
Journal: Journal of Clinical Oncology (2014)

e16540 Background: Dysregulation of the ERBB signaling network occurs in many human cancers and is associated with more aggressive tumor behavior and poor outcome. The data about the status of the family of those four receptor tyrosine kinases and their downstream effectors in endometrial cancer (EC) are scarce. We have previously shown correlation of ERBB, PIK3CA and MYC gene aberrations with more aggressive EC characteristics. Therefore, we aimed to determine the protein expression of ERBB network and its prognostic impact in EC. Methods: The study group included 407 consecutive staged I-IV EC patients treated between 2000 and 2010. ERBB1, ERBB2, ERBB3, ERBB4, MYC, PIK3CA, pAKT1 and STMN1 protein expression levels were examined by immunohistochemistry on tissue-microarrays. The results were juxtaposed with survival data. Results: : Out of the studied samples 107 (26%) were classified as ERBB1-positive, 33 (8%) as ERBB2-positive, 143 (35%) as ERBB3-positive and 228 (56%) as ERBB4-positive, 193 (48%) as pAKT1-positive, 96 (24%) as PIK3CA-positive, 233 (57%) as MYC-positive and 49 (12%) as STMN1-positive. Correlations between ERBB2, pAKT1 and STMN1 expression levels were all statistically significant. Positive ERBB2, pAKT1 and STMN1 expression correlated with shorter overall survival (ERBB2: p=0.02, HR= 1.97, 95% CI: 1.10-3.51; pAKT: p=0.09, HR=1.52, 95% CI: 0.94-2.47; STMN1: p=0.01, HR=2.19, 95% CI: 1.17-4.11). ERBB1, ERBB3, ERBB4, PIK3CA and MYC protein expression levels did not affect patients’ outcome. Conclusions: Increased expression of ERBB2, pAKT1 and STMN1 carries negative prognostic information in endometrial cancer. Clinical usefulness of those potential molecular biomarkers requires, however, further studies.
Clinical utility of tumor measurement (TM)-based metrics in phase II (P2) to predict phase III (P3) overall survival (OS) outcomes using the RECIST 1.1 database.
Authors: Sumithra J. Mandrekar, Ming-Wen An, Yu Han, Daniel J. Sargent
Journal: Journal of Clinical Oncology (2014)

6600 Background: While many alternative TM-based metrics to RECIST tumor response (TR) have been proposed, none have replaced TR in practice. The abilities of TR and previously proposed TM-based metrics to predict OS was assessed using simulation studies. Methods: 2,000 randomized P2 trials of 90 to 160 patients were resampled from 2 (lung) negative (-ve) (each with 2 active treatment arms) and 2 (colorectal) positive (+ve) P3 trials for OS. Cox models (landmarked at 12 weeks (w)), adjusted for baseline tumor size (mm) were fit to each P2 trial – Model 1: slope1 (baseline to 6w, mm/w), slope2 (6w to 12w, mm/w) and linear spline terms for +ve slope1 and slope2; Model 2: %change1(%change/w), %change2 (%change/w) and linear spline terms for +ve %change1 and %change2; Model 3: best TR within 12w. The +ve (-ve) predictive value (PPV/NPV), defined as the probability (Pr) of a +ve (-ve) phase II trial (using model predicted risk score differences, 1-sided p=0.20) yielding a +ve (-ve) P3 trial outcome (OS benefit associated with treatment), was calculated across the 2000 P2 trials for a given P3 trial for a range of false +ve (-ve) rates (FPR (FNR)) and Pr(+ve/-ve P3 trial). Results: Compared to TR, the slope and %change P2 models had lower OS prediction error for all P3 trials and better PPV/NPV for all but one P3 trial; however the absolute differences in PPV/NPV/prediction errors were negligible. Conclusions: TR has similar PPV/NPV as the continuous TM-based metrics, and should not necessarily be replaced. Acknowledgement: CA167326. PPV +ve P3 trials FPR Pr(+ve P3 trial) Model 1 Model 2 Model 3 1: treatment (t) vs control (c) 0.1 0.8 0.1 0.4 0.1 0.4 0.240.650.040.19 0.20 0.61 0.03 0.16 0.21 0.61 0.03 0.16 2: t vs. c 0.1 0.8 0.1 0.4 0.1 0.4 0.12 0.44 0.02 0.09 0.15 0.52 0.02 0.12 0.270.690.040.22 NPV -ve P3 trials FNR Pr(-ve P3 trial) Model 1 Model 2 Model 3 3: t1 vs. c 0.1 0.8 0.9 0.6 0.9 0.6 0.990.930.910.63 0.99 0.89 0.86 0.50 0.98 0.85 0.81 0.41 3: t2 vs. c 0.1 0.8 0.9 0.6 0.9 0.6 0.99 0.93 0.90 0.61 0.990.930.910.62 0.98 0.91 0.88 0.56 4: t1 vs c 0.1 0.8 0.9 0.6 0.9 0.6 0.97 0.86 0.82 0.43 0.990.920.890.58 0.98 0.91 0.88 0.55 4: t2 vs c 0.1 0.8 0.9 0.6 0.9 0.6 0.990.920.890.58 0.97 0.86 0.82 0.43 0.98 0.87 0.83 0.45
Development of a patient preference assessment tool for cancer patients considering phase I research.
Authors: Rebecca D. Pentz, Taylor E White, Tehseen Dossul, Kristopher A Hendershot, Margie Dixon, Carolina Salvador, Jeffrey M. Switchenko, Donald Harvey
Journal: Journal of Clinical Oncology (2014)

e17593 Background: We previously developed and tested a tool for physicians (PHY) to assess advanced cancer patients’ treatment-related preferences (Pentz ASCO abstracts 2011, 2012, 2013.) to inform PHY’s recommendation about phase I trial participation. PPAT is a paradigm shift from patient-targeted aids to a PHY tool. This study shortened PPAT to the most informative 8 preferences based on PHY feedback. Methods: 29 PHYs identified the four preferences most indicative that a phase I trial may or may not be in accord with the patient’s preferences. 15 ranked both the negative and positive preferences and 14 ranked either positive or negative. The optimal time in the care continuum to introduce the tool and potential use in patients without a clinical trial option were also assessed. PHY scores were summed for each question and scaled according to the number of PHYs participating. The top 4 preferences were compared to the bottom 12 using a 2-sample t-test, for both the reduction in preferences for or against a clinical trial. Results: We found a statistically significant difference in scaled scores between the top and bottom groups of preferences for or against phase I participation (p<0.05). The four preferences most indicative of clinical trial interest were: fighting my cancer as much as possible, accessing new treatments, helping other cancer patients by participating in research, and accessing the best cancer treatment. The 4 most indicative of lack of interest were: avoiding extra travel and time away from home, avoiding extra procedures, avoiding trial side effects, and avoiding long clinic hours. Most PHYs thought PPAT could be used in oncology patients without a clinical trial option (90%, 28/31) or for non-oncology terminal patients (84%, 26/31). PHYs thought they should introduce PPAT either at exhaustion of standard of care options (26%, 8/31), before presentation of a Phase I trial (32%, 10/31), or the sooner the better (29%, 9/31). Conclusions: PHYs identified 8 items as most indicative of patient clinical trial preference. PHYs judged PPAT useful outside the phase I setting and were split whether to use the tool at the end of standard of care options, before introducing a phase I trial or earlier in care.
Results from the ITP World IMPACT Survey (I-WISh): Patients with Immune Thrombocytopenia (ITP) Experience Impaired Quality of Life (QoL) Regarding Daily Activities, Social Interactions, Emotional Well-Being and Working Lives
Authors: Nichola Cooper, Alexandra Kruse, Caroline Kruse, Shirley Watson, Mervyn Morgan, James B. Bussel, Waleed Ghanima, Donald M. Arnold, Cristina Santoro, Ming Hou, Yoshiaki Tomiyama, Serge Laborde, Barbara Lovrencic, John Waller, Tom Bailey, Gavin Taylor-Stokes, Miona Stankovic, Andrew Provan
Journal: Blood (2018)
Comparison of primary and secondary breast cancer in adolescents and young adults (AYA).
Authors: Melanie Goldfarb, Claire Sadler
Journal: Journal of Clinical Oncology (2014)

9518 Background: Breast cancer is one of the top malignancies in AYA females (ages 15-39) and may develop de novo or in patients previously treated for cancer. This study compares the tumor characteristics, treatment, and overall survival (OS) of primary and secondary (SMN) breast cancers in the female AYA population. Methods: All cases of invasive AYA breast cancer contained in the 1998-2010 American College of Surgeons National Cancer Database were divided into two cohorts according to primary or secondary occurrence. Comparisons using appropriate statistical methods were performed. Results: Of 107,373 cases of invasive breast cancer, 6,241 (6.2%) had experienced a prior malignancy. Compared with cases of primary breast cancer, patients with SMNs were more often non-Hispanics (OR:1.21, CI:1.05-1.40), insured (OR:1.58, CI:1.17-2.14), and aged 35-39 (OR:1.34, CI:1.22-1.46). SMNs were more often ER- (OR:1.23, CI:1.09-1.41), PR- (OR: 1.16, CI:1.02-1.32), microcarcinomas <1cm (OR:2.08, CI:1.89-2.30) with lobular histology (OR:1.35, CI:1.15-1.57) that presented without positive lymph nodes (OR:1.38, CI:1.27-1.51) but with distant metastases (OR: 1.60, CI:1.33-1.93). Matched by stage, SMN patients underwent more total mastectomies but received less chemotherapy, radiation, or hormonal therapy. However, SMN patients received definitive surgical treatment almost twice as fast compared to primary cancers (36.12 vs. 67.26 days, p<0.001). Patients with SMNs had a significantly decreased 3-year OS (79% vs 88.5%, p<0.001) with SMN status as an independent risk factor for decreased OS (HR: 1.69, CI: 1.483-1.93). Conclusions: AYAs with non-primary breast cancer have smaller, more ER-/PR- tumors but undergo more radical surgery with less adjuvant therapy than AYA’s with primary malignancies. SMN status alone is an independent risk factor for decreased OS; AYAs with a breast SMN have almost a 10% lower 3-year OS. Whether the outcome disparity results from previous cancer treatment or differences in biology, environment, or access to care are areas needing further investigation.
Survival Advantage to Allogeneic Transplant in Patients with Myelofibrosis with Intermediate-1 or Higher DIPSS Score
Authors: Krisstina L. Gowin, Karen K. Ballen, Kwang Woo Ahn, Zhen-Huan Hu, Ying Liu, Lucia Masarova, Srdan Verstovsek, Maria Coakley, Tania Jain, Andrew Kuykendall, Rami Komrokji, Martha Wadleigh, Sarah Patches, Murat Arcasoy, Michael Green, Malathi Kandarpa, Moshe Talpaz, Haris Ali, Vikas Gupta, Rebecca Devlin, Laura C. Michaelis, Gabriela S. Hobbs, Brady Lee Stein, Ashley Pariser, Aaron T. Gerds, Kierstin Kuber, Raajit Rampal, Edwin P. Alyea, Uday Popat, Ronald Sobecks, Bart L Scott, Ruben Mesa, Wael Saber
Journal: Blood (2018)
Effect of adjuvant chemotherapy on stage II colon cancer: Analysis of Korean national data.
Authors: Minki KIM, Daeyoun Won, Seong Taek Oh, In Kyu Lee
Journal: Journal of Clinical Oncology (2018)

798 Background: Debates exist regarding the effectiveness of adjuvant chemotherapy for stage II colon cancer. This study aimed to investigate the current status of adjuvant chemotherapy and its impact on survival for Korean stage II colon cancer patients by analyzing the National Quality Assessment data. Methods: A total of 7880 patients who underwent curative resection for stage II colon adenocarcinoma between Jan 2011 and Dec 2014 in Korea were selected randomly as evaluation subjects for the quality assessment. The factors that influenced overall survival were identified. The high-risk group was defined as having at least one of the following: perforation/obstruction, lymph node harvest less than 12, lymphovascular/perineural invasion, positive resection margin, poor differentiation, or pathologic T4 stage. Results: The median follow-up period was 38 (1-63) months. Chemotherapy was a favorable prognostic factor for either the high- (HR 0.50 [0.40-0.62], p &lt; 0.001) or low-risk group (HR 0.74 [0.61-0.89], p = 0.002) in multivariate analysis. This was also the case in patients over 70 years of age. The hazard ratio was significantly increased as the number of involved risk factors was increased in patients who didn’t receive chemotherapy. However, there was no survival difference between low-risk group patients and patients who only had 1 risk factor among patients who received adjuvant chemotherapy (HR 1.19 [0.93-1.52], p = 0.165). Adding oxaliplatin showed no difference in survival (HR 1.36 [0.91-2.03], p = 0.132). Conclusions: Adjuvant chemotherapy can be recommended for stage II colon cancer patients, but the addition of oxaliplatin to the regimen must be selective.
Organ‐on‐a‐Chip for Cancer and Immune Organs Modeling
Authors: Wujin Sun, Zhimin Luo, Junmin Lee, Han‐Jun Kim, KangJu Lee, Peyton Tebon, Yudi Feng, Mehmet R. Dokmeci, Shiladitya Sengupta, Ali Khademhosseini
Journal: Advanced Healthcare Materials (2019)

Bridging the gap between findings in preclinical 2D cell culture models and in vivo tissue cultures has been challenging; the simple microenvironment of 2D monolayer culture systems may not capture the cellular response to drugs accurately. Three-dimensional organotypic models have gained increasing interest due to their ability to recreate precise cellular organizations. These models facilitate investigation of the interactions between different sub-tissue level components through providing physiologically relevant microenvironments for cells in vitro. The incorporation of human-sourced tissues into these models further enables personalized prediction of drug responses. Integration of microfluidic units into the 3D models can be used to control their local environment, dynamic simulation of cell behaviors, and real-time readout of drug testing data. Cancer and immune system related diseases are severe burdens to our health care system and have created an urgent need for high-throughput, and effective drug development plans. This review focuses on recent progress in the development of "cancer-on-a-chip" and "immune organs-on-a-chip" systems designed to study disease progression and predict drug-induced responses. Future challenges and opportunities are also discussed.
Study of oxidative metabolism in blood of vulvar cancer patients.
Authors: Elena Vladimirovna Shalashnaya, Irina Aleksandrovna Goroshinskaya, Galina Andreevna Nerodo, Ekaterina Igorevna Surikova, Ekaterina Alekseevna Nerodo, Polina Sergeevna Kachesova, Ludmila Anatolievna Nemashkalova, Anastasia Victorovna Leonova
Journal: Journal of Clinical Oncology (2014)

e22233 Background: The purpose of the study was to analyze free-radical processes intensity and antioxidant system activity in blood of vulvar cancer patients with primary process. Methods: Light sum of peroxide-induced luminal chemiluminescence, malondialdehyde content, activity of superoxide dismutase, glutathione peroxidase and catalase in blood of 30 women with stage I-III primary vulvar cancer aged 37-87 years (main group) and 30 women without oncopathology aged 34-73 (control group) were studied. Results: Light sum of peroxide-induced luminal chemiluminescence of blood plasma in vulvar cancer patients was 2.8 times higher than in control group. Malondialdehyde content in plasma was 2 times higher than standard values, in red cells 45% higher. At the same time, superoxide dismutase activity decreased by 15.4%, glutathione peroxidase activity in red cells increased by 51.5%, catalase activity in plasma increased by 15% in comparison with the level in the control (p< 0.001-0.05). Conclusions: Vulvar cancer development is accompanied by increase in generation of reactive oxygen species, intensification of lipid peroxidation processes and disbalance in antioxidant enzymes functioning.
Effect of preoperative chemoradiotherapy on DNA-cytometric parameters of pancreas tumors.
Authors: Inna Arnoldovna Novikova, Oleg Ivanovich Kit, Aleksey Yurievich Maksimov, Alexander V. Snezhko, Roman E. Myagkov, Evgeniy N. Kolesnikov
Journal: Journal of Clinical Oncology (2014)

e15212 Background: DNA content in pancreas tumor cells was studied, as well as cell distribution among cellular cycle phases, tumor proliferative activity after preoperative chemoradiotherapy. Methods: The study of newly removed material of 20 patients with neoadjuvant chemoradiotherapy and 20 patients with standard surgical treatment, T2N1Mo-T3N1Mo, mean age 61.3±0.5 years, was done. CycleTEST PLUS DNA Reagent Kit was used for the DNA analysis, mean constant of variation of DNA histograms was 5.7%. ModFit LT program was used for the data processing. Quantity of cells with different DNA content was calculated as percent of total cells studied. Results: Decrease of average content of aneuploid cells in tumor by 1.3 times (from 32.5±2,7% to 24.1±2.2%) was detected during the DNA-cytometric analysis (p≤0,05). Proliferation rate, determined by the quantity of cells in S-phase, slowed by 1.4 (from 9.1±0.4% to 6.6±0.4%) and 1.3 (from 19.7±1.6% to 15.6±1.2%) times after neoadjuvant chemoradiotherapy of diploid and aneuploid tumors, respectively (p<0,05). Proliferation index of diploid tumors decreased by 1.4 times (from 9.2±0.2% to 6.7±0,2%) and that of aneuploid tumors – by 1,2 times (from 30.5±1.6% to 26.2±1.4%) (p<0.05). Tumors with DNA index up to 1,5 were observed 1.5 times more often after chemoradiotherapy, while tumors with DNA index over 1.5 prevailed in the group without the therapy. Conclusions: The analysis of DNA-cytometric parameters of pancreas tumors showed quantitative changes characterizing the decrease of malignant potential under the influence of preoperative chemoradiotherapy.
Predictors of weight gain in breast cancer survivors.
Authors: Iram T. Azam, Virginia G. Kaklamani, Maureen Sadim
Journal: Journal of Clinical Oncology (2014)

1543 Background: Obesity and weight gain are important risk factors in the development of breast cancer. Weight gain in breast cancer patients is associated with a decreased response to adjuvant chemotherapy, increased cancer recurrence, and worse overall prognosis. Recent genomic studies indicate specific single nucleotide polymorphisms (SNPs) of the fat mass and obesity-associated gene (FTO) are associated with obesity and breast cancer risk. Little is known about factors contributing to weight gain in breast cancer patients receiving different treatment regimens. Methods: We performed a prospective cohort study of 120 women recruited from Northwestern University, Robert H. Lurie Cancer Center. Measurements of body mass index, nutritional status, and exercise levels were obtained at baseline and 6 month increments over a 24-month period. Chart review was conducted to obtain demographics, tumor characteristics (ER/PR/HER2 status, tumor size, stage, lymph node metastases), and treatment regimens. Blood samples were genotyped for 4 single nucleotide polymorphisms in FTO. Results: The percentage of patients gaining weight after diagnosis was 45.3% and 60.9% at the 12 and 24 month follow up, respectively. Chemotherapy and endocrine therapy were not associated with weight gain, even after controlling for age, race, baseline BMI, nutritional status, and exercise levels. PR+ patients were more likely to gain weight (p=0.02). FTO SNPs rs9939609 (A/T) and rs1477196 (A/G) were associated with weight gain. Conclusions: The majority of women with breast cancer gained weight after diagnosis, and this was most frequently observed in women with PR+ status and 2 of the identified FTO SNPs. Future studies should explore if the risk for weight gain associated with these factors may be attenuated by specific lifestyle interventions and treatment regimens.
The value of platelet: Lymphocyte ratio in predicting survival in multiple myeloma patients.
Authors: Jean Paul Atallah, Farhan Mohammad, Alina Bhat, Nileshkumar J Patel, Basem Azab, Abhirami Vivekanandarajah, Marcel Odaimi, Terenig O. Terjanian
Journal: Journal of Clinical Oncology (2014)

e19583 Background: Cancer associated inflammation is one of the key determinants of outcome in patients with cancer. An elevated Platelet: lymphocyte ratio (PLR) has been identified as a predictor of worse survival in patients with various solid tumors compared to hematologic malignancies but no reports yet examined its impact on multiple myeloma. The aim of this study was to examine the prognostic value of an elevated PLR in multiple myeloma. Methods: We had approval by our institutional review board to collect the data on patients diagnosed with multiple myeloma at Staten Island University Hospital between year 2000 and 2012 identified from our local cancer database. Data on demographics, conventional prognostic markers, laboratory analyzes including blood count results, and histopathology were collected and analyzed. A cox proportional survival analysis was carried out to assess the relationship between PLR and mortality. PLR was assessed as a continuous variable as well as categorical variable (quartile 4.5-98.2, 100.4-151.7, 152.1-250.8, and 252.2-589.6). Results: A total of 96 patients were identified with a median age at diagnosis of 70 (IQR of 61 to 79) years. The median platelet count was 227 (183.5-308) x 109/liters, median lymphocyte count 1.5 (1.05-2.4) × 10-9/liters, while the PLR was 151.9 (99.3-251.5). The median overall survival was 147.5 weeks, IQR (88.5-320). PLR did not prove to be a significant predictor of death as a continuous variable (0.99 (0.99-1.01), p =0.118). Furthermore, there was no significant difference in survival with any of the quartiles of PLR. Compare to lowest quartile of PLR, Hazards ratio for the consecutive quartiles were 1.14 (0.49-2.65, p=0.76), 1.85 (0.84-4.08, p=0.126) and 0.61 (0.24-1.55, p=0.305). Conclusions: PLR does not appear to offer useful predictive ability for outcome and survival in multiple myeloma patients. Our study is limited with small sample size; further studies are needed to validate our results
Molecular imaging of fibrosis: recent advances and future directions
Authors: Sydney B. Montesi, Pauline Désogère, Bryan C. Fuchs, Peter Caravan
Journal: Journal of Clinical Investigation (2019)

Fibrosis, the progressive accumulation of connective tissue that occurs in response to injury, causes irreparable organ damage and may result in organ failure. The few available antifibrotic treatments modify the rate of fibrosis progression, but there are no available treatments to reverse established fibrosis. Thus, more effective therapies are urgently needed. Molecular imaging is a promising biomedical methodology that enables noninvasive visualization of cellular and subcellular processes. It provides a unique means to monitor and quantify dysregulated molecular fibrotic pathways in a noninvasive manner. Molecular imaging could be used for early detection, disease staging, and prognostication, as well as for assessing disease activity and treatment response. As fibrotic diseases are often molecularly heterogeneous, molecular imaging of a specific pathway could be used for patient stratification and cohort enrichment with the goal of improving clinical trial design and feasibility and increasing the ability to detect a definitive outcome for new therapies. Here we review currently available molecular imaging probes for detecting fibrosis and fibrogenesis, the active formation of new fibrous tissue, and their application to models of fibrosis across organ systems and fibrotic processes. We provide our opinion as to the potential roles of molecular imaging in human fibrotic diseases.