tbuckley/cabot-search huggingface dataset:
Correlation of tumor marker levels with intensity of FDG uptake on PET imaging in epithelial cancers.
Authors: Dilsa Mizrak, Mine Araz, Hakan Akbulut, Nuriye Ozlem Kucuk, Ali Alkan, Suayip Yalcin, Fikri Icli
Journal: Journal of Clinical Oncology (2014)

e14625 Background: FDG does not enter metabolic processes in contrast to normal glucose and trapped within the cell and its uptake show a correlation with tumor aggressiveness. Tumor markers are commonly used for surveillance of metastatic epithelial tumors but there is no consensus about the timing of PET imaging. We investigated the relationship between tumor marker and FDG intensity in metastatic epithelial cancers. Methods: All metastatic patients with colorectal, breast and over cancer treated in Ankara University Medical Oncology Department between January 2010 and November 2013 were retrospectively evaluated. Metastatic patients who had a PET imaging and tumor marker measurement within 7 days were included in the study. Metastatic lesions with SUV max values over 3 g/dL was regarded as PET positive. Results: A total of 131 breast cancer, 56 ovarian cancer and 169 colorectal cancer patients were included in the study. Median age was 55.3 year(18-84year). Of breast cancer cases 29.8% had an abnormal (≥30ng/ml) CA 15-3 level, and 65.6% had a high FDG (≥3g/dL) intensity. Of patients within a normal CA 15-3 level, FDG intensity was pathologic in 56.3% of patients whereas in patients with a high level CA 15-3 FDG intensity was high in 94.6% of patients (p=0.0001). In ovarian cancer patients CA 125 was high (≥35ng/ml) in 60.7% of patients and 88.2% of this population had a high FDG uptake, whereas FDG uptake was pathologic in only 54.5% of patients with a normal CA 125 level (p=0.004). In patients with colorectal cancer CEA level was high in 42% and FDG uptake was pathologic in 76.3%. In patients with a normal level CEA, 64.3% had ahigh FDG uptake whereas FDG uptake was significantly high (93%) in patients with an elevated CEA level (p=0.0001). Conclusions: Our results suggest that there is a high correlation between tumor marker level and FDG intensity in epithelial tumors. PET Imaging seems to be more helpful in patients with elevated tumor marker.
Implication of polymorphisms in the promoter region of apoptosis-related genes in survival of gastric cancer patients.
Authors: Jinfei Chen, Dongying Gu, Zhi Xu
Journal: Journal of Clinical Oncology (2014)

e15062 Background: The FAS, FAS ligand (FASL) and CASP8 are key regulators for apoptosis and their deregulations play an important role in carcinogenesis. However, the effects of promoter polymorphisms of the FAS, and FASL, and CASP8 genes on the development of gastric cancer are unknown. Methods: In this study, we investigated the association of four polymorphisms (FAS -1377G>A, -670A>G, FASL -844C>T, and CASP8 -652 6N ins>del) with the clinical outcome of 940 gastric cancer patients in a Chinese population. The correlation between genotype and survival outcomes was assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. Results: Our results revealed that individuals with CASP8 -652 6N ins/del + del/del genotypes had a decreased risk of death compared to those with ins/ins genotype [Log-rank P = 0.005; Hazard Ratio (HR) = 0.75, 95% confidence interval (95%CI) = 0.62-0.92]. The protective effect of del allele was further confirmed in subgroups of patients with tumor size ≤ 5 cm (0.66, 0.50-0.86) and T2 depth invasion (0.59, 0.37-0.94), but no significant association observed in subgroups of lymph node metastasis (0.67, 0.47-0.97), distance metastasis (0.73, 0.60-0.90) and chemotherapy (0.73, 0.58-0.93). Conclusions: Our findings suggest that the CASP8 -652 6N ins>del polymorphism may serve as a promising genetic marker for gastric cancer prognosis in the Chinese population.
The Novel Small Molecule Inhibitor KS99 Targets AML and Inhibits Stemness Markers STAT3 and ALDH
Authors: Charyguly Annageldiyev, Krishne Gowda, Dhimant Desai, Viola Devine, Daniel Brosius, Chandrika Gowda, Sinisa Dovat, Shantu Amin, David F. Claxton, Arati Sharma
Journal: Blood (2018)
Absence of occult micrometastases in histologically negative lymph nodes among patients with distant recurrent endometrial cancer.
Authors: Amanda Lynn Jackson, Avani Pendse, Megan J. DiFurio, Emily C. Ko, John T. Soper
Journal: Journal of Clinical Oncology (2014)

5606 Background: Lymph node metastasis is a criterion for adjuvant therapy in endometrial cancer (EC). The incidence of immunohistochemical (IHC) stain-positive micrometastases in H&E-negative lymph nodes is low in surgically staged EC. Ultrastaging, however, is used to detect low volume disease in sentinel lymph node dissection. Our goal was to determine the frequency of occult micrometastases in histologically negative lymph nodes in patients who have distant recurrent endometrial cancer. Methods: The records of patients diagnosed with endometrial cancer from 2005 to 2010 were reviewed. Twenty patients that were previously reported to be negative for lymph node metastases using conventional histologic analysis presented with distant recurrent high-grade endometrioid adenocarcinoma. All nodal tissue was submitted for review and ultrastaging with H&E and IHC staining to detect micrometastasis. Two pathologists interpreted slides and positive IHC staining for micrometastases was defined as positive staining of cells <2 mm in greatest dimension. Results: 1063 patients underwent surgery for endometrial cancer. Twenty patients with early stage, high-grade node negative endometrioid cancers presented with a distant recurrence to sites other than isolated vaginal, pelvic or retroperitoneal sites; 2 patients were excluded secondary to unavailable pathologic samples. The histological grade was 2 in 9 patients and 3 in 9 patients. Nine patients had Stage IA disease, 6 Stage IB, and 3 Stage II. 536 lymph nodes were reviewed from the cohort of 18 patients; the median number of lymph nodes per patient was 27.5(10-52). No micrometastases were identified in any of the lymph nodes. Conclusions: It was previously shown that the incidence of IHC stain-positive micrometastases in H&E-negative lymph nodes is low in surgically staged endometrial cancers. Our study shows that in patients with a distant recurrence the incidence remains very low, suggesting alternative routes of metastasis for these patients and questions the utility for ultrastaging in sentinel lymph nodes to predict distant recurrences.
Development and Validation of a High Risk Multiple Myeloma Gene Expression Index from RNA Sequencing: An Mmrf Commpass Analysis
Authors: Daniel Penaherrera, Sheri Skerget, Austin Christofferson, Jessica Aldrich, Sara Nasser, Christophe Legendre, Martin Boateng, Lori Cuyugan, Jonathan Adkins, Erica Tassone, Jennifer Yesil, Daniel Auclair, Winnie Liang, Sagar Lonial, Jonathan J Keats
Journal: Blood (2018)
The subjective quality of life of young patients with breast cancer and their partners.
Authors: Laurence Vanlemmens, Veronique Christophe, Christelle Duprez, Anne Congard, Anne Lesur, Catherine Loustalot, Cecile Guillemet, Monelle Leclercq, Pascal Antoine
Journal: Journal of Clinical Oncology (2014)

9569 Background: The subjective experience of young breast cancer (BC) women has some specifics related to the impact of illness and treatments on the issues specific to their age. The partner is most often the primary caregiver and is himself affected by the disease. A better understanding of couples facing cancer at every stage of treatment program appears crucial to improve the overall care. This study aims to better understand the quality of life of these young couples (women <45 at diagnosis), by comparing the subjective experience of patients and partners from chemotherapy (CT) to the end of treatments period. Methods: 491 couples in which the woman has non-metastatic BC (28.7% under CT, 10.2% under Trastuzumab, 33% under hormone therapy, 28.1% under supervision) completed a self-administered questionnaire assessing their subjective experience. Results: Patients report more difficulties than partners in terms of management of children and of everyday life, body image and sexuality, career management and financial difficulties. The 2 groups were comparable with regard to the feeling of couple cohesion and the deterioration of relations with relatives. In addition, patients reported more support from relatives than partners, but this support decreases along the treatment program. While overall, patients undergoing CT and Trastuzumab and their partners reported more difficulties than those under hormone therapy or under surveillance, the negative affectivity / apprehension for the futureremains stable and relatively high from CT to the end of treatment, for the patient as well as for her partner. Conclusions: The difficulties of patients appear to be particularly strong in the early course of care and decrease over time, indicating a gradual adjustment to the disease. It is the same for partners, who also have concerns. However, there are differences between the experience of patients and partners. A longitudinal follow-up assessing the couple experience in a dyadic design would allow us to support these findings, and ultimately to better assess the couples’ needs in order to better respond to it by an optimal care management, including the establishment of follow-up consultations for couples.
Adding VEGFR-TKIs to chemotherapy and/or hormonal therapy in advanced breast cancer patients: Results of a meta-analysis.
Authors: Yucai Wang, Zexing Wang, Victor Tsu-Shih Chang, Xiaoxiang Guan
Journal: Journal of Clinical Oncology (2014)

1052 Background: The addition of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) to chemotherapy and/or hormonal therapy for advanced breast cancer management remains controversial. We reviewed data from RCTs and conducted a meta-analysis to systematically evaluate the benefits and risks of adding VEGFR-TKIs therapy to standard treatment for advanced breast cancer. Methods: PubMed, Web of Science and ASCO and ESMO databases were searched. Eligible studies were RCTs that compared treatment outcomes (OS, PFS and/or TTP) of standard therapy with or without addition of VEGFR-TKIs in advanced breast cancer. Study endpoints included OS, PFS, and grade 3 or above adverse events (AEs). Pooled HRs for survival outcomes and RRs for dichotomous data with 95% CI were calculated using comprehensive meta-analysis (v2). Results: Nine eligible trials comprising a total of 2,206 patients were identified. VEGFR-TKIs included sorafenib (3), sunitinib (2), vandetanib (2), axitinib (1), and motesanib (1), and standard therapies included paclitaxel (2), docetaxel (3), gemcitabine (2), capecitabine (2), and fulvestrant (1). The addition of VEGFR-TKIs did not improve OS (HR 1.01; 95% CI 0.88-1.16, P = 0.889) or PFS (HR 0.87; 95% CI 0.72-1.03, P = 0.109). However, adding VEGFR-TKIs increased the risk of hypertension (RR 3.38; 95% CI 1.37-8.30, P = 0.008), rash (RR 2.64; 95% CI 1.14-6.14, P = 0.024), hand-foot syndrome (RR 4.73; 95% CI 1.33-16.81, P = 0.016), and mucosal inflammation (RR 2.41, 95% CI 1.10-5.28, P = 0.028), but not the risk of vomiting, diarrhea or neutropenia. Conclusions: Our meta-analysis demonstrates that adding VEGFR-TKIs to standard treatment in advanced breast cancer did not improve treatment outcomes, and increased the risk of certain severe AEs, such as hypertension, rash, and hand-foot syndrome and mucosal inflammation. Because of patient and treatment heterogeneities among the trials, eg., ER/PR/HER2 status, locally advanced vs. metastatic, first vs. any line of therapy, additional studies are needed to further evaluate the efficacy of VEGFR-TKIs in advanced breast cancer.
Case control study to identify the risk factors for development of lymphoma in patients with hepatitis C infection.
Authors: Josy Mathew, Surbhi Shah, David Zaun
Journal: Journal of Clinical Oncology (2014)

e19519 Background: Multiple studies have demonstrated an increased risk of lymphoid malignancies in patients with hepatitis C infection. It is clear that not all patients with hepatitis C infection will develop lymphoma. The risk factors in patients with hepatitis C infection for the development of lymphoid malignancies are unknown. Methods: We conducted a hospital based case control study to identify the risk factors for the development of lymphomas in patients with hepatitis C infection. The cases consisted of all the patients treated in the Hennepin County Medical Center, cancer center with a diagnosis of any type of lymphoma and had a hepatitis C diagnosis from 2004 to 2011 (35 patients). Two patients with Hepatitis C infection matched to each of the cases for age, sex and within a calendar year of diagnosis of Hepatitis C infection were the controls (70 patients). A conditional logistic regression model was performed to predict patient development of lymphoma. Results: Based on univariate analyses, it appeared that lymphadenopathy, anemia, grade 2, 3, and 4 fibrosis of the liver, and grade 2, 3, and 4 activity in the liver could all be risk factors. When including these factors in a conditional logistic regression model, we found Lymphadenopathy (odds ratio: 71.3, CI: 7.477, 680.0: P <0.0001) and Anemia (odds ratio: 4.8: CI: 0.987, 23.290: P = 0.052) to be significant risk factors. A trend was noted for the reduction of risk of lymphoma development in patients who had been treated for Hepatitis C in the past. However it did not achieve statistical significance.Ethnic origin, genotype of hepatitis C, cytopenias other than anemia, Child- Pugh score, a diagnosis of cirrhosis, Alpha Fetoprotein level and hepatitis C DNA titers were not found to be significant risk factors. There was no significant difference in overall survival between the cases and controls. Conclusions: Lymphadenopathy, anemia, and advanced activity and fibrosis in the liver are risk factors for development of lymphoma in patients with hepatitis C infection. It will be valuable to investigate whether treatment for hepatitis C will reduce the risk of lymphoma in a larger trial.
Marizomib activity as a single agent in malignant gliomas: Ability to cross the blood brain barrier.
Authors: Daniela Annenelie Bota, Frank Pk Hsu, Kaijun Di, Vivek Abraham, Naomi Lomeli, G. Kenneth Lloyd, Francis Burrows, Annick Desjardins, Mohit Trikha
Journal: Journal of Clinical Oncology (2015)

e12644 Background: Glioblastoma (GBM) is a highly aggressive brain tumor which displays innate resistance to multiple treatment modalities. Previous studies have shown that the proteasome plays a vital role in the physiology of GBM, and that proteasome inhibition can be used as a strategy for treating malignant gliomas. Marizomib is a second generation irreversible proteasome inhibitor which has a more lipophilic structure, suggestive of potential for penetration of the blood brain barrier (BBB), and has a broader and more prolonged inhibition proteasome inhibition profile than bortezomib and carfilzomib, the two proteasome inhibitors approved for treatment of multiple myeloma. While bortezomib and carfilzomib have little-no activity against malignant gliomas, marizomib could be a novel therapeutic strategy for primary brain tumors. Marizomib is presently in clinical trial for multiple myeloma. Methods: The in vitro antitumor activity of marizomib was studied in human glioma lines U251 and D54. The ability of marizomib to cross the BBB and regulate proteasome activities was evaluated in cynomolgus monkeys and rats. The anti-tumor effect of marizomib in vivo was tested in an orthotopic xenograft model of human GBM. Results: Marizomib inhibited survival of U251 and D54 by ~90% at 60nM and markedly decreased GBM cell migration and invasion. While marizomib induced increased free radical production and apoptosis, the reactive oxygen species quenching agent NAC blocked these effects. In rats, marizomib distributed into the brain at 30% of blood levels, and the monkey studies revealed robust baseline chymotrypsin-like (CT-L) proteasome activity in brain tissue that was significantly inhibited ( > 30%) in animals treated with marizomib. Similar effects were seen against the caspase-like activity. Encouragingly, mice treated with marizomib survived significantly longer than the control animals (p< 0.05). Conclusions: These preclinical studies demonstrate that marizomib can cross the BBB and inhibit proteasome activity in primate brain, and elicit a significant anti-tumor effect in a rodent intracranial model of malignant gliomas. Marizomib is in Phase 1 clinical testing for malignant gliomas.
Expressions of EGFR, HER2, and HER3 and their correlations with clinical characteristics in oropharyngeal squamous cell carcinoma (OPSCC).
Authors: Nabil F. Saba, Guoquing Qian, Jiang Ning, Sungjin Kim, Zhengjia Chen, Gabriela Garcia, Gavin MacBeath, Dong Moon Shin, Fadlo Raja Khuri, Zhuo Georgia Chen
Journal: Journal of Clinical Oncology (2014)

6068 Background: Epithelial growth factor receptor (EGFR) is overexpressed in squamous cell carcinoma of the head and neck (SCCHN) and is a therapeutic target for this disease. Since other members of the HER receptor family may be valid therapeutic targets in SCCHN we examined the expressions of EGFR, HER2, and HER3 and correlated their expression with clinical patient characteristics. Methods: After IRB approval 96 patients with OPSCC had tissue and clinical information collected and analyzed. Tissue microarray stained by immunofluorescence (IHF) was used to evaluate HER receptor expression. High risk HPV status and p16 status were determined by HPV DNA in situ hybridization (ISH) and immunohistochemistry (IHC) staining, respectively. The correlation with clinical characteristics of each receptor and their effects on disease-free survival (DFS) or overall survival (OS) were assessed. Results: p16 status was inversely correlated with EGFR expression (P=0.012), whereas no significant association between p16 status and HER2 or HER3 expression was found (P= 0.563 and 0.635, respectively). Current smokers had the highest EGFR expression compared to never or former smokers (P= 0.006). Patients with T3 and T4 disease had a higher EGFR expression compared to T1 and T2 disease (P= 0.040). HPV negative smokers had a significantly higher HER2 (P = 0.043) and HER3 expression (P = 0.019) compared to non-smokers. Among patients with low EGFR expression, HPV negative patients had a higher HER3 expression compared to HPV positive patients (P = 0.048). Patients with high EGFR expression were more likely to have disease progression (HR: 1.58; 95% CI: 1.13 – 2.20; P= 0.007) or death (HR: 1.30; 95% CI: 1.01 – 1.68; P=0.042). HER2 or HER3 expression were not related to DFS or OS in OPSCC. Conclusions: EGFR was a prognostic factor for worse DFS and OS in OPSCC. Among patients with low EGFR expression HER3 expression was higher in HPV negative patients. These findings may point to a role for combined EGFR and HER3 targeted therapy in HPV negative disease, but will need to be confirmed in other studies. (This study was supported by a grant from Merrimack Pharmaceuticals to NFS and GZC).
Transcriptomics in Multiple Myeloma Demonstrates an Association between Survival and Expression of T Cell Co-Signaling Ligands in Bone Marrow Derived Myeloma Plasma Cells
Authors: Pim Mutsaers, Rowan Kuiper, Dora Hammerl, Mark van Duin, Bronno Van Der Holt, Sonja Zweegman, Walter M Gregory, Jan J Cornelissen, Annemiek Broyl, Reno Debets, Pieter Sonneveld
Journal: Blood (2018)
Risk of Depression and Anxiety in Adults With Cerebral Palsy
Authors: Kimberley J. Smith, Mark D. Peterson, Neil E. O’Connell, Christina Victor, Silvia Liverani, Nana Anokye, Jennifer M. Ryan
Journal: JAMA Neurology (2018)

Cerebral palsy (CP) is considered a pediatric condition despite most individuals with CP living into adulthood. Thus, there is a lack of evidence in adults with CP, which includes a paucity of research examining mental health in this population.To determine the risk of depression and anxiety in adults with CP compared with an age-, sex-, and practice-matched reference group of adults without CP, using primary care data.Retrospective longitudinal cohort study set in UK primary care. Data were analyzed using Cox proportional hazards regression analyses adjusted for chronic conditions and visits to their physician. The study period ran from January 1987 to November 2015. Data of entry into the study ranged from January 1987 to September 2015. Data for 1705 adults 18 years or older with CP and 5115 matched adults without CP were extracted. Cerebral palsy was identified using diagnostic codes, and each person with CP was compared with 3 age-, sex-, and practice-matched controls.Diagnosis of CP, with a second analysis accounting for comorbidity of intellectual disability (ID).Time to diagnosis for depression or anxiety following the date of entry into the study in adults with CP (with and without ID) compared with matched controls.The mean (SD) age of the 1705 patients with CP and the 5115 adults without CP was 33.3 (15.5) years, and 798 participants (46.8%) were women. Individuals with CP had an increased adjusted hazard of depression (hazard ratio [HR], 1.28; 95% CI, 1.09-1.51) and anxiety (HR, 1.40; 95% CI, 1.21-1.63) compared with the matched reference group. When we accounted for ID comorbidity, there were 363 adults with CP who also had ID (mean [SD] age, 32.1 [13.2] years; 159 women [47.6%]) and 1342 adults with CP who did not have ID (mean [SD] age, 33.6 [16.1] years; 639 women [43.8%]). Only those individuals with CP and no comorbid ID had a higher risk of incident depression (HR, 1.44; 95% CI, 1.20-1.72) and anxiety (HR, 1.55; 95% CI, 1.28-1.87) than their matched controls.Adults with CP have an increased risk of depression or anxiety. In particular, these results indicate that this association is driven largely by those individuals with CP with no co-occurring ID. Future work is needed in community-based samples to fully elucidate the causal mechanisms driving these associations.