tbuckley/cabot-search huggingface dataset:
A prospective study to evaluate the role of procalcitonin in differentiating bloodstream infections from non-infectious fevers among patients with lymphoma.
Authors: Xiao Jun Wang, Alexandre Chan, Vivianne Shih, Thuan Tong Tan, Soon Thye Lim, Farid Mohamad, Miriam Tao, Richard Hong Hui Quek, Tiffany Pool Ling Tang
Journal: Journal of Clinical Oncology (2016)

e19076 Background: Patients with lymphoma experience fevers due to infections (with or without bacteremia), malignant fever or as a complication of cancer treatment. This study was designed to evaluate the role of procalcitonin (PCT) in differentiating bloodstream infections (BSI) from non-infectious fever (NIF) among patients with lymphoma. Methods: Patients with lymphoma and fever ( > 38°C for 2 readings an hour apart or ≥ 38.3°C) were prospectively recruited between August 2014 and November 2015. PCT was measured within 24 hours of fever onset (PCT1) and 24 to 72 hours thereafter (PCT2). The higher PCT value between PCT1 and PCT2 was also documented (PCTmax ). Study subjects were classified into 3 categories: (i) BSI i.e., presence of bacteria or fungus in blood cultures (BC); (ii) Local infections (LI) i.e., clinical evidence of infection without bacteria or fungus in BC; (iii) NIF i.e., absence of clinical or radiological evidence of infection including those with malignant fever and subjects with drug-induced pneumonitis. PCT were compared between these 3 categories, and the optimal PCT cut-off to predict BSI was evaluated by using the receiver operating characteristic (ROC) curve. Results: One hundred and eight eligible cases were included, with 13 cases diagnosed with BSI, 82 with LI and 13 with NIF. PCTmax was statistically different among these three groups (p = 0.006), and patients with BSI had higher PCTmax than those with NIF (median PCTmax : 1.10 ng/mL vs. 0.19 ng/mL; p = 0.004 post hoc testing). PCTmax was not statistically different between patients with BSI and those with LI (median PCTmax : 1.10 ng/mL vs. 0.37 ng/mL; p = 0.069). A PCTmax cut-off of > 0.475 ng/mL predicted for BSI, with a sensitivity of 76.9% and a specificity of 58.9%. Neither PCT1 (p = 0.297) nor PCT2 (p = 0.051) were statistically different among these three groups. Conclusions: PCTmax can differentiate between patients with BSI and those with NIF among patients with lymphoma.
Genomic characterization of malignant pleural mesothelioma and associated clinical outcomes.
Authors: Paul Markowski, Joseph Aisner, Salma Jabbour, Subhajyoti D De, Shridar Ganesan, Jyoti Malhotra
Journal: Journal of Clinical Oncology (2018)

e20555 Background: Malignant pleural mesothelioma (MPM) is a rare malignancy with a poor prognosis. While treatment with pemetrexed and platinum based chemotherapy is the standard of care, many patients develop rapid progression of disease with a median overall survival of ~12 months. New approaches to therapy are needed, but data on the genomic alterations associated with MPM and their clinical correlation to outcomes remains limited. Methods: We report genomic alterations and associated clinical data for 15 patients with advanced/metastatic MPM whose tumors underwent next-generation sequencing. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Results: Median age at diagnosis was 72 years (range 54-84), 57% were male. The most common genomic alterations in the 15 patients were NF2 (47%), BAP1 (47%), CDK2A/B (40%), TP53 (33%), ATM (27%) and SETD2 (13%). The median overall survival (OS) in the 15 patients was 10.1 months. When stratified by mutational status, patients had better OS if they had NF2 (14.3 vs 7.1 months) or BAP1 (10.5 vs 7.1 months) alterations and worse survival if they had CDK2A/B (5.7 vs 10.8 months) or SETD2 (7.1 vs 10.8 months) alterations. Median PFS for patients with advanced/metastatic MPM treated with chemotherapy was 4.8 months. Patients with NF2 (4.8 vs 2.2 months) and BAP1 (4.8 vs 3.8 months) alterations experienced longer PFS, while those with CDK2A/B (2.2 vs 5.0 months) and TP53 (3.8 vs 4.8 months) had a shorter PFS. The overall response rate for these patients was 67%, with NF2 (100% vs 40%) and BAP1 (75% vs 60%) alterations having higher response rates. Conclusions: While the small number of cases precludes definitive conclusions, our study suggests that NF2 and BAP1 alterations confer a better prognosis and response to chemotherapy. Conversely, our study further suggests that CDK2A/B and TP53 alterations are associated with a poor response to chemotherapy. Recognition of prognostic genomic signatures may allow those patients with adverse signatures an opportunity to start with alternative therapy choices such as immunotherapy or enroll on a clinical trial. Further studies to correlate genomic profiles with clinic outcomes are warranted.
Targeting epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 expressing bladder cancer using combination photoimmunotherapy (PIT).
Authors: Mohammad rashid Siddiqui, Reema S. Railkar, Thomas Sanford, Peter L. Choyke, Hisataka Kobayashi, Piyush K. Agarwal
Journal: Journal of Clinical Oncology (2017)

e16026 Background: Bladder cancer (BC) is heterogeneous, expressing various cell surface targets, such as EGFR and Her2. Photoimmunotherapy (PIT) involves antibodies (Abs) conjugated to a photoabsorber (PA), IR Dye 700Dx, and then activated by Near infra-red light (NIR) to specifically target tumors. Our lab has previously shown that tumors expressing high levels of EGFR can be efficiently targeted with PIT. However, PIT is less effective when a tumor lacks “overwhelming” expression of a single target. Here, we present a novel, combinatorial PIT approach for such tumors expressing EGFR and Her2, using Panitumumab-IR700 (PanIR700) and Trastuzumumab-IR700 (TraIR700) antibodies, respectively. Methods: BC cell lines were analyzed for expression of EGFR and Her2 using flow cytometery. Concurrent and optimal binding of both PA-labeled Abs were determined using flow cytometery. NIR LD 50 of multiple treatment regimens were determined to analyze in vitro efficacy of combination PIT. Results: The SW780 and RT112 cell lines showed low to moderate expression of EGFR and Her2. The EGFR expression was 143 fold higher in SW780 and 83 fold higher in RT112 over the isotype control. The Her2 expression was 42 fold higher in SW780 and 27 fold higher in RT112 over the isotype control. Hence, the ratio of cell surface EGFR to Her2 expression in both cell lines was about 3:1. For SW780, NIR LD 50 was 28.66 J/cm 2 for the combination PIT compared to 71.55 J/cm 2 for the PanIR700 alone therapy. The NIR LD 50 for RT112 was 14.66 J/cm 2 for the combination PIT, with LD 50 for PanIR700 alone therapy indeterminate from insufficient cell death. In both cases, the LD 50 for TraIR700 alone therapy could not be determined from lack of sufficient cell death. Conclusions: PIT is a new targeted treatment for bladder cancer that can be effectively used either locally or for metastatic lesions accessible by the NIR light. We demonstrate a novel and promising approach to treating BC by selectively inducing cell death in BC cell lines with low to moderate expression of cell surface markers of EGFR and Her2 using combination PIT. This will be further evaluated in a xenograft model.
miRNA profiling in a case: Control study of African American women with uterine serous carcinoma (USC).
Authors: Larissa Janeen Lee, Brooke E. Howitt, Wojciech Fendler, Konrad Stawiski, Paula Bu, Linda Cho, Dipanjan Chowdhury, Ursula A. Matulonis, Panagiotis A. Konstantinopoulos
Journal: Journal of Clinical Oncology (2017)

e17116 Background: USC is an aggressive subtype of endometrial cancer associated with worse outcomes in African American patients. We evaluated differences in tumor miRNA expression by race, clinical and tumor characteristics, and survival outcomes. Methods: FFPE tumor tissue from hysterectomy specimens was identified for 29 African American cases. Case matching was performed by computer-based random assignment in a 1:1 ratio with Caucasian controls based on age ( &lt; 70 vs. ≥70 years), stage (FIGO I/II vs. III/IV) and histologic subtype (pure vs. mixed). RNA was extracted from 77 specimens with sufficient tumor cellularity (54 tumors and 23 matched normal endometrium). miRNA array profiling was performed by microRNA Hi-Power Labeling (Hy3/Hy5) and hybridization to miRCURY LNA microRNA Array 7 th Gen (Exiqon, Denmark). Analysis was performed with R/Bioconductor using a moderated t-statistic with multiple testing correction. Validation was done using the TCGA dataset. Results: Clinical and treatment characteristics were similar for cases and controls, although use of adjuvant radiation was less common in African Americans (p = 0.03). With a median follow-up of 43 months, 17 patients had recurrent or progressive disease. DFS and OS rates were similar by race (both logrank p &gt; 0.5). Of 968 miRNAs analyzed, 649 were differentially expressed in normal endometrium vs. tumor. When compared by race, histologic subtype, stage or presence of LVI, no differentially expressed miRNAs were identified. In patients with disease recurrence at 3 years, miR-223 was significantly upregulated (fold change 1.5; p = 0.002). In validation using a TCGA dataset of 131 patients with mixed (n = 22) or pure serous (n = 109) histology, increased miR-223 expression ( &gt; median) was associated with worse overall survival (HR 2.47; 95%CI 0.9-6.6). After adjustment for patient age and BMI, upregulation of miR-223 was a significant risk factor for death (adjusted HR 2.94; 95%CI 1.01-8.52). Conclusions: Upregulation of miR-223 was associated with disease recurrence in a cohort of women with uterine serous carcinoma and validated by TCGA data. miRNA profiling did not identify biological differences between African American and Caucasian patients.
Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia
Authors: Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith J. August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). Patients and Methods: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN). Results: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders (N = 8; 74% and 104% higher geometric mean Cmax and AUC0-28d, respectively) with persistence measurable beyond 2 years in responding patients. Cmax increased with occurrence and severity of cytokine release syndrome (CRS). Tisagenlecleucel continued to expand and persist following tocilizumab, used to manage CRS. Patients with B-cell recovery within 6 months had earlier loss of the transgene compared with patients with sustained clinical response. Clinical responses were seen across the entire dose range evaluated (patients ≤50 kg: 0.2 to 5.0 × 106/kg; patients &amp;gt;50 kg: 0.1 to 2.5 × 108 CAR-positive viable T cells) with no relationship between dose and safety. Neither preexisting nor treatment-induced antimurine CAR19 antibodies affected the persistence or clinical response. Conclusions: Response to tisagenlecleucel was associated with increased expansion across a wide dose range. These results highlight the importance of cellular kinetics in understanding determinants of response to chimeric antigen receptor T-cell therapy.
Quality of life (QoL) in older patients (pts) with cancer and prognostic factors for QoL decline.
Authors: Lore Decoster, Chantal Quinten, Cindy Kenis, Johan Flamaing, Philip R. Debruyne, Inge DeGroof, C. N. J. Focan, Frank Cornelis, Vincent Verschaeve, Christian Bachmann, Dominique Bron, Sylvie Luce, Gwenaelle Debugne, Heidi Van Den Bulck, Jean Charles. Goeminne, Dirk L. Schrijvers, Jean Pierre Lobelle, Michelle Lycke, Koen Milisen, Hans Wildiers
Journal: Journal of Clinical Oncology (2018)

10010 Background: QoL is an important outcome parameter for older pts with cancer. This study aims to investigate baseline QoL and its evolution during treatment in older pts with cancer and to determine prognostic factors for QoL decline. Methods: A prospective Belgian multicentre (n = 22) study was performed. Pts ≥70 years with a malignant tumor and abnormal G8 screening tool (≤14/17) underwent geriatric assessment (GA) and baseline QoL evaluation using the European Organization for Research and Treatment Quality of Life Questionnaire core 30 (EORTC QLQ-C30) Global Health Status Scale, with follow up at 2-3 months. QoL change was defined as the difference between follow-up and baseline QoL score and categorized in three groups: decline ( < -10), improvement ( > 10) and no change (≥-10 and ≤10). Uni- and multivariate regression was performed to determine factors associated with baseline QoL and with QoL decline (level of significance at p = 0.05). Results: 3673 pts with abnormal G8 and QoL data available at both time points were included in the present analysis. In multivariate analysis, baseline QOL was significantly worse with decreasing age, poor ECOG-PS (≥2 vs 0/1), higher stage (reference stage I) and abnormal geriatric domains such as functional status by instrumental activities of daily living, pain, fatigue, mental status and nutritional status. Pts with tumors of the digestive system, gynaecological system and thorax presented statistically lower baseline QoL compared to pts with breast cancer, (reference group) (p = 0.030; p = 0.017 and p = 0.017 respectively). During the course of treatment (n = 2972), an improvement in QoL was observed in 1037 pts (35%) and a decline in 838 pts (28.2%). In multivariate analysis, stage, baseline pain and fatigue, malnutrition and absence of comorbidities were prognostic for QoL decline Conclusions: Our study demonstrates that QoL improves in 1/3 of older pts with cancer during treatment, indicating that these pts can benefit from cancer treatment. On the other hand, QoL declines in 1/4 of older pts during cancer treatment and we identified prognostic factors for QoL decline in these pts. Directed interventions against pain, fatigue and malnutrition may subsequently improve QoL for these pts.
Effect of night shift work on the risk of multiple primary cancers in men.
Authors: Xuelei Ma
Journal: Journal of Clinical Oncology (2018)

e13556 Background: In recent decades, an increasing number of male workers are being exposed to night shift work. Previous evidence reported a potential link between night shift work and increased cancer risk such as prostate cancer and colorectal cancer. Methods: Here in our work, a total of 13 cohort studies, 3 case-control studies and 2 nested case-control studies including 22,748 cases and 2,572,287 participants were enrolled to evaluate the association between long-term night shift work and the risks of common cancers at different anatomic sites among men. Results: Our study found that night shift work slightly increased the overall cancer risk in men (OR = 1.33; 1.20, 1.46; P< 0.05), especially prostate cancer (OR = 1.24; 1.05, 1.46; P< 0.05). Furthermore a dose-response meta-analysis was conducted, which showed that cancer risk gradually increased with the accumulation of night-shift years. For every 5 years of night shift work, cancer risk increased by 24.9% (OR = 1.249; 1.146, 1.361; P< 0.05). No potential publication bias (P> 0.05) was observed. Conclusions: In conclusion, night shift work was associated with increased cancer risk of men in a dose-response way. Further researches are of great necessity to update the association and explore its biological mechanisms.
Assessment of dysgeusia and taste identification in patients undergoing chemotherapy for breast cancer.
Authors: Sayaka Kuba, Rie Fujiyama, Kosho Yamanouchi, Chika Sakimura, Toshiko Hatachi, Megumi Matsumoto, Hiroshi Yano, Kazuma Kobayashi, Mitsuhisa Takatsuki, Naomi Hayashida, Takeshi Nagayasu, Susumu Eguchi
Journal: Journal of Clinical Oncology (2017)

e21668 Background: Dysgeusia is a common side effect of chemotherapy (CT) and often impacts negatively on QOL. This study analyzed the prevalence of gustatory test abnormalities in breast cancer (BC) patients undergoing CT. Methods: We enrolled 33 BC patients who were undergoing CT (26 adjuvant CT and 7 CT for advanced BC) and conducted 2 gustatory tests on CT day. In the test of sensitivity using the instillation method (IM), 4 basic taste stimuli (sweet, salty, sour, and bitter) at 5 concentrations were applied to the entire oral cavity. For the electrogustometry method (EM), we measured the amount of current for perception of metallic tastes, examining the front two thirds of the tongue (cranial nerve VII) and the back third of the tongue (cranial nerve IX). We compared awareness of dysgeusia with results of the 2 gustatory tests. Results: Median CT duration was 83 days (12–1,353). Fifteen (45%) patients had awareness of dysgeusia (Grade 1: 11, Grade 2: 4). IM revealed 8 (24%) patients with abnormalities, 7 in a single taste species and 1 in 3 taste species. EM revealed 20 (61%) patients withabnormalities, 7 in the cranial nerve VII and 20 in the cranial nerve IX innervation area. All patients with abnormalities in the cranial nerve VII innervation area also had abnormalities in the cranial nerve IX innervation area. Among 15 patients with awareness of dysgeusia, there were 5 (33%) IM abnormalities and 12 (80%) EM abnormalities (4 in the cranial nerve VII and 12 in the cranial nerve IX innervation area). Among 18 patients without awareness of dysgeusia, there were 3 (16%) IM abnormalities and 8 (44%) EM abnormalities (3 in the cranial nerve VII and 8 in the cranial nerve IX nerve innervation area). Patients with IM abnormalities had a higher frequency of abnormalities in the cranial nerve VII innervation area than the normal range (50% and 12%, respectively; p = 0.04); there was no significant difference in the cranial nerve IX innervation area. Conclusions: Nearly half of the patients reporteddysgeusia, but most of these could correctly identify the four basic tastes. Further studies to clarify the discrepancy between subjective and objective observations could lead to effective prevention and treatment of dysgeusia.
Symptoms and health related quality of life in patients receiving matched therapy.
Authors: Kirstin Anne Williams, Casey B. Williams, Luis Rojas, David Starks, Amy K. Krie, Brian Leyland-Jones, Sandra Bergquist-Beringer
Journal: Journal of Clinical Oncology (2017)

e21648 Background: Genomic sequencing is increasingly being used to select targeted agents that are matched to molecular alterations. Potential differences in symptom occurrence and severity as well as health related quality of life (HRQOL) between patients who receive matched therapy and those who do not receive matched therapy have not been previously explored. Methods: Existing data from the records of patients with breast or gynecologic cancer receiving outpatient care were used for this descriptive correlational research study. Descriptive statistics and multiple linear regression analyses were performed to address the study aims. Symptom occurrence and severity and HRQOL were measured with the previously validated Therapy-Related Symptom Checklist (TRSC) and HRQOL – Linear Analogue Self Assessment (HRQOL-LASA) respectively. A higher total TRSC score indicated high symptom occurrence and severity; a higher total HRQOL-LASA score indicated a high quality of life. Results: Patients receiving matched therapy had lower mean TRSC scores ( M= 14.7, SD= 10.1) compared to patients receiving not matched therapy ( M= 16.1, SD= 11.6). Patients receiving matched therapy had higher mean HRQOL-LASA scores ( M= 48.1, SD = 7.5), compared to patients receiving not matched therapy ( M= 45.4, SD= 9.1). Mean ratings were higher for patients receiving matched therapy on each individual HRQOL domain. Therapy type (matched, not matched) was not significantly associated with TRSC scores (B = -3.0, p= 0.18) or HRQOL scores (B = 2.0, p= 0.18) after controlling for person and disease factors. Conclusions: On average, patients receiving matched therapy had lower symptom occurrence and severity scores and higher HRQOL scores when compared to patients who were not receiving matched therapy. Type of therapy (matched, not matched) was not significantly associated with symptom or HRQOL scores. Study findings provide initial data about the symptom experience and HRQOL and for patients receiving matched therapy.
Analysis of short-term efficacy and pathological outcome of paclitaxel plus platinum as neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer.
Authors: Yue He, Yu-Mei Wu, Qun Zhao, Yu-Ning Geng, Shu-Li Yang, Dominique Finas, Cheng-Hong Yin
Journal: Journal of Clinical Oncology (2017)

e17002 Background:The purpose of this study is to observe the short-term efficacy and pathological outcomes of paclitaxel combined with platinum (TP) as neoadjuvant chemotherapy (NACT) regimen in patients with locally advanced cervical cancer (LACC). Methods: This is a prospective study involving 61 women with histologically confirmed LACC referred for NACT at Beijing Obstetrics and Gynecology Hospital between April 2013 and January 2015. Results: The short-term efficacy of NACT was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST). The short-term efficacy of NACT was 91.8% (complete remission and partial remission). The cervical invasion ≤1/2 was 82.4% in the complete remission (CR) group, 46.2% in the partial remission(PR) group and 20% in the stable disease (SD) group. The difference between groups was statistically significant (p=0.012). The slides of all surgical specimens were reviewed and classified according to Tumor Regression Grade (TRG). The good response was defined by good short-term efficacy (RECIST) and the difference between the groups was statistically significant (p=0.042). The short-term efficacy of NACT in artery intervention (AI) group (70-80%) was better than that in intravenous (IV) group (20%-30%) and the difference was statistically significant (p=0.011). The patients with tumor diameter ≤5cm and multiple cycles of chemotherapy have good short-term efficacy of NACT in LACC. All patients were followed up to the last day of 2015 with the median follow-up time of 21.5 months for NACT. For the 61 patients referred for NACT in LACC, two patients had relapsed and 1 patient died from the disease. Conclusions: The study showed that the Paclitaxel plus platinum as NACT for LACC treatment had a significant local effects. It could reduce tumor myometrial invasion and regress tumor. The short-term efficacy of the treatment in the AI group was more effective than in the IV group, two cycles of NACT of AI treatment to LACC patients would obtain an optimal short-term efficacy. Clinical trial information: NCT02471027.