tbuckley/cabot-search huggingface dataset:
Blood alterations preceding clinical manifestation of glioblastoma.
Authors: Aysegul Ilhan-Mutlu, Ludwig Wagner, Adelheid Woehrer, Jungwirth Susanne, Christine Marosi, Peter Fischer, Matthias Preusser
Journal: Journal of Clinical Oncology (2012)

2024 Background: Glioblastoma is the most common and aggressive primary brain tumour in adults. There is lack of knowledge on biochemical blood alterations prior to clinical diagnosis of glioblastoma. We had the rare opportunity to investigate selected blood markers from plasma samples taken 12, 42 and 72 months before tumor manifestation in a glioblastoma patient. This index patient was enrolled in the longitudinal population based Vienna Transdanube Aging Study (VITA), which prospectively collects blood plasma from 600 participants at baseline (age 75), 30 and 60 months thereafter. Methods: We determined plasma levels of S100B, neuropeptide Y (NPY), secretagogin (SCGN), microRNA-21, microRNA-let7, microRNA-128, and microRNA-342-3p in all three blood samples from our index patient and in consecutive blood samples from five male and five female controls from the VITA cohort. These proteins and microRNAs were previously shown to be relevant for the pathobiology of glioblastomas. None of the controls had a malignant or neurological disease. Protein markers were analysed using commercially available ELISAs and microRNAs were quantified using RT-qPCR. Results: Compared to baseline values, we found a significant increase of microRNA-21 (up to 4-fold) and microRNA-let7 (up to 7-fold) levels in the blood samples of our index patient, whereas control samples showed almost stable levels of these markers. There was no significant difference in S100B, NPY, SCGN, microRNA-128, and microRNA-342-3p plasma levels between the index patient and controls. Conclusions: Increases of microRNA-21 and microRNA-let7 plasma levels may be associated with pre-clinical development of glioblastoma.
Intermittent intensified high-dose intravenous interferon alpha 2b (IFNa2b) for adjuvant treatment of stage III malignant melanoma: Pooled analysis of two randomized phase III trials (NCT00226408 and ISRCTN75125874) with 980 patients.
Authors: Michael Weichenthal, Vanna Chiarion-Sileni, Axel Hauschild, Paola Del Bianco, Uwe Trefzer, Michele Guida, Alexander Enk, Antonella Romanini, Carmen Loquai, Ruggero Ridolfi, Dirk Schadendorf, Mario Mandala, Josef Koller, Barbara Silvestri, Helen Gogas, Michele Medici, Reinhard Dummer, Gian Luca De Salvo, Peter Mohr
Journal: Journal of Clinical Oncology (2013)

e20028 Background: Adjuvant high-dose interferon (HDI) treatment of patients (pts) with malignant melanoma (MM) consists of 4 weeks intravenous (IV) induction with 20 MU/m² interferon (IFN) alpha 2b followed by 11 months of 10 Mio IU/m² IFN subcutaneously (sc). It is unclear whether both parts of the regimen are mandatory for the efficacy of HDI treatment. The adjuvant phase III trials DeCOG MM-ADJ-5 and the Italian Melanoma Intergroup (IMI) trial evaluated intermittent IV HDI (iHDI) regimens as compared to standard HDI. In both trials, the experimental arm consisted of iHDI for 3 or 4 cycles, respectively. To gain more insight into the role of iHDI in the adjuvant setting we performed a pooled analysis of both trials. Methods: Based on the intent-to-treat populations, the German DeCOG trial contributed data on 627 MM pts. with stage III (AJCC 2002) resected intransit or lymph node metastasis. From the Italian IMI trial 330 pts. with stage III regional lymph node metastasis excluding intransit metastasis were evaluable. We performed a combined analysis with respect to relapse free survival (RFS) and overall survival (OS), and toxicity using Cox regression models. Results: Median follow-up was 4.6 years in the DeCOG trial and 7.2 years in the IMI trial. There were 320 relapses in the DeCOG trial (51%) and 179 relapses in the IMI trial (54%) resulting in a combined hazard ratio (HR) for RFS of 1.11 (95% CI 0.93; 1.33) comparing iHDI vs.conventional HDI. OS was similar for iHDI vs. conventional HDI (HR 1.04; 95% CI 0.84; 1.29). There was no significant heterogeneity comparing different substages (IIIA vs. IIIB vs. IIIC) or ulcerated versus non-ulcerated primary tumors. In both studies more patients discontinued treatment due to toxicity or impairment of quality of life with conventional HDI as compared to iHDI (DeCOG: 31.0% vs. 16.7%; IMI: 31.2% vs. 23.8%). Conclusions: The pooled analysis of the two pulsed adjuvant HDI treatments showed no significant differences for RFS or OS as compared to conventional HDI. There is a favorable safety profile and less overall toxicity in the pulsed regimens.
Effect of sex, weight, and body mass index on plasma lanreotide levels.
Authors: Eugene Woltering, Melissa A Stevens, J Philip Boudreaux, Yi-Zarn Wang, Pam Ryan, Anne Porter Uhlhorn, Gregg Mamikunian
Journal: Journal of Clinical Oncology (2015)

e15189 Background: Long acting forms of lanreotide and octreotide are commonly used for the control of symptoms associated with neuroendocrine tumors (NETs). Lanreotide concentrations that approach levels where the somatostatin receptor subtype 2 is effectively saturated can be achieved by monitoring plasma levels via radioimmunoassay. We hypothesized that plasma lanreotide levels are inversely proportional to patient weight, body mass index (BMI) and body surface area (BSA). Methods: NET patients in our clinic who had been treated with lanreotide for at least 4 months and had plasma levels measured by radioimmunoassay were identified (n = 46). Most patients in this cohort (41/46, 89.1%) switched from traditional octreotide LAR therapy to lanreotide therapy for management of their neuroendocrine tumor due to failure of octreotide LAR therapy to adequately control symptoms and tumor growth. The majority (34/46, 71.7%) of patients received 120mg of lanreotide every 2 weeks. The remaining 12 patients were either receiving doses of lanreotide greater than 240 mg/month (n = 9) or less than 180 mg/month (n = 3). The effect of a patient’s sex, weight and BMI on lanreotide levels was evaluated for those patients receiving lanreotide therapy at 120mg every 2 weeks. Results: The patient cohort that received 120mg lanreotide every 2 weeks had mean plasma lanreotide levels of 8324±3477 pg/ml (n = 34). The mean level for males (n = 20) and females (n = 14) were 8116±3044 pg/ml and 8621±4121 pg/ml, respectively (p = NS). When adjusted for BMI, the mean lanreotide level for the cohort was 306±177 pg/ml/kg/m2. The BMI-adjusted mean for males was 284±144 and 338±217 for females (p = 0.006). The mean weight-adjusted lanreotide level for the cohort was 103±63 pg/ml/kg versus 87±45 for males and 125±78 for females (p = 0.000). The mean BSA-adjusted lanreotide level for the cohort was 4181±2137 pg/ml/m2. The BSA adjusted levels for males and females were 3740±1650 and 4810±2624, respectively (p = 0.004). Conclusions: Plasma lanreotide levels vary widely among patients and are affected by sex, weight and BMI. Thus, monitoring plasma lanreotide levels may be a useful tool for guiding lanreotide dosing, thereby maximizing antitumor efficacy and symptom control in NET patients.
Inflammatory and autoimmune manifestations in X-linked carriers of chronic granulomatous disease in the United Kingdom
Authors: Alexandra C. Battersby, Helen Braggins, Mark S. Pearce, Catherine M. Cale, Siobhan O. Burns, Scott Hackett, Stephen Hughes, Dawn Barge, David Goldblatt, Andrew R. Gennery
Journal: Journal of Allergy and Clinical Immunology (2017)
Using a mobile app to enhance the uptake of survivorship care plans (SCP) for adolescent and young adult survivors of childhood cancer.
Authors: Lisa Schwartz, Dava Szalda, Alexandra M Psihogios, Elizabeth Shea Ver Hoeve, Lauren Daniel, Eliana Butler, Wendy Hobbie, Linda A. Jacobs, Jill P. Ginsberg, Linda Fleisher, Carolyn Vachani, Margaret K. Hampshire, James M. Metz, Christine E. Hill-Kayser
Journal: Journal of Clinical Oncology (2017)

74 Background: Survivorship self-management, including adherence to survivorship care plans (SCPs), is variable, especially among adolescents and young adults (AYA). Methods:The present study describes the development of a mobile application (app) for AYA survivors (AYA STEPS), which strives to improve survivorship self-management via a combined texting self-management program (THRIVE 2.0) and an electronic survivorship care plan generator (Smart-ALACC [Smart-Adult Living After Childhood Cancer], hosted on Oncolink.org). Results: AYA STEPS was developed by modifying an existing disease management app, LSTCare. The main feature of the app is the delivery of two-way text messages that are tailored to an individual’s SCP. The messages are designed to enhance uptake of the SCP with information, strategies for adherence, motivational messages, and appointment reminders. Patients may also text back with questions. The SCP and its related text information are customized based on input of patient characteristics and treatment history, such as age, time off treatment, and type of treatment (e.g., anthracycline chemotherapy, mediastinal radiation, cranial radiation). The app also houses a copy of the complete SCP document. The SCP is generated, via patient or provider, via an electronic platform that incorporates patient demographic information, cancer diagnosis, and cancer treatments received with checklist of options. Feedback on the app was provided by AYA ages 15 to 21 via a focus group (n = 5) and interviews (n = 5), through which qualitative data were collected. AYA reported high acceptability of a mHealth intervention to improve self-care as cancer survivors, especially the inclusion of tailored content from an individualized SCP as text messages. They also reported the app as feasible to download and maintain on their phones. Conclusions: We are about to begin a RCT that will test adherence to SCP for those who received the app and the SCP versus the SCP alone. We will report details of the app and the launch of the RCT. We expect high acceptability and feasibility with measured benefit to receiving the self-management app.
Covariation of psychological and inflammatory variables in patients with chronic lymphocytic leukemia receiving ibrutinib.
Authors: Neha Niranjan Godiwala, Kami J. Maddocks, Travis Westbrook, John C. Byrd, Barbara L. Andersen, Amy J. Johnson
Journal: Journal of Clinical Oncology (2014)

7057 Background: Ibrutinib has been shown to induce durable responses in patients with high risk relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) (Byrd et al., 2013). Psychological factors, particularly stress, have been shown to covary with immunity and cytokines in solid tumor cancers. This pilot study examines temporal changes and covariation in inflammatory/angiogenic markers and psychological variables among r/r CLL patients receiving Ibrutinib. We hypothesized that these variables would improve during treatment and would covary over time. Methods: Patients enrolled in our single-institution phase II trial of Ibrutinib with r/r CLL (N=148) provided blood and psychological data on day 1 (of 28) of cycles 1-3. For this pilot, ELISA assays were performed on a subset (N=24; mean age=65; 50% female) of patients representing a distribution of scores (0-33) on a cancer-specific stress measure. Depressive symptoms, mood disturbance, fatigue, and quality of life (QOL) were also assessed. Assays measured IL-6, TNF-alpha, VEGF, CRP, BAFF, CCL3, and IL-16 levels in the patients’ plasma. Hierarchical linear modeling examined change over time for all variables and covariation between psychological and inflammatory/angiogenic markers. Results: Improvements were observed in stress, depressive symptoms, fatigue, and QOL (p-values < 0.05). Decreases were observed in IL-16, TNF-alpha, and CCL3 (p-values < 0.05). Controlling for age, chromosome 17p deletion, and gender, covariation between the following variables was found: TNF-alpha with stress, depressive symptoms, mood disturbance, and QOL; IL-6 with mood disturbance, fatigue, and QOL; and VEGF with depressive symptoms (all p-values <0.05). That is, changes in inflammatory/angiogenic markers were correlated with changes in psychological variables. Conclusions: These pilot data suggest that in addition to providing clinical benefit, Ibrutinib treatment contributes to improvements in psychological functioning and decreases in inflammation. Clinical trial information: NCT01589302.
Phase IV trial of dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma
Authors: M. Reni, S. Cereda, P. Passoni, E. Bonetto, M. G. Viganò, G. Balzano, A. Zerbi, C. Staudacher, V. Di Carlo
Journal: Journal of Clinical Oncology (2006)

4121 Background: In a phase III trial (Reni, Lancet Oncol 2005), PEFG regimen (cisplatin and epirubicin 40 mg/m 2 day 1, gemcitabine 600 mg/m 2 day 1 and 8, 5-fluorouracil (FU) 200 mg/m 2 /day continuous infusion) significantly improved the outcome of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine. This regimen was subsequently modified by increasing dose-intensity (FU unmodified, cisplatin and epirubicin both at 30 mg/m 2 , and gemcitabine at 800 mg/m 2 every 14 days; Dell’Oro, Ann Oncol 2004). The present study assessed activity and feasibility of dose-intense (DI) PEFG. Methods: DI-PEFG was administered to chemotherapy-naive patients with stage III-IV pancreatic adenocarcinoma, ≤ 75 years, performance status (PS) &gt; 50, till progressive disease or for a maximum of 6 months. Analyses were conducted in the intent-to-treat population. Results: Between January ’04 and June ’05, 49 (31 or 63% metastatic) patients, median age 62 yrs, median PS 80, were treated with DI-PEFG at our institution. Partial response and stable disease was observed in 25 (51%) and 15 (31%) patients, respectively; 31 patients were progression-free at 6 months (PFS-6 = 63%). Median survival was 8.5+ months and 1-yr overall survival (OS) was 46%. 211 courses (range 1–6, median 5) of DI-PEFG were delivered. Main grade 3–4 toxicity was: neutropenia in 9% of cycles, anaemia, stomatitis, fatigue in 3%, nausea/vomit, deep venous thrombosis and diarrhoea in 2%, thrombocytopenia, febrile neutropenia and hand-foot syndrome in 1%. Dose intensity (mg/m 2 /week) was 13 for both epirubicin and cisplatin, 338 for gemcitabine and 1106 for FU. Conclusion: With respect to classical PEFG, DI-PEFG was not inferior in terms of PFS-6 (63% vs. 42%), 1-yr OS (46% vs. 38.5%) and response rate (49% vs. 38.5%); allowed to increase dose intensity for gemcitabine by 32%, for cisplatin and epirubicin by 36% (FU reduced by 3%), to reduce grade 3–4 hematological toxicity (neutropenia 9% vs. 43%; thrombocytopenia 1% vs. 28.5%) and to reduce by one third the number of outpatients accesses. No significant financial relationships to disclose.
Effect of cognitive behavioral therapy for insomnia (CBT-I) and/or armodafinil on insomnia in cancer survivors.
Authors: Anita Roselyn Peoples, Joseph A. Roscoe, Charles E. Heckler, Michelle Shayne, Luke Joseph Peppone, Gary R. Morrow
Journal: Journal of Clinical Oncology (2014)

9531 Background: Insomnia is an underreported distressing side effect of cancer and its treatment, which can persist for months after treatment affecting the course of cancer survival. It exacerbates fatigue and results in reduced quality of life (QOL), allowing for the possibility that treatment of insomnia may improve associated symptoms and QOL. Although CBT-I is considered the nonpharmacologic treatment of choice for insomnia in the general population, it often results in short-term daytime sleepiness. The present study examines whether CBT-I in combination with a wakefulness promoting agent, armodafinil (A), results in greater overall reduction in insomnia in cancer survivors. Methods: Primary analyses examine if one or more of the intervention conditions (i.e., CBT-I, A, or both), when compared to placebo (P) group, reduce insomnia in cancer patients following completion of chemotherapy and/or radiotherapy. We report on 88 cancer survivors (mean age 56, 88% female, breast cancer 68%) randomized to one of four 7-week long intervention conditions: 1) CBT-I+A, 2) CBT-I+P, 3) A only, and 4) P only. Insomnia severity was assessed by the validated Insomnia Severity Index (ISI) questionnaire at consent, following the intervention (post), and again three months later (follow-up), with higher scores indicating greater insomnia. Results: Mean post ISI scores in groups 1-4 were 4.12, 5.61, 11.32, and 10.28, respectively. ANCOVA with multiple imputation and controlling for scores at time of consent showed that both CBT-I+A (p=0.001) and CBT-I+P (p=0.01) groups had significantly less insomnia than those in the placebo group, with effect sizes of 1.31 and 1.02, respectively. Armodafinil and placebo groups were not significantly different (p=0.584); nor was the CBT-I+A group significantly different from the CBT-I+P group (p=0.421). Follow-up ISI scores were essentially the same as post scores. Conclusions: These findings show that CBT-I results in clinically significant improvement in insomnia, with effects that persist long term. Armodafinil had no significant effect on insomnia nor on the efficacy of CBT-I. Supported by NCI grant 5 R01 CA126968. Study medication was provided by Teva Pharmaceutical USA. Clinical trial information: NCT01091974.
Correlation of HuR cytoplasmic expression in pancreatic cancer and overall patient survival when treated with gemcitabine in the adjuvant setting
Authors: J. Brody, A. Dasgupta, C. L. Costantino, E. Kennedy, C. J. Yeo, A. K. Witkiewicz
Journal: Journal of Clinical Oncology (2009)

11097 Background:The Hu/ELAV mRNA binding protein HuR is normally localized to the nucleus and is activated upon stress. Previously, we observed that HuR expression is predominantly cytoplasmic in aggressive forms of pancreatic ductal adenocarcinomas (PDA). Additionally, we have shown that overexpression of HuR in pancreatic cancer cell lines renders them hypersensitive to gemcitabine (GEM). GEM is the standard first line therapy used against PDA. This study was designed to determine the relationship between endogenous HuR expression levels and patient outcome. Methods: We analyzed tissue from 29 resected PDA patients who did not receive neoadjuvant therapy. We determined the intensity of cytoplasmic HuR expression. All patients received adjuvant GEM, alone or in combination with radiation therapy or other chemotherapeutics. Correlation between HuR expression levels and overall survival was evaluated. Results: The median overall survival was 20.6 months, with 18 deaths observed. Median overall survival for low HuR expression was 15.3 months. Median overall survival for high HuR expression was not reached at a follow up of 40 months. A univariate Cox regression model gives a hazard ratio of low to high HuR of 3.36 (p=0.025) [95% CI 1.09–10.35]. Adjusting for age, sex, and radiation therapy in this patient group gives an adjusted hazard ratio of 5.04 (p = 0.03) [95% CI 1.15–22.02]. This indicates a 5-fold increase in risk of death in patients with low HuR levels compared to high HuR levels among patients receiving GEM. Conclusions: This is the first report of a correlation between levels of cytoplasmic HuR expression and overall survival in GEM treated patients. Together with our previously reported experimental data, HuR is regulating the key metabolic enzyme for GEM activation (deoxycytidine kinase). Therefore, HuR is a marker for therapeutic efficacy of GEM based regimens and is a candidate target for the optimization of GEM based treatment strategies. [Table: see text] No significant financial relationships to disclose.
Consensus treatment guidelines for urgent symptoms in cholangiocarcinoma (CC) patients (pts) with biliary stents or catheters using the modified RAND/UCLA Delphi process.
Authors: Renuka V. Iyer, Susan G. Acquisto, John A. Bridgewater, Michael A. Choti, Theodore S. Hong, Bela Kis, Peter A Mead, Neehar D. Parikh, Lewis R. Roberts, Rebecca Roberts, Jason K. Sicklick, Richard S. Siegel, Jonathan R. Whisenant, Dasha Cherepanov, Michael S. Broder, Juan W. Valle
Journal: Journal of Clinical Oncology (2017)

452 Background: CC pts with biliary stents or catheters often present with fever and/or jaundice requiring urgent treatment for which there is no uniform guideline. We aimed to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: We recruited 13 physician experts from relevant specialty, geography, and practice settings. Patient scenarios were developed based on a literature review, and therapies were rated by the experts before and after a face-to-face discussion. The appropriateness of various therapies was rated on a 1-9 scale and classified as appropriate, inappropriate, or uncertain. Scenarios with &gt; 2 ratings of 1-3 (inappropriate) and &gt; 2 ratings of 7-9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions (92%) and the UK (8%); had practiced for a mean 16.5 years (4-33 years) and reported seeing an average of 120 unique CC patients a year (0-900 pts). Panelists rated 288 clinical scenarios. Experts decided that ongoing treatment with chemotherapy did not influence decision-making. Disagreement decreased from 37.5% before the meeting to 10.4% after. Consensus statements are summarized in table 1. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in urgent management of ascending cholangitis in pts with CC. Studies of the impact of these guidelines on cost of care and pt outcomes are warranted. (Support: The Cholangiocarcinoma Foundation)[Table: see text]