tbuckley/cabot-search huggingface dataset:
Ongoing, prospective multicenter safety study of subcutaneous amifostine for non-small cell lung cancer (NSCLC)
Authors: R. C. Nichols, K. R. Fullmer
Journal: Journal of Clinical Oncology (2005)

7251 Background: Amifostine (Ethyol) is a radioprotectant that protects mucosal tissue from chemotherapy- and radiotherapy (RT)-induced damage. Intravenous administration is the approved route, but subcutaneous (SC) administration may offer greater ease of administration and reduced toxicity. Methods: The safety of SC amifostine is under investigation in an ongoing, prospective, open-label, multicenter study. All patients receive 500 mg SC amifostine before daily RT. Five targeted adverse events (AEs) are evaluated as to their occurrence and possible relationship with amifostine. This report focuses on enrolled patients with a diagnosis of NSCLC. Results: Two hundred thirty-nine patients (159 men, 80 women; median age, 66 yrs) with NSCLC have been enrolled. Mean cumulative amifostine dose was 10,264 mg (range, less than 5,000 to >20,000 mg): median dose was 500 mg and median total number of doses per patient was 22. The most common AE was nausea/vomiting, which occurred in 56% of patients. Radiation dermatitis occurred in 37% of patients, local skin reaction in 35%, hypotension in 23%, and skin rashes in 20% of patients. Eighty-one (20%) of all reported targeted AEs required permanent discontinuation of amifostine owing to: local injection site reactions (n=11), radiation dermatitis (n=2), skin rash (n=27), hypotension (n=6), and nausea/vomiting (n=35). The majority (88%) of reported targeted AEs were mild to moderate (grade ≥2), and 65% of all serious (grade 3/4) AEs reported were either not related or remotely related to amifostine. Ninety-one percent of patients did not require changes in amifostine dosage. Conclusions: SC amifostine was well tolerated by patients with NSCLC in this prospective safety study, with a low incidence of severe (grade 3/4) AEs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MedImmune
Small bowel carcinoid: Location isn’t everything.
Authors: Danielle M. Hari, Heidi M Hari Reich, Anna Mary Leung, Ji Hey Hey Lee, Myung-Shin Sim, Edward M. Wolin, Farin F. Amersi
Journal: Journal of Clinical Oncology (2013)

292 Background: Contemporary data has revealed that small bowel carcinoid (SBC) accounts for the majority of gastrointestinal carcinoids. However, data remains limited regarding prognostic factors that impact survival for SBC patients. Using a population-based analysis, we investigate the significance of the primary site of disease for SBC. Methods: The Surveillance, Epidemiology, and End Results database was queried for histologically confirmed SBC between the years 1988 and 2009. Patients were excluded if adequate demographic and staging information was unknown. Overall and disease survival curves (OS and DSS respectively) were analyzed using the Kaplan-Meier method and compared using Log rank testing. Log rank and multivariate Cox regression analysis was used to identify predictors of survival using age, year of diagnosis, race, gender, tumor histology/size/location, TNM stage, number of lymph nodes (LNs) examined and percent of LNs with metastases. Results: Of the 3,834 patients analyzed, the mean age was 62.13 years and 51.2% were male. Median follow up was 50 months. The 10-year OS (63%) and DSS (91%) for duodenal primaries was statistically significant when compared to jejunal (53%, 74%), ileal (50%, 68%) and overlapping primaries (50%, 78%), (p = 0.0290 and &lt; 0.0001, respectively). However, more the 90% of duodenal primaries had stage I and II disease only. On multivariate Cox regression analysis, after adjusting for multiple factors, primary site location was not a significant predictor of survival (p = 0.948 for OS and = 0.625 DSS) while TNM stage, age, tumor size and number of LNs examined portend improved OS and DSS. Conclusions: This population-based study of SBC over the past 30 years refutes the concept that the location of the SBC influences survival. A key element to consider is that more than 90% of duodenal primaries present at early stages. Further screening and diagnostic methods to detect other SBC primary sites could significantly impact survival.
Phase II Trial of Darbepoetin Alfa in Myelodysplastic Syndrome (MDS): Preliminary Efficacy, Safety, and In Vitro Results.
Authors: Jason Gotlib, Sylvia Quesada, Jyoti Bhamidipati, Kamran Chaudry, Kunju Sridhar, Kathleen Dugan, Richard Stein, Germaine Tupper, Peter L. Greenberg
Journal: Blood (2004)
Prognosis Using Planar Imaging in Cardiac Amyloidosis
Authors: Brett W. Sperry, Richard Brunken, Wael A. Jaber
Journal: JAMA Cardiology (2017)

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Association of high histone H3K4 trimethylation level and prognosis of patients with low-TNM-stage hepatocellular carcinoma.
Authors: Junyao Xu, Chuanchao He, Jianlong Zhang, Jie Wang
Journal: Journal of Clinical Oncology (2012)

171 Background: Along with genetic events, tumor associated epigenetic alterations including DNA methylation and post-translational histone modifications are important determinants in the initiation and progression of hepatocellular cancer (HCC) and represent promising biomarkers and therapeutic targets. Locus-specific trimethylation of histone H3 lysine 4 (H3K4me) is a well-known modification linked to the enhanced transcriptional expression of many genes activated in HCC. However its expression and association with prognosis of HCC patients remain unclear. Our aim was to assess the cellular expression pattern of H3K4me3 in HCC and its association with clinicopathologic variables and outcome. Methods: Expression of H3K4me3 and the histone methyltransferase SMYD3 was studied by western blotting and immunohistochemistry in human HCC cell lines and tumor tissue micmicroarray, which is from a well–characterized series of HCC patients(n=168). Tissue staining were assessed using blinded semiquantitative scoring. The optimal cut-point of H3K4me3 expression for prognosis was determined by the X-tile program. The prognostic significance was evaluated using Kaplan-Meier survival estimates and log-rank tests. Tumor tissue micmicroarray from another independent HCC patients cohort(n=147) was used for validation studies. Results: Expression of H3K4me3 and the histone methyltransferase SMYD3 were enhanced in HCC cell lines.In clinical tumor specimens, enhanced expression of H3K4me3 was correlated with reduced overall survival (P &lt; 0.0001), especially in early-stage HCC patients(TNM I/II).Furthermore,both univariate and multivariate analysis revealed that H3K4me3 level was a significant and independent predictor of poor survival (hazard ratio,3.592; 95% CI, 2.302-5.605). In addition, H3K4m3 expression was positively correlated with SMYD3 expression in both testing and validation cohorts (P&lt;0.0001). Conclusions: H3K4me3 level defines previously unrecognized subsets of HCC patients with distinct epigenetic phenotype and clinical outcome, thus can be a novel predictor for poor prognosis of HCC patients, especially within TNM I/IIstage.
Comparable Outcomes of Patients Eligible Versus Ineligible for Southwest Oncology Group (SWOG) Leukemia Studies
Authors: Abby Statler, Megan Othus, Harry P. Erba, Thomas R. Chauncey, Jerald P. Radich, Steven E. Coutre, Anjali S. Advani, Sucha Nand, Farhad Ravandi, Sudipto Mukherjee, Mikkael A. Sekeres
Journal: Blood (2016)
Clinical study on medical value of adoptive immunotherapy with chemotherapy for stage IV colorectal cancer (COMVI study).
Authors: Yoichiro Yoshida, Masayasu Naito, Teppei Yamada, Naoya Aisu, Daibo Kojima, Toshiyuki Mera, Syu Tanimura, Toshihiro Tanaka, Keiko Naitoh, Kosei Yasumoto, Takashi Kamigaki, Shigenori Goto, Yuichi Yamashita
Journal: Journal of Clinical Oncology (2016)

628 Background: Adoptive immunotherapy of cancer is evolving with the development of novel technologies for generating a large number of activated killer cells such as αβ T cells, γδ T cells, and natural killer (NK) cells. We conducted a pilot study to evaluate the safety and feasibility of the combination treatment of adoptive immunotherapy with chemotherapy for stage IV colorectal cancer. Methods: The COMVI study was a prospective and single-arm pilot trial. Therapy in each 21-day treatment cycle consisted of XELOX (130 mg/m2 of oxaliplatin on day 1 plus 1,000 mg/m2 of capecitabine twice daily on days 1–14), bevacizumab (7.5 mg/kg on day 1) and αβ T lymphocytes (over 5 ×10 9 on day 18) cultured ex vivo with an immobilized anti-CD3 antibody and interleukin-2. Results: A total of 6 patients were enrolled from June 2013 to September 2014. Baseline characteristics included a median age of 66 years (range: 55-75) for 2 men and 4women. Median PFS was 567 days. Overall response rate was 100 % (CR 33.3%, PR 66.7%, SD 0%, PD 0%). The tumor reduction rate was 53% (38.0–100%). The majority of adverse events were mild to moderate in intensity, and no grade 4 adverse events occurred in the 6 patients. Only one patient experienced grade 3 hypertension and ileus. Immunotherapy-associated toxicity was minimal in this study. Conclusions: The combination treatment of adoptive immunotherapy with chemotherapy for stage IV colorectal cancer is feasible and safe. Phase II prospective studies are warranted to confirm the safety and efficacy of this chemoimmunotherapy. Clinical trial information: UMIN000010908.
Metabolite assay and histology on exactly the same tissue.
Authors: Dean A. Troyer, Jeffrey R. Shuster, Sarah Baxter, Mingming Su, Ray Lance
Journal: Journal of Clinical Oncology (2013)

235 Background: Metabolites are emerging biomarkers of cancer described as a link between genotype and phenotype. In previous studies we used molecular preservation by extraction and fixation (mPREF) on a metabolomics platform to screen for candidate metabolites using 18 gauge core needle biopsies of prostate tissues obtained ex vivo. Methods: Single core needle biopsies are immediately placed in 80% aqueous alcohol and transferred to formalin after 12-24 hours. The alcohol is retained, dried down and the residue reconstituted with 95 µL of acetonitrile plus 95 µL of water. Histology is performed on exactly the same tissue. Results: Using metabolomics, 83 metabolites showed differences between cancer containing vs. non-cancer containing biopsies. For nine of these differential metabolites, quantitative LC-MS assays have been developed using the same 18 gauge needle biopsy protocol. Thirty mPREF samples including tumor/non-tumor were analyzed using the developed method and the concentration ranges obtained. These analytes were selected in part because they could all be assayed on a single LC/MS run. Results comparing no tumor/tumor normalized to surface area of the biopsy core were as follows (see Table). Histology and immunohistochemistry (IHC) were satisfactory, and as the biopsy cores were moved to formalin, the work flow fits well with existing histopathology processing and microtomy methods. Conclusions: Our results confirm the original discovery trends and indicate that metabolites can be quantitated in single core biopsies fixed in aqueous methanol. From our experience and the literature, the performance of DNA/RNA extraction methods, in-situ hybridization, and proteomic analysis should differ very little from the use of formalin as primary fixative. The ability to quantitate any constituent of intact tissue is significant since most available methods such as IHC are subject to many variables and are difficult to quantitate. [Table: see text]
Postchemotherapy residual masses (rm) in testicular nonseminomatous germ cell tumor (TNSGCT): Role of prognostic factors and adjuvant chemotherapy
Authors: A. P. Fraccon, T. Sava, G. Martignoni, S. Pessa, M. Frisinghelli, F. Merlin, M. A. Bassetto, T. Franceschi, C. Sava, G. L. Cetto
Journal: Journal of Clinical Oncology (2005)

4662 Background: Different factors have been proposed to predict necrosis in rm after chemotherapy in TNSGCT, although no diagnostic tool have been developed that reliably predicts the viability of the residual mass; the role of adjuvant chemotherapy in these patients (pts) is also a matter of debate. Methods: Surgery of rm after chemotherapy was performed in 64 pts (25 were stage II and 39 stage III). We retrospectively evaluated the histology of testis tumour, computer tomography (CT) scan shrinkage (< or > 50%), dimension of rm, the value of serum tumor markers (aFP and HCG) and their time to normalisation: all these factors were compared with the histology of rm. The role of adjuvant chemotherapy was also investigated. Results: The histology of rm was 42.5% necrosis, 23.7% teratoma and 33.8% viable cells. The presence of teratoma in testis specimen was frequently associated with the presence of teratoma (37%) or viable cells (72%) in the rm. No correlation was found between CT shrinkage, dimension of rm, markers value or their half-life and the histology of rm. Six pts, due to the presence of viable cells in the rm, were subdue to adjuvant chemotherapy: 2 of them relapsed and none died of disease. On the other hand 14 pts, with viable cell in the rm, were not treated with adjuvant chemotherapy: 6 of them relapsed and all of them died of disease. Conclusions: All pts with a rm after chemotherapy should be operated. The presence of teratoma in the testis specimen highly predict teratoma or viable cell in the rm. CT shrinkage, dimension of rm, markers value or their half-life can not predict the viability of the residual mass. In case of viable cell in the rm adjuvant chemotherapy should be recommended: in fact in our series it reduces relapses (33% vs 43%) and increase overall survival (100% vs 57%). No significant financial relationships to disclose.
Results from a phase 3, randomized, double-blind, multicenter, placebo-controlled trial of orteronel (TAK-700) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or following docetaxel-based therapy (ELM-PC 5 trial).
Authors: Robert Dreicer, Robert Jones, Stephane Oudard, Eleni Efstathiou, Fred Saad, Ronald De Wit, Johann Sebastian De Bono, Yuanjun Shi, Bindu Tejura, David B. Agus, Niels Geert Borgstein, Joaquim Bellmunt, Karim Fizazi
Journal: Journal of Clinical Oncology (2014)

7^ Background: Orteronel is an investigational, non-steroidal selective inhibitor of 17,20-lyase; a key enzyme in the production of steroidal hormones. Methods: Eligible men with metastatic castration-resistant prostate cancer (mCRPC) had progressive disease (PD; radiographic or prostate-specific antigen), castrate levels of testosterone, and had received more than or equal to 360 mg/m 2 docetaxel within the prior 6 months. Prior orteronel, abiraterone, or ketoconazole was not permitted. Patients were randomized 2:1 to continuous 28-day cycles of oral orteronel 400 mg BID + prednisone 5 mg BID, or placebo + prednisone without regard to food. Primary endpoint: overall survival (OS); other key endpoints: radiographical progression-free survival (rPFS), 50% or more PSA decrease at 12 weeks, pain response at 12 weeks and safety (NCT01193257). Results: One thousand ninety nine patients were randomized.The study was terminated for failing to meet its primary endpoint: median overall survival (OS) was 17.0 months (95% CI 15.2, 19.9) in patients receiving orteronel versus 15.2 months (95% CI 13.5, 16.9) in those receiving placebo (HR: 0.886 [95% CI: 0.739, 1.062]; P=0.1898). Substantial regional differences were seen in OS benefit: median OS (orteronel vs. placebo) was 20.9 vs. 16.9 mo (HR: 0.889) in North America (n=112), 18.3 vs. 17.8 mo (HR: 1.048) in Europe (n=590), and 15.3 vs 10.1 mo (HR: 0.709) in the rest of the world (n=397). In the overall population, rPFS was significantly improved in the orteronel arm, with a median of 8.3 months vs. 5.7 months in the placebo arm (HR: 0.76 [95% CI: 0.653, 0.885]; P=0.00038). Drug-related adverse events (AEs; any grade) included (orteronel/placebo) nausea (30/16%), vomiting (23/8%), fatigue (17/11%), and diarrhea (16/9%); grade 3 or higher drug-related AEs included increased lipase (12/less than 1%), increased amylase (8/less than 1%), and fatigue (3/3%). Additional sub-analyses looking at potential factors that affected OS will also be reported. Conclusions: Whileorteronel + prednisone did not show a statistically significant overall OS improvement versus placebo + prednisone, rPFS findings and striking regional OS differences suggest that orteronel has clinically meaningful activity. Clinical trial information: NCT01193257.
Gene Expression Signature of Acute Myeloid Leukemia (AML) with T(8;16)(P11;P13) and MYST3-CREBBP Rearrangement: A Microarray Study Validated by Multiple Real-Time PCR.
Authors: Mireia Camos, Jordi Esteve, Dolors Colomer, Pedro Jares, Maria Rozman, Neus Villamor, Dolors Costa, Ana Carrio, Josep F. Nomdedeu, Emili Montserrat, Elias Campo
Journal: Blood (2005)
Patient and physician perspectives on access to off-protocol cancer therapy.
Authors: J. M. Peppercorn, D. Bloom, K. Weinfurt, G. E. Henderson
Journal: Journal of Clinical Oncology (2011)

e16588 Background: Experimental interventions are frequently available outside of oncology clinical trials by virtue of FDA approval for different indications. Previous work found that “off-protocol” therapy (OPRx) may be requested by patients with little consensus among oncologists regarding access. Methods: We conducted 4 focus groups among 23 patients with breast cancer and 3 focus groups among 12 medical oncologists (MO) to evaluate attitudes and beliefs regarding trial participation and access to OPRx. Discussion guides were developed to explore views of “experimental” and “standard” therapy, and to elicit responses to 2 hypothetical scenarios in which trial eligible patients with breast cancer (curable disease vs. metastatic disease) requested OPRx from their MO. Focus groups were led by a trained moderator, audiotaped, and transcribed verbatim for qualitative analysis. Results: Among patients, major themes that emerged were access to therapy and patient autonomy. Patients understood distinctions between standard and experimental therapy, but had highly variable views and knowledge about the purpose of clinical trials. They trusted their MO and acknowledged MO influence over treatment decisions. Their top-of-mind assumption was that “newer is better” and they tended to focus on potential benefits of experimental therapy, not risks. Among MO, major themes that emerged were patient safety and evidence based medicine. In discussions of hypothetical scenarios, patients almost universally felt the doctor should provide OPRx upon request, while MO believed they should not. However, in the course of discussion, patients identified multiple reasons to withhold OPRx, including safety, cost, and need to help future patients, and MO identified scenarios where OPRx might be considered, including trial ineligibility, poor prognosis, and lack of trial access. Conclusions: Patients with breast cancer and MO share concerns regarding access to appropriate care, safety of novel interventions, and cost of cancer care. Patients tend to view trials in terms of access to new therapy, while MO see trials as means of evidence development. Professional guidelines aimed at supporting clinical decisions regarding OPRx should be considered.
Utilization of an innovative tool to improve oncology patient outcomes.
Authors: Dana McNeil, Jessica O'Driscoll, Jaimika Patel, Marie Decker, Joanne McGovern
Journal: Journal of Clinical Oncology (2016)

231 Background: Introduction of an electronic board can improve interdisciplinary communication to ensure early intervention and improve patient outcomes. Early detection and prevention is key. The early stages of physiologic demise may be demonstrated by subtle changes in the patient’s vital signs. The purpose of this study was to implement a visual tool to indicate and update the acuity of patients on the oncology unit. The parameters displayed included vital signs, Hendrich, and Braden scale. The goal of the electronic board was to create a continuously accessible resource for the interdisciplinary team for rapid assessment of the patient’s condition throughout rounds and all shifts. Methods: This electronic board produces a color-coded alarm for abnormal parameters. Vital signs highlighted in red indicate the urgency for assessment and intervention. The Hendrich score displayed in yellow alerts all disciplines of fall risk patients. The Braden scale, color-coded purple, identifies patients at risk for skin breakdown. Improvement in early and rapid identification of patient deterioration and risk was analyzed using two months of post implementation data from the electronic health record. A survey was sent to all disciplines to qualitatively measure the value of this tool. Results: Abnormal vital signs identified from the facility board led to clinician interventions impacting 27% of admitted patients in the first two months. Falls decreased by 33% after the first month of implementation. The number of specialty beds ordered increased by 32% for patients identified at risk for skin breakdown. Twenty-five survey responses illustrated 71% of the interdisciplinary team that replied used the facility board and 68% confirmed improvement in interdepartmental communication. Conclusions: There is a significant association between early intervention and decreased mortality rate in acutely ill cancer patients. The continuous display of pertinent patient data on an electronic board holds clinicians accountable to recognize and provide early intervention thus impacting oncology patient outcomes. This innovative tool will further enhance outcomes as we move to interfacing our vital signs monitor into our electronic health record.
Statin side effects are strongest predictor of inadequate cholesterol control, study shows
Authors: Susan Mayor
Journal: BMJ (2017)

Statin specific side effects are the strongest predictor of patients with coronary heart disease failing to achieve low density lipoprotein (LDL) cholesterol targets, followed by poor adherence and the use of moderate or low intensity statin therapy, a cross sectional study has found.1

Statin prescribing has increased over the past few years, and control of LDL cholesterol has improved slightly. But the EUROASPIRE 4 study …