tbuckley/cabot-search huggingface dataset:
Influence of tumor type, disease status, and patient age on self-reported interest regarding participation in cancer clinical trials
Authors: S. E. Rivkin, M. Markman, J. Petersen, R. Montgomery
Journal: Journal of Clinical Oncology (2006)

6100 Background: There is limited data available regarding the reasons cancer patients decide to enter clinical trials. Methods: To explore this issue, aggregate responses to the question, “Are you interested in learning about clinical trials for your condition?” obtained from &gt; 115,000 cancer patients (or their families) who entered data into one of several proprietary decision-support programs embedded within approximately 100 cancer-related Internet sites, were analyzed. Results: The proportion of patients (or their families) who expressed interest in learning of the availability of clinical trials ranged from as low as 21% (endometrial and cervix cancer patients &gt; 80 years old; n=178) to as high as 85% (recurrent ovarian cancer patients, aged 51–60; n=842). Patients &gt; 80 years old, regardless of sex, tumor type, or disease status, were substantially less likely to desire such information. Patients with self-declared more “serious conditions” (e.g., metastatic breast cancer [71%; n=5,444], recurrent prostate cancer [70%; n=4,121]), and those with cancers widely known to have a poor prognosis (e.g., non-small cell lung cancer [75%; n=23,298]), were more likely to request data on trials, than those with an overall more “favorable” prognosis (e.g., newly diagnosed prostate cancer [46%; n=21,348]). There were no observed differences in interest between men and women with similar conditions. Conclusion: In this large data base, major differences in self-expressed interest regarding availability of clinical trails were observed. Particularly notable were the reduced interest among the very elderly, and the increased interest by patients with the most serious cancer-related conditions. [Table: see text]
Application of stable isotopic tracing in an ex-vivo system to reveal heterogeneous patterns of androgen metabolism in localized, hormone-naïve prostate cancer.
Authors: Charles Dai, Nima Sharifi, Yoon-Mi Chung, Eric A. Klein
Journal: Journal of Clinical Oncology (2017)

109 Background: The 5α-androstanedione (5α-dione) pathway is the demonstrated route through which adrenal precursor steroids bypass testosterone (T) to form dihydrotestosterone (DHT) in metastatic castration-resistant prostate cancer (mCRPC). However, accessible pathways of DHT synthesis are less clear in localized, hormone-naïve prostate cancer (HNPCa), where steroidogenic enzyme expression may differ and circulating T and adrenal steroids could act as competing substrates for 5α-reductase. We employed a dual substrate, ex-vivo system with selective stable isotopic labeling of DHT precursors to better understand alterations in androgen synthesis that occur in the transition of HNPCa to mCRPC. Methods: Under IRB approval and patient consent, tumor and adjacent benign prostate tissues were procured from radical prostatectomy specimens of men with HNPCa (n = 16). Tissues were grossly homogenized and incubated ex-vivo in serum-free media spiked with 1 µM of 13 C 3 -AD +/- equimolar unlabeled T. Media was collected over 48 hours and subjected to liquid-liquid extraction to capture free and glucuronidated steroid metabolites for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both AD and T were readily 5α-reduced in treated prostate tissues. 13 C labeling revealed DHT originating from metabolism of AD. Co-incubation with T did not dramatically alter the efficiency of AD metabolism. Minimal differences were found in metabolism between PZ and TZ tissue. No glucuronidated steroid was detected in media, in contrast to in prostate cancer cell lines and xenograft tumor tissue. Considerable heterogeneity was observed in measurements of reaction efficiency across different patients. Conclusions: AD is an active substrate for 5α-reductase comparable to T in HNPCa. Adrenal steroids may therefore contribute to DHT in HNPCa via the 5α-dione pathway. Metabolic heterogeneity may reflect currently unappreciated genotypic differences in patient tumors.
A new equation to predict glomerular filtration rate one year after radical nephrectomy in Japanese patients.
Authors: Shuichi Shimada, Hideo Saito, Akihiro Ito, Naomasa Ioritani, Sadafumi Kawamura, Tatsuo Tochigi, Takuhiro Yamaguchi, Yoichi Arai
Journal: Journal of Clinical Oncology (2013)

e15570 Background: Strong associations have been reported between chronic kidney disease (CKD) and outcomes such as the development of ischemic cardiovascular disease and heart failure, as well as all-cause mortality. In many patients, CKD develops immediately after radical nephrectomy (RN) for renal cortical tumors and the prevalence of CKD after RN increases steadily thereafter. Therefore, it is important to predict postnephrectomy renal function. To evaluate renal function one year after radical nephrectomy for renal cortical tumors (RCT), predictive factors for postnephrectomy renal function were investigated, and an equation to predict estimated glomerular filtration rate (eGFR) one year after RN was developed. Methods: A total of 525 patients who underwent RN between May 2007 and August 2011 at Tohoku University Hospital and its affiliated hospitals were prospectively evaluated. Overall, 429 patients were analyzed in this study, of whom 257 were randomly selected as the training dataset, and the remaining 172 patients constituted the validation dataset. The prediction equation was developed by stepwise regression applied to the training dataset. Results: Independent factors associated with postnephrectomy eGFR included tumor size (cm), preoperative serum creatinine (mg/dL), sex, and age (years), but body mass index (BMI) and body surface area (BSA) were not significant factors. An equation to predict eGFR one year after RN was developed: Predicted eGFR mL/min/1.73m 2 =211 × Age -0.454 × Pre SCr -0.841 × Tumor size 0.069 × 0.90 (if female). The equation was validated with the validation dataset (R 2 =0.55, P&lt;0.0001). Conclusions: The equation developed provided predicted postnephrectomy GFR and will be helpful for preoperative patient counseling and selecting the type of surgical procedure, especially in elective partial or radical nephrectomy cases.
Stimulant Use and Bone Mineral Density—Reply
Authors: Alexis J. Feuer, Ashley Thai
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Epigenetic biomarkers associated with antitumour necrosis factor drug response in moderate-to-severe psoriasis
Authors: M.C. Ovejero-Benito, T. Cabaleiro, A. Sanz-García, M. Llamas-Velasco, M. Saiz-Rodríguez, R. Prieto-Pérez, M. Talegón, M. Román, D. Ochoa, A. Reolid, E. Daudén, F. Abad-Santos
Journal: British Journal of Dermatology (2017)

It has recently been discovered that epigenetic modifications, specially DNA methylation, participates in the pathology of psoriasis. DNA methylation is a covalent modification dynamic and heritable that takes place in Cytosine-Phosphate-Guanine (CpG) sites and may exert transcriptional effects. Although anti-tumour necrosis factor α (TNF) therapies (adalimumab, etanercept and infliximab) are efficient drugs for moderate-to-severe psoriasis, around 30–50% of psoriasis patients present an inadequate response.

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Characterization of glioblastoma (GBM) vasculature and protein expression of surrounding tumor cells on single FFPE sections with a multicycle multiplexed in situ immunofluorescent staining technology.
Authors: Jingyu Zhang, Colin McCulloch, Yunxia Sui, Sean Dinn, Qing Li, Alberto Santamaria-Pang, Christopher J Sevinsky, Jeremy Richard Graff, Lawrence Weiss, Teng Jin Ong, Fiona Ginty
Journal: Journal of Clinical Oncology (2013)

2097 Background: GBM is the most common brain tumor in humans and has a dismal prognosis. Although antiangiogenic therapy (bevacizumab) is an option for GBM, there is still unmet need to understand tumor pathophysiology and predictive biomarkers. We built a tissue based multiplexed immunofluorescent assays and developed algorithms to identify and quantify tumor vasculature, that enabled quantification, visualization, and colocalization of multiple protein in surrounding tumor cells at single cell and subcellular levels. This assay provides unique opportunity to explore tumor heterogeneity of tissue morphology and their relationships to vasculature, and is a novel tool for biomarker and treatment discovery. Methods: Tissue micro arrays (TMAs) were constructed from 141 GBM patients. Fluorescent dye labeled antibodies against 18 biomarkers were sequentially applied on single sections of these TMAs. Metrics were built to identify vessels, quantify distance of tumor cells to vessels, and analyze expression profiles of biomarkers, including signaling molecules in EGFR, PI3K/AKT, TGF-beta pathways, and hypoxia marker Glut1, in proximity to blood vessels. Results: CD31 was successfully used to identify blood vessels in GMB. Vessel segmentation and quantification were performed on all of the images. Biomarker profiling in the context of blood vessels demonstrated different patterns in close proximity to vessels, with some biomarkers showing increased levels (e.g. SMA, EGFR, pS6), some showing decreased levels (e.g. p4EBP), and others remain the same (FOXO3a, S6). Quantification of biomarkers showed heterogeneous expression within the same sample and across the cohort. In addition, co-localization of the above markers was visualized and demonstrated on single cell and subcellular levels. Conclusions: We were able to use a novel fluorescent multiplexing technology (MultiOmyx) to study GBM biology. This technology allowed the simultaneous analyses of multiple biomarkers of GBM, and provides new insights on the relationship of markers to each other, tumor heterogeneity and angiogenesis.
Effects of radium-223 (Ra-223) with docetaxel versus docetaxel alone on bone biomarkers in patients with bone-metastatic castration-resistant prostate cancer (CRPC): A phase I/IIa clinical trial.
Authors: Michael J. Morris, Yohann Loriot, Karim Fizazi, Christopher Sweeney, Charles J. Ryan, Daniel H. Shevrin, Emmanuel S. Antonarakis, Monica Seger, Chengxing Lu, Celestia S. Higano
Journal: Journal of Clinical Oncology (2017)

154 Background: Interactions between metastatic prostate cancer cells, osteoblasts, osteoclasts, and other participants in bone metabolism are complex and result in pathologic bone physiology. Ra-223, a targeted alpha therapy, accumulates at sites of bone metastases and prolongs survival. Ra-223 and docetaxel (D), acting through different mechanisms of action, may have beneficial effects on bone pathophysiology and tumor microenvironment. Prior data suggest treatment with Ra-223 results in favorable alterations in bone biomarkers that are associated with survival. Methods: 53 patients with progressing CRPC and ≥ 2 bone metastases were randomized 2:1 to Ra-223 (55 kBq/kg q6wk × 5) + D (60 mg/m 2 q3wk × 10) versus D (75 mg/m 2 q3wk with step-down option to 60 mg/m 2 ). Bone resorption (CTX-1, ICTP) and formation (P1NP, bALP) markers, tALP, and PSA were analyzed at wk 19 (after 3 Ra-223 injections) and 3 wk after end of treatment (EOT). Results: Mean % change at wk 19 and EOT are shown (Table). tALP, bALP, P1NP, and PSA declined early during treatment, reaching an average of &gt; 30% decline from baseline by wk 19 in both arms. Mean % declines were greater in the Ra-223 + D versus the D-alone arm at wk 19 and EOT. Bone resorption markers CTX-1 and ICTP showed little decline at wk 19. Conclusions: Ra-223 + D patients had greater % decline in tALP and in bone formation markers bALP and P1NP. Due to small patient numbers and preliminary data, further analysis and correlation with clinical outcomes in a larger study is warranted. Clinical trial information: NCT01106352. [Table: see text]
Periodontal health in early-stage postmenopausal breast cancer survivors on aromatase inhibitors.
Authors: L. Susan Taichman, Marita Inglehart, William Giannobile, Thomas Braun, Giselle Kolenic, Catherine Van Poznak
Journal: Journal of Clinical Oncology (2013)

568 Background: Aromatase inhibitors (AIs) are associated with profound estrogen deprivation resulting in reduced bone mineral density (BMD). Periodontal diseases and tooth loss are associated with estrogen withdrawal and decreased systemic BMD. Little is known as to the impact of AIs on oral health. To investigate oral health as a breast cancer (BCA) survivorship concern, a prospective study was initiated to determine the prevalence of periodontal diseases in postmenopausal early stage (I-IIIA) BCA survivors on adjuvant AI therapy. Baseline assessments are presented here. Methods: Women within 6 months of initiating adjuvant AI for hormone receptor positive BCA were eligible to participate in this study of serial assessments of oral health. A control group of women without BCA and not on AI underwent parallel assessments. Periodontal status was evaluated by the following established dental techniques; (1) periodontal pocket depth (PD), (2) number of teeth with bleeding on probing (BOP), (3) the number of teeth with clinical attachment loss (CAL). Questionnaires regarding socio-demographic and dental utilization were administered to all participants. Linear regression modeling was used to analyze the outcomes. Results: The study met its target accrual of 58 postmenopausal women; 29 with BCA on AI and 29 controls. Demographics were similar regarding age, education, income level, frequency of dental visits, and dental insurance status across both groups. Baseline assessments demonstrated no differences in PD (2.0 mm vs. 2.0 mm; p &lt; 0.95) or the number of teeth (26.6 vs 26.1; p&lt; 0.39). Interestingly, the AI group had significantly more sites of BOP (27.9 vs 16.7; p &lt; 0.02), and higher CAL (5.2 mm vs 4.0 mm; p &lt; 0.01) than did controls. In linear regression analysis adjusted for income, AI use increased CAL by 1 mm (95% CI: 0.15 -1.88). There was also a trend for decreased CAL in subjects with incomes over $75,000 per year (p&lt; 0.06). Conclusions: This first investigation of the periodontal status of women initiating adjuvant AI therpay identifies this population to have signs of increased risk for periodontal disease. Serial oral health assessments are being conducted to assess AI therapy and periodontal changes over time. Clinical trial information: NCT01693731.
Genomic architecture of radioresistant prostate cancer.
Authors: Melvin Chua, Erle Holgersen, Veronica Sabelnykova, Adriana Salcedo, Alice Meng, Michael Fraser, Theodorus Van Der Kwast, Paul Christopher Boutros, Robert G. Bristow
Journal: Journal of Clinical Oncology (2017)

26 Background: Spatial intra-tumoral heterogeneity of prostate cancer is secondary to genomic diversity and multi-clonality. These unique features potentially promote resistance to treatment. Here, we investigated if clonal selection or adaptation of new clones dominates in prostate cancer at the time of recurrence following radiotherapy. Methods: We identified 11 patients with biopsy-proven multifocal recurrent prostate cancer following radiotherapy. Copy number aberration (CNA) profiling was performed on 33 anatomically distinct tumor foci with 11 matched-normals. 4 cases had matched pre-radiotherapy tumors for CNA profiling to assess for clonality. We evaluated for recurrent gene amplifications and deletions, and determined genomic instability by percent genome aberration (PGA). We also compared these genomic indices against 373 sporadic prostate cancers from the Canadian Prostate Cancer Gene Network. Results: We observed large intra- and inter-patient variation (p &lt;0.001, one-way ANOVA) in PGA scores among the radioresistant tumors. Interestingly, although total CNA counts did not differ between the radioresistant and sporadic cohorts (median = 40, radioresistant vs 33, sporadic, p = 0.20], there was a trend for increased genomic instability in the radioresistant cohort (median PGA = 8.8 vs 4.9, p = 0.059). Spatial resolution of gene-level CNAs revealed the acquisition of CNAs that were both common and non-recurrent in the multi-focal radioresistant tumors, thus suggesting a common clonal origin, with subsequent divergent evolution. Importantly, we observed a mixture of CNAs, including known prognostic genes in prostate cancer, namely NKX3-1, PTEN, TP53, CDKN1B, and CDH1,that was shared between pre-treatment and radioresistant tumors, favoring clonal selection. We also discovered a novel deleted region on Chr3p, consisting of RAD18 and FANCD2, which was uniquely present in the radioresistant tumors. Conclusions: Our novel observations in a small cohort of radioresistant prostate cancers favor the model of clonal selection, as opposed to new-onset tumors. These results support the discovery of biomarkers a priori, and targeted treatment of these radioresistant clones to improve the therapeutic ratio of precision radiotherapy.
Up front tandem high-dose chemotherapy (HD) compared to standard chemotherapy with doxorubicin and paclitaxel (AT) in metastatic breast cancer (MBC): Final results of a randomized trial
Authors: P. Schmid, W. Schippinger, T. Nitsch, G. Huebner, R. Kreienberg, W. Schultze, H. Hausmaninger, M. Wischnewsky, H. Samonigg, K. Possinger
Journal: Journal of Clinical Oncology (2004)

641 Background: Trials with late intensification HD have failed to show an advantage in overall survival (OS) for patients with MBC. This trial was initiated to compare up front tandem HD with cyclophosphamide, mitoxantrone and etoposide or standard-dose therapy with AT in patients with MBC. Methods: Between 04/98 and 02/02, 93 pts below 60 ys of age without prior chemotherapy for metastatic disease were randomly assigned to 6–9 courses of AT q3 wks or double HD with PBSCT. G-CSF-mobilized stem cells were collected before and after the 1st course of HD. HD was repeated after 6 weeks. Pts were stratified by menopausal status and hormone receptor (HR) status. HR positive pts received in addition tamoxifen. The primary objective was to compare complete response rates (CR). Results: Due to inadequate accrual the trial was terminated early in 03/02.Treatment groups (HD 48 pts, AT 45 pts) were well balanced for baseline characteristics (median age 49.7 ys, range 27–60; visceral metastases 87.1%; HR+ 71.0%; premenopausal 40.9%). Intent-to-treat (ITT) objective response rate (RR) was 66.7% for HD vs 64.4% for AT (p=0.82). Per protocol (PP) analysis showed 78.0% RR for HD and 64.4% for AT (p=0.26). There was no significant difference in CR (ITT: HD 12.5% vs AT 11.1%; PP: HD 14.6% vs AT 11.1%). After a median follow-up of 22.5 mths, 75 pts have progressed (HD 36, AT 39) and 66 pts have died (HD 34, AT 32). ITT analysis showed no significant difference in median TTP (HD 11.1 mths, AT 10.6 mths; p=0.39), duration of response (DR) (HD 13.9 mths, AT 14.3 mths; p=0.98), treatment-free interval (HD 9.7 mths, AT 6.6 mths; p=0.24) and OS (HD 26.9 mths, AT 23,4 mths; p=0.60). As expected, HD was associated with significantly more grade 3/4 myelosuppression, nausea/vomiting, infection and stomatitis, but less neuropathy than AT. Conclusions: In contrast to our previous analysis (Schmid, ASCO 2002), there are no significant differences in CR, RR, TTP, DR and OS between HD and AT. HD was associated with more acute adverse effects. No significant financial relationships to disclose.
Canadian ALK (CALK): A pan-Canadian multicenter study to optimize and standardize ALK immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for <i>ALK</i> gene rearrangements.
Authors: Ming Sound Tsao, Kenneth Craddock, Guilherme Brandao, Zhaolin Xu, Wenda Greer, Yasushi Yatabe, Diana Ionescu, Sungmi Jung, Ronald F Carter, Aly Karsan, Anna Bojarski, Harmanjatinder S. Sekhon, Gilbert Bigras, Jean Deschenes, Roula Albadine, Melania Pintilie, Jean-Claude Cutz, Danh Tran-Thanh, Emina Torlakovic, Christian Couture
Journal: Journal of Clinical Oncology (2013)

8096 Background: ALK gene rearrangement (ALK+) has been found in 3-5% of advanced non-small cell lung cancer patients. FISH is considered the “gold standard” for identification of ALK+ tumors, but its cost-effectiveness and adoption as a screening assay has been debated. Recent reports suggested that ALK IHC may serve as an alternative screening or possibly a diagnostic method. In this context, CALK was initiated to assess the feasibility of implementing ALK IHC and/or FISH assays across Canadian hospitals. Methods: FISH-confirmed 22 ALK+ and 6 ALK- tumors were used as study samples. Unstained sections and scanned images of HE-stained slides from each tumor block were distributed to participating centres. IHC protocols with best signal to noise ratio using the 5A4 (Novocastra) or ALK-1 (Dako) antibodies were developed for various auto-stainers and implemented to suit the existing conditions of the participating centres. A common FISH protocol using the ALK break-apart probe (Abbott Molecular, Chicago, IL) was developed based on published reports. H-score was used to assess IHC. FISH signals were scored in 100 tumor cells/case by 2-3 pre-trained persons. A second round IHC study using newly distributed slides was completed by 8 centres. Results: Independent IHC scores from 12 centres and FISH scores from 11 centres were collected and analysed. The intraclass correlation coefficients (ICC) between centres for IHC and FISH were 0.84 and 0.68, respectively. Following the analysis of initial IHC results, a second round study resulted in improved ICC of 0.94. One of 23 tumors revealed IHC-/FISH+ discrepancy, with the FISH revealing unusual signal configurations that suggested an atypical rearrangement. However, the sensitivity and specificity of FISH results across centres using the 15 aberrant signals cut-off ranged from 86.7-100% and 100%, respectively. Conclusions: Standardization across multiple centres for ALK testing by IHC and FISH can be achieved. IHC detected all FISH+ ALK tumors, except for one discrepant case with atypical FISH finding of unknown clinical implication. The study was supported by a Pfizer Canada grant.