tbuckley/cabot-search huggingface dataset:
Continuous vs intermittent imatinib treatment in advanced GIST after one year: A prospective randomized phase III trial of the French Sarcoma Group
Authors: J.-Y. Blay, P. Berthaud, D. Perol, I. Ray-Coquard, B. Bui, F. Duffaud, A.-C. Braud, M. Rios, F. Ducimetiere, A. Le Cesne
Journal: Journal of Clinical Oncology (2004)

9006 Background: Imatinib (Im) is usually given in advanced GIST until progression or intolerance. Secondary resistance to Im is often related to the clonal expansion of clones with Im insensitive KIT mutations. Whether intermittent administration of Im may prevent the long term emergence of resistant clones is unknown. Methods: BFR14, a prospective multicentric phase III study of continuous vs interrupted imatinib treatment in advanced GIST, was initiated in June 2002. Inclusion criterias were: advanced GIST, expressing KIT or PDGFRa mutation. After 1 year of treatment with Im, patients are randomized between 1) continuous (CONT) or 2 ) interruption (STOP) of Im until progression and restart. Patients declining randomization were followed. Primary endpoint was progression free survival. Early stopping rule in case of high rates of re-progression at 3 months were scheduled after the randomisation of 14 patients (n>5) and 29 pts (n>10). Results: As of December 2003, 159 pts were included: 61% were males, 39% emales (39%), with gastric 27%, small bowel (32%), large bowel (12%), mesenteric (20%), or other primaries (9%). Metastatic sites were: liver (55%), peritoneum (35%), nodes (6%), others (19%). 13% pts experienced immediate progression. At 6 months, CR was achieved in 10%, PR in 42%, SD in 36%, PD in 6%, NE in 6% . 41 SAE were observed in 29 pts. Surgery was perfomed in 6 (4%) pts during the 1st year. As of Dec 15, 46 of the 74 (62%) candidate pts were randomized, 23 in both arms: 0 and 5 (21%) pts have a documented reprogression at 3 months in the CONT and STOP arms respectively; Im reintroduction enabled tumor control in all pts with sufficient follow-up so far. Conclusions: Although the early stopping rule on progression at 3 months was not met in the first 14 pts randomized in the STOP arm of the BFR14 trial, advanced GIST pts stopping Gleevec® experience frequent re-progression at 3 months. Supported by Grants from the Centre L.Bérard, Cancéropole Rhone Alpes and Novartis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Soluble HER2 (sHER2) as a prognostic serum biomarker of non-small cell lung cancer.
Authors: Bethany Cox Wilson, Andres Cardenas, Kimberly D. Kimbler, Tamas Gal, Lisa A Witt, Susanne M. Arnold, Adam J. Branscum, Andre T. Baron
Journal: Journal of Clinical Oncology (2012)

e21000 Background: The human epidermal growth factor receptor (EGFR/HER) gene family encodes four homologous tyrosine kinases that regulate cell growth and proliferation, survival, motility, and adhesion. HER2 gene amplification and receptor overexpression have been observed in &lt; 20% of non-small cell lung cancers (NSCLC). Serum concentrations of soluble HER2 (sHER2), a proteolytic fragment of the receptor’s extracellular domain, have been associated with tumor HER2 overexpression, advanced stage, and high grade. This study evaluated serum sHER2 as a prognostic biomarker of NSCLC. Methods: Patients with primary NSCLC (n=149) were recruited at the University of Kentucky prospectively between 2002 and 2008 by the Markey Cancer Center Biospecimen Core Program and linked to the Kentucky Cancer Registry - a population-based cancer registry of the NCI Surveillance, Epidemiology and End Results (SEER) Program - to obtain clinicopathological data. Serum samples were collected prior to surgery and quantified to determine sHER2 concentrations by sp185 HER-2 ELISA (Bender MedSystems Diagnostics GmbH). Non-parametric tests were performed to assess whether sHER2 concentrations differed between NSCLC patients stratified by gender, stage, histology, and grade. Cox regression analyses were performed to assess whether sHER2 concentrations, age, gender, stage, histology, and grade are associated with progression free and overall survival. Results: Mean patient age in this case series is 62 years (SD = 10.84 years) and median overall survival is 30 months. Over 97% of patients are smokers. Although serum concentrations do not differ between males and females (p = 0.12), high sHER2 concentrations portend a 72% lower relative risk of death (H.R. = 0.283, p = 0.009) and longer overall survival among men, but not among women (H.R. = 1.012, p = 0.965) adjusted for stage. Conclusions: The results show that low serum sHER2 concentration is an adverse prognosticator of overall survival in males, but not females, and suggest that low serum sHER2 could be useful for stratifying male NSCLC patients for HER2-targeted therapy. Further investigation is warranted to assess sHER2 as a gender dependent prognostic (and potential theragnostic) biomarker of NSCLC.
Parental Sharing on the Internet
Authors: Bahareh Ebadifar Keith, Stacey Steinberg
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
Phase I clinical trial of external hyperthermia and intravesical mitomycin C to treat BCG-refractory bladder cancer.
Authors: Michael Abern, Zeljko Vujaskovic, Mark W. Dewhirst, Lan Lan, Oana I. Craciunescu, Paul Stauffer, Brant Allen Inman
Journal: Journal of Clinical Oncology (2013)

e15560 Background: Patients with non-muscle-invasive bladder cancer (NMIBC) that fail intravesical bacillus Calmette-Guérin (BCG) are at high risk for progression. Radical cystectomy is an effective but morbid treatment option. We tested the safety and efficacy of combined intravesical mitomycin C (MMC) and external deep regional hyperthermia (HT) as a bladder-sparing approach for BCG-refractory NMIBC. Methods: Patients with BCG-refractory NMIBC were eligible for this phase I clinical trial. Treatment consisted of intravesical MMC (40 mg in 40 mL) with concurrent HT with target temperature of 42°C. MMC dwell time was 60-120 min and heating time was 40-60 min. HT was delivered using a BSD2000 device and temperatures monitored with skin, bladder and rectal probes. Treatment was given weekly for 6 weeks (induction) then monthly for 4 months (maintenance). The primary endpoint was toxicity which was assessed using CTCAE 3.0. Secondary endpoints included recurrence-free survival (RFS), progression-free survival (PFS), cystectomy, and overall survival (OS) which were assessed at 3 month intervals with cystoscopy and cytology for 2 years. Results: Fifteen patients were eligible and consented to the clinical trial. Median age was 66 years and 87% were male. Median follow-up was 2.85 years. One patient did not tolerate supine position, two completed induction but recurred prior to maintenance, one recurred after 3 maintenance treatments, and 11 patients received all 10 treatments. The 2 year RFS was 33% (median RFS = 15.4 mos). Six patients (40%) required cystectomy (median time = 20.1 mos). No patient had bladder progression but two patients developed ureteral tumors (not present on baseline imaging). Two patients died, one from ureteral cancer and one of cardiovascular disease, for a 3-year OS of 83% (median OS not reached). No grade III toxicities were observed. Common toxicities were abdominal pain (36%), cystitis (22%), pruritis and urinary tract infection (14%). Conclusions: The combination of MMC and HT for BCG refractory NMIBC was safe and associated with low grade toxicity. While recurrence was common, progression did not occur, and recurrent patients were safely salvaged with cystectomy. Clinical trial information: NCT00734994.
Superior prognosis prediction performance of deep learning for gastric cancer compared to Yonsei prognosis prediction model using Cox regression.
Authors: Woo Jin Hyung, Taeil Son, Minseok Park, Hansang Lee, Youn Nam Kim, Hyoung-Il Kim, Jong Won Kim, Jae-Ho Cheong, Seung Ho Choi, Sung Hoon Noh, Junmo Kim
Journal: Journal of Clinical Oncology (2017)

164 Background: Staging systems for cancer are critical to predict the prognosis of patients. Current staging systems for gastric cancer have limitations to predict individualized and precise prediction of patient’s survival after treatment. We aimed to develop prediction model based on deep learning by estimating the survival probability of patients who underwent gastrectomy. Methods: To predict the survival probability, we used a deep neural network model which consisted of 5 layers: input layer, 3 fully connected layer, and output layer with 8 characteristics (age, sex, histology, depth of tumor, number of metastatic and examined lymph node, presence of distant metastasis, and resection extent) of patients which was previously published Yonsei prediction model using Cox regression. Each layer functioned as the nonlinear weighted sum of lower layer. Five-year overall survival was predicted using the deep learning method and it was compared to Yonsei prediction model. The average area under the curve (AUC) was compared between the models. For internal validation, 5-fold cross validations were carried out. We also performed external validation with a dataset from another hospital (n = 1549). . Results: Deep learning predicted 5-year overall survival of patients with an average accuracy of 83.5% in the test set. The average AUC of deep learning by integrating 8 characteristics was significantly higher than that of Yonsei prediction model (AUC: 0.844 vs. 0.831, P &lt; 0.001) with the same variables. In the external validation the average accuracy of survival prediction was 84.1%. The AUC was also greater in a dataset from other hospital in Korea (AUC: 0.852 vs. 0.847, P = 0.023) Conclusions: Prognosis prediction with deep learning showed superior survival predictive power compared to prediction model using Cox regression. It can provide individualized and precise stratification based on the risk using characteristics of gastric cancer patients.
Overexpression of SETDB1 in relation to poor outcome in gastric carcinoma.
Authors: Wataru Okajima, Shuhei Komatsu, Daisuke Ichikawa, Takuma Ohashi, Taisuke Imamura, Keiji Nishibeppu, Eigo Otsuji
Journal: Journal of Clinical Oncology (2017)

71 Background: SETDB1 is a Histone H3 lysine 9-specific Methyl Transferase belonging to the SET domain. In this study, we tested whether SETDB1 acts as a cancer-promoting gene through its overexpression in gastric cancer (GC). Methods: We analyzed5 GC cell lines and 135 primary GC samples curatively resected in our hospital. Results: Overexpression of the SETDB1 protein was detected in all GC cell lines and primary GC samples (115/135 cases, 85%). Knockdown of SETDB1 using specific siRNA inhibited the proliferation, migration and invasion. Overexpression of the SETDB1 was significantly correlated with lymphatic invasion, deeper tumor depth and higher recurrence rate. Patients with SETDB1-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0041, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SETDB1 was independently associated with worse outcome (P = 0.0178, HR 3.1 (1.20-9.83)). Conclusions: These findings suggest that SETDB1 has a crucial role in tumor cell proliferation and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.
Plasma biomarker analysis of ramucirumab in Japanese patients with advanced gastric cancer: Preliminary results.
Authors: Daisuke Takahari, Takeru Wakatsuki, Tetsuo Mashima, Takashi Ichimura, Keisho Chin, Mariko Ogura, Izuma Nakayama, Tomohiro Matsushima, Hiroki Osumi, Masato Ozaka, Mitsukuni Suenaga, Eiji Shinozaki, Hiroyuki Seimiya, Naoya Fujita, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2017)

72 Background: Ramucirumab, anti-VEGFR2 receptor antibody, showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use; however, no validated biomarker has been available until today. The aim of this study is 1) to reveal the dynamics of plasma biomarkers, 2) to assess the associations between these baseline levels or dynamics and efficacy. Methods: Plasma samples were collected at three points: base line, day 8, and after disease progression. Nine kinds of plasma biomarker involved in angiogenesis were measured by means of ELISA. Progression-free survival (PFS) was estimated using Kaplan-Meier methods and compared using the log-rank test. Comparisons of plasma biomarker levels were performed using Mann-Whitney-U test. Results: Samples were collected from 35 patients. Among them, 25 patients were evaluated when analyzed and 6 patients showed disease progression at the first evaluation. In VEGF-A and PlGF, plasma biomarker levels of day 8 were dramatically elevated in all patients; Day8/ baseline ratios were 18.1 folds in VEGF-A and 19.3 folds in PlGF. On the other hand, Day8/ baseline ratio of VEGFR1 and NRP1 were 0.7 and 0.8, respectively. The others appeared to show variable change at day 8. In survival analysis, lower than median Day8/ baseline ratios of VEGF-A were significantly associated with longer PFS with 6.3 months in &lt; median vs. 2.4 months in ≥ median (p = 0.004). In addition, patients with disease progression at the first evaluation by CT showed higher Day8/ baseline ratios of VEGF-C, Angiopoietin 1, and lower baseline NRP1 levels than those of patients with non-disease progression. Conclusions: Dramatic changes of biomarker levels at day 8 were observed among patients in each biomarker. These changes in VEGF-A, C, and Angiopoietin-1 may be candidate predictive marker of ramucirumab in Japanese patients with gastric cancer.
Hyposensitization in asthmatics with mPEG‐modified and unmodified house dust mite extract
Authors: H. Mosbech, A. Dirksen, S. Dreborg, L. Frølund, J. H. Heinig, U. G. Svendsen, M. Søborg, E. Taudore, B. Weeke
Journal: Allergy (1990)

A double‐blind study on hyposensitization (HS) with two extracts prepared from the house dust mite Dermatophagoides pteronyssinus (Dp) was performed on a group of asthmatics with bronchial sensitivity to Dp. In 18 patients, aluminiumhydroxide was added to the Dp‐extract to give a depot effect (Dp‐group). Nineteen patients were treated with a similar extract in which allergenicity had been reduced by coupling to monomethoxy‐polyethylene glycol (mPEG‐Dp‐group). This extract had previously been shown to have less effect on clinical symptoms and skin sensitivity compared to the Dp‐extract. In the Dp‐ and mPEG‐Dp‐groups, 778 and 675 injections were administered. Fifteen and 12 patients in the Dp‐ and mPEG‐Dp‐groups had systemic reactions ( P &gt; 0.05). The frequency of injections giving systemic reactions was reduced in the mPEG‐Dp‐group: 5.1 % compared to 9.0% in the Dp‐group ( P &lt; 0.01). In the mPEG‐Dp‐group, reactions were mild to moderate, mainly late‐occurring asthma and urticaria, whereas two episodes of anaphylaxis and four of severe asthma occurred in the Dp‐group. The reduction in side effects seems promising, but a further dose increase in the mPEG‐Dp‐group would be necessary to compare the side effects of doses with equal therapeutic effectiveness. High frequency of late local reactions made dose increase impossible with the present slightly modified extract. The systemic side effects occurred more frequently in patients highly skin test‐sensitive to Dp prior to treatment. All patients skin test‐positive to: ≤ 100 BU had systemic reactions. Systemic side effects could not be predicted from the size of previous local reactions.
Evolution of heterogeneous mechanisms of acquired resistance to cetuximab-based therapy in colorectal cancer.
Authors: Clara Montagut, Beatriz Bellosillo, Iria Gonzalez, Alejandro Martinez, Alba Dalmases, Mar Iglesias, Joana Vidal, Marta Salido, Mar Garcia, Marcos Busto, Guadalupe Aguilar, Ester Moragon, Blanca Espinet, Sergi Serrano, Ana Rovira, Joaquim Bellmunt, Joan Albanell
Journal: Journal of Clinical Oncology (2014)

3526 Background: Anti-EGFR drug resistance is a major challenge in metastatic colorectal cancer (mCRC). The aim of this study was to elucidate molecular mechanisms of acquired resistance in mCRC patients treated with cetuximab-based therapy. Methods: 37 mCRC patients with acquired resistance to cetuximab-based therapy with paired tumor samples (prior and at progression to treatment) were prospectively included. In three patients, multiple biopsies were obtained over the course of the disease. Mutations in EGFR, KRAS, NRAS, BRAF and PIK3CA genes were evaluated by next-generation pyrosequencing. Gene amplification was evaluated by FISH. Mutations were also assessed in plasma in 7 representative cases. Results: Eighty-one percent of patients harbored a molecular event (comprising mutations and amplifications) in post-treatment biopsies. In one third of patients, multiple molecular events (range 2-5) coexisted in the same sample. RAS mutations were the most frequent event (40% of patients) and mostly affected exons 3 and 4, followed by mutations in PIK3CA (19%), BRAF (11%), EGFR S492R (8%) and novel mutations in EGFR ectodomain (5%). Of note, in 9 patients the mutations were already detected at diagnosis by next-generation sequencing. Multiple repeat biopsies revealed that the percentage of mutant alleles increased under drug pressure and became undetectable following drug withdrawal. Mutations were detected in plasma samples in 62% of tested cases. Conclusions: We provide comprehensive evidence for the evolution of multiple mechanisms of acquired resistance to cetuximab-based therapy in mCRC. This data establishes the need of routine molecular studies at disease progression to individualize further therapeutic decisions.
Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer’s Disease by Vitamin E and Selenium Trial (PREADViSE)
Authors: Richard J. Kryscio, Erin L. Abner, Allison Caban-Holt, Mark Lovell, Phyllis Goodman, Amy K. Darke, Monica Yee, John Crowley, Frederick A. Schmitt
Journal: JAMA Neurology (2017)

Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia.To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men.The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms.Participants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment.Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen.The mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo.Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.
Discordant ER, PR, and HER2 status between primary and metastatic breast cancer as prognostic factor.
Authors: Hee-Chul Shin, Wonshik Han, Hyeong-Gon Moon, Seock-Ah Im, Woo Kyung Moon, In-Ae Park, Sung Jun Park, Dong Young Noh
Journal: Journal of Clinical Oncology (2013)

1039 Background: The receptor status including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) of metastases may be different from that of the primary breast cancer. This discordance of receptor status may influence patient prognosis. We investigated discordance of receptor status between primary breast cancer and distant metastases in the same patients and its effect on prognosis. Methods: ER, PR, and HER2 status in metastases were available in 173 patients. The receptor status was compared between primary tumors and metastases. Tumors were classified as triple-negative breast cancer (TNBC) or non-triple-negative breast cancer (non-TNBC) according to receptor status and as concordant and discordant depending on the difference of receptor status between primary and metastatic breast cancer. Survival analysis was performed depending on concordant or discordant receptor status. Results: Discordance for ER, PR, and HER2 was 18.5%, 23.7%, and 10.4%, respectively. Concordant non-TNBC and TNBC between primary tumors and metastases was 69.9% and 17.9%, respectively. Discordant TNBC was 12.1%. On multivariate analysis, patients with discordant TNBC had unfavorable survival compared with patients with concordant non-TNBC (relative risk 2.544, 95% confidence interval, 1.220-5.303, p = 0.013). The median survival after recurrence was 41.8 months for patients with concordant non-TNBC, 20.7 months for patients with concordant TNBC, and 19.9 months for patients with discordant TNBC (p &lt; 0.0001). Conclusions: The change of ER, PR, and HER2 status between primary and metastatic tumors occur and discordant TNBC is associated with poor survival.