tbuckley/cabot-search huggingface dataset:
ALK chromosomal alterations in colon cancer patients.
Authors: C. Montagut, A. B. Galvan, M. Gallen, M. Salido, F. Sole, F. G. Rojo, E. Arriola, A. Rovira, J. Bellmunt, J. Albanell
Journal: Journal of Clinical Oncology (2010)

10537 Background: The identification of oncogenic chromosomal alterations in anaplastic lymphoma kinase (ALK) in lung cancer and neuroblastoma has revealed ALK as a potential candidate for anticancer targeted therapy. Thus, ongoing clinical trials with ALK inhibitors are showing promising results. ALK chromosomal alterations in other solid tumors are controversial. The aim of this study was to analyze ALK translocations and gene copy number status in a series of colorectal cancer patients and correlate these findings with tumor pathological features including TNM staging, KRAS and BRAF mutations as well as clinical outcome. Methods: ALK status was retrospectively evaluated by fluorescence in situ hybridization (FISH) with a break-apart ALK probe and centromeric probe of chromosome 2 in biopsies from colorectal cancer primary tumors, as were KRAS and BRAF by mutational analysis. Survival was analyzed by Kaplan-Meier method. Immunohistochemistry to assess ALK expression is ongoing. Results: Ninety-eight colorectal cancer patients were evaluated. Normal colon mucosa from 10 patients was used as negative control. Thirty-seven per cent of the patients had an increase in ALK gene copy number (3-5 copies) with the percentage of cells with ALK copy gain within a tumor ranging between 6%-46% (mean 22%). There was no correlation between ALK gene amplification and KRAS mutational status. BRAF mutations were observed in five patients and interestingly all these patients had ALK normal copy number. ALK translocations were not observed. ALK amplification was correlated with nodal status. Forty-three per cent of patients with positive nodal status had an increase in ALK copy number, while only 15% of patients with negative lymph nodes had ALK amplification (p = 0.05). ALK amplification was not correlated with overall survival. Conclusions: The identification of ALK gene amplification in colorectal cancer patients reveals a potential new therapeutic target for this tumor. Moreover, the correlation between ALK amplification and nodal status suggests that ALK amplified tumors have a more aggressive phenotype. Further evaluation of the biological meaning of ALK amplification in colorectal cancer is ongoing. No significant financial relationships to disclose.
Short-term treatment with dextromethorphan attenuated enclothelial dysfunction, inflammation, and oxidative stress in healthy male smokers
Authors: Ping-Yen Liu, Chih-Chan Lin, Wei-Chaun Tsai, Yi-Heng Li, Li-Jen Lin, Jyh-Hong Chen, Jau-Shyong Hong, Hua-Lin Wu
Journal: Journal of the American College of Cardiology (2008)
Trends in Health-Related Quality of Life After a Diagnosis of Ductal Carcinoma In Situ
Authors: Vicki Hart, Brian L. Sprague, Susan G. Lakoski, John M. Hampton, Polly A. Newcomb, Ronald E. Gangnon, Amy Trentham-Dietz
Journal: Journal of Clinical Oncology (2016)

Studies of quality of life (QoL) are scarce among survivors of ductal carcinoma in situ (DCIS). The objective of this study was to assess long-term QoL in DCIS survivors in relation to age at diagnosis, time since diagnosis, and treatments received.
Multi-centre, phase II study of combination antibody therapy with epratuzumab plus rituximab in relapsed/refractory indolent and aggressive NHL: Promising preliminary results
Authors: S. J. Strauss, T. A. Lister, F. Morschauser, M. Gramatzki, P. Solal-Céligny, P. L. Zinzani, A. Engert, B. Coiffier, D. F. Hoelzer, I. D. Horak
Journal: Journal of Clinical Oncology (2004)

6579 Background: The humanised anti-CD22 monoclonal antibody, epratuzumab has shown clinical single agent anti-lymphoma activity. Here, we report interim results from a multi-centre, open-label, single-arm study of epratuzumab in combination with rituximab in patients with relapsed/refractory B-cell NHL. Methods: Sixty-five pts (57% male; 43% female) with a median age of 61 yrs (range 23–87, 30% >65) were enrolled, 45 with indolent histology (36, follicular lymphoma) and 20 pts with aggressive histology (13, DLBCL). Three pts had stage II, 20 stage III, and 42 stage IV disease; 43% had bone marrow involvement; 37% an elevated LDH; 35% had >2 prior treatments with a median time from last therapy of 1.1 yr (range 0.1–12); and 77% of pts were rituximab-naïve. Pts received 360 mg/m2 of epratuzumab i.v. over 60 mins followed by infusion of 375 mg/m2 of rituximab weekly for four consecutive weeks. Results: Combination antibody therapy was well tolerated; 44 pts (68%) experienced 1 or more adverse events (AEs). The most frequent AEs were rigors (22%), fever (15%), hypotension (14%) and nausea (11%). One infusion reaction (hypotension) required termination of therapy. To date, 20 (57%) of 35 evaluable pts with indolent follicular lymphoma (FL) achieved an objective response (OR) as determined using the IWG response criteria, including 8 (23%) complete responses/unconfirmed complete responses (CR/CRu) and 12 (34%) partial responses (PR), while 6 (46%) of 13 pts with DLBCL achieved an OR, including 3 (23%) each having CR/CRu or PR. At this time, at the 15 month assessment, the median TTP has not been reached in pts with indolent FL (31% have progressed so far, whereas 69% of pts with DLBCL have progressed). Conclusions: This combination monoclonal antibody therapeutic regimen appears feasible, well tolerated, and has promising anti-lymphoma activity that warrants further study in a prospective, randomised clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunomedics, Inc. Immunomedics, Inc. Immunomedics, Inc. Immunomedics, Inc. Immunomedics, Inc.
Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor
Authors: A Bacigalupo, G Piaggio, M Podesta, MT Van Lint, M Valbonesi, G Lercari, PG Mori, M Pasino, E Franchini, L Rivabella
Journal: Blood (1993)
Can the short screening test Vulnerable Elders Survey 13 (VES-13) substitute for the time-consuming comprehensive geriatric assessment (CGA) to identify vulnerable/frail elderly breast cancer patients?
Authors: S. Monfardini, U. Basso, P. Fiduccia, A. Brunello, Z. Baretta, C. Soldàa, E. Lamberti, F. Bozza, A. Jirillo, C. Falci
Journal: Journal of Clinical Oncology (2010)

9114 Background: The aim of this prospective, double-blind study was to evaluate sensitivity, specificity, positive and negative predictive values of VES-13, a 13-item function-based self-report questionnaire, as a rapid tool to uncover vulnerability/frailty compared with full CGA. Methods: All consecutive breast cancer patients aged ≥70 years referred from April 2008 to January 2010 to our medical oncology division underwent both CGA and VES-13. Tests were performed by two different investigator groups, not interchangeable and reciprocally blinded. A final score of 3 or more at the VES-13 was considered as predictive for vulnerability/frailty. At CGA patients were divided into fit, vulnerable and frail (Balducci et al Oncology 2000). Results: 150 patients entered the study, median age 76 years (range 70-94). One hundred twenty-five patients (83.3%) presented with early disease. Ninety-five patients (63.3%) were able to complete VES-13 autonomously, 8 patients (5.3%) required help while in 47 cases (31.4%) the questionnaire was completely administered by a research nurse. With CGA, 84 patients were fit (56.0%), 66 were vulnerable/frail (44%). The median time to perform VES-13 was 4 minutes (range 2-12) compared to 29 minutes (range 11-65) for CGA. Twenty five point nine percent of elderly patients with favourable VES-13 score were vulnerable/frail at full CGA while 34.8% of patients with unfavourable VES-13 were fit, the negative and positive predictive values being 74.1% and 65.2%, respectively. Sensibility and specificity of VES-13 to uncover vulnerability/frailty at full CGA were 68% and 71%, respectively. Conclusions: One third of elderly breast cancer patients had significant troubles in self-compiling the questionnaire. VES-13 significantly reduced the time of geriatric assessment, but sensitivity and specificity were unsatisfactory. Caution should be recommended in using VES-13 as a substitute for full CGA in both everyday practice and clinical trials. No significant financial relationships to disclose.
Determination of thresholds for the assessment of response to therapy relying on volume-based tumor burden in pulmonary CT images.
Authors: Hubert Beaumont, Jean Marc Labatte, Simon Souchet, Antoine Iannessi, Dag Wormanns
Journal: Journal of Clinical Oncology (2013)

e18508 Background: Image-based biomarkers play an increasing role in the assessment of response to therapy. The widely adopted Response Evaluation Criteria in Solid Tumor (RECIST) mainly rely on the assessment of the Longest Axial Diameter (LAD) of tumors. A growing community suggests that quantifying the tumor volume addresses some of the RECIST limitations. However no consensus has yet emerged regarding the applicable thresholds classifying volume-based response. This study aims at determining such threshold values for tumors observable in pulmonary CT images. Methods: Our study is based on published data from the Quantitative Imaging Biomarker Alliance (QIBA) which reports a 15% variability in measuring the tumor volume. We analyzed additional clinical data in a retrospective study involving 10 patients with Non-Small Cell Lung Cancer (NSCLC), followed over 7 time points in average with CT. 2 expert radiologists and 5 imaging scientists measured the volume of each tumor at each time point. Response evaluation was modelled according to statistical inference of the ratio of two longitudinal measurements by the Geary-Hinkley (GH) transformation. We hypothesised a normal distribution of the measurements. Results: The study confirmed the previously published 15% variability in measuring tumor volume. From our data, the GH transformation appeared suitable to infer the evaluation while considering a normal distribution of the variability.We found that, using the volume of lesions, a tumor burden reduction corresponds to a decrease of at least -35 %, whereas a tumor burden growth is associated with an increase of at least +55%. These thresholds featured a 5% type I error. Applying the model to clinical data, we confirmed the impact on inter-reader agreement. Conclusions: Based on a well established evaluation of the variability of measurement and relying on an analytical model, we determined thresholds required to classify patient’s response to treatment when monitoring the volume of lesions. Our approach provides a couple of threshold values for given precisions of measurements and Type I error, making our approach generic and applicable to other longitudinal evaluations.
Comparison of p53 genotype and phenotype: Site of mutation predicts outcome in patients with bladder cancer
Authors: S. J. Beil, B. George, L. Wu, J. Cai, N. Patten, L. Young, S. Groshen, R. H. Datar, R. J. Cote
Journal: Journal of Clinical Oncology (2005)

9561 Background: p53 alterations at the protein or gene level are important in the development and progression of bladder transitional cell carcinoma (TCC). We studied the association of p53 phenotype and genotype with patient outcome and identified specific exonic mutations that may influence clinical outcome. Methods: p53 status in archival paraffin embedded tissues was investigated by immunohistochemistry (IHC) (phenotype) and complete sequencing of the coding region using Affymetrix p53 GeneChip analysis (genotype) in invasive TCC of the bladder from 162 patients Results: Nuclear accumulation of p53 protein by IHC (alt phenotype) showed concordance with p53 gene mutations (mut p53) by GeneChip analysis (p<0.001). When examined separately, alt p53 phenotype and mut p53 genotype were significantly associated with increased rates of bladder cancer recurrence (p<0.001) and (p=0.0037) respectively. As a single determinant p53 phenotype appeared to be a better predictor of outcome than genotype. When the site of mutation was examined, bladder cancers with mutations in exon 5 had a significantly lower recurrence rate than tumors with mutation at other exons and were identical in outcome with tumors showing no p53 mutations (wt genotype) (p<0.002). We then examined if patients could be better stratified for risk of recurrence by combining p53 phenotype and genotype status. Tumors with exon 5 mutations were grouped with those with no p53 mutations (wt p53 genotype). The 5 year recurrence-free survival rates were 76% (wt phenotype - wt genotype, n=89), 45% (wt phenotype - mut genotype, n=11), 42% (alt phenotype - wt genotype, n=32) and 27% (alt phenotype - mut genotype, n=30) (p<0.01). Conclusions: This study indicates that mutations in exon 5 of the p53 gene do not adversely impact outcome in patients with bladder cancer. When taking site of mutation into account, the combination of p53 phenotype and genotype stratifies patients into low, intermediate, and high risk for recurrence, providing better prediction of risk than p53 genotype or phenotype alone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Molecular Systems
Preliminary report of a randomized trial of different docetaxel schedules in non-small cell lung cancer patients failing previous chemotherapy
Authors: Y.-M. Chen, J.-F. Shih, C.-M. Tsai, R.-P. Perng, J. Whang-Peng
Journal: Journal of Clinical Oncology (2004)

7112 Background: To evaluate and compare the efficacy of different docetaxel schedules in NSCLC patients who failed previous chemotherapy. Methods: Treatment consisted of (A) docetaxel 35 mg/m2 intravenous infusion (IV) on days 1, 8, and 15 of every 4 weeks; (B) docetaxel 40 mg/m2 IV on days 1 and 8 of every 3 weeks; and (C) docetaxel 75 mg/m2 IV on day 1 of every 3 weeks. Patients were randomised at a ratio of 2:2:1, with (C) arm as a control arm. Between January 2002 and October 2003, 113 patients were enrolled into the study, and 101 patients were already off-study during that period. Results: Analysis of these 101 patients showed a patient number of 41:38:22, mean age: 67:67:64.5, median cycles received: 4:3:3, and objective response rates of 22%:10.5%:0%. Grade 3/4 neutropenia was significantly higher in the (C) arm. The majority of (C) arm patients needed a decrease in the treatment dose due to grade 4 or febrile neutropenia. Median survival was 7.1, 6.6, and 4.6 months, respectively. Conclusions: Weekly docetaxel chemotherapy produces a relatively lower toxicity profile, and better compliance and response rate than the conventional 3-week schedule. No significant financial relationships to disclose.
Long-term survivorship in patients (pts) with metastatic renal cell cancer (mRCC): A retrospective study from the MD Anderson Cancer Center (MDACC).
Authors: Matthew T. Campbell, Amishi Yogesh Shah, Neda Hashemi, Kirtan Das Nautiyal, Paul Gettys Corn, Lance C. Pagliaro, Eric Jonasch, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2015)

510 Background: The overall survival (OS) of pts with mRCC has improved since the introduction of targeted therapies (TT). We sought to characterize the baseline characteristics, management, and outcomes of pts who survived &gt; 4 yrs from date of diagnosis of metastatic disease (Met Dx). Methods: We retrospectively reviewed medical records of consecutive pts who were diagnosed with mRCC and evaluated at MDACC from 1/1/2001 to 12/31/2008. Descriptive statistics and Kaplan-Meier methods were used to estimate OS times. Results: For 729 mRCC pts identified, median OS was 2.3 years (95% CI: 2.1, 2.5); 219 (30.0%) pts have survived &gt;4 yrs, and 167 (22.9%) pts have survived &gt;5 yrs. For pts diagnosed in the cytokine era (2000 to 2004) median OS was 2.3 yrs (95%CI: 2-2.6) compared to median OS 2.4 yrs (95%CI: 2.0-3.0) for pts diagnosed in the targeted era (2005-2008). Of the 219 pts, 205 pts had adequate baseline information. Conclusions: Since 2000, approximately 30% of mRCC pts have survived &gt;4 yrs and 23% have survived &gt;5 yrs. Patients spent more time on treatment in the targeted compared to the cytokine era. Understanding the health problems and costs long-term survivors face is essential to devise therapeutic and coping strategies. [Table: see text] [Table: see text] [Table: see text]
Randomized phase II study of picoplatin in combination with 5-fluorouracil and leucovorin (FOLPI) as a neuropathy-sparing alternative to modified FOLFOX-6 as first-line therapy for colorectal cancer (CRC)
Authors: R. Earhart, S. Cheporov, O. Gladkov, M. Biakhov, H. Breitz, R. De Jager
Journal: Journal of Clinical Oncology (2009)

4026 Background: Picoplatin (Pico) was designed to overcome platinum resistance and has the potential for improved safety compared to other platinum agents. FOLFOX (5-FU, LV, oxaliplatin [oxali]) treatment for advanced CRC has dose-limiting oxali- related neurotoxicity. The incidence of grade (G) 3–4 neurotoxicity with single-agent Pico across studies was &lt;2%, suggesting that Pico may provide a neuropathy-sparing alternative to oxali. A Phase I trial identified the Pico MTD at 150 mg/m 2 when infused Q4W with Q2W FU/LV. The present study evaluates Pico when administered Q4W with Q2W FU and LV (FOLPI) vs. modified (m) FOLFOX-6 (FOLFOX) as 1st line treatment for patients (pts) with advanced CRC. Methods: Each pt received LV and infusional FU per mFOLFOX-6 Q2W. Pts with no prior chemotherapy for advanced CRC received Pico Q4W (150 mg/m 2 ) or oxali Q2W (85 mg/m 2 ). Tumor response was assessed by RECIST using CT scans. Adverse events (AEs) were assessed with CTCAE. Neuropathy was assessed using the FACT-Neurotoxicity questionnaire and by a neurologist blinded to treatment. Results: 101 pts were randomized (50 to FOLPI, 51 to FOLFOX). Pts have received 213 (median 4, max 11) 4-week cycles of FOLPI and 414 (median 8, max 21) 2-week cycles of FOLFOX. Median dose intensity of Pico = 28 mg/m 2 /wk (range 19–44); mean relative dose intensity = 77%. Median dose intensity of oxali = 36 mg/m 2 /wk (range 28–43); mean relative dose intensity = 86%. Neurotoxicity was observed in 65% of pts on FOLFOX (10% G 3/4) and 28% of pts on FOLPI (no G 3/4). Most frequent G 3/4 AEs on FOLPI were neutropenia (60%), thrombocytopenia (40%) and anemia (14%). In the FOLFOX arm, other than neuropathy, the most frequent G 3/4 AEs were neutropenia (20%) and thrombocytopenia (12%). Disease control (CR+PR+SD) was 76% for FOLPI and 76% for FOLFOX. In the FOLPI arm there were 1 CR (2%) and 11 PR (22%). In the FOLFOX arm there were no CRs and 13 PR (26%). Conclusions: In this ongoing trial, FOLPI with Pico Q4W shows comparable disease control as measured by RECIST compared to FOLFOX. Neurotoxicity was less frequent and less severe in the FOLPI arm compared to the FOLFOX arm. Pico therefore may be a neuropathy-sparing alternative to oxaliplatin in CRC. [Table: see text]
Loss of potential reward is best motivator in workers’ wellness programme, study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

Many workplace wellness programmes seek to encourage participation by providing financial incentives, either by rewarding workers who achieve certain goals or penalising them for failing to do so. Nevertheless, most workplace activity programmes to date have not proved effective, especially in motivating the most sedentary workers to increase their level of physical activity.

In a new US study1 Mitesh S Patel, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues sought to compare the effectiveness of three financial designs for …
Rate and Clinical Presentation of Macrophage Activation Syndrome in Patients With Systemic Juvenile Idiopathic Arthritis Treated With Canakinumab
Authors: Alexei A. Grom, Norman T. Ilowite, Virginia Pascual, Hermine I. Brunner, Alberto Martini, Daniel Lovell, Nicolino Ruperto, Karolynn Leon, Karine Lheritier, Ken Abrams
Journal: Arthritis & Rheumatology (2015)

Objective In pivotal trials, canakinumab has been shown to be effective in the treatment of systemic juvenile idiopathic arthritis (JIA), but reported adverse events have included macrophage activation syndrome (MAS). This study was undertaken to assess the impact of canakinumab on MAS incidence. Methods An independent MAS Adjudication Committee (MASAC), consisting of 3 of the authors, was convened, and a search of databases from clinical studies of canakinumab treatment in systemic JIA was performed using MASAC‐specified adverse event terms to identify potential MAS events. These were then adjudicated as “probable MAS,” “possible MAS,” or “MAS unlikely,” using criteria developed by the MASAC. MAS rates were expressed as numbers of cases per 100 patient‐years. Results Of 72 potential MAS cases identified, 21 events (19 with canakinumab treatment; 2 with placebo treatment) in 19 patients were adjudicated as being probable MAS and 10 events in 9 patients as being possible MAS. Systemic JIA was well controlled in the majority of canakinumab‐treated patients at the time of MAS. The time period between initiation of canakinumab treatment and onset of MAS ranged from 3 to 1,358 days (median 292 days). When the rates of probable MAS events were compared between canakinumab‐treated patients (2.8 per 100 patient‐years) and placebo‐treated patients (7.7 per 100 patient‐years), the difference was not significant (−4.9 [95% confidence interval −15.6, 5.9]). There were 3 deaths due to MAS‐related complications (2 in patients receiving canakinumab; 1 in a patient receiving placebo); full recovery was reported in all other patients. Infections were the most common trigger of MAS, and the clinical features of MAS were not modified by canakinumab. Conclusion Canakinumab does not have a significant effect on MAS risk or its clinical features in patients with systemic JIA. Infections are the most common trigger, and MAS occurs even in patients whose systemic JIA is well controlled with this treatment.
Getting Warmer on Critical Care for Head Injury
Authors: Claudia S. Robertson, Allan H. Ropper
Journal: New England Journal of Medicine (2015)

Unlike the successes for almost every other organ, resuscitation of the brain has been a fitful pursuit, punctuated by enthusiasm in early trials and subsequent disappointment. Even hypothermia after cardiac arrest, a seeming success, was tempered by a study in the Journal showing that cooling to either 33°C or 36°C gives the same results.1 One strong point in the field had been the treatment of raised intracranial pressure, but trials involving patients with severe head trauma that were also published in the Journal have suggested that removing part of the skull to reduce intracranial pressure is ineffective2 and that in . . .