tbuckley/cabot-search huggingface dataset:
Randomized phase II study of maintenance vandetanib (ZD6474) in small cell lung cancer (SCLC) patients who have a complete or partial response to induction therapy: NCIC CTG BR.20
Authors: A. M. Arnold, M. Smylie, K. Ding, Y. Ung, B. Findlay, C. W. Lee, M. Djurfeldt, L. Seymour, P. Langmuir, F. Shepherd
Journal: Journal of Clinical Oncology (2007)

7522 Background: Vandetanib (V) is an inhibitor of vascular endothelial and epidermal growth factor receptors. This trial sought to determine whether maintenance V, given after standard chemotherapy (CT) and radiation (RT), prolonged progression-free survival (PFS) in responding patients with SCLC. Secondary endpoints: overall survival (OS) and toxicity. Methods: Phase II randomized, study of V 300 mg PO daily or placebo (P). Eligibility: complete (CR) or partial response (PR) to platinum-based CT, ECOG PS 0–2 and completion of RT (thoracic or prophylactic cranial). Statistics: 80% power to detect a 2.5 months improvement in median PFS (estimate for P of 4 months) using a 1-sided 10% level test (100 eligible patients; 77 events). Results: Between May 2003 and March 2006, 107 patients were accrued from 17 centres. Median follow up: 13.5 months. 46 had limited disease (LD); 61 extensive disease (ED). There were fewer PS 0 patients (11 vs. 20), and fewer had CR to initial CT (4 vs. 8) in the V arm. V patients were more likely to experience toxicity and require dose modification. The most frequent toxicities leading to dose modifications were gastrointestinal and rash. Clinically asymptomatic QTc prolongation was observed in 8 V patients. 83 of 107 patients developed progressive disease (43 on V; 40 on P). The median PFS for V was 2.7 months (80% C.I.: 1.1 –4.5) and 2.8 months for P (80% C.I.: 1.9 –5.6); estimated hazard ratio (HR) was 1.01 for V vs P (80% C.I.: 0.75 –1.36, 1-sided P-value = 0.51). Median OS for V was 10.6 months vs. 11.9 months for P; HR was 1.43 for V vs. P (80% C.I.: 1.00 –2.05, 1-sided P-value = 0.90). In a planned subgroup analysis, a significant interaction was noted (P-value = 0.01); with LD patients randomized to V having a longer OS (HR: 0.45, 1-sided P-value = 0.07), whereas ED patients randomized to V had a shorter OS compared to P (HR: 2.27, 1-sided P-value = 0.996). Conclusion: V failed to demonstrate efficacy as maintenance therapy for SCLC. Future targeted therapies should probably be explored concurrently with chemotherapy. This study was supported by the Canadian Cancer Society and AstraZeneca. [Table: see text]
Clinical Relevance of Tyrosine Kinase Fusion Genes in Pediatric BCR-ABL1-like Acute Lymphoblastic Leukemia
Authors: Judith M. Boer, Aurélie Boeree, João R.M. Marchante, Berna Beverloo, Gabriele Escherich, Hester A. de Groot-Kruseman, Rob Pieters, Monique L. Den Boer
Journal: Blood (2015)
Systemic treatment of elderly patients with NSCLC: Results of a German prospective observational study.
Authors: Karl Matthias Deppermann, Gert Hoeffken, Dieter Wuerflein, Matthias Feurer, Achim Rittmeyer, Sabine Bohnet, Sylke Nagel, Christian Schumann, Rudolf M. Huber, Wolfgang Gleiber, Ernst Müller, Frank Feldmeyer, Martin Wolf, Hans Werner Tessen, Ulrich Hutzschenreuther, Christoph Schulz, Sieglinde Stern, Dirk Pott, Clemens Schulte, David Heigner
Journal: Journal of Clinical Oncology (2014)

e19052 Background: In various trials designed especially for elderly patients with NSCLC stage IIIB/IV (≥ 70 years) survival and QoL benefit from single or combination chemotherapy could be demonstrated. Treatment decision concerning single or combination chemotherapy should be based on performance status and co-morbidities. We prospectively evaluated treatment behaviours for elderly patients in Germany in clinical practice. Methods: Between November 2009 and October 2013 a total of 253 patients were included. Participating centres were limited to 20 patients and had to enroll consecutive NSCLC patients ≥ 70 years with stage IIIB or IV. Co-morbidities accrued prospectively in questionnaire and weighted according to Charlson Score. Results: Median age was 75.5 years ranging from 70 through 92 years. 75% of all patients were male. Co-morbidities: 2% none, 5% one, 15% two, 24% three and 55% with more than three concomitant diseases. Most common co-morbidities were hypertension (69%), COPD (42%) and diabetes (22%). In total 237 patients (94%) received a systemic cancer treatment. Of those, 172 patients (73%) received combination and 58 patients (24%) single-agent therapy. Combination was mainly based on platinum therapy (Carboplatin 66%, Cisplatin 30%), whereas Vinorelbine was the most frequent single-agent therapy seen in 50% of cases. A total of 38 patients were aged > 80 years. Of these 20 patients (53%) received single-agent therapy, 11 patients (29%) a platinum doublet (Carboplatin) and 6 patients (16%) no systemic treatment. No patient > 80 years received Cisplatin. Median survival of all patients was 16.9 months. Patients with a Charlson Score of ≤ 6 achieved a median survival of 17.9 months, whereas patients with a score of > 6 reached 12.0 months, respectively. In comparison, in the selected group of patients receiving combination therapy median survival was 23.5 months. Patients aged > 80 years showed a median survival of 5.7 months. Conclusions: Nearly all patients elder 70 years received systemic chemotherapy. Similar to younger patients elderly patients receive a platinum doublet in clinical practice. In patients elder 80 years single agent therapy is the most frequent treatment.
Impact of the LIVESTRONG at the YMCA Program on physical activity, fitness, and quality of life in cancer survivors.
Authors: Melinda L Irwin, Brenda Cartmel, Maura Harrigan, Tara Beth Sanft, Celeste Wong, Meghan Hughes, Norbert Hootsmans, Bridget Winterhalter, Laura Shockro, Keelin O'Connor, Sara M. Tolaney, Erica L. Mayer, Rachel Lynn Yung, Rachel A. Freedman, Jennifer A. Ligibel
Journal: Journal of Clinical Oncology (2015)

9508 Background: Physical activity (PA) has been linke d to cancer risk and outcomes, yet many survivors are inactive. We evaluated the impact of the LIVESTRONG at the YMCA program, an exercise program available for cancer survivors at YMCA’s across the USA, on PA, fitness, and quality of life (QOL). Methods: Participants were recruited through Yale Cancer Center/Smilow Cancer Hospital and Dana-Farber Cancer Institute. Key eligibility criteria included having a cancer diagnosis and being able to walk. Participants were randomized to immediate participation in a 12-week LIVESTRONG at the YMCA program at a participating YMCA in CT or MA, or to a wait-list control group. Study measures were collected at baseline and 12-weeks. Intervention effects were evaluated using chi-square tests and generalized linear models, with change at 12-weeks in PA and fitness (assessed through the 6-Minute Walk Test [6MWT]) as primary endpoints. Results: A total of 186 participants were randomized (95 to the LIVESTRONG Program and 91 to control). The majority of patients had stage I-II disease and 50% had breast cancer. A majority of participants were inactive at baseline, with only 34% reporting 150+ min/wk of PA. Participants randomized to the LIVESTRONG Program attended on average 83% of scheduled sessions over the 3-month program and experienced significant increases in physical activity (75% exercising at 150+ min/wk vs. 25% of controls, p < .05), and improvements in fitness and QOL compared to controls (Table). Conclusions: The LIVESTRONG program was effective in increasing PA, fitness and QOL in cancer survivors. Additional work is needed to evaluate sustainability of these effects, but this program could provide a platform to increase physical activity in thousands of cancer survivors across the USA. Clinical trial information: NCT02112149.Baseline to 12-week changes in PA, fitness, and QOL, means (SD). Baseline Changes over 12 weeks Exercisers Control p-value Exercisers Control p-value Physical Activity (min/wk) 158.5 (215.0) 119.9 (169.8) 0.18 71.0 (243.4) -23.6 (180.2) 0.004 6MWT (ft) 1592 (254) 1578 (335) 0.50 111 (204) 15 (220) 0.007 FACT-G 90.5 (14.4) 88.7 (12.3) 0.35 2.5 (1.1) -0.3 (1.1) 0.024
Distinct Effects of SCF and Hes1 On Normal Hematopoietic Stem and Progenitor Cells During Leukemic Cell Expansion in a T-ALL Mouse Model
Authors: Chen Tian, Zhipan Cao, Qiao Li, Jinhong Wang, Zhenyu Ju, Weiping Yuan, Guoguang Zheng, Tao Cheng
Journal: Blood (2012)
Phase II trial of intravenous carboplatin (C), oral everolimus (E), and prednisone (P) in docetaxel-pretreated (DP) metastatic castrate-resistant prostate cancer (mCRPC): A Prostate Cancer Clinical Trials Consortium study.
Authors: Muthu Kumaran Veeraputhiran, Daniel H. Shevrin, Mark N. Stein, Lance K. Heilbrun, Daryn Smith, Jing Li, Brenda Dickow, Elisabeth I. Heath, Ulka N. Vaishampayan
Journal: Journal of Clinical Oncology (2013)

5041 Background: A phase II clinical trial was conducted of the combination of C and E due to the synergy noted. Methods: The primary endpoint was time to progression (TTP). Intravenous C at a target AUC of 5 on day 1, and oral E 5mg once daily and P 5mg twice daily were administered in 21 day cycles. PSA was assessed every 21 days and radiologic response was assessed every 3 cycles. Secondary endpoints included overall survival (OS), the correlation of TTP with phosphorylated (p) mTOR, pAKT, p70S6, and circulating tumor cells (CTC). A 1-stage study design assumed: a reference median TTP = 1.5 months; 1-sided alpha = 0.15; and power = 0.90, requiring 26 patients (pts). Results: 26 pts enrolled; median age 69 years (range 54-86) ;8 African American and 18 Caucasians. Median pretherapy PSA was 190 ng/ml (range 13 - 2174). 18 pts (69%) each had bone pain and Gleason score &gt; 8. 125 cycles have been administered; median 3 cycles (range 1 - 16). Predominant grade 3 or 4 toxicities were thrombocytopenia in 8 pts, pulmonary embolism in 2 and neutropenia in 3. No treatment related deaths occurred. 4 (15%) had a &gt; 30% PSA decline and 1 had a &gt;90% PSA decline. 8/19 pts had stable disease but no objective responses in MD. The median TTP and OS were 2.5 months (90% CI: 1.8 - 4.3), and 12.5 months (90% CI: 6.7 - 16.1), respectively. Median area under curves were 5.9 (range, 4.3 – 11.0) and 4.5 (range, 4.1 – 7.1) mg/mL*min with C given alone and in combination with E, respectively. E did not influence pharmacokinetics of C. Median baseline CTC (n=18) was 30 (range 0-2372). 5/18 pts had favorable CTC (CTC&lt;5/7.5 mL) pretherapy. Patients with TTP &gt;18 weeks had reduction in post-therapy CTC with a median decrease of 63% (range 11%-100%). Lack of IHC staining for pAKT was noted in 2/2 pts on therapy for &gt; 30 weeks vs increased expression was noted in 8/8 pts on therapy for &lt; 9 weeks. Testing for TSC1 mutation is planned and will be reported. Conclusions: The combination was tolerable but revealed modest clinical efficacy. Biomarker evaluations such as pAKT may help identify a subset likely to benefit from mTOR inhibitor strategy in mCRPC. Clinical trial information: NCT01051570.
Clofarabine (Clo) and Busulfan (Bu) as a Novel Reduced Toxicity Conditioning Regimen for Allogeneic Hematopoietic Cell Transplantation (HCT) In Patients (pts) with Acute Lymphoblastic Leukemia (ALL).
Authors: Partow Kebriaei, Celina Ledesma, Kirk Culotta, Elizabeth J. Shpall, Stefan O. Ciurea, Amin M Alousi, Marcos De Lima, Uday Popat, Deborah A Thomas, Richard E. Champlin, Borje S Andersson
Journal: Blood (2010)
The Role of DAF-21/Hsp90 in Mouth-Form Plasticity in Pristionchus pacificus
Authors: Bogdan Sieriebriennikov, Gabriel V. Markov, Hanh Witte, Ralf J. Sommer
Journal: Molecular Biology and Evolution (2017)

Phenotypic plasticity is increasingly recognized to facilitate adaptive change in plants and animals, including insects, nematodes, and vertebrates. Plasticity can occur as continuous or discrete (polyphenisms) variation. In social insects, for example, in ants, some species have workers of distinct size classes while in other closely related species variation in size may be continuous. Despite the abundance of examples in nature, how discrete morphs are specified remains currently unknown. In theory, polyphenisms might require robustness, whereby the distribution of morphologies would be limited by the same mechanisms that execute buffering from stochastic perturbations, a function attributed to heat-shock proteins of the Hsp90 family. However, this possibility has never been directly tested because plasticity and robustness are considered to represent opposite evolutionary principles. Here, we used a polyphenism of feeding structures in the nematode Pristionchus pacificus to test the relationship between robustness and plasticity using geometric morphometrics of 20 mouth-form landmarks. We show that reducing heat-shock protein activity, which reduces developmental robustness, increases the range of mouth-form morphologies. Specifically, elevated temperature led to a shift within morphospace, pharmacological inhibition of all Hsp90 genes using radicicol treatment increased shape variability in both mouth-forms, and CRISPR/Cas9-induced Ppa-daf-21/Hsp90 knockout had a combined effect. Thus, Hsp90 canalizes the morphologies of plastic traits resulting in discrete polyphenism of mouth-forms.
Treatment patterns and characteristics of post-menopausal women with HR+/HER2- metastatic breast cancer receiving everolimus.
Authors: Francis Vekeman, Yanni Hao, Wendy Y Cheng, Jonathan Fortier, Marie-Noelle Robitaille, Mei Sheng Duh
Journal: Journal of Clinical Oncology (2015)

e11502 Background: The use of everolimus (EVE) in combination with exemestane in postmenopausal women with HR+/HER2- metastatic breast cancer (mBC) has been studied in clinical trials, yet little is known of its real-world utilization. We aimed to characterize treatment patterns and characteristics of HR+/HER2- mBC patients (pts) with first-line endocrine therapy (Tx), who ever vs. never used EVE in real-world settings. Methods: Data were from a community oncology electronic medical records database from Altos Solutions, Inc. Eligible pts were postmenopausal women, with ≥ 1 medical record with a BC diagnosis, confirmed HR+/HER2- status, first mBC diagnosis after July 1, 2012, and received first-line endocrine Tx. Characteristics of pts who ever vs. never received EVE were compared. Potential predictors of EVE use, including age at index date and at first breast cancer diagnosis, race, region, insurance type, metastatic sites, ECOG performance status, and disease recurrence, were assessed using logistic regressions. Results: Of the 676 pts who met the inclusion criteria, 83 (12%) ever received EVE vs. 593 (88%) never. EVE was initiated primarily in second line (42.2%), followed by first line (41.0%), third line (10.8%), and fourth + lines (6%). Pts receiving EVE were younger at first mBC diagnosis (mean, 62 vs. 69 years; p < 0.001) and at first BC diagnosis (58 vs. 66 years; p < 0.001). Distribution of ECOG was similar between the 2 cohorts. Controlling for other characteristics, age was a significant predictor of EVE use in first-line Tx (odds ratio: 0.95, p = 0.003), but not in later lines. While not statistically significant, pts with higher ECOG were more likely to receive EVE in first line, and not in later lines. Pts with bone metastases were less likely to receive EVE in first line, but more likely in second + lines. Insurance type was not a predictor of EVE use. Conclusions: EVE is typically used in second line in pts with HR+/HER2- mBC with first-line endocrine Tx. Pts who start EVE earlier tend to be younger with worse prognosis for mBC. Studies with larger sample sizes are needed to further characterize EVE pts and assess their treatment outcomes.
Design, validation, and application of a PTEN quantitative reference standard for oncology assay development.
Authors: Jonathan Mark Frampton, Vicky Spivey, John Goodall, Karin Schmitt, Paul Morrill
Journal: Journal of Clinical Oncology (2013)

e22164 Background: The phosphatase PTEN is a tumor suppressor whose deletion is associated with tumor progression and results in loss of PTEN protein expression. This results with the activation of both phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase pathways. The PI3K/PTEN pathway is a potential target for molecular therapy and controls multiple cellular functions (cell metabolism, proliferation, apoptosis, migration, and survival). Both PI3K and PTEN are frequently mutated in human cancer. Diagnostic testing for PTEN deletion can be performed using sequencing based methods across the coding region, intron-exon borders and promoter or alternatively using an antibody IHC based assay. Currently, however, reliable and reproducible methods for measuring PTEN expression on formalin-fixed tissue are not standardized. Methods: An isogenic X-Man (gene-X, Mutant And Normal) PTEN heterozygous deletion cell line was developed using our gene editing technology (GENESIS) using a HCT116 human colon carcinoma cell background. A 10kb fragment of PTEN, containing both exon6 and exon7, was deleted to generate a PTEN (Δex6Δex7/+) cell line. The engineering event was confirmed using sequencing, gene expression analysis and digital PCR. Metaphase spreads of the mutant and corresponding matched wild type cell line were generated for CISH and SISH analysis. In addition to this FFPE blocks containing either an allelic frequency of 25% PTEN (Δex6Δex7/+) or 100% PTEN (+/+) were developed for CISH, SISH and IHC analysis. Results: Cell validation results indicated that the PTEN (Δex6Δex7/+) was successfully engineered in a HCT116 background and digital PCR data confirmed the allelic frequency of the PTEN (Δex6Δex7/+) mixed FFPE block at 25%. Preliminary data indicates that the metaphase spreads and FFPE reference slides provide consistent results for CISH, SISH and IHC and are continuing to be used for assay development. Conclusions: Here we show data for the requirement of a Quantitative Reference Standard that can be used to standardize PTEN assay development as well as facilitate the development of potentially new diagnostic assays using SISH and CISH.
Abstract 11344: Impaired SIRT1 Nucleocytoplasmic Shuttling in the Senescent Heart during Ischemic Stress
Authors: Chao Tong, Alex Morrison, Jun Wang, D P Thomas, Ji Li
Journal: Circulation (2012)

Background - A decreased ability to tolerate ischemic stress with aging is observed in both animal models and humans. A ‘longevity’ gene, sirtuin 1 (SIRT1), has been reported to attenuate the age-dependent induction of left ventricular dysfunction. We hypothesize that SIRT1 is involved in intolerance of the aged heart to ischemic stress.

Methods and Results - Male C57BL/6 young (4-6 months) and aged (24-26 months) mice were used to determine SIRT1’s role in myocardial ischemia/reperfusion (I/R) tolerance. We for the first time found that SIRT1 is predominantly expressed in a sumoylated form in cardiomyocyte nuclei, and that overexpression of desumoylase, sentrin-specific protease 2(SENP2), can reduce nuclear sumoylated SIRT1 levels. Interestingly, SIRT1 protein levels in aged hearts are lower than those seen in young hearts ( p <0.05). Immunoblotting and confocal fluorescence data demonstrated that I/R triggers desumoylation and translocation of nuclear SIRT1 into the cytoplasm in aged but not in young hearts. In addition, nuclear SIRT1 activity in ischemic young hearts was 3.2-fold higher than that seen in ischemic aged hearts ( p <0.05), suggesting that aging causes impaired nucleocytoplasmic shuttling and activation of SIRT1 in response to ischemic stress. Wild type (WT) and Sirt1 +/- knockout mice (all C57BL/6 background) were subjected to 30 min ischemia via left anterior descending (LAD) coronary artery occlusion followed by 4 hours reperfusion, the infarct size in aged and Sirt1 +/- knockout hearts was markedly higher than that observed in young and Sirt1 +/+ WT littermate hearts, respectively. Furthermore, the SIRT1 agonist, SRT1720, significantly reduced infarct size in both aged and Sirt1 +/- hearts via activation of cardiac SIRT1.

Conclusions - Impaired cardiac SIRT1 activity plays a key role in the observed increase in susceptibility of the aged heart to ischemia/reperfusion (I/R) injury. Pharmacological SIRT1 activation can restore this aging-related loss of cardioprotection against I/R injury.
SHORTER- VERSUS LONGER-DURATION TRIPLE ANTITHROMBOTIC THERAPY FOR PATIENTS WITH CORONARY STENTS WHO REQUIRE ORAL ANTICOAGULATION: AN UPDATED COMPREHENSIVE META-ANALYSIS
Authors: Mohamed Morsy, Mark Heckle, Muhammad Shahreyar, Glenda Delgado, Kodangudi Ramanathan, Kelly Rogers, Rahman Shah
Journal: Journal of the American College of Cardiology (2017)
Anatomic variations of inferior mesenteric artery and left colic artery evaluated by 3-dimensional CT angiography: Insights into rectal cancer surgery – A retrospective observational study
Authors: Jia Ke, Jiawei Cai, Xiaofeng Wen, Xianrui Wu, Zhen He, Yifeng Zou, Jianping Qiu, Xiaowen He, Xiaosheng He, Lei Lian, Xiaojian Wu, Zhiyang Zhou, Ping Lan
Journal: International Journal of Surgery (2017)
UNA COLONOSCOPIA DE REVISIÓN AUMENTA EL RENDIMIENTO EN EL DIAGNÓSTICO DE SÍNDROME DE POLIPOSIS SERRADA EN POBLACIÓN DE CRIBADO DE CÁNCER COLORRECTAL
Authors: L Rivero-Sánchez, M Lopez-Ceron, S Carballal, X Bessa, C Hernandez, A Serradesanferm, A Pozo, L Moreira, M Cuatrecasas, J Llach, A Castells, F Balaguer, M Pellisé
Journal: Endoscopy (2015)

Introducción: El síndrome de poliposis serrada (SPS) es infradiagnosticado en una única colonoscopia. Las recomendaciones de vigilancia post-polipectomía concernientes a lesiones serradas (LS) son insuficientes.
Outcomes of surveillance in unselected patients with clinical stage I testicular germ cell tumors: Results of a modern single institution series
Authors: C. J. Moore, S. Daneshmand, B. Hayes-Lattin, W. Stott, C. R. Nichols
Journal: Journal of Clinical Oncology (2007)

5085 Background: Orchiectomy is curative in 50–80% of patients (pts) with clinical stage I testicular germ cell cancer (CSITC) and modern chemotherapy at the time of relapse is nearly always curative. Traditional management in the US and Europe, which includes retroperitoneal lymph node dissection (RPLND) or adjuvant radiation or chemotherapy, imposes a significant treatment burden on all patients with CSITC. This study investigated outcomes of active surveillance in all pts with CSITC, with additional post-orchiectomy therapy reserved for only those pts who recur. Methods: Since 1998, Oregon Health &amp; Science University’s institutional policy has been to recommend active surveillance alone to all CSITC pts after orchiectomy, independent of known risk factors. We retrospectively identified and reviewed the charts of 90 pts with CSITC treated between 1998 and 2006. Prognostic factors for relapse, time to relapse, post-orchiectomy treatment required, and overall survival rates were tabulated. Results: Of the 53 pts with CSI nonseminoma, complete data are currently available for 36. 12 (33%) relapsed at a median of 6 months (range 3–48) and all received 3 cycles of bleomycin, etoposide, and cisplatin (BEP). 2 pts (5.5% of total population) required RPLND post-chemotherapy for residual teratoma. No additional relapses have been seen, and all 36 pts are alive at a median follow-up of 51 months. Of 37 pts with CSI seminoma, complete data are available for 28. Seven pts (25%) experienced abdominal relapse, at a median of 10 months (range 3–14 months) after orchiectomy. All 7 pts were treated with abdominal radiation. Two pts subsequently relapsed and were cured with chemotherapy. All CSITC pts are alive without disease at a median follow-up of 60 months. Complete data on all 90 pts will be available this spring. Conclusion: This, the largest modern US series of surveillance alone after orchiectomy, resulted in uniformly excellent outcomes suggesting that primary active surveillance reduces the global burden of treatment for pts with CSITC and is appropriate for all pts with clinical stage I disease, independent of clinical risk factors or pathological subtype. No significant financial relationships to disclose.