tbuckley/cabot-search huggingface dataset:
Incidence of benign versus malignant renal tumors in selected studies.
Authors: Paul Russo, Robert G. Uzzo, William Thomas Lowrance, Aviva Asnis-Alibozek, Norman David LaFrance, John A. Libertino, Daniel A. Pryma, Chaitanya R. Divgi
Journal: Journal of Clinical Oncology (2012)

357 Background: Use of cross-sectional imaging has increased the detection rate for small renal tumors; more patients now present with early-stage renal cell carcinoma (RCC) or benign or indolent renal masses. Histopathology after surgical resection is the definitive method for characterizing renal tumors. Stage migration of renal masses creates uncertainty about the percentage of resected masses that will be benign vs malignant. We sought to better define these proportions through a targeted review of the literature. Methods: PubMed/select congresses were searched to identify the histologic classification of renal masses in a representative sample from the contemporary literature: [search] incidence AND (renal cell carcinoma AND benign); incidence AND (renal tumor AND benign); percentage AND (renal cell carcinoma AND benign); limit: 2003–2011. Results: Most representative studies included procedures conducted in the mid-1990s to the mid-to-late 2000s. Studies origin was US (n=8), Korea (n=3), China, Japan, Germany, Austria, Australia, and multisite (Israel/France/US; all n=1). Only 8 studies had n≥500 (range, 70–10,404). The proportion of benign masses are shown (see Table); half of the studies reported values between 16% and 17%. The majority found that benign tumors were more likely to be smaller in size (&lt;4 or &lt;7 cm) than malignant tumors. 11 studies reported the RCC subtype (% clear cell range, 46%–83%). Conclusions: Benign renal tumors occur ~15% of the time and are more prevalent among small masses. Nearly 25% of resected lesions are benign or indolent and may not require surgery. Preoperative discrimination of more aggressive renal masses would be an important clinical advance that could improve clinicians’ diagnostic confidence and guide patient management. Funding: Wilex AG/IBA Molecular. [Table: see text]
Genetic Diversity and the Efficacy of Purifying Selection across Plant and Animal Species
Authors: Jun Chen, Sylvain Glémin, Martin Lascoux
Journal: Molecular Biology and Evolution (2017)

A central question in evolutionary biology is why some species have more genetic diversity than others and a no less important question is why selection efficacy varies among species. Although these questions have started to be tackled in animals, they have not been addressed to the same extent in plants. Here, we estimated nucleotide diversity at synonymous, πS, and nonsynonymous sites, πN, and a measure of the efficacy of selection, the ratio πN/πS, in 34 animal and 28 plant species using full genome data. We then evaluated the relationship of nucleotide diversity and selection efficacy with effective population size, the distribution of fitness effect and life history traits. In animals, our data confirm that longevity and propagule size are the variables that best explain the variation in πS among species. In plants longevity also plays a major role as well as mating system. As predicted by the nearly neutral theory of molecular evolution, the log of πN/πS decreased linearly with the log of πS but the slope was weaker in plants than in animals. This appears to be due to a higher mutation rate in long lived plants, and the difference disappears when πS is rescaled by the mutation rate. Differences in the distribution of fitness effect of new mutations also contributed to variation in πN/πS among species.
Retrospective comparison of long-term outcomes in patients with stage II/III (UICC-TNM6th) esophageal squamous cell carcinoma treated with 60 Gy or 50.4 Gy of definitive chemoradiotherapy with fluorouracil and platinum.
Authors: Hidekazu Hirano, Ken Kato, Shoko Nakamura, Yusuke Sasaki, Naoki Takahashi, Satoru Iwasa, Yoshitaka Honma, Natsuko Okita, Atsuo Takashima, Tetsuya Hamaguchi, Yoshinori Ito, Jun Itami, Narikazu Boku
Journal: Journal of Clinical Oncology (2016)

109 Background: Deﬁnitive chemoradiotherapy (dCRT) is one of the treatment options for stage II/III esophageal squamous cell carcinoma (ESCC). RTOG9405 demonstrated that a higher dose of radiation (64.8 Gy) offered no additional survival benefit over the standard dose (50.4 Gy). We compared the long-term outcomes of dCRT with radiation doses of 60 Gy and 50.4 Gy for ESCC. Methods: Selection criteria included thoracic ESCC, stage II/III (non T4), performance status (PS) 0-2, age 20-75 years, adequate organ function and no other active malignancy. We retrospectively analyzed patients who received dCRT as a first-line therapy between Jan. 2000 and Nov. 2011 in our hospital. Group A (n = 180) received 2 cycles of cisplatin (C) (40 mg/m 2 on day 1 and 8) with fluorouracil (F) infusion (400 mg/m 2 /day on day 1-5 and 8-12), or 2 cycles of C (70 mg/m 2 on day 1) with F infusion (700 mg/m 2 /day on day 1-4) repeated every 4 weeks and concurrent radiotherapy at a dose of 60 Gy. Group B (n = 62) received 2 cycles of C (75 mg/m 2 on day 1) with F infusion (1000 mg/m 2 /day on days 1–4) repeated every 4 weeks and concurrent radiotherapy at a dose of 50.4 Gy. Overall survival (OS) and progression free survival (PFS) were estimated with the Kaplan-Meier method and compared with log-rank test. The Cox regression model was used for multivariate analysis to assess the prognostic factors for OS. Results: Characteristics of both groups were as follows (Group A: Group B): median age, 64:62; male/female, 154/26:55/7; PS 0/1/2, 81/98/1:46/16/0; T1/2/3, 39/27/114:19/9/34; N0/1, 41/139:6/56. Median follow-up period was longer than 40 months for both groups. 5-year survival rates were 44.5% for Group A and 60.0% for Group B. Median PFS and median OS were 16.5 months and 36.2 months for Group A, 41.1 months and 98.3 months for Group B. By multivariate analysis, Group B (hazard ratio [HR] 0.617: 95% confidence interval [CI]:0.400-0.951, p = 0.029), T1/2([HR] 0.383: 95% [CI]: 0.260-0.566, p &lt; 0.001) were significant prognostic factors for OS. Conclusions: CRT with 50.4 Gy showed better long-term survival than with 60 Gy.
ITIH5 mediates epigenetic reprogramming of breast cancer cells
Authors: Michael Rose, Vera Kloten, Erik Noetzel, Lukas Gola, Josef Ehling, Timon Heide, Steffen K. Meurer, Aljona Gaiko-Shcherbak, Antonio S. Sechi, Sebastian Huth, Ralf Weiskirchen, Oliver Klaas, Wiebke Antonopoulos, Qiong Lin, Wolfgang Wagner, Jürgen Veeck, Felix Gremse, Julia Steitz, Ruth Knüchel, Edgar Dahl
Journal: Molecular Cancer (2017)

Extracellular matrix (ECM) is known to maintain epithelial integrity. In carcinogenesis ECM degradation triggers metastasis by controlling migration and differentiation including cancer stem cell (CSC) characteristics. The ECM-modulator inter- α-trypsin inhibitor heavy chain family member five (ITIH5) was recently identified as tumor suppressor potentially involved in impairing breast cancer progression but molecular mechanisms underlying its function are still elusive. ITIH5 expression was analyzed using the public TCGA portal. ITIH5-overexpressing single-cell clones were established based on T47D and MDA-MB-231 cell lines. Colony formation, growth, apoptosis, migration, matrix adhesion, traction force analyses and polarization of tumor cells were studied in vitro. Tumor-initiating characteristics were analyzed by generating a metastasis mouse model. To identify ITIH5-affected pathways we utilized genome wide gene expression and DNA methylation profiles. RNA-interference targeting the ITIH5-downstream regulated gene DAPK1 was used to confirm functional involvement. ITIH5 loss was pronounced in breast cancer subtypes with unfavorable prognosis like basal-type tumors. Functionally, cell and colony formation was impaired after ITIH5 re-expression in both cell lines. In a metastasis mouse model, ITIH5 expressing MDA-MB-231 cells almost completely failed to initiate lung metastases. In these metastatic cells ITIH5 modulated cell-matrix adhesion dynamics and altered biomechanical cues. The profile of integrin receptors was shifted towards β1-integrin accompanied by decreased Rac1 and increased RhoA activity in ITIH5-expressing clones while cell polarization and single-cell migration was impaired. Instead ITIH5 expression triggered the formation of epithelial-like cell clusters that underwent an epigenetic reprogramming. 214 promoter regions potentially marked with either H3K4 and /or H3K27 methylation showed a hyper- or hypomethylated DNA configuration due to ITIH5 expression finally leading to re-expression of the tumor suppressor DAPK1. In turn, RNAi-mediated knockdown of DAPK1 in ITIH5-expressing MDA-MB-231 single-cell clones clearly restored cell motility. Our results provide evidence that ITIH5 triggers a reprogramming of breast cancer cells with known stem CSC properties towards an epithelial-like phenotype through global epigenetic changes effecting known tumor suppressor genes like DAPK1. Therewith, ITIH5 may represent an ECM modulator in epithelial breast tissue mediating suppression of tumor initiating cancer cell characteristics which are thought being responsible for the metastasis of breast cancer.
Outcome of patients with adrenal metastasis from lung cancer: Selection criteria for surgery.
Authors: C. S. Landry, N. D. Perrier, D. D. Karp, Y. Xing, J. E. Lee, E. G. Grubbs
Journal: Journal of Clinical Oncology (2010)

e18071 Background: Adrenalectomy is an accepted treatment for patients with isolated adrenal metastasis (AM) from nonsmall cell lung cancer (NSCLC); however, selection criteria for resection and the role for adrenalectomy in patients with extra-adrenal disease are poorly defined. We reviewed the outcome of patients with AM from NSCLC in a large single-institution cohort to identify factors associated with overall survival (OS) and survival from the time of AM diagnosis (AS). Methods: Retrospective review of NSCLC patients (pts) seen at our institution 2002-2009 was performed. Pts who developed distant metastasis (DM) were included. OS was measured from primary diagnosis (dx) and AS from dx of AM. Comparison of OS among subgroups was performed by anatomic location and extent of DM, and for patients with AM, comparison of AS by treatment group (chemotherapy, surgery, radiation, none). Results: With a median follow-up of 11 months (mo), 6,577 NSCLC pts presented with and/or developed DM (874 [13%] 1 site, 2,288 [35%] 2 sites, 3,415 [52%] 3+ sites). 4,243 (64.5%) pts died. Pts with isolated AM (n = 17) had a significantly better OS compared to pts with isolated DM of other anatomic sites (p < 0.0001; median OS not reached vs 17 mo, HR .159, 95%CI 0.051-0.495). In contrast, pts with non-isolated AM (n = 330, adrenal plus at least 1 other DM site) had a very poor OS (median OS 7 mo). Factors associated with improved AS in pts with AM (n = 399) on multivariate analysis included control of extraadrenal disease (p < 0.0001; median AS 19 mo vs 3 mo, HR .202 95%CI 0.12-0.34) and treatment of AM with surgery (n =19; p < 0.0001; median AS not reached vs 5 mo, HR .03, 95%CI 0.01- 0.10). Pts who underwent surgery for AM tended to present with earlier stage at dx (p < 0.0001) and were more likely to have isolated AM (p < 0.0001) compared to pts who underwent nonsurgical management. Conclusions: Pts with isolated AM from NSCLC have a favorable survival compared to pts with isolated DM to other sites, and adrenalectomy in selected pts with AM is associated with improved survival. These observations provide a rationale for surgery in selected patients with AM. Factors to consider when selecting pts for adrenalectomy include control of extraadrenal disease and metastasis isolated to the adrenal gland. No significant financial relationships to disclose.
Safety of lenalidomide monotherapy in patients with relapsed or refractory aggressive non-Hodgkin’s lymphom
Authors: T. M. Habermann, T. E. Witzig, I. S. Lossos, J. M. Vose, P. H. Wiernik, L. Weiss, A. Ervin-Haynes, D. Pietronigro, J. B. Zeldis, M. Czuczman
Journal: Journal of Clinical Oncology (2008)

8603 Background: Lenalidomide is active in non-Hodgkin s Lymphoma (NHL). The aim of this analysis was to evaluate the safety of lenalidomide monotherapy in patients with relapsed/refractory aggressive NHL enrolled in 2 phase II clinical trials (NHL-002 and NHL-003). Methods: Patients with relapsed/refractory aggressive NHL with measurable disease after ≥1 prior treatment regimen were treated with oral lenalidomide (25 mg) once daily on Days 1–21 every 28 days and continued therapy as tolerated or until disease progression. Safety was evaluated using the NCI CTC criteria. Results: The intent-to-treat population (n=136) was used to report data, except for dosage data (safety population n=131). The median age was 66 (21–86) years, 63% were male, 52% had an international prognostic index score of ≤2, and 23% had prior stem cell transplantation. The median dose of lenalidomide was 25.0 (8.8–25.0) mg/day. Common (≥10%) adverse events (AEs; all grades) were fatigue, neutropenia, rash, thrombocytopenia, constipation, anemia, diarrhea, pyrexia, nausea, peripheral edema, decreased white blood cell count, anorexia, and cough. Most common grade 3/4 AEs were neutropenia (21%) and thrombocytopenia (15%). Serious AEs (≥2% of patients) were disease progression, febrile neutropenia, pyrexia, and pneumonia in 4%, and back pain, deep vein thrombosis, dehydration, and diarrhea in 2%. No events of tumor lysis syndrome were reported. Lenalidomide dose was reduced or interrupted for AEs in 37 patients. Seventy-three patients discontinued therapy for lack of therapeutic effect (n=48), AEs (n=12), death (n=5), consent withdrawn (n=3), lost to follow-up (n=1), or other (n=4); 63 patients remain on the study. Conclusions: Lenalidomide monotherapy has a favorable safety profile in patients with relapsed/refractory aggressive NHL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation Celgene Corporation
High-Density Genomic Scan with 50K SNP Arrays Reveals Existence of Cryptic Chromosomal Lesions and Germ Line Allelic Polymorphism That Might Determine Predisposition to MDS.
Authors: Lukasz P. Gondek, Christine L. O’Keefe, Marcin W. Wlodarski, Mikkael M. Sekeres, Martina L. Veigl, Debora Poruban, Jaroslaw P. Maciejewski
Journal: Blood (2005)
VENUS - A Study To Validate Centrally Adjudicated Venous Ultrasound Against Venography after Major Orthopaedic Surgery.
Authors: Sebastian M. Schellong, Jan Beyer, Kai Halbritter, Benjamin Schmidt, Alexander G.G. Turpie, Bengt I. Eriksson, Frank Misselwitz, Peter Kälebo
Journal: Blood (2005)
Monocytic Differentiation of Myeloid Leukemia Cell Lines Induced by ATRA and 5-Aza-2'-Deoxycitidine.
Authors: Atsushi Fujiki, Toshihiko Imamura, Yoshifumi Hirashima, Mitsuru Miyachi, Shigeki Yagyu, Takuya Nakatani, Kanji Sugita, Hajime Hosoi
Journal: Blood (2009)
Factors Determining Survival after Unrelated Donor Stem Cell Transplantation in Primary Refractory Acute Myeloid Leukemia
Authors: Charles F. Craddock, Myriam Labopin, J. ürgen Finke, Gerhard Ehninger, Donald Bunjes, Hans-Jochem Kolb, Hildegard Greinix, Axel Zander, Emmanuelle Polge, Christoph Schmid, Dietrich Beelen, Vanderson Rocha
Journal: Blood (2008)
Efficacy of eribulin in patients (pts) with metastatic breast cancer (MBC): A pooled analysis by HER2 and ER status.
Authors: Peter Kaufman, Chris Twelves, Javier Cortes, Linda T. Vahdat, Martin Olivo, Yi He, Ahmad Awada
Journal: Journal of Clinical Oncology (2014)

137 Background: Eribulin (E) has been assessed in two phase 3, open-label trials in pts with locally recurrent or MBC progressing after an anthracycline (A) and taxane (T). E significantly increased overall survival (OS) compared with treatment of physician’s choice (TPC) in one study (EMBRACE) and there was a non-significant trend for improved OS with E vs capecitabine (cape) in the other (Study 301). We present an unplanned pooled analysis of these data. Methods: In the EMBRACE trial, women had received 2–5 lines of chemotherapy for advanced disease. In this ≥ 3rd line setting, pts were randomized 2:1 to E mesylate (1.4 mg/m 2 iv on days 1 and 8 every 21 days) or TPC. In study 301, pts who had received 0-2 prior chemotherapies for advanced disease were randomized 1:1 to either E (as above) or cape (1.25 g/m 2 orally b.i.d. days 1–14 every 21 days). We analysed OS by 2-sided stratified log-rank tests and Cox regression in the overall intent-to-treat population and in the HER2-, triple negative (TNBC) and HER2+ subgroups. Results: 1,864 pts (median age 54 yrs) were included; most had been treated in the 2nd (31.5%) or 3rd line (32.7%) MBC settings. Overall, E provided significantly improved OS vs control; this benefit was also significant in HER2− and TNBC, but not HER2+ pts (Table). E improved progression-free survival overall (4.0 vs 3.4 months, HR = 0.90, 95%CI = 0.81, 0.997, p = 0.046), in HER2– (3.7 vs 3.0 months, HR = 0.84, 95%CI = 0.74, 0.95, p = 0.006) and TNBC pts (2.8 vs 2.6 months, HR = 0.78, 95%CI = 0.63, 0.96, p= 0.018). As reported before, the E safety profile was similar in the studies. Conclusions: E significantly improved OS vs standard therapies in MBC pts with HER2− and TNBC in this pooled analysis; in pts with HER2+ disease the difference did not reach statistical significance but numbers were smaller. Clinical trial information: NCT00337103 and NCT00388726. [Table: see text]
Evaluation of efficacy and safety of ZD1839 as monotherapy for Chinese patients with advanced non-small cell lung cancer: Experience from a compassionate-use programme
Authors: M. Z. Wang, L. Y. Li, S. L. Wang, X. T. Zhang, W. Zhong, L. Zhang
Journal: Journal of Clinical Oncology (2005)

7254 Background: The tolerability and efficacy of ZD1839 have been explored extensively in the West and Japan. This paper reports the outcome of ZD1839 for Chinese patients with advanced NSCLC from Expanded Access Programme (EAP) at the Peking Union Medical College Hospital. Methods: From Oct 2002 to Oct 2004, 151 patients with advanced NSCLC received oral ZD1839 250 mg/day treatment. 90 (59.6%) men and 61 (40.4%) women between 25 and 85 years of age. 31 (20.5%) patients had squamous cell carcinoma, 88 (58.3%) adenocarcinoma, 21(13.9%) bronchioloalveolar carcinoma, 6(4.0%) adenosquamous carcinoma, and 5(3.3%) unspecified. 15 patients had no history of chemotherapy, 34 had no disease progression after chemotherapy, and 102 failed to prior one or more regimens. Median overall survival (OS) were calculated using the Kaplan-Meier method and a log-rank test was used to detect differences OS between strata. Results: Adverse events (AEs) were generally mild (grade1 and 2) and reversible. The most frequent AEs were rash(73.6%), diarrhea(36.4%), nasal/oral hemorrhage(10.7%), anorexia(10.0%), and transaminase elevating(7.1%). The objective tumour response rate and stable disease rate was 29.8%(95% confidence interval [CI], 22.5–37.1) and 36.4%(95% CI, 28.8–44.0) respectively, and median overall survival(OS) was 15.3 months (95% CI, 11.5–19.2). The median OS were significantly related with ECOG scores, pathology types, efficacy of ZD1839, changes of symptoms and rash. Partial responses was significantly higher in women, non-smokers, patients with adenocarcinomas, and patients with rashes induced by ZD1839. The median progression-free survival (PFS) and median OS for patients who failed to prior regimens were 8.9 months (95% CI, 6.7–11.0) and 11.7 months (95% CI, 8.3–15.2). Conclusions: Our study suggest that treatment with ZD1839 may be well tolerate and beneficial for some Chinese patients after failure of prior chemotherapy. No significant financial relationships to disclose.
Propensity-score matched pair comparison of brachytherapy-based accelerated partial breast irradiation versus whole breast Canadian hypofractionation.
Authors: Peter Y. Chen, John Ben Wilkinson, Chirag Shah, Jessica Wobb, Michelle Wallace, Hong Ye, Ovidiu Marina, Pamela Benitez, Nayana Dekhne, Donald S. Brabbins, Frank Vicini
Journal: Journal of Clinical Oncology (2013)

65 Background: Given the initial report of the RAPID trial with greater morbidity for 3-D conformal external beam APBI [3D-APBI] vs. Canadian Hypofractionation [CHfx], a propensity-score matched-pair analysis of brachytherapy-based APBI [B-APBI] vs. CHfx was performed to assess efficacy, toxicities, and cosmesis. Methods: Early-stage breast cancer patients treated with B-APBI or CHfx were reviewed. With ≥ 1y follow-up [FU], B-APBI (n=108) pts were matched 1:1 to CHfx (n=108) by age, T-stage, nodal/ER status, endocrine or chemotherapy and laterality. Ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastasis (DM), contralateral breast cancer (CLBC), cause-specific survival (CSS), overall survival (OS) and disease-free survival (DFS) were compared by Kaplan-Meier (log-rank test). Toxicities were graded per CTCAE v3 and comesis per Harvard criteria. Results: Median FU was 5.7 y (1.0-17.8) for B-APBI and 2.1 y (1.0-5.7) for CHfx [p &lt; 0.001]. Patients did not differ by match criteria. In comparing B-APBI to CHfx, median age was 69.0 vs. 70.0 [p = 0.72]; for laterality, T-stage, nodal/ER status, endocrine or chemotherapy, no significance [NS] was noted between the 2 groups [p = 0.79, 1.0, 0.60, 0.09, 0.15, and 0.16 respectively]. Comparing B-APBI to CHfx, NS was seen in 5-y actuarial rates of IBTR [1% vs. 0% p = 0.35], RR [0% both], DM [3.4% vs. 0% p = 0.25], CLBC [2.3% vs. 2% p = 0.63], CSS [94.3% vs. 100% p = 0.47], OS [87.7% vs. 88.3% p = 0.71] &amp; DFS [97.5% vs. 100% p = 0.52]. The majority of maximal late toxicities were Gr 1-2. Of toxicities analyzed, including pigmentary changes, edema, pain, induration, volume reduction, telangiectasia, fat necrosis and seroma, only Gr 2-3 hyperpigmentation was significantly higher in the CHfx [8% B-APBI vs. 22% CHfx p = 0.017]. Good/excellent cosmesis was seen in &gt; 93% in both groups. Conclusions: With FU of &gt;5 yrs, B-APBI has similar efficacy and cosmesis but less morbidity vs. CHfx; the lesser toxicity of B-APBI vs. CHfx is in contradistinction to the RAPID results comparing 3D-APBI vs. CHfx. Further FU and more patients are needed to substantiate these findings.