tbuckley/cabot-search huggingface dataset:
Extragonadal germ cell tumors: Retrospective analysis at a single institution in Japan
Authors: K. Kakimoto, Y. Ono, N. Meguro, K. Takezawa, T. Yoshida, T. Kinouchi, M. Usami
Journal: Journal of Clinical Oncology (2008)

16135 Background: Extragonadal germ cell tumors (EGGCT) are rare and account for only 2% to 5% of all malignant germ cell neoplasms. Although multimodality treatment, including cisplatin-based chemotherapy and postchemotherapy surgery, has improved the prognosis of patients with EGGCT, few findings are available for these tumors. We therefore performed a retrospective analysis of Japanese patients with EGGCT. Methods: We performed a retrospective review of the medical records of 28 male patients ranging in age from 18 to 62 years (median age, 31 years) treated at our institution between 1982 and 2006. Twelve patients (43%) had primary mediastinal EGGCT, 13 patients (46%) had primary retroperitoneal EGGCT, and three patients (11%) had primary mediastinal and retroperitoneal EGGCT. Results: Twenty-three patients (82%) had nonseminomatous EGGCT, and five patients (18%) had seminomatous histology. Surgical procedures were performed in four patients (14%) as induction treatment. Two of them had seminomatous histology and were continuously disease-free after adjuvant chemotherapy. Twenty-four patients (86%) had received cisplatin-containing regimen as induction therapy. Nineteen patients underwent post-chemotherapy surgery, and 12 of them (63%) had residual viable malignant cells. On univariate analysis, nonseminomatous EGGCT (P=0.007) and resistance to cisplatin (lack of achievement of CR/PRm- by induction chemotherapy; P=0.009) were identified as negative prognostic factors for survival. Sixteen of 28 patients (57%) were alive without disease, and twelve patients with nonseminomatous histology died of disease progression. The overall 5-year survival rate for all patients was 53%. Conclusions: Patients with seminomatous EGGCT have a very good prognosis, while nonseminomatous histology and resistance to cisplatin were found to be negative prognostic factors. No significant financial relationships to disclose.
The prevalence and severity of urogenital symptoms in postmenopausal women receiving endocrine therapy for breast cancer
Authors: S. N. Chin, M. E. Trinkaus, C. Simmons, C. Flynn, R. Bolivar, M. Clemons
Journal: Journal of Clinical Oncology (2008)

20551 Background: The urogenital side effects of endocrine therapy for breast cancer are well recognized but neither their prevalence nor severity is well described in the non-trial setting. These symptoms can negatively impact quality of life (QoL) and may seriously impact the efficacy of therapy if they compromise adherence to the recommended endocrine treatment. Methods: In this questionnaire study, we utilized a 5-point Likert type scale to assess the prevalence and severity of vulvovaginal and urinary tract symptoms and we also assessed the impact of these symptoms on sexual functioning (Sexual Activity questionnaire) and QoL (FACT-ES questionnaire) in a group of post-menopausal women receiving endocrine therapy for adjuvant or metastatic breast cancer. We also asked if women considered non- adherence to treatment due to adverse effects. Results: 252 post-menopausal women were surveyed, with median age 60 (range 32–91). All women were currently receiving endocrine treatment for breast cancer; 84% in the adjuvant and 16% in the metastatic setting. Tamoxifen was used by 30% of women and Aromatase inhibitors by 67%. Of the women surveyed, 63% reported some degree of urogenital symptoms related to their treatment. 48% reported symptoms of vaginal dryness, 32% dyspareunia, 26% vaginal discharge, 27% vaginal itching/irritation, 5% vaginal bleeding and 12% reported urinary symptoms. 48% of patients who reported vaginal dryness had severe/very severe symptoms. Only 9 patients admitted that they had considered discontinuing treatment because of urogenital side effects. Conclusions: Urogenital side effects are common and were found in 63% of patients. The most common urogenital side effect reported was vaginal dryness, which was reported as severe or very severe in 48%. Despite this degree of severity, only 9 patients reported considering discontinuing therapy because of these side effects. No significant financial relationships to disclose.
Quantitative computed tomography assessment of airway dimensions by combining tiotropium and indacaterol in patients with COPD
Authors: Makoto Hoshino
Journal: European Respiratory Journal (2014)

Background:

Combining LAMA (long-acting muscarinic antagonist) with LABA (long-acting s2 agonist) has been shown to be pharmacologically useful in patients with COPD.

Aims and objectives:

The aim of the present study was to evaluate the effectiveness of the dual bronchodilators on airway dimensions in COPD.

Methods:

Patients (n = 54) were randomly assigned receive to tiotropium (18 µg once daily), indacaterol (150 µg once daily), or tiotropium plus indacaterol for 16 weeks. Quantitative computed tomography (CT) analysis, pulmonary function and health status SGRQ (St. George's Respiratory Questionnaire) were performed.

Results:

Compared with tiotropium or indacaterol alone, combination therapy had a significant decrease in percentage wall area (WA%) and wall thickness (T) corrected for body surface area BSA (T/√BSA), and a increase in luminal area (Ai/BSA). Concurrent treatment was superior to monotherapy in physiological indices including forced vital capacity, FEV1 and inspiratory capacity. The changes in WA% and Ai/BSA were significantly correlated with changes in FEV1 (r = -0.44, p < 0.01 and r = 0.37, p < 0.01).There were more significant improvements in SGRQ scores after treatment with combining therapy than either treatment alone.

Conclusions:

Concurrent therapy of tiotropium and indacaterol is effective for COPD patients to promote reducing airway wall thickness, bronchodilation and improvement of lung function compared with a single inhaler.
BLMH1 single nucleotide polymorphism correlation with bleomycin chemotherapy in patients with testicular germ cell tumors.
Authors: M. Grgic, M. Jokic, T. Catela Ivkovic, S. Kapitanovic, M. Gamulin
Journal: Journal of Clinical Oncology (2010)

e15100 Background: Bleomycin, the main component of chemotherapy protocol for metastatic testicular germ-cell tumor (TGCT), may be inactivated by bleomycin hydrolase, encoded by BLMH1 gene. SNP A1450G is thought to be involved in controling enzymatic activity and thus the level of bleomycin-induced DNA damage. We suggested hypotesis that this SNP A1450G might influence toxicity in TGCT patients. Methods: Fiftynine patients with metastatic TGCT (6 seminomas, 14 nonseminomas and 39 with mixed germ cell tumors) were treated with three (10 patients) or four cycles (47 patients) of BEP chemotherapy (bleomycin/etoposide/cisplatin), except for 2 patients with bleomycin toxicity who were treated with 1 and 2 cycles of BEP. Blood samples of 59 patients were analysed using the real-time PCR method performed by ABI PRISM 7000 Sequence Detection System (Applied Biosystems) and pre-developed TaqMan SNP genotyping assay (rs1050565) according to the manufactures' instructions Results: We observed a wide range of adverse events casued by toxicity of bleomycin: cough, dyspnea, pneumonitis, pulmonary fibrosis, nail changes, hyperpigmentation, hypersensitivity, pruritus, leukocytopenia, vomiting, nausea and the fever. Two patients revealed severe adverse events (who were treated with 1 and 2 cycles of BEP), one a pulmonary fibrosis (x-ray verified) and the second as a significant dyspnea.The most common adverse effects were dermatological (hyperpigmentation, pruritus, hypersensitivity and nail changes) as well as fever. Patients with AG or GG genotypes developed more adverse events (25) than patients with AA (16) although results didn't reach statistical significance. Conclusions: Our results suggests that application of SNPs in future as a routine method will enable individual approach and recognition of patients who are genetically predisposed for higher toxicological effects of bleomycin. It can be expected that as number of subjects in this cohort will increase statistical significance will be reached. No significant financial relationships to disclose.
Quality-of-life index: Implications for prognosis in colorectal cancer
Authors: R. Neelam, C. G. Lis, D. L. Citrin, S. Williams, P. G. Vashi, C. A. Lammersfeld, T. Wodek, J. F. Grutsch, J. Granick, D. Gupta
Journal: Journal of Clinical Oncology (2006)

16032 Background: Quality of Life (QoL) assessment is important to evaluate the impact of disease and treatment in patients with advanced cancer. Recently, it has been hypothesized that patient satisfaction with their QoL may have a prognostic role in cancer, however, there is little evidence in the literature to support this view. The Ferrans and Powers Quality of Life Index (QLI) is one such instrument. QLI defines QoL as a person’s sense of well-being that stems from satisfaction or dissatisfaction with the areas of life that are important to him/her. The purpose of this study was to determine whether baseline QLI would predict length of survival in patients with colorectal cancer undergoing care in a non-clinical trial setting. Methods: We examined a case series of 177 colorectal cancer patients treated at Cancer Treatment Centers of America between 04/01 and 11/04. QLI measures global QoL and QoL in four major subscales: health and physical, social and economic, psychological and spiritual, and family. All scores range from 0 to 30 with higher scores indicating better QoL. QLI subscales were dichotomized at the median to split the patient population into 2 distinct groups. Kaplan Meier method with Log Rank test was used to calculate survival. Results: Of 177 patients, 46 were newly diagnosed and 131 had prior treatment history. The median age was 53 years (range 25– 85 years). 8 patients had stage I disease, 16 stage II, 51 stage III, and 77 stage IV. Table 1 describes the median survival for all QLI subscales. Conclusions: Baseline levels of patient satisfaction with their health and physical functioning provided useful prognostic information in colorectal cancer. Interestingly, the other subscales that evaluate various existential and economic issues did not provide statistically significant differences in survival. These findings need to be evaluated further to ascertain which subscales of QLI have a role in predicting patients’ prognosis. [Table: see text] No significant financial relationships to disclose.
Vascular endothelial growth factor (VEGF)-targeted therapy for the treatment of adult metastatic Xp11 translocation renal cell carcinoma.
Authors: Z. Dubauskas Lim, T. K. Choueiri, M. S. Hirsch, E. Jonasch, U. N. Vaishampayan, P. Tamboli, P. G. Corn, D. Y. Heng, N. M. Tannir
Journal: Journal of Clinical Oncology (2010)

4606 Background: Adult translocation renal cell carcinoma (RCC), bearing TFE3 gene fusions, is a recently recognized entity for which prognosis and therapy remain poorly understood. The effect of vascular-endothelial growth factor (VEGF)-targeted therapy in this histologic subtype is characterized. Methods: Clinical characteristics and treatment outcomes were evaluated in 15 patients with metastatic RCC with strong TFE-3 nuclear immunostaining who received anti-VEGF therapy at 4 US institutions. Response rate by RECIST and overall survival were documented. Results: Fifteen patients were included in this analysis for which 10, 3, and 2 received sunitinib, sorafenib and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of patients was 40.8 years (range 18.3-64.8) and the male:female ratio was 3:12. All patients had an initial histologic diagnosis of clear cell (N=8), papillary (n=1) or mixed clear cell/papillary RCC (n=6). Five patients had prior systemic therapy (2 immunotherapy, 1 chemotherapy, 1 vaccine, 1 temsirolimus), 12 patients had prior nephrectomy, 13/15 had lymph node metastases and 6/15 had lung metastases. MSKCC risk groups were favorable, intermediate, poor and missing in 2, 9, 3, and 1 respectively. Four patients had FISH analysis and all demonstrated a translocation involving chromosome Xp11. When treated with VEGF-targeted therapy, 3 patients had a partial response, 7 patients had stable disease and 5 patients had progressive disease. The median tumor shrinkage was by 4.5% (range 48% shrinkage to 67% growth). The median progression-free survival and overall survival of the entire cohort was 7.13 and 14.3 months respectively. Conclusions: Adult-onset translocation-associated mRCC is an aggressive disease that affects a younger population with female predominance. VEGF targeted agents demonstrated efficacy in this small retrospective series. No significant financial relationships to disclose.
Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons
Authors: Shan Meltzer, Smita Yadav, Jiae Lee, Peter Soba, Susan H. Younger, Peng Jin, Wei Zhang, Jay Parrish, Lily Yeh Jan, Yuh-Nung Jan
Journal: Neuron (2016)
Gene signature of cancer stem cells in an intrinsic subgroup of breast cancers with mesenchymal properties
Authors: J. C. Chang, C. Creighton, M. Landis, M. T. Lewis, X. Li, A. Pavlick, J. Rosen, C. M. Perou, J. Rosen
Journal: Journal of Clinical Oncology (2008)

11009 Background: Breast cancer stem cells characterized by CD44+/CD24−/low may be resistant to therapy and responsible for relapse. Mammospheres (MSs) can be propogated as an in vitro surrogate assay for increased self-renewal. We set out to define a “signature” expression pattern associated with CD44+/CD24−/low, mammosphere-forming cells. Methods: Breast cancer biopsies (n=19) were digested, stained with CD24, CD44, and lineage antibodies, and analyzed by flow cytometry. A portion of the unsorted cells were plated under serum-free conditions to form MSs (n=16). Gene expression, using the Affymetrix U133 GeneChip platform, of cancer cells bearing CD44+/CD24−/low vs. other sorted cells, and between cancer MS vs. the primary invasive cancers were analyzed. Gene expression data from two trials (neoadjuvant letrozole N=18, and docetaxel, N=12) were used as validation studies. Results: In the flow-sorted CD44+/CD24−/low vs. other cells, 1,424 named genes were elevated (p<0.01, fold change>1.5, FDR=0.20). The comparison between MSs vs. primary cancers yielded 1,890 elevated genes (FDR=0.25). Between the two sets, 380 genes were in common, a highly significant overlap (p=1E-5, one-sided Fisher’s exact). This overlap was ∼40% greater than what would be expected (n=110) if the two sets had no biological relevance. Differential pathways included genes in PI3K/AKT signaling (PI3K3R3, ErbB3, FGFR2, PRLR), and the Notch pathway - a known regulator of normal and malignant stem/progenitor cells (Jagged-2, MAML2, Deltex, HES1). This signature was found exclusively activated in tumors of the recently identified “claudin-low” subtype, characterized by overexpression of many mesenchymal genes. In two independent data sets comparing the expression profiles of paired breast cancer core biopsies before vs. after letrozole or docetaxel chemotherapy, both the tumorigenic and “claudin-low” signatures were elevated in post-treatment samples. Conclusions: This mesenchymal association provides a possible explanation for the intrinsic resistance of breast cancer stem cells to therapy. No significant financial relationships to disclose.
Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial.
Authors: Martine J. Piccart-Gebhart, Shinzaburo Noguchi, Kathleen I. Pritchard, Howard A. Burris, Hope S. Rugo, Michael Gnant, Gabriel N. Hortobagyi, Bohuslav Melichar, Katarina Petrakova, Francis P. Arena, Cindy Xu, Ayelet Cahana, Tanya Taran, Tarek Sahmoud, David Edward Lebwohl, Mario Campone, José Baselga
Journal: Journal of Clinical Oncology (2012)

559 Background: Current treatment options for postmenopausal patients with estrogen-receptor–positive (ER + ) breast cancer (BC) who relapse or progress on a nonsteroidal aromatase inhibitor (NSAI) are limited. The BOLERO-2 trial supports the activity of everolimus (EVE; an oral mammalian target of rapamycin [mTOR] inhibitor) added to the steroidal aromatase inhibitor exemestane (EXE) to prolong progression-free survival (PFS) in this patient population. Long-term PFS and survival data are awaited. Methods: BOLERO-2 is a phase III double-blind, randomized, international trial comparing EVE (10 mg once daily) plus EXE (25 mg once daily) versus placebo (PBO) plus EXE in postmenopausal women with advanced ER + BC progressing or recurring after NSAIs (letrozole or anastrozole). Patients were randomized (2:1) to EVE + EXE or PBO + EXE. The primary endpoint was PFS by local investigator assessment. Main secondary endpoints included centrally assessed PFS, overall survival (OS), safety, bone turnover, and overall response rate (ORR). Results: Baseline disease characteristics including tumor burden and prior cancer therapy were well balanced between treatment arms (N = 724). Median PFS was doubled and response rates were consistently improved with EVE + EXE (n = 485) vs PBO + EXE (n = 239) in interim analyses. Median PFS by local assessment was ~3 mo with PBO + EXE vs 6.9 mo (hazard ratio [HR] = 0.43; P &lt; .0001) and 7.4 mo (HR = 0.44; P &lt; .0001) with EVE + EXE at 7.5 mo and 12.5 mo follow-up, respectively. Fewer deaths were reported with EVE + EXE (17.2%) vs PBO + EXE (22.7%) at 12.5 mo follow-up. Safety profiles were consistent with previous reports for mTOR inhibitors. PFS data including 528 events (protocol-specified final analysis), and updated OS and safety data will be presented. Conclusions: Adding EVE to EXE markedly prolonged PFS in patients with NSAI-refractory advanced ER + BC. There were fewer deaths among patients receiving EVE, and further follow-up will evaluate the effect of EVE on OS.
Time-course MALDI-TOF-MS serum peptide profiling of non-small cell lung cancer patients treated with bortezomib, cisplatin and gemcitabine
Authors: J. Voortman, T. V. Pham, J. C. Knol, G. Giaccone, C. R. Jimenez
Journal: Journal of Clinical Oncology (2008)

8007 Background: A limited number of patients with advanced stage non-small cell lung cancer (NSCLC) respond to chemotherapy. Serum peptide profiling of patients treated with gemcitabine, cisplatin and bortezomib was performed at baseline, during, and at end of treatment, aiming to discover biomarkers associated with NSCLC, therapy response and treatment-related effects. Methods: Using automated magnetic C18 bead-assisted serum peptide capture coupled to matrix-assisted laser desorption/ ionization time of flight mass spectrometry (MALDI-TOF MS), serum peptide profiling of 27 NSCLC patients was conducted and peptide mass profiles (spectra) obtained. Spectra were compared to those generated from 13 healthy volunteers. Data analyses of pretreatment serum peptide profiles, as well as dynamic changes in peptide abundancy during treatment, were performed to establish support-vector machine-based algorithms that can 1. discriminate healthy subjects from cancer patients 2. predict clinical outcome 3.classify for treatment specific effects. Results: A signature based on 47 differential m/z features was established, discriminating NSCLC patients from healthy individuals with 98% accuracy at 100% sensitivity and 96% specificity using support vector machine and leave one out cross validation. A 13 ion-peptide signature could discriminate with a sensitivity of 100% and specificity of 73% patients with a relatively short (< 5 months) or long (> 5 months) progression free survival. A pattern based on 5 peptides could separate partial response NSCLC patients from others with an accuracy of 89% at 100% sensitivity and 83% specificity. MALDI-TOF/TOF-based MS/MS identification of selected peptides is ongoing. Conclusions: (dynamic) serum peptidome profiling using MALDI-TOF-MS coupled to pattern diagnostics may aid in the prediction of clinical outcome of NSCLC patients treated with chemotherapy, potentially enabling pretreatment selection of appropriate subgroups and preventing overtreatment. No significant financial relationships to disclose.
Subjective Global Assessment—An independent predictor of survival in breast cancer
Authors: S. Dahlk, P. G. Vashi, D. Gupta, C. A. Lammersfeld, A. Aslam, C. G. Lis
Journal: Journal of Clinical Oncology (2008)

17541 Background: The Subjective Global Assessment (SGA) which is an easy-to-use, inexpensive, and non-invasive validated clinical instrument to assess nutritional status, combines data from subjective and objective aspects of medical history and physical examination. Since malnutrition can be a frequent manifestation in breast cancer, we investigated the prognostic role of SGA in patients with breast cancer treated in an integrative cancer treatment setting. Methods: We evaluated 305 histologically confirmed case series of breast cancer patients treated at Cancer Treatment Centers of America. Using SGA, patients were classified as well nourished (SGA A), moderately malnourished (SGA B) or severely malnourished (SGA C). Kaplan Meier method was used to calculate survival. Cox proportional hazard models were constructed to evaluate the prognostic effect of SGA independent of stage at diagnosis and prior treatment history. Results: Of 305 patients, 91 were newly diagnosed at our hospital while 214 had received prior treatment elsewhere. 69 had stage I disease at diagnosis, 131 had stage II, 51 had stage III and 41 had stage IV. The median age at diagnosis was 49 years (range 25 - 74 years). 216 patients were well-nourished (SGA A) while 89 were malnourished (SGA B or C). Well nourished patients had a median survival of 49.9 months (95% CI: 29.9 to 69.9), while malnourished patients had a median survival of 15.7 months (95% CI: 8.7 to 22.6); the difference being statistically significant (p < 0.001). Multivariate Cox modeling, after adjusting for stage at diagnosis and prior treatment history found that malnourished status was associated with a relative risk (RR) of 2.7 (95% CI: 1.8 to 4.0, p < 0.001). Stage at diagnosis was associated with a RR of 1.9 (95% CI: 1.3 to 3.0; p = 0.002) and prior treatment history was associated with a RR of 8.8 (95% CI: 4.6 to 16.9; p = 0.002). Conclusions: In this cohort, we found that low SGA scores (well-nourished status) versus high SGA scores (moderate to severe malnourished status) identified patients with better survival outcomes. At our center, we continue to investigate the role of nutritional intervention in improving prognosis in patients with breast cancer. No significant financial relationships to disclose.
Aberrant 5-Hydroxymethylcytosine Levels Correlate With Poor Overall Survival In Acute Myeloid Leukemia
Authors: Leonie I Kroeze, Mariam G Aslanyan, Arno van Rooij, Theresia N Koorenhof-Scheele, Marion Massop, Thomas Carell, Jan B Boezeman, Jean-Pierre Marie, Constantijn J.M. Halkes, Theo M. de Witte, Gerwin Huls, Stefan Suciu, Ron Wevers, Bert A. van der Reijden, Joop H. Jansen
Journal: Blood (2013)