tbuckley/cabot-search huggingface dataset:
Application of serum protein fingerprint pattern models based on artificial nerual networks for detection liver cancer from liver cirrhosis
Authors: S. Zheng, J. K. Yu, J. Liu, J. X. Wang, B. Zhang
Journal: Journal of Clinical Oncology (2005)

4121 Background: To set up a serum protein fingerprint pattern model for detection of the liver cancer from liver cirrhosis and health individuals by using the protein chip technology. Methods: One hundred and six serum samples form subjects with liver cancer, liver cirrhosis, and healthy individuals were detected with protein biochip surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and WCX2 weak cationic chip for setting up protein fingerprint pattern, and analyzed with the artificial neural network. The 106 samples were randomly divided into a training group (n=70, 35 patients with liver cancer, 14 patients with liver cirrhosis, and 21 healthy individuals) and a blind test group (n=36, 17 patients with liver cancer, 8 patients with liver cirrhosis, and 11 healthy individuals). Results: The serum protein fingerprint pattern model including 7759Da and 13134Da two Biomarkers were obtained by the BP artificial neural network from the training group, which has been was used to detect the 36 unknown serum samples. The sensitivity and specificity of this method in detection of liver cancer from liver cirrhosis were 88.2% (15/17) and 94.6% (18/19) respectively. Conclusions: In comparison with the traditional methods, this serum protein fingerprint model has higher sensitivity and specificity in detection of liver cancer from liver cirrhosis, this initial work is valuable to be further studied. No significant financial relationships to disclose.
Vascular endothelial growth factor (VEGF) therapy in metastatic renal cell carcinoma (mRCC): Differences between Asian and non-Asian patients.
Authors: Ying Wang, Toni K. Choueiri, Jae-Lyun Lee, Min-Han Tan, Sun Young Rha, Scott A. North, Christian K. Kollmannsberger, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2012)

451 Background: Several reports have indicated that VEGF targeted therapy in metastatic renal cell carcinoma (mRCC) may be more toxic in the Asian versus Caucasian populations. Comparative efficacy of these agents with respect to ethnicity is not well characterized. Methods: Eight centers participating in the International mRCC Database Consortium with available dose reduction data on patients with mRCC treated with VEGF targeted therapy were included in this analysis. Asian patients were derived from centers in Korea and Singapore. Results: 1024 patients with a median follow-up of 29.4 months were included in this analysis. Baseline characteristics are below. The percentage of dose modifications/reductions between non-Asians and Asians was similar (55% vs 61% p=0.1197) but more patients completely discontinued treatment due to toxicity in the non-Asian vs the Asian group (28% vs 21% p=0.0197). When adjusted for the Heng et al poor prognostic criteria, there was no difference in overall survival (HR 0.887, 95%CI 0.729-1.08, p=0.2322) or progression-free survival (HR 1.069, 95%CI 0.910-1.256, p=0.4184) between non-Asians and Asians. Interestingly, when patients were dose reduced due to toxicity, they had a longer treatment duration and overall survival than those that did not require a dose reduction in both the non-Asian (10.6 vs 5.0 months p&lt;0.0001 and 22.6 vs 16.1 months p=0.0016, respectively) and in the Asian populations (8.9 vs 5.4 months p=0.0028 and 28.0 vs 18.7 months p=0.0069). Conclusions: After adjusting for risk groups, there appears to be no difference in outcome between Asians vs. non-Asian patients with mRCC treated withVEGF-targeted therapy. Judicious dose reductions may allow for better outcomes in both populations possibly due to longer treatment durations, but direct comparisons are needed. [Table: see text]
Evaluation of never-smoking status and male gender as clinical predictive factors for survival with erlotinib treatment of non-small cell lung cancer.
Authors: M. Faehling, R. Eckert, S. Kuom, T. G. Kamp, K. Stoiber, C. Schumann
Journal: Journal of Clinical Oncology (2010)

e18134 Background: In non-small cell lung cancer (NSCLC), EGFR-mutation status predicts response to treatment with erlotinib. However, often EGFR-mutation analysis is not available. Therefore, clinical response predictors are needed. Available data suggest that never-smokers, females and patients with adenocarcinoma (AC) histology may benefit most from treatment with erlotinib. Methods: Using Cox proportional-hazard regression, we retrospectively analyzed 121 consecutive patients with advanced inoperable NSCLC treated with erlotinib to test whether these clinical parameters predict response and survival in a routine setting. Results: In our Caucasian population, partial remission (PR) was achieved in 16.5% with higher PR rates for never-smokers (46.9%), females (23.1%, males 13.4 %) and AC histology (25.0%). Progression free survival (PFS) was 3.0 months and overall survival (OS) was 7.5 months. Male patients had slightly longer survival than female patients (OS 8.5 vs. 7.0 months). After adjustment for smoking and histology, the gender difference was significant (adjusted hazard ratio (HR) 0.57, CI 0.34-0.97). This unexpected finding may reflect the large proportion of males achieving stable disease (41.5 %, females 17.9 %). Histology had no effect on PFS and OS. Never smokers had a longer PFS and OS (7 and 13 months) than smokers and ex-smokers (PFS 1.75 and 3.5 months, OS 5.5 and 7.5 months). The duration of ex-smoking had no significant effect on PFS (p for trend 0.80). The HR for OS of ever-smokers vs. never-smokers was 2.73 (OS, CI 1.53-4.86). Most useful prognostic parameters during erlotinib treatment were radiological response (OS 23 months, HR for PR vs. SD or PD 0.19, CI 0.09-0.40) and skin toxicity (OS 13.5 months, HR for grade 2 or 3 toxicity vs. grade 0, 1 toxicity 0.54, CI 0.33-0.88). Conclusions: Our results indicate that the clinical predictors (never-smoking status, female gender, AC histology) are useful to predict PR to erlotinib. However, only never-smoking status and male gender were associated with an improved OS. During treatment, objective response and higher degree skin toxicity predict prolonged OS. No significant financial relationships to disclose.
Heterogeneity of prostate-specific membrane antigen (PSMA) expression in classic and apoptotic circulating tumor cells (CTC) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Karen A. Autio, Aseem Anand, Rachel Krupa, Jessica Louw, Zaina Arslan, Ryan Dittamore, Howard I. Scher
Journal: Journal of Clinical Oncology (2014)

198 Background: Prostate-specific membrane antigen (PSMA) is a folate hydrolase expressed on the surface of PC cells that has been used as a target to detect disease and selectively deliver cytotoxic agents and radionuclides. The ability to detect PSMA levels on circulating tumor cells (CTCs) may identify patients likely to benefit from such targeted therapy. Technology developed by Epic Sciences utilizes high definition imaging of plated nucleated cells. Methods: Blood samples were obtained from patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Cells were stained for CK, CD45, PSMA and categorized as classic CTC (CK+, CD45-, intact/morphologically distinct nuclei) or apoptotic CTC (CK+, CD45-, morphology suggesting apoptosis). Clinical data including treatment, metastatic sites, Veridex CellSearch CTC enumeration, prostate-specific antigen, and alkaline phosphatase was collected. Results: Fourteen pts with mCRPC, including eight with serial samples were analyzed (33 samples in total). At the first draw (t1), classic CTC were detected in 13 pts (93%), (median two cells/ml, range 0 to 40 cells/ml) and apoptotic CTC in 14 pts (100%) (median four cells/ml, range 1 to 18 cells/ml), including six pts (42%) with no CTC by Veridex CellSearch. PSMA expression was detected in five pts (36%) with classic CTC of which a median of 32% of cells (range 5 to 100%) expressed the antigen. Similar intra-patient heterogeneity was seen for the 10 pts (71.4%) with PSMA+ apoptotic CTCs (median 33.5%, range 11 to 75% cells). During treatment, often with more complete androgen suppression, PSMA was detected in 3 of the 8 (38%) pts with no PSMA+ classic CTCs at t1. The presence of PSMA expression in apoptotic CTCs did not appear to change while on therapy. Conclusions: A larger percentage of PSMA expression was seen in mCRPC pts in apoptotic CTC (10 out of 14) than classic CTC (5 out of 14) at t1, with intra-patient cell heterogeneity of PSMA expression in both CTC populations. Serial measures suggest dynamic changes in PSMA expression over time. The threshold of detectable cells and proportion and degree of PSMA expression that associates with drug sensitivity is unknown. Larger samples of pts at discrete time points on therapy are underway to further elucidate the potential clinical relevance.
Treatment of cervical intraepithelial neoplasia with topical imiquimod.
Authors: S. Polterauer, C. Grimm, C. Natter, J. Rahhal, L. Hefler, A. Reinthaller, P. Speiser
Journal: Journal of Clinical Oncology (2011)

5041 Background: Alternatives to surgical therapy are needed for the treatment of high-grade cervical intraepithelial neoplasia (CIN). We investigated the effectiveness of a treatment with imiquimod (IMQ), a topical immune-response modulator, for patients with CIN 2 and 3. Methods: In this placebo-controlled trial 59 patients with CIN 2 and 3 were randomized to receive either a 16-week treatment with topical IMQ or placebo. The main outcome was effectiveness, defined as histologic regression (to CIN1 or less) four weeks after end of treatment; secondary outcomes were complete histologic remission, human papillomavirus (HPV) clearance and treatment tolerability. Results: Of the patients 27 (46%) and 32 (54%) presented with CIN 2 and 3, respectively. Histologic regression was significantly increased in the IMQ group (75%) compared to the placebo group (41%) (P=0.01). Complete histologic remission was significantly increased in the IMQ group (46%) as compared with the placebo group (15%) (P=0.02). At baseline, all 59 patients (100%) were tested positive for HPV DNA. HPV clearance rate was increased in the IMQ group (61%), as compared with the placebo group (15%) (P<0.001). The lesion progressed to micro-invasive cancer in 2 of 59 patients (3%)—both within the placebo group. Topical IMQ treatment was well tolerated. Due to local and/or systemic side effects, eight patients (27%) within the IMQ group switched to 50%-dose medication and one patient (3%) prematurely quit the treatment. Conclusions: Topical IMQ is an effective treatment for high-grade CIN and is well tolerated.
MicroRNA profile and KRAS status in metastatic colorectal cancer.
Authors: M. Valladares-Ayerbes, M. Blanco, M. Reboredo, M. J. Lorenzo-Patiño, F. Arnal, M. Haz Conde, V. Medina Villaamil, I. Santamarina Caínzos, L. M. Antón Aparicio, M. Calvo Martinez
Journal: Journal of Clinical Oncology (2011)

453 Background: microRNAs (miRNAs) are small non-coding RNA with regulatory functions. miRNAs expression is deregulated in cancer. Our objective is to establish a miRNA expression profile as a prognostic and predictive signature in Colorectal Cancer (CRC). In this cohort, patients with metastatic (m) CRC have been included. The expression of miRNAs have been analyzed and correlated with clinical and pathologic parameters, including KRAS status, disease free survival (DFS), and overall survival (OS). Methods: Tissue samples of mCRC were obtained as formalin-fixed paraffin-embedded (FFPE) specimens from the archives of our institution, after obtaining informed consent of patients. Genomic DNA was extracted using Qiaamp DNA mini kit (Qiagen). For the mutational testing of KRAS gene, we use the TheraScreen KRAS PCR kit (Qiagen). miRNA-enriched RNA was extracted using High Pure miRNA Isolation Kit (Roche). miRNA expression was analyzed by quantitative reverse transcription PCR (RT-qPCR) using LNA technology (Exiqon) in a LightCycler 480 (Roche) device. REST2009 (Qiagen), SPSS 19 (IBM), and Prism (GraphPad) software was used to data analysis. Results: One-hundred and forty mCRC patients have been included. To date, we have extracted DNA and performed KRAS mutational testing for 127 FFPE specimens. From these, 72 (56.7%) were wt while the remaining 55 (43.3%) were mt. We have performed a miRNA expression studies in 28 tumors. miRNAs let-7a, miR-17, miR-21, and miR-200c were analyzed. 5S rRNA and U6 snRNA were amplified as reference genes. miR-21, miR-17, and let-7a were found upregulated (p&lt;0.05) in mCRC samples versus healthy colon. However, for all 4 miRNAs analyzed, there were no significant differences of expression between wt and mt tumor samples for KRAS gene. Conclusions: The expression of 4 miRNAs analyzed is not correlated with mutations in KRAS gene. However, 3 of 4 miRNAs analyzed were found upregulated in tumors. The results for the association of the expression of miRNAs analyzed with the response to treatment and other clinical parameters will be presented during the symposium. Supported in part by SERGAS, Xunta de Galicia, Grant PS08/77. No significant financial relationships to disclose.
Clinical Relevance of Complex Chromosomal Aberrations in Bone Marrow Cells of 107 Children with ETV6/RUNX1 Positive Acute Lymphoblastic Leukemia (ALL).
Authors: Zuzana Zemanova, Kyra Michalova, Libuse Babicka, Lenka Pavlistova, Marie Jarosova, Milena Holzerova, Alexandra Oltova, Martina Hruba, Katerina Muzikova, Jan Zuna, Jan Trka, Vladimir Mihal, Jiri Sterba, Renata Formankova, Petr Sedlacek, Alena Vrzalova, Jan Stary
Journal: Blood (2006)
Bupropion for hot flashes control in breast cancer survivors: A prospective, double-blind, randomized cross-over pilot phase II trial.
Authors: G. R. Nuñez, A. Del Giglio, H. Pinczowski, R. M. Zanellato, L. C. Tateyama, F. Schindler, F. A. Fonseca
Journal: Journal of Clinical Oncology (2011)

9102 Background: Hot flashes and sexual dysfunction often affect breast cancer's survivors compromising their quality of life. Approximately 65% of women after treatment for breast cancer complain of hot flashes. Bupropion is an antidepressive medication used for smoking cessation and was also studied previously for sexual dysfunction. We aimed at evaluating bupropion’s activity for the control of hot flashes, improvement of sexual dysfunction, depression and quality of life in breast cancer's survivors. Methods: This is a randomized, double-blind, crossover, placebo-controlled pilot study that enrolled 55 breast cancer survivors who reported more than 7 hot flashes per week and randomized them to either bupropion 150 mg twice daily for 4 weeks followed by 1 week of washout and more 4 weeks of placebo twice daily or vice versa. The primary end point was average daily hot-flashes activity (number of hot flashes and a score combining number and severity) reported while on bupropion or placebo. Secondary end points were sexual dysfunction, depression and quality of life evaluated through the ASEX, Beck and EORTC-Q30 scales, respectively. Forty eight patients concluded all phases of the study whereas 6 were only evaluated at baseline and withdrew from the study (3 in the bupropion group and 3 in placebo) and 1 patient was excluded because didn't fill out the hot flashes diaries properly. This pilot study was designed to detect a 50% reduction in hot flashes for bupropion as compared to placebo, with a power of 0.80 and a type one error of 0.05. Results: Bupropion reduced by 1,26 hot flashes per day and 6,31% hot flashes score while placebo reduced 2,25 (p>0,05) hot flashes per day and 30,47% (p>0,05) hot flashes score. We saw no statistically significant differences in the ASEX, Beck and EORTC-Q30 scales between bupropion and placebo. At the end of the study, 47% of the patients preferred bupropion whereas 53% preferred placebo. There were no statistically significant differences in side effects frequency between study groups. Conclusions: As compared to placebo, bupropion did not show a minimum of 50% activity for the control of hot flashes in this group of breast cancer's survivors.
Comparison of prognostic factors and biochemical disease-free survival (BDFS) in men with prostate cancer younger than age 65, age 65 to 75, and age 75 or older treated with combined simultaneous radiotherapy.
Authors: J. B. Benton, F. A. Critz, P. D. Shrake, M. L. Merlin, F. J. Schnell, B. Song, S. E. Rosenbaum, C. A. Levitt, L. R. Holmes
Journal: Journal of Clinical Oncology (2011)

e15029 Background: Recent reports have questioned the utility of screening and/or treating men 75 years of age or older with prostate cancers because of presumed indolent nature of these cancers, and efficacy of treatment in such population Methods: Between September 1992 and January 2006, we reviewed 4,209 consecutive patients who had clinical stage (T1, T2, N0, M0), hormonal naive prostate cancers treated with I-125 seed implants, followed by external beam image guided radiotherapy (combined simultaneous radiotherapy). These men were followed for a minimum of five years. The primary end points were biochemical disease free survival (BDFS), and evaluation of pre-treatment prognostic factors between age groups < 65, 65 to 74, and 75 or older. Results: Of the 4,209 eligible men, 2160, 1758, and 291 were in the < 65, 65 to 74, and 75 or older groups, respectively. Utilizing the National Comprehensive Cancer Network (NCCN) risk group stratification, the < 65 group contained 1291(60%), 527(24%), and 342(16%) patients in the low, intermediate, and high risk group, respectively (Chi-square test P < 0.01). In the 65 to 74 age group, there were 849(48%), 516(30%), and 293(22%) patients in the low, intermediate, and high risk group, respectively (Chi-square test P < 0.01). In the 75 or older group, there were 104(36%), 104(36%), and 83(28%) patients in the low, intermediate, and high risk, respectively, (Chi-square test P< 0.01). There was a significant difference between the < 65 group and 75 or older group in overall BDFS (PSA <_ 0.2) at ten years (87% in the group < 65, and 81% in the group 75 or older, P= 0.01). There was no significant difference between the 65 to 74 group, and the 75 or older group (82% and 81%, respectively, P= 0.7). Conclusions: Elderly men (75 or older) do not usually have indolent prostate cancers. Many of these men present with aggressive disease, and diminished BDFS after treatment with radiotherapy. They should be offered aggressive local therapy.
The use of whole genome copy number variation (CNV) to measure genomic instability in mCRPC CTCs.
Authors: Yipeng Wang, Stephanie Greene, Angel Rodriguez, Jerry Lee, Mark Landers, Ryan Vance Dittamore, Dena C. Marrinucci
Journal: Journal of Clinical Oncology (2016)

307 Background: AR targeted therapies in combination with PARP inhibitors have recently shown efficacy in mCRPC patients with specific DNA repair gene mutations in metastatic tissue biopsies. Homologous recombination DNA repair deficiencies (HRD), associated with response to PARP inhibitors, can also be assessed by genomic instability/scarring. Accurate genomic scarring measurement in tumors can be confounded by intra-tumor heterogeneity and/or non-tumor genome contamination. To better identify PARPi sensitivity in mCRPC patients, we developed a genomic instability and scarring assay starting from single CTCs. Methods: VCaP, LnCaP or PC3 cell lines were spiked into healthy donor blood. Individual spiked cells were identified and recovered for genomic analysis using the standard Epic CTC assay. Post recovery, cells were lysed, whole genome amplified, constructed into shotgun libraries and sequenced to ~2M 2x150bp PE reads. Following alignment, whole genome copy number and instability analysis was performed to identify large scale transitions (LST, n of chromosomal breaks between adjacent regions of at least 10 Mb), % of genome altered (percentage of 1Mbp bins with copy number alterations), as well as specific tumor suppressor/oncogene copy number alterations. The association of PTEN loss with increases in genomic instability and scaring was performed. Results: Loss of PTEN function was previously shown to be associated with genomic instability. Our assessment of PTEN deletion was confirmed in PC3, while at least one genomic copy was observed in LnCaP and VCaP. The number of LSTs and % of genome altered was higher in PC3 (n = 19 +/- 3; 9.3% +/- 2.6%) than both VCaP and LnCap (n = 8 +/- 2; 6.1% +/- 0.4%). Conclusions: The association of higher genomic instability in a PTEN null cell line (PC3) vs. those with either heterozygous (LnCaP) or wild type (VCaP) PTEN status, matches published reports associating PTEN loss with increased genomic instability. Although, PC3 only demonstrates mild PARPi sensitivity in vitro, the detection of increased genomic scarring vs. cells with at least 1 functional PTEN allele confirms the assays ability to quantify genome instability at the single cell level from CTCs in a liquid biopsy.
RALDH2 Is Regulated by an LMO/SCL(TAL1) Associated Protein Complex in T Cell Acute Lymphoblastic Leukemia.
Authors: Gerlinde Layh-Schmitt, Wei Wang, Antonia Rosenstiel, Stefanie Koch, Chuck Klanke, Kathleen Anderson, Peter McCaffery, Christof von Kalle
Journal: Blood (2005)
Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Can Induce Durable Remission in Heavily Pretreated Relapsed Hodgkin Lymphoma. (HL).
Authors: Robert Chen, Joycelynne Palmer, Leslie Popplewell, Jessica Shen, Eileen Smith, Maria Delioukina, Neil Kogut, Joseph Rosenthal, Stephen J Forman, Auayporn P. Nademanee
Journal: Blood (2009)
Relationship between physician characteristics and the use of newer chemotherapy for the treatment of colon cancer.
Authors: D. J. Becker, D. L. Hershman, B. J. Insel, A. I. Neugut
Journal: Journal of Clinical Oncology (2011)

6106 Background: Oxaliplatin has been a standard part of adjuvant colon cancer treatment since 2003, while patients with metastatic cancer receive oxaliplatin and/or irinotecan. We investigated the frequency and predictors of oxaliplatin use in stage III colon cancer and of oxaliplatin/irinotecan use for metastatic colon cancer in the elderly. Methods: We identified patients >65 yrs diagnosed with stage III colon cancer, 9/1/04- 12/31/05, in the SEER-Medicare database who were treated with oxaliplatin within 6 months of diagnosis. We also identified patients >65 yrs diagnosed with stage IV or recurrent colon cancer, 1/1/05-12/31/05, treated with oxaliplatin or irinotecan. We used multivariable logistic regression models and Generalized Estimating Equations to assess the relationship between patient/physician characteristics and receipt of drug. Results: Among 1884 patients with stage III colon cancer, only 825 (43.8%) were treated with chemotherapy and of those 443 (53.7%) were treated with oxaliplatin. Younger age (OR 3.64 95% CI 2.38-5.57), white race (OR 1.93 95% CI 1.06-3.49), being married (OR 2.21 95% CI 1.60-3.07), fewer comorbidities (OR 2.84 95% CI 1.81-4.45), urban location (OR 2.37 95% CI 1.35-4.05), moderate/poorly differentiated cancer (OR 2.47 95% CI 1.30-4.67) and having a younger physician (OR 1.66 95% CI 1.12-2.46) were associated with oxaliplatin receipt. Among 1,119 patients with stage IV or recurrent colon cancer, only 441 (39.4%) received chemotherapy, however 361 (81.9%) received either oxaliplatin (291, 66.0%) or irinotecan (70, 15.9%). Younger age, being married, fewer comorbidities, having a younger physician (OR 2.43 95% CI 1.47-4.01), a US trained physician (OR 1.45 95% CI 1.02-2.06), and a physician who saw more patients in the sample (OR 1.60 95% CI 1.14-2.25) were associated with receipt of oxaliplatin and/or irinotecan. Conclusions: Uptake of newer chemotherapy drugs for the treatment of colon cancer has been rapid in the metastatic setting, but less rapid in the adjuvant setting. Younger physicians are more likely to treat patients with newer treatments than older physicians. Additional studies of the influence of physician characteristics on practice patterns are needed.