tbuckley/cabot-search huggingface dataset:
Outcomes following induction chemotherapy in patients with AML arising from MDS: Analysis of prognostic factors
Authors: C. M. Bello, D. Yu, W. Zhu, G. A. Wetzstein, J. E. Lancet
Journal: Journal of Clinical Oncology (2009)

7088 Background: Secondary acute myeloid leukemia (sAML) arising from myelodysplasia (MDS) or a myeloproliferative neoplasm (MPN) has a poor prognosis. To date, there is limited knowledge about risk factors that determine how sAML will respond to treatment. This analysis evaluated possible prognostic factors in patients with sAML that were treated with anthracycline-based induction therapy. Methods: Retrospective chart review of patients with untreated AML from MDS/MPN treated with standard induction therapy from January 2004 to September 2008. Age, IPSS, ECOG PS, cytogenetics, duration of MDS, and prior MDS treatment were evaluated for their impact on obtaining complete remission (CR) or CR with low platelets (CRp) and overall survival (OS). Results: Sixty-one patients with sAML who received induction therapy were evaluated: median age (range) = 66 (36–82) years; M = 67%, ECOG PS 0 or 1 = 86%; poor-risk (PR) cytogenetics = 33%; IPSS &gt; 1 = 43%; prior therapy for MDS with decitabine or azacitidine (DM) or lenalidomide (L) = 41% (25 pts). Of the entire group, 59% (36 pts) achieved CR/CRp (95% CI: 46%-71%) and the median OS was 6.5 (95% CI: 3.9–8.1) mo. Multivariable analysis indicated that the same three factors were significantly negatively associated with CR/CRp as well as OS: PR cytogenetics, prior treatment with DM/L, and long transformation to AML on log scale. Only 32% of the group that received prior treatment with a DM/L achieved CR/CRp compared to 78% in non DM/L-treated patients (OR = 0.13, 95% CI: 0.04–0.42). The CR/CRp rate for those with intermediate risk (IR) cytogenetics was 70% compared to only 35% for those with PR cytogenetics (OR = 4.33, 95% CI: 1.38–13.6). Those with PR cytogenetics had a median OS of 2.8 mo compared to 7.5 mo for IR (p = 0.01). The median OS for those treated with a DM/L was 3.7 mo compared to 10.5 mo for non DM/L-treated patients (p &lt; 0.0001). Conclusions: Prior MDS treatment with a DM/L, PR cytogenetics and long transformation to AML are independent negative prognostic factors for response and OS in patients with sAML following induction therapy, suggesting that such patients may be better served by novel approaches, and that stratification for these risk factors should be considered in future clinical trials. Larger-scale confirmation of these data is ongoing. No significant financial relationships to disclose.
Relapses of lupus nephritis (LN): Incidence, risk factors, serology and outcome. A prospective analysis of 46 LN from the louvain lupus cohort
Authors: M El Hachmi, Michel Jadoul, AN Toukap, Geneviève Depresseux, Frédéric Houssiau
Journal: Annals of the Rheumatic Diseases (2003)
Proteomics identification of stress-induced phosphoprotein (STIP1) as a potential biomarker for human ovarian cancer
Authors: T. Wang, A. Chao, H. Huang, C. Lai
Journal: Journal of Clinical Oncology (2008)

16533 Patients with ovarian cancers are often associated with poor prognosis and limited survival rates because their cancers were not detected at earlier stages. Currently, CA125 is the most commonly used tumor marker for ovarian cancer, but it only results in 78% sensitivity, 82 to 95% specificity, and 82% positive predictive value. Therefore, discovery of new tumor markers for detecting ovarian cancer is warranted. Peripheral blood is a convenient source of tumor markers. However, screening for new tumor markers from blood is difficult because tumor markers, usually at low concentrations in blood, are easily obscured by serum abundant common proteins. Alternatively, tumor interstitial fluid (TIF) represents a rich source for secreted proteins from both cancer cells and neighboring stromal tissues, and the contents of TIF are eventually drained into blood circulation. In this study, we attempted to identify cancer-specific proteins from TIF derived from human ovarian cancer with proteomics approaches. Using statistical analysis of 596 protein spots in two-dimensional gels between the TIF of ovarian cancer and normal interstitial fluid (NIF) of normal ovaries, we identified several differentially expressed proteins, including stress-induced phosphoprotein 1 (STIP1). Specific elevations of STIP1 in TIF and ovarian cancer tissues were confirmed with Western blot analysis and immunohistochemistry, respectively. Subsequent enzyme-linked immunosorbent assay (ELISA) experiments revealed serum levels of STIP1 were significantly higher in ovarian cancer patients than in healthy controls. Receiver operating characteristics (ROC) curve analysis suggested the value of STIP1 to be comparable to CA125. These results suggest STIP1 has the potential as a biomarker for human ovarian cancer. No significant financial relationships to disclose.
Clinical outcome of single agent volasertib (BI 6727) as second-line treatment of patients (pts) with advanced or metastatic urothelial cancer (UC).
Authors: W. M. Stadler, D. J. Vaughn, G. Sonpavde, N. J. Vogelzang, S. T. Tagawa, D. P. Petrylak, P. J. Rosen, C. Lin, J. F. Mahoney, S. S. Modi, P. Lee, M. S. Ernstoff, W. Su, A. I. Spira, M. Ould Kaci, T. Taube, R. Vinisko, C. Schloss, C. Zhao, M. A. Carducci
Journal: Journal of Clinical Oncology (2011)

4567 Background: No standard therapy exists for metastatic UC pre-treated with a platinum-based regimen. Polo-like kinase 1 (Plk1) controls multiple essential steps of mitosis and is therefore an interesting target for anticancer therapy. Volasertib is a cell cycle kinase inhibitor that targets Plk1 and has shown preliminary antitumor activity in different malignancies, including a partial response in a pretreated UC pt. We report preliminary efficacy and safety data of a phase II trial of volasertib as second-line therapy for metastatic UC. Methods: Pts with metastatic UC who progressed after 1 prior chemotherapy or relapsed within 2 years of (neo)adjuvant chemotherapy received 300 mg volasertib (2-hour iv infusion) on day 1 every 3 weeks (w). If well tolerated, dose escalation to 350 mg in cycle 2 was encouraged. Primary endpoint was objective tumor response (RECIST) assessed every 6 w; secondary endpoints were PFS, OS, duration of response, safety and PK. An early stopping rule required ≥10% objective response rate in the first 20 pts. Results: Recruitment has completed. Since December 2009, 50 pts were enrolled and treated; 9 pts are still on treatment as of January 19, 2011. All pts are evaluable for safety and efficacy analyses. Pt characteristics were: median age 69 years (52-83), ECOG PS (%): 0 (50), 1 (46), 2 (4); 40% of pts had >2 metastatic sites; 29% of pts relapsed >6 months after prior therapy. Median number of cycles was 2 (range: 1-19), 22 pts had dose escalation to 350 mg. Preliminary best response data are: 7 pts (14%) had partial response, 12 pts (24%) had stable disease and 31 (62 %) progressed within 6 weeks after study entry. To date, median duration of response is 25 w (12-53 w) and median PFS is 6 w. Drug-related grade 3 or 4 adverse events (AEs) were neutropenia (24%), thrombocytopenia (16%), anemia (10%). Nonhematologic AEs were mild and uncommon, and no cumulative toxicity was observed. Overall survival data are pending. Conclusions: Single agent volasertib as second-line treatment of advanced/metastatic UC was well tolerated and showed antitumor activity. Further assessment of volasertib in combination with other active compounds in metastatic UC is warranted.
Audit of open breast biopsies in a Nigerian teaching hospital
Authors: A. C. Adisa
Journal: Journal of Clinical Oncology (2007)

11091 Background: Open biopsy is an accurate method for diagnosis of breast tumors especially where facilities for needle biopsies like tru cut needle biopsy or aspiration cytology method are not readily available. We report a 10-year retrospective study of the clinical and pathological characteristics of excised breast masses in our centre. Methods: Clinical records and pathological results of all breast biopsies of consecutive patients referred to the Breast Clinic of the Abia State University Teaching Hospital, Aba, Nigeria were studied from January 1994 to December 2003. We present the outcome of the histology reports from breast biopsy for a period of 10 years (1994- 2003) in Abia State University Teaching Hospital. Results: A total of 421 patients had open biopsies for breast masses. The age ranged from 12 years to 80 years with the median age of 34 years. The commonest symptom was painless breast lump in 90% of patients; breast pain was present in less than 5% of cases. Malignancies were discovered in 24% of the cases and the predominant histological type was infiltrating ductal carcinoma (NOS) which was found in 78% of cases, lobular carcinoma was found in 2% of cases. 79% of the breast cancers occur in pre menopausal women and the majorities (85%) were late stages. 79% of the patients with cancer of the breast were 50 years old or younger and the youngest patient was 14 years. The benign lesions in order of frequency were fibroadenoma (45%), fibroadenosis (41%), granulomas (5%), breast cyst (3%), and galactocele (2%).Other less common pathologies include lipoma, chronic abscesses and parasitic cysts. Conclusions: Majority of breast masses in Nigerian women are benign. The preponderance of late staged tumors and pre menopausal patients call for early detection, public awareness and improved screening methods No significant financial relationships to disclose.
Genetic variants of the organic anion transporter SLCO2B1 as pharmacogenomic determinants of response to androgen deprivation therapy (ADT) for prostate cancer.
Authors: Philip W. Kantoff, Xiaodong Wang, Wanling Xie, Mari Nakabayashi, Mark Pomerantz, Gwo-Shu Mary Lee
Journal: Journal of Clinical Oncology (2015)

137 Background: Genotypes at three SNPs (rs12422149; rs1789693; rs1077858) within SLCO2B1 were associated with time to progression (TTP) on ADT in the Dana-Farber Cancer Institute (DFCI) Prostate CRIS ADT cohort (J Clin Oncol. 2011 29(18): 2565). Variation at exonic SNP rs12422149 (Gln to Arg) allows more efficient import of DHEAS, enhances AR signaling and cell growth, and as a result, is associated with shorter TTP on ADT. We further externally validated the association of SLCO2B1 variants with TTP on ADT in an independent ADT cohort and estimate their association with overall survival (OS) in both cohorts. Methods: An independent ADT cohort (N=616) was established for validation. TTP was defined using the same criteria as for the original cohort. The associations of genetic variants with TTP on ADT and OS were estimated from multivariable Cox regression and adjusted by known prognostic factors. Effects of one intronic SNP rs1077858 on SLCO2B1 and DHEAS uptake activity were characterized in cell cultures. Results: Association between genotype at rs12422149 and TTP on ADT was confirmed in univariable (P= 0.0187) and multivariable (adjusted HR= 1.31 for GG vs AA/AG, P= 0.0489) analyses. The Median OS from ADT initiation was 6.5 years in all patients (N= 1094, original plus validation cohort). The intronic SNP rs1077858 was significantly associated with the OS from ADT initiation in both univariable (P= 0.0091) and multivariable (adjusted HR= 1.34 for GG vs AA/AG, P= 0.014) analyses. The difference of median OS was 18 months. SLCO2B1 expression in normal prostate tissue carrying the major allele of SNP rs1077858 (AA) was significantly lower than those carrying the risk allele (GG) (Ptrend= 0.0193), suggesting that the association of the SNP rs1077858 with the OS on ADT may be due to its impact on the SLCO2B1 expression. SLCO2B1 knockdown in vitro decreased DHEAS uptake and diminished DHEAS-induced prostate cancer cell growth. Conclusions: Germline variants within SLCO2B1 modulate function or expression of SLCO2B1, subsequently affecting the uptake of androgen precursors and affecting TTP or OS in prostate cancer patients.
Advantages of percutaneus dilatational tracheostomy
Authors: Georgiy Pakhomov, Otabek Eshonkhodjaev, Rustem Hayaliev, Anvar Yormuhammedov
Journal: European Respiratory Journal (2014)

Objective: to clarify the safety, benefits and common techniques of percutaneous dilatational tracheostomy (PDT).  Material and methods: 62 patients in the RSCS and 14 patients in resuscitation on the road in other hospitals were performed PDT from 2007 to 2012y. All patients were on prolonged mechanical ventilation due to different severe complications. We use Ciaglia9s techniques for PDT. This Seldinger-based technique involves cannulation of trachea between 1st & 2nd or 2nd & 3rd tracheal ring with a guide wire. This is followed by graded dilatation of the trachea using multiple dilators.  Results: Duration of PDT in the initial stages was 12-30 minutes, after acquiring enough experience, it fell to 7-10 min. Minor bleeding from small vessels that do not pose a threat and quickly eliminated by coagulation were observed in 8 (12.9%) patients. In 6 (9.7%) patients had inflammatory changes in the tracheostomy tube. In 2 (3.2%) cases were observed delamination of tracheal mucosa. And only in 2 (3.2%) cases were observed posttraheostomic tracheal stenosis which in tracitional tracheostomy observes on 16-64% cases. In conventional tracheostomy posttraheostomic complication as tracheoesophageal fistula (3-7%) subsequently require reconstructive surgery. It should be noted, that the advantages of the procedure PDT Ciaglia over conventional tracheostomy procedure is - the speed of the procedure; minimally invasive techniques; low rate of various complications.  CONCLUSIONS: PDT is minimally invasive, less traumatic and is reasonably safe. Our experience allows to recommend PDT as an alternative to conventional tracheostomy in patients on prolonged mechanical ventilation with forecasting long-term respiratory support hardware.
18F-FDG PET/CT in the Management of Aortitis
Authors: Samuel Bruls, Audrey Courtois, Betty Nusgens, Jean-Olivier Defraigne, Philippe Delvenne, Roland Hustinx, Michel Moutschen, Natzi Sakalihasan
Journal: Clinical Nuclear Medicine (2015)

Aortitis is a generic term defined as an inflammatory condition involving the aortic wall, of infectious or noninfectious origin. This inflammatory process may deteriorate the aortic wall, resulting in potentially life-threatening vascular complications. Therefore, it is important to establish a diagnosis as early as possible.During a 4-year period, 428 consecutive patients referred to our department for aortic diseases underwent FDG PET/CT examinations. Among these, 18 patients (4.2%) were suspected to have aortitis. All of them had an initial positive FDG PET/CT uptake occurring in the aorta and major branches as evaluated by visual analysis of images and assessed with the final diagnosis of aortitis. During follow-up, after surgery and/or upon immunosuppressive treatment, each of these patients underwent a second PET/CT that was compared with the initial evaluation. In all cases, normalization of FDG uptake was correlated with clinical improvement.Our study aimed to illustrate the potential clinical value of functional monitoring with PET/CT in the management of aortitis. FDG PET/CT constitutes a valuable imaging modality to establish an early diagnosis, monitor disease progression and treatment, and evaluate vascular complication and relapse. We highlight the importance of an early detection of inflammatory large-vessel pathology, which may represent a major threat.
Megestrol acetate increases the incidence of deep venous thrombosis in patients with non small cell lung cancer
Authors: S. Hussain, M. Singh, R. Shi, R. Mansour, G. Mills, J. Marion
Journal: Journal of Clinical Oncology (2006)

18510 Background: To evaluate the incidence of deep venous thrombosis (DVT) in patients with non small cell lung cancer who take megestrol acetate as an appetite stimulant. Methods: A retrospective study of patients with non small cell lung cancer (NSCLC) was performed to determine the incidence of deep venous thrombosis. We reviewed medical records of patients with NSCLC who were treated with and without megestrol acetate as an appetite stimulant during the course of their treatment or follow up. Cochran-Mantel-Hansel statistics was performed. Results: We reviewed the charts of 179 patients with NSCLC. 86 patients received megestrol acetate during the course of treatment or follow up whereas 93 did not. Within the treatment group, 28 patients were female and 58 were male. In the control group 43 patients were female and 50 were male. There was no significant difference in the ECOG performance status of those in the treatment group from those in the control group. The frequency of DVT was 3.4 times higher in the treatment group as compared to the control group adjusting for gender (p &lt; 0.02). Similarly, the frequency of DVT was 2.8 times higher in the treatment group as compared to the control group adjusting for stage (P &lt; 0.045). Conclusions: After adjusting for gender or stage, the incidence of DVT appears to be higher for patients with NSCLC who took megestrol acetate as compared to those who did not. Even though megestrol acetate was being used as an appetite stimulant, the observed differences were not due to differences in the performance status of the two groups. Further prospective study of the risks and benefits of megestrol acetate as an appetite stimulant in patients with advanced NSCLC and other malignancies is warranted. No significant financial relationships to disclose.
In vitro chemosensitivity testing of mammospheres cultured from circulating epithelial tumor cells (CETCs) of breast cancer patients: Comparision to chemosensitivity of total CETCs.
Authors: Monika Pizon, Dorothea Zimon, Ulrich A. Pachmann, Katharina Pachmann
Journal: Journal of Clinical Oncology (2014)

50 Background: In vitro chemosensitivity testing of circulating epithelial tumor cells (CETCs) provides real-time information about the sensitivity of the tumor cells present in the patient. Nevertheless, a fraction of CETCs can survive after conventional chemotherapy and grow into distant metastasis. This may be a subpopulation of CETCs with proliferation activity which has the ability to form floating spheres in suspension culture. Spheroids exhibit stem cell-like properties and may be responsible for chemotherapeutic resistance. Therefore, the aim of our study was to determine the efficacy of chemotherapeutics on spheroids cultured from CETCs. Methods: The enumeration of CETCs from patients with solid tumors in clinical stage I to IV was performed using the maintrac method. Subsequently, CETCs in the context of the surrounding white blood cells were cultured in a suspension culture allowing for spheroid formation. To evaluate the cytotoxic effect of drugs on CETCs and spheroids we exposed them to anticancer drugs in short time culture in different concentrations and for different periods of time. Results: In contrast to CETCs, spheroids were significantly more chemotherapy resistant. Active drugs led to disintegration of tumor spheres. Interestingly, some cells in the spheres were able to survive. Epirubicin and especially salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, showed high efficacy in a high proportion of cells. Furthermore, our data suggested that curcumin, a natural biologically active compound that is extracted from the plant Curcuma longais a promising agent for cancer treatment. Docetaxel, cyclophosphamide, and 5-fluoruracil showed lower cytotoxic effects onto the cells in the spheres. Conclusions: Our results show, for the first time, that stem cells circulating in peripheral blood, capable of forming spheroids are way more resistant to anticancer drugs than the remnant circulating tumor cells. We, furthermore, demonstrate that salinomycin and curcumin efficiently destroy spheroids cultured from CETCs, strengthening their role as promising anticancer therapeutics.
Neoplasms Among A-Bomb Survivors in Hiroshima: First Report of the Research Committee on Tumor Statistics, Hiroshima City Medical Association, Hiroshima, Japan&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Harada, Tomin, Ishida, Morihiro
Journal: JNCI Journal of the National Cancer Institute (1960)

Journal Article Neoplasms Among A-Bomb Survivors in Hiroshima: First Report of the Research Committee on Tumor Statistics, Hiroshima City Medical Association, Hiroshima, Japan Get access Tomin Harada, M.D., Tomin Harada, M.D. Hiroshima City Medical Association and Atomic Bomb Casualty Commission,4National Institute of Health, Hiroshima, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Morihiro Ishida, M.D. Morihiro Ishida, M.D. Hiroshima City Medical Association and Atomic Bomb Casualty Commission,4National Institute of Health, Hiroshima, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 25, Issue 6, December 1960, Pages 1253–1264, https://doi.org/10.1093/jnci/25.6.1253 Published: 01 December 1960 Article history Received: 02 May 1960 Revision received: 25 August 1960 Published: 01 December 1960
Loss of heterozygosity (LOH) as a measure of whole-genome instability in ovarian cancer correlates with clinical outcomes.
Authors: G. Korpanty, K. Timms, V. Abkevich, M. Carey, A. Gutin, Y. Li, J. Li, M. Markman, R. Broaddus, J. S. Lanchbury, K. H. Lu, G. B. Mills, B. Hennessy
Journal: Journal of Clinical Oncology (2011)

5027 Background: The aim of the study was to assay the amount of loss of heterozygosity (LOH) across the whole genome as a measure of genomic instability in ovarian tumors and to determine the correlation between the fraction of the ovarian cancer genome with LOH and the clinical outcomes of ovarian cancer patients. Methods: We assessed the prevalence of LOH in 100 unselected ovarian cancer tumors using whole genome 500K Single Nucleotide Polymorphism (SNP) arrays (Affymetrix, Inc.). Allele dosage, copy number, and degree of contamination with benign tissue were used to estimate the likelihood of various genotypes in tumor tissue. Regions with the copy number of more than 3 were eliminated from the analysis since LOH data are unreliable when copy number exceeds 3. Results: We found that copy number changes of 1, 2 and 3 composed 12.6%, 45.7% and 21.5% of the genome in ovarian cancer, respectively. These changes contributed to 42.4%, 43.8% and 13.8% of LOH in ovarian cancer, respectively. The average fraction of the whole genome with LOH in ovarian cancer was 35%. The fraction of the genome with LOH was significantly correlated with tumor grade. The fraction of the ovarian cancer genome with LOH was statistically highly correlated with both overall survival (OS;p=3.4x10-6) and progression-free survival (PFS; p=0.0016) after debulking surgery and platinum/taxane-based chemotherapy. In multivariate analyses with clinical variables, only the fraction of the genome with LOH and residual tumor size (RTS) after debulking surgery were independent predictive factors for OS and PFS. Conclusions: Increased fraction of the genome with LOH as a measure of genomic instability in ovarian cancer is a significant and independent negative prognostic factor for both OS and PFS. The validation of the fraction of the ovarian cancer genome with LOH as an independent predictor of RFS and OS in a second ovarian cancer sample set will also be presented at the meeting.