tbuckley/cabot-search huggingface dataset:
Evaluation of quality-of-life side effects and duration of therapy in a phase III study of intermittent monotherapy versus continuous combined androgen deprivation
Authors: F. E. Calais da Silva, F. M. Calais da Silva, F. Gonçalves, A. Santos, J. Kliment, P. Whelan, R. T. Oliver, N. Antoniou, S. Pastidis, C. Robertson, M. Queimadelos
Journal: Journal of Clinical Oncology (2008)

5064 Background: We propose this phase III study comparing the intermittent monotherapy with continuous combined androgen deprivation using an LHRH analogue and ciproterone acetate and associated components of quality of life. Methods: 1045 men with a median PSA of 15.9ng/ml were registered between October 1999 and September 2007. 24% of registered patients have a PSA less than 10ng/ml; 39.3% of registered patients have a PSA greater than 20ng/ml. 90.1% have a T3 tumour and only 13.5% have metastatic prostate cancer. 914 patients (mean age 72) have been randomized 460 to Intermittent therapy and 454 to Continuous. Results: The maximum follow up is 7 years with a median of 2 years. The incidence of side effects is not too high in the Intermittent arm, with 7% of patients reporting Hot Flushes, 10% Gynocomastia, 5% Headaches. There are significantly higher rate of side effects in the Continuous arm (p<0.0001). 30% of patients reported that they were sexually active in the month before registration.There was no significant difference in sexual activity at randomsiation (p=0.67). After randomisation, sexual activity increases in the intermittent group to 33% (6 months), 29% (12 months), 28% (24 months) while in the Continuous arm the corresponding percentages are 20% (p=0.002), 19% (p=0.06), 8% (p=0.0001), respectively. Among the Intermittent patients only 20% (95% CI 15%, 23%) returned to therapy within one year of randomisation because of symptoms or an increase in PSA and 40% (95% CI 30%, 48%) have yet to return to therapy within 3.5 years of randomisation. Patients whose PSA reduces to less than 1 ng/ml at randomisation are off therapy longer than those whose PSA is between 1 and 4 ng/ml ( p<0.05). The median times off therapy are 174 and 100 weeks, respectively.The time on therapy did not depend upon PSA at randomisation, p=0.17. Conclusions: Side effects are less in the Intermittent arm than in the Continuous. Quality of Life is better in the Intermittent arm and namely sexual activity. Among the Intermittent patients only 20% returned to therapy within one year and 40% have yet to return to therapy within 3.5 years. No significant financial relationships to disclose.
Serum YKL-40 levels in patients with cervical cancer are elevated compared to patients with cervical intraepithelial neoplasia and healthy controls
Authors: J. S. Johansen, A. Roslind, C. Palle, I. J. Christensen, H. J. Nielsen, P. A. Price, D. Nielsen, B. Mosgaard
Journal: Journal of Clinical Oncology (2006)

5047 Background: YKL-40 is secreted by cancer cells, macrophages and neutrophils. The exact function of YKL-40 is unknown. It may be a growth or differentiation factor, play a role in angiogenesis or protect against apoptosis. High serum YKL-40 is associated with poor prognosis in breast-, colorectal-, ovarian-, prostate-, small cell lung cancer and malignant melanoma. The aim was to examine serum YKL-40 in patients with cervical cancer and cervical intraepithelial neoplasia (CIN). Methods: YKL-40 was determined by ELISA (Quidel, Santa Clara, CA) in pretreatment serum samples from 116 patients with cervical cancer (FIGO stage Ia (N = 5), Ib (N = 55), II (N = 27), III (N = 25) and IV (N = 4); median age 50, range 27–87 years) and 152 patients with cervical CIN (34 years, 20–80 years). The controls included 63 healthy women undergoing sterilization (36 years, 25–59 years) and a group of 134 healthy women (51 years, 18–79 years). Results: Serum YKL-40 was increased (p &lt; 0.001) in the patients with cervical cancer (median 76 μg/l, range 20–2310) compared to patients with CIN (45 μg/l, 20–288), women undergoing sterilization (37 μg/l, 20–125) and healthy women (43 μg/l, 20–172). Patients with CIN had slightly elevated serum YKL-40 levels. Serum YKL-40 increased with increasing stage (Ia: median 36 μg/l, range 26–137; Ib: 56 μg/l, 20–984; II: 92 μg/l, 28–2310; III: 163 μg/l, 40–1474; and IV: 224 μg/l, 137–391; p &lt; 0.001 Kruskal-Wallis test). All stage IV patients, 72% stage III, 52% stage II, 24% stage Ib, 40% stage Ia and 13% of patients with CIN had elevated serum YKL-40 compared to healthy controls (95 th percentile). Patients with squamous cell carcinoma had higher serum YKL-40 (median 92 μg/l, range 27–2310, N = 86) compared to patients with adenosquamous (67 μg/l, 20–93, N = 9, p = 0.027) and adenocarcinoma (43 μg/l, 20–1472, N = 20, p &lt; 0.001). Conclusion: Median serum YKL-40 is elevated in patients with stage Ib - IV cervical cancer. The serum level of YKL-40 seems to be correlated to the stage. No significant financial relationships to disclose.
Efficacy and Safety of Vorapaxar in Elderly Patients With Non-ST-Segment Elevation Acute Coronary Syndrome : Insights From the TRACER Trial
Authors: Luciana Armaganijan, Renato Lopes, Zhen Huang, Pierluigi Tricoci, Claes Held, Frans Van de Werf, Paul W Armstrong, Philip E Aylward, Harvey D White, David J Moliterno, Lars Wallentin, Edmond Chen, Robert A Harrington, John Strony, Kenneth W Mahaffey
Journal: Circulation (2013)

Efficacy and Safety of Vorapaxar in Elderly Patients With Non-ST-Segment Elevation Acute Coronary Syndrome : Insights From the TRACER Trial
Pretreatment diffusion weighted imaging for clinical outcome assessment in patients undergoing definitive chemoradiation for pancreatic adenocarcinoma.
Authors: Zachary S Buchwald, Jeffrey R. Olsen, Shahed Nicolas Badiyan, Todd A. DeWees, Yanle Hu, Ryan C. Fields, Andrea Wang-Gillam, Parag J. Parikh
Journal: Journal of Clinical Oncology (2015)

432 Background: Factors predicting patterns of failure for pancreatic ductal adenocarcinoma (PDA) are not well-established. Diffusion-weighted MRI (DWI) is useful in predicting recurrence for other gastrointestinal malignancies. The purpose of this study was to evaluate for correlation between tumor DWI parameters and clinical outcomes following chemoradiotherapy (CRT) for pancreatic adenocarcinoma. Methods: From 2009 to 2013, 27 patients with locally advanced (n=14), borderline resectable (n=12) or resectable (n=1) PDA underwent CRT. All patients received upfront FOLFIRINOX or gemcitabine-based chemotherapy prior to CRT, and gemcitabine (median weekly dose 800 mg/m 2 ) concurrent with radiotherapy. DWI was obtained during radiotherapy treatment planning, and apparent diffusion coefficient (ADC) maps were generated to allow determination of median tumor ADC. Tumor-directed CRT was administered with respiratory gated intensity modulated radiation therapy, 55Gy in 25 fractions without elective nodal coverage. Patients were followed by imaging every 2-3 months. Log rank test was used to estimate an optimal ADC cut-point of 1.4*10 -3 mm2/sec based on distant metastasis free survival (DMFS) and overall survival (OS). Analysis of local recurrence was not performed due to limited events. The log-rank test was used to evaluate differences in outcome between groups based on ADC classification. Results: The median time to last follow-up from completion of CRT was 9.7 months for all patients and 11 months among living patients. 5 patients underwent resection following CRT. The 1-year DMFS for patients with median ADC&lt;1.4*10 -3 mm2/sec was 79.5 percent, compared to 47.6 percent for those with median ADC &gt;1.4. The 1-year OS for patients with median ADC&lt;1.4 was 100 percent, compared to 46.3 percent for those with median ADC &gt;1.4. Both DMFS (p=.041) and OS (p=.003) were significantly improved on log-rank test for ADC&lt;1.4 compared to ADC&gt;1.4. Conclusions: A correlation was observed between DWI parameters and clinical outcomes for PDA. Further prospective study should be explored to validate DWI as a prognostic imaging biomarker.
A phase II trial of gefitinib monotherapy in patients with unresectable adrenocortical carcinoma (ACC)
Authors: V. Samnotra, R. Vassilopoulou-Sellin, A. T. Fojo, W. K. Oh, R. V. LaRocca, M. S. Ernstoff, V. A. Memoli, B. F. Cole, D. I. Quinn, P. A. Simmons, C. P. Tretter
Journal: Journal of Clinical Oncology (2007)

15527 Background: ACC is a rare malignancy with a very poor prognosis. Surgery is the only potential curative option. Gefitinib is an oral EGFR inhibitor that may have activity in solid tumors that express EGFR. ACC over expresses EGFR in a high proportion of cases. Methods: From April 2004 through December 2006, the ACC Working Group conducted a phase II trial of Gefitinib as second line, monotherapy in patients with pathologically confirmed unresectable ACC who had progressed on mitotane or chemotherapy. All prior systemic therapy was discontinued 28 days prior to starting gefitinib. Patients were ineligible if: had received prior therapy with any EGFR inhibitor, pregnant or breast feeding, had other co-existing malignancies (other than basal cell carcinoma or cervical cancer in situ), had an ECOG PS &gt; 2, absolute neutrophil counts &lt; 1,500, or platelets &lt; 20,000. Patients were not allowed concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, or St John’s Wort. Patients took gefitinib 250 mg orally once a day. Each cycle was 21 days with radiological assessment every 6 weeks.Response rate as determined by RECIST criteria was the primary endpoint. Results: 19 patients accrued to the study (18 with measurable disease and 1 without). Pt Characteristics: Female 79% (15/19); Median age 48 (range 26–74); 84% (12 female and 4 male =15/19) of the patients had steroid secreting tumors. Grade 3 toxicity was noted in 2 patients and included, hypertension and lower extremity edema and elevated liver transaminases. No grade 4 toxicities occurred. Of 19 patients evaluable, there were no complete responders, partial responders or patients with stable disease (0% response rate; 95% CI: 0%-18%). Conclusions: Gefitinib demonstrated no activity in patients with unresectable ACC. This study is now closed. This study demonstrated the ability to successfully accrue to a trial of novel agents in rare tumors in a multicenter setting. [Table: see text]
Compliance and persistency with a new oral iron chelator in patients with myelodysplastic syndromes
Authors: R. J. Faris, D. McCrone, N. Mody-Patel, V. Barghout, S. Dutta
Journal: Journal of Clinical Oncology (2007)

17510 Background: Patients with myelodysplastic syndromes (MDS) frequently receive blood transfusions and are at risk for iron overload (IO). The aim of this study was to estimate compliance and persistency rates of a new oral iron chelator, deferasirox, in patients with MDS in a real world setting. Methods: A retrospective analysis of patients provided deferasirox by Accredo Nova Factor database was conducted. Patients diagnosed with MDS and receiving deferasirox were followed from Jan 1, 2006 to Nov 30, 2006. Patients with at least 2 filled prescriptions were included in the analysis. Compliance was defined by medication possession ratio (MPR = # of days of medication supplied/# of days in refill interval). MPR&gt;0.80 is categorized as good compliance. Persistency was defined as the continuous prescription refill without an interruption of longer than 30 days and Kaplan Meier curves were analyzed. Reasons for discontinuation and differences in compliance rates were explored. Results: A total of 294 patients with MDS and at least 2 filled prescriptions filled were included in the analysis. The average age was 72.2 ±12.3 years and 53.7% were male. 64.1%, 30.3%, and 3.7% of patients were covered by private insurance, Medicare, and Medicaid, respectively. The average compliance with deferasirox was 0.89 ± 0.17. 67.9% of patients had an MPR greater than 0.90 (data left-skewed as ratio truncated at 1.0). Overall, 86.4% of patients were considered persistent with deferasirox during the analysis period. Reasons for discontinuing therapy included side effects (n=14; 5%), physician choice (n =10; 3%), patient choice (n=4; 1%), or a change in provider (n=6; 2%). Conclusion: MDS patients with transfusional IO when treated with deferasirox are highly compliant and persistent. Given the decreased survival associated with IO due to chronic blood transfusions in low and intermediate-1 risk MDS patients, compliance and persistency are important factors to consider when selecting therapies. [Table: see text]
The Influence of the Tropics on Rickets
Authors: ROGER  BROOKE
Journal: Annals of Internal Medicine (1928)

Article1 September 1928The Influence of the Tropics on RicketsROGER BROOKEROGER BROOKESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-2-3-281 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAbout the year 1650 Glisson, the distinguished English physician and physicist, as the result of an extended study concerning what was believed to be a new disease, published a monograph on rickets. Since the appearance of his notable paper down to scarcely more than a decade ago, progress in our knowledge of this common disease of childhood has been slow and of little clinical value. During the past ten years, however, many material and valuable discoveries have been made, due in great part to the able investigations of Mellanby, Huldschinsky, Howland, Schmorl, Findlay, McCollum, and that tireless and fruitful worker... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: U. S. Army Fort Sam Houston, Texas*Read before the American College of Physicians at the Annual Clinical Session, March 9, 1928, New Orleans, La. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDie Bedeutung der Vitaminlehre mit besonderer Berücksichtigung der KinderheilkundeDie Behandlung und Verhütung der Rachitis und Tetanie 1 September 1928Volume 2, Issue 3Page: 281-288KeywordsPhysicists Issue Published: 1 September 1928 PDF downloadLoading ...
A feasibility analysis from the patient preference randomized phase III clinical trial of second-line chemotherapy (SLC) in advanced gastric cancer (AGC) patients pretreated with both fluoropyrimidines and platinum.
Authors: S. Park, S. Lee, J. Kang, I. Hwang, J. Lee, J. Park, Y. Park, H. Lim, W. Kang
Journal: Journal of Clinical Oncology (2010)

4147 Background: There is no evidence that SLC in AGC patients will result in substantial prolongation of survival when compared to best supportive care (BSC), and there is potential for toxicity from the treatment. However, SLC is often offered to pretreated AGC patients for anecdotal reasons. Methods: The study comprises two parts: patient preference trial (PPT) and randomized controlled trial (RCT). In a prospective, multicenter trial, pretreated AGC patients with a performance status (PS) ≤ 1 were first offered randomization. If willing to participate RCT, the patient was randomly assigned 2:1 to SLC or BSC. If the patient refused randomization, but nevertheless agreed to receive treatment of their preferences, the patient received their treatment of choice (SLC or BSC). In the SLC regimen, single-agent docetaxel or irinotecan was selected at the discretion of investigator. Primary endpoint is the overall survival in the RCT patients, and the target sample size is 200 RCT patients. The main outcome measure in this feasibility analysis is the proportion of patients enrolled onto RCT compared with the proportion of those enrolled onto PPT. Results: As of Dec 2009, a total of 182 eligible patients were entered onto this study. Eighty-one patients entered RCT (SLC, n = 55; BSC, n = 28), and 101 patients received treatment of their preferences (SLC, n = 70; BSC, n = 29). The degree of RCT refusal was more pronounced in patients with a PS of 0 (vs. 1; p = 0.04). In the PPT patients, those without measurable disease (p < 0.01) and aged > 55 years (p < 0.01) declined SLC. Conclusions: This analysis suggests that pretreated AGC patients clearly prefer SLC. The high degree of RCT refusal is, at least in part, due to concern about random assignment or difficulty with accepting BSC without the possibility of anticancer effects. No significant financial relationships to disclose.
Scientific Review of Phase I Protocols With Novel Dose-Escalation Designs: How Much Information Is Needed?
Authors: Alexia Iasonos, Mithat Gönen, George J. Bosl
Journal: Journal of Clinical Oncology (2015)

Article Tools STATISTICS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2014.59.8466 Journal of Clinical Oncology - published online before print May 4, 2015 PMID: 25940721 Scientific Review of Phase I Protocols With Novel Dose-Escalation Designs: How Much Information Is Needed? Alexia IasonosxAlexia IasonosSearch for articles by this author , Mithat GönenxMithat GönenSearch for articles by this author , George J. BoslxGeorge J. BoslSearch for articles by this author Show More All authors: Memorial Sloan Kettering Cancer Center, New York, NY. https://doi.org/10.1200/JCO.2014.59.8466 First Page Full Text PDF Figures and Tables © 2015 by American Society of Clinical Oncology
Persistance of circulating tumor cells (CTCs) in peripheral blood of breast cancer (BC) patients two years after primary diagnosis
Authors: B. K. Rack, C. Schindlbeck, A. Schneeweiss, I. Schrader, R. Lorenz, M. Beckmann, K. Pantel, W. Lichtenegger, H. Sommer, W. Janni
Journal: Journal of Clinical Oncology (2009)

554 Background: In metastatic BC, CTCs have shown to predict treatment efficacy and reduced survival. Recent data also indicate a potential prognostic relevance of CTCs after adjuvant chemotherapy. The SUCCESS trial evaluates the role of persisting CTCs two years after diagnosis in primary BC patients treated with zoledronate. Methods: We analyzed 23 mL of peripheral blood in N+ and high-risk N- primary BC pts receiving 3xFEC(500/100/500)-3xDoc100 q3w vs. 3xFEC(500/100/500)-3xDocgemcitabine (75/1000 d1+8) chemotherapy followed by 2 yrs (4mg q3mx24m) vs. 5 yrs (4mg q3mx24m followed by q6mx36m) of zoledronate. CTC results after two years are shown. CTCs were assessed with the CellSearchSystem (Veridex, Warren, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies. Pts were examined after a mean of 29 months (range 20–43). Results: The data of 579 pts two years after diagnosis are available. 4.3% of pts (n = 25) presented with &gt;1CTC in peripheral blood. In pts with the detection of CTCs, the mean number of cells was 1 (range 1–29). While we found 1 CTC in 5.9% and 2 CTCs in 1.6% of pts, 1.5% had 3–5 CTCs, 1.2% &gt;5 CTCs. The presence of &gt;1CTC did not correlate with tumor size (p = 0.41), nodal status (p = 0.41), grading (p = 0.45), hormonal status (p = 0.92) or HER-2-Status of the tumor (p = 0.59). In this patient group, 9.7% and 6.9% of pts had presented with &gt;1CTC at primary diagnosis and after chemotherapy, respectively. While the presence of CTCs at diagnosis was associated with CTCs after two years (p = 0.03), there was no correlation of CTCs after chemotherapy with the results at primary diagnosis (p = 0.08) or at two years (p = 0.23). In 184 postmenopausal HR+ pts endocrine treatment data was analyzed. CTCs at two years were detected in 6.8% of pts on tamoxifen (n = 9), while 1.9% of pts were positive on anastrozole treatment (n = 1; p = 0.19). Conclusions: CTCs persisting cytostatic, endocrine and zoledronate treatment, can be observed in a relevant number of clinically recurrence-free BC patients. Longer follow-up within the German SUCCESS study will give further insight in their prognostic relevance and show whether they can be used for real time tumor phenotyping or serve as treatment target. [Table: see text]
Intraoperative radiotherapy (IORT) using low-energy x-rays as tumour-bed boost in breast cancer patients
Authors: U. Kraus-Tiefenbacher, C. Herskind, L. Bauer, F. Melchert, F. Wenz
Journal: Journal of Clinical Oncology (2005)

883 Background: Recurrences after breast-conserving therapy mostly appear close to the primary tumor site. Therefore, a boost is often applied using external beam radiotherapy (EBRT), brachytherapy or IORT. Since February 2002, IORT is delivered in our department by a mobile miniature x-ray source (Intrabeam) producing an isotropic field of 50 kV x-rays. Methods: Until 11/04, 82 patients received IORT as a tumour bed boost, followed by EBRT with a total dose of 46 Gy to the whole breast. The median patient age was 65 years (43.1–86.5) and the median tumour size was 15 mm (6–45). Spherical applicators (3.0–5.0 cm diameter) were inserted into the cavity left by the excised tumour, giving a single dose of IORT with 20 Gy at the applicator surface. Follow-up included physical examination with photographic documentation and ultrasound every 6 months and mammography at yearly intervals. Radiobiological modelling of the expected spatial distribution of late reaction was done for typical cases using the linear-quadratic model with special consideration of relative biologic effectivity (RBE), spatial dose distribution and dose rate. Results: Postoperative acute reactions in 14/86 patients included skin erythema (4), delayed wound-healing (4), hematoseromas (5) and abcess formation (1). At a median follow-up of 13 months, four patients developed mastitis and one patient developed severe (°III), homogeneous fibrosis within the whole breast leading to a secondary mastectomy. Except for one patient with multifocal in-breast-recurrence 10 months after treatment, all patients are under local control. Conclusions: Acute reactions were transient at an acceptable level. Only one case of fíbrosis has occurred which was spatially unrelated to the IORT boost. The low level of clinically observed late reactions is in agreement with radiobiologic predictions. No significant financial relationships to disclose.