tbuckley/cabot-search huggingface dataset:
A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin in localized uterine sarcomas: Results from 81 randomized patients.
Authors: P. Pautier, A. Floquet, L. Gladieff, D. Berton-Rigaud, S. Piperno-Neumann, F. Selle, C. Guillemet, I. L. Ray-Coquard, B. Weber, P. Duvillard, C. Haie-Meder, A. Rey
Journal: Journal of Clinical Oncology (2011)

10022 Background: Uterine sarcomas (US) have a high risk of metastatic relapse. No benefit was shown with doxorubicin as adjuvant treatment even though a trend emerged in favour of chemotherapy (CT) (Omura 1985). A multichemotherapy approach in US achieved a good response rate (DECAV therapy: 54% overall response rate), though toxic. Adjuvant API (doxorubicin, ifosfamide and cisplatin) followed by radiotherapy (RT) is a feasible protocol. We conducted a phase III multicenter study of adjuvant CT with API. All patients received pelvic RT (45 grays); vaginal brachytherapy was optional. The objective was to detect an increase ≥ 20% (35 to 55%) of 3 years PFS (a = 5%, power = 80%) in the CT arm. Study was stopped on 8-2008 because of lack of recruitment. We present the results of the 81 pts who actually entered the study. Methods: Pts with FIGO modified stage ≤ III US with complete surgery, normal thoracic, abdominal and pelvic CT scan, physiological age ≤ 65 years, PS ≤ 2, left ventricular ejection fraction >50%, were randomized and stratified (carcinosarcomas versus others). Chemotherapy consisted in 4 cycles of doxorubicin 50 mg/m2 d1, ifosfamide 3 g/m2/d d1d2 + mesna, cisplatin 75 mg/m2 d3, + G-CSF; q 3 wks Results: 81 patients were randomized, 39 in arm A (CT + RT) and 42 in arm B (RT); median age 55y (39-69), 52 stage I, 16 stage II, 12 stage III, (1 missing); 53 leiomyosarcomas, 9 indifferenciated sarcomas, 19 carcinosarcomas. Gr 3-4 toxicity during API (/37 pts): hematologic gr 3 (16%) and 4 (68%); febrile neutropenia (22%) with 2 toxic deaths; renal gr 4 (1 pt); nausea-vomiting gr 3-4 (24%); 28% of pts needed dose reduction. With median follow-up of 48 mo, 41/81 pts recurred (51%) at a median time of 13 mo (5-43 mo), 15 in arm A (38,5%) and 26 in arm B (62%); median PFS is 27 mo; recurrences sites: pelvis-11, pelvis + meta-3, meta-27 (25/30 meta : lung). 3 years PFS is 52% in arm A (IC95%:36-67%) and 41% in arm B (IC95%:27-57%). 3 years OS is 80% in arm A (IC95%:64-90%) and 67% in arm B (IC95%:49-80%). Conclusions: Even if there is a trend in favour of CT, we cannot answer to the important question of adjuvant CT in US. Results have to be confirmed with longer follow-up to see real impact on relapse and OS.
Estrogen activation of microglia underlies the sexually dimorphic differences in <i>Nf1</i> optic glioma–induced retinal pathology
Authors: Joseph A. Toonen, Anne C. Solga, Yu Ma, David H. Gutmann
Journal: The Journal of Experimental Medicine (2016)

Children with neurofibromatosis type 1 (NF1) develop low-grade brain tumors throughout the optic pathway. Nearly 50% of children with optic pathway gliomas (OPGs) experience visual impairment, and few regain their vision after chemotherapy. Recent studies have revealed that girls with optic nerve gliomas are five times more likely to lose vision and require treatment than boys. To determine the mechanism underlying this sexually dimorphic difference in clinical outcome, we leveraged Nf1 optic glioma (Nf1-OPG) mice. We demonstrate that female Nf1-OPG mice exhibit greater retinal ganglion cell (RGC) loss and only females have retinal nerve fiber layer (RNFL) thinning, despite mice of both sexes harboring tumors of identical volumes and proliferation. Female gonadal sex hormones are responsible for this sexual dimorphism, as ovariectomy, but not castration, of Nf1-OPG mice normalizes RGC survival and RNFL thickness. In addition, female Nf1-OPG mice have threefold more microglia than their male counterparts, and minocycline inhibition of microglia corrects the retinal pathology. Moreover, pharmacologic inhibition of microglial estrogen receptor-β (ERβ) function corrects the retinal abnormalities in female Nf1-OPG mice. Collectively, these studies establish that female gonadal sex hormones underlie the sexual dimorphic differences in Nf1 optic glioma-induced retinal dysfunction by operating at the level of tumor-associated microglial activation.
Phase II trial of bevacizumab monotherapy in nonmetastatic castrate-resistant prostate cancer (CRPC).
Authors: S. Ogita, S. Tejwani, L. K. Heilbrun, J. A. Fontana, E. I. Heath, S. Freeman, D. W. Smith, K. Baranowski, U. N. Vaishampayan
Journal: Journal of Clinical Oncology (2011)

33 Background: To this day, no therapy has proven efficacy in the clinical management of PSA relapse non-metastatic CRPC. Investigating novel therapeutic agents that will induce a PSA response, and delay progression to overt metastases is of paramount importance. Methods: A single arm multi-center phase II clinical trial is being conducted. Inclusion criteria are PSA only progression despite androgen deprivation therapy, defined as three rising PSA levels with a measurement interval of at least 2 weeks, and minimum PSA level ≥ 1 ng/mL. Patients with radiologic evidence of bone metastases were excluded. Bevacizumab single agent was administered at 10 mg/kg every 14 days. PSA was evaluated at least every 6 weeks and bevacizumab was continued until PSA progression or new metastasis. Results: 15 patients (see Table ) have been enrolled on this ongoing trial. Toxicities observed were grade 4 pulmonary embolism, grade 3 hypertension, and grade 3 proteinuria in one patient each, but no treatment related mortality. Median treatment duration was 12.6 weeks (range 11–33.1 wks). 12 patients are evaluable for PSA response. Four patients had PSA decline of 14, 20.9, 24, and 45% respectively. Median PSA doubling time during bevacizumab increased to 5.93 months (range 0.81–27.09 months) from pretherapy median of 4.08 months, a 45% improvement. Five patients have progressed to develop bone metastases at median of 7.7 months (range 2.8–18.2) after protocol registration. Conclusions: Bevacizumab was well tolerated, and impacted PSA kinetics in non-metastatic CRPC. Further investigations are warranted. Supported in part by Genentech Inc. (clinicaltrials.gov NCT00478413 ). [Table: see text] [Table: see text]
An evaluation of the role of Src in renal cancer.
Authors: T. Qayyum, P. A. McArdle, M. Seywright, D. C. Mcmillan, M. Aitchison, J. E. Edwards
Journal: Journal of Clinical Oncology (2011)

358 Background: The aim of the current study was to assess the expression levels of c-Src, phosphorylated Src, dephosphorylated c-Src at 530 and the downstream marker Fak 861 in renal cancer. Methods: In all, 60 patients undergoing potentially curative nephrectomy for localised renal cancer were included. Imunohistochemical staining was utilised to assess expression of c-Src, dephosphorlated c-Src at 530, phosphorylated Src at the Y416 site, and Fak 861. Expression was assessed using the weighted histoscore method. Results: High membrane c-Src was associated with increased cancer specific survival (p=0.032). In addition, increased cancer-specific survival was associated with high levels of cytoplasm and membrane expression of c-Src (p=0.039). When assessed individually, membrane, cytoplasm and nuclear expression of phosphorylated Src was not significantly associated with cancer specific survival. However when membrane and cytoplasm expression was combined, high expression was associated with decreased cancer specific survival (p=0.001). Low cytoplasm Fak expression was associated with increased cancer specific survival (p=0.029). When expression of Fak was combined with phosphorylated Src, high expression was associated with decreased cancer specific survival (p=0.003). When taking together high membrane c-Src and phosphorylated Src expression, this was associated with increased cancer specific survival (p=0.029). On multivariate analysis, combined expression of membrane c-Src and phosphorylated Src (HR 0.49, 95% CI 0.24-0.99, p=0.047) and combined Fak and phosphorylated Src expression (HR 1.88, 95% CI 1.06-3.34, p=0.030) were significant independent predictors of cancer specific survival. Conclusions: The results suggest that activated c-Src is associated with improved survival and activated Src family members are associated with decreased survival. This would suggest that another member of the Src family maybe associated with decreased survival. Further work is required to identify which of the Src family members are expressed in renal cancer and would therefore allow specific inhibitors for these Src family members to be developed. No significant financial relationships to disclose.
Apricot-P: A randomized placebo-controlled phase II study of COX-2 inhibitor apricoxib or placebo in combination with gemcitabine and erlotinib in advanced or metastatic adenocarcinoma of the pancreas.
Authors: Manuel Modiano, George P. Keogh, Robert Manges, Philip J. Stella, Ginger Milne, Ella Looper, Sara L. Zaknoen
Journal: Journal of Clinical Oncology (2012)

253 Background: Apricoxib is an oral, selective inhibitor of COX-2. COX-2 and EGFR signaling regulate the dominant ERK/MAPK, AKT and ß-catenin pathways in pancreatic cancer; combinations of COX-2 and EGFR inhibitors are of particular interest in this disease. ß-catenin activity is implicated in gemcitabine resistance. In addition, apricoxib has been demonstrated to potently reverse EMT in xenograft models of pancreatic cancer. In a completed Phase II study NSCLC patients were selected based on a decrease in PGEM, a urinary biomarker of COX-2 activity. As pancreatic cancer patients overwhelmingly over express COX-2 PGEM was measured for the purpose of secondary analysis in this study. Methods: Pts with locally advanced or metastatic adenocarcinoma of the pancreas were treated with erlotinib 100 mg PO daily and apricoxib/placebo 400mg PO daily and gemcitabine per previously published schedule (Burris JCO 2007). The primary objective PFS. Results: 109 patients were randomized (70 AP/GE:39 P/GE). Characteristics were balanced between the arms, 63% had elevated baseline PGEM. Most common adverse events included; rash (69%), diarrhea (59%), nausea (59%) and fatigue (57%). Drug-related SAEs included GI bleeding, MI and CVA and were more numerous on the apricoxib arm. The primary study endpoint was not met, HR 0.7; 95% CI (NA, 1.2). Trends in OS favoring the addition of apricoxib were demonstrated in 2 subgroups; elevated baseline PGEM and pts with a ≥ 50% drop from baseline PGEM. Conclusions: This study is the first randomized placebo controlled trial combining chemotherapy with COX-2 inhibition and EGFR kinase inhibition. The apricoxib containing arm had increased GI toxicity including GI hemorrhage. Although the primary endpoint was not met, overall survival in patients with a PGEM response to COX-2 inhibition favored addition of apricoxib. Further study in a biomarker selected population is warranted. [Table: see text]
Predictive factors for acute and late urinary toxicities after permanent prostate brachytherapy.
Authors: Ryuta Tanimoto, Kensuke Bekku, Yasuyuki Kobayashi, Shin Ebara, Motoo Araki, Norihisa Katayama, Yasutomo Nasu, Hiromi Kumon
Journal: Journal of Clinical Oncology (2012)

90 Background: To describe the frequency of acute and late Radiation Therapy Oncology Group (RTOG) urinary toxicity associated with predictive factors and International Prostate Symptom Score (IPSS) in consecutive prostate brachytherapy patients. Methods: From January 2004 to April 2011, 466 patients underwent permanent 125 I-seed brachytherapy (median follow-up, 48 months). The IPSS and RTOG toxicity data were prospectively collected. The prostate volume, IPSS before and after brachytherapy and postimplant analysis were examined for an association with urinary toxicity which was defined as urinary RTOG toxicity 1 or more. Logistic regression analysis was used to examine the factors associated with urinary toxicities. Results: The rate of RTOG urinary toxicity Grade 1 or more at 1, 6, 12, 24, 36, 48 months was 67%, 40%, 21%, 31%, 27%, 28%, respectively. Grade 2 or more urinary toxicities were less than 1% at an each point. IPSS was highest at 3 months and returned to normal level at 12 months after brachytherpapy. On univariate analysis, patients with larger prostate size, greater baseline IPSS, the higher post V100 (volume of the prostate covered by 100% of the dose), higher post V150 and higher post D90 (dose that 90% of the target volume received) had more acute urinary toxicities 1 month as well as 12 months after brachytherapy. On multivariate analysis, the significant predictors for urinary toxicities were a greater baseline IPSS and post V100 one month as well as 12 months after brachytherapy (shown below). Conclusions: Most urinary symptoms were tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicities after brachytherapy were strongly related with baseline IPSS and the post V100.
Exploring the relation between overall survival (OS) and progression-free survival (PFS) in gastrointestinal stromal tumor (GIST) via meta-analysis.
Authors: R. L. Keyser, K. E. Tranbarger Freier, D. C. Hoaglin, S. Tzivelekis, I. Ozer-Stillman
Journal: Journal of Clinical Oncology (2011)

10058 Background: OS is the generally accepted measure of efficacy in cancer trials because it is clinically meaningful and objectively measured. However, using OS as a primary endpoint in RCTs (randomized controlled trials) requires large samples and long follow-up. Also, the likelihood of changes in therapy following progression makes it difficult to assess survival benefit. Using an alternative endpoint, such as PFS, as a study endpoint would accelerate the drug development process and bring new treatments to patients more rapidly. This project explored the relation between OS and PFS in unresectable and/or metastatic GIST. Methods: A systematic literature search identified 9 RCTs and observational studies published in the past 15 yrs (13 treatment arms and 1,252 patients); they encompassed 1st and later lines of treatment with a variety of cancer therapies (chemo and targeted agents). Scatter plots and linear regressions (weighted by number of patients) were used to assess the relation between median OS (mOS) and median PFS (mPFS) for all arms combined, by treatment line and by therapy. Sensitivity analyses investigated the impact of individual arms and study quality. Results: Overall, mOS and mPFS (in mo) had a positive relation, with no prominent outliers; the regression line had slope = 1.29 (SE 0.34), intercept = 21.82 (SE 6.77), and R2 = 0.57. However, the relation between mOS and mPFS differed between 1st-line and 2nd/3rd-line. For the 6 1st-line arms, slope = 0.26 (SE 0.29), intercept = 47.92 (SE 6.64), and R2=0.17. For the 7 2nd/3rd-line arms, slope = 0.82 (SE 0.34), intercept = 13.90 (SE 2.87), and R2=0.54. Conclusions: The moderately strong linear relation of mOS and mPFS is partly due to a lack of overlap; furthermore, the longer mPFS and mOS in 1st-line arms steepen the regression line. Separated by line of therapy, the relation between mOS and mPFS is stronger for 2nd/3rd-line patients compared to 1st-line patients. These exploratory findings are based on a relatively small number of studies with half of the arms having <50 patients. Analyses of patient-level data and of hazard ratios reported by RCTs are needed to assess the validity of PFS as a surrogate endpoint for OS.
Re-evaluating the efficacy of axillary ultrasound in the detection of nodal metastasis and its impact on clinical practice.
Authors: B. Lee, A. Lim, J. Krell, K. Satchithananda, J. S. Lewis, J. Stebbing, F. Meric-Bernstam
Journal: Journal of Clinical Oncology (2011)

4 Background: Recent reports have indicated a lack of overall survival benefit for axillary node dissection versus sentinel lymph node biopsy in early breast cancer. To study this further, we wished to assess the accuracy and effectiveness of ultrasound guided fine needle aspiration (FNA) cytology in detecting lymph node involvement in breast cancer patients, in order to refine and evaluate our current clinical pathways as newly diagnosed invasive breast cancer patients routinely undergo pre-surgical axillary ultrasound. Methods: An FNA was taken from nodes of consecutive patients, which appeared abnormal on ultrasonography based on size, morphology, fatty hilum and cortical thickness measurements. Ultrasound and FNA cytological findings were correlated with histology following axillary node dissection. Of 260 cases, 123 (47.3%) had metastatic nodal involvement. Of these cases, only 66 (53.7%) were reported as positive on US findings. Results: The overall positive predictive value (PPV) of ultrasound for detecting metastatic nodal involvement measured 0.82, and the negative predictive value (NPV) was 0.60. The sensitivity was 0.54, specificity measured 0.85 and the accuracy was 0.68. The ultrasound morphological nodal features with the greatest correlation with malignancy were absence of a fatty hilum (p=0.003) and an increased cortical thickness (p=0.03). Cases with a metastatic nodal burden density of a least 20% were also more likely to be detected as abnormal on axillary ultrasound. (p=0.009). Conclusions: Axillary ultrasound has a low NPV and negative sonographic results do not exclude node metastases with sufficient sensitivity in most cases, to justify its routine clinical use. [Table: see text]
Pregnancy-associated breast cancer (PABC): Czech Young Breast Cancer Study Group Project 35.
Authors: M. Zimovjanova, P. Tesarova, B. Konopasek, J. Barkmanova, P. Brabec, J. Novotny, D. Pavlista, L. B. Petruzelka
Journal: Journal of Clinical Oncology (2011)

265 Background: Breast cancer (BC) is the most common cancer in women. 12% of BC occur in women age 20–34. BC is classified as “pregnancy associated” if it is diagnosed during pregnancy or within one year after the delivery (PABC). We propose two distinct subtypes of PABC: BC diagnosed during pregnancy and BC diagnosed post-partum. This distinction is important because epidemiologic data highlights worsened outcomes specific to post-partum cases. The safety of pregnancy after treatment of BC is an important issue for many young women. Current research does not indicate that pregnancy negatively affects survival. Methods: There are about 95 young women being diagnosed each year with BC in the Czech Republic. A project of clinical registry named “Project 35” was launched in 2005 with the aim to collect data on epidemiology of the disease in young women. The standardization of the multidisciplinary medical treatment, genetic counselling and psychosocial support should result in better clinical outcomes and improve the quality of life. Results: In our project (n=225) were referred 25 women with PABC, 9 patients with the diagnosis of breast cancer during the pregnancy, 16 patients within one year after the delivery. 2 patients underwent termination of the pregnancy (first trimester) before oncological treatment, in 2 patients anthracycline-based chemotherapy was administered (second trimester), and in 5 patients were induced preterm delivery (third trimester). After delivery we followed standard therapeutic guidelines. All patients are alive but three of them have metastatic disease. From 16 women treated for post-partum BC, 11 patients have complete remission, 2 are alive with metastatic disease, 1 is recovering after the surgery for local recurrence and 2 patients died due to progressive disease. 8 women are BRCA1/2 carriers. 8 women after the successful treatment of breast cancer have delivered of healthy children and are in a complete remission, despite 1 of them with local reccurence of breast cancer. Conclusions: PABC is rare situation, which needs to be managed individually. These patients should be treated under the supervision of the Oncological Centres. Project 35 is useful framework for the counselling in PABC.
A phase III, randomized, controlled study to compare tivozanib with sorafenib in patients (pts) with advanced renal cell carcinoma (RCC).
Authors: R. J. Motzer, P. Bhargava, B. Esteves, M. Al-Adhami, W. Slichenmyer, D. Nosov, T. Eisen, C. N. Sternberg, T. E. Hutson
Journal: Journal of Clinical Oncology (2011)

310 Background: Drugs that block vascular endothelial growth factor (VEGF) pathway signaling, such as the tyrosine kinase inhibitor sorafenib, have become standard treatment for pts with RCC. Tivozanib (AV-951) is a potent, selective small-molecule pan-VEGF receptor (VEGFR) inhibitor, with activity against the VEGFR-1, -2, and -3 kinases at subnanomolar concentrations. Preliminary results from a phase II randomized discontinuation trial of tivozanib (1.5 mg/d; 3 wks on, 1 wk off) in pts with RCC demonstrated an objective response rate (ORR) of 27% and a median progression-free survival (PFS) of 11.8 mo by independent radiology review, with a favorable safety profile. Patients with clear cell RCC who had undergone nephrectomy had an ORR of 32% and median PFS of 14.8 mo (Bhargava, et al. ASCO 2010. Abstract 4599). Based on this antitumor activity a phase III, randomized, controlled, global, multicenter trial is currently in progress to compare tivozanib with sorafenib in pts with advanced RCC. Methods: Approximately 500 adults with clear cell RCC who have undergone nephrectomy and received ≤ 1 prior systemic treatment (no prior VEGF-targeted therapy) were randomized 1:1 to treatment with tivozanib or sorafenib. Pts are receiving 1.5 mg/d tivozanib orally in 4-week cycles (3 wks on, 1 wk off) or continuous 400 mg sorafenib orally twice daily. The primary endpoint will be PFS by independent radiology review; secondary endpoints will include overall survival, ORR, and duration of response. Safety is being monitored through adverse event reporting and laboratory analyses; toxicities are graded using the NCI Common Terminology Criteria for Adverse Events, version 3.0. The effect of therapy on health-related quality of life will be compared between arms using kidney cancer-specific (FKSI-DRS), oncology (FACT-G), and general (EQ-5D) assessments. Pharmacokinetics and biomarker analyses will be performed. Results: Pending. Conclusions: Enrollment completed in August 2010. An ongoing extension study will allow access to tivozanib for pts who demonstrate progressive disease on sorafenib, as well as long-term treatment with tivozanib or sorafenib for pts who demonstrate clinical benefit. [Table: see text]
Short Telomeres Are Associated with Genetic Instability and the Occurrence of High Risk Genomic Aberrations in Chronic Lymphocytic Leukemia.
Authors: Alexander Kröber, Pawel Grabowski, Andreas Bühler, Till Seiler, Hartmut Döhner, Richard Rosenquist, Göran Roos, Stephan Stilgenbauer
Journal: Blood (2005)
Reports of the Committee upon the Physiology of Vision. II. Dark Adaptation. (A Review of the Literature.)
Journal: JAMA (1930)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal