tbuckley/cabot-search huggingface dataset:
EORTC 26101 phase III trial exploring the combination of bevacizumab and lomustine in patients with first progression of a glioblastoma.
Authors: Wolfgang Wick, Alba Ariela Brandes, Thierry Gorlia, Martin Bendszus, Felix Sahm, Walter Taal, Martin J.B. Taphoorn, Julien Domont, Ahmed Idbaih, Mario Campone, Paul M. Clement, Roger Stupp, Michel Fabbro, Emilie Le Rhun, François Dubois, Martin Klein, Michael Platten, Michael Weller, Vassilis Golfinopoulos, Martin J. Van Den Bent
Journal: Journal of Clinical Oncology (2016)

2001 Background: Phase II data from BELOB suggested the combination of bevacizumab and lomustine to produce an overall survival (OS) benefit for patients with progressive glioblastoma. EORTC 26101 aimed investigating whether the combination of bevacizumab and lomustine improves OS in patients with first progression of a glioblastoma compared to lomustine alone. Methods: Patients with progressive disease after standard chemoradiation at least 3 months off the concomitant part were randomized 2:1 between lomustine 90 mg/m2 (cap. 160 mg with toxicity-driven escalation to cap. 200 mg from cycle 2 on) every six weeks plus 10 mg/kg bevacizumab every two weeks and lomustine single agent 110 mg/m2(cap. 200 mg) every six weeks followed by best investigators choice at further progression. Targeted hazard ratio (HR) was 0.72 for the comparison of OS as the primary endpoint. Progression-free survival (PFS) was an important secondary endpoint. Neuroimaging according to a standard protocol was assessed locally and centrally. Results: A total of 437 (288 and 149, respectively) patients were included. Median number of treatment cycles was 1 in the lomustine arm and 3 in the combination arm. With 329 OS events (75.3%) OS was not superior in the combination therapy arm (HR 0.95 (confidence interval (CI) 0.74, 1.21), p = 0.650, analyses stratified by EORTC online randomization system), whereas locally assessed PFS was longer with the addition of bevacizumab to lomustine (HR 0.49 (CI 0.39, 0.61). Median efficacy outcomes were: OS 9.1 (8.1, 10.1) versus 8.6 (7.6, 10.4) months and PFS 4.2 (3.7, 4.3) versus 1.5 (1.5, 2.5) months in the combination arm versus the lomustine arm, respectively. Toxicity was in the expected range with more events in the combination arm being also longer on treatment. Crossover to bevacizumab occurred in 35.5% of patients in the control arm; whereas 19% of patients in the combination arm continued bevacizumab at progression. Conclusions: Bevacizumab treatment in patients with progressive glioblastoma despite prolonged PFS does not confer a survival advantage. Future molecular and neuroimaging research should identify those patients deriving benefit from that treatment. Clinical trial information: NCT01290939.
<i>HER2</i> Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials
Authors: Michael F. Press, Guido Sauter, Marc Buyse, Hélène Fourmanoir, Emmanuel Quinaux, Denice D. Tsao-Wei, Wolfgang Eiermann, Nicholas Robert, Tadeusz Pienkowski, John Crown, Miguel Martin, Vicente Valero, John R. Mackey, Valerie Bee, Yanling Ma, Ivonne Villalobos, Anaamika Campeau, Martina Mirlacher, Mary-Ann Lindsay, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2016)

Purpose ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes. Patients and Methods The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]-positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]). Results Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only group 1 showed a significant benefit from trastuzumab therapy (DFS HR, 0.71; 95% CI, 0.60 to 0.83; P < .0001; OS HR, 0.69; 95% CI, 0.55 to 0.85; P = .0006), whereas group 2 did not. Conclusion Our findings support the original categorizations of HER2 by FISH status in BCIRG/Translational Research in Oncology trials.
Legislation to Increase Generic Drug Alternatives
Authors: Rita Rubin
Journal: JAMA (2016)

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
Cancers of the brain and CNS: global patterns and trends in incidence
Authors: Adalberto Miranda-Filho, Marion Piñeros, Isabelle Soerjomataram, Isabelle Deltour, Freddie Bray
Journal: Neuro-Oncology (2016)

Cancers of the brain and CNS constitute a group of rare and heterogeneous tumors. Increasing incidence in Western populations has been linked to improvements in diagnostic technology, although interpretation is hampered by changes in diagnosis and reporting. The present study examines geographic and temporal variations in incidence rates of brain and CNS cancers worldwide. Data from successive volumes of Cancer Incidence in Five Continents were used, including 96 registries in 39 countries. We used Joinpoint regression to estimate the average annual percentage change and its 95% CI. Globally, a large variability in the magnitude of the diagnosis of new cases of brain and CNS cancer was found, with a 5-fold difference between the highest rates (mainly in Europe) and the lowest (mainly in Asia). Increasing rates of brain and CNS cancer were found in South America, namely in Ecuador, Brazil, and Colombia; in eastern Europe (Czech Republic and Russia), in southern Europe (Slovenia), and in the 3 Baltic countries. Trends were similar between sexes, although decreasing trends in men and women were seen in Japan and New Zealand. Important regional variations in brain and CNS cancers exist, and given an increasing burden and risk worldwide, there is a need for further etiological research that focuses on the elucidation of environmental risk. The trends are sufficiently complex and diffuse, however, to warrant a cautious approach to interpretation.
Curative hepatitis C treatment is effective in drug users, trial shows
Authors: Susan Mayor
Journal: BMJ (2016)

Patients with hepatitis C infection being treated for opioid addiction have high rates of virologic response to oral, once daily treatment with a fixed combination of elbasvir and grazoprevir regardless of ongoing drug use, a randomised trial has shown.1

Injecting drug users are the main group affected by hepatitis C in high income countries, but most trials of …
Two-year outcomes of RTOG 0529: A phase II evaluation of dose-painted IMRT in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal.
Authors: L. A. Kachnic, K. A. Winter, R. J. Myerson, M. D. Goodyear, J. Willins, J. Esthappan, M. G. Haddock, M. Rotman, P. J. Parikh, C. G. Willett
Journal: Journal of Clinical Oncology (2011)

368 Background: 5-Fluorouracil (5FU) and mitomycin-C (MMC) chemoradiation for anal cancer is associated with high rates of acute morbidity. We have previously shown that dose-painted IMRT (DP-IMRT) significantly reduces grade 3+ GI and dermatologic acute toxicity, as compared to the RTOG 9811 5FU/MMC arm, which used non-conformal radiation techniques. We now report on the two-year outcomes of this DP-IMRT approach. Methods: T2-4N0-3M0 anal canal cancers received 5FU (1,000 mg/m 2 /day 96 hour infusion) and MMC (10 mg/m 2 bolus) days 1 and 29 of DP-IMRT prescribed as follows - T2N0: 42 Gy elective nodal and 50.4 Gy anal tumor planning target volumes (PTVs), 28 fractions; T3-4N0-3: 45 Gy elective nodal, 50.4 Gy ≤ 3 cm and 54 Gy &gt; 3 cm metastatic nodal and 54 Gy anal tumor PTVs, 30 fractions. The following two-year outcomes were assessed: local-regional (LRF) and colostomy failures (CF) using the cumulative incidence method, and disease-free (DFS), overall (OS) and colostomy-free survivals (CFS) using the Kaplan-Meier method. Results: Of 63 accrued patients, 52 were analyzable. Median age was 58 years; 81% female; 54% stage II; 25% IIIA; 21% IIIB. Median follow-up was 23.2 months (0.2-33). Two-year LRF, CF, DFS and 95% confidence intervals are 20% (9%, 31%), 8% (0.4%, 15%) and 77% (62%, 86%), respectively. The causes of death for the 7 patients that died are: anal cancer in 5, morbidity in one and second primary outside the radiation field in one. Two-year comparison data from the RTOG 9811 5FU/MMC arm are shown in the table below. Conclusions: DP-IMRT with 5FU/MMC for the treatment of anal canal cancer yields similar two-year outcomes as the RTOG 9811 conventional radiation, 5FU/MMC arm. Because of the associated acute toxicity sparing, DP-IMRT will be used as the platform, and may allow for radiation dose escalation, in future RTOG anal canal trials. Supported by RTOG U10 CA21661, CCOP U10 CA3742 and ATC U24 CA 81647 NCI grants. [Table: see text] No significant financial relationships to disclose.
Frozen Pre-embryos
Authors: Jonathan Lewin
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Like the Board of Trustees, I too understand the important role pre-embryos can play in research. I am all the more disappointed by the legal and logical flaws in the Board's rationale for permitting pre-embryo destruction. The Board compares pre-embryos with children and concludes that gamete providers should have broad discretion, since "the law has deferred to parental choices... as long as the child is not neglected or abused."1 But having said this much, the Board's report quickly changes the subject, perhaps to avoid the obvious conclusion. In the analogy to parental discretion, a gamete provider's attempt to destroy frozen pre-embryos becomes comparable to neglect and abuse. The report implies that physicians should not interfere with the gamete providers' decisions because, where "the individual's freedom of reproductive choice" is at stake, "the government does not grant decision-making authority to private third parties." But this is simply inaccurate.
P1088 : Morphometrical quantification of fibrosis correlates with clinical cirrhosis stage and predicts long-term survival in patients with alcoholic cirrhosis
Authors: L. Binder, F. Rainer, J. Haybaeck, S. Xu, W. Spindelboeck, A. Wee, R. Stauber, C. Lackner
Journal: Journal of Hepatology (2015)
Survival outcomes of patients with esophageal cancer enrolled in a community-based hospital: Twenty-year experience.
Authors: S. Santhanam Ethiraj, A. Akl, K. Katato
Journal: Journal of Clinical Oncology (2010)

e14615 Background: Esophageal cancer is one of the least studied and the most aggressive neoplasm with high mortality. Various survival studies are based on tertiary care based cancer registries but community registry based studies are lacking. Hence here we describe the survival outcome of esophageal cancer patients enrolled in a community based hospital. Methods: All patients diagnosed with esophageal cancer in the registry between 1987 and 2006 were retrieved for demographic and pathologic details, cancer recurrence and vital status at last follow-up. These patients were divided into four 5-year periods of cohorts to study the demographic and survival outcomes. Stages I-III (93 patients) were included in the study and stage IV (48) and pt lost to follow-up were excluded for final analysis. Results: Total numbers of patients studied were 141 patients of which 93 stage I-III patients were analyzed using SPSS software.The median follow-up was 15 months interquartile range of 8- 36 months. Overall survival (O.S) was 57 % at 1 yr, 23% at 3 yrs, and 12% at 5 yrs. Disease-free survival was 50% at 1 yr, 16% at 3 yrs, and 7.5% at 5 yrs. The median survival of stage I-III versus IV was 14.5 months and 4 months (p=0.0001) respectively. Subgroup analysis showed that perioperative chemoradiation with surgery group showed median survival of O.S of 80% at 1 yr, 35% at 3 yr whereas chemoradiation alone group showed OS of 51% at 1 yr and 14% at 3 yr and median survival of 31 months versus 13 months (RR=0.536, p=0.02). The OS of squamous cell carcinoma versus adenocarcinoma group at the end of 3 yr was 23.2% and 19.23 % (p=0.99) respectively. Conclusions: Chemoradiation with surgery significantly improved median survival time over chemoradiation alone. The survival was significantly better in stage I-III compared to stage IV median survival. There was no survival significance by the histological type. Cohorts A B C D Year 1987-1991 1992-1996 1997-2001 2002-2006 Total Stage I-III /(all stages) 33/49 17/32 20/29 29/31 141 Gender: Male 24 13 18 15 71 Female 9 4 2 9 23 Histology: Adeno Ca 11 6 10 15 42 Squamous Ca 22 11 10 9 52 Treatment: CR 19 10 12 10 51 CRS 7 6 4 7 26 RT 4 1 5 5 14 Median survival 16M 17M 9M 17M No significant financial relationships to disclose.
Domestication history and geographical adaptation inferred from a SNP map of African rice
Authors: Rachel S Meyer, Jae Young Choi, Michelle Sanches, Anne Plessis, Jonathan M Flowers, Junrey Amas, Katherine Dorph, Annie Barretto, Briana Gross, Dorian Q Fuller, Isaac Kofi Bimpong, Marie-Noelle Ndjiondjop, Khaled M Hazzouri, Glenn B Gregorio, Michael D Purugganan
Journal: Nature Genetics (2016)
Baseline characteristics, chromosomal alterations, and treatment affecting prognosis of deletion 17p in newly diagnosed myeloma
Authors: Maximilian Merz, Thomas Hielscher, Anja Seckinger, Dirk Hose, Elias K. Mai, Marc S. Raab, Hartmut Goldschmidt, Anna Jauch, Jens Hillengass
Journal: American Journal of Hematology (2016)

Deletion 17p13, del(17p), is associated with poor outcome in myeloma but some patients show long-term survival. With the current study we intended to identify factors impacting outcome of such high risk patients. We analyzed 110 newly diagnosed, symptomatic patients with del(17p) detected by fluorescence in situ hybridization (FISH) in CD138-purified myeloma cells to identify prognostic factors for survival. Age >65 years, ISS III, and elevated LDH negatively impacted survival. Patients with subclonal (10-60% of plasma cells) del(17p) had longer progression-free survival (PFS) than patients with del(17p) in >60% of plasma cells (26 vs. 19 months, P = 0.03). Additional gain of 1q21 was associated with shorter PFS (17 vs. 25 months, P = 0.01). Hyperdiploidy did not ameliorate impact of del(17p), but gain 19q13 predicted longer PFS (30 vs. 18 months, P = 0.01) and overall survival (50 vs. 29 months, P = 0.01). Multivariate analysis in transplant eligible patients (≤65 years) revealed better survival for patients treated with upfront autologous transplantation (hazard ratio, [95% confidence interval]: 0.15 [0.04, 0.58], P = 0.006). Application of maintenance therapy was associated with better survival in transplant-eligible patients (0.30 [0.09, 0.99], P = 0.05). We demonstrate heterogeneous outcome of patients with del(17p) according to baseline characteristics and treatment. 19q13 should be included in routine FISH panel, since gains were associated with better survival. Am. J. Hematol. 91:E473-E477, 2016. © 2016 Wiley Periodicals, Inc.
Bilateral Infarction of the Corpus Callosum in a Patient With a Single Pericallosal Artery
Authors: Antonio Cruz-Culebras, Rocío Vera, Juan Martinez San Millan
Journal: JAMA Neurology (2016)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Differences in Uptake of 18F-FDG and 11C-Choline in a Case of Acute Myeloid Leukemia
Authors: Chunxia Qin, Zhijian Wu, Ji Li, Xun Sun, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2016)

A 26-year-old man had unilateral facial numbness. A brain MRI suggested possible brain metastases. F-FDG and C-choline PET/CT revealed multiple sites of abnormal activity in the body. However, C-choline PET/CT was more impressive than FDG PET/CT. Especially, the brain lesions revealed by MRI had only elevated C-choline uptake but had FDG uptake levels similar to adjacent brain. Acute myeloid leukemia was diagnosed after bone marrow biopsy.
Selective inhibition of autoimmune exacerbation while preserving the anti-tumor clinical benefit using IL-6 blockade in a patient with advanced melanoma and Crohn’s disease: a case report
Authors: Marc Uemura, Van A. Trinh, Cara Haymaker, Natalie Jackson, Dae Won Kim, James P. Allison, Padmanee Sharma, Luis Vence, Chantale Bernatchez, Patrick Hwu, Adi Diab
Journal: Journal of Hematology & Oncology (2016)

Novel immunotherapies, or checkpoint inhibitors, targeting programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) have significantly improved outcomes for patients with numerous different cancer types. However, owing to their exclusion from clinical trials and risk for autoimmune exacerbation on these treatments, the impact on safety and degree of toxicity of these potentially life-prolonging therapies is not well characterized in patients with an underlying autoimmune disease or previous organ transplant. We report a case of a patient with advanced melanoma and refractory Crohn's disease who was treated concurrently with pembrolizumab (anti-PD-1 antibody) and tocilizumab (anti-interluekin-6 receptor antibody). This novel treatment strategy was well tolerated and did not result in Crohn's disease exacerbation for at least 16 weeks. Importantly, this treatment resulted in marked, durable antitumor responses. This outcome suggests that targeted immunosuppression combined with checkpoint inhibitors may hold promise as a treatment strategy for this unique patient population and may warrant additional study.
Association of Adipose Tissue Fatty Acids With Cardiovascular and All-Cause Mortality in Elderly Men
Authors: David Iggman, Johan Ärnlöv, Tommy Cederholm, Ulf Risérus
Journal: JAMA Cardiology (2016)

The major polyunsaturated fatty acids in adipose tissue objectively reflect long-term dietary intake, and may provide more reliable information than would self-reported intake. Whether adipose tissue fatty acids predict cardiovascular and all-cause mortality needs investigation.To investigate associations between adipose tissue fatty acids and cardiovascular and overall mortality in a cohort of elderly men.We hypothesized that polyunsaturated fatty acids reflecting dietary intake, are inversely associated with cardiovascular and all-cause mortality. In the Swedish cohort study Uppsala Longitudinal Cohort of Adult Men, buttock fatty acid composition was analyzed by gas-liquid chromatography in 1992 to 1993 and 2008. The study participants were followed during 11 311 person-years, between 1991 and 2011 (median follow-up, 14.8 years). In this community-based study that took place from 1970 to 1973, all men born in 1920 to 1924 in Uppsala, Sweden, were invited and 2322 (82%) were included (at age 50 years). At the reinvestigation at age 71 years, 1221 (73%) of the 1681 invited men participated. Adipose tissue biopsy specimens were taken in a subsample of 853 men. There was no loss to follow-up.Adipose tissue proportions of 4 polyunsaturated fatty acids that were considered to mainly reflect dietary intake (linoleic acid, 18:2n-6; α-linolenic acid, 18:3n-3; eicosapentaenoic acid, 20:5n-3; and docosahexaenoic acid, 22:6n-3) comprised primary analyses, and all other available fatty acids were secondary analyses.Hazard ratios (HRs) for cardiovascular and all-cause mortality using Cox proportional hazards regression analyses, performed in 2015.Among the 853 Swedish men, there were 605 deaths, of which 251 were cardiovascular deaths. After adjusting for risk factors, none of the 4 primary fatty acids were associated with cardiovascular mortality (HR, 0.92-1.05 for each standard deviation increase; P ≥ .27). Linoleic acid was inversely associated with all-cause mortality (HR, 0.90; 95% CI, 0.82-0.98; P = .02) and directly associated with intake (P < .001). In secondary analyses, palmitoleic acid, 16:1n-7 (HR, 1.11; 95% CI, 1.02-1.21; P = .02) was associated with higher all-cause mortality, whereas heptadecanoic acid, 17:0, tended to be associated with lower all-cause mortality (HR, 0.89; 95% CI, 0.79-1.00; P = .05). Arachidonic:linoleic acid ratio was associated with both cardiovascular (HR, 1.15; 95% CI, 1.05-1.31; P = .04) and all-cause (HR, 1.13; 95% CI, 1.04-1.23; P = .005) mortality.Adipose tissue linoleic acid was inversely associated with all-cause mortality in elderly men, although not significantly with cardiovascular mortality.