tbuckley/cabot-search huggingface dataset:
Association of <i>VEGFA</i> SNP rs2010963 with prognosis and prediction of vascular toxicity of bevacizumab in recurrent glioblastomas.
Authors: Anna Luisa Di Stefano, Giuseppe Lombardi, Jaime Gallego Perez-Larraya, Blandine Boisselier, Marianne Labussiere, Francois Ducray, Vittorina Zagonel, Caroline Cheneau, Jean-Yves Delattre, Marc Sanson
Journal: Journal of Clinical Oncology (2013)

2028 Background: VEGFA has become an attractive target in high grade gliomas but there is no predictor of response or toxicity to anti-VEGF therapy. We investigated here the association between functional single nucleotide polymorphism (SNP) +405 G&gt;C (rs2010963), located in 5’ untranslated terminal region of VEGFA gene, survival, response to bevacizumab (BVZ), and vascular toxicity. Methods: The rs2010963 was analyzed in blood DNA using a Taqman SNP Genotyping Assay and confronted to Progression Free Survival (PFS), Overall Survival (OS) in the general population of gliomas, and -for the glioblastomas (GBM) treated with BVZ at recurrence- with Response, PFS, and thrombo-hemorragic events. Results: In the general population of 954 gliomas stratified per grade (362 grade 2, 269 grade 3, 323 grade 4) there was no association between rs2010963 and OS or PFS. In the population of 123 recurrent GBM treated with BVZ, we observed a favourable trend in PFS associated with the C allele of rs2010963 (5.4 vs 4.2 months, p = 0.07). Most importantly the CC genotype was associated with the occurrence of thrombo-hemorragic events (6/16 vs 2/107 in CG+GG, p &lt;0.0001). Conclusions: Our data suggest that rs2010963 status has not prognostic significance in gliomas, but is associated with vascular events in recurrent GBM treated with BVZ. The impact of rs2010963 on response to BVZ needs to be further investigated.
Pharmacokinetics (PK) of bendamustine in pediatric patients with relapsed/refractory acute leukemia.
Authors: Mona Darwish, Gail C. Megason, Mary Bond, Edward Hellriegel, Philmore Robertson, Regina Clementi, Luann Phillips, Thaddeus Grasela, Christopher Fraser
Journal: Journal of Clinical Oncology (2012)

9547 Background: The PK profile of bendamustine in adult patients is well characterized. The objective of this analysis was to describe the pediatric PK profile of bendamustine relative to the adult PK profile and correlate the systemic exposure of bendamustine to efficacy and safety parameters. Methods: Samples were obtained after a single dose from patients aged 1-19 years with relapsed/refractory acute leukemia who were enrolled in an open-label, nonrandomized study of bendamustine (90–120 mg/m 2 , infused over 60 minutes). Samples were obtained prior to bendamustine infusion and preselected time points through 24 hours after start of infusion on day 1. Population PK modeling was performed using plasma concentration data from these patients. PK data from adults were used for comparison. Results: Systemic exposure of pediatric patients to bendamustine was similar to that obtained previously in adult patients. Mean C max was 6806 ng/mL and mean AUC 0-24 was 8240 ng*hr/mL in pediatric patients, compared with a mean C max of 5746 ng/mL and AUC 0-24 of 7121 ng*hr/mL in adults. Similarity in exposure despite the large range of body surface area across the pediatric and adult populations confirms appropriateness of the body surface area–based dosing scheme. In pediatric patients, age, race, sex, or disease state had no statistically significant effect on systemic exposure to bendamustine. No changes in systemic exposure to bendamustine in the presence of a CYP1A2 inhibitor/inducer were observed. Differences in PK were not observed in pediatric patients with mild renal impairment as compared with patients with normal renal function. Exposure in 2 pediatric patients with moderate hepatic dysfunction appeared to be higher. No clear exposure-response relationship was observed. Infection was the only adverse event for which the probability of occurrence increased with increase in exposure to bendamustine. Conclusions: The PK profile of bendamustine in pediatric patients was similar to the known PK profile in adults, demonstrating that exposures reflective of the therapeutic range in adults were attained following administration of 120 mg/m 2 to pediatric patients. Support: Teva Pharmaceutical Industries Ltd., Frazer, PA.
A phase 1 study of alpha-1,3-galactosyltransferase-expressing allogeneic renal cell carcinoma immunotherapy in patients with metastatic renal cell cancer.
Authors: Hans J. Hammers, Charles G. Drake, Yousef Zakharia, Eugene Paul Kennedy, Nicholas N. Vahanian, Charles J. Link, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2017)

528 Background: HyperAcute Renal (HAR) immunotherapy consists of two allogeneic renal cancer cell lines that have been genetically modified to express the carbohydrate α(1,3)Gal, to which humans have an inherent pre-existing immunity. HAR is designed to leverage this mechanism to educate the immune system towards antigens expressed by the patient’s own tumor cells. Methods: This study is a Phase 1 dose escalation trial of HAR for patients with Renal cell carcinoma (RCC). Eligible patients had recurrent or metastatic RCC with a clear cell component. Trial was a standard 3+3 design with patients receiving weekly intradermal injection of HAR (150 x10 6 cells/300 x10 6 cells intradermally) for 4 weeks followed by biweekly injections for 10 weeks. After the initial determination of dose-limiting toxicity, an expansion cohort up to 14 patients was enrolled. The primary endpoint was safety and determination of a maximum tolerated dose (MTD). Secondary endpoints are efficacy and immunological correlates. Results: A total of 18 patients (4 low dose, 14 high dose) were enrolled. The MTD was set at 300 x10 6 cells intradermally with no dose limiting toxicity (DLT). The most frequently reported adverse events (regardless of attribution), occurring in ≥ 20% of subjects, were abdominal pain, fatigue, pain, and injection site reactions. The most frequently reported laboratory abnormality (regardless of attribution) was anemia in 20% of subjects. There have been 5 reported serious adverse events, none deemed related to HAR. Conclusions: RCC is considered an immunogenic tumor based on its response rate to immune checkpoint blockade and IL-2, occasional spontaneous regression, and the high level of tumor T cell infiltration. HAR was well tolerated in this patient population. Therefore, RCC is an appropriate tumor type to target with combination immunotherapy including HAR. Updated results will be presented. Clinical trial information: NCT02035358.
Error in Table in Defining Rates and Risk Factors for Readmissions Following Emergency General Surgery
Authors: Joaqium M. Havens
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
A central review of resectability of optimally unresectable colorectal liver metastases following neoadjuvant chemotherapy (KSCC0802).
Authors: Mitsuhisa Takatsuki, Susumu Eguchi, Shoji Tokunaga, Yasunori Emi, Eiji Oki, Shinji Uchida, Masahiko Sakoda, Yoshihiro Kakeji, Ken Shirabe, Yoshito Akagi, Toru Beppu, Hideo Baba, Shinichi Ueno, Shoji Natsugoe, Yutaka Ogata, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2013)

e14633 Background: Kyushu Study group of Clinical Cancer (KSCC) conducted the phase II study that evaluated the neoadjuvant chemotherapy for optimally-unresectable colorectal liver-limited metastases (KSCC0802, Samura et al, J Clin Oncol 30:4s, 2012). We carried out a central review for the purpose of obtaining an objective assessment of how resectability changed during treatment. Methods: We reviewed the CT or MRI images before and after protocol treatment, according to the method of CELIM study. A surgical review was done by five independent hepatobiliary special surgeons from five different centers. A resectability was reviewed based on radiological images only. Individual surgeons were blinded to the time when the CT scan was taken. The surgeons voted for (1) curative resection, (2) exploratory laparotomy with aim of resection (3) borderline resectable with chemotherapy preferred first, (4) unresectable, (5) non-evaluable. Patients were considered resectable if 50% (non-evaluable is excluded) or more of surgeons voted for categories (1) and (2), and images were considered evaluable if more than three surgeons voted with categories (1)–(4). Results: In KSCC0802 study, of the 40 pts. enrolled from Sept. 9 2008 to Aug. 10 2010. The number of cases to intent operation after chemotherapy was 17 (42.5%), and the actual liver resectability was 16/40 (40.0 %). The number of R0 cases was 10 pts. . In total, 77 images were presented for this central review. Only three follow-up scans were not available. Following review, 17 (42.5%) of 40 patients were judged to be resectable after chemotherapy, compared with 14 (35.0%) patients at baseline. Of 36 cases in which both imaging studies were available to be evaluated before and after chemotherapy, 7 cases (19.4%) judged as unresectable before chemotherapy were finally determined as resectable after chemothrerapy. Conclusions: With the central review by 5 independent liver surgeons, the resectability was fairly determined before and after chemotherapy. mFOLFOX6 with Bevacizumab regimen is safe and effective for unresectable liver limited-metastases from colorectal cancer, and might be to lead the liver resectability. Clinical trial information: UMIN000001308.
Princess Margaret Cancer Centre (PMCC) Integrated Molecular Profiling in Advanced Cancers Trial (IMPACT) using genotyping and targeted next-generation sequencing (NGS).
Authors: Philippe L. Bedard, Amit M. Oza, Ming-Sound Tsao, Natasha B. Leighl, Frances A. Shepherd, Eric Xueyu Chen, Ian Tannock, Monika K. Krzyzanowska, Neesha C. Dhani, Blaise Clarke, Hal K. Berman, Stefano Serra, Kenneth J. Craddock, Dianne Chadwick, Tong Zhang, Mahadeo A. Sukhai, Celeste Yu, Aaron Richard Hansen, Suzanne Kamel-Reid, Lillian L. Siu
Journal: Journal of Clinical Oncology (2013)

11002 Background: IMPACT is an institution-wide screening program to identify patients (pts) treated at PMCC with somatic alterations that can be matched to targeted therapies. Methods: Pts with advanced breast, colorectal (CRC), non-small cell lung (NSCLC), ovarian cancers and selected other solid tumors treated at PMCC were eligible. Tumor DNA was isolated from a FFPE archived sample and genotyped using a customized Sequenom panel (23 genes, 280 mutations) in a CLIA-certified laboratory. Verified mutations were reported in pts electronic health records. Selected FFPE samples were further characterized by NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons, ≥500x coverage) for platform validation. Results: From Mar 1/12-Jan 10/13, 485 pts were enrolled with median 1 prior treatment for advanced disease (range 0-6). Of 33 (7%) screen failures, 5% were for insufficient tissue and 2% for clinical deterioration. Median DNA quantity from FFPE = 4250ng (range 15-32550ng). The median time from tissue receipt to reporting was 5 weeks (range 1-23). Mutations were identified by Sequenom in 137/349 (39%) pts, including 24/79 (30%) breast, 40/80 (50%) CRC, 54/88 (61%) NSCLC, 17/78 (22%) ovarian, and 2/24 (8%) other cancers. Mutations detected were: 76 KRAS, 35 PIK3CA, 22 EGFR, 5 NRAS, 5 ERBB2, 5 CTNNB1, 4 BRAF, and 1 AKT1. MiSeq was concordant with Sequenom in 112/113 (99%) pts, with mutations identified in 94/114 (82%). The average number of mutations detected by MiSeq was 1.72/pt (range 0-7) compared with 0.49/pt by Sequenom (range 0-2). After a median follow up of 5.0 months, 31/137 (23%) pts with mutations have been matched to targeted therapies, including 14 pts enrolled in clinical trials (15 trials) matched to their genotype. Of the 10 trial pts with at least one response assessment, 3 PR (1 confirmed) and 2 SD ≥ 24 weeks have been observed. Conclusions: Molecular profiling can be integrated into the routine care of advanced cancer pts. Genotyping and targeted NGS are feasible in a clinical laboratory using stored archival FFPE tumor samples. NGS identifies additional actionable mutations to inform clinical-decision making. Clinical trial information: NCT01505400.
A randomized phase II study of bortezomib (Btz)/dexamethasone (dex) with or without elotuzumab (Elo) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Authors: Andrzej J. Jakubowiak, Massimo Offidani, Brigitte Pegourie, Javier De La Rubia, Laurent Garderet, Kamel Laribi, Alberto Bosi, Roberto Marasca, Jacob Laubach, Ann Mohrbacher, Angelo Michele Carella, Anil K. Singhal, Claire Tsao, Mark John Lynch, Eric W. Bleickardt, Ying-Ming Jou, Antonio Palumbo
Journal: Journal of Clinical Oncology (2015)

8573 Background: Elo, a monoclonal antibody (mAb) targeting Signaling Lymphocytic Activation Molecule F7 (SLAMF7), kills myeloma cells with minimal effects on normal tissue. Elo showed enhanced activity when combined with Btz in a preclinical myeloma model, (van Rhee F, et al. Mol Cancer Ther 2009;8:2616–24) and encouraging clinical activity in a Ph 1 study (Jakubowiak A, et al. J Clin Oncol 2012;30:1960–65). This Ph 2 open-label study (NCT01478048, CA204-009) investigated the efficacy and safety of Elo + Btz/dex (Bd) in pts with RRMM. Methods: Pts with RRMM, 1–3 prior therapies, were given Elo + Bd (EBd) or Bd in 21-d (Cycles 1–8) or 28-d cycles (9+) to disease progression/unacceptable toxicity. Elo (10 mg/kg IV): wkly Cycles 1–2, D1+11 Cycles 3–8, then D1+15; Btz (1.3 mg/m2 IV/SC): D1, 4, 8+11 Cycles 1–8, then D1, 8+15; dex 20 mg non-Elo days, 28 mg PO + 8 mg IV Elo days. Primary endpoint: PFS (ITT population). A 2-sided 0.30 significance level was specified (80% power, 103 events) to detect a hazard ratio (HR) of 0.69. Results: 152 pts were randomized; 77 EBd, 75 Bd. At data cut-off (12 Sep 2014), 18% (EBd) vs 10% (Bd) of pts remained on therapy. Discontinuation was mainly for disease progression (52%). Median PFS was 9.7 mo (EBd) vs 6.9 mo (Bd) (HR 0.71; 70% CI 0.58, 0.87; p = 0.08). PFS HR, adjusting for prognostic factors, was 0.58 (70% CI 0.47, 0.72; p = 0.01). ORR was 66% (EBd) vs 63% (Bd). Early overall survival (OS) results revealed a HR of 0.61 (70% CI 0.43, 0.85); 40 deaths (17 EBd, 23 Bd) were observed, mainly from disease. Common ≥ G3 adverse events (EBd, Bd): thrombocytopenia 7 (9%), 13 (17%); infections 14 (19%), 11 (15%). Infusion reactions (IRs; all grade 1–2, none at max 5 mL/min rate) occurred in 7% of pts with EBd. Conclusions: This study met the primary endpoint. PFS was longer with EBd than with Bd (HR 0.71). More pts continue on EBd vs Bd and early OS data favor EBd vs Bd. A low rate of IRs was seen with EBd. In patients with RRMM, Elo, an immunotherapeutic mAb, provides clinical benefit with limited added toxicity when combined with Bd vs Bd alone. Clinical trial information: NCT01478048.
Evolution in multimodality management of locally advanced rectal cancer.
Authors: Campbell SD Roxburgh, Paul Strombom, Patricio B Lynn, Andrea Cercek, Leonard Saltz, Marc Jeffrey Gollub, Christopher H Crane, Abraham Jing-Ching Wu, Jinru Shia, Efsevia Vakiani, Jesse Joshua Smith, Larissa K. F. Temple, Garrett Michael Nash, Jose G. Guillem, Philip Paty, Julio Garcia-Aguilar, Martin R. Weiser
Journal: Journal of Clinical Oncology (2017)

684 Background: This study reports the evolving multimodality management of locally advanced rectal cancer (LARC) and associated outcomes at a high volume center. Methods: Patients with Stage II/III LARC &lt;15cm from the anal verge evaluated by the colorectal surgery service were identified from a prospective database. Clinical management including neoadjuvant therapy (NT) and surgical treatment along with pathologic and perioperative outcomes were collected. Results: Between June 2009 and March 2015, 798 patients were evaluated and received NT for LARC. Majority were staged cT3/T4 (84%) or cN+ (78%), and 635 had surgery within 26wks following NT. Reliance on MRI staging increased from 57% to 98% during the study period (P &lt; 0.001). There was increased usage of total NT (NEO) with pre-op chemotherapy (CT) and chemoradiotherapy (CRT) (17% to 76%, p &lt; 0.001) with a concomitant decrease in use of CRT alone (77% to 16%, p &lt; 0.001) and post-op CT (70% to 15%, p &lt; 0.001). The proportion undergoing surgery beyond 8wks after NT rose from 41% to 62% (P &lt; 0.001) and beyond 8 wks after CRT rose from 45% to 72% (p &lt; 0.001). The percentage of patients not undergoing resection by 26wks (nonoperative management) rose from 12% to 27%, P &lt; 0.001). Minimally invasive surgery (MIS) increased from 33% to 71% (P &lt; 0.001); in 2014-15 98% of MIS was robot-assisted. Over the study period there was a decrease in LOS (mean 8.1 to 6.5 days, p &lt; 0.001), grade III-V complications (13% to 7%, p &lt; 0.05), surgical site infections (25% to 8%, p &lt; 0.001), and anastomotic leak (11% to 3%, p &lt; 0.05). The proportion undergoing ileostomy closure within 15 wks rose from 7% to 73% (P &lt; 0.001). Involved CRM rates decreased from 9% to 3% (P &lt; 0.01). TNM downstaging increased from 62% to 74% (p = 0.002). Complete response rates (clinical and pathologic) at 26wks was 26% in 2009-10 and 32% in 2014/5 (p = 0.067). Conclusions: Over the past decade, there has been a shift to MRI staging, total NT (NEO), and MIS rectal resection at 8-12 weeks. This has been associated with higher response rates, shorter LOS, and fewer complications.
Development of Peptidomimetic Inhibitors of the ERG Gene Fusion Product in Prostate Cancer
Authors: Xiaoju Wang, Yuanyuan Qiao, Irfan A. Asangani, Bushra Ateeq, Anton Poliakov, Marcin Cieślik, Sethuramasundaram Pitchiaya, Balabhadrapatruni V.S.K. Chakravarthi, Xuhong Cao, Xiaojun Jing, Cynthia X. Wang, Ingrid J. Apel, Rui Wang, Jean Ching-Yi Tien, Kristin M. Juckette, Wei Yan, Hui Jiang, Shaomeng Wang, Sooryanarayana Varambally, Arul M. Chinnaiyan
Journal: Cancer Cell (2017)
A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto).
Authors: Andreas Schneeweiss, Volker Moebus, Hans Tesch, Claus Hanusch, Carsten Denkert, Kristina Luebbe, Jens Bodo Huober, Peter Klare, Sherko Kummel, Michael Untch, Karin Kast, Christian Jackisch, Jörg Thomalla, Barbara Ingold Heppner, Jens U. Blohmer, Mahdi Rezai, Matthias Frank, Valentina Nekljudova, Gunter Von Minckwitz, Sibylle Loibl
Journal: Journal of Clinical Oncology (2017)

518 Background: The sequential use of intense does-dense (idd) epirubicin, paclitaxel, cyclophosphamide (EPC) and weekly paclitaxel/liposomal doxorubicin (+/- carboplatin (Cb) in triple negative breast cancer (TNBC) (PM(Cb)) are considered highly efficient regimens for high-risk early stage breast cancer (BC). Methods: GeparOcto (NCT02125344) patients (pts) received 18 weeks (wks) either EPC (3x E 150mg/m² q2w followed by 3x P225 mg/m² q2w followed by 3x C 2000mg/m² q2) or PM(Cb) (12x P 80mg/m² plus M 20 mg/m² q1w, plus Cb AUC 1.5 q1w in TNBC). For HER2+ BC trastuzumab 6 (8) mg/kg q3w and pertuzumab 420 (840) mg q3w cycles were given concomitantly with P and C. Pts with histologically confirmed, cT1c - cT4a-d BC and central receptor assessment were included. Pts with HER2+ or TNBC were eligible irrespective of nodal status, luminal B-like tumours only if pN+. Primary objective compared pathologic complete response (pCR) rates (ypT0/is ypN0). Sample size calculations assumed a pCR rate of 50% for EPC and 60% for PM(Cb), requiring 950 pts to show superiority of PM(Cb). Secondary objectives compared pCR rates within the stratified subgroups (BC subtype, HER2+ vs HER2- HR+ vs HER2- HR-), amongst others. Results: 961 pts were recruited between 12/2014 and 05/2016, 945 started treatment. Median age was 48 years, 4% T3, 2% T4d, 46% N+, 82% ductal invasive, 66% G3 tumors; 40% were HER2+, 43% TNBC. 347 pts reported SAEs (176 EPC/171 PM(Cb)) and 2 pts died. 35 pneumonias (2 EPC vs 33 PM(Cb)) and 18 pneumonitis (3 EPC vs 15 PM(Cb)) were reported. 16.4% pts with EPC and 33.8% with PM(Cb) discontinued treatment (p&lt;0.001), mainly due to AEs (47 EPC vs 113 PM(Cb)). Mean treatment duration was 17 wks with EPC and 16 wks with PM(Cb). pCR rate was 48.3% with EPC and 47.6% with PM(Cb)(OR 0.97 (95%CI 0.75-1.25), p=0.876). pCR rate in TNBC was 48.5% with EPC and 51.7% with PM(Cb); in HER2+ 62.0% vs 57.4% and in Luminal B 14.1% vs 14.6%. Conclusions: In high-risk early stage breast cancer pts pCR rates of idd EPC compared to weekly PM(Cb) were not significantly different. PM(Cb) appeared to be less feasible. Clinical trial information: NCT02125344.
Influenza vaccines differentially regulate the interferon response in human dendritic cell subsets
Authors: Shruti Athale, Romain Banchereau, LuAnn Thompson-Snipes, Yuanyuan Wang, Karolina Palucka, Virginia Pascual, Jacques Banchereau
Journal: Science Translational Medicine (2017)

The monovalent H1N1 vaccine failed to promote human DC activation and to induce a type I IFN signature, which may have contributed to its limited efficacy.
Exercise During Pregnancy
Authors: María Perales, Raul Artal, Alejandro Lucia
Journal: JAMA (2017)

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