tbuckley/cabot-search huggingface dataset:
A pharmacogenomic scoring system predicting median time to progression (mTTP) on sunitinib (SUN) as first-line treatment in patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Benoit Beuselinck, Alexandra Karadimou, Gabrielle Couchy, Bart Claes, Diether Lambrechts, Joost Berkers, Robert Paridaens, Patrick Schoffski, Hendrik Van Poppel, Pascal Wolter, Mejean Arnaud, Evelyne Lerut, Brigitte Laguerre, Christine Theodore, Claude Linassier, Remy Delva, Emmanuel Sevin, Francois Goldwasser, Jessica Zucman-Rossi, Stephane Oudard
Journal: Journal of Clinical Oncology (2012)

359 Background: There are no established biomarkers predicting outcome of SUN treatment in mRCC. Methods: We assessed 30 single nucleotide polymorphisms (SNPs) in 10 genes on fresh frozen clear cell RCC nephrectomy specimens originating from pts who developed metastatic disease. Results: We processed 79 samples. In 49 pts, normal kidney tissue adjacent to the tumor was used, in 30 pts only tumoral tissue was available. After nephrectomy and in presence of synchronous or metachronous metastasis, all pts received SUN as 1st line treatment. We observed associations between several SNPs and mTTP: In the promotor region of the gene encoding for IL-8 (proangiogenic growth factor): rs4073: TT or TA versus (vs) AA variant: mTTP 12 mo vs not reached (NR) (p=0.02). In ABCB1 (involved in drug transport): rs2032582: TA or TT vs GT/GA or GG: 9 vs 16 mo (p=0.03). rs1128503: TT vs CT or CC: 9 vs 16 mo (p=0.02). In VEGFR3 (a target of SUN): rs307826 : GA vs AA: 9.3 vs 18 mo (p=0.01). rs307821 : GT vs GG: 10 vs 16 mo (p=0.08). rs448012 : CC/CG vs GG: 12 mo vs NR (p=0.02). In NR1/2 (promotor leading to increased CYP3A4 expression): rs3814055: TT vs CC/CT: 13 vs 18 mo (p=0.02). rs1054190: CC vs CT: 14 vs 20 mo (p=0.14). In PDGFR-alpha (another SUN target): rs1800812: TT vs GG/GT: 3.5 vs 16 mo (p&lt;0.0001). A scoring system combining 7 non-overlapping SNPs was build and pts were classified in a favorable, intermediate and unfavorable SNP profile group. A link with mTTP and response rate was found, but not with established clinical prognostic scores (MSKCC). Conclusions: SNPs in genes linked to the pharmacokinetics and -dynamics of SUN can probably predict outcome of SUN treatment in mRCC. Our results confirm in part previous observations made by other groups in pazopanib or SUN (in IL-8, VEGFR3 and NR1/2) and highlight the potential role of other SNPs (in ABCB1, NR1/2 and PDGFR). Extension of the series and univariate/multivariate validation are ongoing. [Table: see text]
Comparison of patterns of relapse in thymic carcinoma and thymoma
Authors: J. Huang, N. Rizk, W. Travis, G. J. Riely, B. J. Park, M. S. Bains, R. M. Flores, R. J. Downey, V. W. Rusch
Journal: Journal of Clinical Oncology (2008)

7539 Background: Thymic carcinomas (TC) are considered to be more aggressive than thymomas and carry a worse prognosis. Given their rarity, our knowledge about their clinical behavior and optimal management is limited. We reviewed our recent experience with the surgical management of thymic tumors and compared the outcomes and patterns of relapse between TC and thymoma. Methods: Retrospective review of a single institution surgical database. Data included patient demographics, stage, treatment, pathologic findings, and postoperative outcomes. Results: During the period 1995–2006, 120 patients with thymic tumors underwent surgery, including 24 patients with TC and 96 patients with thymoma by the WHO 2004 histologic classification. At a median follow-up of 41 months (range 6–154), the overall 5 year survival was significantly different between TC and thymoma (TC 57%, thymoma 89%, p=0.01). Data on relapse was available for 112 patients. The progression-free 5 year survival was also significantly different between TC and thymoma (TC 36%, thymoma 75%, p<0.01). Complete macroscopic resection (R0 and R1) resulted in significantly higher progression-free survival in both TC and thymoma. Relapses in TC occurred earlier and more frequently at distant sites than in thymoma. Sites of distant relapse included lung (4), bone (3), brain (1), liver (1) and skin (1), with some patients having multiple sites. Details are listed in the table below. Conclusions: Patterns of relapse differ between TC and thymoma with lower progression-free survival, earlier onset and more distant relapses in TC. Complete macroscopic resection affords significantly longer freedom from disease progression in both TC and thymoma. Despite significantly higher rates of distant relapse, good overall survival in TC can be achieved. Comparison of Patterns of Relapse in Thymoma and Thymic Carcinoma Thymic Carcinoma (n=22) Thymoma (n=90) 5 yr Progression-free Survival by Resection Status 5 yr Progression-free Survival by Resection Status Complete Resection (n=14) 59% p=0.01* Complete Resection (n=81) 87% p<0.01* Incomplete Resection (n=8) 0% Incomplete Resection (n=9) 0% Site of Progression (n=10) Site of Progression (n=14) Locoregional (n=4) 40% Locoregional (n=13) 93% p<0.01** Distant (n=6) 60% Distant (n=1) 7% Time to Progression (mo) Time to Progression (mo) Mean 14.0 Mean 31.1 p=0.05*** Median (Range) 9 (6–33) Median (Range) 21(4–95) * Log-Rank Test, Complete vs. Incomplete; ** Fisher’s Exact Test, TC vs. Thymoma; *** T-test, TC vs. thymoma. No significant financial relationships to disclose.
Doctors win right to keep private income confidential
Authors: Matthew Limb
Journal: BMJ (2017)

NHS England has dropped plans to make doctors reveal how much they earn from private work.

The proposal was made in a consultation issued last September but met strong opposition from some medical groups.

Clinical staff will have to declare what private practice they do, how long they spend doing it and where, but not their earnings, new guidance for NHS staff and organisations on managing conflicts of interest says.1

NHS work was expected to “take precedence” over private practice, where there would otherwise be a conflict or potential conflict of interest, it said.

NHS England had originally proposed that clinical staff should declare their earnings from private practice and whether they earned less than £50 000 (€59 000; $63 000); …
Platelet Kinetic Study (PKS) May Early Identify a Subset of Patients with Immune Thrombocytopenia (ITP) Probably Cured by Romiplostim. Two Years Follow-up
Authors: Francesco Iuliano, Alessia Perricelli, Eleonora Iuliano, Stefania Infusino, Angelo Pomillo, Maria Luci, Filippo Barbano
Journal: Blood (2012)
Next generation sequencing of solid tumor and circulating tumor DNA (ctDNA) in metastatic melanoma.
Authors: Erica L. Carpenter, Stephanie S. Yee, Devon Soucier, Jennifer J. Morrissette, Wei Xu, Shannon R. Harmon, Neeraj Salathia, Yue Zhao, Jill Waters, Jian-Bing Fan, Lynn Mara Schuchter, Ravi K. Amaravadi, Giorgos Constantine Karakousis, Tara C. Gangadhar
Journal: Journal of Clinical Oncology (2015)

9077 Background: Capture and molecular analysis of ctDNA represents a promising strategy for noninvasive detection of circulating tumor material. This approach is particularly promising for melanoma, in which detection of intact circulating tumor cells has low sensitivity. We conducted a pilot study using ultra-deep sequencing ctDNA in melanoma patients. Methods: Plasma samples ranging from 1-5ml were obtained from 9 metastatic melanoma patients. DNA was extracted using Qiagen Circulating Nucleic Acid Kit. Ultra-deep sequencing of ctDNA was conducted using the Illumina Melanoma Gene Panel to detect variants in a panel of 38 genes. Matched tumor tissue samples were obtained for 5 of these patients; next generation sequencing in the tumor tissue DNA was conducted using a separate assay, the Illumina TrueSeq Cancer Amplicon panel of 47 genes. Results: Nonsynonymous variants of known significance were detected in ctDNA from 8 of 9 patients. 13 mutations were detected in 6 genes, including BRAF, KIT, TSC2, MET, FGFR3, and AKT3. More than one mutation was detected in 5/9 patients. BRAF mutations were detected in 5 of 9 patient ctDNA samples. For 5 patients with matched solid tumor data, 11 variants were detected by either the ctDNA panel, the solid tumor panel, or both panels. Among these 11 variants, 7 were covered by both panels, 2 by the ctDNA panel only, and 2 by the solid tumor panel only. Among the 7 covered by both panels, 3/7 variants were identified identically on both panels and were therefore deemed concordant, while 2/7 variants were only detected on the ctDNA panel and not the solid tumor panel, and the remaining 2/7 variants were only detected on the solid tumor panel and not the ctDNA panel. Possible reasons for these 4/7 discordant calls include tumor heterogeneity over time, with solid tumor tissue collected earlier in the disease course and/or the higher sensitivity of the ctDNA panel. Conclusions: Non-invasive monitoring for ctDNA via plasma detection of mutational variants is feasible in metastatic melanoma. Comparison of tumor DNA and plasma ctDNA yields a discordance that underscores the need to validate ctDNA assays in clinical trials, while accounting for assay sensitivity and tumor heterogeneity.
ATIM-10. PHASE I/II TRIAL OF RADIATION THERAPY, TEMOZOLOMIDE AND PEMBROLIZUMAB FOLLOWED BY TEMOZOLOMIDE AND PEMBROLIZUMAB IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Karan Dixit, Priya Kumthekar, Timothy Kruser, Orin Bloch, James Chandler, Matthew Tate, Jeffrey Raizer
Journal: Neuro-Oncology (2016)

Patients with glioblastoma (GBM) have a poor prognosis despite maximal resection, and standard of care radiation (RT) with temozolomide (TMZ) [SOC]. Immune checkpoint inhibitors have shown antitumor activity in solid tumors and Hodgkin’s lymphoma. GBM have been shown to express programmed cell death ligand-1 (PD-L1) with anti-tumor activity demonstrated in animal models. A single arm phase I/II trial was done to determine the safety and efficacy of pembrolizumab (anti PD-1 monoclonal antibody) in combination with SOC in newly diagnosed GBM patients. Phase I data are presented. Standard adult eligibility criteria were used but > 25% resection was required. Patients received pembrolizumab (200mg intravenously every 3 weeks) starting on day 1 of RT+TMZ with plans for dose de-escalation if a DLT occurred in cohort 1. The DLT window was 9 weeks from the start of RT. Treatment then consisted of pembrolizumab every 3 weeks along with TMZ (9 week cycles). The primary endpoint was maximum tolerated dose (MTD) and determine the recommended phase 2 dose (RP2D). Four patients with GBM were treated (3 men, 1 woman). Median age was 64 (range 39–67) and median KPS was 90 (range 80–100). The most common toxicities were leukopenia (grade 2, n = 2; grade 1, n = 2), anemia (grade 1, n = 4), and fatigue (grade 1, n = 2). There were no grade 3 or 4 toxicities or interruptions in treatment. One patient withdrew without toxicity. The remaining 3 patients are alive and still on treatment having completed 3, 2, and 1 cycles post-RT thus far. The combination of pembrolizumab at 200mg added to SOC in patients with newly diagnosed GBM seems to be tolerable. No immune related adverse events were seen in 4 subjects receiving the combination. The RP2D is 200mg every three weeks.
AAV-Nrf2 Promotes Protection and Recovery in Animal Models of Oxidative Stress
Authors: Katharine J. Liang, Kenton T. Woodard, Mark A. Weaver, John Paul Gaylor, Ellen R. Weiss, R. Jude Samulski
Journal: Molecular Therapy (2017)

NRF2 is a transcription factor that drives antioxidant gene expression in multiple organ systems. We hypothesized that Nrf2 overexpression could be therapeutically applied toward diseases in which redox homeostasis is disrupted. In this study, adeno-associated virus (AAV)-Nrf2 was tested in a mouse model of acute acetaminophen-induced liver toxicity and successfully conferred protection from hepatotoxicity, validating the vector design and early onset of NRF2-mediated protection. Furthermore, therapeutic potential of AAV-Nrf2 in chronic disease also was tested in a light-induced mouse model of age-related macular degeneration. Adult BALB/c mice were intravitreally injected with AAV-Nrf2 and subject to light damage following injection. Retinal thickness and function were monitored following light damage using optical coherence tomography and electroretinography, respectively. By 3 months post-damage, injected eyes had greater retinal thickness compared to uninjected controls. At 1 month post-damage, AAV-Nrf2 injection facilitated full functional recovery from light damage. Our results suggest a therapeutic potential for Nrf2 overexpression in acute and long-term capacities in multiple organ systems, opening up doors for combination gene therapy where replacement gene therapy requires additional therapeutic support to prevent further degeneration. NRF2 is a transcription factor that drives antioxidant gene expression in multiple organ systems. We hypothesized that Nrf2 overexpression could be therapeutically applied toward diseases in which redox homeostasis is disrupted. In this study, adeno-associated virus (AAV)-Nrf2 was tested in a mouse model of acute acetaminophen-induced liver toxicity and successfully conferred protection from hepatotoxicity, validating the vector design and early onset of NRF2-mediated protection. Furthermore, therapeutic potential of AAV-Nrf2 in chronic disease also was tested in a light-induced mouse model of age-related macular degeneration. Adult BALB/c mice were intravitreally injected with AAV-Nrf2 and subject to light damage following injection. Retinal thickness and function were monitored following light damage using optical coherence tomography and electroretinography, respectively. By 3 months post-damage, injected eyes had greater retinal thickness compared to uninjected controls. At 1 month post-damage, AAV-Nrf2 injection facilitated full functional recovery from light damage. Our results suggest a therapeutic potential for Nrf2 overexpression in acute and long-term capacities in multiple organ systems, opening up doors for combination gene therapy where replacement gene therapy requires additional therapeutic support to prevent further degeneration.
Creation of an mHealth Decision Tree Support Program for Epinephrine Auto-injector (EAI) Administration Training of Adolescents
Authors: Joel L. Gallagher, Robert Rivera, Kirk Shepard, Tanvir Roushan, Golam Ahsan, Shiekh Iqbal Ahamed, Cheng Wen, Karina Gobin, Christina Eldredge, Asriani Chiu
Journal: Journal of Allergy and Clinical Immunology (2017)
Pre-emptive monitoring of scheduled chemotherapy reduced toxicity without diminishing efficacy in patients (pts) over age75 with gynecologic (GC) or lung cancer (LC) treated with paclitaxel and carboplatin (PC).
Authors: K. Belfihadj, H. Aboudagga, E. Fabre, F. Scotte, J. Fouque, B. Bonan, S. Oudard, O. Saint-Jean, J. Medioni
Journal: Journal of Clinical Oncology (2011)

e19530 Background: Advanced lung and gynecologic cancers are common in elderly pts but not optimally treated. Chemotherapy with PC is not recommended because of toxicity. The objective is to investigate whether a pre-emptive monitoring on the phone a few days before administration of PC can decrease toxicity. Methods: A retrospective monocentric study were conducted in Georges Pompidou European Hospital, Paris, France, in adjuvant or metastatic pts older than 75 years, treated for LC or GC with paclitaxel (175 mg/m2) and carboplatin (AUC 5) every 3 weeks. In arm A (pts treated between Sept 2003 and May 2008), pts were followed on a practice routine. In arm B (pts treated between Oct 2008 and Jul 2010), voluntary pts were included in the program “PROCHE” of Chemotherapy Optimization Program to pre-emptively confirm scheduled chemotherapy(ASCO 2010, abst 9152). Primary endpoints was toxicity (assessed with the CTC-NCI v3.0) and secondary endpoints were the number of cycles administered, reductions of doses and efficacy in metastatic pts using radiological RECIST criteria. Results: 25 pts (9 men, 16 women) were included. Median age was 78 [min 75–max 86]. Pts characteristics were well balanced in the 2 arms. Median PS was 1 [0–3] and Charlson index was 7 [3–10]. Primary and secondary endpoints are summarized in the table. For metastatic pts, response rate was higher in arm B (Partial Response: 82 vs 29% [p: 0.02]). Conclusions: In patients (pts) aged over 75 years, pre-emptive monitoring a few days before the administration of scheduled chemotherapy with PC can reduce toxicity without diminishing efficacy. Comparison of toxicity and dose administered of PC in elderly pts with and without PROCHE. Without PROCHE With PROCHE P Neutropenia 57% 9% Febrile neutropenia 14% 0% Anemia/thrombopenia 29% 18% 0.02 Neuropathy 28% 18% 0.01 Toxic death 1 0 Median number of cycles [min-max] 6 [3-9] 6 [2-9] Dose reduction per pt 42% 100% 0.002 Reduction of carboplatin per protocol 23% 29% Reduction of paclitaxel per protocol 23% 44%
Genetic testing referral patterns and clinical outcomes among high-risk breast cancer survivors.
Authors: Rashmi Krishna Murthy, Huiqin Chen, Caimiao Wei, Michelle Jackson, Ashley Henriksen Woodson, Jennifer Keating Litton, Banu Arun, Vicente Valero, Carlos Hernando Barcenas
Journal: Journal of Clinical Oncology (2014)

9589 Background: Referral patterns for genetic testing in breast cancer survivors are not well understood. We sought to identify a cohort of high-risk breast cancer survivors who had not been refer...
Phase II study of temozolomide and celecoxib in the treatment of metastatic melanoma
Authors: R. Hakim, R. Poggi, M. Pantaleo, G. Benedetti, G. Brandi, G. Zannetti, M. Astorino, S. Fanello, S. Dell’arte, G. Biasco
Journal: Journal of Clinical Oncology (2006)

18015 Background: There is increasing evidence that the expression of Cyclo-oxygenase 2 correlates with development and progression of malignant melanoma. Celecoxib (C) has demonstrated some kind of activity in monotherapy in melanoma. Temozolomide (T) has consistent activity in melanoma, either as monotherapy or in combination. We designed a phase II study to determine the efficacy and toxicity of the combination of Celecoxib and Temozolomide in advanced melanoma as first line of therapy Methods: From January 2004 to October 2005, 13 patients with metastatic melanoma were enrolled in the study. There were 4 males and 9 females. The median age was 59 years. Patients received Temozolomide 200/mg/mq day po for 5 days every 4 weeks and Celecoxib 400 mg BID for 10 days every 4 weeks. Results: Among 12 evaluable patients there were 4 partial responses (30.8%), no complete response or disease stabilization. Progression occurred in 8 patients (61.5%). The median TTP was 3.14 months and the median survival was 9.06 months. The median number of cycles was 2, only 2 patients completed four cycles of treatment. Most commonly seen toxicities were nausea/vomiting (46%), fatigue (93%), thrombocytopenia (15.3%), leukopenia (7.6%). Two patients discontinued the treatment due to grade 4 thrombocytopenia. Conclusions: The combination of Temozolomide and Celecoxib is safe, manageable and provides clinical benefit, but its activity is not superior to standard therapy. No significant financial relationships to disclose.
529P Exploratory study for preventing nausea and vomiting by switching from pranisetron + dexamethasone (Days 1-3) + aprepitant (Days 1-3) to palonosetron + pexamethasone (Day 1) in patients undergoing moderatelyemetogenic chemotherapy
Authors: T. Kimura, K. Otsuka, M. Yaegashi, M. Hakozaki, T. Matuo, H. Fujii, K. Sato, M. Kamishima, T. Miyake, T. Takahara, Y. Akiyama, T. Iwaya, S. Nishizuka, H. Nitta, K. Koeda, M. Mizuno, Y. Kimura, A. Sasaki
Journal: Annals of Oncology (2016)
A Correction to the Research Article Titled: “Structural, Biochemical, and Clinical Characterization of Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Lung Cancer” by H. Yasuda, E. Park, C.-H. Yun, N. J. Sng, A. R. Lucena-Araujo, W.-L. Yeo, M. S. Huberman, D. W. Cohen, S. Nakayama, K. Ishioka, N. Yamaguchi, M. Hanna, G. R. Oxnard, C. S. Lathan, T. Moran, L. V. Sequist, J. E. Chaft, G. J. Riely, M. E. Arcila, R. A. Soo, M. Meyerson, M. J. Eck, S. S. Kobayashi, D. B. Costa
Journal: Science Translational Medicine (2014)
High-Throughput Genotyping of Haemophilia A and B Using Next-Generation Sequencing Technology in Lille University Hospital
Authors: Fanny Lassalle, Antoine Rauch, Benedicte Wibaut, Christine Vinciguerra, Mathilde Fretigny, Bertrand Vaast, Valerie Gomanne, Sophie Susen, Jenny Goudemand, Christophe Zawadzki
Journal: Blood (2015)
Does ATRA Confirm to Play a Role in the Better Relapse Free Survival of Infants with Acute Lymphoblastic Leukemia?
Authors: Larisa Fechina, Egor Shorikov, Olga Streneva, Olga Khlebnikova, Igor Vyatkin, Larisa Vakhonina, Grigory Tsaur, Alexander Popov, Leonid Saveliev, Natalia Miakova, Dmitry Litvinov, Konstantin Kondratchik, Anastasia Shamardina, Elmira Boichenko, Karapet Aslanyan, Elena Lapotentova, Olga Aleinikova, Alexander Karachunsky, Alexander Roumyantsev
Journal: Blood (2011)
BOLERO-4: Phase 2 trial of first-line everolimus (EVE) plus letrozole (LET) in estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2-) advanced breast cancer (BC)
Authors: M. Royce, C. Villanueva, M. Ozguroglu, T. Bachelot, S. Azevedo, F. Melo Cruz, R. Hegg, M. Debled, W.J. Gradishar, C. Manlius, A. Ridolfi, J. Lin, F. Ringeisen, F. Cardoso
Journal: Annals of Oncology (2016)
Hypogammaglobulinemia Following Rituximab and High-Dose Therapy and Autologous Stem-Cell Transplant: Incidence and Predictors of Prolonged Immunoglobulin Deficiencies
Authors: Nancy Pennell, Matthew Cheung, Lisa K Hicks, Rena Buckstein, Kevin R Imrie, Eugenia Piliotis, David Spaner, Zeina Ghorab, Marciano D. Reis, Violet Milliken, Angela Boudreau, Neil Berinstein
Journal: Blood (2008)
The evidence base in support of breast cancer surveillance guidelines: Flying without a net?
Authors: Shrujal S. Baxi, Rubaya Yeahia, Deborah Korenstein
Journal: Journal of Clinical Oncology (2016)

25 Background: There are a growing number of breast cancer survivors, and they are often followed by primary care providers (PCP). With limited specialized cancer knowledge, PCPs may rely on guidelines (GL), but surveillance recommendations vary based on source. The data informing post-treatment surveillance is limited. We reviewed the evidence in support of varying breast cancer surveillance recommendations found in national GLs. Methods: We included breast cancer GLs containing surveillance recommendations from professional societies and government organizations in North America, the UK, and Europe (2010-5). We used online search engines and organization websites to identify GLs. Surveillance testing recommendations were recorded; relevant citations for each recommendation were identified and classified by evidence type. Results: We identified 6 breast cancer GLs from US, UK, and Europe; all recommended mammography. Other recommendations varied, with contradictory recommendations regarding MRI and US. Overall, 13 systematic reviews (SR) were cited; 9 related to mammography. One SR of MRI and one of mammography were cited by 2 GLs; remaining SRs were each cited by 1 GL. Other references included 34 primary studies, 9 narrative reviews and 11 older GLs. Among 23 surveillance testing recommendations from the 6 GLs, the highest level of supporting evidence was a SR in 44% and a primary study in 22%; the remainder cited no direct evidence. At times, the same citation supported contradictory recommendations in different guidelines. Conclusions: Evidence for surveillance recommendations is often low-level and cited references vary across GLs; the same evidence is used to support contradictory recommendations. Better evidence and its more consistent application would facilitate high quality breast cancer survivorship care.