tbuckley/cabot-search huggingface dataset:
P11.07 BRAF V600E mutation: has it a role in pediatric gliomas?
Authors: M. Guidi, L. Giunti
Journal: Neuro-Oncology (2017)

Introduction: Pediatric high-grade gliomas (HGGs) represent a malignancy with a low survival rate. The genetic analysis of these tumors has identified useful mutations for an improved prognostic framing, as well as potential targets for new generation drugs. Previous studies have shown that the presence of BRAF V600E mutation in 23% of all pediatric gliomas reaching about 10% in WHO-grades III and IV, suggesting this alteration is one of the most common gene alterations in pediatric gliomas. BRAF mutation may help to differentiate indolent cancer from aggressive ones; tumors with BRAF V600E have a strong trend toward an increased risk for progression, developing a second cancer with anaplastic evolution. Moreover, BRAF mutation is a possible target for improved adjuvant treatment of residual or recurrent tumors. Materials and Methods: We performed a retrospective analysis of a population of pediatric patients with HGGs. Mutation analysis was carried out on DNA from each tumor sample. Portions coding and their flanking regions were amplified by PCR. The data were obtained after the purification of the samples and analysis by means of specific software. Results: We retrospectively evaluated 41 cases of pediatric HGGs. The median age at diagnosis was 7 years (range 0-32). The histological samples included: 9 cases of glioblastoma multiforme, 28 cases of anaplastic astrocytoma (AA), 3 glioneuronal tumor with neuropil-like islands (GTNI) and 1 glioma with mist components (2,45%). BRAF V600E mutation was analyzed in 27 samples: 21 patients did not have the mutation (77.77%), 6 patients showed the mutation (22,22). Four of 6 AA patients derived from a previous low grade tumor (3LGGs, and 1 GTNI) (p: 0.001). The BRAF V600E mutation seems therefore associated with increased risk of anaplastic progression. Finally, we have valuated the correlation between the presence of BRAF mutation and the tumor histology without statistically significant results (p: 0.12). Conclusions: The genetic analysis of tumor samples from children with HGGs represents an essential contribution to the prognostic stratification for each new diagnosis. BRAFV600E mutation is a negative prognostic factor in pediatric gliomas and a potential target of specific inhibitors. Considering the high rate of recurrence of these tumors and the limited impact on disease control of the following treatments, BRAF V600E detection is essential for a new therapeutic approach of poor responsive diseases.
Mindfulness-Based Stress Reduction for Treating Low Back Pain
Authors: Dennis Anheyer, Heidemarie Haller, Jürgen Barth, Romy Lauche, Gustav Dobos, Holger Cramer
Journal: Annals of Internal Medicine (2017)

Mindfulness-based stress reduction (MBSR) is frequently used to treat pain-related conditions, but its effects on low back pain are uncertain.To assess the efficacy and safety of MBSR in patients with low back pain.Searches of MEDLINE/PubMed, Scopus, the Cochrane Library, and PsycINFO to 15 June 2016.Randomized controlled trials (RCTs) that compared MBSR with usual care or an active comparator and assessed pain intensity or pain-related disability as a primary outcome in patients with low back pain.Two reviewers independently extracted data on study characteristics, patients, interventions, outcome measures, and results at short- and long-term follow-up. Risk of bias was assessed using the Cochrane risk-of-bias tool.Seven RCTs involving 864 patients with low back pain were eligible for review. Compared with usual care, MBSR was associated with short-term improvements in pain intensity (4 RCTs; mean difference [MD], -0.96 point on a numerical rating scale [95% CI, -1.64 to -0.34 point]; standardized mean difference [SMD], -0.48 point [CI, -0.82 to -0.14 point]) and physical functioning (2 RCTs; MD, 2.50 [CI, 0.90 to 4.10 point]; SMD, 0.25 [CI, 0.09 to 0.41 point]) that were not sustained in the long term. Between-group differences in disability, mental health, pain acceptance, and mindfulness were not significant at short- or long-term follow-up. Compared with an active comparator, MBSR was not associated with significant differences in short- or long-term outcomes. No serious adverse events were reported.The number of eligible RCTs was limited; only 3 evaluated MBSR against an active comparator.Mindfulness-based stress reduction may be associated with short-term effects on pain intensity and physical functioning. Long-term RCTs that compare MBSR versus active treatments are needed in order to best understand the role of MBSR in the management of low back pain.None.
Mortality of necrotizing fasciitis: relative influence of individual and hospital-level factors, a nationwide multilevel study, France, 2007-12
Authors: E. Audureau, C. Hua, N. de Prost, F. Hemery, J.W. Decousser, R. Bosc, R. Lepeule, O. Chosidow, E. Sbidian
Journal: British Journal of Dermatology (2017)

Background Necrotizing soft‐tissue infections (NSTI) are rare, life‐threatening conditions. Objectives To assess whether admitting hospital characteristics were associated with NSTI mortality. Methods We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted in the period 2007–12 with an International Classification of Diseases 10 code of necrotizing fasciitis were eligible. We extracted data on the patients (age, sex, intensive care unit admission, comorbidities) and hospitals (public vs. private proprietary; for public hospitals, teaching, yes/no; and number of NSTI admissions, ≥ 3 NSTI cases/year, yes/no). Multivariable analyses were performed to identify independent predictors of 28‐day mortality and in‐hospital mortality using mixed logistic regression and Cox proportional hazards models, respectively. Results We identified 1537 patients (915 males) with a median age of 60 years (interquartile range 48–75), admitted to 326 hospitals, public (82%) and admitting < 3 NSTI cases/year (93%). Overall, 364 patients died [23·7%; 95% confidence interval (CI) 21·6–25·9]. Patients treated in public teaching centres with ≥ 3 NSTI cases annually had lower 28‐day mortality (adjusted odds ratio 0·68; 95% CI 0·46–0·99; P = 0·045) and in‐hospital mortality rates than patients treated in local hospitals, even after adjusting for potentially relevant individual risk factors. No significant association was found between mortality and interhospital transfer. Conclusions Our findings highlight an increased survival in teaching centres with high‐volume NSTI procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition.
P12.22 Factors influencing recurrence of atypical meningioma following surgical resection
Authors: A. P. Perera, N. Mukerji
Journal: Neuro-Oncology (2017)

Introduction: Atypical (WHO II) meningiomas represent a small proportion of those presenting with meningiomas, however pose a greater threat to the patient; having a propensity to recur following surgery and progress more rapidly. Recent NICE guidelines published in the United Kingdom have acknowledged the use and consideration of adjuvant radiotherapy and more aggressive treatment in these patients, however little is known about who will progress and guidance is not overt in who should have radiotherapy at the time of surgery. METHODS: This study was designed as a retrospective case review. MDT records were searched for patients who presented with a suspected meningioma who had a subsequent resection and proven to be WHO II (atypical) meningioma. The patient records and scans were searched for baseline characteristics, radiological features at presentation, pathological features defining the lesion as grade II and patient outcome including recurrence and time to recurrence. RESULTS: 26 patients had a histologically proven WHO II meningioma presenting between 2008 and 2015. 17 females and 9 males were identified with an average age at presentation of 53 (34-68 years). The average length of follow up was 64 months (20-113 months). During the follow-up period one patient died as a result of haemorrhage into their tumour. 6 patients had tumour recurrence after surgery. The average time to recurrence from surgery was 3.5 years ranging from 1.8 to 5.4 years. The main factors which differed between the recurrence group and the no recurrence group were the presence of oedema (100% vs 70%), brain invasion (66% vs 20%) and residual disease (66% vs 20%) all of which increased the chance of recurrence. CONCLUSION: Residual tumour and brain invasion are the most important factors in determining the likelihood of recurrence. Gross total resection should be aimed for unless prevented anatomically. Further research is required to determine whether patients with proven residual tumour at the first post-operative scan or brain invasion on histology would benefit from early radiosurgery or repeat surgical management as opposed to surveillance post-operatively. One patient demonstrated late recurrence at 5 years suggesting that long term surveillance post-operatively would be required with follow up of 5 years as a minimum standard.
Topical corticosteroid phobia in atopic dermatitis: International feasibility study of the <scp>TOPICOP</scp> score
Authors: J. F. Stalder, H. Aubert, E. Anthoine, M. Futamura, D. Marcoux, M. A. Morren, M. Trzeciak, Z. Szalai, K. Veres, M. Deleuran, C. Vestergaard, F Boralevi, C. Y. Chu, L De Raeve, A. Svensson, R. Fölster-Holst, M Buchner, R. Takaoka, V. Aoki, P. Chernyshov, L. Chernyshova, Dedee F. Murrell, C. Zhao, C. D. Mckinster, L. Von Kobyletzky, L. F. Eichenfield, C. Totri, P. Lio, J. Seneschal, L. Moret, S Barbarot
Journal: Allergy (2017)

Adherence to topical corticosteroids (TCS) is essential for the effective treatment of atopic dermatitis but can be limited by concerns about their use. This study examined the feasibility of applying the validated TOPICOP score for assessing TCS phobia across different countries.This was a prospective multicentre feasibility study conducted in 21 hospitals in 17 countries. Patients >3 months of age with atopic dermatitis or their parents or legal representatives completed a validated translation of the TOPICOP questionnaire in the country's native language. Respondents also completed questionnaires collecting opinions about the feasibility and acceptability of the TOPICOP questionnaire.A total of 1564 participants in 15 countries were included in the analysis. 81% of respondents considered the questions clear or very clear, and 79% reported that it took less than 5 minutes to complete. Each of the individual items in the TOPICOP questionnaire was considered to be not at all difficult to answer by 49% to 74% of participants. The mean global TOPICOP score was 44.7%±20.5. Mean TOPICOP subscores were 37.0±22.8% for knowledge and beliefs, 54.7±27.8% for fears and 50.1±29.1% for behaviours. Global scores and subscores differed between countries, although the subscores did not always vary in parallel, suggesting different levels of TCS phobia and different drivers for each country.The TOPICOP score can be feasibly applied across countries and may therefore be useful for obtaining qualitative and quantitative data from international studies and for adapting patient education and treatment.
Perceptions concerning clinical trials in oncology patients.
Authors: Dana Lee, Ju-Hsien Chao, Sandy Stevens, Goetz H. Kloecker
Journal: Journal of Clinical Oncology (2012)

e16533 Background: Accrual to clinical trials among adult cancer patients is persistently low. Patient preference plays an important role in enrollment. To identify the reasons why patients decline study participation, it is important, to evaluate the perceptions of newly diagnosed oncology patients about clinical trials. Methods: Patients were given a ten-question survey reflective of their attitudes regarding clinical trials as a treatment option at their initial visit. The self-directed questionnaire was scored on an ordinate scale from strongly agree (1) to strongly disagree (5). Results: Ninety-two new patients were surveyed in the cancer - specific multispecialty clinics in an academic cancer center. The patients expected information relating to eligible clinical trials and privacy protection by university sponsored studies as they strongly concurred with “I expect my doctor to inform me about clinical trials that I am eligible for” (mean score 2.15, p=0.001) followed by “all possible measures to protect my privacy are likely to be taken in a clinical trial that is sponsored by a university” (2.36, p=0.36). The strongest disagreement was “If enrolled in a clinical trial, I am comfortable being assigned by a method such as ‘flipping a coin’ or ‘throwing a dice’” (3.73, p=0.001) and “I would be willing to participate in a clinical trial as a first line treatment option” (3.50, p=0.001). Industry sponsored trials, phase 1 trials, second line treatment trials, privacy concerns and investigator initiated trials and time commitment and altruistic reasons did not significantly deviate from the mean preference (2.5) by a one sample T-test analysis. Conclusions: Patients consider the option of clinical trials as important in their treatment, and expect to be informed by their oncologist about clinical trials. Newly diagnosed cancer patients perceive randomization and first line trials negatively. Since randomized data provides new standards for care and hope for improved treatment, patients and their families must be educated about their importance.
P14.20 Local control an overall survival after frameless LINAC radiosurgery: a single center experience
Authors: A. C. Bilger, F. Frenzel, O. Oehlke, M. Schmucker, R. Wiehle, D. Milanovic, C. Nieder, A. Grosu
Journal: Neuro-Oncology (2017)

Introduction: Stereotactic radiosurgery (SRS) has been increasingly advocated for 1-3 small brain metastases. Goal of this study was to evaluate the clinical results in patients with brain metastases treated with SRS using a thermoplastic mask non-invasive fixation system and image-guided treatment. MATERIAL AND METHODS: In this single-institution study 48 patients with 77 brain metastases were treated between February 2012 and January 2014. The head fixation was realized using a BrainLAB thermoplastic mask. The prescribed dose was 20 Gy or 18 Gy as a single dose. The SRS were performed with a True Beam STX Novalis Radiosurgery LINAC (Varian Medical Systems). The verification of positioning was done using the BrainLAB ExacTrac ® X-ray 6D system and cone-beam CT. Results: In 69 of 77 (89.6%) treated brain metastases the follow-up was documented on MR imaging performed every 3 months. In 7/69 (10.1%) brain metastases local failure was diagnosed with a mean follow-up time of 10.7 months (range 1-43 months). Estimated 1-year local control was 83.1%. Median progression free survival (PFS) was 3.7 months, largely due to distant brain relapse. A GTV of ≤ 2.0 cm3 was significantly associated with a better PFS than a GTV > 2.0 cm3. We observed 2 cases of radiation necrosis diagnosed by histology after surgical resection. No other cases of severe side effects (CTACE≥3) were observed. CONCLUSION: In our experience local control after frameless (ringless) LINAC based SRS with mean follow-up of 10.7 months is 89.9%. Without the invasive head fixation radiotherapy is more comfortable for the patients.
PAX3–FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability
Authors: Berkley E. Gryder, Marielle E. Yohe, Hsien-Chao Chou, Xiaohu Zhang, Joana Marques, Marco Wachtel, Beat Schaefer, Nirmalya Sen, Young Song, Alberto Gualtieri, Silvia Pomella, Rossella Rota, Abigail Cleveland, Xinyu Wen, Sivasish Sindiri, Jun S. Wei, Frederic G. Barr, Sudipto Das, Thorkell Andresson, Rajarshi Guha, Madhu Lal-Nag, Marc Ferrer, Jack F. Shern, Keji Zhao, Craig J. Thomas, Javed Khan
Journal: Cancer Discovery (2017)

Abstract Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and adolescent young adults, driven primarily by the chimeric transcription factor PAX3–FOXO1. The mechanisms by which PAX3–FOXO1 dysregulates chromatin are unknown. We find PAX3–FOXO1 reprograms the cis-regulatory landscape by inducing de novo super enhancers. PAX3–FOXO1 uses super enhancers to set up autoregulatory loops in collaboration with the master transcription factors MYOG, MYOD, and MYCN. This myogenic super enhancer circuitry is consistent across cell lines and primary tumors. Cells harboring the fusion gene are selectively sensitive to small-molecule inhibition of protein targets induced by, or bound to, PAX3–FOXO1-occupied super enhancers. Furthermore, PAX3–FOXO1 recruits and requires the BET bromodomain protein BRD4 to function at super enhancers, resulting in a complete dependence on BRD4 and a significant susceptibility to BRD inhibition. These results yield insights into the epigenetic functions of PAX3–FOXO1 and reveal a specific vulnerability that can be exploited for precision therapy. Significance: PAX3–FOXO1 drives pediatric fusion-positive rhabdomyosarcoma, and its chromatin-level functions are critical to understanding its oncogenic activity. We find that PAX3–FOXO1 establishes a myoblastic super enhancer landscape and creates a profound subtype-unique dependence on BET bromodomains, the inhibition of which ablates PAX3–FOXO1 function, providing a mechanistic rationale for exploring BET inhibitors for patients bearing PAX-fusion rhabdomyosarcoma. Cancer Discov; 7(8); 884–99. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 783
Emerging therapies for breast cancer
Authors: Xichun Hu, Wei Huang, Minhao Fan
Journal: Journal of Hematology & Oncology (2017)

HER2 and CDK4/6 are undoubted two most important biological targets for breast cancer. Anti-HER2 treatments enhance objective response and progression-free survival/disease-free survival as well as overall survival. Three CDK4/6 inhibitors consistently improve objective response and progression-free survival; however, overall survival data are waited. Optimization of chemotherapy and endocrine strategies remains an unmet need. Check point inhibitor-based immunotherapy combined with chemotherapy is a promising field, especially for triple-negative breast cancer.
SURG-01. COMPLETE RESECTION IS NOT ASSOCIATED WITH IMPROVED SURVIVAL IN MGMT NON-METHYLATED GLIOBLASTOMA: RESULTS FROM THE GLARIUS TRIAL
Authors: Sied Kebir, Walter Stummer, Joachim Steinbach, Astrid Weyerbrock, Peter Hau, Roland Goldbrunner, Martin Proescholdt, Hartmut Vatter, Ulrich Herrlinger, Martin Glas
Journal: Neuro-Oncology (2017)

Although it is known that upfront complete surgical resection is associated with improved survival in glioblastoma, studies are lacking to confirm whether this holds true for the unfavorable patient population of O-6-methylguanine-DNA methyltransferase (MGMT) non-methylated glioblastoma. Here, we investigated the association of survival with the extent of resection in the GLARIUS study, a randomized phase II trial of bevacizumab/irinotecan (BEV/IRI) versus standard temozolomide (TMZ) in MGMT non-methylated glioblastoma. Patients included in the modified intention-to-treat (ITT, n=170) population were stratified by extent of resection (partial vs. complete) as determined by early (>72h) postoperative contrast-enhanced MRI. In a Kaplan-Meier analysis, we compared overall survival (OS) between the groups in each treatment arm. A Cox regression analysis was used to detect whether complete resection was of prognostic value and independent of canonical prognostic markers, including age and Karnofsky performance score (KPS). In the BEV/IRI arm, 58 patients (50%) each underwent partial (PR) and complete resection (CR). In the TMZ arm, 29 patients (55%) underwent partial and 24 (45%) complete resection. Prognostic factors, including age and KPS, were balanced between patients with PR and CR. Neither in the BEV/IRI arm (CR, median OS [mOS], 17.3 [95% CI, 15.5-21.4] versus PR, mOS, 16.5 [95% CI, 14.9-17.9]; Hazard Ratio [HR], 0.79 [95% CI, 0.53-1.20]; p=0.28) nor in the TMZ arm (CR, mOS, 18.0 [95% CI, 17.1-21.3] versus PR, mOS, 15.3 [95% CI, 10.6-21.1]; HR, 0.77 [95% CI, 0.43-1.40]; p=0.40) patients with CR derived a significant OS benefit compared to those with PR. In a multivariable Cox regression analysis, this effect did not change after accounting for canonical prognostic markers. In the GLARIUS trial, patients with complete resection derived no relevant survival benefit as compared with partially resected patients. However, the small sample size, in the TMZ arm in particular, limits our analysis.
A phase I/II study of CR011-vcMMAE, an antibody-drug conjugate, in patients (pts) with locally advanced or metastatic breast cancer (MBC)
Authors: N. Peacock, M. Saleh, J. Bendell, A. A. Rose, Z. Dong, P. M. Siegel, E. Crowley, R. Simantov, L. Vahdat
Journal: Journal of Clinical Oncology (2009)

1067 Background: Glycoprotein NMB (GPNMB), also known as osteoactivin, has been shown to regulate metastasis of breast cancer in vivo. CR011-vcMMAE, a fully-human monoclonal anti-GPNMB antibody conjugated to the tubulin inhibitor monomethylauristatin E, is safe and active in pts with advanced melanoma. This is the first study of CR011-vcMMAE in breast cancer. Methods: Eligible pts with MBC had ≥ 2 prior chemotherapy regimens, including a taxane, an anthracycline, and capecitabine; and ECOG PS ≤ 2. Doses were escalated to 1.88 mg/kg IV q3w (the maximum tolerated dose [MTD] in melanoma) using a standard 3+3 design. Immunohistochemistry (IHC) with goat polyclonal antibody to GPNMB was performed on pt biopsy specimens and on tissue microarrays containing normal breast, DCIS, breast tumor and lymph node metastases. Results: 10 pts with MBC (median age 57, range 36 - 69) had a median of 7 prior regimens and were treated with CR011-vcMMAE for a median of 2 cycles (range 1–4). In the first 2 pts at 1.34 mg/kg, dose limiting toxicity of worsening peripheral sensory neuropathy was observed. Pts with baseline neuropathy worse than grade 1 were subsequently excluded. Pts were treated at 1.0 mg/kg (n = 3), 1.34 mg/kg (n = 5), and 1.88 mg/kg (n = 2); enrollment at 1.88 mg/kg is continuing. Other adverse events (AEs) were grade 1/2 anorexia and pain in 4 pts; diarrhea, rash, fatigue, and neuropathy in 3 pts; and grade 3 rash in 1 pt. Evidence of antitumor activity has been observed. A response of 37% tumor shrinkage was seen in a pt after only 2 cycles and is ongoing. A second pt had a 51% reduction after 2 cycles, but had PD after 12 weeks. Breast tumor samples were more likely to stain positive for GPNMB than normal breast tissues. Conclusions: CR011-vcMMAE 1.34 mg/kg IV q3w is well-tolerated in heavily pretreated pts with MBC. The 1.88 mg/kg q3w dose is being assessed and phase II expansion is planned at the MTD. IHC of pt tumor specimens is being evaluated. [Table: see text]