Combined treatment of adenoid cystic carcinoma with cetuximab and IMRT plus C12 heavy ion boost: ACCEPT [ACC, Erbitux® and particle therapy]

<p>Abstract</p> <p>Background</p> <p>Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent leading to the establishment of particle therapy in this indication. However, even modern techniques leave space for improvement of local control by intensification of local treatment. Radiation sensitization by exploitation of high EGFR-expression in ACC with the EGFR receptor antibody cetuximab seems promising.</p> <p>Methods/design</p> <p>The ACCEPT trial is a prospective, mono-centric, phase I/II trial evaluating toxicity (primary endpoint: acute and late effects) and efficacy (secondary endpoint: local control, distant control, disease-free survival, overall survival) of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 49 patients with histologically proven (≥R1-resected, inoperable or Pn+) ACC. Patients receive 18 GyE carbon ions (6 fractions) and 54 Gy IMRT (2.0 Gy/fraction) in combination with weekly cetuximab throughout radiotherapy.</p> <p>Discussion</p> <p>The primary objective of ACCEPT is to evaluate toxicity and feasibility of cetuximab and particle therapy in adenoid cystic carcinoma.</p> <p>Trial Registration</p> <p>Clinical Trial Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01192087">NCT 01192087</a></p> <p>EudraCT number: 2010 - 022425 - 15</p

RadioImmunotherapy for adenoid cystic carcinoma: a single-institution series of combined treatment with cetuximab

<p>Abstract</p> <p>Background</p> <p>Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent. However, some clinical situations do not allow application of tumouricidal doses (i.e. re-irradiation) hence radiation sensitization by exploitation of high endothelial growth factor receptor (EGFR)-expression in ACC seems beneficial. This is a single-institution experience of combined radioimmunotherapy (RIT) with the EGFR-inhibitor cetuximab.</p> <p>Methods</p> <p>Between 2006 and 2010, 9 pts received RIT for advanced/recurrent ACC, 5/9 pts as re-irradiation. Baseline characteristics as well as treatment parameters were retrieved to evaluate efficacy and toxicity of the combination regimen were evaluated. Control rates (local/distant) and overall survival were calculated using Kaplan-Meier estimation.</p> <p>Results</p> <p>Median dose was 65 Gy, pts received a median of 6 cycles cetuximab. RIT was tolerated well with only one °III mucositis/dysphagia. Overall response/remission rates were high (77,8%); 2-year estimate of local control was 80% hence reaching local control levels comparable to high-dose RT. Progression-free survival (PFS) at 2 years and median overall survival were only 62,5% and 22,2 mo respectively.</p> <p>Conclusion</p> <p>While local control and treatment response in RIT seems promising, PFS and overall survival are still hampered by distant failure. The potential benefit of RIT with cetuximab warrants exploration in a prospective controlled clinical trial.</p

Toward improvement of knowledge of financial conflicts of interest in a large medical school in France.

IntroductionConflict of interests (COIs) adversely affect the integrity of science and public health. The role of medical schools in the teaching and management of COIs has been highlighted by the publication of an annual evaluation of American medical schools based on their COIs policies by the American Medical Student Association (AMSA). A deontological charter was adopted by French medical schools in 2018 but its impact on COI comprehension by students and its effects on COI prevention were not evaluated.MethodsA 10-item direct survey was conducted among about 1000 students in Paris-Cité University in order to investigate the respect of the charter regarding COIs both in the medical school and in affiliated teaching hospitals.ResultsCumulative results show a satisfying respect of prevention policies regarding COIs in the medical school and hospitals despite the fact that the existence of the charter and its major aspects were insufficiently known. Disclosure of COIs by teachers was insufficient.ConclusionThis first direct study among students shows better results than expected according to current non-academic surveys. Moreover, this study demonstrates the feasibility of this kind of survey whose repetition should be an appropriate tool to improve the implementation of the charter within medical schools and teaching hospitals, in particular mandatory disclosure of COIs by teachers

Radiomic Phenotypes for Improving Early Prediction of Survival in Stage III Non-Small Cell Lung Cancer Adenocarcinoma after Chemoradiation

We evaluate radiomic phenotypes derived from CT scans as early predictors of overall survival (OS) after chemoradiation in stage III primary lung adenocarcinoma. We retrospectively analyzed 110 thoracic CT scans acquired between April 2012−October 2018. Patients received a median radiation dose of 66.6 Gy at 1.8 Gy/fraction delivered with proton (55.5%) and photon (44.5%) beam treatment, as well as concurrent chemotherapy (89%) with carboplatin-based (55.5%) and cisplatin-based (36.4%) doublets. A total of 56 death events were recorded. Using manual tumor segmentations, 107 radiomic features were extracted. Feature harmonization using ComBat was performed to mitigate image heterogeneity due to the presence or lack of intravenous contrast material and variability in CT scanner vendors. A binary radiomic phenotype to predict OS was derived through the unsupervised hierarchical clustering of the first principal components explaining 85% of the variance of the radiomic features. C-scores and likelihood ratio tests (LRT) were used to compare the performance of a baseline Cox model based on ECOG status and age, with a model integrating the radiomic phenotype with such clinical predictors. The model integrating the radiomic phenotype (C-score = 0.69, 95% CI = (0.62, 0.77)) significantly improved (p0.005) upon the baseline model (C-score = 0.65, CI = (0.57, 0.73)). Our results suggest that harmonized radiomic phenotypes can significantly improve OS prediction in stage III NSCLC after chemoradiation

18F-FDG-PET/CT in the quantification of photon radiation therapy-induced vasculitis

Radiation therapy (RT) is an important component of care for head and neck cancers (HNC). Photon RT vasculitis is a complication of incidental dose delivery to nearby vascular structures. However, optimal methods for early diagnosis are not clearly established. The aim of this study was to evaluate 18F-FDG-PET/CT in detecting radiation-induced vasculitis of the left common carotid (LCC) and the arch of the aorta (AoA) in patients treated for HNC. 18F-FDG-PET/CT scans obtained before RT (Pre-RT) and 3 months after RT (Post-RT) were retrospectively reviewed in 30 HNC patients (25 males, 5 females; average age 57.9±8.1 years) treated with photon RT. All subjects underwent 18F-FDG-PET/CT imaging 60 minutes after 5.0 MBq/kg 18F-FDG injection. Average standard uptake values (Avg SUVmean) of the LCC and AoA were obtained by global assessment. A two-tailed paired t-test was used to assess the difference in Avg SUVmean between pre- and post-RT imaging. Subjects demonstrated significant increased Avg SUVmean within the LCC post-RT (pre = 1.42, post = 1.65, P<0.001), with a mean increase of 0.23 SUV. Similarly, subjects exhibited higher 18F-FDG uptake in the AoA post-RT (pre = 1.44, post = 1.69, P<0.01), with a mean increase of 0.23 SUV. 18F-FDG-PET/CT may be used to detect and quantify photon RT vasculitis in HNC patients. Further investigation is warranted to evaluate the clinical implications of this pathology and the role for alternative treatment strategies in minimizing tissue toxicity

Implementation of FDG-PET/CT imaging methodology for quantification of inflammatory response in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (

Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development

What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice , and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor in regulating RGC fate, and further describe a newly identified, Sox4-regulated site for post-translational modification with small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11's nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system. These data define novel regulatory mechanisms for this SoxC molecular network, and suggest pro-RGC molecular approaches for cell replacement-based therapies for glaucoma and other optic neuropathies. Glaucoma is the most common cause of blindness worldwide and, along with other optic neuropathies, is characterized by loss of retinal ganglion cells (RGCs). Unfortunately, vision and RGC loss are irreversible, and lead to bilateral blindness in ∼14% of all diagnosed patients. Differentiated and transplanted RGC-like cells derived from stem cells have the potential to replace neurons that have already been lost and thereby to restore visual function. These data uncover new mechanisms of retinal progenitor cell (RPC)-to-RGC and human stem cell-to-RGC fate specification, and take a significant step toward understanding neuronal and retinal development and ultimately cell-transplant therapy

The influence of age, anthropometrics and range of motion on the morphometry of the synovial folds of the lateral atlanto-axial joints: a pilot study

The purpose of this study was to investigate the effect of age, anthropometrics and cervical range of motion upon synovial fold volume. Ten healthy female subjects aged 20-40 years were included in the study. Age, height, body mass, dimensions of the head and neck and cervical range of motion of each subject were measured. Magnetic resonance (MR) images of the cervical spine were acquired; the volume of the ventral and dorsal synovial folds of the right and the left lateral atlanto-axial joints was measured using seed growing and thresholding methods. Using Spearman's correlation coefficient, it was determined that there was no correlation between synovial fold volume and age. Synovial fold volume was positively correlated with subject height and neck length but negatively correlated with body mass, body mass index and the circumference of the head and neck. The relationship between synovial fold volume and range of cervical motion varied with the plane of movement. The ability to image the synovial folds of the lateral atlanto-axial joints using MR imaging to determine their normal morphology provides the basis for investigating synovial fold pathology in patients with neck pain and headache