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Purpose: To develop a tumor growth inhibition model for adult diffuse low-grade gliomas (LGG) able to describe tumor size evolution in patients treated with chemotherapy or radiotherapy.Experimental Design: Using longitudinal mean tumor diameter (MTD) data from 21 patients treated with first-line procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine (PCV) chemotherapy, we formulated a model consisting of a system of differential equations, incorporating tumor-specific and treatment-related parameters that reflect the response of proliferative and quiescent tumor tissue to treatment. The model was then applied to the analysis of longitudinal tumor size data in 24 patients treated with first-line temozolomide (TMZ) chemotherapy and in 25 patients treated with first-line radiotherapy.Results: The model successfully described the MTD dynamics of LGG before, during, and after PCV chemotherapy. Using the same model structure, we were also able to successfully describe the MTD dynamics in LGG patients treated with TMZ chemotherapy or radiotherapy. Tumor-specific parameters were found to be consistent across the three treatment modalities. The model is robust to sensitivity analysis, and preliminary results suggest that it can predict treatment response on the basis of pretreatment tumor size data.Conclusions: Using MTD data, we propose a tumor growth inhibition model able to describe LGG tumor size evolution in patients treated with chemotherapy or radiotherapy. In the future, this model might be used to predict treatment efficacy in LGG patients and could constitute a rational tool to conceive more effective chemotherapy schedules. Clin Cancer Res; 18(18); 5071–80. ©2012 AACR.

PDF file, 258K, Figure S 1: Stepwise procedure applied to build the model structure (left panel); non-specific and specific evaluation criteria for model selection (right panel). Figure S 2: Results of the sensitivity analysis for the model on the 21 patients treated with PCV. The analysis consists of repeating the estimations, leaving out one patient's data at a time. Parameter estimates are represented with histograms indicating the number of patients (y-axis) for each value of the parameter (x-axis). It appears that no single patient substantially influenced the estimation. Figure S 3: Comparison of parameter estimates in the 21 patients treated with PCV when the variability of KDE is fixed to 0 or fixed to 70%. Figure S 4: Comparison of parameter estimates between the PCV dataset (n = 21) and the pooled dataset (n = 40, comprising patients from the PCV and radiotherapy datasets). The probability density functions calculated using the standard errors on the estimates are represented in continuous and dashed lines for the PCV and pooled datasets, respectively. They show that with the exception of two treatment-specific parameters (the efficacy parameter γ and the transfer rate from Qp to P, ), the parameters are homogeneous. Figure S 5: MTD observations (symbols) and individual predictions (solid line) for six individuals sampled from the PCV dataset. Included is the 90% confidence interval around the individual predictions obtained by simulations using the standard errors of the empirical Bayes estimates.

Hartmut P.H. Neumann is supported by grants from the Deutsche Krebshilfe (Grant 107995 to H.P.H.N.). Stephane Richard is supported by grants from the Direction Generale de l’Organisation des Soins (French Department of Health), the Institut National du Cancer (INCa; French NCI), and the Ligue Nationale contre le Cancer (Comites du Cher et de l’Indre; French League against Cancer).

Background. Endolymphatic sac tumors (ELSTs) are, with a prevalence of up to 16%, a component of von Hippel-Lindau (VHL) disease. Data from international registries regarding heritable fraction and characteristics, germline VHL mutation frequency, and prevalence are lacking. Methods. Systematic registration of ELSTs from international centers of otorhinolaryngology and from multidisciplinary VHL centers' registries was performed. Molecular genetic analyses of the VHL gene were offered to all patients. Results. Our population-based registry comprised 93 patients with ELST and 1789 patients with VHL. The prevalence of VHL germline mutations in apparently sporadic ELSTs was 39%. The prevalence of ELSTs in patients with VHL was 3.6%. ELST was the initial manifestation in 32% of patients with VHL-ELST. Conclusion. Prevalence of ELST in VHL disease is much lower compared to the literature. VHL-associated ELSTs can be the first presentation of the syndrome and mimic sporadic tumors, thus emphasizing the need of molecular testing in all presentations of ELST. (C) 2015 Wiley Periodicals, Inc.

Purpose: To develop a tumor growth inhibition model for adult diffuse low-grade gliomas (LGG) able to describe tumor size evolution in patients treated with chemotherapy or radiotherapy. Experimental Design: Using longitudinal mean tumor diameter (MTD) data from 21 patients treated with first-line procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine (PCV) chemotherapy, we formulated a model consisting of a system of differential equations, incorporating tumor-specific and treatment-related parameters that reflect the response of proliferative and quiescent tumor tissue to treatment. The model was then applied to the analysis of longitudinal tumor size data in 24 patients treated with first-line temozolomide (TMZ) chemotherapy and in 25 patients treated with first-line radiotherapy. Results: The model successfully described the MTD dynamics of LGG before, during, and after PCV chemotherapy. Using the same model structure, we were also able to successfully describe the MTD dynamics in LGG patients treated with TMZ chemotherapy or radiotherapy. Tumor-specific parameters were found to be consistent across the three treatment modalities. The model is robust to sensitivity analysis, and preliminary results suggest that it can predict treatment response on the basis of pretreatment tumor size data. Conclusions: Using MTD data, we propose a tumor growth inhibition model able to describe LGG tumor size evolution in patients treated with chemotherapy or radiotherapy. In the future, this model might be used to predict treatment efficacy in LGG patients and could constitute a rational tool to conceive more effective chemotherapy schedules. Clin Cancer Res; 18(18); 5071–80. ©2012 AACR.

Resume Introduction La chirurgie oncologique n’est pas une specialite en elle-meme en France, mais une sur-specialisation a laquelle certains jeunes chirurgiens decident de se former, notamment via le DESC de cancerologie de type II. Leurs motivations et formation sont actuellement mal decrites. Materiel et methode Nous avons realise une enquete en ligne specifique, adressee aux 102 etudiants inscrits au DESC de cancerologie option II – traitement chirurgical des tumeurs. Resultats Le taux de reponses etait de 60 %. La population comprenait 61 % d’hommes, d’âge median 31 ans, en majorite internes (33 %). La majorite d’entre eux ont choisi leur specialite en debut d’internat, leur sur-specialisation a mi-parcours, apres une rencontre avec un chirurgien titulaire. Concernant leur formation, 85 % ont beneficie de videos chirurgicales, 62 % de simulateurs mecaniques, 60 % d’enseignement sur l’animal et 38 % de dissections sur cadavres. Concernant leurs aspirations, 62 % voudraient travailler dans un centre anticancereux, 51 % dans un hopital universitaire et 26 % dans le prive. Un interet pour la recherche et pour l’enseignement etait note respectivement chez 51 % et 65 % des personnes interrogees. Conclusion Cette etude revele le role important du compagnonnage dans l’orientation vers la chirurgie oncologique et le manque de formations pratiques en dehors du bloc operatoire.

Forestier's disease, also known as diffuse idiopathic skeletal hyperostosis (DISH), is a pathology of vertebral bodies characterised by exuberant osteophytis formation. Forestier's disease is usually managed conservatively. Surgical resection of the osteophytes is reported to be an effective treatment for severe cases and/ or cases with airway obstruction. We report a 55-year-old man presenting with 6 months' progressive dysphagia and dysphonia. He was managed successfully with an anterior cervical osteophytectomy without fusion. A literature review is included.

In France, surgical oncology is not recognized as a unique specialty, but as a sub-specialization offered to surgeons in training. To date, their motives and training have not been studied.We set a dedicated online survey suggested to 102 surgeons applying for the specific national degree in surgical oncology.The answer rate was 60%. Responders were constituted of a majority of male (61%), their median age was 31 years. They were mainly residents (33%) and fellows working in university (25%) or non-university (28%) hospitals. Most responders have chosen their organ specialization at the beginning, and their oncologic sub-specialization at the middle of their residency, after a meeting with a senior surgeon. Regarding practical education, 85% used surgical videos, 62% mechanical training devices, 60% animal surgery, and 38% cadaver dissection. Regarding career expectations, 67% would like to work in a cancer centre, 51% in a university hospital, and 26% in a private institution. To explain these choices, 51% referred to research and 65% to teaching interests.This study outlines the role of mentorship and the lack of practical teaching outside the operating room during the training in surgical oncology in France.

Purpose The molecular pathogenesis of pediatric ependymoma remains unclear. Our study was designed to identify genetic changes implicated in ependymoma progression. Patients and Methods We characterized 59 ependymoma samples (33 at diagnosis and 26 at relapse) using array-comparative genomic hybridization (aCGH). Specific chromosomal imbalances were confirmed by fluorescent in situ hybridization, and candidate genes were assessed by real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry, sequencing, and in vitro functional studies. Results aCGH analysis revealed a significant increase in genomic imbalances on relapse compared with diagnosis, such as gain of 9qter and 1q (54% v 21% and 12% v 0%, respectively) and loss of 6q (27% v 6%). Supervised tumor classification showed that gain of 9qter was associated with tumor recurrence, age older than 3 years, and posterior fossa location. Using a candidate-gene strategy, we found an overexpression of two potential oncogenes at the locus 9qter: Tenascin-C and Notch1. Moreover, Notch pathway analysis (qPCR) revealed overexpression of Notch ligands, receptors, and target genes (Hes-1, Hey2, and c-Myc), and downregulation of Notch repressor Fbxw7. We confirmed by immunohistochemistry the overexpression of Tenascin-C and Hes-1. We detected Notch1 missense mutations in 8.3% of the tumors (only in the posterior fossa location and in case of 9q33-34 gain). Furthermore, inhibition of Notch pathway with a γ-secretase inhibitor impaired the growth of ependymoma stem cell cultures. Conclusion The activation of the Notch pathway and Tenascin-C seem to be important events in ependymoma progression and may represent future targets for therapy. We report, to our knowledge for the first time, recurrent oncogenic mutations in pediatric posterior fossa ependymomas.