2012 Activity Report of the Regional Research Programme on Hadrontherapy for the ETOILE Center

2012 is the penultimate year of financial support by the CPER 2007-2013 for ETOILE's research program, sustained by the PRRH at the University Claude Bernard. As with each edition we make the annual review of the research in this group, so active for over 12 years now. Over the difficulties in the decision-making process for the implementation of the ETOILE Center, towards which all our efforts are focussed, some "themes" (work packages) were strengthened, others have progressed, or have been dropped. This is the case of the eighth theme (technological developments), centered around the technology for rotative beam distribution heads (gantries) and, after being synchronized with the developments of ULICE's WP6, remained so by ceasing its activities, coinciding also with the retirement of its historic leader at IPNL, Marcel Bajard. Topic number 5 ("In silico simulations") has suffered the departure of its leader, Benjamin Ribba, although the work has still been provided by Branka Bernard, a former postdoctoral fellow in Lyon Sud, and now back home in Croatia, still in contract with UCBL for the ULICE project. Aside from these two issues (and the fact that the theme "Medico-economical simulations" is now directly linked to the first one ("Medical Project"), the rest of the teams are growing, as evidenced by the publication statistics at the beginning of this report. This is obviously due to the financial support of our always faithful regional institutions, but also to the synergy that the previous years, the European projects, the arrival of the PRIMES LabEx, and the national France Hadron infrastructure have managed to impulse. The Rhone-Alpes hadron team, which naturally includes the researchers of LPC at Clermont, should also see its influence result in a strong presence in France Hadron's regional node, which is being organized. The future of this regional research is not yet fully guaranteed, especially in the still uncertain context of ETOILE, but the tracks are beginning to emerge to allow past and present efforts translate into a long future that we all want to see established. Each of the researchers in PRRH is aware that 2013 will be (and already is) the year of great challenge : for ETOILE, for the PRRH, for hadron therapy in France, for French hadrontherapy in Europe (after the opening and beginning of treatments in the German [HIT Heidelberg, Marburg], Italian [CNAO, Pavia] and Austrian [MedAustron, Wien Neuerstadt]) centers. Let us meet again in early 2014 for a comprehensive review of the past and a perspective for the future ..

A single formula to describe radiation-induced protein relocalization Towards a mathematical definition of individual radiosensitivity

International audienceImmunofluorescence with antibodies against DNA damage repair and signaling protein is revolutionarising the estimation of the genotoxic risk. Indeed, a number of stress response proteins relocalize in nucleus as identifiable foci whose number, pattern and appearance/disappearance rate depend on several parameters such as the stress nature, dose, time and individual factor. Few authors proposed biomathematical tools to describe them in a unified formula that would be relevant for all the relocalizable proteins. Based on our two previous reports in this Journal (. Foray et al., 2005; Gastaldo et al., 2008), we considered that foci response to stress is composed of a recognition and a repair phase, both described by an inverse power function provided from a Euler's Gamma distribution. The resulting unified formula called "Bodgi's function" is able to describe appearance/disappearance kinetics of nuclear foci after any condition of genotoxic stress. By applying the Bodgi's formula to DNA damage repair data from 45 patients treated with radiotherapy, we deduced a classification of human radiosensitivity based on objective molecular criteria, notably like the number of unrepaired DNA double-strand breaks and the radiation-induced nucleo-shuttling of the ATM kinase. © 2013 Elsevier Ltd

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Postoperative Radiation Therapy in Patients with Extracranial Chondrosarcoma: A Joint Study of the French Sarcoma Group and Rare Cancer Network

Purpose: Postoperative radiation therapy (poRT) of intracranial/skull base chondrosarcomas (CHSs) is standard treatment. However, consensus is lacking for poRT in extracranial CHS (eCHS) owing to their easier resectability and intrinsic radioresistance. We assessed the practice and efficacy of poRT in eCHS. Methods and Materials: This multicentric retrospective study of the French Sarcoma Group/Rare Cancer Network included patients with eCHS who were operated on between 1985 and 2015. Inverse propensity score weighting (IPTW) was used to minimize poRT allocation biases. Results: Of 182 patients, 60.4% had bone and 39.6% had soft-tissue eCHS. eCHS were of conventional (31.9%), myxoid (28.6%; 41 extraskeletal, 11 skeletal), mesenchymal (9.9%), or other subtypes. En-bloc surgery with complete resection was performed in 52.6% and poRT in 36.8% of patients (median dose, 54 Gy). Irradiated patients had unfavorable initial characteristics, with higher grade and incomplete resection. Median follow-up time was 61 months. Five-year incidence of local relapse was 10% with poRT versus 21.6% without (P = .050). Using the IPTW method, poRT reduced the local relapse risk (hazard ratio, 0.27; 95% confidence interval, 0.14-0.52; P < .001). Five-year disease-free survival (DFS) was 71.8% with poRT and 64.2% without (P = .680). Using the IPTW method, poRT improved DFS (hazard ratio, 0.51; 95% confidence interval, 0.30-0.85; P = .010). The benefit of poRT on local relapse and DFS was confirmed after exclusion of the extraskeletal subtype. There was no difference in overall survival. Prognostic factors of poorer DFS in multivariate analysis were deeper location, higher grade, incomplete resection, and no poRT. Conclusions: poRT should be offered in patients with eCHS and high-grade or incomplete resection, regardless of the histologic subtype

Postoperative Radiation Therapy in Patients with Extracranial Chondrosarcoma: A Joint Study of the French Sarcoma Group and Rare Cancer Network.

Postoperative radiation therapy (poRT) of intracranial/skull base chondrosarcomas (CHSs) is standard treatment. However, consensus is lacking for poRT in extracranial CHS (eCHS) owing to their easier resectability and intrinsic radioresistance. We assessed the practice and efficacy of poRT in eCHS. This multicentric retrospective study of the French Sarcoma Group/Rare Cancer Network included patients with eCHS who were operated on between 1985 and 2015. Inverse propensity score weighting (IPTW) was used to minimize poRT allocation biases. Of 182 patients, 60.4% had bone and 39.6% had soft-tissue eCHS. eCHS were of conventional (31.9%), myxoid (28.6%; 41 extraskeletal, 11 skeletal), mesenchymal (9.9%), or other subtypes. En-bloc surgery with complete resection was performed in 52.6% and poRT in 36.8% of patients (median dose, 54 Gy). Irradiated patients had unfavorable initial characteristics, with higher grade and incomplete resection. Median follow-up time was 61 months. Five-year incidence of local relapse was 10% with poRT versus 21.6% without (P = .050). Using the IPTW method, poRT reduced the local relapse risk (hazard ratio, 0.27; 95% confidence interval, 0.14-0.52; P &lt; .001). Five-year disease-free survival (DFS) was 71.8% with poRT and 64.2% without (P = .680). Using the IPTW method, poRT improved DFS (hazard ratio, 0.51; 95% confidence interval, 0.30-0.85; P = .010). The benefit of poRT on local relapse and DFS was confirmed after exclusion of the extraskeletal subtype. There was no difference in overall survival. Prognostic factors of poorer DFS in multivariate analysis were deeper location, higher grade, incomplete resection, and no poRT. poRT should be offered in patients with eCHS and high-grade or incomplete resection, regardless of the histologic subtype

ANOCEF Consensus Guideline on Target Volume Delineation for Meningiomas Radiotherapy

Purpose/Objective(s)Meningiomas are the most common primary intracranial tumor. They are developed at the expense of the dura, with an overall incidence which has increased over the past decade. To date, there is no published specific guideline about meningiomas target volume. No prospective study has defined a consensus for delineation in meningiomas’ radiotherapy. Therefore, target volume definition is mainly based on retrospective studies, with a heterogeneous population of patients. The aim of this paper is to describe delineation guidelines for meningiomas’ radiotherapy as an adjuvant or definitive treatment with Intensity Modulated Radiation Therapy (IMRT) and stereotactic radiation therapy (SRT) techniques.Materials/MethodsThis guideline is based on a consensus endorsed by a global multidisciplinary group of brain tumor experts’ member of the ANOCEF (French neuro-oncology association). A two round modified Delphi consensus was achieved, and the consensus was adopted by the RAND/UCLA method. The third round was carried out in videoconference, in order to allow experts to debate and argue on remaining uncertain proposals.ResultsTwenty experts from 17 radiotherapy center participated. After 3 rounds, all the proposals resulted in a consensus. The ANOCEF guideline committee proposed to perform an unenhanced planning CT scan, merged with a post-contrast MRI obtained at the time of radiotherapy and preoperative MRI in case of adjuvant treatment. GTV is defined by T1 contrast-enhancing lesion, thickened meninges, and directly invaded bone. For IMRT, the CTV include: Grade I: No margin around the GTV. Grade II: Margin of 5mm to expand GTV in normal brain tissue, hyperostosis, along the unthickened meninges and venous sinuses if the GTV is coming into contact. Grade III: Margin of 10mm to expand GTV in normal brain tissue, hyperostosis, along the unthickened meninges, and optic or cranial nerves in contact with GTV. In case of bone invasion, a margin of 5 or 10mm in the healthy bone around the GTV is recommended, for grade II or III respectively. Otherwise, it is considered as an anatomical barrier and does not need to be included in the target volume. In case of post-operative radiotherapy, no additional margin is required for CTV for grade I around tumor bed. A 5 and 10mm margin is required for grade II and III. The cranial flap should only be included in the CTV only over 5 or 10mm for grades II or III, in case of initially invaded bone. The drill holes and osteotomy areas should be included if they come into contact with target volume. SRT is not recommended for grades II and III, excluding relapse situation. CTV corresponds to GTV without additional margin.ConclusionThe current consensus provides a detailed delineation guideline for meningioma, suggesting smaller margins than the major studies published to date