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Abstract A first generation clone-based physical map for the bovine genome was constructed combining, fluorescent double digestion fingerprinting and sequence tagged site (STS) marker screening. The BAC clones were selected from an Inra BAC library (105 984 clones) and a part of the CHORI-240 BAC library (26 500 clones). The contigs were anchored using the screening information for a total of 1303 markers (451 microsatellites, 471 genes, 127 EST, and 254 BAC ends). The final map, which consists of 6615 contigs assembled from 100 923 clones, will be a valuable tool for genomic research in ruminants, including targeted marker production, positional cloning or targeted sequencing of regions of specific interest.

Se estudió la presencia de los anticuerpos anti-AgsHB en 1 280 niños con edades entre 7 meses y 3 años, que recibieron la vacuna cubana antihepatitis B, Heberbiovac-HB al nacimiento, al mes y 6 meses de edad dentro del Programa Nacional de Inmunización en Cuba. Se determinó la presencia del AgsHB y se cuantificaron los anticuerpos en el suero mediante métodos ELISA sandwich, desarrollados y validados en el Laboratorio de Inmunología. Teniendo en cuenta el tiempo transcurrido desde el final de la vacunación, la muestra se dividió en 3 grupos: entre 7 meses y 1 año, entre 1 y 2 años, y entre 2 y 3 años. Ninguno de los niños presentó marcadores de infección y los porcentajes de seroprotección fueron 96,6 en el grupo de 7 meses a 1 año, y de 100 en los grupos de 1 a 2 y de 2 a 3 años. Los porcentajes de niños con cifras de anti-AgsHB superiores o iguales a 100 UI/L fueron de 93,1, 90,7 y 77,8, respectivamente. Las medias geométricas de anti-AgsHB fueron de 1 056, 699 y 483 UI/L para cada grupo. Se encontraron diferencias significativas en los porcentajes de seroprotección, hiperrespuesta y medias geométricas de anti-AgsHB cuando se compararon estas variables entre niños con historia de asma bronquial (687,8, 620,2, y 402,9 UI/L) y otros sin este antecedente en los 3 grupos (1 341, 1 047,8, y 528,3 UI/L); las concentraciones fueron mucho más elevadas en los no asmáticos. Estos resultados podrían indicar que aún con antígenos no alergénicos se puede inducir una respuesta a predominio Th 2 en asmáticos y que por causa de la citofilia de las inmunoglobulinas de clase E los anticuerpos no son detectados, o bien que la respuesta es de hecho menor como consecuencia del carácter de disreactor de los asmáticos. Se concluye que la inmunogenicidad de la vacuna en una población abierta es comparable a la de los estudios controlados, y que no se necesita dosis de refuerzo al menos después de transcurridos 4 años de finalizado el esquema, si se tiene en cuenta la cinética de desaparición del anti-AgsHB. Se requiere un estudio controlado en poblaciones de asmáticos, que permita verificar los resultados obtenidos y darles explicaciónThe presence of anti-AgsHB antibodies was studied in 1 280 children aged from 7 months to 3 years, who were administered the Cuban anti-hepatitis B vaccine Heberbiovac HB when they were born, at 1 and 6 months of age as part of the National Immunization Program in Cuba. AgsHB was detected and serum antibodies were determined by ELISA sandwich methods, developed and validated in the Immunology Laboratory. Considering the time elapsed from the end of the vaccination, the sample was divided into 3 groups: 7 months to 1 year, 1-2 years, and 2-3 years of age. None of the children exhibited infection markers and seroprotection percentages were 96.6 in 7months to 1 year old group, and 100% in 1-2 years-old and 2-3 years-old groups. The percentages of children with anti-HbsAg values equal to or over 100 UI/L were 93.1%, 90.7% and 77.8% respectively. The geometric means of anti-HbsAg were 1 0567, 699 and 483 UI/L respectively. Significant differences were found in seroprotection and hyperesponse percentages and in anti-HbsAg geometric means when comparing these variables between children with bronchial asthma history (687.8, 620.2 and 402.9 UI/L) and non-asthmatic children of the 3 groups(1 341, 1 047.8 and 528.3 UI/L); the concentrations were much higher in non-asthmatics. These outcomes could signal that even with non-allergenic antigens, a predominant Th2 response may be induced in asthmatic children and that wither antibodies are not detected due to IgE cytophilia or response is in fact lower as a result of the disreactor nature of the asthmatics. It is concluded that immunogenicity of the vaccine in a population is comparable to that of the controlled studies and that a reinforcement dose is not needed at least 4 years after the completion of the immunization schedule if one takes into account the kinetics of anti-HbsAg elimination. A controlled study of asthmatic populations is required to verify the achieved results with due explanations

Abstract Advances in imaging and biological targeting have led to the development of stereotactic body radiation therapy (SBRT) as an alternative treatment of extracranial oligometastases. New radiobiological concepts, such as ceramide-induced endothelial apoptosis after hypofractionated high-dose SBRT, and the identification of patients with oligometastatic disease by microRNA expression may yet lead to further developments. Key factors in SBRT are delivery of a high dose per fraction, proper patient positioning, target localisation, and management of breathing–related motion. Our review addresses the radiation doses and schedules used to treat liver, abdominal lymph node (LN) and adrenal gland oligometastases and treatment outcomes. Reported local control (LC) rates for liver and abdominal LN oligometastases are high (median 2-year actuarial LC: 61 -100% for liver oligometastases; 4-year actuarial LC: 68% in a study of abdominal LN oligometastases). Early toxicity is low-to-moderate; late adverse effects are rare. SBRT of adrenal gland oligometastases shows promising results in the case of isolated lesions. In conclusion, properly conducted SBRT procedures are a safe and effective treatment option for abdominal oligometastases.

Abstract Background Emerging evidences suggest that enteric glial cells (EGC), a major constituent of the enteric nervous system (ENS), are key regulators of intestinal epithelial barrier (IEB) functions. Indeed EGC inhibit intestinal epithelial cells (IEC) proliferation and increase IEB paracellular permeability. However, the role of EGC on other important barrier functions and the signalling pathways involved in their effects are currently unknown. To achieve this goal, we aimed at identifying the impact of EGC upon IEC transcriptome by performing microarray studies. Results EGC induced significant changes in gene expression profiling of proliferating IEC after 24 hours of co-culture. 116 genes were identified as differentially expressed (70 up-regulated and 46 down-regulated) in IEC cultured with EGC compared to IEC cultured alone. By performing functional analysis of the 116 identified genes using Ingenuity Pathway Analysis, we showed that EGC induced a significant regulation of genes favoring both cell-to-cell and cell-to-matrix adhesion as well as cell differentiation. Consistently, functional studies showed that EGC induced a significant increase in cell adhesion. EGC also regulated genes involved in cell motility towards an enhancement of cell motility. In addition, EGC profoundly modulated expression of genes involved in cell proliferation and cell survival, although no clear functional trend could be identified. Finally, important genes involved in lipid and protein metabolism of epithelial cells were shown to be differentially regulated by EGC. Conclusion This study reinforces the emerging concept that EGC have major protective effects upon the IEB. EGC have a profound impact upon IEC transcriptome and induce a shift in IEC phenotype towards increased cell adhesion and cell differentiation. This concept needs to be further validated under both physiological and pathophysiological conditions.

Abstract Background Several approaches can be used to determine the order of loci on chromosomes and hence develop maps of the genome. However, all mapping approaches are prone to errors either arising from technical deficiencies or lack of statistical support to distinguish between alternative orders of loci. The accuracy of the genome maps could be improved, in principle, if information from different sources was combined to produce integrated maps. The publicly available bovine genomic sequence assembly with 6× coverage (Btau_2.0) is based on whole genome shotgun sequence data and limited mapping data however, it is recognised that this assembly is a draft that contains errors. Correcting the sequence assembly requires extensive additional mapping information to improve the reliability of the ordering of sequence scaffolds on chromosomes. The radiation hybrid (RH) map described here has been contributed to the international sequencing project to aid this process. Results An RH map for the 30 bovine chromosomes is presented. The map was built using the Roslin 3000-rad RH panel (BovGen RH map) and contains 3966 markers including 2473 new loci in addition to 262 amplified fragment-length polymorphisms (AFLP) and 1231 markers previously published with the first generation RH map. Sequences of the mapped loci were aligned with published bovine genome maps to identify inconsistencies. In addition to differences in the order of loci, several cases were observed where the chromosomal assignment of loci differed between maps. All the chromosome maps were aligned with the current 6× bovine assembly (Btau_2.0) and 2898 loci were unambiguously located in the bovine sequence. The order of loci on the RH map for BTA 5, 7, 16, 22, 25 and 29 differed substantially from the assembled bovine sequence. From the 2898 loci unambiguously identified in the bovine sequence assembly, 131 mapped to different chromosomes in the BovGen RH map. Conclusion Alignment of the BovGen RH map with other published RH and genetic maps showed higher consistency in marker order and chromosome assignment than with the current 6× sequence assembly. This suggests that the bovine sequence assembly could be significantly improved by incorporating additional independent mapping information.

Abstract Background Comparative mapping provides new insights into the evolutionary history of genomes. In particular, recent studies in mammals have suggested a role for segmental duplication in genome evolution. In some species such as Drosophila or maize, transposable elements (TEs) have been shown to be involved in chromosomal rearrangements. In this work, we have explored the presence of interspersed repeats in regions of chromosomal rearrangements, using an updated high-resolution integrated comparative map among cattle, man and mouse. Results The bovine, human and mouse comparative autosomal map has been constructed using data from bovine genetic and physical maps and from FISH-mapping studies. We confirm most previous results but also reveal some discrepancies. A total of 211 conserved segments have been identified between cattle and man, of which 33 are new segments and 72 correspond to extended, previously known segments. The resulting map covers 91% and 90% of the human and bovine genomes, respectively. Analysis of breakpoint regions revealed a high density of species-specific interspersed repeats in the human and mouse genomes. Conclusion Analysis of the breakpoint regions has revealed specific repeat density patterns, suggesting that TEs may have played a significant role in chromosome evolution and genome plasticity. However, we cannot rule out that repeats and breakpoints accumulate independently in the few same regions where modifications are better tolerated. Likewise, we cannot ascertain whether increased TE density is the cause or the consequence of chromosome rearrangements. Nevertheless, the identification of high density repeat clusters combined with a well-documented repeat phylogeny should highlight probable breakpoints, and permit their precise dating. Combining new statistical models taking the present information into account should help reconstruct ancestral karyotypes.

Purpose: High-risk (HR) prostate cancer patients usually receive high-dose radiotherapy (RT) using a two-phase sequential technique, but data on a simultaneous integrated boost (SIB) technique are lacking. We prospectively evaluated the long-term results of urinary (GU) and digestive (GI) toxicity and survival data for high-dose RT using a SIB technique in HR and very high-risk (VHR) prostate cancer., Methods: Patients were treated using an SIB technique in 34 fractions, at a dose of 54.4 Gy to the pelvis and seminal vesicles and 74.8 Gy to the prostate, combined with 36 months of androgen-depriving therapy in a prospective multicenter study. Acute and late GU and GI toxicity data were collected. Overall survival (OS), biochemical-relapse-free survival (bRFS), loco-regional-relapse-free survival (LRRFS), metastasis-free-survival (MFS) and disease-free-survival (DFS) were assessed., Results: We recruited 114 patients. After a median follow-up of 62 months, very few patients experienced acute (M0-M3) (G3-4 GU = 3.7 %; G3-4 GI = 0.9 %) or late (M6-M60) severe toxicity (G3-4 GU = 5.6 %; G3-4 GI = 2.8 %). The occurrence of acute G2 + GU or GI toxicity was significantly related to the consequential late G2 + toxicity (p < 0.01 for both GU and GI). Medians of OS, bRFS, LRRFS, MFS and DFS were not reached. At 60 months, OS, bRFS, LRRFS, MFS and DFS were 88.2 % [82.1; 94.7], 86.0 % [79.4 %;93.2 %], 95.8 % [91.8 %;99.9 %], 87.2 % [80.9 %;94.0 %] and 84.1 % [77.2 %;91.6 %] respectively., Conclusion: SIB RT at a dose of 54.4 Gy to the pelvis and 74.8 Gy to the prostate is feasible, leading to satisfying tumor control and reasonable toxicity in HR and VHR prostate cancer., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: IM, LL, MAM, PP, NMN, PG, DP, BC, PD, NS, GN, JK, IL, CGC, SS: none. DA declares conflicts of interest with Novagray, which has nothing to do with this study., (© 2023 The Authors.)

Background: Preoperative chemoradiotherapy (CRT) is the standard treatment for T3-4 rectal cancer. Here, we compared image-guided and intensity-modulated RT (IG-IMRT) with a simultaneous integrated boost (SIB) (instead of concomitant chemotherapy) versus CRT in a multi-centric randomized trial., Methods: cT3-4 rectal cancer patients were randomly assigned to receive preoperative IG-IMRT 46 Gy/23 fractions plus capecitabine 825 mg/m² twice daily (CRT arm) or IG-IMRT 46 Gy/23 fractions with an SIB to the rectal tumor up to a total dose of 55.2 Gy (RTSIB arm)., Results: A total of 174 patients were randomly assigned between April 2010 and May 2014. Grade 3 acute toxicities were 6% and 4% in the CRT and RTSIB arms, respectively. The mean fractional change in SUVmax at 5 weeks after completion of preoperative RT were -55.8% (±24.0%) and -52.9% (±21.6%) for patients in the CRT arm and RTSIB arm, respectively ( p = 0.43). The pathologic complete response rate was 24% with CRT compared to 14% with RTSIB. There were no differences in 5-year overall survival (OS), progression-free survival (PFS) or local control (LC)., Conclusions: The preoperative RTSIB approach was not inferior to CRT in terms of metabolic response, toxicity, OS, PFS and LC, and could be considered an available option for patients unfit for fluorouracil-based CRT.

Purpose: A second intensification is an option at first relapse in multiple myeloma (MM) after more than 36 months of initial remission. Many conditioning regimens have been tested, with or without total body irradiation (TBI). Recently, it was found that TBI could be replaced by total marrow irradiation (TMI) using helical tomotherapy, with promising results., Methods and Materials: This study was a prospective multicenter phase 1 trial that aimed to determine the maximum tolerated dose (MTD) of TMI administered in association with melphalan 140 mg/m², followed by autologous stem cell transplantation as consolidation at first relapse in MM. Four dose levels were explored: 8 Gy, 10 Gy, 12 Gy, and 14 Gy. The dose-limiting toxicity (DLT) was defined as grade 4 neutropenia >15 days, grade 4 thrombopenia >28 days, and all other grade 4 nonhematologic toxic effects except nausea, vomiting, alopecia, mucositis, and reaction to autologous stem cell infusion., Results: Thirteen patients were included; only 1 DLT at the third escalated dose level (12 Gy) was observed, whereas 1 patient was treated at 14 Gy with no adverse events. The MTD was not reached. The rate of acute toxicity was low: 38% of grade 3-4 diarrhea, mucositis, or unexplained fever. Regarding the lungs, the mean dose administered was systematically less than 8 Gy. After a median follow-up of 55 months, 70% of participants were alive. Of these 13 patients, 38.5% were in very good partial response and 30.8% were in complete response. Three of them were progression-free. Six patients were long survivors, still alive after 55 months of follow-up., Conclusions: Total marrow irradiation provides good results with a good tolerance profile at first relapse in MM and makes it possible to increase the dose delivered to the planning target volume while sparing organs at risk. This technique could be discussed for all regimens before auto- or allo-stem cell rescue when TBI is required., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: The Radiation Induced Sarcoma (RIS) is a rare but serious adverse event following radiotherapy (RT). Current RT techniques are more precise, but irradiate a larger volume at a low dose. This study aimed to describe radiation characteristics in a large series of patients suffering from RIS., Materials and Methods: Patient-representative voxel-based anthropomorphic phantoms were used to reconstruct patient-specific RT fields for 125 patients diagnosed with RIS after primary breast cancer. For each patient, the location of the RIS onset site was determined and transferred onto the phantom as a contour. Using a treatment planning system (TPS), the dose distribution on the RIS in the phantom was calculated., Results: The mean dose (Dmean) received in the area where RIS subsequently developed was 47.8 ± 11.6 Gy. The median dose in the zones where RIS later developed ranged from 11 Gy to 58.8 Gy. The median time from RT to RIS development was 8 years (range 2-32 years). Analysis for predictors of time to radiation-induced sarcoma development highlighted a significant impact of age of patient during the RT whereas in multivariable analysis chemotherapy and hormonotherapy for primary breast cancer were not associated with a significant difference in time to diagnosis of RIS., Conclusions: This study highlights that the dose received by the tissue in which the RIS developed was almost 47 Gy. These results are encouraging for the use of new RT techniques increasing volumes receiving low doses, without fear of an excess of RIS over the next 10 years., Competing Interests: Declaration of interests CGFL (Centre Georges François Leclerc, Dijon, FRANCE) received an unrestricted educational grant (PHRC 2011) to cover the expenses of the investigators for undertaking this trial. All authors declared no conflict of interests related to this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Radiotherapy for Hodgkin lymphomas has evolved a lot over time, but still plays an important role, almost always in addition to chemotherapy, for the management of the early stages. The major objective is to preserve the quality of life of patients who will be cured from this disease in the vast majority of cases. Also, the personalization of the indications for the purpose of de-escalating toxicity is very refined and is essentially based on the pre- and pertherapeutic assessment by FDG-PET. The indications for radiotherapy are more limited for non-Hodgkin lymphomas, but the same principles are found, regardless of the histological type. We present the update of the recommendations of the French society of oncological radiotherapy for radiotherapy of lymphomas, which remains a very evolving field in terms of therapeutic strategy and evaluation., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The purpose of this article is to describe the external irradiation process and updated recommendations of the French society for radiation oncology for patient follow-up., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

The purpose of the first two editions of the guidelines for external radiotherapy procedures, published in 2007 and 2016 respectively, was to issue recommendations aimed at optimising, harmonising and standardising practices. The purpose of this third edition, which includes brachytherapy, is identical while also taking into account recent technological improvements (intensity modulation radiation therapy, stereotactic radiotherapy, and three-dimension brachytherapy) along with findings from literature. Part one describes the daily use of general principles (quality, security, image-guided radiation therapy); part two describes each treatment step for the main types of cancer., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Intensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation., Material and Methods: We used data from the "RCMI pelvis" prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting., Results: The mean total cost for HT, €2019 3,069 (95% CI, 2,885-3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443-2,651) (p <.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment., Conclusion: Use of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis., Competing Interests: DA declares conflict of interest with Novagray, which has nothing to do with this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Masson, Bellanger, Perrocheau, Mahé, Azria, Pommier, Mesgouez-Nebout, Giraud, Peiffert, Chauvet, Dudouet, Salem, Noël, Khalifa, Latorzeff, Guérin-Charbonnel and Supiot.)

Purpose: The aim of this study is to correlate locoregional relapse with radiation therapy volumes in patients with rectal cancer treated with neoadjuvant chemoradiation in the ACCORD 12/0405-PRODIGE 02 trial., Patients and Methods: We identified patients who had a locoregional relapse included in ACCORD 12's database. We studied their clinical, radiological, and dosimetric data to analyze the dose received by the area of relapse., Results: 39 patients (6.5%) presented 54 locoregional relapses. Most of the relapses were in-field (n = 21, 39%) or marginal (n = 13, 24%) with only six out-of-field (11%), 14 could not be evaluated. Most of them happened in the anastomosis, the perirectal space, and the usual lymphatic drainage areas (presacral and posterior lateral lymph nodes). Only patients treated for a lower rectum adenocarcinoma had a relapse outside of the treated volume. 2 patients with T4 tumors extending into anterior pelvic organs had relapses in anterior lateral and external iliac lymph nodes., Conclusions: Lowering the upper limit of the treatment field for low rectal tumors increased the risk of out of the field recurrence. For very low tumors, including the inguinal lymph nodes in the treated volume should be considered. Recording locoregional involvement, treated volumes, and relapse areas in future prospective trials would be of paramount interest to refine delineation guidelines., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background : Stereotactic body radiotherapy (SBRT) is a recognized treatment for colorectal cancer (CRC) metastases. We postulated that local responses could be improved by SBRT with a concomitant radiosensitizing agent (irinotecan). Methods : RADIOSTEREO-CAMPTO was a prospective multi-center phase 2 trial investigating SBRT (40-48 Gy in 4 fractions) for liver and/or lung inoperable CRC oligometastases (≤3), combined with two weekly intravenous infusions of 40 mg/m 2 Irinotecan. Primary outcome was the objective local response rate as per RECIST. Secondary outcomes were early and late toxicities, EORTC QLQ-C30 quality of life, local control and overall survival. Results : Forty-four patients with 51 lesions (liver = 39, lungs = 12) were included. Median age was 69 years (46-84); 37 patients (84%) had received at least two prior chemotherapy treatments. Median follow-up was 48.9 months. One patient with two lung lesions was lost during follow-up. Assuming maximum bias hypothesis, the objective local response rate in ITT was 86.3% (44/51-95% CI: [76.8-95.7]) or 82.4% (42/51-95% CI: [71.9-92.8]). The observed local response rate was 85.7% (42/49-95% CI: [75.9-95.5]). The 1 and 2-year local (distant) progression-free survivals were 84.2% (38.4%) and 67.4% (21.3%), respectively. The 1 and 2-year overall survivals were 97.5% and 75.5%. There were no severe acute or late reactions. The EORTC questionnaire scores did not significantly worsen during or after treatment. Conclusions : SBRT with irinotecan was well tolerated with promising results despite heavily pretreated patients.

Objectives: This prospective, observational, non-randomized multicentric study was conducted to compare efficiency and toxicity using different modalities of stereotactic body radiation therapy (SBRT) in early-stage peripheral non-small cell lung cancer (NSCLC)., Methods: From 9 April to 11 December, 106 patients were treated according to the local equipment availability for peripheral NSCLC with SBRT: 68 by linear accelerator equipped for SBRT and 38 by Cyberknife ® . Multivariate analysis and propensity score analysis using Inverse Probability Treatment Weighting (IPTW) were undertaken in an effort to adjust for potential bias due to non-randomization., Results: 2-year local control rates were 97.0% (95% CI: [90.6%; 99.4%]) with SBRT by Linac vs 100% (95% CI: ([100%; 100%]) with Cyberknife ® ( p = 0.2839). 2-year PFS and 2-year OS rates were 52.7% (95% CI [39.9%;64.0%]) versus 54.1% (95% CI [36.8; 68.6%]) ( p = 0.8582) and 65.1% (95% CI: [51.9%; 75.5%] versus 83.9% (95% CI: [67.5%; 92.4%] ( p = 0.0831) using Linac and Cyberknife ® respectively. Multivariate regression analysis indicates no significant effect of SBRT treatment type on PFS or OS. Local relapse could not be modeled due to the small number of events ( n = 2). Acute and late toxicity rates were not significantly different. After IPTW adjustment, results were unchanged., Conclusions: No difference in efficiency or toxicity was shown after SBRT of peripheral NSCLC treatment using Linac or Cyberknife ® ., Advances in Knowledge: This is the first large prospective non-randomized study focusing on peripheral localized NSCLC comparing SBRT using an appropriately equipped linac with Cyberknife ® . No significant difference in efficiency or toxicity was shown in this situation.

The aim of this retrospective multicentric study was to develop and evaluate a prognostic 18 F-FDG PET/CT radiomic signature in early-stage non-small cell lung cancer patients treated with stereotactic body radiotherapy (SBRT). Methods: Patients from 3 different centers ( n = 27, 29, and 8) were pooled to constitute the training set, whereas the patients from a fourth center ( n = 23) were used as the testing set. The primary endpoint was local control. The primary tumor was semiautomatically delineated in the PET images using the fuzzy locally adaptive Bayesian algorithm, and manually in the low-dose CT images. In total, 184 Image Biomarkers Standardization Initiative-compliant radiomic features were extracted. Seven clinical and treatment parameters were included. We used ComBat to harmonize radiomic features extracted from the 4 institutions relying on different PET/CT scanners. In the training set, variables found significant in the univariate analysis were fed into a multivariate regression model, and models were built by combining independent prognostic factors. Results: Median follow-up was 21.1 mo (range, 1.7-63.4 mo) and 25.5 mo (range, 7.7-57.8 mo) in training and testing sets, respectively. In univariate analysis, none of the clinical variables, 2 PET features, and 2 CT features were significantly predictive of local control. The best predictive models in the training set were obtained by combining one feature from PET (Information Correlation 2) and one feature from CT (flatness), reaching a sensitivity of 100% and a specificity of 96%. Another model combining 2 PET features (Information Correlation 2 and strength) reached sensitivity of 100% and specificity of 88%, both with an undefined hazard ratio ( P < 0.001). The latter model obtained an accuracy of 0.91 (sensitivity, 100%; specificity, 81%), with a hazard ratio undefined ( P = 0.023) in the testing set; however, other models relying on CT radiomic features only or the combination of PET and CT features failed to validate in the testing set. Conclusion: We showed that 2 radiomic features derived from 18 F-FDG PET were independently associated with local control in patients with non-small cell lung cancer undergoing SBRT and could be combined in an accurate predictive model. This model could provide local relapse-related information and could be helpful in clinical decision making., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Among over 100 proton therapy centres worldwide in operation or under construction, French proton therapy is coming to full maturity with the recent opening of the Nice (1991, upgrade in 2016) and Caen (2018) facilities next to the Orsay (1991, upgrade in 2010) centre. Proton therapy is a national priority for children and young adults in all three centres. The patient-related activity of the three French centres is coordinated via the Protonshare portal to optimise referral by type of indication and available expertise in coordination with the French society of radiation oncology SFRO and French radiotherapy centres. The centres are recognised by the French Health Care excellence initiative, promoted by the ministry of Foreign Affairs. The three centres collaborate structurally in terms of clinical research and are engaged at the international level in the participation to European databases and research initiatives. Concerted actions are now also promoted in preclinical research via the Radiotransnet network. Ongoing French developments in proton therapy are well presented in international hadron therapy meetings, including European Proton Therapy Network and Particle Therapy Cooperative Oncology Group. Proton therapy teaching in France is offered at several levels and is open to colleagues from all radiation oncology centres, so that they are fully informed, involved and trained to facility recognition of possible indications and thereby to contribute to appropriate patient referral. This close collaboration between all actors in French radiation oncology facilitates the work to demonstrate the required level of medical and scientific evidence for current and emerging indications for particle therapy. Based on that, the future might entail a possible creation of more proton therapy facilities in France., (Copyright © 2019. Published by Elsevier Masson SAS.)

Purpose: Radiation-induced sarcoma (RIS) is a rare but serious event. Its occurrence has been discussed during the implementation of new radiation techniques and justified appropriate radioprotection requirements. New approaches targeting intrinsic radio-sensitivity have been described, such as radiation-induced CD8 T-lymphocyte apoptosis (RILA) able to predict late radio-induced toxicities. We studied the role of RILA as a predisposing factor for RIS as a late adverse event following radiation therapy (RT)., Patients and Methods: In this prospective biological study, a total of 120 patients diagnosed with RIS were matched with 240 control patients with cancer other than sarcoma, for age, sex, primary tumor location and delay after radiation. RILA was prospectively assessed from blood samples using flow cytometry., Results: Three hundred and forty-seven patients were analyzed (118 RIS patients and 229 matched control patients). A majority (74%) were initially treated by RT for breast cancer. The mean RT dose was comparable with a similar mean (± standard deviation) for RIS (53.7 ± 16.0 Gy) and control patients (57.1 ± 15.1 Gy) (p = .053). Median RILA values were significantly lower in RIS than in control patients with respectively 18.5% [5.5-55.7] and 22.3% [3.8-52.2] (p = .0008). Thus, patients with a RILA >21.3% are less likely to develop RIS (p < .0001, OR: 0.358, 95%CI [0.221-0.599]., Conclusion: RILA is a promising indicator to predict an individual risk of developing RIS. Our results should be followed up and compared with molecular and genomic testing in order to better identify patients at risk. A dedicated strategy could be developed to define and inform high-risk patients who require a specific approach for primary tumor treatment and long term follow-up., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Intensity-modulated radiation therapy (IMRT) is currently indicated to treat anal squamous cell carcinoma (ASCC). Conformal dose delivery and steep dose gradients may cause marginal misses. We analyzed patterns of locoregional recurrences (LRR) and delineation quality to determine IMRT-specific predictive factors., Material and Methods: Lymph node area delineation was classified as "compliant" or "non-compliant" according to experts' workgroup recommendations. The recurrence volume (V recur ) was delineated on initial planning-CT by recurrence imaging registration. The V recur was determined to be "in-field" (IF), "marginal" (ML), or "out-of-field" (OF) in regard to the 95% isodose coverage., Results: Out of 165 patients, 30 had LRR. Among the 27 local recurrences (LR), 20 (74%) were IF, 4 (15%) ML, and 2 (7%) OF. Fourteen patients had regional recurrence (RR), amounted to 33 separate recurrence sites (RS). RS were mostly localized in inguinal (n = 12;36,4%), external iliac (n = 7;21.1%), presacral (n = 4;12.1%) and common iliac (n = 3;9.1%) nodes. Eighteen (54.5%) RS were IF, 6 (18.2%) ML, and 9 (27.3%) OF. Performance status ≥2 (p = 0.007) and active smoking (p = 0.025) were predictors of LR. Immunodepression (p = 0.012), external iliac involvement (p < 0.001), and non-compliant delineation for ≥10 areas (p = 0.005) were predictors of RR., Conclusions: New predictive factors for recurrences of ASSC treated with IMRT have been found, suggesting that the delineation accuracy is essential for regional control., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Cancer caregivers are at high risk of burn-out, with potential severe consequences on professionals' health and on patients' care. We have investigated the prevalence of burn-out and its impact in terms of psychological morbidity among French radiation oncologists., Methods and Materials: An anonymous online questionnaire was advertised in all French senior radiation oncologists and residents, including demographical data, job-related stress factors, drug use, the Maslach Burn-out Inventory (MBI) and the General Health Questionnaire (GHQ-12)., Results: The response rates were 37% (76 out of 204) for radiation oncologists and 22% (166 out of 751) for residents. Sixty-four (84%) radiation oncology residents and 104 (63%) radiation oncologists met criteria for moderate/severe burn-out (odd ratio 2.1 [95% confidence interval 1.0-4.8], P=0.03). Radiation oncology residents were more prone to depersonalization (P<0.001) and lower personal accomplishment (P<0.001). Burn-out was more frequent in radiation oncologists working for public facilities. Symptoms of depression (GHQ-12≥4) were reported by 42% of residents and 36% of radiation oncologists (P=0.40). Psychological morbidity, suicidal ideation and anxiolytic consumption were more frequent in burnt out responders., Conclusion: Our figures are in the highest range of published data. Active screening and prevention of burn-out should be implemented and particularly aimed at radiation oncology residents., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: In 2008, the French national society of radiation oncology (SFRO) and the association for radiation oncology continued education (AFCOR) created Siriade, an e-learning website dedicated to contouring., Material and Methods: Between 2015 and 2017, this platform was updated using the latest digital online tools available. Two main sections were needed: a theoretical part and another section of online workshops., Results: Teaching courses are available as online commented videos, available on demand. The practical section of the website is an online contouring workshop that automatically generates a report quantifying the quality of the user's delineation compared with the experts'., Conclusion: Siriade 2.0 is an innovating digital tool for radiation oncology initial and continuous education., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objective: The purpose of this study was to determine the characteristics of early second breast cancer (SBC) among survivors of childhood and young adult malignancy treated with irradiation., Methods: We conducted a multicenter retrospective study of women who presented with breast cancer aged 50 years or younger in nine French centers., Results: 121 patients and 141 SBC were analyzed (invasive = 130; non-invasive = 11). The mean age at first cancer diagnosis was 15 years and at initial SBC diagnosis was 38 years. Bilateral disease before the age of 51 years was diagnosed in 16% of the females. The majority of SBC were invasive carcinomas (92%). Among the invasive carcinomas, 39% had a histoprognostic score of III, 3.1% overexpressed HER2 and 29% were triple negative. The proportion of triple negative phenotype SBC was higher in patients older at first cancer diagnosis [RR = 1.2, 95% CI (1.1-1.3)]. 94% of triple negative SBCs developed in breast tissue which had received >20 Gy., Conclusion: We found a high proportion of aggressive SBC following thoracic radiotherapy in childhood or early adulthood. Advances in knowledge: SBC screening is recommended by scientific societies for these child/young-adulthood cancer survivors in the same way as the one for high risk women because of constitutional mutations. Our results support these recommendations, not only because of a similar cumulative risk, but also because of the aggressive histological characteristics.

Chemo- and radiotherapy are treatments very helpful to cure cancers but are also well known for adverse effects such as secondary cancers. Breast cancers following Hodgkin lymphoma have been relatively well studied. Breast cancers after radiotherapy covering or nearby breasts or nipples are usually carcinomas or secondary sarcomas. Among the big cohort of patients treated for breast carcinomas, breast lymphomas developed in the same area are not usual. Nevertheless, published studies described a significant increased risk of non-Hodgkin lymphoma after initial radiotherapy for a solid cancer. Here, we report a case of a secondary breast lymphoma observed in a 53-year-old woman treated 13 years before for a ductal carcinoma and analyse such second tumors with a review of the literature. This case report emphasizes the importance of the biopsy in case of recurrence in breast cancer to give the appropriate treatment., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To determine the patterns of locoregional failure (LRF) in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy (RT)., Patients and Methods: One hundred and fifty-four patients from the Gating 2006 prospective randomized trial were treated with conformal RT with or without respiratory motion management. For patients with a LRF as first event, treatment planning with simulation CT, pre-treatment 18 FDG PET-CT and post-treatment images demonstrating recurrence were registered and analyzed. Measurable LRF was contoured (rGTV) and classified as in-field, marginal, or out-of-field., Results: Median follow-up was 27.8 months. Forty-eight patients presented with LRF. One-year and 2-year locoregional disease-free survival rates were 77% (95% CI 70-83) and 72% (95% CI 64-79) respectively. 79% of the patients with LRF as first event relapsed within the RT field (55% isolated), 30% had marginal LRF component. Isolated out-of-field failure occurred in only 3% of all patients. The regions of highest FDG-uptake on pre-treatment PET-CT were located within the recurrence in 91% of patients with in-field LRF., Conclusion: In-field failure was the most common pattern of failure. Escalated dose RT with high-dose fractions guided by PET parameters warrants further investigation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Stereotactic body radiation therapy for primary and metastatic hepatic malignancies can be performed in association and/or as an alternative to surgery and radiofrequency. The consequences of the great number of techniques available are heterogeneity in contouring, dose prescription and in determination of dose constraints for organs at risk. The objective of this paper is to improve the quality and safety and to help the diffusion of this technique for a majority of patients. In 2016, the French Society of Radiation Oncology (SFRO) published guidelines for external radiotherapy and brachytherapy ("Recorad"). This paper is an update of these recommendations considering recent publications., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: Irradiation (>3Gy) to the breast or axillae before 30years of age increases the risk of secondary breast cancer (SBC). The purpose of this article is to describe the clinical characteristics of SBC and the way of diagnosis in young women (before the age of national screening) in France who had received previous radiotherapy for a childhood or a young adulthood cancer., Patients and Methods: This retrospective, multicentre study reviewed the medical records of women with SBC before the age of the national screening who had received irradiation (≥3Gy) on part or all of the breast before 30years of age, for any type of tumour except BC., Results: A total of 121 SBC were detected in 104 women with previous radiotherapy. Twenty percent of SBC were detected during regular breast screening and 16% of the women had a regular radiological follow-up., Conclusion: Our results points out that the main proportion of childhood cancer survivors did not benefit from the recommended breast cancer screening. This result is comparable to other previously published studies in other countries. A national screening programme is necessary and should take into account the patient's age, family history, personal medical history and previous radiotherapy to reduce the number of SBC diagnosed at an advanced stage., (Copyright © 2017. Published by Elsevier B.V.)

See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant 18 F-misonidazole ( 18 F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The 18 F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In 18 F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-β = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were 18 F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the 18 F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the 18 F-FMISO-negative patients ( P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the 18 F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. 18 F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Survival of childhood, adolescent and young adult (CAYA) cancers has increased with progress in the management of the treatments and has reached more than 80% at 5 years. Nevertheless, these survivors are at great risk of second cancers and non-malignant co-morbidities in later life. DeNaCaPST is a non-interventional study whose aim is to organize a national screening for thyroid cancer and breast cancer in survivors of CAYA cancers. It will study the compliance with international recommendations, with the aim, regarding a breast screening programme, of offering for every woman living in France, at equal risk, an equal screening., Method: DeNaCaPST trial is coordinated by the INSERM 1018 unit in cooperation with the LEA (French Childhood Cancer Survivor Study for Leukaemia) study's coordinators, the long term follow up committee and the paediatric radiation committee of the SFCE (French Society of Childhood Cancers). A total of 35 centres spread across metropolitan France and la Reunion will participate. FCCSS (French Childhood Cancer Survivor Study), LEA and central registry will be interrogated to identify eligible patients. To participate, centers agreed to perform a complete "long-term follow-up consultations" according to good clinical practice and the guidelines of the SFCE (French Society of Children Cancers)., Discussion: As survival has greatly improved in childhood cancers, detection of therapy-related malignancies has become a priority even if new radiation techniques will lead to better protection for organs at risk. International guidelines have been put in place because of the evidence for increased lifetime risk of breast and thyroid cancer. DeNaCaPST is based on these international recommendations but it is important to recognize that they are based on expert consensus opinion and are supported by neither nonrandomized observational studies nor prospective randomized trials in this specific population. Over-diagnosis is a phenomenon inherent in any screening program and therefore such programs must be evaluated.

Purpose: Bilateral pulmonary radiotherapy in children and young adults aims to reduce the recurrence of lung metastases. The radiation field includes liver tissue, which is sensitive to even low radiation doses. We investigated the feasibility of respiratory gating radiotherapy using voluntary deep inspiration breath hold and its toxicity in these patients., Patients and Method: A retrospective clinical review was conducted for all patients who had undergone bilateral pulmonary radiotherapy, with or without deep inspiration breath hold, treated in our institution between October 1999 and May 2012. A dosimetric study was conducted on seven consecutive children using 4D-scan data on free-breathing and a SpiroDyn'RX-system-scan on deep inspiration breath hold. A radiation treatment of 20Gy was simulated., Results: Concerning the clinical study, seven patients of mean age 11.9 years (range: 4.9-21.1 years) were treated with free-breathing and ten patients of mean age 15.6 years (range: 8.6-19.7 years) were treated with deep inspiration breath hold for mainly Ewing sarcoma and nephroblastoma. Within six months of radiotherapy, all patients experienced mild liver toxicity (grade 1 or 2 altered levels of alanine/aspartate aminotransferase [n=8 of 9] or cholestasis [n=1 of 9]), which resolved completely with no difference between deep inspiration breath hold and free-breathing technique. Over a median follow-up of 2.6 years (range: 0.1-9.3 years), four patients died from disease progression (mean 1.5 years post-radiotherapy [range: 1.1-1.6 years]) and three experienced grade III-V lung toxicity. Concerning the dosimetric study, the irradiated liver volume was significantly lower with deep inspiration breath hold than free-breathing, for each isodose (V5: 73.80% versus 86.74%, P<0.05; V20: 5.70% versus 26.44%, P<0.05)., Conclusions: The dosimetric data of respiratory-gated bilateral pulmonary radiotherapy showed a significantly spare of normal liver tissue. Clinical data showed that this technique is feasible even in young children. However, no liver toxicity difference between deep inspiration breath hold and free-breathing was shown., (Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To evaluate the efficacy and toxicity of helical tomotherapy (HT) in the management of spine chordomas when proton therapy is unavailable or non-feasible., Methods and Materials: Between 2007 and 2013, 30 patients with biopsy-proven chordomas were treated by HT in five French institutions. Information regarding local control (LC), overall survival (OS), progression-free survival (PFS) and metastasis-free survival (MFS) was collected. Clinical efficacy, toxicity and treatment quality were evaluated., Results: Two-year actuarial LC, OS, PFS and MFS were 69.9%, 96.7%, 61.2% and 76.4%, respectively. HT treatments were well tolerated and no Grade 4-5 toxicities were observed. HT permitted the delivery of a mean dose of 68 Gy while respecting organ at risk (OAR) dose constraints, in particular in the spinal cord and cauda equina., Conclusions: This multicentric, retrospective study demonstrated the feasibility of HT in the treatment of spine chordomas, in the absence of hadron therapy.

Purpose: This study aimed to analyse the positioning protocols with the ExacTrac ® system, associated with a dedicated linear accelerator such as Novalis ® , for stereotactic treatment of brain metastases in several French centres., Materials and Methods: A survey, including three questions about the prescription of irradiation and twenty-one questions about how the ExacTrac ® system is used, was sent to nine French centres owning a dedicated Novalis ® accelerator. Five centres have accepted to participate in the study., Results: All centres checked the positioning before each treatment's bow, with residual mismatch tolerances of 0.5 to 0.7mm for the translations and 0.5 to 1° for the rotations. All centres except one also realised orthogonal planar images of classic incidences to help operators ensure proper isocentre positioning. Prescribed doses were 20Gy in one fraction, 30Gy and 33Gy in three fractions or 34Gy in four fractions, mainly depending on the size of the lesion. Finally, a physician validated the images at the treatment station before starting the irradiation., Conclusions: The practices of the different centres concerning the positioning protocols were rather homogeneous, in agreement with the literature data on ExacTrac ® system's accuracy, as well as proposed fractionations. The systematic medical validation at the treatment station may, however, be questioned because of the waiting time between the doctor's call and validation itself and because of its usefulness; indeed, corrections by the radiation oncologist are very rare and in some centres, non-existent., (Copyright © 2016. Published by Elsevier SAS.)

Purpose: To evaluate toxicity and early disease outcome among patients treated for cervical cancer with extended-field helical tomotherapy to the para-aortic nodes., Patients and Methods: Thirty-eight patients (International Federation of Gynecology and Obstetrics [FIGO] stage IB2-IVA) from four institutions received extended-field helical tomotherapy and were retrospectively evaluated. All had nodal disease. Para-aortic lymph nodes were involved in 31 patients. Patients were assessed for toxicity using version 4 of the National Cancer Institute's common terminology criteria for adverse events. Survival curves were plotted using Kaplan-Meier estimates., Results: All patients underwent radiation to the tumor region (median dose: 45Gy; range: 44-66Gy), pelvic lymph nodes and para-aortic lymph nodes (median dose: 45Gy; range: 44-60Gy). The median dose to positive lymph nodes was 55Gy (range: 45-65Gy). All received platinum-based chemotherapy (31 concurrently). The median follow-up was 15months. Acute toxicity events observed included one patient with grade 5 febrile neutropenia, 11 patients (29%) with grade 3 hematologic complications. Grades 3-4 gastrointestinal and genitourinary toxicities occurred in six (16%) and four (11%) patients, respectively. Three patients had grade 3 pelvic pain (8%). The 6- and 18-month overall survival rates were 94.7 and 63.9%, respectively. The 18-month locoregional control, disease-free survival, and late grade 3 toxicity rates were 60.2, 43.3 and 7.3%, respectively., Conclusion: Extended-field helical tomotherapy was associated with low rates of acute gastrointestinal and genitourinary toxicities with early survival and locoregional control similar to other published series., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy., Patients and Methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis (NCT01219790). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival., Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences)., Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: Late abdominal irradiation toxicity during childhood included renal damage, hepatic toxicity and secondary diabetes mellitus. We compared the potential of conformal radiotherapy (CRT), helical tomotherapy (HT) and proton beam therapy (PBT) to spare the abdominal organs at risk (pancreas, kidneys and liver- OAR) in children undergoing abdominal irradiation., Methods: We selected children with abdominal tumors who received more than 10 Gy to the abdomen. Treatment plans were calculated in order to keep the dose to abdominal OAR as low as possible while maintaining the same planned target volume (PTV) coverage. Dosimetric values were compared using the Wilcoxon signed-rank test., Results: The dose distribution of 20 clinical cases with a median age of 8 years (range 1-14) were calculated with different doses to the PTV: 5 medulloblastomas (36 Gy), 3 left-sided and 2 right-sided nephroblastomas (14.4 Gy to the tumor + 10.8 Gy boost to para-aortic lymphnodes), 1 left-sided and 4 right-sided or midline neuroblastomas (21 Gy) and 5 Hodgkin lymphomas (19.8 Gy to the para-aortic lymphnodes and spleen). HT significantly reduced the mean dose to the whole pancreas (WP), the pancreatic tail (PT) and to the ipsilateral kidney compared to CRT. PBT reduced the mean dose to the WP and PT compared to both CRT and HT especially in midline and right-sided tumors. PBT decreased the mean dose to the ispilateral kidney but also to the contralateral kidney and the liver compared to CRT. Low dose to normal tissue was similar or increased with HT whereas integral dose and the volume of normal tissue receiving at least 5 and 10 Gy were reduced with PBT compared to CRT and HT., Conclusion: In children undergoing abdominal irradiation therapy, proton beam therapy reduces the dose to abdominal OAR while sparing normal tissue by limiting low dose irradiation., Competing Interests: The authors have declared that no competing interests exist.

There are very few data on the expansion from the clinical target volume (CTV) to the planning target volume (PTV) in the anal cancer treatment. This article aims to collect the different elements needed for the construction of a PTV from scientific data based on a literature analysis. We reviewed the articles published in the medical literature from the last 20years. They concerned setup errors and internal organ mobility of the different volumes of patients treated by conformational radiotherapy and intensity-modulated radiotherapy (anal canal, meso-rectum, common, intern and extern, inguinal and pre-sacral lymph nodes). CTV to PTV margins admitted in the guidelines and atlas of consensus groups (SFRO, RTOG, AGITG) are from 0.7 to 1cm in all directions, based on expert's opinions but not on scientific data. There are no specific studies on the canal anal mobility. Most of the data are from other pelvis cancers (gynecologic, rectum and prostate). Setup errors can be reduced by daily imaging. Patient repositioning and immobilization modalities are mostly local habits rather than scientific consensus. A three-dimensional 1cm margin is generally admitted. Margins reduction must be careful and has to be assessed., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)