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Does oligometastatic breast cancer (OMBC) deserve a dedicated treatment? Although some authors recommend multidisciplinary management of OMBC with a curative intent, there is no evidence proving this strategy beneficial in the absence of a randomized trial. The existing literature sheds little light on OMBC. Incidence is unknown; data available are either obsolete or biased; there is no consensus on the definition of OMBC and metastatic sites, nor on necessary imaging techniques. However, certain proposals merit consideration. Knowledge of eventual specific OMBC biological characteristics is limited to circulating tumor cell (CTC) counts. Given the data available for other cancers, studies on microRNAs (miRNAs), circulating tumor DNA (ctDNA) and genomic alterations should be developed Finally, safe and effective therapies do exist, but results of randomized trials will not be available for many years. Prospective observational cohort studies need to be implemented., Highlights • The incidence of oligometastatic breast cancer is unknown. • Only one publication provides information regarding the biology of these cancers. • Oligometastatic breast cancer and metastatic site definitions should be harmonized. • Prospective observational cohort studies are needed.

Purpose The optimal dose in esophageal cancer patients treated with definitive chemoradiation (CRT) remains debated. We herein report on the dosimetric results, treatment-related toxicities and long-term outcomes of escalated dose up to 60 Gy delivered with intensity-modulated radiotherapy (IMRT). Materials and methods All consecutive patients that received a definitive CRT > 50 Gy for an unresectable esophageal carcinoma between 2010 and 2015 were retrospectively evaluated for this study. Methodology included data base search, delayed toxicity grading, statistical testing including frequency analysis and survival analysis. Results A total of 51 patients were irradiated for a squamous cell carcinoma (86.3%) or an adenocarcinoma (13.7%). The median age at diagnosis was 62 years. Seven patients were simultaneously irradiated for another synchronous primary tumor. Forty-six patients (90.2%) received concurrent platin-based chemotherapy. The median prescribed doses were 60 Gy (54–66) and 48 Gy (44.8–56) delivered in 30 (27–35) fractions to the high and the low risks PTV respectively. The mean dose delivered to the lungs was 11.4 Gy (IC 95%: 4.8–19.8), the median volumes receiving up to 20 Gy (V20) and 30 Gy (V30) were 13.5% (3.0–46.0) and 4.6% (0.7–19.8) respectively. The mean dose delivered to the heart was 13.9 Gy (IC 95%:0.3–31.3) with a median V40 of 3.3% (0.0–25.0). One treatment-related death occurred within days after RT completion (neutropenic aplasia). After a median follow-up of 2.7 years (95% CI: 1.9–4.3), the 2-year overall survival, disease free survival and loco-regional control rates were 53.6%, 42.0% and 72.8% respectively. Delayed treatment related-toxicities ≤ grade 3 occurred among 25 patients (62.5%) mostly esophageal stricture (79.2%). Conclusion We demonstrated in this study that dose escalation using IMRT in combination with platin-based chemotherapy as a definitive treatment for esophageal carcinoma is safe and results in higher loco-regional and control survival when compared to previously reported data.

Background: Currently, clinico-pathological characteristics (CPC) such as tumor size, lymph node status, tumor grade, proliferation, lympho-vascular invasion and percentage of cells expressing estrogen (ER) and progesterone receptors (PR) are usually considered in order to guide decisions on adjuvant systemic therapy for women with early-stage breast cancer (EBC). The indication of adjuvant chemotherapy (ACT) or not is relatively easy in women with ER+/HER2- EBC with either poor or very good CPC. However, this decision is much more difficult in those with intermediate CPC (essentially defined by grade II tumor with low PR expression and/or intermediate proliferation). The PAM50-based Prosigna risk of recurrence (ROR) is one of the multigene assays that have been evaluated and recommended for guiding treatment decision. We report here our experience on the impact of ROR in treatment decision-making in women with intermediate CPC. Patients and methods: Between March 2016 and May 2019, ROR was performed in 200 consecutive women with intermediate CPC ER+/HER2- EBC. The clinical decision (ACT or not) was prospectively recorded before and after ROR assessment and finally after the consultation with each patient. Data were summarized by frequency and percentage for categorical variables and by median and range for continuous variables. Associations between variables will be assessed using Chi-square or Fisher’s exact test for qualitative variables and the Mann-Whitney for continuous variables. All reported p-values were two-sided. For all statistical tests, differences were considered significant at the 5% level. Statistical analysis was performed using STATA v13 software. Results: Median age at diagnostic was 57 years [30-79] and 119 (59.5%) were post-menopausal. Median tumor size was 18mm [8-70mm]. Most tumors were PR+ (n=153, 76.5%), no special type (NST) carcinomas (n=172, 86%), Elston and Ellis grade II (n=183, 91.5%), with Ki67 value between 10 and 20 % (n=117, 62.6%). Lympho vascular invasion was observed in 38 tumors (19%), 124 patients were pN0 (62%), 20 pNmi (10%) and 55 pN1a (27.5%). Using the immunohistochemical (IHC)-based definition proposed by Prat et al. (JCO 2013), 90 tumors were luminal A (45%) and 110 luminal B (55%). There was 59.5% of concordance between IHC subtype classification and PAM50. ROR distribution was as follows: ROR-low (n=33; 16.5%); ROR-intermediate (n=75; 37.5%); and ROR-high (n=92; 46%). The clinical decision of modalities of adjuvant medical therapy switched after ROR assessment for 74 patients (37%): -26 patients from ACT plus endocrine therapy (ET) to ET only (13%); 9 and 17 have respectively a ROR-low or -intermediate and 23 a luminal A tumor according to PAM50, -48 patients from ET only to ACT plus ET (24%); 7 and 41 have respectively a ROR-intermediate or high and 44 a luminal B tumor. Importantly, 8 of them don’t received ACT at the issue of the consultation with the medical oncologist. Conclusion: In our experience, the use of ROR leads us more often to escalate than de-escalate adjuvant therapy, proving that the definition of the group with intermediate prognosis remains uncertain and variable according medical teams. Citation Format: Vincent Nicolaï, Julia Gilhodes, Jean Louis Lacaze, Mony Ung, Eleonora De Maio, Raphaelle Duprez-Paumier, Charlotte Vaysse, Thomas Filleron, Eva Jouve, Gabrielles Selmes, Camille Franchet, Carole Massabeau, Cyprian Chira, Francoise Izar, Henri Roché, Anne Pradines, Florence Dalenc. Value of PAM50 risk of recurrence score in patients with HR positive HER2 negative early breast cancer and intermediate risk: A single cancer center institution prospective observational study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-18-06.

Intra-operative radiotherapy for breast cancer has been developed throughout the last two decades. It is already well-established regarding local control and toxicity for intra-operative radiotherapy using electrons as we now have the necessary background knowledge. However, very few data on later toxicity are available for intra-operative radiotherapy using low-energy photons. We report here the case of a 36-year-old woman who experienced rib fracture following intra-operative and external radiotherapy. This patient has been included in the Targit-boost trial. The intra-operative irradiation has been operated with an INTRABEAM device delivering low-energy photons of 50-kV.

Patients with hepatocellular carcinoma who are on liver transplant waiting list usually require local treatment to limit any risk of tumour growth. Historically percutaneous radiofrequency ablation or transarterial chemoembolization represented the major therapeutic alternatives. Depending on the size, or the topography of the lesion these two techniques may not be feasible. Radiation therapy under stereotactic conditions has recently emerged in the management of localized hepatocellular carcinoma as an alternative to the focused therapies performed to date. We herein report the case of a 43-year-old patient harbouring a complete histological response on explant after liver stereotactic irradiation and discuss its role in the management of hepatocellular carcinoma before liver transplantation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. © 2020, The Author(s).

Resume L’optimisation de la radiotherapie dans la prise en charge d’un lymphome de Hodgkin localise pose la question de l’interet d’utilisation des techniques modernes. Le choix de la technique d’irradiation doit tenir compte de l’incidence des effets secondaires en relation avec le rayonnement. Les recommandations internationales sur les champs de traitement reposent sur le concept « involved node radiotherapy ». La meilleure technique d’irradiation a utiliser reste a definir. L’utilisation de la radiotherapie avec modulation d’intensite permet d’ameliorer la couverture et de diminuer la dose aux organes a risque, avec un gain variable en fonction de la topographie des ganglions : mediastin superieur ou inferieur, lateralisation droite ou gauche, les techniques utilisees. L’inspiration bloquee entraine une augmentation du volume pulmonaire, un allongement du mediastin avec un abaissement du cœur ce qui peut permettre d’eloigner le volume cible previsionnel des structures cardiaques. L’arctherapie volumetrique modulee (volumetric-modulated arc radiotherapy, VMAT) avec plusieurs arcs anterieurs peut etre particulierement interessante pour reduire la dose aux seins, de meme la tomotherapie lors d’atteintes etendues. La protontherapie, compte tenu de la specificite de pic de Bragg, peut jouer un role cle dans la limitation des doses delivrees aux organes a risque, sous reserve d’une planification robuste qui va prendre en compte les incertitudes geometriques et physiques. L’heterogeneite de presentation clinique des lymphomes de Hodgkin concernant le volume, la forme et la localisation initiale sont les elements cles a prendre un compte dans le choix de la technique de radiotherapie a privilegier.

Purpose Helical TomoTherapy® allows precise and homogeneous tumour coverage and excellent sparing of organs at risk. We present here our treatment technique, dosimetric results, and our first clinical data for patients receiving total body irradiation as part of the conditioning regimen before hematopoietic stem cell transplantation. Patients and methods The cohort consisted of 11 patients who were treated in our institution between August 2014 and January 2016. The total dose was 12 Gy in six fractions in three days. We collected the dose distribution information in the treatment volumes, organs at risk and area of junction. We report retrospectively the clinical events during the first 6 months after the procedure. Results Median age was 31 years (range, 18–57 years). Median D98% was 11.5 Gy (range: 6.6–11.9 Gy). The median of the mean doses to the lungs was 8.7 Gy (range: 8.5–9.3 Gy). The mean dose for the junction area was 12 Gy (range: 11.9–12.1 Gy). All patients had the total procedure, and all underwent successful engraftment. During the first six months, nine patients had at least one grade 3 or 4 toxicity that was due essentially to graft versus host disease. No patient had radiation pneumonitis. The toxicities were both more frequent and of higher grade during the first three months. Conclusion Total body irradiation using helical TomoTherapy® is feasible. It allows a very good homogeneity of dose and conformity with an acceptable tolerance. It could deliver higher doses to sites at high risk of recurrence (bone marrow, sanctuary sites), while sparing major normal organs like lungs, liver, and kidneys. This reduction of dose could lead to reduced severity and frequency of late complications.

Radiotherapy's main skin toxicities are now well-separated, acute (acute radiation dermatitis) or chronic complications (chronic radiation dermatitis, induced cutaneous carcinoma, aesthetic sequelae). Exceptionally, radiotherapy may induce, by isomorphic reaction or Koebner's phenomenon, some specific dermatosis. In this article, we report five new observations of these unusual complications of radiation therapy, occurring in very variable time after breast irradiation and remaining strictly localized in the irradiated field (cutaneous mastocytosis, Sweet syndrome, lichen planus, vitiligo). These cases emphasize the need to realize a systematic histological exam if any atypical skin lesion appears after radiotherapy, even long after.

Resume Objectif de l’etude La tomotherapie permet d’ameliorer la distribution de dose pour les volumes de forme complexe et de grande taille. L’objectif de l’etude etait d’evaluer la toxicite aigue de cette technique apres chirurgie mammaire conservatrice ou mastectomie. Patientes et methodes La toxicite cutanee, pulmonaire et œsophagienne, ainsi que le lymphœdeme mammaire ont ete recueillis retrospectivement selon la Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) chez 292 patientes prises en charge par tomotherapie pour un cancer du sein entre mai 2010 et decembre 2014. Apres traitement conservateur, les doses delivrees au volume mammaire et au lit tumoral etaient respectivement de 52,2 Gy et de 63,8 Gy en 29 fractions. Apres mastectomie, la dose etait de 50 Gy en 25 fractions. Des analyses uni- et multifactorielles ont ete realisees pour rechercher les facteurs de risque de radiodermite et d’œdeme mammaire. Resultats Les taux de radiodermite de grade 2 et 3 etaient respectivement de 22,9 % et 1,7 %. En analyse unifactorielle, les facteurs associes a la radiodermite aigue etaient le volume mammaire (p = 0,002), l’indice de masse corporelle (IMC) (p Conclusion La tomotherapie des cancers du sein est bien toleree et permet de diminuer les fortes doses d’irradiation recues par les organes a risque.

Intra-operative radiotherapy for breast cancer has been developed throughout the last two decades. It is already well-established regarding local control and toxicity for intra-operative radiotherapy using electrons as we now have the necessary background knowledge. However, very few data on later toxicity are available for intra-operative radiotherapy using low-energy photons. We report here the case of a 36-year-old woman who experienced rib fracture following intra-operative and external radiotherapy. This patient has been included in the Targit-boost trial. The intra-operative irradiation has been operated with an INTRABEAM device delivering low-energy photons of 50-kV.

Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma (n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation. Furthermore, previous anti-CTLA4 ICB exposure was associated with different predictors of response compared to tumors that were naive to ICB, suggesting selective immune effects of previous exposure to anti-CTLA4 ICB. Finally, we developed parsimonious models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 ICB in individual tumors, with validation in smaller independent cohorts limited by the availability of comprehensive data. Broadly, we present a framework to discover predictive features and build models of ICB therapeutic response. © 2019, The Author(s).

Patients with hepatocellular carcinoma who are on liver transplant waiting list usually require local treatment to limit any risk of tumour growth. Historically percutaneous radiofrequency ablation or transarterial chemoembolization represented the major therapeutic alternatives. Depending on the size, or the topography of the lesion these two techniques may not be feasible. Radiation therapy under stereotactic conditions has recently emerged in the management of localized hepatocellular carcinoma as an alternative to the focused therapies performed to date. We herein report the case of a 43-year-old patient harbouring a complete histological response on explant after liver stereotactic irradiation and discuss its role in the management of hepatocellular carcinoma before liver transplantation.

Aim To investigate the feasibility of dose escalation using rapid arc (RA) and Helical Tomotherapy (HT) for patients with upper, middle and distal esophageal carcinomas, even for large tumor volumes. Background In esophageal cancer, for patients with exclusive radio-chemotherapy, local disease control remains poor. Planning study with dose escalation was done for two sophisticated modulated radiotherapy techniques: Rapid arc against Tomotherapy. Materials and methods Six patients treated with a RA simultaneous integrated boost (SIB) of 60 Gy were re-planned for RA and HT techniques with a SIB dose escalated to 70 Gy. Dose volume histogram statistics, conformity indices and homogeneity indices were analyzed. For a given set of normal tissue constraints, the capability of each treatment modality to increase the GTV dose to 70 Gy was investigated. Results Either HT or VMAT may be used to escalate the dose delivered in esophageal tumors while maintaining the spinal cord, lung and heart doses within tolerance. Adequate target coverage was achieved by both techniques. Typically, HT achieved better lung sparing and PTV coverage than did RA. Conclusions Dose escalation for esophageal cancer becomes clinically feasible with the use of RA and HT. This promising result could be explored in a carefully controlled clinical study which considered normal tissue complications and tumor control as endpoints.

Helical TomoTherapyThe cohort consisted of 11 patients who were treated in our institution between August 2014 and January 2016. The total dose was 12Gy in six fractions in three days. We collected the dose distribution information in the treatment volumes, organs at risk and area of junction. We report retrospectively the clinical events during the first 6 months after the procedure.Median age was 31 years (range, 18-57 years). Median D98% was 11.5Gy (range: 6.6-11.9Gy). The median of the mean doses to the lungs was 8.7Gy (range: 8.5-9.3Gy). The mean dose for the junction area was 12Gy (range: 11.9-12.1Gy). All patients had the total procedure, and all underwent successful engraftment. During the first six months, nine patients had at least one grade 3 or 4 toxicity that was due essentially to graft versus host disease. No patient had radiation pneumonitis. The toxicities were both more frequent and of higher grade during the first three months.Total body irradiation using helical TomoTherapy

Purpose Recent improvements in the detection of breast cancer at an early stage have resulted in a rising incidence of breast ductal carcinoma in situ with microinvasion. So far, there is no consensus regarding its optimal management. We hereby report on our 10-year single institutional experience in breast ductal carcinoma in situ with microinvasion including pathological reviewing.

Introduction et but de l’etude La radiotherapie en conditions stereotaxiques s’est recemment developpee dans la prise en charge des tumeurs hepatiques primitives localisees, carcinome hepatocellulaire ou cholangiocarcinome, en alternative aux autres therapies focales. L’objectif de ce travail etait l’evaluation du controle local, de la survie sans progression, de la survie globale ainsi que de la toxicite de la radiotherapie en conditions stereotaxiques des tumeurs hepatiques primitives. Materiel et methodes Tous les patients pris en charge par radiotherapie en conditions stereotaxiques entre avril 2015 et septembre 2018 dans notre centre pour un carcinome hepatocellulaire ou un cholangiocarcinome ont ete inclus dans cette etude. La radiotherapie etait delivree en arctherapie dynamique avec asservissement respiratoire sur un accelerateur TrueBeam Novalis STX. Le controle local etait evalue selon les Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (relecture centralisee), la toxicite selon les Common Terminology Criteria for Adverse Effects. L’analyse de la survie a ete realisee avec la methode de Kaplan-Meier. Resultats et analyse statistique Parmi les 55 patients traites, 49 avaient un carcinome hepatocellulaire et six un cholangiocarcinome. La taille mediane des lesions etait de 35 mm (extremes : 13-115 mm). La dose mediane prescrite dans le volume cible previsionnel etait de 50 Gy (extremes : 30–55 Gy) en trois ou cinq fractions. La dose equivalente biologique (BED10, avec un rapport α/β de 10 Gy) mediane etait de 100 Gy (extremes : 48–151 Gy). Apres un suivi median de 15 mois, le taux de controle local a 1 an etait de 81 % (intervalle de confiance a 95 % [IC 95 %] : 64–90 %). Les taux de survie sans progression et de survie globale a 1 an etaient respectivement de 49 % (extremes : 34–62 %) et 83 % (extremes : 69–91 %). Le diametre de la lesion inferieur a 5 cm et une BED10 superieure ou egale a 100 Gy etaient associes a une meilleure probabilite de survie sans progression. Quatre patients (7 %) ont souffert d’une toxicite tardive de grade 3–4. Conclusion Nos resultats sont concordants avec les donnees publiees de la litterature, confirmant que la radiotherapie en conditions stereotaxiques est une technique efficace et bien toleree. Des donnees prospectives sont necessaires afin de preciser sa place dans la strategie therapeutique en association ou comme alternative aux autres traitements locaux.

In this paper we propose a method to solve the inverse kinematic of a 3 DOF parallel manipulator, best know as Stewart platform. Using the entities of the rotors and motors it is possible define an algorithm to find the joint values of each actuator that allow to reach the desired position and orientation of the manipulator, describing only one geometric solution for one arm of the platform and applying a rigig transformation to this solution in order to define the solution for the rest of the arms of the robot. Simulations and real time implementation of the algorithm were done to prove the effectiveness of the proposal.

Radiotherapy's main skin toxicities are now well-separated, acute (acute radiation dermatitis) or chronic complications (chronic radiation dermatitis, induced cutaneous carcinoma, aesthetic sequelae). Exceptionally, radiotherapy may induce, by isomorphic reaction or Koebner's phenomenon, some specific dermatosis. In this article, we report five new observations of these unusual complications of radiation therapy, occurring in very variable time after breast irradiation and remaining strictly localized in the irradiated field (cutaneous mastocytosis, Sweet syndrome, lichen planus, vitiligo). These cases emphasize the need to realize a systematic histological exam if any atypical skin lesion appears after radiotherapy, even long after.

Helical radiation intensity modulated by tomotherapy improves dose distribution to complex and large volumes. The aim of the study was to assess acute toxicity of this technique during breast cancer irradiation after conserving surgery or mastectomy.Cutaneous toxicities, lung and oesophageal side effects, and breast lymphedema were retrospectively collected according to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) in 292 patients treated for a breast cancer by tomotherapy between May 2010 and December 2014. After conservative surgery, the dose administered to breast volume and the tumour bed was respectively 52.2Gy and 63.8Gy in 29 fractions. After mastectomy, the dose was 50Gy in 25 fractions. Univariate and multivariate analyses were performed to highlight risk factors for dermatitis and breast oedema.The rate of dermatitis grade 2 and 3 were 22.9% and 1.7% respectively. In univariate analysis, factors associated with acute radiation dermatitis were breast volume (P=0.002), body mass index (BMI) (P0.0001), the use of chest compression mask (net) (P=0.005) and the localization of the irradiation (P0.0001). In multivariate analysis, BMI greater than 25kg/mThe helical irradiation intensity modulation tomotherapy is a well-tolerated treatment for breast cancer that reduces the high radiation doses to organs at risk.

Introduction Magnetic Resonance Imaging (MRI) acquisition in treatment position was implemented in our institution for the need of stereotactic body radiotherapy (SBRT) program. During imaging acquisition, significant liver motion is usually observed due to breathing motion. The aim of this study is to report the benefits of setting out a breath-triggered MRI protocol optimized for radiotherapy (RT) planning in order to account for liver motion. Material and methods Prior to imaging, three internal gold fiducials were implanted under echo or CT guidance in the vicinity of the lesion site in order to improve images registration, patient’s positioning and target volume tracking during SBRT treatment. A 4D CT scan was acquired in treatment position. Images were reconstructed in six phases across the respiratory cycle with CT50 being the exhale image set used for MR image registration. MRI was acquired with a 18-channel design body ex coil on a 1.5T MR scan. The patients were set up with the same immobilization and positioning devices as for CT imaging thanks to a MR compatible table. The three sequences were systematically used:- For lesion visualization, axial single shot fast spin echo T2-weighted (T2) with fat saturation was first acquired with breath triggering on exhale. – Fiducials are visible on ultra-fast gradient echo T1-weighted DIXON (T1 DIXON) water reconstructed images acquired in exhale breath hold. – Lesion are also well defined after injected T1-weighted Fast Low Angle Shot (T1 TFL) imaging sequence acquired with breath triggering on expiration phase. Gold fiducials are also visible on this sequence. Slice thickness was set to 2 mm and all sequences were acquired in the same plane with the same slice position in order to ease image registration in the treatment planning software. The entire MRI protocol acquisition lasts around 20 min depending on the regularity of the patient’s breathing pattern. Results The lesion was not always visible on 4D CT scan, even on images with contrast enhancement hence the need of MRI to better define the lesion. Target motion range was assessed based on fiducials’ displacement. Most frequently, treatment planning is performed on expiration phases but when lesion movement is small with breathing, target contouring is done over all phases and treatment planning is achieved in free breathing. The use of the same table and immobilization device for MRI minimized uncertainties due to patient position for image registration. An example of MR/CT50 registration and target volume definition is illustrated on Fig. 1. Download : Download high-res image (447KB) Download : Download full-size image Conclusion The use of MR imaging sequences optimized to account for fiducial visualization and tumor delineation allow high precision target delineation for treatment planning. Increasing cases of patients eligible for SBRT and its proof of benefit have stimulated the effort to setup and improve new imaging protocols at our institute for a personalized and optimal SBRT treatment. Recent developments in 4D MRI demonstrated the possibility to sort and reconstruct the images according to the respiratory phases [1] , [2] , [3] . Future implementation of 4D MRI in our institution would allow better registration with 4D CT planning over the entire breathing cycle and delineation accuracy will benefit from significant improvements.

Resume Objectif de l’etude Presenter les resultats d’une enquete nationale sur la pratique de la curietherapie dans le cancer du sein en 2009. Materiel et methode Un questionnaire ecrit a ete envoye aux centres hospitaliers universitaires et generaux et les centres regionaux de lutte contre le cancer. Ce questionnaire comportait les items suivants : type d’etablissement, participation aux essais cliniques d’irradiation du cancer du sein, nombre de curietherapies pratiquees par an, indications de la curietherapie, materiel vecteur et debit de dose utilises. Resultats Sur les 76 questionnaires envoyes, 35 reponses (46 %) ont ete obtenues, 9 % des centres hospitaliers universitaires et generaux et 50 % des centres regionaux de lutte contre le cancer pratiquent la curietherapie dans le cancer du sein. Le nombre de curietherapies realisees par an est estime entre 300 et 350. Les indications de curietherapie du sein sont : un complement d’irradiation ( boost ) (100 %), une irradiation partielle du sein (20 %) et un second traitement conservateur en cas de recidive locale (53 %). Le materiel vecteur utilise etait des aiguilles (27 %) ou des tubes plastiques (73 %). Le debit de dose utilise etait bas (50 %), pulse (25 %) ou haut (25 %). Conclusion La curietherapie du cancer du sein represente une technique validee pour le boost , en cours d’evaluation pour l’irradiation partielle et acceleree du sein et les seconds traitements conservateurs. Des regles de bonnes pratiques cliniques, techniques et dosimetriques doivent etre proposees. Une analyse de son impact medicoeconomique est souhaitable.

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Objectif de l’etude Le traitement curatif des cancers de l’œsophage non resecables repose sur une chimioradiotherapie de 50 Gy. De nombreux patients sont atteints de recidive locoregionale et plusieurs equipes ont demontre la faisabilite dosimetrique d’une escalade de dose grâce a la modulation d’intensite et la technique du boost integre. Cette technique a ete mise en place en routine dans notre centre. Nous en rapportons les resultats a long terme. Materiel et methode Il s’agissait d’une etude retrospective incluant tous les patients ayant recu une dose de plus de 50 Gy. L’analyse a porte sur les resultats dosimetriques, la toxicite aigue et tardive (plus de 6 mois) evaluee avec la Common Terminology Criteria for Adverse Events (CTCAE) v4.3 et les donnees de survie. Resultats Cinquante et un patients ont ete pris en charge entre 2008 et 2015 pour un adenocarcinome (14 %) ou un carcinome epidermoide (86 %) a une dose mediane de 60 Gy (extremes : 54–66 Gy) en 30 fractions (extremes : 27–33 fractions) dans les volumes tumoraux et ganglionnaires macroscopiques et 48 Gy (extremes : 45–56 Gy) a visee prophylactique dans les volumes adjacents. La dose moyenne delivree aux poumons etait de 12 Gy (extremes : 4–19,7 Gy), le V20 (volume recevant 20 Gy) de 14 % (extremes : 1,6–45,2 %) le V30 (volume recevant 30 Gy) de 5 % (extremes : 0,1–16,4 %). La dose moyenne delivree au cœur etait de 14 Gy (extremes : 0,3–31 Gy) et le V40 (volume recevant 40 Gy) etait de 3,3 % (extremes : 0,3–31 %). Quarante-six patients (90 %) ont recu une chimiotherapie concomitante (5-fluoro-uracile, acide folinique et oxalipaltine [folfox] ou cisplatine et 5-fluoro-uracile). Trois patients sont decedes a l’issue du traitement, dont un d’aplasie febrile. Vingt-six patients ont souffert d’une toxicite tardive de grade 3 ou moins, essentiellement a type de stenose œsophagienne. Aucun n’a souffert de pneumopathie radique. Apres un suivi median de 2,6 ans (intervalle de confiance a 95 % : 2–4,2), les taux de survie globale, sans progression et de controle locoregional etaient de 53,6 %, 42 % et 73 % a 2 ans. Conclusion La RCMI avec la technique du boost integre a permis une escalade de dose sans augmenter la toxicite liee au traitement. Les resultats en termes de survie et de controle locoregional de notre serie de patients non selectionnes apparaissent superieurs aux donnees publiees dans la litterature.

Introduction Since April 2015, patients are treated in our department with liver stereotactic body radiation therapy on a linear accelerator equipped with flattening filter free (FFF) photon beams. The energy and the use of respiratory gating are adapted for each patient. This study presents the results for the first 14 patients. Material and methods. Three gold fiducials are implanted inside or in the vicinity of the lesion 7–10 days prior planning imaging. The minimum 4 h fasting patient undergoes first a 4D CT scan with systematic audio coaching and a thoracic thermoplastic mask (Orfit Industries, Wijnegem, Belgium). An MRI scan in treatment position is acquired and registered to the CT images based on the fiducials. The radiation oncologist outlines the GTV on each of the six respiratory phases. A 6 phases ITV (entire breathing cycle) and a 3 phases ITV (expiratory phases) are then created. The corresponding PTVs are created by adding a 5 mm margin. When the ratio PTV 6/ PTV 3 is higher than 1.5, the treatment is achieved with respiratory gating. The beam used is a conformal dynamic arc of 180 to 200° amplitude, conformed to the PTV. 10 MV FFF beams were preferably used as the dose rate is higher than for 6 MV FFF beams (2400 and 1200 MU/min respectively). For organs at risk, constraints from Timmerman et al. [1] were used. Results For the past year, 14 patients have been treated (8 with 3 fractions of 18 Gy, 3 with 5 fractions of 11 Gy and 3 with 5 fractions of 10 Gy), without any restriction on PTV size (from 11 to 273 cm 3 ). The prescription isodose is 80%. 5 patients were treated in free breathing (PTV 6) and 9 with respiratory gating (PTV 3). Sometimes it has been necessary to treat with respiratory gating in order to fulfill the constraints to the organs at risk. The systematic comparison for the first 10 patients between the two FFF energies showed that the dosimetric objectives were fulfilled similarly for both energy except when the PTV was close to an organ at risk. In this case, better results were obtained with 6MV FFF beam. Conclusion Despite the fact that the liver is a very mobile organ, it has been possible to treat some patients in free breathing, without compromising the dosimetric objectives, thus allowing a better patient comfort (treatment time 3 times faster). The 10 MV FFF with its 2400 MU/min dose rate was most often used, allowing treatment times lower than 10 min even with respiratory gating and the highest prescribed dose.

Introduction L’atteinte cutanee de la mastocytose systemique (MS) est classiquement diffuse et symetrique. La tomotherapie (TT) ou « radiotherapie guidee par l’image » permet de reduire les risques pour les organes sains adjacents. Nous rapportons le premier cas de MS avec atteinte cutanee limitee de type urticaire pigmentaire (UP) localisee sur le champ de TT pour un cancer mammaire. Observations Une femme de 37 ans avait dans ses antecedents un GIST (KIT negatif) opere en 2013 et un cancer mammaire droit opere et traite par chimiotherapie jusque fin 2014. Apres pose de prothese, immediatement, soit du 2 janvier au 10 fevrier 2015, elle a recu de la TT 50 Gray. Il n’a pas eu de signe radiodermite. En juin 2015, elle remarquait l’apparition de lesions sur le champ de TT. Elle consultait fin 2015 pour ces lesions qui persistaient dans le temps. Le signe de Darier etait discretement positif, elle ne se plaignait d’aucun symptome et la tryptase serique etait normale. La biopsie cutanee confirmait l’UP. Le bilan complementaire confirmait le caractere systemique de cette mastocytose. La peau et la moelle etaient D816 V positives. Discussion Ce cas est original par le caractere localise de l’UP bien que cela survienne dans un contexte d’une MS. Dans la litterature n’ont ete rapportes que 4 cas de mastocytose cutanee localisee sur le champ de la radiotherapie classique. Il s’agit de 3 cas d’UP et un cas de telangiectasia macularis eruptiva perstans. Tous ces cas relevaient de mastocytose cutanee isolee et le statut du KIT n’etait pas precise. Les delais de survenue apres le debut de la radiotherapie varient entre 1 et 14 mois. Bien que ce type de radiotherapie soit utilise aussi pour d’autres cancers, il est interessant de souligner que tous les cas de mastocytose sur le champ de radiotherapie sont survenus apres le traitement d’un cancer mammaire. Il semble que le microenvironnement inflammatoire du cancer mammaire, la chirurgie et la radiotherapie aient favorise l’activation, le recrutement de precurseurs mastocytaires et/ou la proliferation des mastocytes dans la peau. L’apparition de lesions 5 mois apres le debut de la TT dans notre cas suggere un recrutement cutane de precurseurs mastocytaires tumoraux sanguins associes eventuellement a une proliferation de mastocytes cutanes residents possiblement tumoraux. Une autre hypothese pour cette atteinte localisee serait que les mastocytes tumoraux etaient deja localises en nombre augmente et regroupes en amas dans la peau et que les modifications entrainees par la TT ont favorise une activation de ces mastocytes avec l’apparition de la pigmentation caracteristique de l’UP. Dans ce second cas de figure, on s’attendrait cependant a ce que les lesions surviennent plus vite et pas 5 mois apres le debut de la TT. Conclusion L’UP peut etre localisee meme quand elle est associee a l’atteinte systemique.

Recent improvements in the detection of breast cancer at an early stage have resulted in a rising incidence of breast ductal carcinoma in situ with microinvasion. So far, there is no consensus regarding its optimal management. We hereby report on our 10-year single institutional experience in breast ductal carcinoma in situ with microinvasion including pathological reviewing.All consecutive patients treated for a ductal carcinoma in situ with microinvasion at the Institut Claudius-Regaud (Toulouse, France) over a 10-year period were included in this study. We reviewed all available histological materials.Sixty-three patients were eligible for this study. Two patients presented with a lymph node invasion at diagnosis. Each patient benefited from initial surgical management, which consisted either in mastectomy (n=25) or conservative resection (n=37). Axillary exploration was performed in 52 patients (82%). After a median follow-up of 61.3 months [46.9;69], the 5-year overall survival and disease free survival were 98.2 (95% CI=[88.2;99.7]) and 89.5% (95% CI=[76.3;95.6]) respectively. Two delayed invasive relapses occurred leading to one specific death. The pathological review highlighted a trend towards a loss of HR and HER2 expression (9%) in the microinvasive component in comparison with its surrounded in situ carcinoma.The risk of initial lymph node involvement and delayed invasive local relapse deserve an optimal locoregional management including lymph node evaluation. The non-negligible discrepancy's rate between in situ and microinvasive components justifies HR status and HER2 expression assessment on the microinvasive component.

From January, 1975 to December, 1987, 241 patients with rectal cancer underwent pre-operative irradiation and surgical resection. The radiation was delivered with 25 MeV photons, 5 days per week by 2.4 grays fractions up to a total dose of 36 grays. Surgery was curative in 195 patients; 57% had abdomino-perineal resection. Irradiation had to be discontinued in 3 patients and 4 patients subsequently developed severe acute ileitis. Postoperative mortality rate was 2.9%. The most frequent postoperative complications were delayed healing of abdominal wounds (18%) and perineal wounds (14%). Severe late complications occurred in 27 (13%) patients. The incidence of intestinal obstruction was 5%. Follow-up survivors ranged from 18 months to 13 years. Local failure occurred in 24 (12%) of the 195 patients. Local failure rates were 10% for Dukes' A tumors, 11.6% for Dukes' B, and 22.7% for Dukes' C tumors. Five and 10 year actuarial survival rates after curative surgery were 70% and 52%. The Dukes' classification was the only factor that influenced survival.

Purpose To assess the interobserver variability in clinical target volume (CTV) definitions when using registered 18 F-labeled deoxyglucose positron emission tomography (FDG-PET-CT) versus side-by-side image sets in pediatric Hodgkin's disease (HD). Methods and Materials Prechemotherapy FDG-PET-CT scans performed in the treatment position were acquired from 20 children (median age, 14 years old) with HD (stages 2A to 4B) and registered with postchemotherapy planning CT scans. The patients had a median age of 14 years and stages of disease ranging between 2A and 4B. Image sets were coregistered using a semiautomatic coregistration system. The biological target volume was defined on all the coregistered images as a guide to defining the initial site of involvement and to avoid false-positive or negative results. Five radiation oncologists independently defined the CTV for all 20 patients: once using separate FDG-PET-CT images as a guide (not registered) to define CTVa and once using the registered FDG-PET-CT data to define CTVb. The total volumes were compared, as well as their coefficients of variation (COV). To assess the interobserver variability, the percentages of intersection between contours drawn by all observers for each patient were calculated for CTVa and for CTVb. Results The registration of a prechemotherapy FDG-PET-CT scan caused a change in the CTV for all patients. Comparing CTVa with CTVb showed that the mean CTVb increased in 14 patients (range, 0.61%–101.96%) and decreased in 6 patients (range, 2.97%–37.26%). The COV for CTVb significantly decreased for each patient; the mean COVs for CTVa and CTVb were 45% (21%–65%) and 32% (13%–57%), respectively ( p = 0.0004). The percentage of intersection among all CTVbs for the five observers increased significantly by 89.77% (1.99%–256.41%) compared to that of CTVa ( p = 0.0001). Conclusions High observer variability can occur during CT-based definition of CTVs for children diagnosed with HD. Registration of FDG-PET and planning CT images resulted in significantly greater consistency of tumor volume definition.

To present the national survey patterns in France for breast cancer brachytherapy in 2009.A written questionnaire was sent to the academic and general hospitals and the anticancer centres. The different items were type of institution; breast cancer clinical trial participation; number of breast brachytherapy per year; its indications; material and dose rate used.Among the 76 sent questionnaires, 35 (46 %) answers were available: 9 % of academic hospitals and 50 % of cancer centres performed breast brachytherapy. The number of breast brachytherapy per year ranged between 300 and 350. The indications were boost (100 %), partial breast irradiation (20 %) and second conservative treatment for local recurrence (53 %). The implanted material consisted in needles (27 %) and plastic tubes (73 %). The dose rate was low (50 %), pulsed (25 %) and high (25 %).Breast brachytherapy appears as a validated technique in case of boost but remains under investigation for partial breast irradiation and second conservative treatments. Good clinical practice rules as well as technical and dosimetric guidelines are needed. A cost-effective analysis of breast brachytherapy is warranted.

252 evaluable patients were treated in the Centre Claudius Regaud from January 1974 to December 1983 for stage Ib, IIa or proximal IIb carcinoma of the uterine cervix. This retrospective analysis compares results obtained either by radio-surgical combination therapy (113 patients = RS group) or by exclusive irradiation (139 patients = RT group). The comparison of the two groups in terms of patient age, obesity, associated vascular pathology and previous abdomino-pelvic surgery favored the RS group significantly. The distribution according to clinical stage also significantly favored the RS group. The proportion of patients with stage IIb disease was 12% in the RS group as opposed to 25% for the RT group. Despite unfavorable patient and tumor characteristics, therapeutic results in the RT group were similar to those of the RS group. Pelvic recurrences developed in 18/110 (16%) and 18/139 (13%) of the patients in the RS and RT groups, respectively. Distant metastases occurred in 5/92 (5%) patients in the RS group and 13/121 (11%) patients in the RT group, but the difference was not significant (p less than 0.1). Five year corrected actuarial disease-free survival was 82% in both groups. There were no major early complications in the RT group while four were found in the RS group, of which three were fatal. 2% of patients had major late complications in the RS group versus 6% in the RT group and none were lethal. 25% of the RT group patients had a moderate or mild complication versus 10% in the RS group but 2/3 of these complications recovered without sequellae.

This is a report of a nonrandomized comparison of treatment results of 139 patients with stage IB, IIA and proximal IIB carcinoma of the uterine cervix treated by radiation alone and 113 treated with a combination of radiation and surgery. The five-year tumor free acturial survival for the patients with stage IB either with irradiation alone (RT) or combined with surgery (RS) was approximately 87%. For stage II the tumor free actuarial five-year survival 79% with patients of RS, and 76% with RT. In the 113 patients treated with RS there were 18 (16%). In the 139 patients treated by RT there were 18 (13%) recurrences of pelvic, 4 local recurrences, 11 combined with parametrial, and free parametrial recurrences. There was no significant difference in the survival and recurrence rate of the patients treated with either method. Major complications were comparable in both groups (RT approximately 25% and RS approximately 10%), but 2/3 of those complications recovered without sequelae. The most frequent minor complication in the patients treated with RT was rectosigmoiditis.

Introduction Treatment of chestwall with lymph nodes (internal mammary and clavicular nodes) is achieved in most of the centers with conventional radiotherapy using photons and electrons beams with junctions. The aim of this study is to do a dosimetric comparative study between two technics using modulation irradiation: Tomotherapy and Rapid Arc (RA). Material and methods Seven patients (5 left, 2 right) were treated using Tomotherapy. For these patients a RA plan was prepared retrospectively. Patients were positioned supine with two arms above the head. The prescribed dose was 50 Gy for the chestwall and 46–50 Gy for the lymph nodes. Optimisation constraints were increased until the PTV coverage was acceptable. Tomotherapy plans were computed with a 2.5–5 cm collimation and a 0.287 pitch. RA plans were computed using a 5 mmbolus on the chestwall, 2 arcs (60–180°) and a +/-10° collimator rotation. Doses delivered to targets, heart and both lungs are reported. Results For the 7 patients the heart mean dose was 7.1–8.6 Gy (mean 7.5 Gy) with Tomotherapy and 4.4–18.1 Gy (mean 9.9 Gy) for RA. For the ipsilateral lung, the mean dose, V5, V20 and V30 were respectively 10.1–14.7 Gy, 56.4–85.7%, 14.8–25.9% and 6.2–16.6% for Tomotherapy. For RA, these values were 10.5–16.0 Gy, 65.3–96.0%, 14.8–30.0% and 6.2–16.6%. Conclusion For 5/7 patients RA plans were acceptable but the OAR doses were generally higher than Tomotherapy plans (in particular V5 of lungs and lung mean dose). For 2/7 patients (left side) RA plans were not acceptable.

Introduction Treatment of breast cancer with lymph nodes (internal mammary and clavicular nodes) is achieved in most of the centers using a conventional radiotherapy based on electron-photon beams with junctions and wedge filters. Wedge filters correct for surface obliquities but do not provide optimal dose homogeneity within the breast volume. This study aims at comparing treatment plans using the ‘‘field in field” technique, equivalent to a ‘‘simplified” intensity modulation with treatment plans using wedge filters. Material and methods This study focused on eight patients (for half of the patients, the internal mammary nodes were included in the breast fields) treated for breast cancer with lymph nodes using wedge filters. For these patients a ‘‘field in field” plan was prepared retrospectively. Patients were positioned supine with ipsilateral arm above the head and head turned to the opposite treatment side. The prescribed dose was 50 Gy to the PTV breast and 46–50 Gy for the lymph nodes. For both technics, after treatment plan optimization, doses delivered to targets, heart and ipsilateral lung are reported. Results For the 8 patients and for the same coverage of breast and lymph nodes PTV, the volume of 105% (52.5 Gy) of the dose remaining in the breast volume was 2.65–24.29 cc (mean 13.9 cc) with the ‘‘field in field” technic and 9.49–231.63 cc (mean 98.5 cc) with wedge filters technic. For ipsilateral lung, the mean dose, V20 and V30 were respectively 15.1–16.6 Gy (average 15.8 Gy), 25.4–27.1 Gy (average 26.1 Gy), and 17.3–19 Gy (mean 17.9 Gy) for both technics. Conclusion For 8 patients, ‘‘field in field” treatment plans showed that remaining volume of 105% of the dose was up to 10 times smaller than using wedge filters treatment plans. This technics allowed reducing significantly overdosage areas and therefore having a better dose homogeneity in the breast.

Thirteen patients with intra-abdominal malignancies entered a phase I study of fluorouracil (5-FU) given by continuous infusion (96 h) iv and ip, simultaneously, and modulated by high-dose folinic acid-iv. Severe but reversible stomatitis was the only dose-limiting toxicity at a dose of 5-FU of 550 mg/m2/day. Local toxicity (5-FU-induced abdominal pain) was a significant side effect in patients receiving more than 1 cycle. The pharmacokinetic advantage of 5-FU-ip was confirmed in our study (ratio AUC peritoneum/plasma between 160 and 328). The systemic exposure to 5-FU (plasmatic AUC ranging from 73.4 to 173.21 microM) and to AF were found in efficacious ranges. The recommended dose of 5-FU iv and ip is 500 mg/m2/day. This regimen is feasible and may potentially have application for adjuvant chemotherapeutic programs after surgery for colorectal cancer.

Most pancreatic carcinomas are clinically observed when the tumoral spread is well advanced. Consequently, surgical excision is very often either partial or unfeasible. However, evolutive patterns of pancreatic carcinomas show a long past history of loco-regional spread before the onset of visceral metastasis. Consequently, radiotherapy could be proposed to treat locally advanced pancreatic tumors or residual disease after surgical excision in curative intend. The major challenge dealing with radiotherapeutic management of pancreatic carcinomas is to safely deliver doses as high as 60-70 Gy into the upper half of the abdominal cavity. Several technical conditions must be fulfilled before this can take place: high energy and multiple convergent photon beams, precise surgical and/or radiological description of tumoral extent, careful sparing of critical tissues such as spinal cord and kidneys. Usually, radiotherapeutic planning is administered in 2 successive sessions: 40-45 Gy are first administered to the tumor and main nodal drainage over 4-6 weeks, then a 15-25 Gy boost dose is given to the primary tumor bed only. However, postoperative irradiation after complete removal of a gross tumor gives a 10% survival rate only at 2 years. Improvement of these results, are eventually expected from intra-operative irradiation techniques or radiochemotherapy combined treatments.