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Resume Objectifs de l’etude Nous presentons les resultats du PHRC Tridicol, etude prospective francaise de phase II dont l’objectif etait d’augmenter la dose delivree au volume cible lors de la curietherapie des cancers du col de l’uterus localement evolues. Materiel et methodes Huit centres ont inclus 48 patientes, prises en charge par chimioradiotherapie concomitante, puis curietherapie uterovaginale. Resultats Le suivi median etait de 63 mois. La dose mediane de curietherapie delivree en equivalent biologique d’une irradiation delivree par fractions de 2 Gy (EQD2) dans 90% du volume cible anatomoclinique a haut risque (D90 CTV HR) etait de 80 Gy. Le taux de controle local a 5 ans etait de 84 %, proche de l’hypothese de 86,7 %. Le taux de complications severes (de grade 3–4) etait de 23 % a 5 ans. La dose recue par le rectum etait correlee au risque de complications severes. Conclusion La dose dans le CTV HR a ete inferieure a l’objectif (85 Gy) du fait d’une faible utilisation des applicateurs avec aiguilles interstitielles parametriales, les centres participants ne disposant pas toujours d’un applicateur adequat, ou parce qu’ils etaient a l’epoque au debut de leur courbe d’apprentissage. Le taux de controle local a 5 ans etait ameliore par rapport a celui du groupe comparable du STIC PDR (programme de soutien aux techniques innovantes couteuses curietherapie de debit pulse) ([78 %] mais inferieur a la cohorte retroEMBRACE du GEC ESTRO (Groupe Europeen de Curietherapie -European Society for Radiotherapy) (89 %). Le taux de complications etait plus eleve que dans le groupe comparable du STIC PDR mais proche de celui de retroEMBRACE (intErnational study on MRI-guided BRachytherapy in locally Advanced CErvical cancer). La formation des equipes de curietherapie a l’implantation interstitielle ou l’adressage des patientes a des centres de recours doit permettre d’ameliorer l’indice therapeutique des cancers du col de l’uterus.

Summary Purpose In the ACOSOG Z0011 trial, patients with primary breast cancer and 1–2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. Methods Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-Francois Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. Results Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR) = 6.1; 95% confidence interval (CI): 1.4-26.7; P = 0.02)) and only one SLN removed (OR = 9.1; 95%CI: 2.2-33.3; P = 0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR = 5.1; 95%CI: 1.2-22.2; P = 0.03) was associated with the failure to perform completion ALND when recommended. Conclusion Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

Primary vaginal cancers are rare tumours, for which external beam radiotherapy and brachytherapy are major treatment tools. Given the complexity of brachytherapy techniques, the treatment should be performed in specialised centres. We present the recommendations of the French society for radiation oncology on the indications and techniques for external beam radiotherapy and brachytherapy for primary vaginal cancer.

PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p

Resumen El tratamiento del cancer de mama infiltrante localizado ha evolucionado de forma significativa en los ultimos 10 anos. La comprension de los mecanismos biologicos, genomicos y moleculares ha permitido situar el concepto de optimizacion y personalizacion, asi como el de desescalada, en el centro de los tratamientos. El objetivo es proponer un tratamiento optimo y reducir la morbilidad inherente a los tratamientos.

Resume La prise en charge des maladies myeloides et lymphoides repose essentiellement sur la chimiotherapie et les therapies ciblees. La radiotherapie pouvant etre responsable de toxicite tardive severe liee, entre autres, aux techniques d’irradiation classique en deux dimensions, de nombreux essais ont tente d’omettre la radiotherapie ou de desescalader la dose dans leur strategie therapeutique. Neanmoins, la radiotherapie garde une place a visee curative ou symptomatique.

Resume Le cancer du pancreas est un cancer de pronostic defavorable dont l’incidence ne cesse de croitre. Il representera d’ici 2030 la deuxieme cause de mortalite par cancer en France et dans le monde. La chirurgie, seul traitement potentiellement curatif, n’est possible au moment du diagnostic que dans 20 % des cas avec un risque significatif de resection incomplete. L’interet d’une strategie neoadjuvante par chimiotherapie ou chimio-radiotherapie est de plus en plus admise permettant une meilleure selection des patients en situation non-evolutive pouvant beneficier d’une resection, une augmentation du taux de resection complete et une conversion a la resecabilite des tumeurs localement evoluees ou borderline. Toutefois, la place de la radiotherapie fait encore debat a ce jour. De par ses avantages dosimetriques, son etalement court et sa bonne tolerance en lien avec la reduction des volumes d’irradiation, la radiotherapie stereotaxique a ete largement etudiee. En comparaison a la chimioradiotherapie, cette technique pourrait ameliorer l’indice therapeutique afin de garantir un etat general preserve aux patients pouvant acceder secondairement a une chirurgie. Elle demeure une technique prometteuse toujours en cours d’evaluation, devant etre dispensee au mieux, dans le cadre d’un essai clinique, ou a defaut au sein d’une equipe experimentee, maitrisant cette technique.

Resume Objectif de l’etude La radiotherapie stereotaxique pulmonaire est realisee dans l’equipe du centre Georges-Francois-Leclerc (CGFL) a Dijon depuis 2008 sur un accelerateur Truebeam® (Varian®) avec la technique RPM. Materiels et methodes Cinquante patients atteints d’un cancer bronchique primitif de stade T1–T2 (n = 30) ou une metastase bronchique (n = 20) ont ete inclus dans l’etude. Depuis 2014, trois scanographies quadridimensionnelles successives a j1, j2 et j3, sont realisees afin de s’assurer de la reproductibilite des ITV (Internet Target Volume). Les trois ITV sont delinees (ITV 1,2 et 3) a partir de la MIP (Maximum Intensity Projection) de chacune des trois scanographies. Un ITV global est cree a partir des ITV des trois scanographies (fusion des MIP2 et 3 avec la MIP1). Une CBCT (Cone Beam Computerised Tomography) est realisee au debut de chaque seance d’irradiation pour positionner le patient. L’etude consistait a analyser la pertinence de la realisation de trois scanographies differentes avant la dosimetrie pour definir l’ITV et a comparer les volumes delinees sur les differentes CBCT a l’ITV pour s’assurer que le volume tumoral est bien inclus dans l’ITV au cours des seances. Resultats Il existe une forte correlation entre les differents ITV 1, 2, 3 et global, ainsi qu’entre les volumes obtenus sur les differentes CBCT (p = 0,977). Le coefficient de correlation entre les differents ITV et les volumes delinees sur CBCT etait eleve pour les lesions lobaires superieures. En termes de tolerance, le VEMS (volume maximal expire pendant la premiere seconde) ne semblait pas etre un facteur significatif influant sur la correlation entre les ITV et les volumes delinees sur CBCT. Conclusion La realisation d’une seule scanographie de centrage quadridimensionnelle est suffisante pour envisager une irradiation stereotaxique pulmonaire, quelle que soit la localisation des lesions pulmonaires. Le coefficient de correlation entre les ITV et les CBCT etait eleve pour les lesions lobaires superieures.

This section highlights selected specific new recommendations and/or updates that have been published during the very last years in the fields of stereotactic radiotherapy, pediatrics, lung cancer, gynecologic and breast cancer, as well as in the area of radiation oncology of urogenital cancer.

Resume Les strategies de prise en charge en cas de ganglion(s) sentinelle(s) micro ou macrometastatique(s) dans les cancers du sein ont ete profondement modifiees depuis une dizaine d’annees et la publication de cinq essais randomises : ACOSOG Z0011, IBCSG 23-01, et AATRM comparant curage axillaire versus abstention ; et AMAROS et OTOASOR comparant curage axillaire versus radiotherapie axillaire. Malgre les limites methodologiques de certains de ces essais, notamment de l’ACOSOG Z0011, les recommandations internationales (ASCO, NCCN) et le consensus d’experts de St Gallen ne preconisent pas la realisation d’un curage axillaire complementaire en cas d’envahissement macro ou micrometastatique des ganglions sentinelles si l’ensemble des criteres d’inclusions de l’ACOSOG Z0011 sont reunis. De plus, en cas de mastectomies avec un ou deux ganglions sentinelles envahis et une indication d’irradiation de paroi, la realisation d’une radiotherapie axillaire peut etre proposee en alternative au curage axillaire. En dehors de ces indications, un curage axillaire reste indique, notamment lorsque trois ou plus ganglions sentinelles sont metastatiques, ou en cas de rupture capsulaire. Ce changement de strategie a conduit a une diminution importante du nombre de curage axillaire et l’abandon de l’examen extemporane des ganglions sentinelles. Se pose egalement la question de la pertinence de systematiquement realiser une microbiopsie ou une cytologie des ganglions axillaires suspects lors du bilan initial. En France, il n’existe pas de recommandations nationales sur la prise en charge axillaire en cas d’envahissement du ganglion sentinelle. A l’inverse, une multitude de referentiels tous plus differents les uns que les autres conduisent dans notre pays a des pratiques tres heterogenes. La prochaine evolution dans la strategie de prise en charge axillaire sera la realisation d’une procedure du ganglion sentinelle apres chimiotherapie neoadjuvante pour les patientes ayant un envahissement ganglionnaire prouve avant chimiotherapie neoadjuvante et chez qui la chimiotherapie neoadjuvante a permis un downstaging axillaire.

External beam radiotherapy and brachytherapy are major treatments in the management of cervical cancer. For early-stage tumours with local risk factors, brachytherapy is a preoperative option. Postoperative radiotherapy is indicated according to histopathological criteria. For advanced local tumours, chemoradiation is the standard treatment, followed by brachytherapy boost, which is not optional. We present the update of the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for cervical cancer.

The first intent upfront treatment of endometrial cancer is surgery. External radiotherapy and brachytherapy; however, are important tools in adjuvant setting, according to histopathological risk factors for locoregional recurrence or in the event of an inoperable tumor. We present the update of the recommendations of the French society of oncological radiotherapy on the indications and technical methods of performing radiotherapy and brachytherapy for endometrial cancer.

Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer.

Background and Purpose: Recent phase 3 clinical trials have evaluated the addition of bevacizumab (B) to standard chemotherapy in the treatment of patients with non-metastatic breast cancer. But few data are available about the tolerance of B with locoregional radiation therapy (RT). The objective was to evaluate the 5 years late toxicities of the concurrent B and RT in non-metastatic breast cancer. Material and methods: This is a multicenter prospective study including non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT (BEATRICE, BETH, BEVERLY 1, BERVERLY 2) versus RT alone. All patients received neo-adjuvant or adjuvant chemotherapy and normo-fractionated breast or chest wall RT, with or without regional lymph nodes RT. B was administrated as an equivalent of 5 mg/kg every week for 1 year. The safety profile (using the Common Terminology Criteria for Adverse Events version 3.0) was evaluated at 1, 3 and 5 years after the completion of radiotherapy. Results: From October 2007 to January 2012, 151 patients totally included. Median follow-up was 60 months (36-84) and 5 years late toxicities were available for 104 patients (46 with B and RT, 58 with RT alone). Median age was 51 (22-81). 61% of patients received regional lymph nodes RT. The majority of tumor was triple negative (65.6%), tumor size Conclusion: Concurrent B and locoregional RT provides acceptable 5-years toxicities in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed. Citation Format: Clément-Zhao A, Tanguy M-L, Cottu P, De La Lande B, Bontemps P, Lemanski C, Baumann P, Levy C, Peignaux K, Reynaud-Bougnoux A, Gobillion A, Kirova Y. TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-06.

Pancreatic cancer has poor prognosis and a continuously growing incidence. By 2030, it should become the second cause of death by cancer worldwide and in France. The only curative treatment is surgery that is achievable in only 20% of patients at the time of initial diagnosis, with a high rate of incomplete resection. Neoadjuvant treatments using chemotherapy with or without radiotherapy are more often admitted to play an important role by selecting non-progressing cases who will benefit from surgery, by increasing the number of complete resection, and by making locally advanced and borderline tumours accessible to resection. However, the role of radiotherapy is still debated. Because of its dosimetric advantages, its short total duration, and its good tolerance with reduced volumes of irradiation, stereotactic radiotherapy has been largely studied. Compared to chemoradiotherapy, this technique could improve the therapeutic index helping to preserve the general status of patients in order to give them access to secondary surgery. It remains a promising technique still under evaluation, to be delivered ideally, as part of a clinical trial, or within an experimented team.

The management of myeloid and lymphoid disease is essentially based on chemotherapy and targeted therapies. Since radiotherapy could be responsible for severe late toxicities, essentially due to conventional bidimensional irradiation techniques, many trials have attempted to omit radiotherapy or to scale down the dose in their therapeutic strategy. Nevertheless, radiotherapy still plays a role for curative or symptomatic purposes.

PURPOSE/OBJECTIVE(S) With the progress of systemic therapies, the opportunity to treat synchronous multiple abdominal lesions of unresectable oligometastatic patients is increasing. With a limited number of fractions and high dose per fraction, stereotactic radiotherapy (SBRT) is a treatment of choice in many indications. Magnetic resonance image-guided radiation therapy (MRgRT) offers a satisfying image quality and contrast especially for abdominal diseases. Indeed, this technique makes possible a daily adaptative radiotherapy (ART) in order to manage inter-fraction motion and live tumor visualization and gating to take into account intra-fraction motion. This work presents our experience in the management of SMART for double synchronous abdominal lesions treatment. MATERIALS/METHODS Three patients have received a SMART for double synchronous abdominal lesions on our MR-Linac. Patient 1: a 43-years-old woman with two liver metastases from breast cancer. Patient 2: a 44-years-old man with two pancreatic metastases from leiomyosarcoma. Patient 3: a 45-years-old man with one liver metastasis and the pancreatic head primitive cancer. The proximity of the lesions was from 3.5 to 6.5 cm. The prescribed dose was 30 to 35 Gy in 5 fractions for pancreatic lesions and 40 to 60 Gy in 5 or 6 fractions for liver lesions. Patients have been selected according to their ability to hold and reproduce apneas. Each lesion has been treated in breath hold position on alternate days. A step-and-shoot intensity modulated radiation therapy (IMRT) technique has been initially planned for each lesion including an optimization volume permitting to reduce as low as possible the contribution to the second lesion. Each lesion has been gated on a unique sagittal slice with limited margin in the direction of the second lesion. RESULTS For each patient, the treatment has been carried out properly in terms of comfort, respect of the limit of dose contribution to the second lesion and volume detection for the gating of the tumor. For patient 1, 2 and 3, no acute toxicity neither in-field progression has been reported, respectively 8, 7 and 6 months after the end of the treatment. CONCLUSION Thanks to SMART, we have been able to define a feasible and robust methodology permitting double synchronous abdominal metastases treatment. The three patients have successfully followed up the treatment without identified comfort or technical issues. After minimum 6 months, no toxicity nor progression have been reported. AUTHOR DISCLOSURE M. Rouffiac: None. C. Chevalier: None. D. Thibouw: None. M. Quivrin: None. K. Peignaux-Casasnovas: None. G. Truc: None. L. Aubignac: None. J. Boudet: None. A. Petitfils: None. I. Bessieres: None.

We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers.Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy.The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications.HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Stereotactic lung radiosurgery has been carried out in the team at the Georges-François-Leclerc centre (CGFL) in Dijon since 2008 on a Truebeam® accelerator (Varian®) with the RPM technique.Fifty patients with primary T1-T2 stage lung cancer (n=30) or lung metastasis (n=20) were included in the study. Since 2014, 3 successive 4D scanners on D1, D2 and D3, have been produced in order to ensure the reproducibility of ITV (Internet Target Volume). The 3 ITVs are contoured (ITV 1, 2 and 3) from the MIP (Maximum Intensity Projection) of each of the 3 scanners. A global ITV is created from the ITV volumes of the 3 scanners (MIP 2 and 3 merged with MIP 1). A CBCT (Cone Beam Computerised Tomography) is performed at the start of each irradiation session to position the patient. The study consisted in analysing the relevance of the realisation of 3 different scanners before dosimetry to define the ITV and in comparing the volumes contoured on the different CBCT to the ITV to make sure that the tumour volume is well included in the ITV during the sessions.There is a strong correlation between the different ITVs 1, 2, 3 and global, as well as between the volumes obtained on the different CBCTs. The correlation coefficient between the different ITVs and the volumes contoured on CBCT was high for upper lobar lesions. In terms of tolerance, the FEV1 (Maximum volume expired during the first second) did not seem to be a significant factor influencing the correlation between the ITV and the volumes bypassed on CBCT.Performing a single 4D planification CT is sufficient to consider stereotactic lung irradiation, regardless of the location of the lung lesions. The correlation coefficient between ITV and CBCT was high for upper lobar lesions.

Purpose To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. Material and methods This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. Results Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18–77 months). Median age was 53 years old (range: 23–68 years). The 3-years overall survival was 93% (range: 87–100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. Conclusions Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

Purpose/Objective(s) Surface imaging systems are becoming a reference in radiotherapy treatments to improve patient setup. Thanks to an important database of patient positioning, a clinical retrospective evaluation of the system has been realized. For this evaluation, three relevant endpoints have been identified and analyzed: the time-saving setup, the accuracy setup, the number of additional X-Ray images performed to validate the patient setup. Materials/Methods Two groups of patients have been defined including all localizations except head & neck treatments. Patients have been all treated on the same Linac following the same positioning and imaging protocol. The first group, the reference one, includes 700 patients with a treatment positioning based on skin marks using lasers. The second group includes 250 patients with treatment positioning based on surface imaging system. In parallel, clinical data (BMI, age, localization etc.) and treatment data (immobilizing system, treatment technique etc.) have been extracted from the Hospital Information System (HIS) and Treatment Planning System (TPS) databases thanks to homemade program. Afterwards, statistical analyses have been carried out for both groups in order to correlate the clinical and technical data with the three defined endpoints. Results Different correlations have been pointed out. First results confirm that the surface imaging system gives relevant and better set-up information for different sub-groups (breast, skinny pelvis etc.). Nevertheless, for others sub-groups, no correlation nor improvements have been observed (pelvic high BMI etc.) in comparison to laser positioning. Conclusion Different changes in our patient positioning practices have been defined with the help of surface imaging system. For many patients, we improved our imaging workflow efficiency. For several sub-groups of patients, we still have to investigate the system and its best use.

Introduction La radiotherapie post-operatoire (RPO) est un sujet de discussion depuis la meta-analyse montrant que la RPO pouvait etre deletere en particulier chez les patients (pts) pN0 et pN1. Cependant, la question restait ouverte pour les pts pN2, d’autant que de nombreux changements ont eu lieu dans la prise en charge des pts traites pour un carcinome bronchique non a petites cellules (CBNPC) de stade IIIAN2. Methodes Lung ART est un essai de phase III randomise europeen comparant une RPO mediastinale (54 Gy/27–30 fractions) a l’absence de RPO. Les pts etaient eligibles s’ils etaient PS 0-2, avaient une resection complete avec exploration nodale, une maladie N2 averee; la CT (neo) adjuvante etait autorisee. Le critere principal etait la survie sans maladie (DFS). Les criteres d’evaluation secondaires comprenaient la toxicite, le controle local, les modalites de rechute, la survie globale (SG), et les seconds cancers. Resultats Entre aout 2007 et juillet 2018, 501 patients ont ete randomises apres chirurgie ou apres CT adjuvante, dont 427 dans IFCT-0503: 252 pts ont ete alloues au bras RPO, et 244 pts au bras temoin. L’âge median etait de 61 ans (intervalle = 36–85), 66 % d’hommes, adenocarcinome (73 %). La plupart des pts ont recu une CT (post-operatoire 77 %, pre-operatoire 18 %). Le suivi median est de 4,8 ans. La compliance en terme de RPO etait bonne: 7 pts l’ont interrompu. Une toxicite cardio-pulmonaire tardive de grade 3-5 a ete rapportee chez 47 pts (19,5 %) dans le bras RPO vs 19 (7,7 %) dans le bras controle: il n’y avait pas de difference en ce qui concerne les toxicites de grade 5. Le «Hasard Ratio (HR))» pour la DFS etait de 0,847 (IC a 95 % 0,67; 1,07); p = 0,156; la DFS mediane etait de 30,5 mois dans le bras RPO [24; 48] et de 22,8 mois dans le bras controle [17; 37]; La DFS a 3 ans etait de 47,11 % avec la RPO contre 43,8 % sans RPO. Le risque de rechute mediastinale est reduit de pres de moitie avec la RPO (46 % dans le bras controle versus 25 % dans le bras RPO). Le taux de SG a 3 ans etait de 66,48 % avec PORT contre 68,53 % sans PORT. Conclusion Lung ART est la premiere etude randomisee europeenne evaluant une RPO 3D apres resection complete, chez des patients selectionnes principalement par TEP et ayant recu une CT (neo) adjuvante. Le taux de DFS a 3 ans etait plus eleve que prevu dans les deux bras et la RPO etait associee a une augmentation non statistiquement significative de 15 % de la DFS parmi les pts operes de facon complete d’un CPNPC de stade IIIAN2.

Purpose/Objectives The purpose of this study was to determine early and late toxicities among patients with non-metastatic breast cancer (BC) receiving concurrent bevacizumab (BV) and radiation therapy (RT). Materials/Methods Multicentre, prospective study, of the toxicity of adjuvant concomitant association of BV and RT in patients with non-metastatic BC enrolled in Phase 3 BEATRICE, BEVERLY and BETH trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during RT, 12 months and 36 months after its completion. Results Sixty-four patients were included from october 2007 to august 2010. They all received adjuvant RT and BV concomitant treatment, plus neo-adjuvant BV for 24 patients. RT was adjuvant and normo-fractionated. Twelve months toxicity was available for 60 patients and 36 months toxicity was available for 43 patients. Median follow-up was 46 months (18-77). Median age was 51 years old (23-68). Among 63 evaluated patients during RT, acute radiation dermatitis was observed in 48 (76%) patients : Grade 1 for 27 (43%), grade 2 for 17 (27%), grade 3 for 4 patients (6%). Grade 2 acute oesophagitis was observed in 1 patient. At 3 years, few toxicities were observed : 6 patients (14%) had grade 1 pain, 4 (9%) had grade 1 fibrosis, one (2%) had grade 1 telangiectasis, one (2%) had grade 1 paresis, 3 (7%) had grade 1 lymphoedema and one grade 3 lymphoedema. No grade 4 toxicity was observed. At 12 months, only one evaluated patient had a LVEF Conclusions Concurrent bevacizumab with locoregional RT is associated with acceptable early and late 3-years toxicities in patients with BC. Determination of late toxicity at 60 months is currently underway. Citation Format: Dautruche A, Belin L, Cottu P, Bontemps P, Lemanski C, De La Lande B, Baumann P, Missohou F, Levy C, Peignaux K, Reynaud-Bougnoux A, Denis F, Gobillion A, Ady Vago N, Fourquet A, Kirova Y. Radiotherapy associated with concurrent bevacizumab in patients with non-metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-17.

Introduction et but de l’etude Les accelerateurs de radiotherapie couples a l’imagerie par resonance magnetique sont particulierement adaptes aux traitements stereotaxiques des localisations tumorales soumises aux variations physiologiques quotidiennes (digestion, respiration, etc.) et situees a proximite d’organes a risque sensibles dont le traitement pouvait etre jusqu’a present perilleux, voire impossible sur accelerateurs traditionnels. Ils permettent d’envisager une escalade de dose en toute securite pour esperer un meilleur controle tumoral. Materiel et methodes Nous rapportons les donnees des cinq premiers patients pris en charge sur accelerateurs de radiotherapie couples a l’imagerie par resonance magnetique, par guidage IRM en temps reel avec une adaptation a chaque fraction du plan de traitement (« Cine MR gating »). Tous les patients etaient atteints d’une tumeur situee a moins de 2 cm d’un organe a risque (cœur, colon, grele, duodenum, etc.) : deux patients recevaient un traitement pour un adenocarcinome de la tete du pancreas, deux patients etaient atteints d’une localisation secondaire hepatique d’un cancer solide et un d’un carcinome hepatocellulaire. Le maintien d’une apnee etait indispensable a la realisation du traitement de ces localisations fortement soumises aux mouvements respiratoires. La dose prescrite etait de 35 Gy en cinq fractions de 7 Gy pour les tumeurs pancreatiques et de 50 Gy en cinq fractions de 10 Gy pour les localisations hepatiques. Une adaptation de dose a 40 Gy en cinq fractions de 8 Gy a ete necessaire pour une localisation hepatique a proximite immediate du colon. L’objectif de validation dosimetrique etait d’assurer une couverture d’au moins 90 a 95 % de la dose prescrite au volume cible previsionnel sans gradient de dose particulier en limitant les points chauds a 110 %, sous reserve du respect strict des contraintes aux organes a risque. Pour chaque fraction, les durees de chaque etape ont ete relevees (installation, repositionnement, adaptation du plan, traitement). Resultats et analyse statistique Pour l’ensemble des 25 fractions de radiotherapie stereotaxique abdominale adaptative sur accelerateurs de radiotherapie couples a l’imagerie par resonance magnetique avec « Cine MR gating », la duree mediane totale de traitement des patients etait de 104 minutes (extremes : 84-146 min), comprenant une duree mediane de 31 minutes (extremes : 16-58 min) d’activation du faisceau. Le temps median destine a la procedure adaptative etait de 35 minutes (extremes : 16-62 min), dont 10 minutes de duree mediane de nouvelle delineation des organes a risques (extremes : 2-19 min), 7 minutes de correction de densite des electrons (extremes : 1-16 min) et 6 minutes de calcul et validation dosimetrique (extremes : 1-32 min). Conclusion Les traitements stereotaxiques adaptatifs realises sur accelerateurs de radiotherapie couples a l’imagerie par resonance magnetique permettent d’assurer une escalade de dose dans le volume cible tumoral tout en limitant la dose dans les organes a risque pour des patients atteints de lesions mobiles a proximite d’organe a risque sensible. Cette technologie engendre une augmentation du temps total de traitement et necessite une collaboration multidisciplinaire entre medecins, physiciens et manipulateurs.

Resume Le traitement des lymphomes de Hodgkin de stades I/II repose sur la chimiotherapie et la radiotherapie. Ces associations therapeutiques ont change le pronostic et la survie des patients. Actuellement, la problematique est de diminuer leur toxicite. Grâce a la tomographie par emission de positons, essentielle dans la prise en charge initiale de ces lymphomes, la definition des volumes cibles en radiotherapie est devenue plus precise, ce qui a pu permettre une radiotherapie plus ciblee de type « involved node » ou « involved site ».

Background and purposeFew data are available concerning the safety of bevacizumab (B) in combination with locoregional radiation therapy (RT). The objective of this study was to evaluate the 5-year late toxicity of concurrent B and RT in non-metastatic breast cancer.Materials and methodsThis multicentre prospective study included non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT versus RT alone. All patients received neoadjuvant or adjuvant chemotherapy and normofractionated breast or chest wall RT, with or without regional lymph node RT. B was administered at an equivalent dose of 5 mg/kg once a week for 1 year. The safety profile was evaluated 1, 3 and 5 years after completion of radiotherapy.ResultsA total of 64 patients were included between November 2007 and April 2010. Median follow-up was 60 months (12-73) and 5-year late toxicity data were available for 46 patients. The majority of tumours were triple-negative (68.8%), tumour size ConclusionConcurrent B and locoregional RT are associated with acceptable 5-year toxicity in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed.

External irradiation and brachytherapy still have a major place in the treatment of cervix and endometrial carcinoma. This review presents the French guidelines in terms of preparation and choice of irradiation techniques of these gynecological malignancies.

Purpose The present study evaluated the outcomes of concurrent weekly docetaxel and platinum-based drug doublet in association with concurrent thoracic radiotherapy (TR) in the curative treatment of stage III locally advanced non-small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIA/B NSCLC were retrospectively included. Patients received weekly docetaxel and either cisplatin or carboplatin intravenous injections during concurrent TR (60 to 66 Gy). Patients who received induction chemotherapy with the same drug doublet were also included. The endpoints were: disease control rate (DCR), overall recurrence rate, survival rates [disease-free survival (DFS) and overall survival (OS)] and toxicity. Results Eighty-nine consecutive patients treated with this association were included. Median follow-up time was 57.8 months. DCR was 76.5% at the first follow-up CT scan (6 to 12 weeks after the end of concurrent treatment). Median DFS and OS was 14.3 and 29.9 months respectively. Three-year survival was 43%. The overall recurrence rate was 65.9%. During overall treatment, grade 3 to 4 adverse events occurred in 29.2% of patients, the most common being esophagitis (12.4% of patients). Only 13.5% of patients presented with a grade 3 or higher adverse event after the end of concurrent treatment. Conclusions Weekly docetaxel and platinum-based drug doublet combined with TR yielded promising results in stage III NSCLC, with high survival rates. The toxicity of this association is acceptable, with mainly manageable esophagitis. These findings warrant validation in a prospective study before considering this association for standard of care.

// Celine Bourgier 1 , Florence Castan 1 , Olivier Riou 1 , Tan-Dat Nguyen 2 , Karine Peignaux 3 , Claire Lemanski 1 , Jean-Leon Lagrange 4 , Youlia Kirova 5 , Eric Lartigau 6 , Yazid Belkacemi 4 , Sofia Rivera 7 , Georges Noel 8 , Sebastien Clippe 9 , Francoise Mornex 10 , Christophe Hennequin 11 , Sophie Gourgou 1 , Muriel Brengues 1 , Pascal Fenoglietto 1 , Esat Mahmut Ozsahin 12 and David Azria 1 1 Institute de Recherche en Cancerologie de Montpellier, Inserm U1194, Universite de Montpellier, Institut Regional du Cancer de Montpellier, Montpellier, France 2 Institute Jean Godinot, Reims, France 3 Centre GF Leclerc, Dijon, France 4 AP-HP Henri Mondor, Creteil, France 5 Institute Curie, Paris, France 6 Centre Oscar Lambret, Lille, France 7 Gustave Roussy, Villejuif, France 8 Centre Paul Strauss, Strasbourg, France 9 Centre Marie Curie, Valence, France 10 Centre Hospitalier Lyon Sud, Pierre Benite, France 11 AP-HP Saint-Louis, Paris, France 12 Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland Correspondence to: David Azria, email: david.azria@icm.unicancer.fr Keywords: radiotherapy; breast cancer; hormonotherapy; individual radiosensitivity; late effects Received: November 30, 2017 Accepted: February 25, 2018 Epub: March 02, 2018 Published: March 20, 2018 ABSTRACT Background: To evaluate risk of severe breast fibrosis occurrence in patients treated by breast-conserving surgery, adjuvant radiotherapy and hormonotherapy (HT) according to individual radiosensitivity (RILA assay). Results: HT – and RILA high were the two independent factors associated with improved breast-fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with RILA low and HT + than in patients with RILA high and HT – (75.8% and 100%, respectively; p = 0.004, hazard ratio 5.84 [95% confidence interval (CI) 1.8–19.1]). Conversely, BFFS at 36 months was comparable in patients with RILA high and HT + and in patients with RILA low and HT – (89.8% and 93.5%, respectively; p = 0.39, hazard ratio 1.7 [95% CI 0.51–5.65]), showing that these two parameters influenced independently the occurrence of severe breast fibrosis. BFFS rate was not affected by the HT type (tamoxifen or aromatase inhibitor) and timing (concomitant or sequential with radiotherapy). Conclusions: HT and RILA score independently influenced BFFS rate at 36 months. Patients with RILA high and HT – presented an excellent BFFS at 36 months (100%). Materials and methods: Breast Fibrosis-Free Survival (BFFS) rate was assessed relative to RILA categories and to adjuvant HT use (HT + and HT – , respectively) in a prospective multicentre study (NCT00893035) which enrolled 502 breast cancer patients (456 evaluable patients). Breast fibrosis was recorded according to CTCAE v3.0 grading scale; RILA score was defined according to two categories (

Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2–IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups. Clin Cancer Res; 21(11); 2530–7. ©2015 AACR.

Resume La radiotherapie pulmonaire en conditions stereotaxiques est le traitement de choix a proposer aux patients non operables atteints d’un carcinome bronchique non a petites cellules de stade T1-T2, N0 M0 ou de metastase(s) pulmonaire(s) a croissance lente et a tumeur primitive controlee. Elle permet un excellent taux de controle local, de plus de 80 % a 2 ans. Or, bien que le taux de toxicite clinique soit faible, inferieur a 5 %, les reactions radiologiques post-radiques peritumorales, appelees « pneumopathie radique radiologique » sont quasi systematiques et rendent l’evaluation de la reponse tumorale difficile. Cette revue de la litterature decrit, tout d’abord, les lesions de pneumopathie radique aigue et chronique et les signes scanographiques devant faire evoquer une recidive tumorale. Puis, elle evalue l’apport de la TEP-scanographie et sa place dans la surveillance postradiotherapie en conditions stereotaxiques. Enfin, elle propose un algorithme pour la surveillance des patients traites.

Purpose/Objectives Few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (RT) in breast cancer, especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicities among patients with non-metastatic breast cancer treated with this combination. Materials/Methods In our prospective and descriptive study, we analyzed loco-regional toxicities of adjuvant RT in patients with non-metastatic breast cancer receiving either concurrent bevacizumab or not in the randomized trial BEATRICE. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment. Statistical analysis was performed to analyze toxicity between the two groups. Results From September 2007 to July 2009, we included 84 patients from the randomized trial BEATRICE which evaluate the efficacy and safety of the addition of bevacizumab to standard adjuvant therapy in patients with triple negative breast cancer; 39 women received an adjuvant RT with concurrent bevacizumab and 45 women received an adjuvant RT alone. Evaluation at 12 months was available for all the patients. All patients had a triple negative non-metastatic breast cancer and had an adjuvant chemotherapy then RT. Among patients receiving concurrent bevacizumab with RT, a total of 35 patients (90%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 4 patients (10%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 19 patients (49%) with internal mammary chain RT in 12 patients (31%). Mean time of bevacizumab treatment was 11.7 months [2.1-12.6] and mean total dose of bevacizumab was 15000 mg [3330-28080]. Among patients receiving RT alone, 38 patients (84%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 7 patients (16%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 21 patients (47%) with internal mammary chain RT in 14 patients (31%). Radiation treatment parameters were not significantly different between the two groups. Incidence of acute grade 3 dermatitis was 10% in patients receiving bevacizumab associated with RT and 6% in patients receiving RT alone without significant difference. One year after the end of RT, the most common late toxicities in the group receiving bevacizumab and RT were grade 1-2 pain (18%), grade 1-2 fibrosis (8%), grade 1-2 arm lymphedema (8%) and grade 1-2 telangiectasia (6%).There was no significant difference in pain, radiation fibrosis, telangiectasia, arm lymphedema and dyspnea between the two groups. No patient experienced grade 3-4 toxicity in the two groups. Conclusions Our results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-11.

External irradiation and brachytherapy still have a major place in the treatment of cervix and endometrial carcinoma. This review presents the French guidelines in terms of preparation and choice of irradiation techniques of these gynecological malignancies.

Background Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast (WB) in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. The phase III randomized trial “BONBIS” is elaborated to evaluate the impact of a 16-Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. Methods: A total of 1950 patients DCIS breast cancer patients are planned to be enrolled in this trial. Patients will receive the following treatment: (A) WB radiotherapy of 50 Gy in 25 fractions vs. (B) WB radiotherapy of 50 Gy in 25 fractions plus a localized 16-Gy boost in 8 fractions. The primary endpoint is local-relapse free survival (LRFS). This trial is designed to detect an expected rate in control arm of 7% and 4 % in experimental arm. With 90% power and a=0.05, 137 events are necessary to achieve the main goal. An interim analysis is planned after 50% of observed event. Stratifications are made based on recognized prognostic factors: age, hormonal treatment, differentiation, circumstance of diagnosis, surgical margin, centre. Secondary endpoints are relapse free survival, overall survival, acute and late toxicities, cosmetic results, and quality of life. Translational researches are also planned to identify intrinsic radiosensitivity of normal tissues (radiation-induced apoptosis assay, genome-wide association study) but also predictive models of tumor recurrences. Inclusions have started in November 2008 and are not so far than the planned estimation. This trial is granted by the French National Cancer Institute (PHRC 2008) and supported by the French National Society of Radiation Oncology (SFRO). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-06-01.

Preoperative chemoradiation (P-CRT) remains a controversial strategy in the treatment of squamous cell cancer (SCC) and adenocarcinoma (ADC) of the oesophagus. Until recently, randomised studies mixed the two, often without any distinction. In randomised studies involving exclusively SCC, P-CRT increases the rate of local control, R0 resection, pCR and disease-free survival. The absence of any impact on overall survival may be linked to the toxic effects of this treatment. Meta-analyses have revealed a survival benefit of approximately +13% at 2 years. However, the methodology used was perhaps questionable. Five randomised trials involving ADC patients compared P-CRT with surgery alone. The results were contradictory with insufficient statistical power in selected positive studies to answer this issue once and for all. P-CRT is unsatisfactory as a standard treatment. Although local control rates were increased with P-CRT, it should be considered only for selected patients in selected centres.

Resume Objectif de l’etude Cette etude avait pour objet d’evaluer le cout de la curietherapie de debit pulse avec optimisation de la repartition de la dose par rapport aux traitements traditionnels (fils d’iridium, cesium, curietherapie de debit pulse non optimisee) et de rapprocher ce cout de la tarification. Materiel et methodes Une etude prospective, multicentrique et non randomisee a ete conduite dans le cadre d’un programme de soutien aux techniques innovantes couteuses (Stic) dans 21 centres. Les patientes incluses recevaient une curietherapie classique ou innovante pour un cancer du col de l’uterus. Les couts directs medicaux de personnel, equipements, sources, consommables et travaux specifiquement lies a la curietherapie de debit pulse ont ete evalues en adoptant le point de vue de l’hopital et ont ete rapportes a une curietherapie. Resultats Quatre cent soixante patientes ont ete incluses sur deux ans. Les principaux postes de cout pour la curietherapie de debit pulse correspondaient aux sources radioactives (1053 €) et aux projecteurs (735 €). Les couts d’imagerie et de dosimetrie de la curietherapie de debit pulse optimise s’elevaient respectivement a 130 € et 367 € contre 47 € et 75 € en l’absence d’optimisation tridimensionelle. Le differentiel de cout entre la curietherapie de debit pulse optimisee et la strategie la moins couteuse (fils d’iridium) atteignait plus de 2100 € par curietherapie. Ce differentiel pourrait etre reduit de moitie dans l’hypothese d’activite de 40 patientes traitees par an (contre 24 dans l’etude). Conclusion A l’heure actuelle, si les couts de personnel sont relativement bien pris en compte par la tarification, les couts correspondant a l’equipement et aux sources sont, en revanche, tres sous-cotes.

Purpose To compare the impact of an unilateral post-operative irradiation or a bilateral irradiation in terms of loco-regional control and survival in patients with cervical lymph node of squamous cell carcinoma from an unknown primary (CUP). Methods and materials Ninety five patients with epidermoid carcinoma involving unilateral cervical lymph nodes from an unknown primary were treated in two institutions from 1990 to 2007. Post-operative radiation therapy was delivered to one side of the neck in 59 cases, to both sides of the neck in 36 cases. There were 11 women and 84 men ranging in age from 38 to 80years (median 59years). Neck dissection was performed in 79 patients while 16 patients underwent single lymph node sampling only. Results After a median follow-up of 3.3years, the nodal relapse rate was 34% after unilateral neck irradiation and 25% after bilateral radiotherapy ( p =0.21). Six contralateral lymph node relapses occurred after unilateral irradiation (10%). The 5-year overall survival rate of the entire group was 24%. The 5-year OS rates were 22% after unilateral irradiation and 23%, after bilateral radiotherapy ( p =0.944). The occult primary occurred in 12% after unilateral irradiation and 6% after bilateral radiotherapy. The radiation technique (3D-CRT or IMRT vs. 2D: p =0.026) was prognostic on loco-regional control. Independent prognostic determinants on overall survival were the WHO status ( p =0.013) and the radiation technique (2D vs.3D-CRT or IMRT; p =0.029). There was no difference in loco-regional control ( p =0.639) and no difference in survival ( p =0.493) when chemotherapy was associated. Conclusions Retrospective comparisons between bilateral and unilateral neck radiotherapies did not show differences in terms of loco-regional control and survival. However, patient's local regional control and survival are significantly improved after 3D-CRT or IMRT.

Most endometrial cancers are diagnosed at stage I (disease limited to the uterine corpus). The definitive treatment for endometrial carcinoma consists in total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy. The decision of adjuvant treatment depends on risk factors. Postoperative radiotherapy plays a major role in the management of stage I endometrial cancer but the respective place of external radiotherapy and vaginal brachytherapy remains controversial. Adjuvant external beam radiotherapy reduces locoregional recurrences, but carries a risk of toxicity without overall survival benefits. Recent data suggest that vaginal brachytherapy is effective in preventing vaginal recurrence with lower toxicity and should be the treatment of choice for intermediate risk endometrial cancer.

At cellular level, signalization pathway activated by ErbB receptors participate to the proliferation, migration and differenciation of many cellular types. Observed alterations are mutations, overexpressions with or without gene amplification or abnormal stimulation by their ligands. The most frequently observed mutation is an extracellular deletion aiming to activate tyrosine kinase activity without ligand. Strategies to target the EGFr receptor include antisens oligonucleotids, antibodies directed to extracellular component of tyrosine kinase receptor. Only monoclonal antibodies and TKI have been developed in clinical research, mainly for oesophageal and rectal carcinomas. Solid tumor proliferation is under control of tumoral mechanisms and the interaction between tumor and microenvironment. In particular, angiogenesis is important during invasive and metastasis phases. The major role of Vasculoendothelial Growth Factor (VEGF) in angiogenesis is useful for tumor growth, which has been demonstrated by many convergent studies. Radiosensitivation or reversion of radioresistance could be obtained by inhibition of VEGF pathway. Antibodies directed against this molecule have been introduced in GI tract malignancies for the treatment of pancreatic and colic carcinomas.

Resume La tomotherapie est une nouvelle modalite de radiotherapie externe reprenant le principe d'une irradiation helicoidale avec modulation d'intensite. Elle peut s'affranchir de l'obligation d'isocentres multiples necessaires a l'irradiation des volumes importants. Le systeme integre l'acquisition d'images, la planification du traitement, le positionnement du patient et l'irradiation dans une machine unique. Robot a six degres de liberte supportant un accelerateur lineaire de 6 MV lui permettant de multiples incidences avec une precision millimetrique, le Cyberknife™ fonctionne actuellement en France dans trois centres choisis par l'Inca (Institut national du cancer). Un accelerateur de derniere generation est une machine multifonctions capable de realiser des traitements conformationnels avec ou sans modulation d'intensite, des irradiations de type stereotaxiques intra- et extracrâniennes avec ou sans modulation d'intensite avec ou sans arctherapie. Les performances respectives de chacune de ces machines doivent etre mesurees et comparees dans l'inevitable cadre medicoeconomique.