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Soft tissue sarcomas are a rare and heterogeneous disease. For localized disease, treatment is based on surgery and radiotherapy with or without chemotherapy depending on risk factors. Upfront metastases are present in 7 to 20% of cases, and are localized to the lungs in most of cases. Disseminated disease is generally considered incurable but in selected cases, aggressive local treatment of metastases allowed long survival. Treatment of primary tumour is often debated. Our purpose is to evaluate the literature concerning the role of radiotherapy in the management of primary metastatic soft tissue sarcomas. [ABSTRACT FROM AUTHOR]

Résumé Les sarcomes des tissus mous sont des tumeurs rares. La chirurgie conservatrice suivie de radiothérapie postopératoire représente le standard de traitement dans la majorité des cas, la radiothérapie postopératoire améliorant le taux de contrôle local sans influencer la survie. Outre la qualité de l’exérèse chirurgicale qui reste le facteur pronostique majeur, l’importance du volume d’irradiation et en particulier des marges utilisées en radiothérapie externe se sont avérées influencer le contrôle local de la maladie. Dans cet article, nous proposons de réaliser une revue de la littérature, sur l’état actuel de nos connaissances sur ce sujet, sous la forme d’une controverse articulée de la sorte : pour ou contre des marges importantes en radiothérapie externe. Soft tissue sarcomas are rare tumours. Conservative surgery followed by postoperative radiation therapy represents the gold standard in the majority of cases. Postoperative radiotherapy improves local control without affecting survival. Besides the quality of surgical excision, which remains the major prognostic factor, the importance of the irradiation volume and particularly margins used in external beam radiotherapy were also found to influence local control of the disease. In this study, we propose to conduct a literature review on the present state of our knowledge on this subject in the form of an articulated controversy: in favour or opposed to large margins in external radiotherapy. [ABSTRACT FROM AUTHOR]

Résumé Objectif de l’étude Cette étude rétrospective a évalué les modalités de prise en charge et le pronostic des cancers du rectum chez le sujet âgé en comparaison avec ceux des sujets plus jeunes. Patients et méthodes Les données de 160 patients de plus 80 ans, ayant reçu un traitement pour un cancer du rectum diagnostiqué entre 2006 et 2008, en région Provence-Alpes-Côte-d’Azur, indépendamment du stade et du traitement de la maladie ont été analysées rétrospectivement. Les taux de survie globale et sans rechute ont été corrélés avec les caractéristiques de la tumeur et les traitements administrés. Le traitement administré a ensuite été comparé aux standards thérapeutiques recommandés pour les patients plus jeunes. Résultats Avec 36 mois de suivi médian, les taux de survie globale et sans rechute à 3 ans étaient respectivement de 59,2 % et 76,6 % pour les 117 patients ayant reçu un traitement à visée curative. En analyse multifactorielle, la survie globale était indépendamment influencée par le statut N et l’exérèse chirurgicale, alors que la survie sans rechute était influencée par l’âge, le statut N, et le sexe. Les tumeurs de stade T0–T2 ont été traitées conformément aux recommandations pour les patients plus jeunes, avec respectivement des taux à 3 ans de 83,6 % et 95,2 % de survie globale et de survie sans rechute. Pour les patients atteints de tumeur de stade T3–T4, le taux de survie sans rechute à 3 ans était de 65 %, malgré une stratégie moins agressive. Conclusion Sous réserve d’une bonne évaluation oncogériatrique, la chirurgie reste le standard de traitement des tumeurs localisées (de stade T0–T2) des patients âgés. Pour les tumeurs localement évoluées (de stade T3–T4), les résultats obtenus dans cette étude suggèrent qu’une approche conservatrice pourrait être envisagée. Purpose Rectal cancer is increasingly prevalent in elderly patients. Their clinical history and outcome after treatment are poorly described. This retrospective study was undertaken to provide more data and to compare therapeutic strategies to the standard of care for younger patients. Patients and methods Patients concerned were aged 80 years or older, with a rectal cancer diagnosed between 2006 and 2008 and treated in Provence-Alpes-Côte-d’Azur (PACA), irrespective of stage and treatment of the disease. Overall survival and relapse-free-survival were correlated with patients’ characteristics and treatment. The adopted therapeutic strategy was then compared to the standard-of-care for younger patients. Results With a median follow-up of 36 months, among the 160 patients included, the 3-year overall survival and relapse-free survival were 59.2% and 76.6%, respectively for the 117 patients who received a treatment with curative intent. In the multivariate analysis, node status and surgery independently influenced overall survival, while relapse-free survival was influenced by age, N status, and gender. For T0–T2 tumours, patients were treated similarly to younger patients with an overall survival of 83.6% and a relapse-free survival of 95.2%. For T3–T4 tumours, the 3-year relapse-free survival was 65%, even with a less aggressive strategy. Conclusion Surgical resection after evaluation using the Comprehensive Geriatric Assessment (CGA) test should be the standard treatment for localized rectal cancer (T0–T2) in elderly patients, as it is in younger patients. For locally advanced lesions (T3–T4), results obtained after a conservative approach suggest that a non-surgical strategy can be used in elderly patients. [ABSTRACT FROM AUTHOR]

Aims Recent data suggest that patients with pulmonary metastases from sarcomas might benefit from ablation of their metastases. Some data are available regarding osteosarcomas/angiosarcomas and lung metastases. The purpose of this study was to assess the efficacy of local ablative treatment on the survival of patients with oligometastases (one to five lesions, any metastatic site, any grade/histology) from sarcomas. Materials and Methods A multicentric retrospective study of the French Sarcoma Group was conducted in sarcoma patients with oligometastases who were treated between 2000 and 2012. Survival was analysed using multivariate sensitivity analyses with propensity scores to limit bias. Results Of the 281 patients evaluated, 164 patients received local treatment for oligometastases between 2000 and 2012. The groups' characteristics were similar in terms of tumour size and remission of the primary tumours. The median follow-up was 25.7 months; 129 (45.9%) patients had died at this point. The median overall survivals were 45.3 (95% confidence interval = 34–73) months for the local treatment group and 12.6 for the other group (95% confidence interval = 9.33–22.9). Survival was better among patients who received local treatment (hazard ratio = 0.47; 95% confidence interval = 0.29–0.78; P < 0.001). Subgroup analyses revealed similar findings in the patients with single oligometastases (hazard ratio = 0.48; 95% confidence interval = 0.28–0.82; P = 0.007); a significant benefit was observed for grade 3, and a trend was observed for grade 2. Conclusion Local ablative treatment seemed to improve the overall survival of the patients who presented with oligometastatic sarcomas, including soft tissue and bone sarcomas. The survival benefit remained after repeated local treatments for several oligometastatic events. Surgery yielded the most relevant results, but alternative approaches (i.e. radiofrequency ablation and radiotherapy) seemed to be promising. The relevance of these results is strengthened by our analysis, which avoided biases by restricting the population to patients with oligometastatic disease and used propensity scores. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumour response to survival and to identify predictive factors for tumour response after chemoradiation. Patients and methods: From 1998 to 2008, 168 patients with histologically-proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45Gy with a concomitant 5-fluoro-uracil-based chemotherapy. Analysis of tumour response was based on the lowering of T stage between pre-treatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival was correlated with tumour response. Tumour response was analysed with predictive factors. Results: The median follow-up was 34 months. Five-year disease-free survival and overall survival were respectively of 44.4% and 74.5% in the whole population, 83.4% and 83.4% in patients with pathological complete response, 38.6% and 71.9% in patients with tumour downstaging, 29.1% and 58.9% in patients with absence of response. A pre-treatment concentration of carcinoembryonnic antigen below 5ng/mL was significantly associated with tumour downstaging and significantly independently associated with pathologic complete tumour response (P =0.019). Conclusion: Downstaging and complete response after chemoradiation improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pre-treatment concentration of carcinoembryonnic antigen below 5ng/mL was associated with complete tumour response, hence with tumour downstaging. [Copyright &y& Elsevier]

Abstract: Purpose: To assess the safety and efficacy of a new neoadjuvant chemoradiation (CRT) docetaxel-based regimen in patients with resectable adenocarcinoma of the pancreatic head or body. Patients and methods: 34 patients with histologically-confirmed resectable pancreatic adenocarcinoma were included in this prospective two-center phase II study. Radiotherapy was delivered at the dose of 45 Gy in 25 fractions of 1.8 Gy per fractions, 5 days/week, over 5 weeks. Docetaxel was administered as a 1-h intravenous (IV) infusion repeated every week during 5 weeks. The dose was 30 mg/m2/week. All patients were restaged after completion of CRT. Results: Tumor progression was documented in 11 patients (32%), stable disease was documented in 20 patients (59%), and partial remission was documented in 3 patients (9%). 23 patients still with local disease at restaging underwent explorative laparotomy. Of this, 17 patients (50%) had a curative pancreaticoduodenectomy with lymphadenectomy. Morbidity and mortality rates were 29% and 0%, respectively. Three patients (17%) had complete histological responses and 5 patients had minimal residual disease. All resected patients (n = 17) underwent R0 resection. The median and five-year survival times for the resected patients were 32 months and 41%, respectively. Among the resected patients, ten (59%) died as a result of recurrent pancreatic cancer without local tumor bed recurrence. Conclusions: Neoadjuvant docetaxel-based chemoradiation is well-tolerated. Resected patients had a prolonged survival time. Further studies are needed to confirm our findings and determine the role of such a neoadjuvant approach. [ABSTRACT FROM AUTHOR]

Abstract: Background: The most accepted treatment for locally advanced pancreatic adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated by neoadjuvant CRT. Methods: From January 1996 to December 2006, 64 patients with LAPA (borderline, n =49; unresectable, n =15) received 5-fluorouracil-cisplatin-based CRT. Of the 64 patients, 47 had progressive disease at restaging. Laparotomy was performed for 17 patients, and PD was performed in 9 patients (resected group). Fifty-five patients had CRT followed by gemcitabine-based chemotherapy (unresected group). Results: The median survival and overall 5 years survival duration of all 64 patients were 14 months and 12%, respectively. The mean delay between diagnosis and surgical resection was 5.5 months. Mortality and morbidity from PD were 0% and 33%, respectively. The median survival of the resected group vs. the unresected group was 24 months vs. 13 months. Three specimens presented a major pathological response at histological examination. No involved margins were found and positive lymph nodes were found in one patient. Resected patients developed distant metastases. Conclusions: PD after CRT was safe and resected patients had interesting survival rates. However, resected patients developed metastatic disease and new neoadjuvant regimens are needed to improve the survival of these patients. [Copyright &y& Elsevier]

Abstract: Purpose. – To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. Patients and methods. – A series of 271 patients, treated by surgery, radiotherapy±systemic therapy was analysed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, N =37), DIP and medium or high SPF (DMH, N =76), ANEUP and low SPF (AL, N =24), ANEUP and medium or high SPF (AMH, N =68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). Results. – On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N– patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N– stage I and II breast cancer. [Copyright &y& Elsevier]

Abstract: Purpose. – To study the impact of fused 18F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiation therapy (CRT) planning for patients with esophageal carcinoma. Patients and Methods . – Thirty-four patients with esophageal carcinoma were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. PET-images were coregistered using five fiducial markers. Target delineation was initially performed on CT images and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. Results. – FDG-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative CRT. The Gross Tumor Volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and was increased in 7 patients (20.5%). The GTV reduction was≥25% in 4 patients due to reduction of the length of the esophageal tumor. The GTV increase was≥25% with FDG-PET in 2 patients due to the detection of occult mediastinal lymph node involvement in one patient and an increased length of the esophageal tumor in the other patient. Modifications of the GTV affected the planning treatment volume (PTV) in 18 patients. Modifications of delineation of GTV and displacement of the isocenter of PTV by FDG-PET also affected the percentage of total lung volume receiving more than 20 Gy (VL20) in 25 patients (74%), with a dose reduction in 12 patients and a dose increase in 13 patients. Conclusion. – In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of patients with esophageal carcinoma related to modifications of GTV. The impact on treatment outcome remains to be demonstrated. [Copyright &y& Elsevier]

Résumé: Objectifs. – Analyse rétrospective du traitement et identification des facteurs pronostiques des premières rechutes locales isolées de sarcomes des tissus mous (tronc ou extrémités). Patients et méthodes. – Il s’agit d’une étude rétrospective portant sur une cohorte de 83 patients adultes traités entre 1980 et 1999. La taille tumorale moyenne était de 6 cm. La plupart des sarcomes étaient situés au niveau des extrémités (n = 74), étaient profonds (n = 60), et proximaux (n = 53) ; trente étaient au contact des axes vasculonerveux. Il s’agissait principalement de 49 % d’histocytofibrosarcomes et de liposarcomes (20 %), de grade 2 (42 %) ou 3 (36 %), selon les critères de la Fédération nationale des centre de lutte contre le cancer (FNCLCC). Le traitement chirurgical de la rechute locale a consisté en une exérèse large dans 32 cas, une résection marginale dans 46 cas, et cinq patients ont dû avoir une amputation. Les tranches de section d’exérèse ont été classées R0 (n = 33), R1 (n = 47) et R2 (n = 3). Six patients ont reçu une chimiothérapie néoadjuvante et sept patients une chimiothérapie adjuvante. Vingt-trois patients ont reçu une irradiation externe postopératoire de dose moyenne 55 Gy et 26 une curiethérapie interstitielle de bas débit de dose par iridium 192 de dose moyenne de 45 Gy si délivrée seule, et de 22 Gy si associée à la radiothérapie externe, 19 patients ayant été ré-irradiés. Résultats. – Avec un suivi en médiane de 59 mois, 37 patients (45 %) ont souffert d’une rechute, uniquement locale pour 61 % d’entre eux. Dix-neuf patients ont eu secondairement des métastases à distance. En analyse multifactorielle, seule la profondeur tumorale (p = 0,05) et la réintervention chirurgicale lors de la prise en charge de la récidive après une première chirurgie incomplète (p = 0,018) étaient des facteurs pronostiques de survie sans rechute, la radiothérapie (externe et/ou interstitielle) étant significative uniquement après analyse unifactorielle (p = 0,05). Les taux de survie globale étaient respectivement de 73, 54 et 47 % à 3, 5 et 10 ans et décroissaient respectivement à 65, 35 et 32 % après la seconde rechute locale. Après analyse multifactorielle, la localisation tumorale au niveau du tronc (p = 0,0001) ou des membres inférieurs (p = 0,023), les tumeurs symptomatiques (p = 0,001), profondes (p = 0,01) et de haut grade (p = 0,01), ainsi que la survenue d’une seconde rechute locale (p = 0,004) étaient des facteurs pronostiques indépendants de survie globale. Conclusion. – L’analyse des résultats obtenus dans cette série montre qu’une première rechute locale isolée de sarcome des tissus mous augmente considérablement le risque de développer une nouvelle rechute locale. La qualité du traitement local de la première rechute est capitale. Lorsqu’un traitement conservateur est envisageable, il doit autant que possible associer exérèse chirurgicale et radiothérapie externe, la curiethérapie étant prioritairement réservée aux rechutes en territoire irradié. Les efforts doivent être poursuivis pour améliorer la qualité de la prise en charge des tumeurs primitives au mieux réalisée dans des centres expérimentés. [Copyright &y& Elsevier]

Objectif de l’étude L’objectif de cette étude prospective monocentrique était d’étudier l’impact de la pose de marqueurs fiduciels dans la délinéation des volumes cibles d’irradiation des cancers œsophagiens et/ou rectaux. Matériel et méthode Les patients inclus tétaient atteints d’un cancer de l’œsophage ou du rectum avec indication d’irradiation et franchissables par l’échoendoscope. Une fibroscopie œso-gastroduodénale, une échoendoscopie, et une première scanographie de simulation ont été réalisées avant la pose de marqueurs fiduciels en or sous échoendoscopie et scopie sous anesthésié générale, aux pôles supérieur et inférieur de la lésion et dans les adénopathies suspectes après biopsie. Une seconde scanographie de simulation a été ensuite effectuée. La délinéation des volumes cibles a été réalisée avant et après cette pose. Les critères d’évaluation étaient la variation du volume tumoral macroscopique ( gross tumour volume [GTV]), et du volume cible anatomoclinique ( clinical target volume [CTV]) (significatives en cas de variation de plus de 5 mm dans le plan axial ou coronal et/ou de plus de10 mm dans le plan sagittal, et/ou d’une variation de volume de plus de 20 % entre les deux scanographies). Résultats Vingt-neuf patients ont été inclus de décembre 2014 à décembre 2015, parmi lesquels les dossiers de 27 étaient analysables : 15 patients pour un cancer œsophagien et 12 pour un cancer rectal (sex-ratio femmes/hommes : 13/10). Aucun échec de pose de marqueurs fiduciels et aucune complication n’ont été observés. La migration d’un marqueur fiduciel a été rapportée chez un patient. Le volume tumoral macroscopique a été significativement modifié dans 89 % des cas après la pose de marqueurs fiduciels (pour 13 cancers de l’œsophage sur 15 et 11 cancers du rectum sur 12), principalement dans le sens sagittal (67 % des cas, en moyenne 21 mm). Six patients (pour un cancer de l’œsophage, cinq du rectum), ont nécessité un déplacement de l’isocentre (en moyenne de 23 mm). Un patient était atteint d’une tumeur œsophagienne invisible sur la scanographie et chez un autre une adénopathie est passée inaperçue sur la scanographie initiale. Le volume cible anatomoclinique a significativement été modifié dans 96 % des cas par l’implantation de marqueurs fiduciels (pour 13 cancers de l’œsophage sur 15 et tous les cancers du rectum). Conclusion La pose de marqueurs fiduciels sous échoendoscopie, dans les cancers de l’œsophage et du rectum, impacte significativement la délinéation des volumes cibles en radiothérapie. [ABSTRACT FROM AUTHOR]

Résumé Les sarcomes des tissus mous de l’adulte font partie des tumeurs rares et relèvent d’une prise en charge pluridisciplinaire en milieu spécialisé. L’objectif de cet article est de rapporter les indications et les modalités de la radiothérapie dans les principales localisations de cette pathologie. Incidence of soft tissue sarcoma is low and requires multidisciplinary treatment in specialized centers. The objective of this paper is to report the state of the art regarding indications and treatment techniques of main soft tissue sarcoma localisations. [ABSTRACT FROM AUTHOR]

We present the update of the recommendations of the French s ociety of radiation oncology on soft tissue sarcomas. Currently, the initial management of sarcomas is very important as it may impact on patients' quality of life, especially in limb soft tissue sarcomas, and on overall survival in trunk sarcomas. Radiotherapy has to be discussed within a multidisciplinary board meeting with results of biopsy, eventually reexamined by a dedicated sarcoma pathologist. The role of radiotherapy varies according to localization of soft tissue sarcoma. It is part of the standard treatment in grade 2 and 3 sarcomas of the extremities and superficial trunk > 5 cm. In case of R1 or R2 resection, reexcision should be discussed. In such cases, it may be delivered preoperatively (50 Gy/25 fractions of 2 Gy) or postoperatively. In retroperitoneal sarcomas, preoperative conformal radiotherapy with or without modulated intensity cannot be proposed systematically in daily practice. Concomitant chemoradiotherapy cannot be considered a standard treatment. Intensity-modulated radiotherapy has become widely available. Other soft tissue sarcoma sites such as trunk, head and neck and gynaecological soft tissue sarcomas will be addressed, as well as other techniques that may be used such as brachytherapy and proton therapy. [ABSTRACT FROM AUTHOR]

We present the update of the recommendations of the French society for radiation oncology on external radiotherapy and brachytherapy of anal canal carcinoma. The following guidelines are presented: indications, treatment procedure, as well as dose and dose-constraints objectives, immediate postoperative management, post-treatment evaluation, and long-term follow-up. [ABSTRACT FROM AUTHOR]

La qualité de la prise en charge initiale des sarcomes est fondamentale, car elle conditionne la qualité de vie du patient et sa survie globale. La radiothérapie doit être discutée en réunion de concertation pluridisciplinaire dans le cadre du réseau Netsarc+. La place de la radiothérapie, chez les patients atteints d'un sarcome des tissus mous ou osseux, dépend de l'histologie et de la localisation tumorale, en sachant qu'elle est le plus souvent associée à la chirurgie, qui reste le traitement essentiel. Elle fait partie du traitement standard des sarcomes des membres profonds de grade II et III, de taille égale ou supérieure à 5 cm, et des sarcomes d'Ewing. Dans ces indications, la radiothérapie conformationnelle avec modulation d'intensité guidée par l'image est utilisée en routine. Dans d'autres localisations, comme les sarcomes rétropéritonéaux ou les sarcomes utérins, la radiothérapie n'est pas un standard de prise en charge et doit être discutée en réunion de concertation pluridisciplinaire en fonction des critères pronostiques liés au patient, à la tumeur, et aux traitements préalablement reçus. Les nouvelles techniques, comme la protonthérapie, l'hadronthérapie (ions carbones), sont particulièrement adaptées aux sarcomes osseux considérés radiorésistants. Pourtant, les larges essais prospectifs manquent dans ces indications rares, expliquant l'absence de recommandations de niveau de preuve élevé. The quality of the initial management of sarcomas is fundamental because it conditions the patient's quality of life and his overall survival. Radiotherapy should be discussed in a multidisciplinary consultation meeting within the framework of the Netsarc + network. The place of radiotherapy in patients with soft tissue or bone sarcoma depends on the histology and tumour location, knowing that it is most often associated with surgery which remains the main treatment. It is part of the standard treatment for grade II and III deep limb sarcomas of 5 cm or greater in size and Ewing's sarcomas. In these indications, conformal radiotherapy with modulation of intensity is used routinely, in combination with IGRT. In other locations, such as retroperitoneal sarcomas or uterine sarcomas, radiotherapy is not a standard of care and must be discussed according to the prognostic criteria related to the patient, the tumour, and the previously received treatments. New techniques, such as proton therapy, hadron therapy (carbon ions) are techniques particularly suited to bone sarcomas considered to be radioresistant. However, large prospective trials are lacking in these rare indications, explaining the lack of recommendations of a high level of evidence. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. Methods and materials Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. Results For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. Conclusion Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability. [ABSTRACT FROM AUTHOR]

Background Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. Patients and methods The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m2 i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. Results Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). Conclusion The addition of sorafenib to gemcitabine does not improve PFS in APC patients. [ABSTRACT FROM AUTHOR]

Purpose. – To evaluate our updated data concerning survival and locoregional control in a study of locally advanced non inflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation.Patients and methods. – Between 1982 and 1998, 120 patients (75 stage IIIA, 41 stage IIIB, and 4 stage IIIC according to AJCC staging system 2002) were consecutively treated by four courses of induction chemotherapy with anthracycline-containing combinations followed by preoperative irradiation (45 Gy to the breast and nodal areas) and a fifth course of chemotherapy. Three different locoregional approaches were proposed, depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of chemotherapy and a maintenance adjuvant chemotherapy regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months.Results. – Mastectomy and axillary dissection were performed in 49 patients (with residual tumour larger than 3 cm in diameter or located behind the nipple or with bifocal tumour), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumour bed; 32 had residual mass ≤3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after irradiation alone, 23% after wide excision and irradiation, and 4% after mastectomy (p =0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size (<6 vs. ≥6 cm in diameter, p =0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (stage IIIA-B vs. IIIC, p =0.0003), N-stage (N0 vs. N1-2a, and 3c, p =0.017), initial tumour size (<6 vs. ≥6 cm in diameter, p =0.008), and tumour response after induction chemotherapy and preoperative irradiation (clinically complete response + partial response vs. non-response, p =0.0015). In the non conservative breast treatment group, of the 32 patients with no change in clinical tumour size after induction chemotherapy, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) following axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by irradiation alone and in 51.5% of patients after wide excision and irradiation.Conclusion. – Despite the poor prognosis of patients with locally advanced non inflammatory breast cancer resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative irradiation and mastectomy with axillary dissection offers a possibility of long term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumour response following induction chemotherapy and breast-conserving treatment combining preoperative irradiation and large wide excision. [Copyright &y& Elsevier]

Purpose. – To evaluate preliminary results in terms of toxicity, local tumour control, and survival after preoperative concomitant chemoradiation for operable bulky cervical carcinomas.Patients and methods. – Between December 1991 and October 2001, 42 patients (pts) with bulky cervical carcinomas stage IB2 (11 pts), IIA (15 pts), and IIB (16 pts) with 1/3 proximal parametrial invasion. Median age was 45 years (range: 24–75 years) and clinical median cervical tumour size was 5 cm (range: 4.1–8 cm). A clinical pelvic lymph node involvement has been observed in 10 pts. All patients underwent preoperative external beam pelvic radiation therapy (EBPRT) and concomitant chemotherapy during the first and the fourth radiation weeks combining 5-fluorouracil and cisplatin. The pelvic dose was 40.50 Gy over 4.5 weeks. EBPRT was followed by low-dose-rate uterovaginal brachytherapy with a total dose of 20 Gy in 17 pts. After a rest period of 5–6 weeks, all pts underwent class II modified radical hysterectomy with bilateral lymphadenectomy. Para-aortic lymphadenectomy was performed in eight pts without pathologic para-aortic lymph node involvement. Twenty-one of 25 pts who had not received preoperative uterovaginal brachytherapy underwent postoperative low-dose-rate vaginal brachytherapy of 20 Gy. The median follow-up was 31 months (range: 3–123 months).Results. – Pathologic residual tumour or lymph node involvement was observed in 23 pts. Among the 22 pts with pathologic residual cervical tumour (<0.5 cm: nine pts; ≥0.5 to ≤1 cm: three pts; >1 cm: 10 pts), seven underwent preoperative EBRT followed by uterovaginal brachytherapy vs. 15 treated with preoperative EBRT alone (P = 0.23). Four pts had pathologic lymph node involvement, three pts had vaginal residual tumour, and four pts had pathologic parametrial invasion. The 2- and 5-year overall survival rates were 85% and 74%, respectively. The 2- and 5-year disease-free survival (DFS) rates were 80% and 71%, respectively. After multivariate analysis, the pathologic residual cervical tumour size was the single independent factor decreasing the probability of DFS (P = 0.0054). The 5-year local control rate and metastatic failure rate were 90% and 83.5%, respectively. Haematological effects were moderate. However, six pts had grade 3 acute intestinal toxicity. Four severe late complications requiring surgical intervention were observed (one small bowel complication, three ureteral complications).Conclusion. – Primary concomitant chemoradiation followed surgery for bulky operable stage I–II cervical carcinomas can be employed with acceptable toxicity. However, systematic preoperative uterovaginal brachytherapy should increase local tumour control. [Copyright &y& Elsevier]

Purpose. – To identify predicting factors of local control and survival after isolate local failure by statistical analysis of the data after breast-conserving treatment for early breast cancer.Methods and Patients. – In time of local failure, mean age was 54.7 years old , mean tumor size was 19.3 mm and recurrence was more often infiltrating ductal carcinoma (88%). Local recurrence was unifocal in 44 cases and localised outside of the site of the primary tumorectomy in 35 cases. Local failure treatment was a radical mastectomy or parietectomy (53 patients). Hormonotherapy was delivered in 36 patients and chemotherapy was delivered in 26 patients. Mean follow-up was 62 months.Results. – Fifteen patients developed second local recurrence in a mean time of 36 months. Five years local control rate was 68% after the first local failure. Surgery treatment (non-conservative surgery vs. conservative surgery) was the only factor which influenced local control. Six patients developed homolateral axillary and/or supraclavicular node recurrence. Twelve patients underwent metastasis in a mean time of 36 months after the first local recurrence. Five years metastasis free survival rate was 80%. Peritumoral vascular invasion in time of the first local failure increased metastasis risk and node recurrence. Second local failure did not alter metastasis free survival.Conclusion. – Peritumoral vascular invasion in time of the first local failure decreased node and metastasis free survival. Surgery should be radical, but the place of chemotherapy and hormonotherapy was not definite. [Copyright &y& Elsevier]

Objectif de l’étude Dans les sarcomes des tissus mous des membres, la définition du volume d’irradiation permettant un taux de contrôle local optimal et limiter la toxicité reste controversée. Nous avons évalué la définition du volume d’irradiation selon des facteurs cliniques, de chirurgie et histologiques. Matériel et méthode Entre janvier 2008 et décembre 2009, les dossiers de 173 patients sur 11 centres ont été évalués. Le traitement comportait une chirurgie et une radiothérapie pré- (12 %) ou postopératoire (88 %). L’objectif principal était l’évaluation de la dose et du volume d’irradiation et leur impact sur le taux de contrôle local et la toxicité. L’impact de la qualité de la chirurgie sur le volume d’irradiation, le taux de contrôle local et le mode de récidive a été également évalué. Résultats L’âge médian était 60 ans. La taille médiane était de 75 mm. La résection était R0 dans 73 % des cas et R1 dans 27 %. Six pour cent des tumeurs ont été morcelés pendant l’opération dans les centres experts et 16 % dans les centres non experts. La dose médiane était de 54 Gy. Le taux de récidive locale était de 11,2 %, 45 % des récidives étaient dans le premier volume cible prévisionnel (PTV1), 28 % dans le deuxième (PTV2), 18 % en bordure et 9 % hors volume irradié. Il y avait 15,2 % de fibroses de grade 2, 12,5 % d’œdèmes de garde 2, 6,9 % de raideurs articulaires de garde 2, 6,9 % de neuropathies de grade 2 et 3,2 % de fractures. Il n’y avait pas de toxicité ≥ G3. Le morcellement tumoral était corrélé avec plus de récidives locales (22 % contre 8 % p = 0,004) et à distance (50 % contre 17 % p = 0,0029). Une dose de plus de 60 Gy n’avait pas d’impact sur le taux de contrôle local. Conclusion Dans cette étude, la qualité de la chirurgie était le facteur pronostique le plus important. La majorité des récidives locales sont survenues dans le volume irradié, ce qui traduit traduisant une bonne définition de ce volume mais suggère une certaine radiorésistance. La toxicité était acceptable. [ABSTRACT FROM AUTHOR]