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The oligometastatic disease concept suggests that patients with a limited number of metastases have a favorable prognosis. Radical local treatment of oligometastatic patients has then increased given developments in imaging (mainly positron emission tomography and brain magnetic resonance imaging) and access to effective and better tolerated treatments. Stereotactic radiotherapy has the advantage of being noninvasive, allowing a good rate of local control and a limited number of side effects. A better definition of oligometastatic disease, particularly for non-small cell lung cancer (NSCLC), has recently been published. For patients with NSCLC, two randomized phase II trials also suggested that the addition of a radical local treatment results in encouraging survival data, with a good safety profile. A single-arm phase II finally showed a benefit when combining a radical local treatment with an anti-PD1 immunotherapy. This review describes the definitions of oligometastatic disease, the main prospective findings including radiation therapy, and prospects for oligometastatic NSCLC patients.

Introduction Thymomas are rare intrathoracic malignancies that may be aggressive and difficult to treat. Knowledge and level of evidence for treatment strategies are mainly based on retrospective studies or expert opinion. Currently there is no strong evidence that postoperative radiotherapy after complete resection of localized thymoma is associated with survival benefit in patients. RADIORYTHMIC is a phase III, randomized trial aiming at comparing postoperative radiotherapy versus surveillance after complete resection of Masaoka-Koga stage IIb/III thymoma. Systematic central pathologic review will be performed before patient enrollment as per the RYTHMIC network pathway. Patients and Methods Three hundred fourteen patients will be included; randomization 1:1 will attribute either postoperative radiotherapy (50-54 Gy to the mediastinum using intensity-modulated radiation therapy or proton beam therapy) or surveillance. Stratification criteria include histologic grading (thymoma type A, AB, B1 vs B2, B3), stage, and delivery of preoperative chemotherapy. Patient recruitment will be mainly made through the French RYTHMIC network of 15 expert centers participating in a nationwide multidisciplinary tumor board. Follow-up will last 7 years. The primary endpoint is recurrence-free survival. Secondary objectives include overall survival, assessment of acute and late toxicities, and analysis of prognostic and predictive biomarkers. Results The first patient will be enrolled in January 2021, with results expected in 2028.

Sarcomas are rare tumours arising from mesenchymal tissue. A multimodal management in an expert centre combining surgery and radiotherapy is the current standard of care for localized soft-tissue sarcomas of the extremities, to enable limb-sparing strategies. The delivery of pre- radiotherapy or postoperative radiotherapy offers similar local control and survival rates but the toxicity profile is quite different: preoperative radiotherapy increases the risk of wound complications and postoperative radiotherapy affects long-term functional outcomes. While postoperative radiotherapy has long been the rule, especially in Europe, technical improvements with image-guided- and intensity-modulated radiotherapy associated with a better management of postoperative wounds has tended to change practices with more frequent preoperative radiotherapy. More recently the possibilities of a hypofractionated regimen or potentiation by nanoparticles to increase the therapeutic index plead in favour of a preoperative delivery of radiotherapy. The aim of this paper is to report pros and cons of pre- and post-operative radiotherapy for soft-tissue sarcomas.

Resume La chimioradiotherapie concomitante est le standard therapeutique chez les patients atteints de cancer bronchique non a petites cellules non resecable de stade III, quels que soient leurs sous-types histologiques et leurs caracteristiques moleculaires. Dans ce cadre, seuls 15 a 30 % des patients demeurent en vie cinq ans apres la chimioradiotherapie et ce chiffre n’a pratiquement pas change malgre de multiples essais randomises. Au cours des cinq dernieres annees, le blocage des points de controle immunitaires par anti-PD-(L)1 a revolutionne la prise en charge du cancer bronchique non a petites cellules metastatique, devenant un standard en premiere ligne et deuxieme ligne de traitement. Plusieurs etudes precliniques ont mis en evidence une liberation accrue d’antigenes tumoraux, une presentation amelioree de ces antigenes et l’augmentation de l’infiltration des lymphocytes T dans les tumeurs irradiees. L’immunotherapie a recemment ete evaluee pour les patients atteints de cancer bronchique non a petites cellules localement evolue ayant recu une irradiation thoracique. Suite a l’essai PACIFIC, l’anticorps anti-PD-L1 durvalumab est apparu comme un nouveau standard en consolidation pour les patients atteints de cancer bronchique non a petites cellules de stade III non resecable dont la maladie n’a pas progresse apres une chimioradiotherapie concomitante a base de sels de platine. L’immunoradiotherapie apparait donc comme une nouvelle association encourageante chez les patients atteints de cancer bronchique non a petites cellules localisees. De nombreux essais evaluent donc actuellement l’interet d’une immunotherapie concomitante a la chimioradiotherapie et/ou de l’ajout d’une chimiotherapie associee a l’immunotherapie de consolidation chez les patients atteints de cancer bronchique non a petites cellules localement evolue.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR)= 1.02 (0.66-1.58), two-sided P= 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR= 0.95 (0.59-1.52), P= 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade =3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Resume Au cours des vingt dernieres annees, plusieurs evolutions ont revolutionne la prise en charge des cancers du poumon, composes a plus de 85 % de carcinomes bronchiques non a petites cellules et de pres de 15 % de carcinomes bronchiques a petites cellules. La question des volumes cibles ganglionnaires s’est posee lorsqu’est apparue la possibilite d’une plus grande precision des traitements avec la radiotherapie conformationnelle tridimensionnelle. S’appuyant initialement sur des series chirurgicales, de nombreuses etudes retrospectives et prospectives ont evalue le risque de recidive ganglionnaire isolee des traitements ou seules les aires envahies etaient ciblees (involved-field radiotherapy, IFRT) par rapport aux traitements standards de l’epoque, irradiant systematiquement les aires ganglionnaires envahies mais egalement d’autres aires ganglionnaires a risque de recidive, de facon prophylactique (elective nodal irradiation, ENI). Pour ce qui concerne les carcinomes bronchiques non a petites cellules localement evolues, pris en charge par association de chimiotherapie et de radiotherapie ou en situation postoperatoire et pour les carcinomes bronchiques a petites cellules, la grande majorite des publications a retrouve des taux de recidive ganglionnaire isolee inferieurs a 5 % a 2 ans, a condition que le stade pretherapeutique ait ete etabli avec les techniques modernes d’investigations (tomographie par emission de positrons-tomodensitometrie, endoscopie, etc.). L’abandon de l’irradiation prophylactique ganglionnaire est donc devenu un standard, et a permis le developpement des approches avec escalade de dose tout en diminuant la toxicite œsophagienne, cardiaque et pulmonaire de la radiotherapie. En consequence, les grands essais cliniques developpes a partir des annees 2000 impliquant la radiotherapie et les recommandations des differentes societes savantes ont fait le choix d’abandonner les techniques d’irradiation prophylactique ganglionnaire au profit de la radiotherapie limitee aux aires ganglionnaires envahies.

Purpose/Objective(s) NBTXR3, a novel radioenhancer activated by radiotherapy (RT) demonstrated superior efficacy, as preoperative treatment in patients with locally advanced soft tissue sarcoma (LA STS) compared to RT alone. Primary endpoint of pCR rate (16% vs 8%; P = 0.044) and main secondary endpoint of R0 margin rate (16% vs 8%; P = 0.042) were met while no modification of the early RT-associated safety profile was observed, leading to market authorization. Here we report on the long-term safety, limb function and quality of life. Materials/Methods This phase II/III randomized (1:1), international trial included adult patients with LA STS of the extremity or trunk wall, requiring preoperative RT. Patients received either a single intratumoral injection of NBTXR3 (equivalent to 10% of tumor volume, at 53.3g/L), plus EBRT (arm A) or EBRT alone (arm B) (50 Gy in 25 fractions), followed by surgery. Here we report on safety of NBTXR3+RT which was evaluated as secondary endpoint. Data were recorded on the “all treated population” during at least a two-year follow-up. Important parameters related to HR-QoL including functional outcome were studied using the EQ-5D, RNLI, TESS and MSTS questionnaires. Results Patients had at least two-year follow-up and the lost to follow-up rate was very low (1.9%). RT-related SAEs were observed in 11.2% (10/89) vs 13.3% (12/90) in A vs B. Post-treatment AEs, any grade, were observed in 51.7% (46/89) vs 57.8% (52/90) and serious post-treatment AEs in 13.5% (12/89) vs 24.4% (22/90) of patients in A vs B. Long-term safety continues to demonstrate that NBTXR3 plus RT has no impact on post-surgical wound complications (24.7% vs 36.7%, A vs B). Furthermore, the evaluation of radiation late toxicities in limbs such as fibrosis, arthrosis and edema that may alter limb function showed no difference between arms (4.5% vs 7.7%, 2.2% vs 0.0% and 6.7% vs 2.2% respectively in A vs B). In addition, sequelae or chronic tissue disturbances at the former tumor localization were similar in both treatment arms, confirming that the increase of energy dose deposit and the physical presence of NBTXR3 did not impact post-treatment limb functions. Accordingly, HR-QoL evaluation yielded no difference in functional outcome. Finally, second primary cancer was observed in 1 patient in arm A and 6 patients in arm B and the intratumoral injection of NBTXR3 did not induce cancer cell seeding at the former tumor site. Conclusion These results demonstrate that the use of NBTXR3 did not change the late onset toxicity profile of EBRT, nor modified its bystander effect. Taken together, the long-term safety data presented here, and the previously published efficacy data reinforce the favorable benefit-risk ratio of the use of NBTXR3 in patients with LA STS. NCT02379845

The purpose of this study was to compare efficacy and tolerance between radiofrequency ablation (RFA) and surgery for the treatment of oligometastatic lung disease.This retrospective study reviewed patients treated in two institutions for up to 5 pulmonary metastases with a maximal diameter of 4cm and without associated pleural involvement or thoracic lymphadenopathy. Patient demographics, tumor characteristics, treatment outcome, and length of hospital stay were compared between the two groups. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and pulmonary or local tumor progression rates.Among 204 patients identified, 78 patients (42 men, 36 women; mean age, 53.3±14.9 [SD]; age range: 15-81 years) were treated surgically, while 126 patients (59 men, 67 women; mean age, 62.2±10.8 [SD]; age range: 33-80 years) were treated by RFA. In the RFA cohort, patients were significantly older (P0.0001), with more extra-thoracic localisation (P=0.015) and bilateral tumour burden (P=0.0014). In comparison between surgery and RFA cohorts, respectively, the 1- and 3-year OS were 94.8 and 67.2% vs. 94 and 72.1% (P=0.46), the 1- and 3-year PFS were 49.4% and 26.1% vs. 38.9% and 14.8% (P=0.12), the pulmonary progression rates were 39.1% and 56% vs. 41.2% and 65.3% (P0.99), and the local tumour progression rates were 5.4% and 10.6% vs. 4.8% and 18.6% (P=0.07). Tumour size2cm was associated with a significantly higher local tumor progression in the RFA group (P=0.010). Hospitalisation stay was significantly shorter in the RFA group (median of 3 days; IQR=2 days; range: 2-12 days) than in the surgery group (median of 9 days; IQR=2 days; range: 6-21 days) (P0.01).RFA should be considered a minimally-invasive alternative with similar OS and PFS to surgery in the treatment of solitary or multiple lung metastases measuring less than 4cm in diameter without associated pleural involvement or thoracic lymphadenopathy.

Background: Brain metastases (BM) are common in patients with small cell lung cancer (SCLC). In recent years, the role of whole brain radiotherapy (WBRT) for brain metastases in lung cancer is being reevaluated, especially in the context of new systemic treatments available for SCLC. With this analysis, we investigate decision-making in SCLC patients with BM among European experts in medical oncology and radiation oncology.Methods: We analyzed decision-making from 13 medical oncologists (selected by IASLC) and 13 radiation oncologists (selected by ESTRO) specialized in SCLC. Management strategies of individual experts were converted into decision trees and analyzed for consensus.Results and conclusion: In asymptomatic patients, chemotherapy alone is the most commonly recommended first line treatment. In asymptomatic patients with limited volume of brain metastases, a higher preference for chemotherapy without WBRT among medical oncologists compared to radiation oncologists was observed.For symptomatic patients, WBRT followed by chemotherapy was recommended most commonly. For limited extent of BM in symptomatic patients, some experts chose stereotactic radiotherapy as an alternative to WBRT.Significant variation in clinical decision-making was observed among European SCLC experts for the first line treatment of patients with SCLC and BM. (C) 2020 Published by Elsevier B.V.

Aims Primary tracheal–bronchial adenoid cystic carcinoma (thoracic adenoid cystic carcinoma; TACC) is a rare and aggressive malignant tumour. Radiotherapy results have not been previously individualised in this setting. Patients and methods Records of 31 patients with TACC (74% tracheal and 26% bronchial) who received radiotherapy between February 1984 and September 2014 were retrospectively analysed. Results Surgical removal of the primary tumour was carried out for most (71%) patients, and 13/22 (59%) had R1 or R2 (1/22) margins. The mean tumour size was 4.1 cm, 10 (32%) had associated lymph node involvement and 13 (41%) had perineural invasion (PNI). Adjuvant and definitive radiotherapy were delivered for 22 (71%) and nine patients, respectively. The mean delivered dose was 62 Gy (40–70 Gy) and eight patients had a radiotherapy boost (mean 19 Gy, range 9–30 Gy, two with endobronchial brachytherapy). At a median follow-up of 5.7 years, the 5 year overall survival and progression-free survival (PFS) rates were 88% and 61%, respectively. There were three local relapses and 10 metastatic relapses (mean delay 3.2 years), resulting in 5 year local and metastatic relapse rates of 10% and 26%, respectively. The prognostic factors in the univariate analysis for both decreased overall survival and PFS were: age ≥50 years (hazard ratio 6.2 and 3.8) and the presence of PNI (hazard ratio 10.3 and 4.1); and for PFS only: a radiotherapy dose ≤ 60 Gy (hazard ratio 3.1). Late toxicities were: tracheotomy due to symptomatic tracheal stenosis ( n = 5), G3 dyspnoea ( n = 4), hypothyroidism ( n = 5) and pericarditis ( n = 4). Conclusion Radiotherapy dose may affect local control and the presence of PNI should be considered as an adverse prognostic factor. TACC irradiation conferred good local control rates, when comparing these results with historical series.

Resume Les cancers bronchiques non a petite cellules (CBNPC) de stade III regroupent des maladies heterogenes en termes de presentation clinique initiale et d’histologie. En cas d’envahissement ganglionnaire mediastinal minime, la chirurgie est une option soit d’emblee, soit apres traitement neoadjuvant par chimiotherapie a base de sels de platine. Si le patient a ete opere d’emblee et qu’il est de stade III, la chimiotherapie adjuvante est un standard. La radiotherapie post-operatoire est recommandee en cas de resection R1 ou R2, mais l’evidence recente n’a pas pu demontrer un benefice en termes de survie globale pour les patients pN2. Si le patient est inoperable, une chimiotherapie (2 a 4 cycles d’un doublet a base de platine) associee de facon concomitante a une radiotherapie (60-66 Gy en 6 semaines) est recommandee preferentiellement a un schema sequentiel. Recemment, l’essai PACIFIC a demontre le benefice en survie globale d’un an de consolidation par Durvalumab, apres radiochimiotherapie (en l’absence de progression). L’association de l’immunotherapie a la radiotherapie selon divers schemas est a l’etude. En cas de contre-indication a la chimiotherapie, des schemas de radiotherapie exclusive hypo ou hyperfractionnee acceleree peuvent etre proposes. La meilleure selection des patients, les ameliorations techniques de la radiotherapie conformationnelle (la meilleure prise en compte des mouvements respiratoires, le meilleur controle des incertitudes positionnelles, et la modulation d’intensite permettent d’etendre les indications de radiotherapie et de diminuer certaines toxicites) ainsi que l’implementation de l’imagerie metabolique dans les planifications des traitements ont egalement contribue a l’amelioration des resultats. © 2021 SPLF. Publie par Elsevier Masson SAS. Tous droits reserves.

Background The recent identification of molecular alterations in some lung adenocarcinomas has led to the emergence of effective targeted therapies thus drastically improving their prognosis.The aim of our study was to investigate the association between driver oncogene alterations and metastatic patterns on imaging assessment, in a large cohort of metastatic lung adenocarcinoma patients. Methods From January 2010 to May 2017, 656 patients with stage IV lung adenocarcinoma with molecular analysis were studied retrospectively including 135 EGFR, 81 ALK, 47 BRAF, 141 KRAS, and 146 negative tumors for these 4 mutations (4N). After review of the complete imaging report by two radiologists (junior and senior) to identify metastatic sites, univariate correlation analyzes were performed. Results We found differences in metastatic tropism depending on the molecular alteration type when compared to the non-mutated 4N group: in the EGFR group, pleural metastases were more frequent (32% versus 20%; p = 0.021), and adrenal and node metastases less common (6% versus 23%; p Conclusions The application of these correlations between molecular status and metastatic tropism in clinical practice may lead to earlier and more accurate identification of patients for targeted therapy, savings in iterative biopsies, as well as improved and personalized imaging interpretation. Legal entity responsible for the study Alison Dormieux. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

International audience; BackgroundNETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry.Patients and methodsPatients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497).ResultsAmong the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P

International audience; Lung cancer is the leading cause of cancer-related mortality and more than half of the cases are diagnosed at a metastatic stage. Major progress in terms of systemic treatments has been achieved in recent decades. Access to new anti-PD-(L) 1 immunotherapies and targeted therapies for non-small cell lung cancer (NSCLC) with oncogenic addiction such as EGFR mutation or ALK rearrangement have led to improved outcomes. Patients with limited progression of their disease during systemic treatment may be a particular subgroup. This oligoprogressive state is characterized by a limited number of sites in progression, implying that the other sites remain controlled and therefore sensitive to systemic treatments. The advent of non-invasive techniques such as stereotactic radiotherapy, radiofrequency, and mini-invasive surgery has led to a precise re-evaluation of local ablative treatments in this situation. Local treatment of the oligoprogressive lesion(s) may allow modification of the natural history of the disease, maintenance of effective systemic targeted treatment and, ultimately, to improved survival. Data validating an aggressive local therapeutic approach in oligoprogressive NSCLC patients are currently limited and essentially retrospective. Several international trials are underway that could confirm the clinical benefit of radical local treatment in oligoprogressive advanced NSCLC patients.

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.

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.

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.

Resume Les patients presentant un carcinome bronchique non a petites cellules et survivant a long terme sont surtout ceux dont le traitement a comporte une chirurgie d'exerese complete. Neanmoins, leur risque de recidive reste eleve, non seulement metastatique mais egalement locoregionale, d'autant plus que le stade est eleve. La chimiotherapie adjuvante fait partie du traitement standard des patients operes de stades II et IIIA, et le benefice absolu en termes de survie a 5 ans en faveur de la CT varie entre 4 et 15 %. Concernant la radiotherapie adjuvante, son role n'est toujours pas clairement etabli surtout dans les stades III. En effet, la meta-analyse publiee en 1998, qui avait evalue la radiotherapie mediastinale postoperatoire chez 2 128 patients inclus dans 9 essais comparant chirurgie a chirurgie plus radiotherapie postoperatoire (RPO), a montre une diminution absolue de la survie de 7 % a 2 ans (55 % en cas de chirurgie seule vs 48 % en cas de RPO). Les analyses de sous-groupes ont montre que la RPO pouvait âtre deletere en termes de survie globale principalement chez les patients n'ayant pas d'envahissement mediastinal. D'apres la meta-analyse, la RPO n'a donc pas de place dans le traitement des patients pN0 ou pN1, mais son role devrait âtre mieux evalue chez les patients ayant une atteinte ganglionnaire mediastinale (pN2). Mâme si plusieurs etudes plus recentes (retrospectives ou de sous-groupes d'essais randomises ayant evalue la chimiotherapie adjuvante) ont pu montrer une diminution du taux de rechutes locales, grâce a une radiotherapie mediastinale plus moderne, et suggerer un benefice de la RPO chez les patients pN2 en resection complete, il n'y a pas d'etude randomisee recente prouvant son benefice. Il en est de mâme pour les patients avec envahissement N2 prouve, operes apres une chimiotherapie neoadjuvante. En se basant sur ces donnees de la litterature, la RPO peut donc âtre une option therapeutique, chez les patients ayant un envahissement ganglionnaire mediastinal prouve, en association a une chimiotherapie adjuvante ou neoadjuvante. Une etude de phase III, actuellement en cours ( Lung ART IFCT 0503) devrait permettre d'etablir la place de la RPO dans ce groupe de patients. Chez les patients ayant une resection incomplete (R1 ou R2) et en l'absence de reprise chirurgicale possible, il existe un fort consensus en faveur d'une RPO, malgre l'absence d'essai randomise sur la question.

Background This phase I study evaluated the safety and efficacy of the oral mTOR inhibitor everolimus in combination with thoracic radiotherapy followed by consolidation chemotherapy in locally advanced or oligometastatic untreated non-small-cell lung cancer (NSCLC). Patients and methods Everolimus dose was escalated in incremental steps [sequential cohorts of three patients until the occurrence of dose-limiting toxicity (DLT)] and administered orally weekly (weekly group: dose of 10, 20 or 50 mg) or daily (daily group: 2.5, 5 or 10 mg), 1 week before, and during radiotherapy until 3.5 weeks after the end of radiotherapy. Two cycles of chemotherapy (cisplatin–navelbine) were administrated 4.5 weeks after the end of radiotherapy. Results Twenty-six patients were included in two centers, 56% had adenocarcinoma and 84% had stage III disease. In the weekly group (12 assessable patients), everolimus could be administered safely up to the maximum planned weekly dose of 50 mg; however, one patient experienced a DLT of interstitial pneumonitis at the weekly dose level of 20 mg. In the daily group (9 assessable patients): one DLT of interstitial pneumonitis with a fatal outcome was observed at the daily dose level of 2.5 mg; two other DLTs (one grade 3 esophagitis and one bilateral interstitial pneumonitis) were found at the daily dose level of 5 mg. Overall there were five patients with G3–4 interstitial pneumonitis related to treatment. Among 22 assessable patients for response, there were 9 (41%) partial response and 7 (32%) stable disease. At a median follow-up of 29 months, the 2-year overall survival and progression-free survival actuarial rates were 31% and 12%, respectively. Conclusion In previously untreated and unselected NSCLC patients, the recommended phase II dose of everolimus in combination with thoracic radiotherapy is 50 mg/week. Pulmonary toxicity is of concern and should be carefully monitored to establish the potential role of mTOR inhibitor with concomitant radiotherapy. EudraCT N 2007-001698-27.

Background To analyse the natural history of extra-abdominal wall desmoid-type fibromatosis (DF) and compare outcome in patients who underwent initial surgery with those who did not. Patients and methods All consecutive patients affected by primary sporadic extra-abdominal wall DF observed between January 1992 and December 2012 were included. Patients were divided into surgical (SG) or non-surgical groups (NSG) according to initial treatment. Relapse free survival was calculated for SG, and crude cumulative incidence (CCI) of switching to surgery or other treatments for NSG. Results 216 patients were identified, 94 in SG (43%), 122 in NSG (57%). A shift towards a more systematic use of a conservative approach (78% of all comers) was observed in the latter years (2006–2012), although a small proportion of patients (28%) had been offered the conservative strategy even in the early period (1992–2005). Median follow-up (FU) was 49 mo. (interquartile (IQ), 20–89 mo.), 76 months for SG and 39 months for NSG. 5-year relapse-free survival (RFS) for SG was 80% (95% confidence interval (CI), 72–89%). For the NSG, 5-year CCI of switching to surgery was 5% (95% CI: 1.7%, 14%), and 51% to other treatments (95% CI: 41%, 65%). 27 (20%) NSG patients underwent spontaneous regression. Conclusion A non-surgical approach to extra-abdominal wall DF allowed surgery to be avoided in the majority of patients. This approach can be safely proposed and surgery offered as an option in selected cases.

BACKGROUND The role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial. METHODS Two hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment. RESULTS Three of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105). CONCLUSION In this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.

Resume Les cancers bronchiques a petites cellules (CBPC), qui representent moins de 20 % de l’ensemble des cancers bronchiques, ont un risque de dissemination eleve et precoce. Ainsi, deux tiers d’entre eux sont diagnostiques a un stade metastatique. Actuellement, le traitement des formes non metastatiques repose sur une association radiochimiotherapie avec sels de platine et etoposide. Le pourcentage eleve de rechutes cerebrales a conduit a proposer une irradiation prophylactique cerebrale (IPC) chez les bons repondeurs. L’IPC fait partie integrante du traitement standard. Les progres sont surtout lies a une meilleure integration de la radiotherapie thoracique et cerebrale avec la polychimiotherapie. Il reste encore de nombreuses questions et cela devrait stimuler plus d’essais therapeutiques afin d’optimiser les modalites de polychimiotherapie et de radiotherapie (dose, fractionnement optimal), la meilleure facon d’associer ces deux traitements et d’evaluer de nouvelles approches therapeutiques comme l’immunotherapie.

To report on clinical outcome and toxicity profile after combined treatment that included radiation therapy (RT) in patients with localized sarcoma within an irradiated field.Individual clinical data from all consecutive patients diagnosed and treated for a localized SIF between January 2000 and October 2011 at the Institut Claudius Regaud, Toulouse, France, were retrospectively reviewed. Outcomes of patients with SIF who underwent adjuvant or definitive radiotherapy were compared with patients who did not receive further RT.Of the 27 patients eligible for this study: surgery alone (S), surgery followed by RT (S + RT) or definitive RT (RT) was performed in 16, 8 and 2 cases respectively. The rate of unresectable, gross or microscopically positive margin disease among the 10 re-irradiated patients was significantly higher than the non re-irradiated group (90% vs. 12% p0.001). After a median follow-up of 3.8 years, there was a trend toward longer survival and better local control in the subgroup of patients who received adjuvant or definitive RT compared to the rest of the cohort with an acceptable toxicity profile. The 4-year relapse free survival rates of patients treated with and without RT were 53% and 27% respectively (p = 0.09).SIF complete surgical resection is often difficult to achieve, enhancing the risk of relapse. RT should be discussed in case of unresectable tumor or after suboptimal surgery as part of intensified local management that has a curative intent.

Background NETSARC (netsarc.org) is a network of 26 sarcoma reference centers with specialized multidisciplinary tumor boards (MDTB) aiming to improve the outcome of sarcoma patients. Since 2010, presentation to an MDTB and expert pathological review are mandatory for sarcoma patients nationwide. In the present work, the impact of surgery in a reference center on the survival of sarcoma patients investigated using this national NETSARC registry. Patients and methods Patients’ characteristics and follow-up are prospectively collected and data monitored. Descriptive, uni- and multivariate analysis of prognostic factors were conducted in the entire series (N = 35 784) and in the subgroup of incident patient population (N = 29 497). Results Among the 35 784 patients, 155 different histological subtypes were reported. 4310 (11.6%) patients were metastatic at diagnosis. Previous cancer, previous radiotherapy, neurofibromatosis type 1 (NF1), and Li–Fraumeni syndrome were reported in 12.5%, 3.6%, 0.7%, and 0.1% of patients respectively. Among the 29 497 incident patients, 25 851 (87.6%) patients had surgical removal of the sarcoma, including 9949 (33.7%) operated in a NETSARC center. Location, grade, age, size, depth, histotypes, gender, NF1, and surgery outside a NETSARC center all correlated to overall survival (OS), local relapse free survival (LRFS), and event-free survival (EFS) in the incident patient population. NF1 history was one of the strongest adverse prognostic factors for LRFS, EFS, and OS. Presentation to an MDTB was associated with an improved LRFS and EFS, but was an adverse prognostic factor for OS if surgery was not carried out in a reference center. In multivariate analysis, surgery in a NETSARC center was positively correlated with LRFS, EFS, and OS [P