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International audience; PurposeThe purpose of this study was to assess the efficacy in terms of neck failure of an initial neck dissection before definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinomas, as well as the dosimetric impact and the acute and delayed morbidity of this approach.Materials and methodsAll patients consecutively treated between 2009 and 2018 with definitive chemoradiotherapy using intensity-modulated conformal radiotherapy (IMRT) for a histologically proven N2-3 oropharyngeal squamous cell carcinomas were retrospectively included. The therapeutic approach consisted of induction chemotherapy, followed by cisplatine-based chemoradiotherapy preceded or not by neck dissection. Neck dissection was discussed on a case-by-case basis in a dedicated multidisciplinary tumour board for patients with a dissociated response to induction chemotherapy, defined as a better response on the primary than on the node. Chemoradiotherapy without neck dissection was systematically performed in case of a major lymph node response to induction chemotherapy (decrease in size of 90% or more). Intensity-modulated radiotherapy using a simultaneous-integrated boost delivered 70 Gy in 35 fractions on macroscopic tumour volumes, 63 Gy on intermediate-risk levels or extra-nodal extension and 54 Gy on prophylactic lymph node areas.ResultsTwo groups were constituted: 47 patients without an initial neck dissection (62.7%), and 28 patients with a neck dissection prior to definitive chemoradiotherapy (37.3%). Initial patient characteristics were not statistically different between the two groups. The median follow-up was 60.1 months (range: 3.2–119 months). Incidence of neck failure was higher in patients without neck dissection (P = 0.015). The neck failure rate at 5 years was 19.8% (95% confidence interval: 7.4–30.6%; P = 0.015) without neck dissection versus 0% following neck dissection. All lymph node failures occurred in the planned target volume at 70 Gy. Upfront neck dissection suggested a decrease in the mean dose received by the homolateral parotid gland (P = 0.01), mandible (P = 0.02), and thyroid gland (P = 0.02). Acute toxicity of chemoradiotherapy after neck dissection suggested a reduction in grade ≥ 3 adverse events (P = 0.04), early discontinuation of concomitant chemotherapy (P = 0.009) and feeding tube-dependence (P = 0.008) in univariate analysis. During follow-up, there was no difference between the two groups in terms of xerostomia, dysgeusia, dysphagia or gastrostomy dependence in univariate analysis.ConclusionNeck dissection prior to definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinoma was associated with high neck control without additional mid and long-term morbidity.; Objectif de l’étudeIl s’agissait d’évaluer l’efficacité en termes d’échec ganglionnaire du curage ganglionnaire cervical initial dans les carcinomes épidermoïdes de l’oropharynx de stade N2-3 pris en charge par chimioradiothérapie exclusive, ainsi que l’impact dosimétrique et la tolérance aiguë et tardive de cette approche.Matériels et méthodesTous les patients consécutivement pris en charge entre 2009 et 2018 par chimioradiothérapie exclusive à l’aide d’une radiothérapie conformationelle avec modulation d’intensité (RCMI) pour un carcinome épidermoïde de l’oropharynx de stade N2-3 selon la septième édition de la classification TNM American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) ont été rétrospectivement inclus. La stratégie thérapeutique consistait en une chimiothérapie d’induction, suivie d’une chimioradiothérapie exclusive à base de cisplatine précédée ou non d’un curage ganglionnaire cervical. Le curage ganglionnaire cervical a été discuté au cas par cas en réunion de concertation multidisciplinaire dédiée chez les patients en situation de réponse dissociée à la chimiothérapie d’induction, à savoir une réponse de meilleure qualité sur la tumeur primitive que sur les ganglions. Une chimioradiothérapie sans curage ganglionnaire cervical a été systématiquement réalisée en cas de réponse ganglionnaire majeure à la chimiothérapie d’induction (diminution en taille de 90 % ou plus). La RCMI délivrait en boost intégré une dose de 70 Gy en 35 fractions dans les volumes tumoraux macroscopiques, 63 Gy dans les aires ganglionnaires à risque intermédiaire ou en rupture capsulaire et 54 Gy dans celles irradiées à visée prophylactique.RésultatsDeux groupes ont été constitués : 47 (62,7 %) patients sans curage ganglionnaire cervical initial, et 28 (37,3 %) patients avec un curage ganglionnaire cervical avant la chimioradiothérapie. Les caractéristiques initiales des patients n’étaient pas statistiquement différentes entre les deux groupes. Le recul médian était de 60,1 [3,2–119] mois. L’incidence des échecs ganglionnaires était plus élevée chez les patients n’ayant pas eu de curage ganglionnaire cervical (p = 0,015). Le taux d’échec ganglionnaire à 5 ans était de 19,8 % (intervalle de confiance à 95 % : 7,4–30,6) en l’absence de curage ganglionnaire cervical contre aucune rechute (0 %) après curage ganglionnaire cervical. Tous les échecs ganglionnaires se trouvaient dans le volume cible prévisionnel à 70 Gy. Le curage ganglionnaire cervical a permis une diminution de la dose moyenne reçue par la parotide homolatérale (p = 0,01), la mandibule (p = 0,02) et la thyroïde (p = 0,02). La tolérance aiguë de la chimioradiothérapie avait tendance à être meilleure chez les patients ayant eu un curage ganglionnaire avec une réduction des événements indésirables de grade ≥ 3 (p = 0,04), de l’arrêt précoce de la chimiothérapie concomitante (p = 0,009) et du recours à une gastrostomie (p = 0,008) en analyse unifactorielle. Au cours du suivi, il n’existait aucune différence entre les deux groupes en termes de xérostomie, de dysgueusie, de dysphagie ou de dépendance à la gastrostomie en analyse unifactorielle.ConclusionLe curage ganglionnaire cervical avant la chimioradiothérapie exclusive dans les carcinomes épidermoïdes de l’oropharynx de stade N2-3 était associé à un très bon taux de contrôle ganglionnaire sans morbidité supplémentaire à moyen et long termes.

Riassunto La radioterapia e da un secolo una parte imprescindibile dell’arsenale terapeutico contro i cancri oto-rino-laringoiatrici. Gli sviluppi tecnologici hanno permesso, negli ultimi 20 anni, di ottenere una precisione millimetrica nell’erogazione della dose, garantendo trattamenti meno tossici a breve e a lungo termine, con una migliore efficacia. La radioterapia conformazionale a intensita modulata e divenuta lo standard per l’irradiazione esterna e la brachiterapia mantiene alcune indicazioni, in particolare nei tumori del cavo orale. L’associazione dell’irradiazione esterna e di una chemioterapia o di una terapia mirata concomitante ha permesso di aumentare la sua efficacia, e la strategia di conservazione degli organi e divenuta progressivamente un punto di riferimento come alternativa agli interventi chirurgici mutilanti. Questo articolo presenta i principi biologici, tecnici e organizzativi della radioterapia, le indicazioni dei trattamenti sistemici concomitanti e delle irradiazioni postoperatorie, le indicazioni dell’irradiazione nelle localizzazioni piu frequenti, nonche i principi tecnici e i risultati delle reirradiazioni. Sono, inoltre, presentati gli effetti secondari della radioterapia e sono discussi gli sviluppi attuali e futuri della radioterapia per i cancri oto-rino-laringoiatrici.

Resumen La radioterapia es, desde hace un siglo, un elemento imprescindible en el arsenal terapeutico contra los canceres otorrinolaringologicos. Las evoluciones tecnologicas han permitido en los ultimos 20 anos alcanzar una precision milimetrica en la administracion de dosis, lo que garantiza unos tratamientos menos toxicos a corto y a largo plazo, con una mayor eficacia. La radioterapia de intensidad modulada conformacional se ha convertido en el estandar para la irradiacion externa y la braquiterapia conserva algunas indicaciones, en particular en los tumores de la cavidad bucal. La asociacion de irradiacion externa con quimioterapia o con una terapia dirigida concomitante ha permitido aumentar su eficacia y la estrategia de preservacion de organo se ha convertido progresivamente en una referencia como alternativa a las cirugias mutilantes. En este articulo se presentan los principios biologicos, tecnicos y organizativos de la radioterapia, las indicaciones de los tratamientos sistemicos concomitantes y de la radioterapia postoperatoria, las indicaciones de irradiacion en las localizaciones mas frecuentes, asi como los principios tecnicos y los resultados de las reirradiaciones. Tambien se presentan los efectos secundarios de la radioterapia y se mencionan los avances actuales y futuros de la radioterapia de los canceres otorrinolaringologicos.

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.

Resume Objectif de l’etude Evaluer la fatigue et la qualite de vie chez les patients traites par irradiation en conditions stereotaxiques et en determiner les facteurs predictifs. Materiel et methodes La fatigue a ete evaluee avec le questionnaire Brief Fatigue Inventory (BFI) et la qualite de vie par le QLQ-C30, a la premiere seance (T1), la derniere (T2), et 1–3 semaines apres la fin du traitement (T3). Resultats Parmi les 63 patients pris en charge de fevrier a mai 2017, 41 ont ete inclus dans l’analyse (22 exclus pour difficultes de comprehension, d’organisation, troubles psychologiques ou refus). Le nombre moyen de seances etait de 5 (± 2). Les taux de remplissage etaient respectivement de 98 %, 95 % et 81 %. Une majoration de la fatigue et une degradation de la qualite de vie ont ete observees chez 12 (29 %) et 14 (34 %) patients entre T1 et T2. En analyse unifactorielle, fatigue et qualite de vie etaient correlees avec l’indice de performance (p = 0,03 et 0,05), l’hemoglobinemie (p = 0,01 et 0,004), l’albuminemie (p = 0,01 et 0,06), la distance entre le domicile et le service (p = 0,05 et 0,02). En analyse multifactorielle, le sexe feminin (p = 0,012), l’albuminemie (p Conclusion Malgre l’hypofractionnement, la radiotherapie en conditions stereotaxiques entraine une majoration de l’asthenie et une alteration de la qualite de vie.

Resume Objectif de l’etude Pour faciliter la formation a la delineation, la Societe francaise de radiotherapie oncologique (SFRO) et l’association de formation continue en oncologie radiotherapie (Afcor) ont cree en 2008 un site Internet de radioanatomie et d’aide a la delineation. Materiel et methodes Entre 2015 et 2017, une mise a jour du site a ete entreprise, necessitant la mise en place de deux parties : des cours theoriques d’une part, et des ateliers de delineation en ligne d’autre part. Resultats Un nouveau site exploitant l’ensemble des nouvelles technologies numeriques a ete mis en ligne. Les cours ont ete realises sous forme de videos commentees et consultables a tout moment. La partie pratique offre une interface de delineation en ligne qui genere a la fin de l’exercice un rapport permettant de quantifier la qualite de sa delineation. Conclusion Siriade 2.0 est un outil numerique innovant qui s’inscrit en complement des formations initiales et continues deja disponibles.

The purpose of this study was to assess the efficacy in terms of neck failure of an initial neck dissection before definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinomas, as well as the dosimetric impact and the acute and delayed morbidity of this approach.All patients consecutively treated between 2009 and 2018 with definitive chemoradiotherapy using intensity-modulated conformal radiotherapy (IMRT) for a histologically proven N2-3 oropharyngeal squamous cell carcinomas were retrospectively included. The therapeutic approach consisted of induction chemotherapy, followed by cisplatine-based chemoradiotherapy preceded or not by neck dissection. Neck dissection was discussed on a case-by-case basis in a dedicated multidisciplinary tumour board for patients with a dissociated response to induction chemotherapy, defined as a better response on the primary than on the node. Chemoradiotherapy without neck dissection was systematically performed in case of a major lymph node response to induction chemotherapy (decrease in size of 90% or more). Intensity-modulated radiotherapy using a simultaneous-integrated boost delivered 70Gy in 35 fractions on macroscopic tumour volumes, 63Gy on intermediate-risk levels or extra-nodal extension and 54Gy on prophylactic lymph node areas.Two groups were constituted: 47 patients without an initial neck dissection (62.7%), and 28 patients with a neck dissection prior to definitive chemoradiotherapy (37.3%). Initial patient characteristics were not statistically different between the two groups. The median follow-up was 60.1months (range: 3.2-119months). Incidence of neck failure was higher in patients without neck dissection (P=0.015). The neck failure rate at 5years was 19.8% (95% confidence interval: 7.4-30.6%; P=0.015) without neck dissection versus 0% following neck dissection. All lymph node failures occurred in the planned target volume at 70Gy. Upfront neck dissection suggested a decrease in the mean dose received by the homolateral parotid gland (P=0.01), mandible (P=0.02), and thyroid gland (P=0.02). Acute toxicity of chemoradiotherapy after neck dissection suggested a reduction in grade≥3 adverse events (P=0.04), early discontinuation of concomitant chemotherapy (P=0.009) and feeding tube-dependence (P=0.008) in univariate analysis. During follow-up, there was no difference between the two groups in terms of xerostomia, dysgeusia, dysphagia or gastrostomy dependence in univariate analysis.Neck dissection prior to definitive chemoradiotherapy in N2-3 oropharyngeal squamous cell carcinoma was associated with high neck control without additional mid and long-term morbidity.

To evaluate trimodal conservative treatment as an alternative to radical surgery for urothelial muscle-invasive bladder cancer (MIBC). This retrospective study reported the carcinologic and functional results of patients (pts) presenting a cT2/T3 N0M0 operable MIBC and fit for surgery, treated by a conservative strategy. Treatment consisted of a transurethral resection (TURB) followed by concomitant bi-fractionated split-course radiochemotherapy (RCT) with 5FU-Cisplatine. A control cystoscopy was performed six weeks after the induction RCT (eq45Gy) with systematic biopsies. Patients with complete histologic response achieved RCT protocol. Salvage surgery was proposed to pts with persistent tumor. 313 pts (83% cT2 and 17% cT3) treated between 1988 and 2013 were included, with a median follow-up of 59 months and 67-year mean age. After the induction RCT, the histologic response rate was 83%. After five years, overall, disease-free, and functional bladder-intact survival rates were respectively 69%, 61%, and 69%, significantly better for pts in complete response after induction RCT. Late urinary and digestive toxicities were limited, with respective rates of 4% and 1.5% of grade 3 toxicity. Trimodal strategy with RCT after TURB showed interesting functional and oncologic results and should be considered as an alternative to surgery in well-selected pts.

Résumé De nouveaux concepts de consultations sont actuellement en train de profondément changer la façon d’exercer la médecine. L’utilisation de questionnaires standardisés, des questionnaires patients (PRO, patient-reported outcome, et son application informatique, ePRO) ont déjà fait irruption dans nos consultations. En parallèle, la télémédecine, voire l’utilisation d’agents conversationnels automatiques médicaux, permettent d’assurer une consultation à distance, plus accessible. Ces différents outils ont un intérêt majeur en oncologie, notamment dans le contexte de la chronicisation des maladies et du suivi à long terme que les oncologues radiothérapeutes prennent en charge. Dans cet article, nous détaillons chacun de ces nouveaux concepts.

International audience; De nouveaux concepts de consultations sont actuellement en train de profondément changer la façon d’exercer la médecine. L’utilisation de questionnaires standardisés, des questionnaires patients (PRO, patient-reported outcome, et son application informatique, ePRO) ont déjà fait irruption dans nos consultations. En parallèle, la télémédecine, voire l’utilisation d’agents conversationnels automatiques médicaux, permettent d’assurer une consultation à distance, plus accessible. Ces différents outils ont un intérêt majeur en oncologie, notamment dans le contexte de la chronicisation des maladies et du suivi à long terme que les oncologues radiothérapeutes prennent en charge. Dans cet article, nous détaillons chacun de ces nouveaux concepts

The use of adjuvant radiation in the treatment of soft-tissue sarcoma (STS) is equivocal in selected cases. Our objective was to compare the short-term outcomes in patients operated on for a local recurrence who had radiation for the primary tumour to those who were spared radiation. This was a retrospective study of 103 patients treated for a local recurrence: 48 (47%) with previous radiation and 55 (53%) without. Our primary outcome criterion was to identify the differences in the local treatment provided. Secondary outcomes were the cumulative incidence of a surgical site infection/wound complication (SSI/WC), variables associated with SSI/WC, and local recurrence. Amputation and the incidence of re-operation were significantly more frequent in patients who received previous radiation compared to patients without previous radiation (27% vs 9%, p = 0.02, for amputation; 26% vs 36% at 2 years for SSI/WC, p = 0.049). Multivariable regression models found previous radiation (p = 0.049), arteriopathy (p = 0.012), location at lower limb (p = 0.09), and use of a flap (0.0048) associated with the risk of SSI/WC. Previous radiation is associated with an increased risk of amputation and reoperation for SSI/WC when treating a local recurrence. This information should be accounted for when deciding for the use of radiation.

Objectifs Avec un âge median de 73 ans au diagnostic, le cancer de vessie touche frequemment les sujets âges. Or leur prise en charge n’est pas consensuelle, la chirurgie n’etant pas toujours possible lorsqu’il existe des elements de fragilite geriatrique. Le traitement trimodal (TMT) associant resection trans-uretrale (RTUV) puis radiochimiotherapie serait une alternative curative permettant la preservation de la vessie native. Methodes De 1988 a 2017, les patients (pts) des 75 ans ayant une tumeur de vessie infiltrant le muscle (T2-T3N0M0), traitees par TMT ont ete analyses. Le traitement comportait une RTUV suivie d’une radiotherapie HF2SQ pelvienne (3 Gy matin et soir J 1J 3J 15J 17) puis vesicale (2,5 Gy matin et soir J 29J 31 J 42J 44 chez les inoperables et a partir de la semaine 6 chez les operables, apres cystoscopie de controle), en concomitance avec une chimiotherapie par 5 FU et sels de platine. Les pts operables avaient une cystoscopie 5 semaines apres le temps pelvien. Les pts en reponse complete recevaient le complement vesical, les non-repondeurs avaient une cystectomie de rattrapage. Resultats Quatre-vingt-cinq patients (âge median 80 ans), de stade T2 et T3 ont ete selectionnes. Apres induction, le taux de reponse complete etait de 83 %. La survie globale (SG), specifique (SS), sans maladie infiltrante (SSMI) et sans metastase (SSM) a 3 ans etaient de 72 %, 82,5 %, 78,4 % et 84,9 %, a 5 ans de 61 %,77 %, 71,6 % et 82,9 % respectivement. Le taux de survie vessie preservee (SVP) etait de 70 % a 5 ans. Un ACCI > 6 (HR 0,3 ; p = 0,044) et une denutrition (HR 1,9 ; p = 0,032) ont impacte significativement la SG, la SS et la SSM. Un residu tumoral apres induction etait deletere sur la survie : SS (HR 3,6 ; p = 0.008), SSM (HR 3,6 ; p = 0,018) et SVP (HR 3,3 ; p = 0,003). Les toxicites tardives grade ≥ 3 urinaire et gastro-intestinale etaient de 2,6 % et 1,3 %. Conclusion Nous rapportons la plus grande serie de preservation vesicale des sujets de plus de 75 ans. La denutrition, un score de Charlson ajuste a l’âge > 6 et la presence d’un reliquat tumoral apres la phase d’induction sont des facteurs pronostiques defavorables. Le TMT avec l’IHF2SQ semble efficace et bien tolere chez des sujets âges selectionnes.

Local control of soft tissue sarcomas frequently involves adjuvant radiation to the surgical resection. When opting for post-operative radiation, care should be taken that radiation is started within some reasonable time after the surgery. We were interested to the proportion of patients who did not recieve optimal post-operative radiation and the variables associated. We retrospectively analyzed a series of 77 patients operated on for an extremity soft-tissue sarcoma and due for post-operative radiotherapy. Patients were considered to have received radiation optimally if radiation was started within 12 weeks of surgery. Variables associated with not receiving radiation optimally were looked for using univariable and multivariable regression models. Overall, 26 patients (34%; 95% CI: 23–45%) did not receive radiation optimally. Twenty (26%) did not start radiation within the 12-weeks mark and six (8%) could not have radiation at all. The main reason identified for not receiving radiation on time was the occurrence of a wound complication (14 (54%) patients). An increased body mass index (OR: 1.14; 95% CI: 1.02–1.26; p = 0.02) and an older age (OR: 1.55; 95% CI: 1.18–2.14; p = 0.04; of note, the OR are for a 10 year change) were significantly associated with not receiving radiation optimally. Patients with a social fragility (p = 0.04), metastatic spread at presentation (p = 0.04), and increased duration of surgery (p = 0.02) were more likely to develop a wound complication. About 34% of patients do not receive optimal post-operative radiation treatment. Older and obese patients have a higher risk of not receiving radiation optimally. The decision for pre- or post-operative radiation should account for these findings.

Modern radiation therapy techniques are characterized by high conformality to tumor volumes and steep dose gradients to spare normal organs. These techniques require accurate clinical target volume definitions and rigorous assessment of set up uncertainties using image guidance, a concept called image-guided radiation therapy. Due to alteration of patient anatomy, changes in tissue density/volumes and tumor shrinkage over the course of treatment, treatment accuracy may be challenged. This may result in excessive irradiation of organs at risk/healthy tissues and undercoverage of target volumes with a significant risk of locoregional failure. Adaptive radiation therapy (ART) is a concept allowing the clinician to reconsider the planned dose based on potential changes to accurately delivering the remaining radiation dose to the tumor while optimally minimizing irradiation of healthy tissues. There is little consensus on how to apply this concept in clinical practice. The current review investigates the current ART issues, including patient selection, clinical/dosimetric criteria and timing for re-planning, and practical technical issues. A practical algorithm is proposed for patient management in cases where ART is required.

Stereotactic radiotherapy represents a fundamental change in the practice of radiotherapy of lung cancers. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Stereotactic radiotherapy can be realized either by a dedicated accelerator (CyberKnife®) or by a conventional accelerator associated with specific systems. The two modalities deliver a very precise irradiation whose very good results published to date are similar. Some technical characteristics specific to each type of linear accelerator could guide the choice according to the target volume treated.

Stereotactic radiotherapy represents a fundamental change in the practice of radiotherapy of lung cancers. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Stereotactic radiotherapy can be realized either by a dedicated accelerator (CyberKnife

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.

To evaluate prospectively asthenia and the quality of life in patients treated by stereotactic body irradiation and to determine their predictive factors.Quality of life was assessed by the EORTC QLQ-C30 and asthenia was evaluated with the Brief Fatigue Inventory (BFI), on the first day (T1), last day (T2) and 1-3 weeks after the end of treatment (T3).Sixty-three patients were treated with stereotactic body irradiation from February 2017 to May 2017 and 41 were included in the analysis (22 patients excluded for lack of understanding, organization, psychologic disorders or refusal). The mean number of fractions was 5 (±2). The compliance to quality of life assessment was 98%, 95% was 81% at T1, T2 and T3, respectively. An increase of asthenia and a worsened quality of life were found in 12 (29%) and 14 (34%) patients between T1 and T2. Univariate analysis demonstrated a correlation between asthenia and quality of life were correlated with performans status (P=0.03 and 0.05 respectively), hemoglobin level (p=0.01 and 0.004), albumin level (P=0.01 and 0.06), distance between home and radiotherapy department (P=0.05 and 0.02). Multivariate analysis demonstrated a correlation between female gender (P=0.012), albumin level (P0.001), distance over 25km (P0.001) with asthenia, and albumin level (P=0.003), hemoglobin level (P=0.004) and previous chemotherapy (P=0.003) with quality of life. No influence of stereotactic body ratiotherapy parameters was seen.Despite hypofractionation, stereotactic body radiotherapy induced asthenia and deterioration of quality of life.

Goals Prospective evaluation of salivary gland preservation, overall survival and local recurrence-free survival after head and neck cancer treated by helical tomotherapy (HT). Material and methods From March 2007 to February 2009, 30 patients with head and neck cancer were treated by HT. The salivary excretion fraction (SEF) was assessed by technetium salivary gland scintigraphy before, and 6, 12 and 18 months after HT to define salivary gland preservation rates. Patients were reviewed every 3 months to assess clinical toxicity. Results The median follow-up was 4.3 years. The mean dose to the ipsilateral parotid gland (IPG) was 25.4 Gy. Good preservation of parotid gland function was observed in 84% of the 19 patients evaluated by scintigraphy at 18 months. The 5-year local recurrence-free survival (LRFS) was 100% among the 6 patients who received a dose of more than 26 Gy to the parotid gland. The 28-month LRFS was 33% in the group that received a dose of less than 20 Gy versus 91% in the group that received a dose of more than 20 Gy to the IPG. Conclusions Helical tomotherapy reduced the incidence and severity of xerostomia. A mean dose to the parotid between 20 and 26 Gy allowed preservation of salivary function without compromising treatment efficacy. However, parotid-sparing HT requiring a mean dose less than 20 Gy is associated with an increased risk of recurrence.

Resume Buts Evaluation prospective de la preservation des glandes salivaires, des survies globales et sans recidive locale apres traitement de cancers ORL par tomotherapie helicoidale (TH). Materiel et methodes De mars 2007 a fevrier 2009, 30 patients atteints de cancers ORL ont ete traites par TH. La fraction d’excretion salivaire (FES) a ete evaluee par scintigraphie au technetium avant, 6, 12 et 18 mois apres la TH, permettant de definir le taux de preservation glandulaire. Parallelement, les patients ont ete examines tous les 3 mois pour evaluer les toxicites cliniques. Resultats Le suivi median a ete de 4,3 ans. La dose moyenne recue aux glandes parotides homolaterales (GPH) a ete de 25,4 Gy. Dix-neuf patients ont pu etre evalues a 18 mois par scintigraphie, et ils ont eu une bonne preservation des GP (84 %). Parmi les 6 patients ayant recu plus de 26 Gy dans la parotide, la survie sans recidive locale (SSRL) etait de 100 % a 5 ans. La SSRL a 28 mois etait de 33 % dans le groupe ayant recu moins de 20 Gy versus 91 % dans le groupe ayant recu plus de 20 Gy a la GPH. Conclusions La tomotherapie helicoidale nous a permis de reduire l’incidence et la severite de la xerostomie. Nous avons montre qu’une dose moyenne delivree aux parotides entre 20 et 26 Gy preservait la fonction salivaire sans compromettre l’efficacite du traitement. Par contre, la preservation parotidienne limitant la dose moyenne en dessous de 20 Gy augmente le risque de recidive locale.

Purpose To retrospectively analyse female patients treated for urethral adenocarcinoma, modalities of treatment and long-term outcomes. Patients Four cases of primary female urethral adenocarcinoma were treated in the departments of urology and radiation-oncology at Georges-Pompidou and Necker hospitals (France) over a 7-year period. Results All of them underwent surgery, with three presenting stage pT3-pT4 and one a positive cytology on inguinal node. Three patients received adjuvant cisplatin-based chemoradiotherapy up to 60 Gy, and one preoperative chemoradiotherapy at 45 Gy. Two recurrences were observed: one local relapse occurred at 9 months from the diagnosis and was treated by anterior pelvic exenteration followed by chemoradiotherapy, with no recurrence. One tumour relapsed both at the local level and on distant metastatic sites at 9 months from the diagnosis, and died 21 months after this progression. Median survival and progression-free survival are respectively 4.2 years and 13 months. Three patients are alive at 7, 4.5 and 3 years from diagnosis. Conclusion Female urethral adenocarcinoma is a very rare entity and often present in locally advanced stages. Initial extensive surgery with pelvic exenteration should be considered, followed by chemoradiotherapy according to the surgical margins and lymph nodes involvement.

Purpose The main goal of palliative radiotherapy is to reduce patient's discomfort. But sometimes patients do not receive any benefits from this treatment because of rapid worsening of their general condition. This prospective monocentric study assessed the effective delivery of palliative radiotherapy. Materials and methods From 1st December 2015 to 29th February 2016, all consecutive patients receiving palliative radiotherapy in our hospital were included. The primary endpoint was the effective delivery of palliative radiotherapy according to the initial prescription (total dose, overall treatment time and fractionation). The secondary endpoints were the number of treatment breaks, the clinical benefit, the number of deaths and the delays for admission in the palliative care unit. Results Fifty-nine patients were included and 64 treatments were analysed. The treatment sites were: bone (70.3%) and brain (21.9%). The treatment goals were: pain control only (43.8%), decompression only (21.9%), pain control and decompression (32.8%), haemostatic aim (1.6%). Palliative treatment was achieved in 57 cases (89%). Temporary interruption of the radiotherapy treatment was necessary in six cases (9.4%; three for medical reason, three for logistic reason). The main reason of permanent interruption was worsening of performance status (seven cases). Palliation of symptoms (complete or partial responses) was obtained in 44 cases (68.8%). Seven patients (11.9%) died during the month after the end of the treatment. No delay or cancellation for admission in the palliative care unit were observed. Conclusion Palliative radiotherapy was completed as originally planned in 51 cases (79.9%) with a clinical benefit for 44 cases (68.8%). Radiation therapy must not be neglected as a palliative treatment at the end-of-life.

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

Radiotherapy performed to treat head and neck cancer results in considerable side effects and the patient must be provided with all the necessary information and regular monitoring. From the announcement of the diagnosis, during and after the radiotherapy, the nurse coordinator identifies and assesses the needs, expectations and concerns of the patients. Their role helps to simplify and personalise the care pathway, providing a liaison between the different professionals and offering support for the patient.

Objectif de l’etude La radiotherapie hypofractionnee en conditions stereotaxiques est un traitement efficace et reconnu pour les patients oligometastatiques cerebraux. Sa planification est par contre longue du fait des nombreux organes ou structures a delineer. Cette etude compare la performance de deux logiciels commerciaux de segmentation automatique. Materiel et methode Une tomodensitometrie a ete acquise en position de traitement et fusionnee avec une IRM diagnostique. Les volumes ont ete delinees manuellement par un clinicien (yeux, cristallins, nerfs optiques, chiasma, tronc cerebral). Deux segmentations automatiques de ces memes structures ont ete realisees (iPlan© et Smart Segmentation©). Les fichiers RTSTRUCT ont ete compares avec le module de comparaison Artistruct© d’Aquilab. Notre critere de jugement principal etait le pourcentage de volume delinee commun defini comme (A ∩ B)/A avec A le volume delinee manuellement et B le volume obtenu par segmentation automatique. Les criteres secondaires etaient le coefficient de Dice–Sorensen : 2 (A ∩ B)/(A + B), l’overlap ratio : (A ∩ B)/(A U B) et le volume delinee additionnel : (B − A)/B. Resultats Nous avons inclus 20 patients consecutifs. L’accord entre les volumes delinees manuellement et automatiquement etait faible. Les pourcentages de volumes communs etaient compris entre 7,71 % et 82,54 %, les coefficients de Dice–Sorensen entre 0,0745 et 0,8398, l’overlap ratio entre 0,0414 et 0,7275 et les pourcentages de volume additionnels entre 9,80 % et 92,25 % sans superiorite claire de l’un ou l’autre logiciel. Conclusion La precision de la segmentation automatique reste bien trop faible pour une utilisation en routine clinique. Le role du clinicien reste essentiel dans la definition des volumes et ce meme dans une situation aussi reproductible que le crâne.

Ionizing radiation may interfere with electric components of pacemakers or implantable cardioverter-defibrillators. The type, severity and extent of radiation damage to pacemakers, have previously been shown to depend on the total dose and dose rate. Over 300,000 new cancer cases are treated yearly in France, among which 60% are irradiated in the course of their disease. One among 400 of these patients has an implanted pacemaker or defibrillator. The incidence of pacemaker and implanted cardioverter defribillator increases in an ageing population. The oncologic prognosis must be weighted against the cardiologic prognosis in a multidisciplinary and transversal setting. Innovative irradiation techniques and technological sophistications of pacemakers and implantable cardioverter-defibrillators (with the introduction of more radiosensitive complementary metal-oxide-semiconductors since 1970) have potentially changed the tolerance profiles. This review of the literature studied the geometric, dosimetric and radiobiological characteristics of the radiation beams for high energy photons, stereotactic irradiation, protontherapy. Standardized protocols and radiotherapy optimization (particle, treatment fields, energy) are advisable in order to improve patient management during radiotherapy and prolonged monitoring is necessary following radiation therapy. The dose received at the pacemaker/heart should be calculated. The threshold for the cumulated dose to the pacemaker/implantable cardioverter-defibrillator (2 to 5 Gy depending on the brand), the necessity to remove/displace the device based on the dose-volume histogram on dosimetry, as well as the use of lead shielding and magnet are discussed.

Objectif de l’etude Evaluer l’epuisement professionnel dans le service de radiotherapie de l’hopital europeen Georges-Pompidou (Paris), pour ameliorer l’organisation et la qualite de vie au travail. Materiel et methode Toutes les personnes travaillant dans le service de radiotherapie depuis plus de 3 mois ont ete sollicitees pour remplir anonymement le questionnaire valide de burn out de Malasch la semaine 13 de 2018. L’epuisement professionnel (score eleve s’il etait superieur ou egal a 30), la depersonnalisation (score eleve s’il etait superieur ou egal a 12) et l’accomplissement personnel (score faible s’il etait inferieur ou egal a 33) ont ete evalues selon le type de metier et la classe d’âge. Des scores d’epuisement professionnel et depersonnalisation eleves temoignent d’un risque significatif de burn out, notamment en cas de score d’accomplissement personnel bas. Resultats Sur un effectif attendu de 70 employes, 67 ont repondu (66 evaluables). Les scores d’epuisement professionnel et d’accomplissement personnel n’ont pu etre calcules pour trois physiciens jugeant le questionnaire mal adapte a leur metier. Les scores moyens globaux plus ou moins l’ecart-type d’epuisement professionnel, de depersonnalisation et d’accomplissement personnel etaient respectivement de 15,46 ± 8,85 (faible), 4,79 ± 5,23 (faible) et 36,49 ± 7,19 (moyen). Malgre une dispersion importante des valeurs, moins de 10 % des personnes avaient un score d’epuisement professionnel (6 %) ou de depersonnalisation (8 %) eleve. Ces deux scores etaient eleves chez un seul membre de l’equipe. Le score d’accomplissement personnel etait bas chez 14 employes (22 %) de tous types de metier. Il n’a pas ete observe de difference selon l’âge. Le groupe infirmier(e)s–aides-soignant(e)s se distinguait par un score d’epuisement professionnel plus eleve (18,5, moyen), mais un meilleur score d’accomplissement personnel (41,6 eleve). Conclusion L’evaluation de l’epuisement professionnel par le questionnaire de Malasch permet d’avoir une photographie de la qualite de vie au travail et de detecter des difficultes par metier pouvant conduire a une reorganisation du travail. La levee de l’anonymat permettrait une detection des difficultes individuelles eventuellement transmissibles a la medecine du travail.

Introduction: Stereotactic hypofractionated radiotherapy is an effective treatment for brain metastases in oligometastatic patients. Its planning is however time-consuming because of the number of organs at risk to be manually segmented. This study evaluates 2 automated segmentation commercial software. Methods: Patients were scanned in the treatment position. The computed tomography scan was registered on a magnetic resonance imaging and volumes were manually segmented by a clinician. Then 2 automated segmentations were performed (with iPlan and Smart Segmentation). RT STRUCT files were compared with Aquilab’s Artistruct segment comparison module. We selected common segmented volume ratio as the main judging criterion. Secondary criteria were Dice-Sørensen coefficients, overlap ratio, and additional segmented volume. Results: Twenty consecutive patients were included. Agreement between manual and automated contouring was poor. Common segmented volumes ranged from 7.71% to 82.54%, Dice-Sørensen coefficient ranged from 0.0745 to 0.8398, overlap ratio ranged from 0.0414 to 0.7275, and additional segmented volume ranged from 9.80% to 92.25%. Each software outperformed the other on some organs while performing worse on others. Conclusion: No software seemed clearly better than the other. Common segmented volumes were much too low for routine use in stereotactic hypofractionated brain radiotherapy. Manual editing is still needed.

Objectif de l’etude Interet d’une gastrostomie prophylactique avant chimioradiotherapie concomitante d’un carcinome epidermoide des voies aerodigestiuves superieures. Materiel et methodes Etude prospective monocentrique des patienst pris en charge par chimioradiotherapie concomitante avec (groupe A) ou sans gastrostomie prophylactique (groupe B) posee par voie radiologique entre avril 2011 et aout 2012. Resultats Soixante patients (âge median de 58 ans) d’indice de performance selon l’OMS p = 0,042) et a 6 mois (A : − 3,4 % ± 4,3 ; B − 7,8 % ± 5,6 : p = 0,008), mais non significativement a 12 mois ( p = 0,09). L’albuminemie etait comparable en fin de traitement ( p = 0,87). Huit patients (17 %) du groupe B dont la dose moyenne delivree a la muqueuse orale ( p = 0,001) et au muscle pharynge constricteur superieur ( p = 0,005) etait plus elevee ont necessite une gastrostomie prophylactique de rattrapage. La dependance a la gastrostomie prophylactique apres le traitement etait de 4,9 mois ± 7,2 et 7,5 mois ± 7,6 en cas de gastrostomie prophylactique ou de gastrostomie prophylactique de rattrapage (ns), et concernait a 6 et 12 mois deux pts (17 et 18 %) avec la gastrostomie prophylactique contre un et 0 patients (14 et 0 %) avec gastrostomie prophylactique de rattrapage. Conclusion Chez des patients atteints de carcinome epidermoide des voies aerodigestives superieurs localement evolue pris en chage par chimioradiotherapie concomitante, la gastrostomie prophylactique permet de limiter la perte de poids a 1 et 6 mois, avec une faible dependance a long terme.

Introduction Le controle local des sarcomes des parties molles implique une resection chirurgicale et une radiotherapie adjuvante. Certains auteurs ont rapporte un taux de recidive locale accrue lorsque le temps entre la chirurgie et le debut du rayonnement est prolonge. Des etudes ont etudie l’effet de decaler la radiotherapie sur le controle local. Le but de notre etude est d’analyser dans une population de patients ayant beneficie d’une exerese chirurgicale de sarcome des parties molles, le taux de patients qui n’ont pas eu la radiotherapie dans les delais convenables et les raisons. Materiel et methodes Nous avons analyse retrospectivement sur une periode de 4 ans, une serie consecutive de 77 patients operes d’un sarcome des tissus mous des extremites et programmes pour de la radiotherapie postoperatoire. Les patients ont ete consideres comme ayant eu la radiotherapie de facon optimale si les seances ont ete lancees dans les 12 semaines suivant la chirurgie. Resultats Vingt-six patients (34 % ; 95 % CI : 23 %–45 %) n’ont pas recu la radiotherapie de maniere optimale. Vingt (26 %) n’ont pas commence la radiotherapie dans les 12 premieres semaines et 6 (8 %) n’ont pas recu de rayonnement du tout. Les differentes raisons identifiees de retard a la radiotherapie etaient- des complications cicatricielles dans 14 cas (54 %), dont 7 (50 %) ont necessite des reinterventions ; 3 infections (19 %), qui ont tout ete reoperes ; et 3 cas (19 %) de reintervention pour une autre raison (tumorales ou mecaniques) et 6 patients pour des raisons organisationnelles. Les variables associees a une la radiotherapie non optimale etaient (univariee)- l’âge ( p = 0,023) ; le score ASA ( p = 0,081) ; l’indice de masse corporelle (IMC) ( p = 0,04) ; dans le modele final (multivarie), les facteurs associes a une radiotherapie inadaptee etaient IMC (OR : 1,14 ; 95 % CI : 1,02–1,26 ; p = 0,017) et l’âge avance (OR : 1,55 ; 95 % CI : 1,18–2,14 ; p = 0,0085). Discussion et conclusion Environ 34 % des patients ne recoivent pas le traitement optimal radiotherapie postoperatoire. Les patients avec le plus grand risque sont les patients âges et obeses. On peut discuter chez ces malades de l’indication a realiser une radiotherapie preoperatoire pour etre sur de donner l’integralite du traitement.

Objectif de l’etude Evaluer la realisation effective des radiotherapies palliatives dans une cohorte de patients consecutifs traites dans notre centre. Materiel et methode Etude prospective monocentrique incluant tous les patients pris en charge par radiotherapie externe a visee palliative, du 1er decembre 2015 au 29 fevrier 2016. L’objectif principal etait le respect de l’etalement conformement a la prescription initiale. Les objectifs secondaires etaient le nombre de traitements interrompus (transitoirement ou definitivement) et l’evaluation de son efficacite (totale, partielle, aucune) a un mois de la fin de la radiotherapie. Les parametres suivants ont egalement ete analyses : indice de performance selon l’Eastern Cooperative Oncology Group (ECOG), nombre de lignes de traitement, contact avec l’equipe mobile de soins palliatifs, lieu de vie et temps de transport et schema de prescription de radiotherapie. Resultats Cinquante-neuf patients ont ete inclus et 64 traitements analyses (deux traitements chez trois patients, trois chez un). Les principaux sites irradies etaient le rachis (31 %), le bassin (27 %) et l’encephale (22 %). Le traitement etait a visee antalgique seule (44 %), decompressive seule (22 %), antalgique et decompressive (33 %) et hemostatique (2 %). L’etalement etait conforme a la prescription initiale pour 80 % des traitements. Sept traitements (11 %) ont ete interrompus definitivement (dont deux avant la 1e seance), tous en raison d’une alteration de l’etat general. Six traitements ont ete interrompus transitoirement (9 %), trois pour raison medicale, trois pour probleme logistique. L’efficacite a ete evaluee comme totale ou partielle dans 69 % des cas. Conclusion L’etalement a ete conforme a la prescription dans une tres grande majorite des cas. Les arrets de traitements pour alteration de l’etat general ne sont cependant pas rares et justifient d’identifier au mieux les patients susceptibles de tirer benefice de la radiotherapie palliative.

Alcaligenes eutrophus A5 catabolizes biphenyl to CO2 via benzoate and 4-chlorobiphenyl to 4-chlorobenzoate. In curing and conjugation experiments, the A5 endogenous 51-kb IncP1 plasmid pSS50 was found to be dispensable for biphenyl and 4-chlorobiphenyl catabolism. Transfer of the biphenyl- and 4-chlorobiphenyl-degrading phenotype by means of pSS50 was observed at a frequency of 10(-5) per transferred plasmid in matings of A5 with other A. eutrophus strains. Transconjugants harbor enlarged pSS50 derivatives which contain additional genetic information governing the oxidation of biphenyl and 4-chlorobiphenyl to benzoate and 4-chlorobenzoate and originating from the chromosome of strain A5. The following observations indicate that the catabolic genes reside on a 59-kb large transposon (Tn4371) for which a restriction map is presented. (i) Tn4371 transposes between different replicons and at different locations of the same replicon. (ii) Transposition was observed in a Rec- strain of A. eutrophus. (iii) Tn4371 transposes as a single, contiguous piece of DNA. Although an RP4::Tn4371 plasmid was stably maintained in different hosts, the plasmid conferred growth on biphenyl only when present in strains of A. eutrophus and in an Acinetobacter sp. strain.

Ionizing radiation may interfere with electric components of pacemakers or implantable cardioverter-defibrillators. The type, severity and extent of radiation damage to pacemakers, have previously been shown to depend on the total dose and dose rate. Over 300,000 new cancer cases are treated yearly in France, among which 60% are irradiated in the course of their disease. One among 400 of these patients has an implanted pacemaker or defibrillator. The incidence of pacemaker and implanted cardioverter defribillator increases in an ageing population. The oncologic prognosis must be weighted against the cardiologic prognosis in a multidisciplinary and transversal setting. Innovative irradiation techniques and technological sophistications of pacemakers and implantable cardioverter-defibrillators (with the introduction of more radiosensitive complementary metal-oxide-semiconductors since 1970) have potentially changed the tolerance profiles. This review of the literature studied the geometric, dosimetric and radiobiological characteristics of the radiation beams for high energy photons, stereotactic irradiation, protontherapy. Standardized protocols and radiotherapy optimization (particle, treatment fields, energy) are advisable in order to improve patient management during radiotherapy and prolonged monitoring is necessary following radiation therapy. The dose received at the pacemaker/heart should be calculated. The threshold for the cumulated dose to the pacemaker/implantable cardioverter-defibrillator (2 to 5 Gy depending on the brand), the necessity to remove/displace the device based on the dose-volume histogram on dosimetry, as well as the use of lead shielding and magnet are discussed.

Ionizing radiation is frequently used for cancers with a curative intent for many patients. The total dose delivered on the tumour plays a major factor for locoregional control. Increasing the dose to the tumour volume is generally correlated with an increased dose to normal tissue. Dose constraints to organs at risk must be taken into account for the planning of external beam radiation. A high dose will generate more acute and late side effects. Medical doctors should record these toxicities prospectively. Registration and grading should be simple, reproducible and sensitive in order to obtain an accurate and appropriate evaluation for each organ. Several scales have been published in the literature (WHO, EORTC/RTOG, LENT-SOMA, NCI CTCAE) but none have a satisfactory level. The National Cancer Institute has proposed several version of the CTCAE and its latest version 4.0, currently appears to be the most adapted. The advantage of using only this common and universal classification will be to harmonize practices and have a common language.

Objectif Evaluer le respect de l’etalement theorique dans une cohorte de 185 patients consecutifs traites par irradiation a visee curative et les raisons de son allongement, et proposer des actions correctives. Materiels et methodes Etude prospective unicentrique incluant tous les patients traites par irradiation a visee curative quelle que soit la localisation, du 1er decembre 2013 au 28 fevrier 2014, sur les trois accelerateurs du centre. Les motifs de non-realisation d’une seance ont ete recueillis prospectivement. L’analyse a pris en compte les parametres suivants : âge, sexe, activite professionnelle, temps et mode de transport, type tumoral, dose, hospitalisation, chimiotherapie concomitante, poste de traitement (accelerateurs 1, 2 et 3). Resultats Cent quatre-vingt-cinq patients ont ete inclus, les dossiers de 183 etaient evaluables, deux n’ayant pas termine le traitement). L’etalement a ete respecte pour 31 (17 %). Il etait en moyenne allonge de 4,6 jours [0–29 j ; mediane : 3 j]. Le nombre moyen de seances decalees etaient de 3,4 [0–17 seances ; mediane : 2]. Les motifs de non-venue etaient : panne pour 32,2 %, maintenance pour 29,3 %, jour ferie pour 11 %, toxicite du traitement pour 9,4 %, planification inadequate pour 8,6 %, autre maladie pour 3,9 %, refus de traitement pour 2,1 %, convenance personnelle pour 1,5 %, refus d’attente pour 0,8 %, transport pour 0,3 %, defaut de communication pour 0,3 %, autre pour 0,6 %. Aucun des parametres d’analyse n’a eu d’impact significatif sur l’etalement a l’exception du poste de traitement, en raison des pannes (accelerateur 1 : 22/60 patients ; 2 : 20/61 ; 3 : 48/62 ; p Conclusion L’etalement a ete bien respecte a l’exclusion des pannes et des maintenances. Leur impact sur l’etalement a ete minimise par l’ouverture systematique du plateau technique le samedi.

Genetically modified microorganisms (GMMs) are frequently used as producers of mammalian immunomodulatory proteins, e.g. interferons and interleukins. Here we have examined the question of whether such GMMs interact in a way different from that of their non-modified parent micro-organisms with mammalian antimicrobial defence systems. As a typical GMM host micro-organism we used Escherichia coli K12, and as a typical immunomodulatory protein produced by a GMM we used mouse interferon-gamma (MuIFN-gamma). Two experimental systems are described in which synergistic "toxic" biological effects are induced by a combined treatment with E. coli and MuIFN-gamma but not, or less so, by the parental strain and the recombinant protein separately. First, it is shown that the IFN-gamma-producing GMM, or mixtures of E. coli cells and IFN-gamma, are cytolytic for mouse embryo fibroblastoid cells (MEF), whereas no cell killing occurs in MEF cultures treated with control E. coli cells or in those treated with bacteria-free recombinant IFN-gamma. Second, it is demonstrated that intraperitoneal injection in mice of high but not low numbers of control E. coli K12 cells induces a shock-like mortality, whereas co-injection with IFN-gamma induces killing at low numbers. IFN-gamma-producing E. coli cells cause a mortality rate that does not differ from that of control E. coli cells, probably because in these experimental conditions the level of recombinant MuIFN-gamma per cell is insufficiently high. Taken together, these data indicate that synergistic toxic effects induced by bacteria and their recombinant products can occur and may in certain situations enhance the intrinsic toxic capacity of the GMM. Synergistic toxic effects may thus be of relevance for identifying the safety level that should be employed when working with GMMs.

Alcaligenes eutrophus strains exhibiting both plasmid-borne heavy metal resistance and haloaromatic-degrading functions were obtained by intraspecific conjugation. The strains which we constructed expressed catabolic and resistance markers together. Degradation of various polychlorinated biphenyl isomers and 2,4-D (2,4-dichlorophenoxyacetic acid) was observed in the presence of 1 mM nickel or 2 mM zinc, provided that the metal resistance determinant was present in the catabolizing strain. Such strains may be useful for decontamination of sites that are polluted with both organic compounds and heavy metals.

1. Every hot vulcanization of a rubber compound leads to a volume decrease of the vulcanized material, or to an increase of its specific gravity. 2. The increase of the specific gravity of a rubber system depends directly on the condensation of rubber only, and does not depend on fillers. 3. The extent of the increase of the specific gravity of a vulcanized material is proportional to the quantity of rubber in the compound and to the degree of vulcanization. 4. Active fillers, as ZnO, and accelerators can influence the growth of the specific gravity of a vulcanized compound as agents promoting vulcanization; hence carbon black, contrary to Ditmar's opinion, can hardly contribute to condensation.