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Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFRAn ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFROne hundred twenty-eight patients were included and analyzed: 11% had EGFRWe highlighted a link between the EGFR

Despite significant therapeutic advances in the treatment of locally advanced inoperable non-small cell lung cancer (NSCLC), notably through adjuvant immunotherapy, the rate of therapeutic failure remains high. The use of positron emission tomography with fluorodeoxyglucose (FDG-PET), respiratory motion and intensity modulated radiotherapy (IMRT) have led to therapeutic improvements with reduced toxicity and better local control. The optimal dose to be delivered remains unknown due to discordant results of studies for almost 20 years and the way to define the area to benefit from a dose increase (whole volume, subvolume defined by pre- or per-radiotherapy PET).

Objectif Determiner, sur des fantomes et des patients, l’impact de SubtlePET, un algorithme de debruitage developpe par intelligence artificielle basee sur l’apprentissage profond, applique aux donnees brutes de TEP-FDG a moindre statistique par rapport aux temps d’acquisition utilises habituellement, en tenant compte des activites d’injection europeennes. Materiel et methode Des images de spheres faiblement et fortement contrastees en FDG (SBR= 2 et 5) et du fantome NEMA IEC et de micro-spheres fortement contrastees (SBR = 5) du fantome Jaszczak ont ete acquises sur 3 appareils de TEP-TDM differents (General Electric Healthcare Discovery 710, DMI4 et IQ4) ; 110 patients presentant differentes pathologies ont ete inclus. Pour chaque fantome ou patient, les images ont ete acquises avec la statistique d’acquisition habituelle (PET100) et post-traitees avec l’algorithme SubtlePET avec la moitie (PET50 + SP) ou le tiers (PET33 + SP donnees des fantomes uniquement). Resultats Pour 50 % des donnees, le niveau de bruit ainsi que les indices SUVmax sont compenses par SubtlePET (i.e. PET50 + SP). A l’inverse, meme ameliores par SubtlePET, nos resultats suggerent qu’une reduction de 66 % des statistiques (i.e. PET33 + SP) conduit a une perte potentielle d’information en termes d’augmentation du bruit et surtout de detectabilite des lesions. En ce qui concerne l’ensemble des donnees des patients, les images PET100 et PET50 + SP etaient visuellement comparables. L’algorithme SubtlePET a ete capable de recuperer correctement les valeurs SUVmax des lesions et de maintenir un niveau de bruit et une detectabilite equivalents aux images natives. Conclusion Sur la base de nos resultats, SubtlePET semble etre pret a etre utilise en pratique clinique pour des acquisitions a demi-duree ou a demi-dose par rapport aux parametres de temps et d’injection habituellement utilises en France et en Europe. Les consequences d’un tel outil sont potentiellement importantes pour l’organisation et l’activite des services (augmentation des flux de patients, developpement de l’activite par traceurs onereux).

The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small-cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. 2-Deoxy-2-[Thirty-four patients with non-resectable lung cancer underwent [The mean pre-RT and per-RT [The correlation between [

PET/CT has become a standard examination in oncology but is probably still underused for radiotherapy planning. However, except for the clinical research data that shows the interest of this examination in considering personalized and adaptive radiotherapy, it is also important in defining target volumes. However, before using it in clinical practice, a few prerequisites are required to know the acquisition and segmentation methods. Ideally, PET/CT should become a standard examination for radiotherapy departments in the same way as planning CT and tomorrow as MRI.

Background Chemoradiotherapy is the reference curative-intent treatment for nonresectable locally advanced non-small-cell lung carcinoma (NSCLC), with unsatisfying survival partially due to radiation resistance in hypoxic tissues, raising the question of targeted radiotherapy. Objective To evaluate the risk-benefit of radiotherapy boost on hypoxic tumors in NSCLC patients treated by curative-intent chemoradiotherapy in an open-label, nonrandomized, phase II clinical trial developed from 2012 to 2015 with a 3-year follow-up. Multicenter study performed in 15 French academic centers ( NCT01576796 ). Participants: eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. Seventy-nine patients underwent a run-in period, of which 54 were included. Twenty-four patients completed the study at 3 years. 18F-fluoromisonidazole (18F-MISO) positron emission tomography/computed tomography was performed to determine the hypoxic profile of patients (34 positive and 20 negative). Those with positive 18F-FMISO status and without organ-at-risk constraints (n = 24) received radiotherapy boost (70–84 Gy); the others received standard radiotherapy (66 Gy). Overall survival (OS), progression-free survival (PFS), and safety. Hypotheses tested were formulated before data collection. Results: fifty-four patients were evaluated, with a median age of 61 (41–76) years. OS and PFS rates at 1, 2, and 3 years were, respectively, 87%, 58.2%, and 48.5%, and 59.3%, 36.4%, and 28.8%. The median OS in the positive 18F-FMISO group was 25.8 months and was not reached at 3 years in the negative (P = 0.01). A difference was also observed for PFS (12 vs. 26.2 months, P = 0.048). By focusing on positive 18F-FMISO patients, no difference was observed in OS according to the dose, probably because of the small sample size (P = 0.30). However, the median OS seemed to be in favor of boosted patients (26.5 vs. 15.3 months, P = 0.71). In patients who underwent boost, no significant early or late toxicities were observed. Conclusions and relevance 18F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features. In the group of 18F-FMISO-positive patients, radiotherapy boost seems to improve the OS by 11.2 months. These results deserve further attention in a future clinical trial devoted to hypoxic patients to confirm boost efficacy.

Objectif de l’etude La chimioradiotherapie est le traitement de reference des cancers bronchiques non a petites cellules localement evolues. L’efficacite de ce traitement reste mediocre, avec un taux important de recidives locoregionales. Des essais en cours testent une augmentation de doses dans un volume selectionne par tomographie par emission de positons (TEP). L’objectif de ce travail etait d’evaluer l’impact d’une augmentation de doses de radiotherapie de 74 Gy les volumes definis par une TEP au fluoromisonidazole (F-miso) ou au fluorodesoxyglucose (FDG) pretherapeutique et au FDG pendant la radiotherapie (a 42 Gy). Materiel et methode Dans le cadre d’une etude ancillaire RTEP5 (programme hospitalier de recherche clinique [PHRC] de 2011), une etude dosimetrique a ete realisee chez les patients atteints de cancer defini comme hypoxiques par la TEP au F-miso pretherapeutique. Quatre dosimetries ont ete realisees par patient : une etude a 66 Gy sur l’ensemble du volume defini par la tomodensitometrie, trois etudes avec le meme volume a 66 Gy et une augmentation de doses a 74 Gy dans des volumes definis par TEP ( biologic target volume [BTV]) : au FDG, pretherapeutique (seuillage a 70 % de la standard uptake value maximale [SUVmax]), au F-miso, pretherapeutique (seuillage a 1,4) et au FDG pendant la therapeutique a 42 Gy (seuillage a 40 % de la SUVmax). Toutes dosimetries ont ete realisees pour une radiotherapie conformationnelle avec modulation d’intensite (RCMI). Resultats Vingt patients ont ete inclus dans cette analyse. Les volumes definis par TEP traites a 74 Gy etaient plus petits que le volume traite a 66 Gy (volume cible anatomoclinique, CTV) avec un volume cible anatomoclinique traite a 66 Gy moyen de 244 cm 3 contre un volume defini par TEP au FDG pretherapeutique de 4,8 cm 3 , un volume defini par TEP au F-miso de 38,8 cm 3 et un volume defini par TEP au FDG pertherapeutique a 36 cm 3 ( p = 0,0001). La planification a 66 Gy delivrait 62,3 Gy a 95 % du volume cible previsionnel traite a 66 Gy, les dosimetries a 74 Gy delivraient 72,5 Gy dans 95 % (D95) du volume cible previsionnel defini par TEP au FDG pretherapeutique, 72,2 Gy au volume cible previsionnel defini par TEP au F-miso et 73 Gy au volume cible previsionnel pertherapeutique. Les doses delivrees aux poumons (dose moyenne) ( p = 0,2), dans 35 % du cœur (V35) ( p = 0,9), 50 % de l’œsophage (V50) ( p = 0,6) et 2 % du moelle (D2 %) ( p = 0,1) n’etaient pas augmentees significativement lors des differentes planifications avec augmentation de dose. Conclusion Cette etude demontre la possibilite d’augmenter la dose de radiotherapie a differents volumes definis par TEP efficacement sans augmenter la dose aux organes a risque.

Objectifs Le volume tumoral metabolique total (VTMT) mesurable en TEP au FDG est un biomarqueur prometteur de la charge tumorale. Cependant, sa fiabilite depend de la justesse de la segmentation des regions hypermetaboliques, variable en fonction de la qualite des images et de la methode de segmentation utilisee. Nous avons etudie la variabilite du VTMT a partir d’un fantome scanne dans 9 services de medecine nucleaire (SMN). Methodes Une acquisition d’un fantome NEMA IEC contenant 6 spheres remplies de FDG a ete realisee dans 9 SMN equipes de 5 modeles differents de TEP/TDM. Le rapport d’activite sphere/fond etait le meme pour chaque sphere, de valeur moyenne 5,2 ± 0,7 pour les 9 SMN. L’activite totale du fantome au moment de l’acquisition variait de 20 a 27 MBq et les acquisitions ont dure entre 120 et 210 s en fonction de la pratique de chaque SMN. Les images ont ete reconstruites sur site selon 3 protocoles : le protocole de routine (PR) et 2 reconstructions iteratives fixees a l’avance (une avec et une sans temps de vol). Une analyse centralisee des images a ete realisee pour calculer le VTMT, en utilisant 3 methodes de segmentation des spheres (SUV > 2,5, seuil = 40 % du SUVmax, seuil adaptatif). La variabilite du VTMT (valeur vraie = 47,6 ± 0,5 mL) dans chaque SMN et entre SMN a ete caracterisee par le coefficient de variation (COV). Resultats Le biais moyen d’estimation du VTMT etait de 9,9 % ± 14,5 (8,9 % ± 15 en utilisant le PR). Le COV calcule sur toutes les reconstructions, segmentations et SMN etait de 13,5 %. Dans chaque centre, le COV calcule sur les 3 reconstructions pour une methode de segmentation donnee etait en moyenne de 1,6 % ± 1,2, tandis que le COV calcule sur les 3 methodes de segmentation en fixant la reconstruction valait en moyenne 12,2 % ± 1,4. En fixant a la fois la methode de reconstruction et la methode de segmentation, le COV sur les 9 SMN etait de 9,9 % ± 1,9. La plus faible valeur de COV sur les 9 SMN a ete observee avec le seuillage adaptatif (7,6 % ± 2), pour lequel un biais moyen d’estimation de VTMT de 10,4 % ± 8,1 a ete observe avec le PR. Conclusion Dans notre etude, le VTMT s’est avere etre nettement plus variable en fonction de la methode de segmentation qu’en fonction de la methode de reconstruction. Pour une methode de segmentation, le VTMT est correctement reproduit entre SMN, suggerant qu’il est raisonnable de conduire des etudes multicentriques si les lesions sont segmentees avec le meme algorithme.

Pericapsular adipose tissues of five patients with silicone gel breast implants were examined using electron probe microanalysis (EPMA), a sensitive method for detecting the elemental silicon component of silicone using transmission electron microscopy. All five patients had their implants removed secondary to implant complications. Five experimental animals that received subcutaneous silicone injections were also examined. Intracellular silicon was detected in the adipose tissue and in fat globules of macrophages in all patients and experimental animals. Three forms of intracellular silicon were identified: laminated, granular, and amorphous. No silicon was detected by EPMA in the adipose tissue of human and experimental animal controls. Potential origins of this silicon include the following: silicone gel (PDMS—Poly-dimethylsiloxane), silicone gel that may have been converted to another form, and background silicon from food or environmental sources. The absence of detectable silicon in the control human and animal tissue implicates silicone gel as the probable source. To the best of our knowledge, this is the first description of intracellular silicon within fat globules of both adipocytes and macrophages in recipients of silicone breast implants.?

Objectif de l’etude La sarcopenie est un facteur de pronostic defavorable chez les patients operes pour un cancer de l’œsophage. L’influence de la sarcopenie chez les patients pris en charge par chimioradiotherapie n’a jamais ete rapportee. Materiel et methode Les donnees cliniques, nutritionnelles, anthropometriques et d’imagerie fonctionnelle (TEP-scanographie au fluorodesoxyglucose [FDG]) ont ete collectees chez 98 patients pris en charge par chimioradiotherapie pour un cancer de l’œsophage localement evolue entre 2006 et 2012. La surface musculaire squelettique a ete quantifiee sur une coupe scanographique par la surface musculaire squelettique en L3 divisee par la taille au carre (SML3/t2). La sarcopenie etait definie par une surface musculaire squelettique Resultats La TEP-scanographie etait disponible pour 96 des 98 patients, 50 (52 %) etant sarcopeniques. La duree mediane de survie etait de 22 mois chez les 50 patients sarcopeniques (46 deces, 92 %) contre 58 mois chez les 46 patients non sarcopeniques (30 deces, 65 %, p = 0,0013). La sarcopenie etait le seul facteur de risque de deces significatif en analyse unifactorielle (Hazard Ratio [HR] = 2,06 : intervalle de confiance a 95 % [IC95 % : 1,31–3,25]). Un IMC 10 % (HR = 1,2 ; IC95 % : 0,77–2,01) n’etaient pas significativement associes au risque de deces en analyse univariee factorielle. Conclusion La presence d’une sarcopenie est associee a une augmentation du risque de deces chez les patients traites et pris en charge par chimioradiotherapie pour un cancer de l’œsophage localement evolue.

We reviewed 51 serous effusions (50 peritoneal/one pleural) from 38 patients with uterine (30 cases) and ovarian (eight cases) malignant mixed Müllerian tumors (MMMT). There were 16 patients (42%) with positive effusion cytology specimens; 13 cases (81%) were diagnosed as adenocarcinoma with three cases (19%) interpreted as having a sarcomatous component. Eight of 16 positive effusion specimens had cell block material available for immunoperoxidase (IP) study that included cytokeratin (AE1/3), vimentin, muscle specific actin (HHF) and S-100 protein to determine if unsuspected mesenchymal components were present in the cases originally diagnosed as carcinoma (six cases), or sarcomas (two cases). In the six cases originally interpreted as carcinoma, three were diagnosed as adenocarcinoma and three as poorly differentiated carcinoma. All three of the cases considered adenocarcinoma and two of those diagnosed as poorly differentiated carcinoma reacted only with AE1/3 and vimentin. The remaining case, considered a poorly differentiated carcinoma, stained only with vimentin. In the two cases having cell blocks interpreted as having a sarcomatous component, only vimentin was positive in one while AE1/3, vimentin, HHF, and S-100 were positive in the other. The case where all immunohistochemical stains were reactive contained both carcinomatous and sarcomatous components. In the three cases considered sarcomatous, the cytomorphologic features helpful in the recognition of a mesenchymal component included a dissociated smear pattern of pleomorphic round to oval cells and/or spindle cells. In retrospect, the IP stains did not alter any of the original diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Several algorithms from the literature were compared with the original random walk (RW) algorithm for brain perfusion heterogeneity quantification purposes. Algorithms are compared on a set of 210 brain single photon emission computed tomography (SPECT) simulations and 40 patient exams. Methods Five algorithms were tested on numerical phantoms. The numerical anthropomorphic Zubal head phantom was used to generate 42 (6 × 7) different brain SPECT simulations. Seven diffuse cortical heterogeneity levels were simulated with an adjustable Gaussian noise function and six focal perfusion defect levels with temporoparietal (TP) defects. The phantoms were successively projected and smoothed with Gaussian kernel with full width at half maximum (FWHM = 5 mm), and Poisson noise was added to the 64 projections. For each simulation, 5 Poisson noise realizations were performed yielding a total of 210 datasets. The SPECT images were reconstructed using filtered black projection (Hamming filter: α = 0.5). The five algorithms or measures tested were the following: the coefficient of variation, the entropy and local entropy, fractal dimension (FD) (box counting and Fourier power spectrum methods), the gray-level co-occurrence matrix (GLCM), and the new RW. The heterogeneity discrimination power was obtained with a linear regression for each algorithm. This regression line is a mean function of the measure of heterogeneity compared to the different diffuse heterogeneity and focal defect levels generated in the phantoms. A greater slope denotes a larger separation between the levels of diffuse heterogeneity. The five algorithms were computed using 40 99mTc-ethyl-cysteinate-dimer (ECD) SPECT images of patients referred for memory impairment. Scans were blindly ranked by two physicians according to the level of heterogeneity, and a consensus was obtained. The rankings obtained by the algorithms were compared with the physicians' consensus ranking. Results The GLCM method (slope = 58.5), the fractal dimension (35.9), and the RW method (31.6) can differentiate the different levels of diffuse heterogeneity. The GLCM contrast parameter method is not influenced by a focal defect contrary to the FD and RW methods. A significant correlation was found between the RW method and the physicians' classification (r = 0.86; F = 137; p < 0.0001). Conclusions The GLCM method can quantify the different levels of diffuse heterogeneity in brain-simulated SPECT images without an influence from the focal cortical defects. However, GLCM classification was not correlated with the physicians' classification (Rho = −0.099). The RW method was significantly correlated with the physicians' heterogeneity perception but is influenced by the existence of a focal defect.

We assessed in this study the influence of contrast-enhanced CT (ceCT) on PET/CT interpretation and PET/CT on ceCT interpretation in patients with lymphoma, before and after chemotherapy.Fifty patients with Hodgkin disease (N.=17) or non-Hodgkin lymphomas (N.=33) were assessed before and after chemotherapy. PET/CT were performed 60 minutes after injection of FDG. Iopamidol was then injected and followed, 50 seconds later, by another CT. PET images were successively reconstructed using non-enhanced CT (PET-) and ceCT (PET+). Four nuclear physicians rated PET- and PET+ in random order. Three radiologists initially rated ceCT alone and then ceCT along with PET+.Before chemotherapy, global agreement (GA) was 99% (k=0.96) when PET- was compared to PET+. Nine (5%) lesions were discordant, 5 according to PET- and 4 to PET+. After chemotherapy, GA was 99% (k=0.91). Eight (15%) lesions were discordant, 3 according to PET- and 5 to PET+. Before chemotherapy, GA was 97% (k=0.91) when ceCT was compared to ceCT with PET+. Twenty-one (12%) lesions were discordant, 16 when ceCT were analyzed alone and 5 when ceCT was analyzed with PET+. After chemotherapy, GA was 95% (k=0.76). All 30 (35%) discordant lesions were positive according to ceCT alone. A significant difference between the 2 procedures was found in the pelvis and in the groin (P0.05).PET+ did not differ from PET-, before and after chemotherapy. Fewer abnormalities were observed, when ceCT was analyzed with PET+, particularly after chemotherapy, due to residual masses that are better analyzed with functional imaging.

A 2-yr-old child with idiopathic pulmonary hemosiderosis and autoimmune thrombocytopenia developed hepatic veno-occlusive disease after being treated with long-term, low-dose cyclophosphamide. The authors believe that the injury was induced by cyclophosphamide. Although transplant dosages of cyclophosphamide alone or in conjunction with other drugs have been shown to induce hepatic venocclusive disease, this is the first case of hepatic venocclusive disease associated with nontransplant dosages of cyclophosphamide. Histopathologically, the injury was characterized by occlusive lesions of intrahepatic veins, both the terminal hepatic venules and portal veins branches, together with necrosis (predominately involving Zones 3 and 2) and hemorrhages. An added risk factor could have been release of platelet-derived growth factor that in turn activated and promoted proliferation of fibroblasts and smooth muscle cells in the vessels. Previously reported cases of cyclophosphamide-related injury are reviewed.

The acidity and catalytic activity of alumina doped with AlCl3, CH3AlCl2, PCl5, PCl3, I2, Cl2 and H2PO3F were studied. Vapors of AlCl3 and CH3AlCl2 induce superacid sites in alumina, whereas PCl3 and PCl5 produce less acidic systems, which nevertheless catalyze the skeletal isomerization of alkenes. The modification of Al2O3 with other specified compounds affects only slightly the acidity and catalytic activity of alumina.