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Soft tissue sarcomas (STS) are rare malignancies of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Soft Tissue Sarcoma provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as retroperitoneal/intra-abdominal STS, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis and treatment of retroperitoneal/intra-abdominal STS, outlines treatment recommendations, and reviews the evidence to support the guidelines recommendations.

LESSONS LEARNED: The results from the liposarcoma cohort of SARC024 confirm previously published data and do not support the routine use of regorafenib in this patient population. Continued exploration of novel therapies, including combination approaches, is warranted for a patient population in whom limited treatment options exist. BACKGROUND: Regorafenib is a multitargeted kinase inhibitor with a kinase profile overlapping, but distinct from, pazopanib, an agent approved for recurrent and metastatic non-gastrointestinal stromal tumor (GIST), non-adipocytic soft tissue sarcoma. We conducted a randomized, phase II study of regorafenib versus placebo in refractory liposarcoma patients. METHODS: Patients with advanced or metastatic, treatment-refractory liposarcoma were randomized 1:1 to receive regorafenib 160 mg or placebo once daily (3 weeks on, 1 week off). Patients with well-differentiated liposarcoma only were excluded. Crossover for placebo was allowed upon progression. The primary endpoint was progression-free survival (PFS), according to RECIST version 1.1. RESULTS: Forty-eight subjects with liposarcoma (34 dedifferentiated, 12 myxoid/round cell, 2 pleomorphic) were enrolled. Median PFS was 1.87 (95% confidence interval [CI], 0.92-3.67) months for regorafenib versus 2.07 (95% CI, 1.64-3.44) months for placebo; stratified hazard ratio [HR], 0.85 (95% CI, 0.46, 1.58), p = .62. No responses were seen on regorafenib. One PR was observed on placebo. Median overall survival was 6.46 (95% CI, 4.16-23.48) months for regorafenib and 4.89 (95% CI, 3.02-9.77) months for placebo, stratified HR, 0.66 (95% CI, 0.31-1.40), p = .28). Treatment-related adverse events were similar to the known safety profile of regorafenib. CONCLUSION: Regorafenib did not appear to improve PFS in treatment-refractory liposarcoma. No new significant safety signals were observed.

Purpose/Objectives: SCLC accounts for approximately 15% of newly diagnosed lung cancer cases, is driven by RB1 and TP53 lesions and represents the most aggressive pulmonary carcinoma. Current chemotherapies are initially effective in SCLC patients, however tumors rapidly reoccur and patients die within a few months. Results from KEYNOTE-028 revealed that PD-L1 positive late stage SCLC patients who received a human-ized monoclonal anti-PD-1 antibody, showed 25% response rates. This finding is remarkable for SCLC, since targeted therapies for this tumor entity are rare. However, most SCLC patients harbor a primary resistance or acquire resistance during treatment by an immune suppressive microenvironment. Thus, there is a critical need to combine immune checkpoint inhibitors with other therapies to overcome these resistances. Materials/Methods: We implemented a combined therapy concept including anti-VEGF-A and anti-PD-L1 monoclonal antibodies in an autochthonous SCLC mouse model. As a read out, we used X-ray computed tomography, flow cytometry and end-point immunohistochemistry. Results: We found that combined anti-VEGF-A/anti-PD-L1 treatment synergistically improved overall survival, compared to monotherapies, and enhanced T cell infiltration into the tumor. Moreover, we identified in murine SCLC tumors which acquired resistance to anti-PD-L1, a significant increase in PD-1+/TIM-3+ exhausted CD4 and CD8 T-cells accompanied by significantly increased expression of Galectin-9, the major TIM-3 ligand, on TAMs. In addition, we observed a significantly enriched fraction of TAMs with a similar exhausted phenotype indicated by the expression of LAG-3 and CTLA-4 upon acquired resistance to PD-L1 blockade. Importantly, the exhaustion of T-cells and TAMs was reverted upon combined anti-VEGF-A/anti-PD-L1 therapy. In line with the results obtained from the mouse model, we showed mechanistically in PBMCs of SCLC patients, that VEGF-A triggers co-expression of PD-1 and TIM-3 on T-cells, indicating an immunosuppressive function of VEGF-A in SCLC patients during anti-PD-1/PD-L1 therapy. Furthermore, we elucidated using CRISPR-Cas9 technology, that VEGF-A liberated from the tumor microenvironment is the likely mediator of acquired resistance to PD1/PD-L1 blockade in SCLC. Conclusion: Taken together, in SCLC there is evidence for a substantial benefit of implementing combined anti-angiogenic and anti-immune checkpoint therapy approaches in the clinic in order to overcome acquired resistances delivered by T-cells and macrophages in the tumor microenvironment. Remarks: The authors declare no conflicts of interest. This work was published in Cancer Res. 2018 Aug 1;78(15):4270-4281. doi: 10.1158/0008-5472.CAN-17-2176. Epub 2018 May 18 with the title 'Combined VEGF and PD-L1 Blockade Displays Synergistic Treatment Effects in an Autochthonous Mouse Model of Small Cell Lung Cancer'., Proceedings on Cancer-Immuno-Oncology, Vol 1 No 1 (2018)

The lungs are particularly sensitive to RT, and are often the primary dose-limiting structure during thoracic therapy.The alveolar/capillary units and pneumocytes within the alveoli appear to be particularly sensitive to RT.Hypoxia may be important in the underlying physiology of RT-associated lung injury.The cytokine transforming growth factor-beta (TGF-β), plays an important role in the development of RT-induced fibrosis.The histopathological changes observed in the lung after RT are broadly characterized as diffuse alveolar damage.The interaction between pre-treatment PFTs and the risk of symptomatic lung injury is complex. Similarly, the link between changes in PFTs and the development of symptoms is uncertain.The incidence of symptomatic lung injury increases with increase in most dosimetric parameters. The mean lung dose (MLD) and V20 have been the most-often considered parameters. MLD might be a preferable metric since it considers the entire 3D dose distribution.Radiation to the lower lobes appears to be more often associated with clinical symptoms than is radiation to the upper lobes. This might be related to incidental cardiac irradiation. In pre-clinical models, there appears to be a complex interaction between lung and heart irradiation.TGF-β has been suggested in several studies to predict for RT-induced lung injury, but the data are still somewhat inconsistent.Oral prednisone (Salinas and Winterbauer 1995), typically 40–60 mg daily for 1–2 weeks with a slow taper, is usually effective in treating pneumonitis. There are no widely accepted treatments for fibrosis.A number of chemotherapeutic agents have been suggested to be associated with a range of pulmonary toxicities.

Soft tissue sarcomas (STS) are a rare, heterogeneous group of solid tumors in need of improved therapeutic options. First-line chemotherapy is considered the current standard of care for patients with advanced, symptomatic STS, but the median survival is only 8 to 12 months. Efforts to increase response rates by using combination or dose-dense regimens have largely failed to improve patient outcomes. However, increasing evidence supports the use of specific treatments for certain histological subtypes of STS, and novel therapies, including tyrosine kinase and mammalian target of rapamycin inhibitors, are currently under active investigation. In addition, novel treatment approaches (such as maintenance therapy) designed to prolong the duration of response to chemotherapy and delay disease progression are being explored. This article provides an overview of current systemic therapies for patients with advanced STS and discusses ongoing efforts designed to improve patient outcomes through the use of novel therapeutic agents and treatment strategies. Cancer 2011;. © 2011 American Cancer Society. Soft tissue sarcomas (STS) are a rare, heterogeneous group of solid tumors in need of improved therapeutic options. This article provides an overview of current systemic therapies for patients with advanced STS and discusses ongoing efforts designed to improve patient outcomes through the use of novel therapeutic agents and treatment strategies.

R désigne le corps des réels. C désigne le corps des nombres complexes. Z/2Z est le corps fini constitué des 2 seuls éléments notés 0 et 1. Mn(R), Mn(C), Mn(Z/2Z ) désignent respectivement l'ensemble des matrices carrées d'ordre n à éléments dans R, C, Z/2Z . L'objectif de cette étude est de démontrer l'existence d'un Z/2Z-espace vectoriel de dimension égale à n, qui est un sous-espace vectoriel de Mn(Z/2Z ) constitué de matrices bisymétriques dont le produit est commutatif. Ce Z/2Z-espace vectoriel est noté BSCn(Z/2Z ). L'étude démontre que BSCn(Z/2Z) est une Z/2Z-algèbre commutative, la 2ème loi interne étant la multiplication matricielle. Elle définit la base canonique de BSCn(Z/2Z) et met en évidence les principales propriétés spécifiques aux matrices de BSCn(Z/2Z). La conclusion de cette étude établit l'existence d'autres sous-espaces vectoriels constitués de matrices bisymétriques dont le produit est commutatif, mais dont la dimension est inférieure à n. Elle fournit aussi la définition de BSCn(R) et de BSCn(C), et donne des indications relatives à la transposition de certaines propriétés de BSCn(B) à BSCn(R) et BSCn(C).

Rhabdomyosarcomatous dedifferentiation of GIST following tyrosine kinase inhibitor (TKI) therapy is rare, with only a handful of cases previously reported in the literature. Herein we present a case of metastatic GIST initially treated with imatinib that developed radiographic evidence of progression after 8 months of standard dose therapy with continued progression despite attempts at using dose-escalated imatinib 400 mg bid. Due to the patient’s worsening clinical symptoms and radiographic concerns for colonic thickening, abscess, and extraluminal air, the patient underwent a palliative resection of a large heterogeneous mass arising from the posterior stomach and several metastatic foci. Pathology revealed a dedifferentiated GIST with rhabdomyosarcomatous features. This report will highlight the unique features of this case and review the existing literature.

Cette étude complète la publication hal-00675237 consacrée à la définition d'un nouveau critère de compatibilité applicable à tout système linéaire de n équations à p inconnues. Elle développe la notion d'ensemble dérivé associé à un système linéaire de n équations à p inconnues. Elle démontre la condition nécessaire et suffisante suivante : deux systèmes linéaires de n équations à p inconnues sont équivalents si et seulement si leurs ensembles dérivés sont égaux. Cette proposition est vraie que les systèmes concernés soient compatibles ou non compatibles.

L'objet de cette étude est de définir, sous forme de condition nécessaire et suffisante, un critère (dénommé critère de compatibilité, en abrégé CC) permettant de déterminer si un système linéaire de n équations à p inconnues - est compatible ou non. L'originalité de ce critère est de ne faire appel ni à la notion de déterminant ni à la notion de rang, usuellement associées au système concerné. Dans la mesure où le Théorème de Rouché-Fontené énonce lui aussi une condition nécessaire et suffisante de compatibilité d'un système linéaire d'équations, cette étude fait le lien entre le critère CC et le Théorème de Rouché-Fontené. Une démonstration nouvelle du Théorème de Rouché-Fontené en résulte.

Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.

The Spallation Neutron Source (SNS) at Oak Ridge National Laboratory currently holds the Guinness World Record as the world most powerful pulsed spallation neutron source. Neutrons scattered off atomic nuclei in a sample yield important information about the position, motions, and magnetic properties of atoms in materials. A neutron scattering experiment usually involves sample environment control (temperature, pressure, etc.), mechanical alignment (slits, sample and detector position), magnetic field controllers, neutron velocity selection (choppers) and neutron detectors. The SNS Data Acquisition System (DAS) consists of real-time sub-system (detector read-out with custom electronics, chopper interface), data preprocessing (soft real-time) and a cluster of control and ancillary PCs. The real-time system runs FPGA firmware and programs running on PCs (C++, LabView) typically perform one task such as motor control and communicate via TCP/IP networks. PyDas is a set of Python modules that are used to integrate various components of the SNS DAS system. It enables customized automation of neutron scattering experiments in a rapid and flexible manner. It provides wxPython GUIs for routine experiments as well as IPython command line scripting. Matplotlib and numpy are used for data presentation and simple analysis. We will present an overview of SNS Data Acquisition System and PyDas architectures and implementation along with the examples of use. We will also discuss plans for future development as well as the challenges that have to be met while maintaining PyDas for 20+ different scientific instruments.

The glucocorticoid ciclesonide is the 2'R-epimer of 2'-cyclohexyl-11beta-hydroxy-21-isobutyryloxy-16bH-dioxolo[5',4':16,17]pregna-1,4-diene-3,20-dione. The active metabolite desisobutyryl-ciclesonide (des-CIC) is derived from ciclesonide by esterase cleavage of isobutyrate at the C21 position. The relative binding affinities at the rat glucocorticoid receptor were dexamethasone, 100; ciclesonide, 12; des-CIC, 1212; and budesonide, 905. Des-CIC potently inhibited the activation of murine and human lymphocytes in a series of different in vitro systems. With the exception of concanavalin A-stimulated rat spleen cells, des-CIC was more potent than the parent compound. Des-CIC compared well with budesonide in all in vitro systems. Furthermore, the respective 2'S-epimers were always significantly less potent than the 2'R-epimers. In vivo, ciclesonide (intratracheal administration), des-CIC, and budesonide inhibited antigen-induced accumulation of eosinophils, protein, and tumor necrosis factor-alpha into the bronchoalveolar lavage fluid of ovalbumin-sensitized and -challenged Brown Norway rats with an ED(50) value ranging from 0.4 to 1.3 mg/kg, indicating similar potency, which suggests in vivo activation of the parent compound. Ciclesonide and budesonide inhibited the bradykinin-induced protein leakage into the rat trachea. In the rat cotton pellet model, ciclesonide inhibited granuloma formation (ED(50):= of 2 microg/pellet), whereas budesonide and des-CIC were 15- and 20-fold less active; thymus involution was induced with an ED(50) of 303, 279, and 154 microg/pellet, respectively. When applied orally to rats for 28 days, ciclesonide showed low potency in reducing weight of thymus and adrenals, suggesting low oral bioavailability. The in vivo data on ciclesonide highlight its effective local action and a reduced potential for side effects.

Arrangiertes Porträt eines jungen Mannes in einem auffälligen Rahmen, [Robert Breitinger], Bildtitel gemäss Zettelkatalog der Graphischen Sammlung und des Fotoarchivs, Gemäss dem Verzeichnis Breitingers wurde die Fotografie am 4. Dezember 1892 um 11.20 Uhr aufgenommen. Im Verzeichnis Information zu den Wetterverhältnissen: "Regen düster", Eintrag im Adressbuch der Stadt Zürich von 1893: Pfister Otto, Sohn, Buchhalter, Usteristr. 5. Mögligerweise handelt es sich um ihn oder einen Verwandten, "R. [R]iede[l] Z[ür]ich" erkennbar. Otto Pfister wurde von Richard Riedel zwischen 1868-1890 fotografiert. Es ist unbekannt, wer anschliessend das Arrangement machte und wo es stand, Aus der Sammlung Breitinger (1841-1913) Exemplar der Zentralbibliothek Zürich, Graphische Sammlung und Fotoarchiv, Auf der Rückseite oben rechts Vermerk mit roter Tinte: "1869" (Bildnummer der Kabinettkarte) Exemplar der Zentralbibliothek Zürich, Graphische Sammlung und Fotoarchiv

[Robert Breitinger], Bildtitel gemäss Zettelkatalog der Graphischen Sammlung und des Fotoarchivs, Gemäss dem Verzeichnis Breitingers wurde die Fotografie am 5. Februar 1901 um 15.00 Uhr aufgenommen. Im Verzeichnis Information zu den Wetterverhältnissen: "l[eicht] Sonne Schnee", Eintrag im Adressbuch der Stadt Zürich von 1901: Pfister, Ad., Metzger, Ziegelstrasse 4, Aus der Sammlung Breitinger (1841-1913) Exemplar der Zentralbibliothek Zürich, Graphische Sammlung und Fotoarchiv, Auf der Rückseite handschriftliche Notizen und oben rechts Vermerk mit Bleistift: "6220" (Bildnummer der Kabinettkarte) Exemplar der Zentralbibliothek Zürich, Graphische Sammlung und Fotoarchiv

Porträt von Verena Röttinger-Fehr, Ehefrau des Glasmalers Johann Jakob Röttinger, R. Riedel, Die Fotografie stammt aus dem Album 1.1.1 des Nachlasses Röttinger; die Massangaben definieren das Lichtmass, den Bildausschnitt auf der Albumseite, Zuschreibung gemäss Aufdruck verso: "R. Riedel, Zürich [...]"; Datierung aufgrund des Lebensalters von Verena Röttinger sowie datierter Fotos im selben Album, Aus dem Nachlass der Familie Röttinger Exemplar der Zentralbibliothek Zürich, Graphische Sammlung und Fotoarchiv

Porträt Jakob Georg Röttingers, Sohn des Glasmalers Johann Jakob Röttinger, R. Riedel, Die Fotografie stammt aus der Schachtel "lose Fotografien vor 1913" des Nachlasses Röttinger, Mappe 2.2.6, Zuschreibung gemäss Aufdruck recto und verso: "R. Riedel Zürich.[...]"; Datierung gemäss Lebensalter Georg Röttingers, Aus dem Nachlass der Familie Röttinger Exemplar der Zentralbibliothek Zürich, Graphische Sammlung und Fotoarchiv

PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461 ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.