Effects of 3-Dimensional Conformal or Intensity-modulated Radiotherapy on Dental Pulp Sensitivity during and after the Treatment of Oral or Oropharyngeal Malignancies

Introduction: Radiation therapy (RT) of malignant tumors in the head and neck area may have damaging effects on surrounding tissues. The aim of this investigation was to evaluate the effects of RI delivered by 3-dimensional conformal radiotherapy (3D-RT) or intensity-modulated radiotherapy (IMRT) on dental pulp sensitivity. Methods: Twenty patients with oral or oropharyngeal cancer receiving RT with 3D-RT or IMRT underwent cold thermal pulp sensitivity testing (PST) of 2 teeth each at 4 time points: before RT (TP1), the beginning of RT with doses between 30 and 35 Gy (TP2), the end of RT with doses between 60 and 70 Gy (TP3), and 4 to 5 months after the start of RT (TP4). Results: All 40 teeth showed positive responses to PST at TP1 (100%) and 9 at TP2 (22.5%; 3/16 [18.8%] for 3D-RT and 6/24 [25.0%] for IMRT). No tooth responded to PST at TP3 and TP4 (0%). A statistically significant difference existed in the number of positive pulp responses between different time points (TP1 through TP4) for all patients receiving RT (P <= .05), IMRT (P <= .05), and 3D-RT (P <= .05). No statistically significant differences in positive sensitivity responses were found between 3D-RT and IMRT at any time point (TP1, TP3, TP4, P = 1.0; TP2, P = .74). A statistically significant correlation existed between the location of the tumor and PST at TP2 for IMRT (P <= .05) but not for 3D-RT (P = .14). Conclusions: RT decreased the number of teeth responding to PST after doses greater than 30 to 35 Gy. The type of RT (3D-RT or IMRT) had no influence on the pulp responses to PST after the conclusion of RT. (J Endod 2012;38:148-152)

Prediction of clinical toxicity in locally advanced head and neck cancer patients by radio-induced apoptosis in peripheral blood lymphocytes (PBLs)

[EN] Head and neck cancer is treated mainly by surgery and radiotherapy. Normal tissue toxicity due to x-ray exposure is a limiting factor for treatment success. Many efforts have been employed to develop predictive tests applied to clinical practice. Determination of lymphocyte radio-sensitivity by radio-induced apoptosis arises as a possible method to predict tissue toxicity due to radiotherapy. The aim of the present study was to analyze radio-induced apoptosis of peripheral blood lymphocytes in head and neck cancer patients and to explore their role in predicting radiation induced toxicity. Seventy nine consecutive patients suffering from head and neck cancer, diagnosed and treated in our institution, were included in the study. Toxicity was evaluated using the Radiation Therapy Oncology Group scale. Peripheral blood lymphocytes were isolated and irradiated at 0, 1, 2 and 8 Gy during 24 hours. Apoptosis was measured by flow cytometry using annexin V/propidium iodide. Lymphocytes were marked with CD45 APC-conjugated monoclonal antibody. Radiation-induced apoptosis increased in order to radiation dose and fitted to a semi logarithmic model defined by two constants: α and β. α, as the origin of the curve in the Y axis determining the percentage of spontaneous cell death, and β, as the slope of the curve determining the percentage of cell death induced at a determined radiation dose, were obtained. β value was statistically associated to normal tissue toxicity in terms of severe xerostomia, as higher levels of apoptosis were observed in patients with low toxicity (p = 0.035; Exp(B) 0.224, I.C.95% (0.060-0.904)). These data agree with our previous results and suggest that it is possible to estimate the radiosensitivity of peripheral blood lymphocytes from patients determining the radiation induced apoptosis with annexin V/propidium iodide staining. β values observed define an individual radiosensitivity profile that could predict late toxicity due to radiotherapy in locally advanced head and neck cancer patients. Anyhow, prospective studies with different cancer types and higher number of patients are needed to validate these results.

Constitutive gene expression profile segregates toxicity in locally advanced breast cancer patients treated with high-dose hyperfractionated radical radiotherapy

[EN] Breast cancer patients show a wide variation in normal tissue reactions after radiotherapy. The individual sensitivity to x-rays limits the efficiency of the therapy. Prediction of individual sensitivity to radiotherapy could help to select the radiation protocol and to improve treatment results. The aim of this study was to assess the relationship between gene expression profiles of ex vivo un-irradiated and irradiated lymphocytes and the development of toxicity due to high-dose hyperfractionated radiotherapy in patients with locally advanced breast cancer. Raw data from microarray experiments were uploaded to the Gene Expression Omnibus Database http://www.ncbi.nlm.nih.gov/geo/ (GEO accession GSE15341). We obtained a small group of 81 genes significantly regulated by radiotherapy, lumped in 50 relevant pathways. Using ANOVA and t-test statistical tools we found 20 and 26 constitutive genes (0 Gy) that segregate patients with and without acute and late toxicity, respectively. Non-supervised hierarchical clustering was used for the visualization of results. Six and 9 pathways were significantly regulated respectively. Concerning to irradiated lymphocytes (2 Gy), we founded 29 genes that separate patients with acute toxicity and without it. Those genes were gathered in 4 significant pathways. We could not identify a set of genes that segregates patients with and without late toxicity. In conclusion, we have found an association between the constitutive gene expression profile of peripheral blood lymphocytes and the development of acute and late toxicity in consecutive, unselected patients. These observations suggest the possibility of predicting normal tissue response to irradiation in high-dose non-conventional radiation therapy regimens. Prospective studies with higher number of patients are needed to validate these preliminary results.

Untersuchung der zellulären Antwort von Tumor und Endothelium auf radioaktive Bestrahlung in vitro und in vivo

Tumore des Kopf-Hals Bereiches sprechen aufgrund schneller Resistenzbildung häufig schlecht auf die derzeit praktizierten Bestrahlungstherapien an. Der Erfolg dieser Behandlung wird dabei maßgeblich durch die Strahlenresistenz des malignen Gewebes limitiert. Das Verständnis der zugrunde liegenden zellulären und molekularen Mechanismen ist diesbezüglich unvollständig. Die Resistenzzunahme während der klinischen Behandlung könnte durch die Selektion strahlenresistenter Einzelzellen verursacht werden oder durch die Aktivierung von Resistenzmechanismen. Im Rahmen dieser Arbeit wurde die bestrahlungsvermittelte Freisetzung möglicherweise protektiv wirkender Faktoren durch Tumorzelllinien des Kopf-Hals Bereiches untersucht. Durch Bestrahlung erfolgte eine Induktion von VEGF (vascular endothelial growth factor) und FGF-2 (fibroblast growth factor 2), IL-8 (Interleukin-8) und PGE2 (Prostaglandin E2). Die Untersuchung von VEGF und FGF-2 zeigte weiterhin ein zytoprotektives Potential dieser Faktoren, d.h. die T

Bedeutung von Rho-GTPasen bei der Regulation zellulärer Antworten auf genotoxischen Stress

SAPK/JNK regulieren nach genotoxischem Stress eine Vielzahl von Zielsubstraten, die bedeutsam für Reparatur und Überleben der Zelle sind, somit nehmen sie Einfluss auf das zelluläre Schicksal der Zelle. Ob DNA-Schäden eine Phosphorylierung von Stress-Kinasen nach sich ziehen ist bisher noch wenig untersucht. Mit reparaturdefizienten Zellen wurde der Einfluss von DNA-Schäden, durch Cisplatin/Transplatin/UV-C, auf die SAPK/JNK Aktivierung untersucht. Die Aktivierung der Stress-Kinasen erfolgte agenzspezifisch und abhängig von verschieden Reparaturfaktoren. Die Aktivierung korrelierte in reparaturdefizienten Zellen teilweise mit dem späten Auftreten von DNA-Strangbrüchen, war jedoch unabhängig von erhöhten initialen DNA-Schäden. Diese Befunde zeigten, dass die späte Aktivierung der SAPK/JNK DNA-schadensabhängig verläuft und das Cisplatin und Transplatin bei Verwendung von äquitoxischen Dosen zu einer vergleichbaren Aktivierung von SAPK/JNK führten. Die Hemmung der Rho-GTPasen sowohl durch Statine als auch mittels Clostridium difficile Toxin B zeigte weiterhin, dass Rho-GTPasen möglicherweise die späte DNA-schadensabhängige Aktivierung der Stress-Kinasen vermitteln. Die Hemmung von Rho-GTPasen durch physiologisch relevante Konzentrationen von Statinen führte in primären humanen Endothelzellen (HUVECs) zu einer Protektion vor IR-Strahlung und Doxorubicin. In beiden Fällen konnte eine Hemmung des pro-apoptotischen Transkriptionsfaktors p53 sowie der Chk1, welche einen Zellzyklusarrest reguliert, mit der Statin-Behandlung erreicht werden. Effektor-Caspasen wurden dabei durch den HMG-CoA-Reduktase Hemmer nicht beeinflusst. Ausschließlich bei dem Statin-vermittelten Schutz vor Doxorubicin kam es zu einer Reduktion von initialen DNA-Schäden, in Form von DNA-Strangbrüchen. Die IR-induzierten Strangbrüche in der DNA blieben von der Statin-Inkubation hingegen unbeeinflusst. Aufgrund ihrer protektiven Eigenschaften gegenüber IR- und Doxorubicin-induzierter Zytotoxizität in Endothelzellen und ihrer pro-apoptotischen Wirkung auf Tumorzellen könnten Statine möglicherweise die unerwünschten Nebenwirkungen von Zytostatika und einer Strahlentherapie günstig beeinflussen

Einfluss einer Schwerionenbestrahlung auf das Migrationsverhalten von Tumorzellen

Die Bildung von Metastasen und Rezidiven stellt ein großes Problem für eine erfolgreiche Therapie solider maligner Tumoren dar. Dabei ist die Rolle der angewendeten Therapiever-fahren in der Induktion metastasierender Zellen vor allem für eine Schwerionentherapie noch weitestgehend unklar. Die für die Metastasierung entscheidende Tumorzellmigration wurde daher unter dem Einfluss von Röntgen- und Schwerionenstrahlung untersuchen. Dazu wurden drei humane Tumorzelllinien (Gliomzelllinie U87 und kolorektale Zelllinien HCT116 und HCT116 p21-/-) unter standardisierten Bedingungen in einer Boydenkammer direkt und 24 Stunden nach Bestrahlung in vitro auf ihr Migrationsverhalten untersucht. Um mögliche Än-derungen migrationsrelevanter Proteine zu bestimmen, wurden zu denselben Zeitpunkten Zelllysate hergestellt und die Expression der Integrine b1 und b3 sowie der Proteinkinase B Isoformen Akt1 und Akt2 und deren Phosphorylierung untersucht. Gezeigt werden konnten sowohl zelllinien- als auch strahlenspezifische Unterschiede in der Migration und der Proteinexpressionen. Dabei konnten die beobachteten Migrationsänderungen nur zum Teil (vor allem nach Röntgenbestrahlung) durch die veränderte Expressionen der untersuchten Proteine erklärt werden. Daher ist zu vermuten, dass den strahleninduzierten Veränderungen der Migration der verwendeten Zelllinien verschiedene Mechanis-men zugrunde liegen, die auf der Expression unterschiedlicher Proteine beruhen. Bestrahlungen mit 12C-Ionen scheinen prinzipiell andere Expressionsmuster zu induzieren als konventionelle Strahlung und die hier untersuchten Proteine in der Migration der Zellen daher nur eine untergeordnete Rolle zu spielen. Auffällig waren die deutlich zelllinienspezifischen Unterschiede in der Migration nach Röntgenbestrahlung. Dort wurde ein zum Teil erhöhtes Migrationspotential nach klinisch relevanten Bestrahlungsdosen von U87 Gliomzellen festgestellt. Die Migrationsaktivität von kolorektalen Zelllinien hingegen nahm nach Bestrahlung ab. Nach Schwerionenbestrahlung wurden für alle Zelllinien signifikante Abnahmen der Migration festgestellt. Die hier erhaltenen Ergebnisse können aufgrund einer Vielzahl pro- und antimigratorischer Signale im Tumorgewebe nicht direkt in die in vivo Situation übertragen werden, doch können sie durchaus als Hinweise für die Abschätzung eines veränderten Metastasierungsrisikos dienen. Für kolorektale Zellen, unabhängig von ihrem p21-Status scheint eine Behandlung mit Röntgenstrahlen eher nicht mit einem erhöhten Migrationsrisiko einherzugehen. Anders ist dies bei den hier untersuchten Gliomzellen U87. Hier kann ein strahleninduziertes Metastasierungsrisiko aufgrund der erzielten Ergebnisse keinesfalls ausgeschlossen werden. Aus dieser Sicht scheint eine Behandlung von Gliomen mit 12C-Ionen vorteilhafter, da eine sehr gute reproduzierbare strahlenvermittelte Migrationshemmung beobachtet wurde.

Effect of drug physicochemical properties on the release from liposomal systems in vitro and in vivo

Liposomes were discovered about 40 years ago by A. Bangham and since then they became very versatile tools in biology, biochemistry and medicine. Liposomes are the smallest artificial vesicles of spherical shape that can be produced from natural untoxic phospholipids and cholesterol. Liposome vesicles can be used as drug carriers and become loaded with a great variety of molecules, such as small drug molecules, proteins, nucleotides and even plasmids. Due to the variability of liposomal compositions they can be used for a large number of applications. In this thesis the β-adrenoceptor antagonists propranolol, metoprolol, atenolol and pindolol, glucose, 18F-Fluorodeoxyglucose (FDG) and Er-DTPA were used for encapsulation in liposomes, characterization and in vitro release studies. Multilamellar vesicles (MLV), large unilamellar vesicles (LUV) and smaller unilamellar vesicles (SUV) were prepared using one of the following lipids: 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC), 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC), Phospholipone 90H (Ph90H) or a mixture of DSPC and DMPC (1:1). The freeze thawing method was used for preparation of liposomes because it has three advantages (1) avoiding the use of chloroform, which is used in other methods and causes toxicity (2) it is a simple method and (3) it gives high entrapping efficiency. The percentage of entrapping efficiencies (EE) was different depending on the type and phase transition temperature (Tc) of the lipid used. The average particle size and particle size distribution of the prepared liposomes were determined using both dynamic light scattering (DLS) and laser diffraction analyzer (LDA). The average particle size of the prepared liposomes differs according to both liposomal type and lipid type. Dispersion and dialysis techniques were used for the study of the in vitro release of β-adrenoceptor antagonists. The in vitro release rate of β-adrenoceptor antagonists was increased from MLV to LUV to SUV. Regarding the lipid type, β-adrenoceptor antagonists exhibited different in vitro release pattern from one lipid to another. Two different concentrations (50 and 100mg/ml) of Ph90H were used for studying the effect of lipid concentration on the in vitro release of β-adrenoceptor antagonists. It was found that liposomes made from 50 mg/ml Ph90H exhibited higher release rates than liposomes made at 100 mg/ml Ph90H. Also glucose was encapsulated in MLV, LUV and SUV using 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC), 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC), Phospholipone 90H (Ph90H), soybean lipid (Syb) or a mixture of DSPC and DMPC (1:1). The average particle size and size distribution were determined using laser diffraction analysis. It was found that both EE and average particle size differ depending on both lipid and liposomal types. The in vitro release of glucose from different types of liposomes was performed using a dispersion method. It was found that the in vitro release of glucose from different liposomes is dependent on the lipid type. 18F-FDG was encapsulated in MLV 1,2-Dimyristoyl-sn-Glycero-3-Phosphocholine (DMPC), 1,2-Distearoyl-sn-Glycero-3-Phosphocholine (DSPC), Phospholipone 90H (Ph90H), soybean lipid (Syb) or a mixture of DSPC and DMPC (1:1). FDG-containing LUV and SUV were prepared using Ph90H lipid. The in vitro release of FDG from the different types of lipids was accomplished using a dispersion method. Results similar to that of glucose release were obtained. In vivo imaging of FDG in both uncapsulated FDG and FDG-containing MLV was performed in the brain and the whole body of rats using PET scanner. It was found that the release of FDG from FDG-containing MLV was sustained. In vitro-In vivo correlation was studied using the in vitro release data of FDG from liposomes and in vivo absorption data of FDG from injected liposomes using microPET. Erbium, which is a lanthanide metal, was used as a chelate with DTPA for encapsulation in SUV liposomes for the indirect radiation therapy of cancer. The liposomes were prepared using three different concentrations of soybean lipid (30, 50 and 70 mg/ml). The stability of Er-DTPA SUV liposomes was carried out by storage of the prepared liposomes at three different temperatures (4, 25 and 37 °C). It was found that the release of Er-DTPA complex is temperature dependent, the higher the temperature, the higher the release. There was an inverse relationship between the release of the Er-DTPA complex and the concentration of lipid.

Trattamento radioterapico ipofrazionato ad alte dosi del carcinoma prostatico con tecnica ad intensità modulata (IMRT) guidata dalle immagini (IGRT)

Obiettivo: valutare la tossicità ed il controllo di malattia di un trattamento radioterapico ipofrazionato ad alte dosi con tecnica ad intensità modulata (IMRT) guidata dalle immagini (IGRT) in pazienti affetti da carcinoma prostatico a rischio intermedio, alto ed altissimo di recidiva. Materiali e metodi: tutti i pazienti candidati al trattamento sono stati stadiati e sottoposti al posizionamento di tre “markers” fiduciali intraprostatici necessari per l’IGRT. Mediante tecnica SIB – IMRT sono stati erogati alla prostata 67,50 Gy in 25 frazioni (EQD2 = 81 Gy), alle vescichette 56,25 Gy in 25 frazioni (EQD2 = 60,35 Gy) e ai linfonodi pelvici, qualora irradiati, 50 Gy in 25 frazioni. La tossicità gastrointestinale (GI) e genitourinaria (GU) è stata valutata mediante i CTCAE v. 4.03. Per individuare una possibile correlazione tra i potenziali fattori di rischio e la tossicità registrata è stato utilizzato il test esatto di Fisher e la sopravvivenza libera da malattia è stata calcolata mediante il metodo di Kaplan-Meier. Risultati: sono stati arruolati 71 pazienti. Il follow up medio è di 19 mesi (3-35 mesi). Nessun paziente ha dovuto interrompere il trattamento per la tossicità acuta. Il 14% dei pazienti (10 casi) ha presentato una tossicità acuta GI G ≥ 2 e il 15% (11 pazienti) ha riportato una tossicità acuta GU G2. Per quanto riguarda la tossicità tardiva GI e GU G ≥ 2, essa è stata documentata, rispettivamente, nel 14% dei casi (9 pazienti) e nell’11% (7 pazienti). Non è stata riscontrata nessuna tossicità, acuta o cronica, G4. Nessun fattore di rischio correlava con la tossicità. La sopravvivenza libera da malattia a 2 anni è del 94%. Conclusioni: il trattamento radioterapico ipofrazionato ad alte dosi con IMRT-IGRT appare essere sicuro ed efficace. Sono comunque necessari ulteriori studi per confermare questi dati ed i presupposti radiobiologici dell’ipofrazionamento del carcinoma prostatico.

Reti neurali e modelli fisico-predittivi: Dati clinici e analisi di trattamenti in tomotherapy

Il lavoro è parte integrante di un progetto di ricerca del Ministero della Salute ed è stato sviluppato presso la Fisica Sanitaria ed il reparto di Radioterapia Oncologica dell’Azienda Ospedaliero Universitaria di Modena. L’obiettivo è la realizzazione di modelli predittivi e di reti neurali per tecniche di warping in ambito clinico. Modifiche volumetrico-spaziali di organi a rischio e target tumorali, durante trattamenti tomoterapici, possono alterare la distribuzione di dose rispetto ai constraints delineati in fase di pianificazione. Metodologie radioterapiche per la valutazione di organ motion e algoritmi di registrazione ibrida permettono di generare automaticamente ROI deformate e quantificare la divergenza dal piano di trattamento iniziale. Lo studio si focalizzata sulle tecniche di Adaptive Radiation Therapy (ART) mediante la meta-analisi di 51 pazienti sottoposti a trattamento mediante Tomotherapy. Studiando il comportamento statistico del campione, sono state generate analisi predittive per quantificare in tempo reale divergenze anatomico dosimetriche dei pazienti rispetto al piano originale e prevedere la loro ripianificazione terapeutica. I modelli sono stati implementati in MATLAB, mediante Cluster Analysis e Support Vector Machines; l’analisi del dataset ha evidenziato il valore aggiunto apportabile dagli algoritmi di deformazione e dalle tecniche di ART. La specificità e sensibilità della metodica è stata validata mediante l’utilizzo di analisi ROC. Gli sviluppi del presente lavoro hanno aperto una prospettiva di ricerca e utilizzo in trattamenti multicentrici e per la valutazione di efficacia ed efficienza delle nuove tecnologie in ambito RT.

Diagnosi e terapia dei tumori delle cavita' nasali del cane

Lo studio è stato condotto su pazienti affetti da carcinoma nasale trattati con radioterapia presso il Centro Oncologico Veterinario (Sasso Marconi, BO). Lo studio, prospettico, randomizzato e in doppio cieco, ha valutato l’efficacia del trattamento radioterapico in combinazione o meno con firocoxib, un inibitore selettivo dell’enzima ciclossigenasi 2 (COX-2). Sono stati inclusi pazienti con diagnosi istologica di carcinoma nasale sottoposti a stadiazione completa. I pazienti sono stati successivamente suddivisi in due gruppi in base alla tipologia di trattamento: radioterapia associata a firocoxib (Gruppo 1) o solo radioterapia (Gruppo 2). Dopo il trattamento, i pazienti sono stati monitorati a intervalli di 3 mesi sia clinicamente che mediante esami collaterali, al fine di valutare condizioni generali del paziente, un’eventuale tossicità dovuta alla somministrazione di firocoxib e la risposta oggettiva al trattamento. Per valutare la qualità di vita dei pazienti durante la terapia, è stato richiesto ai proprietari la compilazione mensile di un questionario. La mediana del tempo libero da progressione (PFI) è stata di 228 giorni (range 73-525) nel gruppo dei pazienti trattati con radioterapia e firocoxib e di 234 giorni (range 50-475) nei pazienti trattati solo con radioterapia. La sopravvivenza mediana (OS) nel Gruppo 1 è stata di 335 giorni (range 74-620) e di 244 giorni (range 85-505) nel Gruppo 2. Non si sono riscontrate differenze significative di PFI e OS tra i due gruppi. La presenza di metastasi ai linfonodi regionali condizionava negativamente PFI e sopravvivenza (P = 0.004). I pazienti trattati con firocoxib hanno mostrato un significativo beneficio in termini di qualità di vita rispetto ai pazienti trattati con sola radioterapia (P=0.008). La radioterapia può essere considerata un’efficace opzione terapeutica per i cani affetti da neoplasie nasali. Firocoxib non sembra migliorare significativamente i tempi di sopravvivenza, ma risulta utile al fine di garantire una migliore qualità di vita.

Verlauf und Determinanten der Lebensqualität bei Langzeitüberlebenden nach Prostatakarzinom in Schleswig-Holstein : Ergebnisse einer registerbasierten Kohortenstudie

Durch die ansteigende Inzidenz und niedrige Mortalität steigt die Anzahl der überlebenden Männer nach Prostatakarzinom. Mit einer 5-Jahresprävalenz von 279.000 Männern stellte das Prostatakarzinom im Jahr 2010 den größten Anteil der Krebspatienten. Die absolute 5-Jahres-Überlebensrate liegt bei 78 %. Studien zur Lebensqualität dieser Langzeitüberlebenden (> 5 Jahre nach Diagnosestellung) beschränken sich meist auf bestimmte Therapien, schließen höhere Tumorstadien aus oder untersuchen nur die Wirkung von klinischen Einflussfaktoren. In Schleswig-Holstein wurde im Rahmen der populationsbezogenen OVIS- und CAESAR-Studie die Lebensqualität bei Männern mit bzw. nach Prostatakrebs zu drei Zeitpunkten erhoben (15 Monate, 3 ½ und 7 Jahre nach initialer Diagnose). Für die allgemeine krebsspezifische Lebensqualität (EORTC QLQ-C30) erfolgt eine Beschreibung des Verlaufs sowie ein Vergleich mit Referenzdaten aus der deutschen Allgemeinbevölkerung. Aus der dritten Befragung liegen auch Daten zur prostataspezifischen Lebensqualität (EORTC QLQ-PR25) vor. Mittels multipler linearer Regressionen werden für elf ausgewählte Lebensqualitätsskalen (mögliche Werte 0 bis 100) potenzielle Einflussfaktoren (klinisch, soziodemographisch, Lifestyle) untersucht. Die Lebensqualität der 911 Männer (medianes Alter bei Drittbefragung: 72 Jahre) nimmt im zeitlichen Verlauf nur gering, aber nicht klinisch relevant ab. Es zeigen sich nur geringe Unterschiede zur Lebensqualität der Referenzbevölkerung. Im absoluten Vergleich aller Skalen werden zum Zeitpunkt der Drittbefragung auf den prostataspezifischen Skalen die größten Einschränkungen berichtet. In den berechneten multiplen Regressionen war sieben Jahre nach Diagnose eine Krankheitsprogression auf allen untersuchten Skalen signifikant mit einer geringeren Lebensqualität assoziiert (niedrigster Regressionskoeffizient βadj -13,8, 95 %-CI -18,8; -8,8). Eine Strahlentherapie zeigte auf zehn, eine Hormontherapie auf fünf Skalen einen negativen Einfluss. Ebenfalls auf fünf Skalen war ein höherer Body-Mass-Index ein Prädiktor für eine geringere Lebensqualität. Auf allen Funktionsskalen war ein höherer Sozialstatus mit einer besseren Lebensqualität assoziiert und zeigte tendenziell einen größeren Einfluss als die initiale Therapie. Alleinstehende Männer berichteten eine geringere sexuelle Aktivität (βadj -7,5, 95 %-CI -13,8; -1,2) als Männer in einer Partnerschaft. Neben klinischen Faktoren beeinflussen auch soziodemographische Variablen die Lebensqualität von langzeitüberlebenden Männern nach bzw. mit Prostatakarzinom signifikant. Daher sollten in nicht-randomisierten Studien zum Adjustieren die entsprechenden Variablen (wie z. B. Body-Mass-Index, Sozialstatus, Partnerschaft) mit erhoben werden. Klinisch relevante Veränderungen der allgemeinen krebsspezifischen Lebensqualität finden – wenn überhaupt – innerhalb der ersten 15 Monate nach Diagnosestellung statt. Referenzdaten für die prostataspezifische Lebensqualität der Allgemeinbevölkerung liegen nicht vor. Eine Erhebung dieser scheint sinnvoll, da hier größere Unterschiede im Vergleich beider Gruppen erwartet werden.

The Swiss IMRT dosimetry intercomparison using a thorax phantom

In 2008, a national intensity modulated radiation therapy (IMRT) dosimetry intercomparison was carried out for all 23 radiation oncology institutions in Switzerland. It was the aim to check the treatment chain focused on the planning, dose calculation, and irradiation process.

Src inhibitors in lung cancer: current status and future directions

Src tyrosine kinases regulate multiple genetic and signaling pathways involved in the proliferation, survival, angiogenesis, invasion, and migration of various types of cancer cells They are frequently expressed and activated in many cancer types, including lung cancer. Several Src inhibitors, including dasatinib, saracatinib, bosutinib, and KX2-391, are currently being investigated in clinical trials. Preliminary results of the use of single-agent Src inhibitors in unselected patients with lung cancer show that these inhibitors have a favorable safety profile and anticancer activity. Their combination with cytotoxic chemotherapy, other targeted therapy, and radiation therapy is currently being explored. In this review, we summarize the rationale for and the current status of Src inhibitor development and discuss future directions based on emerging preclinical data.

The role of choline positron emission tomography/computed tomography in the management of patients with prostate-specific antigen progression after radical treatment of prostate cancer

Choline positron emission tomography (PET)/computed tomography (CT) is a currently used diagnostic tool in restaging prostate cancer (PCa) patients with increasing prostate-specific antigen (PSA) after either radical prostatectomy (RP) or external-beam radiation therapy (EBRT). However, no final recommendations have been made on the use of this modality for patient management.

Primary tumors of the submandibular glands: a retrospective study based on 41 cases

We report our experience on the diagnostic approach, treatment, and follow-up of primary submandibular gland tumors. Retrospective review. Tertiary referral center. Forty-one adult patients, 22 male and 19 female, with primary submandibular gland tumors, 20 benign and 21 malignant. Age, gender, clinical findings, cyto- and histopathology, treatment and outcome were analyzed. Most tumors presented as a painless submandibular mass. Thirty three patients underwent a fine needle aspiration, the sensitivity, specificity and accuracy of which--in detecting malignant tumors--were 79%, 100% and 88%, respectively. Preoperative radiological imaging was performed in 30 cases. Patients with benign tumors were treated with surgery. Most malignant tumors were treated with a combined modality, including neck dissection and radiation therapy. Five patients developed a postoperative complication. Recurrent disease was encountered in 5 malignant tumors. The 2, 5 and 10 year disease-specific survival of patients with malignancy were 84%, 75% and 41%, respectively. The preoperative assessment of the nature of submandibular gland tumors remains challenging. Aggressive treatment of patients with malignant disease may help to avoid poor prognosis.