Ulrich Schaefer

Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology

PURPOSE We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. METHODS AND MATERIALS Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84μg/L were randomized before RT either to receive 500 μg of selenium (in the form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 μg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. RESULTS A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. CONCLUSIONS Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.

Multicenter, Phase III Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology: Follow-Up Analysis of the Survival Data 6 Years After Cessation of Randomization

Purpose. In 2010, we reported that selenium (Se) supplementation during radiation therapy (RT) is effective for increasing blood Se levels in Se-deficient cervical and uterine cancer patients, and reduced the number of episodes and severity of RT-induced diarrhea. In the current study, we examine whether of Se supplementation during adjuvant RT affects long-term survival of these patients. Patients and Methods. Former patients were identified and questioned with respect to their health and well-being. Results. A total of 81 patients were randomized in the initial supplementation study, 39 of whom received Se (selenium group, SeG) and 42 of whom served as controls (control group, CG). When former patients were reidentified after a median follow-up of 70 months (range = 0-136), the actuarial 10-year disease-free survival rate in the SeG was 80.1% compared to 83.2% in the CG (P = .65), and the actuarial 10-year overall survival rate of patients in the SeG was 55.3% compared to 42.7% in the CG (P = .09). Conclusions. Our extended follow-up analysis demonstrates that Se supplementation had no influence on the effectiveness of the anticancer irradiation therapy and did not negatively affect patients’ long-term survival. In view of its positive effects on RT-induced diarrhea, we consider Se supplementation to be a meaningful and beneficial adjuvant treatment in Se-deficient cervical and uterine cancer patients while undergoing pelvic radiation therapy.

CT simulation in nodal positive breast cancer.

Background: A variety of solutions are used to match tangential fields and opposed lymph node fields in irradiation of nodal positive breast cancer. The choice is depending on the technical equipment which is available and the clinical situation. The CT simulation of a non-monoisocentric technique was evaluated in terms of accuracy and reproducibility. Patients, Material and Methods: The field match parameters were adjusted virtually at CT simulation and were compared with parameters derived mathematically. The coordinate transfer from the CT simulator to the conventional simulator was analyzed in 25 consecutive patients. Results: The angles adjusted virtually for a geometrically exact coplanar field match corresponded with the angles calculated for each set-up. The mean isocenter displacement was 5.7 mm and the total uncertainty of the coordinate transfer was 6.7 mm (1 SD). Limitations in the patient set-up became obvious because of the steep arm abduction necessary to fit the 70 cm CT gantry aperture. Required modifications of the arm position and coordinate transfer errors led to a significant shift of the marked matchline of > 1.0 cm in eight of 25 patients (32%). Conclusion: The virtual CT simulation allows a precise and graphic definition of the field match parameters. However, modifications of the virtual set-up basically due to technical limitations were required in a total of 32% of cases, so that a hybrid technique was adapted at present that combines virtual adjustement of the ideal field alignment parameters with conventional simulation.Hintergrund: Für den Feldanschluss zwischen Brusttangenten und ventrodorsal opponierenen Lymphknotenfeldern bei der Bestrahlung des nodal positiven Mammakarzinoms sind verschiedene Methoden in Gebrauch, wobei für die Auswahl technische und klinische Gegebenheiten maßgeblich sind. Die CT-Simulation einer nicht monoisozentrischen Technik wird in dieser Untersuchung hinsichtlich Genauigkeit und Reproduzierbarkeit geprüft. Patienten, Material und Methode: Feldanschlussparameter wurden mit virtueller Simulation erstellt und mit errechneten Werten verglichen. Der Koordinatentransfer vom CT-Simulator zum konventionellen Simulator wurde bei 25 aufeinanderfolgenden Patienten analysiert. Ergebnisse: Virtuell eingestellte und berechnete Winkel stimmten exakt überein. Die totale Unsicherheit des Koordinatentransfers war 6,7 mm (1 SD) und die mittlere Isozentrumsabweichung der Tangenten betrug 5,7 mm. Einschränkungen der möglichen Patientenlagerung waren auf den beschränkten CT-Gantry-Durchmesser von 70 cm zurückzuführen, die nur eine steile Armhaltung ermöglichte. Notwendige Änderungen der Armposition und Fehler im Koordinatentransfer machten eine signifikante Verschiebung der Anschlusslinie über 1,0 cm bei acht Patientinnen (32%) erforderlich. Schlussfolgerung: Die virtuelle CT-Simulation ermöglicht eine genaue und anschauliche Definition der Feldanschlussparameter. Modifikationen dieser Parameter waren jedoch bei acht von 25 (32%) Patientinnen im Wesentlichen aufgrund von gerätetechnischen Einschränkungen erforderlich, sodass derzeit eine “Hybridtechnik” durchgeführt wird, welche die virtuelle Erstellung der Parameter mit der konventionellen Simulation verbindet.

Impact of treatment planning target volumen (PTV) size on radiation induced diarrhoea following selenium supplementation in gynecologic radiation oncology - a subgroup analysis of a multicenter, phase III trial

BackgroundIn a previous analysis (Int J Radiat Oncol Biol Phys 70:828-835,2010), we assessed whether an adjuvant supplementation with selenium (Se) improves Se status and reduces the radiation-induced side-effects of patients treated by adjuvant radiotherapy (RT) for cervical and uterine cancer. Now, a potential relation between the planning target volume (PTV) of the RT and the Se effect concerning radiation induced diarrhoea was evaluated in detail.MethodsWhole blood Se concentrations had been measured in patients with cervical (n=11) and uterine cancer (n=70) after surgical treatment, during, and at the end of RT. Patients with initial Se concentrations of less than 84 μg/l were categorized as Se-deficient and randomized before RT to receive Se (as sodium selenite) per os on the days of RT, or to receive no supplement during RT. Diarrhoea was graded according to the Common Toxicity Criteria system (CTC, Version 2a). The evaluation of the PTV of the RT was ascertained with the help of a specialised computer-assisted treatment planning software used for radiation planning procedure.ResultsA total of 81 patients had been randomized for the initial supplementation study, 39 of which received Se [selenium group, SeG] and 42 serving as controls [control group, CG]. Mean Se levels did not differ between SeG and CG upon study initiation, but were significantly higher in the SeG compared to the CG at the end of RT. The actuarial incidence of at least CTC 2 radiation induced diarrhoea in the SeG was 20.5% compared to 44.5% in the CG (p=0.04). The median PTV in both groups was 1302 ml (916–4608). With a PTV of <= 1302 ml (n=41) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 22.3% (4 of 18 patients) compared to 34.8% (8 of 23 patients) in the CG (p=0.50). In patients with a PTV of > 1302 ml (n=40) the actuarial incidence of at least CTC 2 diarrhoea in the SeG was 19.1% (4 of 21 patients) versus 52.6% (10 of 19 patients) in the CG (p=0.046).ConclusionsSe supplementation during RT was effective to improve blood Se status in Se-deficient cervical and uterine cancer patients, and reduces episodes and severity of RT-induced diarrhoea. This effect was most pronounced and significant in patients with large PTV (> 1302 ml).

Systemic Mast Cell Disease (SMCD) and Bone Pain A Case Treated with Radiotherapy

Background: Systemic mast cell disease (SMCD) is a rare disease characterized by a multitopic proliferation of cytologically and/or functionally abnormal tissue mast cells. SMCD preferentially involves the skin, spleen, liver, lymph nodes and the bone marrow. The cause of SMCD is unknown. Bony pain, caused by mast cell infiltration of the marrow cavity, is present in up to 28% of cases and is frequently chronic and difficult to palliate with medical therapy. Case Report: We report one case of refractory bone pain in a 54-year-old female Caucasian patient with advanced SMCD and associated bony involvement, which was treated with radiotherapy for pain palliation. Between 1995 and 1998, the patient was irradiated at four different locations: 1) right shoulder and proximal right humerus, 2) both hands, 3) both knees, 4) left humerus with a total dose of 40 Gy in 2.0 or 2.5 Gy daily fractions. Results: Different results of pain palliation were achieved. In one location the pain was reduced for 55 months until her death due to disease progression, whereas in two other locations a pain control was maintained for 3 and 6 months after radiotherapy. In one location, no pain reduction was achieved. Severe side effects were not observed. Conclusion: Palliative radiotherapy has a role in the control of severe intractable bone pain in patients with advanced SMCD, though in some cases the effect may be short or incomplete. The observed palliation of pain can even differ in the same patient.Hintergrund: Systemische Mastozytose (SMCD) ist eine seltene Erkrankung, die durch eine multiokuläre Vermehrung von zytologisch oder funktionell atypischen Gewebemastzellen charakterisiert ist. SMCD ist u. a. durch eine Infiltration der Haut, der Milz, der Leber, der Lymphknoten und des Knochenmarkes durch atypische Mastzellen gekennzeichnet. Der Grund der Erkrankung ist unklar. Knochenschmerzen, die durch eine Knochenmarkinfiltration der atypischen Mastzellen verursacht werden können, werden in bis zu 28% aller Fälle beobachtet und sind vielfach chronisch und schwer medikamentös zu beherrschen. Fallbeschreibung: Wir beschreiben den Fall einer 54-jährigen Patientin mit fortgeschrittener SMCD mit Knochenmarkbeteiligung (Abbildungen 1a bis 1d) und therapierefraktären Knochenschmerzen, welche zur Schmerzpalliation mehrfach bestrahlt wurde. Zwischen 1995 und 1998 wurde die Patientin an insgesamt vier verschiedenen Lokationen (1. rechte Schulter und proximaler rechter Humerus, 2. beide Hände, 3. beide Knie, 4. linker Humerus) mit Gesamtdosen von jeweils 40 Gy in täglichen Fraktionen à 2,0 oder 2,5 Gy bestrahlt. Ergebnisse: Unterschiedliche Ergebnisse der Schmerzlinderung wurden erreicht. An einer Lokalisation wurde eine Schmerzlinderung für 55 Monate bis zum Tod der Patientin aufgrund einer allgemeinen Krankheitsprogression erreicht, wohingegen an zwei weiteren Lokalisationen eine Schmerzkontrolle für 3 bzw. 6 Monate nach Beendigung der Strahlentherapie gelang. An einer Lokalisation wurde überhaupt keine Linderung der Schmerzen erreicht. Schwerwiegende Nebenwirkungen traten nicht auf. Schlussfolgerung: Radiotherapie zur Palliation von ausgeprägten Knochenschmerzen hat ihren Stellenwert bei fortgeschrittener SMCD, obgleich der Linderungseffekt in manchen Fällen nur kurz oder unzureichend sein kann (Tabelle 1). Der beobachtete Effekt der Schmerzlinderung kann sich selbst bei demselben Patienten unterscheiden.