[en] Purpose: To assess uncertainties in the definition of the clinical target volume (CTV) for patients scheduled for primary radiotherapy of cervix carcinoma. Methods and materials: Seven physicians (five radiation oncologists and two gynaecologists) independently contoured the CTVs for three patients. All observers were provided with the same clinical information. CTVs were entered directly in the treatment planning system. Differences were analysed qualitatively and quantitatively. Results: The qualitative analysis revealed a good agreement by all observers on anatomical structures identified to be at risk for tumour spread. Quantitatively, however, a large interobserver variability was found. The ratio between largest and smallest volumes ranged between 3.6 and 4.9 for all observers (3.6-4.9 for the radiation oncologists, 1.3-2.8 for the gynaecologists). The median three-dimensional difference in gravity centres ranged between 10.9 and 26.3 mm for the respective patients. The ratio of common volumes to encompassing volumes ranged between 0.11 and 0.13 for the radiation oncologists, and between 0.30 and 0.57 for the gynaecologists. Conclusions: Although there was a good consistency in outlined anatomical structures, for the radiation therapy of carcinomas of the uterine cervix a large interobserver variability in CTV delineation concerning the magnitude and relative location of volumes was observed. Compared to other factors, e.g. set-up and organ motion, interobserver variability in CTV definition seems to have the highest impact on the geometrical accuracy in the radiotherapy of this tumour entity

[en] Purpose: to evaluate prostate volume changes during external-beam irradiation in consequence of high-dose-rate (HDR) brachytherapy in prostate cancer treatment. Patients and methods: 20 patients who underwent radiotherapy for prostate cancer were included in this prospective evaluation. All patients had a computed tomography (CT) scan for planning of the external-beam irradiation and additional scans after each HDR brachytherapy. For the planning target volume (PTV), a safety margin of 10 mm was added to the clinical target volume (CTV) in each direction. The prostate volume measured in the planning CT was compared with the prostate volumes measured after HDR brachytherapy and, subsequently, the change of prostate volume was calculated. Volume changes which resulted in differences of the prostate radius of > 5 mm for the CTV were defined as a reason for a new treatment-planning procedure for the patient. Results: taking all patients together, prostate volumes before HDR, 1 day and 4-6 days after the first HDR treatment, as well as 1 day and 4-6 days after the second HDR treatment were in median 37.7 cm³, 37.6 cm³, 38.2 cm³, 39.3 cm³, and 40.5 cm³, respectively. In none of the patient, a volume change resulted in a change of the prostate radius of > 5 mm for the CTV. Prerequisite for this calculation was the simplification of the complex prostate geometry to a sphere. No new treatment-planning procedure was necessary during external-beam radiotherapy. Conclusion: HDR brachytherapy does change the prostate volume. Under the condition of a 10-mm safety margin in each direction added to the CTV for the PTV, no new treatment-planning procedure was necessary after HDR brachytherapy. There is no need for CT scans at regular intervals during external-beam radiotherapy. (orig.)

[en] Background and purpose: Migration of leukocytes into tissue is a key element of innate and adaptive immunity. An animal study showed that liver irradiation, in spite of induction of chemokine gene expression, does not lead to recruitment of leukocytes into the parenchyma. The aim of this study was to analyze gene expression of adhesion molecules, which mediate leukocyte recruitment into organs, in irradiated rat liver in vivo and rat hepatocytes in vitro. Material and methods: Rat livers in vivo were irradiated selectively at 25 Gy. Isolated hepatocytes in vitro were irradiated at 8 Gy. RNA extracted within 48 h after irradiation in vivo and in vitro was analyzed by real-time PCR (polymerase chain reaction) and Northern blot. Adhesion molecule concentration in serum was measured by ELISA (enzyme-linked immunosorbent assay). Cryostat sections of livers were used for immunohistology. Results: Significant radiation-induced increase of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), JAM-1 (junctional adhesion molecule-1), β₁-integrin, β₂-integrin, E-cadherin, and P-selectin gene expression could be detected in vivo, while PECAM-1 (platelet-endothelial cell adhesion molecule-1) gene expression remained unchanged. In vitro, β₁-integrin, JAM-1, and ICAM-2 showed a radiation-induced increased expression, whereas the levels of P-selectin, ICAM-1, PECAM-1, VCAM-1, Madcam-1 (mucosal addressin cell adhesion molecule-1), β₂-integrin, and E-cadherin were downregulated. However, incubation of irradiated hepatocytes with either tumor necrosis factor-(TNF-)α, interleukin-(IL-)1β, or IL-6 plus TNF-α led to an upregulation of P-selectin, ICAM-1 and VCAM-1. Conclusion: The findings suggest that liver irradiation modulates gene expression of the main adhesion molecules in vivo and in cytokine-activated hepatocytes, with the exception of PECAM-1. This may be one reason for the lack of inflammation in the irradiated rat liver. (orig.)

[en] To evaluate prospectively the effect of sodium butyrate enemas on the treatment of acute and the potential influence on late radiation-induced proctitis. 31 patients had been treated with sodium butyrate enemas for radiation-induced acute grade II proctitis which had developed after 40 Gy in median. During irradiation the toxicity was evaluated weekly by the Common Toxicity Criteria (CTC) and subsequently yearly by the RTOG (Radiation Therapy Oncology Group) and LENT-SOMA scale. 23 of 31 patients (74%) experienced a decrease of CTC grade within 8 days on median. A statistical significant difference between the incidence and the severity of proctitis before start of treatment with sodium butyrate enemas compared to 14 days later and compared to the end of irradiation treatment course, respectively, was found. The median follow-up was 50 months. Twenty patients were recorded as suffering from no late proctitis symptom. Eleven patients suffered from grade I and 2 of these patients from grade II toxicity, too. No correlation was seen between the efficacy of butyrate enemas on acute proctitis and prevention or development of late toxicity, respectively. Sodium butyrate enemas are effective in the treatment of acute radiation-induced proctitis in patients with prostate cancer but have no impact on the incidence and severity of late proctitis. (orig.)

[en] To evaluate gold marker displacement due to needle insertion during HDR-brachytherapy for therapy of prostate cancer. 18 patients entered into this prospective evaluation. Three gold markers were implanted into the prostate during the first HDR-brachytherapy procedure after the irradiation was administered. Three days after marker implantation all patients had a CT-scan for planning purpose of the percutaneous irradiation. Marker localization was defined on the digitally-reconstructed-radiographs (DRR) for daily (VMAT technique) or weekly (IMRT) set-up error correction. Percutaneous therapy started one week after first HDR-brachytherapy. After the second HDR-brachytherapy, two weeks after first HDR-brachtherapy, a cone-beam CT-scan was done to evaluate marker displacement due to needle insertion. In case of marker displacement, the actual positions of the gold markers were adjusted on the DRR. The value of the gold marker displacement due to the second HDR-brachytherapy was analyzed in all patients and for each gold marker by comparison of the marker positions in the prostate after soft tissue registration of the prostate of the CT-scans prior the first and second HDR-brachytherapy. The maximum deviation was 5 mm, 7 mm and 12 mm for the anterior-posterior, lateral and superior-inferior direction. At least one marker in each patient showed a significant displacement and therefore new marker positions were adjusted on the DRRs for the ongoing percutaneous therapy. Needle insertion in the prostate due to HDR-brachytherapy can lead to gold marker displacements. Therefore, it is necessary to verify the actual position of markers after the second HDR-brachytherapy. In case of significant deviations, a new DRR with the adjusted marker positions should be generated for precise positioning during the ongoing percutaneous irradiation

[en] Background and purpose: transoral laser microsurgery (TLM) and adjuvant radiotherapy are an established therapy regimen for locally advanced laryngeal cancer at our institution. Aim of the present study was to assess value of quality of life (QoL) data with special regard to organ function under consideration of treatment efficacy in patients with locally advanced laryngeal cancer treated with larynx-preserving TLM and adjuvant radiotherapy. Patients and methods: from 1994 to 2006, 39 patients (ten UICC stage III, 29 UICC stage IVA/B) with locally advanced laryngeal carcinomas were treated with TLM and adjuvant radiotherapy. Data concerning treatment efficacy, QoL (using the VHI [Voice Handicap Index], the EORTC QLQ-C30 and QLQ-H and N35 questionnaires) and organ function (respiration, deglutition, voice quality) were obtained for ten patients still alive after long-term follow-up. Correlations were determined using the Spearman rank test. Results: after a median follow-up of 80.8 months, the 5-year overall survival rate was 46.8% and the locoregional control rate 76.5%, respectively. The larynx preservation rate was 89.7% for all patients and 100% for patients still alive after follow-up. Despite some verifiable problems in respiration, speech and swallowing, patients showed a subjectively good QoL. Conclusion: TLM and adjuvant radiotherapy is a curative option for patients with locally advanced laryngeal cancer and an alternative to radical surgery. Even if functional deficits are unavoidable in the treatment of locally advanced laryngeal carcinomas, larynx preservation is associated with a subjectively good QoL. (orig.)

[en] Background and purpose: to assess the late effect of a prostaglandin, given rectally during irradiation, on late rectal toxicity. In the acute treatment setting no significant differences in reducing the incidence of acute proctitis symptoms in patients receiving misoprostol, however, significantly more rectal bleeding had been reported. Patients and methods: a total of 100 patients who had undergone radiotherapy for prostate cancer had been entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. The toxicity was evaluated yearly after cessation of irradiation by the RTOG/LENT-SOMA scale. Results: the median follow-up was 50 months. 20 patients suffered from grade 1, four patients from grade 2 as well, and three patients only from grade 2 toxicity. Frequency, bleeding and urgency were the most commonly reported symptoms. In keeping with other studies and clinical experience, the symptoms peaked within the first 2 years with a median for grade 1 of 13 months and for grade 2 of 15 months. The presence of acute toxicity grade 2 showed a correlation with the development of any late toxicity (p = 0.03). Any acute rectal bleeding was significant correlated with any late rectal bleeding (p = 0.017). Conclusion: misoprostol given as once-daily suppository for prevention of acute radiation-induced proctitis does neither influence the incidence and severity of radiation-induced acute nor late rectal toxicity. Misoprostol has no negative impact on the incidence and severity of late rectal bleeding, in contrast to acute rectal bleeding. The routine clinical use of misoprostol suppositories cannot be recommended. (orig.)

[en] Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracil (1,000 mg/m²total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m²/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of ≥3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of ≥3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical trials.

[en] Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro. LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 – 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation). Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen. The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro

[en] Purpose: Acute radiation proctitis is the most relevant complication of pelvic radiation and is still mainly treated supportively. Considering the negative impact of acute proctitis symptoms on patients' daily activities and the potential relationship between the severity of acute radiation injury and late damage, misoprostol was tested in the prevention of acute radiation-induced proctitis. Methods and Materials: A total of 100 patients who underwent radiotherapy for prostate cancer were entered into this phase III randomized, placebo-controlled, double-blind study with misoprostol or placebo suppositories. Radiation-induced toxicity was evaluated weekly during radiotherapy using the Common Toxicity Criteria. Results: Between the placebo and the misoprostol groups, no significant differences in proctitis symptoms occurred: 76% of patients in each group had Grade 1 toxicity, and 26% in the placebo group and 36% in the misoprostol group had Grade 2 toxicity. No differences were found in onset or symptom duration. Comparing the peak incidence of patients' toxicity symptoms, significantly more patients experienced rectal bleeding in the misoprostol group (p = 0.03). Conclusion: Misoprostol given as a once-daily suppository did not decrease the incidence and severity of radiation-induced acute proctitis and may increase the incidence of acute bleeding