[en] Purpose: The goal of the interdisciplinary Clinical Research Unit KFO179 (Biological Basis of Individual Tumor Response in Patients with Rectal Cancer) is to develop an individual Response and Toxicity Score for patients with locally advanced rectal cancer treated with neoadjuvant radiochemotherapy. The aim of the present study was to find a reliable and sensitive method with easy scoring criteria and high numbers of cell counts in a short period of time in order to analyze DNA damage in peripheral blood lymphocytes. Thus, the cytokinesis-block micronucleus (CBMN) assay and the chromosome aberration technique (CAT) were tested. Materials and Methods: Peripheral blood lymphocytes obtained from 22 patients with rectal cancer before (0 Gy), during (21.6 Gy), and after (50.4 Gy) radiochemotherapy were stimulated in vitro by phytohemagglutinin (PHA); the cultures were then processed for the CBMN assay and the CAT to compare the two methods. Results: A significant increase of chromosomal damage was observed in the course of radiochemotherapy parallel to increasing radiation doses, but independent of the chemotherapy applied. The equivalence of both methods was shown by Westlake's equivalence test. Conclusion: The results show that the CBMN assay and the CAT are equivalent. For further investigations, we prefer the CBMN assay, because it is simpler through easy scoring criteria, allows high numbers of cell counts in less time, is reliable, sensitive, and has higher statistical power. In the future, we plan to integrate cytogenetic damage during radiochemotherapy into the planned Response and Toxicity Score within our interdisciplinary Clinical Research Unit. (orig.)

[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] Purpose: To test for a possible correlation between high-grade acute organ toxicity during preoperative radiochemotherapy and complete tumor regression after total mesorectal excision in multimodal treatment of locally advanced rectal cancer. Patients and Methods: From 2001 to 2008, 120 patients were treated. Preoperative treatment consisted of normofractionated radiotherapy at a total dose of 50.4 Gy, and either two cycles of 5-fluorouracil (5-FU) or two cycles of 5-FU and oxaliplatin. Toxicity during treatment was monitored weekly, and any toxicity CTC (Common Toxicity Criteria) ≥ grade 2 of enteritis, proctitis or cystitis was assessed as high-grade organ toxicity for later analysis. Complete histopathologic tumor regression (TRG4) was defined as the absence of any viable tumor cells. Results: A significant coherency between high-grade acute organ toxicity and complete histopathologic tumor regression was found, which was independent of other factors like the preoperative chemotherapy schedule. The probability of patients with acute organ toxicity ≥ grade 2 to achieve TRG4 after neoadjuvant treatment was more than three times higher than for patients without toxicity (odds ratio: 3.29, 95% confidence interval: [1.01, 10.96]). Conclusion: Acute organ toxicity during preoperative radiochemotherapy in rectal cancer could be an early predictor of treatment response in terms of complete tumor regression. Its possible impact on local control and survival is under further prospective evaluation by the authors' working group. (orig.)