[en] AP1, PASSOS-Heart Study. Background: In breast cancer patients treated in the 1970s and 1980s, radiation therapy (RT) for left-sided tumors has been associated with an elevated risk of cardiac mortality. In recent years, improved RT techniques have reduced radiation exposure of the heart and major coronary vessels, but some exposure remains unavoidable. Aims: To assess the long-term cardiac mortality and morbidity risk of breast cancer survivors treated with modern RT in Germany. To determine the radiation heart dose and radiation dose distribution of the heart after 3D-conformal RT. Methods: A retrospective cohort study included breast cancer patients who were treated for loco-regional breast cancer between 1998 and 2008 at the Medical University Center Mainz, Ulm or partner clinics in the vicinity of Ulm. A systematic mortality follow-up was conducted until December 2012. Questionnaires on cardiac events before or after therapy and on associated risk factors were sent out in 2014. Individual cardiac dose was predicted for a sample of approximately 770 breast cancer patients. Results: A total of 11,982 women met the inclusion criteria. A total of 9.058 (75%) patients received RT. The average mean heart dose (median) was 4.6 Gy (3.7 Gy) for left-sided RT, and 1.7 Gy (1.4 Gy) for right-sided RT. The median follow up-time was 6,5 years (mortality) and 8,3 years for morbidity endpoints. No evidence for an effect of tumor laterality on cardiac mortality or morbidity in irradiated patients was found. AP4; Personalized risks for late effects after radiation therapy. Aim: to develop risk models for cardiovascular late effects and second primaries after radiation therapy. Methods: Systematically Literature search and meta-analysis. Results: Increased risks for cardiovascular late effects and second primaries.

[en] Background and purpose: The intention of this prospective study is to assess the influence of different patient positionings and the use of belly boards on the coverage of the uterus by standard radiation fields. Material and methods: In 21 women with carcinoma of the uterine cervix magnetic resonance imaging (MRI) scans in prone patient position with and without belly board and computed tomography (CT) scans in supine position were analysed after superimposing standard pelvic box fields. Further, all patients underwent a second MRI field control in prone position with belly board to detect intraindividual variations in the uterus position during treatment. Results: Standard portals did not completely cover the uterus in supine position in 7/21 (33%), in prone position with belly board in 7/21 (33%) and without belly board in 5/21 (24%). Insufficient uterine coverage was found only in the anteroposterior direction. The mean distance (± standard deviation) between the field borders of the lateral portals and the uterus was in supine position anteriorly 3.4 cm (±2.2 cm) and posteriorly 1.8 cm (±1.3 cm), in prone position with belly board anteriorly 2.2 cm (±2.7 cm) and posteriorly 2.6 cm (±1.6 cm), prone without belly board anteriorly 3.3 cm (±2.4 cm) and posteriorly 1.9 cm (±1.1 cm). The difference was statistically significant between supine and prone position with belly board and between prone position with and without belly board. Repeated MRI controls during therapy showed no significant changes compared to the MRIs at the beginning of therapy. Conclusions: The use of standard radiation fields results in a high percentage of geographical misfits. Three-dimensional treatment planning is a prerequisite for adequate uterus coverage

[en] Purpose: To define the maximum tolerated dose (MTD) by describing the dose-limiting toxicity (DLT) of weekly paclitaxel (PAC) given as a 1-h IV infusion in patients with head and neck cancer concomitant to irradiation. Methods and Materials: Patients with unresectable or incompletely resected head and neck cancer were enrolled into a prospective, dose-escalating Phase I study. Toxicity was graded according to the WHO toxicity score. MTD dose was defined when two out of six patients developed DLT. The starting dose of PAC was 20 mg/m² once weekly IV over 60 min, with a subsequent dose escalation of 10 mg/m² in cohorts of three new patients. Radiation therapy was administered in three field technique over 6-7 weeks in 2.0 Gy/daily fractions for 5 consecutive days/week up to total doses of 60-70 Gy. Results: >From 1994-1996, 18 patients completing three dose levels were included into the study. Altogether, 101 courses of chemotherapy were evaluable for toxicity. On the second dose level (30 mg/m²) one of three patients experienced DLT with Grade IV mucositis. On the next dose level with 40 mg/m² PAC weekly one patient experienced DLT being prolonged Grade III mucositis. From the following three patients required, two patients showed no DLT. The third patient showed mucositis of WHO Grade 4 and died from hemorrhage caused by a rupture of the a pharyngeal wall. Dose level 2 (30 mg/m²) was repeated and one of the three newly treated patients again suffered from mucositis WHO Grade 4. Conclusion: When PAC is given weekly as a 1-h infusion concomitant to radiotherapy, MTD is 30 mg/m² with mucositis being DLT; hematological and further non hematological toxicity is mild

No abstract available

[en] Purpose: The combined effect of natural Interferon-beta (n-IFN-β) and ionizing radiation was tested in vitro on 5 different tumor cell lines and 1 embryonal lung fibroblast cell line. Materials and Methods: The following cell lines were used: A549 (lung cancer), MCF-7 (breast cancer), CaSki (cervical cancer), WiDr (colon cancer), ZMK-1 (head and neck cancer), and MRC-5 (embryonal lung fibroblast line). Cells were incubated with n-IFN-β (30 I.U./ml to 3000 I.U./ml) 24 h before irradiation. Irradiation was given as single dose between 1 and 6 Gy. Cell survival was evaluated using a standard colony-forming assay. Results: Incubation with n-IFN-β enhanced the effect of radiation in all tumor cell lines tested. The maximum sensitizing enhancement ratios (SER) at the 37% survival level were: 1.66 for A549 cells, 1.47 for CaSki cells, 1.56 for MCF-7 cells, 1.40 for WiDr cells, and 1.57 for ZMK-1 cells. In the nonneoplastic MRC-5 cell line, no radiosensitizing effect of n-IFN-β could be demonstrated. The linear quadratic fit of the survival curves showed an increase of the α-component for all tumor cell lines treated with n-IFN-β. Conclusions: IFN-β enhanced the effect of radiation in the tumor cell lines, but not in the nonmalignant lung fibroblasts. The increase of the α component in the survival curves indicates that impaired radiation repair or the accumulation of sublethal damage might play a role for the radiosensitizing effect of n-IFN-β

[en] 

Background

An improvement in the prognosis of extranodal non-Hodgkin’s lymphoma can be derived from retrospective analyses with historical controls by involved site radiotherapy in the limited stages (I and II). Changes in the histological classification, the definition of extranodal involvement and systemic treatment over the years make the analysis of retrospective data more difficult. This article presents a summary of the treatment concepts as can be derived from the currently available literature.

Material and methods

This study was based on a systematic literature search in the PubMed databank with the keywords lymphoma, extranodal and radiotherapy.

Results

As a general rule radiotherapy of the whole affected organ can be recommended for extranodal involvement in stages I and II. For indolent lymphomas radiotherapy with average doses of 24–30 Gy are curative. For aggressive lymphomas radiotherapy of the organ involved is carried out after chemotherapy. In cases of complete remission 30 Gy is recommended and for incomplete remission 40 Gy. In addition, there are many special cases that necessitate high-dose radiotherapy (e.g. natural killer T‑cell lymphoma and cutaneous CD30 positive lymphoma).

Conclusion

Improvements in imaging and systemic treatment will continue to necessitate an adaptation of these concepts also in the future. Study concepts that test the altered systemic treatment methods should also re-evaluate the role of radiation therapy, if possible in a factorial design.

[en] Purpose: To show the results of treating posterior uveal melanomas with ¹⁰⁶Ru plaque β-ray radiotherapy and to review and discuss the literature concerning the optimal apical dose prescription (100 vs. 160 Gy). Methods and Materials: Forty-eight patients with uveal melanomas (median height 3.85 mm + 1 mm sclera) were treated with ruthenium plaques. The median apical dose was 120 Gy, the median scleral dose 546 Gy. Results: After 5.8 years of follow-up, the overall 5-year survival rate was 90%, the disease specific 5-year survival rate was 92% (3 patients alive with metastasis). Six percent received a second ruthenium application, 10% of the eyes had to be enucleated. Local control was achieved in 90% of the patients with conservative therapy alone. Central or paracentral tumors showed 50% of the pretherapeutic vision after 4 years, and 80% of the vision was preserved in those with peripheral tumors. The main side effects were mostly an uncomplicated retinopathy (30%); macular degeneration or scarring led to poor central vision in 30% of cases. Conclusion: Brachytherapy with ruthenium applicators is an effective therapy for small- and medium-size posterior uveal melanomas. Our results are comparable to other series. The treatment outcome does not seem to be capable of improvement by increasing the apical dose. An internationally accepted model for defining the dosage in brachytherapy is needed

[en] Biodosimetric assessment and comparison of radiation-induced deoxyribonucleic acid (DNA) double-strand breaks (DSBs) by γH2AX immunostaining in peripheral leukocytes of patients with painful heel spur after radiation therapy (RT) with orthovoltage X‑rays or a 6-MV linear accelerator (linac). The treatment response for each RT technique was monitored as a secondary endpoint. 22 patients were treated either with 140-kV orthovoltage X‑rays (n = 11) or a 6-MV linac (n = 11) with two weekly fractions of 0.5 Gy for 3 weeks. In both scenarios, the dose was prescribed to the International Commission on Radiation Units and Measurements (ICRU) dose reference point. Blood samples were obtained before and 30 min after the first RT session. γH2AX foci were quantified by immunofluorescence microscopy to assess the yield of DSBs at the basal level and after radiation exposure ex vivo or in vivo. The treatment response was assessed before and 3 months after RT using a five-level functional calcaneodynia score. RT for painful heel spurs induced a very mild but significant increase of γH2AX foci in patients’ leukocytes. No difference between the RT techniques was observed. High and comparable therapeutic responses were documented for both treatment modalities. This trial was terminated preliminarily after an interim analysis (22 patients randomized). Low-dose RT for painful heel spurs with orthovoltage X‑rays or a 6-MV linac is an effective treatment option associated with a very low and comparable radiation burden to the patient, as confirmed by biodosimetric measurements.

[en] Purpose: The evaluation of radiation-induced chromosomal translocations in peripheral lymphocytes using fluorescent in situ hybridization is a promising method for retrospective dosimetry after a radiation accident. We evaluated the genomic frequency of chromosomal translocations in patients with testicular seminoma who received adjuvant radiotherapy to the retroperitoneal lymph nodes, to evaluate the time-effect relationship of radiation-induced stable aberrations after partial body irradiation. Methods: In 13 patients, peripheral lymphocytes could be evaluated before radiotherapy and at several time points after radiotherapy. In 17 additional patients, lymphocyte samples were obtained after radiotherapy. Thirteen healthy men served as age-matched controls for the aberration frequency before radiotherapy. Fluorescent in situ hybridization was performed using whole chromosome probes against chromosomes No. 4, No. 6, and No. 7. Results: Nearly all patients displayed an increased spontaneous rate of genomic translocations (F_G) before radiotherapy compared to age-matched, healthy men. The difference was significant in the paired ranks test (p<0.0001). After adjuvant radiotherapy, the F_G increased 2- to 8-fold in individual patients. Within 20 months after radiotherapy, the F_G returned to pretherapeutic levels. Conclusions: The frequency of genomic translocations after partial body irradiation is time dependent. A persistence of chromosomal aberrations, which is to be expected after total body irradiation, could not be observed. It is likely that the dose and the volume of the irradiated bone marrow are playing a role in the persistence of stable chromosomal aberrations. Patients with testicular seminoma displayed an increased frequency of spontaneous genomic translocations before the initiation of radiotherapy. This chromosomal instability might be related to the known increased rate of secondary cancers in this patient group

[en] Purpose: A prospective multicenter study was carried out to estimate the treatment outcome of radiotherapy in Stage II seminoma after the application of modern staging and radiotherapy techniques. The lower margin of the iliac field was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remaining testicle. Methods and Materials: The study was carried out in 25 centers in Germany. Patients with pure seminoma, negative AFP-values, and retroperitoneal lymph node metastases of less than 5 cm in diameter were entered into the study. All patients received a ventrodorsal opposed field irradiation of the para-aortic and the ipsilateral iliac lymph nodes. The fields extended from the top of the 11th thoracic vertebra to the top of the acetabulum. Patients in Stage IIA (lymph nodes <2 cm) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. Results: 39 patients in Stage IIA and 19 patients in Stage IIB were evaluated. After a median observation time of 37 months all patients are alive and disease free. Recurrence free survival in stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 months after the end of radiotherapy. The actuarial recurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the mediastinum, one in the mediastinum, and one the lung. Both patients could be salvaged by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% (Grade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. Conclusions: The outcome of para-aortic and ipsilateral iliac irration in Stage IIA/B testicular seminoma is excellent with the currently available staging methods and treatment facilities. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum