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Purpose: The nutritional status of inpatients influences the therapeutic outcome. Malnutrition is a common comorbidity in oncological patients. Both radio- and radiochemotherapy may contribute to the additional deterioration of the nutritional status. The aim of this study was to evaluate the impact of specialized treatment of malnutrition as a clinical routine., Methods: The nutritional status of inpatients was assessed by the Nutritional risk screening (NRS-2002) on the day of admission to the University Department of Radiation Oncology. In case of significantly elevated NRS-2002 (NRS ≥ 3), a guideline-compliant, individual nutritional treatment was initiated by a specialized nutrition support team. The influence of the nutritional status and nutritional treatment on length of stay and complication rate was assessed., Results: Of 840 included patients, 344 patients (40.95%) were at risk for malnutrition. Malnutrition was a significant, independent risk factor for both prolonged hospital stay, represented by the deviation between the actual length of stay and the DRG-associated mean length of stay (dLOS at risk: 0.88 days, dLOS not at risk: -0.88 days, p = 0.0047), as well as for the occurrence of complications (OR: 1.758 CI: [1.286-2.402], p = 0.0006). In the group of 337 (40.12%) rehospitalized patients the nutritional management was able to assimilate the values of length of stay as well as the complication rates to standard values., Conclusions: The high risk for malnutrition and the negative consequences for patients and hospitals underline the urgent need for malnutrition screening on admission and treatment of malnutrition. A specialized, interdisciplinary nutrition support team positively influences patient outcome and should be established routinely in all oncological disciplines.

Background and Purpose: Palliative radiotherapy (RT) is routinely used in end of life care of patients with advanced malignancies; however, unnecessarily burdensome treatment shortly before death should be avoided. There is little knowledge on incidence and causes of intercurrent deaths during palliative RT., Patients and Methods: In this study death events among inpatients receiving palliative RT between January 2009 and December 2011 at this department were retrospectively analyzed. Among epidemiological factors, treatment schedule and chronology, latency and duration of treatment in relation to the actual survival were identified., Results: In this study 52 patients died during or shortly after palliative RT. Symptomatic bone metastases and brain metastases represented the most common RT indications. The general health status was poor with a median Karnofsky performance score of 50 %, RT was realized with a median single dose of 2.5 Gy to a median total dose of 30.5 Gy and was stopped prematurely in 73 % of patients. On average 53 % of the remaining lifetime was occupied by latency to starting RT. Once RT was begun the treatment duration required a median 64 % of the still remaining lifetime., Conclusion: The majority of patients who died had explicitly adverse pre-existing factors and rarely completed RT as scheduled. Latency to RT and RT duration occupied more than half of the remaining lifetime.

Background: Close resection margins < 5 mm (CM) or extra capsular extent at the lymph nodes (ECE) impair the prognosis of patients with squamous cell cancer of the head and neck (SCCHN) scheduled for adjuvant radiochemotherapy. We conducted a multicenter phase II study to investigate toxicity and efficacy of additional cetuximab administered concomitantly and as maintenance for the duration of 6 months following adjuvant radiochemotherapy., Ppreliminary results on feasibility and acute toxicity on skin and mucosa are presented in this article., Methods: Patients with SCCHN following CM resection or with ECE were eligible for the study. In all, 61.6 Gy (1.8/2.0/2.2 Gy, days 1-36) were administered using an integrated boost intensity-modulated radiotherapy (IMRT) technique. Cisplatin (20 mg/m(2), days 1-5 and days 29-33) and 5-fluorouracil (5-FU) as continuous infusion (600 mg/m(2), days 1-5 + days 29-33) were given concurrently. Cetuximab was started 7 days prior to radiochemotherapy at 400 mg/m(2) followed by weekly doses of 250 mg/m(2). Maintenance cetuximab began after radiochemotherapy at 500 mg/m(2) every 2 weeks for 6 months., Results: Of the 55 patients (46 male, 9 female, mean age 55.6, range 29-70 years) who finished radiochemotherapy, 50 were evaluable for acute toxicity concerning grade III/IV toxicities of skin and mucosa. Grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals were documented for 46, 28, and 14 % of patients, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 5 patients due to allergic reactions after the first application. In addition, 22 % of patients discontinued cetuximab within the last 2 weeks or at the end of radiochemotherapy. Of patients embarking on maintenance treatment, 80 % were still on cetuximab at 3 months and 63 % at 5 months. Concurrent and maintenance treatment with cetuximab could be administered as scheduled in 48 % of patients., Conclusion: Adjuvant radiochemotherapy with concomitant and maintenance cetuximab is feasible and acute toxicities are within the expected range. Compliance within the first 3-5 months is moderate.

Background and Purpose: As treatment results for high-risk soft tissue sarcoma are still disappointing, treatment intensification is warranted. We performed a retrospective analysis of multimodal preoperative treatment to evaluate the additional effect of concurrent chemotherapy and/or locoregional hyperthermia in comparison to radiotherapy alone., Patients and Methods: Between 1999 and 2011, 28 patients were treated with neoadjuvant radiotherapy to a median 45 Gy for high-risk soft tissue sarcoma. All tumors were deep-seated and grade 2 or 3, 86% (n = 24) larger than 5 cm. Multimodal treatment (n = 12) consisted of ifosfamide (n = 7), locoregional hyperthermia (n = 3), or both modalities (n = 2) concurrent to radiotherapy., Results: Prognostic factors (grade, size, histology, location) were balanced in the groups with and without concurrent multimodal treatment. There was a significant improvement of disease-specific survival (100% vs. 70% at 3 years, p = 0.03) with multimodal treatment. Distant metastases-free survival was influenced, but was not statistically significant. Local control and disease-free survival did not differ in the two groups., Conclusion: Our data suggest that multimodal treatment with ifosfamide and/or locoregional hyperthermia in combination with neoadjuvant radiotherapy might improve outcome in high-risk soft tissue sarcomas.

We report on an 83-year-old woman who suffered from seven manifestations of at least five different nonmetastasizing malignancies during a period spanning more than three decades. Although suspected, an inherited genetic tumor syndrome could not be detected. This patient history exemplifies the development of interdisciplinary oncology and specifies the success but also the risks of intensified locoregional treatments. In particular, radiation oncologists routinely have to perform a risk-benefit analysis, rendering their work both challenging and fascinating.

Background and Purpose: This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0)., Patients and Methods: Pelvic IMRT to 45-50.4 Gy was applied in 39 cases either after previous surgery of involved lymph nodes (n = 18) or with a radiation boost to suspicious nodes (n = 21) with doses of 60-70 Gy, usually combined with androgen deprivation (n = 37). The prostate and seminal vesicles received 70-74 Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66-70 Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria., Results: Acute radiation-related toxicity higher than  grade 2 occurred in 2 patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1-2) after a median follow-up of 70 months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over  5 years., Conclusion: Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort.

Background: Reasons for inferior outcome of male compared to female breast cancer are still under debate. Therefore, we retrospectively analyzed male breast cancer cases to figure out possible treatment- and gender-related differences., Patients and Methods: A total of 40 men (median age 62 years) were curatively treated with mastectomy and postoperative radiotherapy from 1982-2007. They presented predominantly in stages II and IIIb. Postoperative radiotherapy was applied with doses of 1.8-2.5 Gy to a median of 50 Gy including regional lymphatics in 22 patients. Adjuvant systemic treatment consisted of chemotherapy (22.5%) and antihormonal treatment (55%). For reasons of comparison, we estimated outcome of a virtual female matched cohort for no/equal to men/optimal adjuvant treatment with the Adjuvant!Online(®) 8.0 algorithm., Results: After a median follow-up of 47 months, the estimated 5-year local control rate was 97%, disease-free and distant metastasis-free survival rates reached 79% and 82%, respectively. With update of survival data by tumor registry, mean overall survival reached 120 months with 5- and 10-year overall survival rates of 66% and 43%, respectively. Predominant prognostic factor was T-stage for overall survival (T1/2 vs. T4: > 80% vs. 30%). The generated virtual matched cohorts of women with equal characteristics reached superior 10-year-overall survival for no/equal to men/optimal adjuvant treatment with 55/59/68%., Conclusion: Compared to historical and virtual matched cohorts of women, male breast cancer patients had inferior outcome despite of equal stage and treatment which indicates that biological differences (of tumor or population) may contribute to worse prognosis.

Background and Purpose: The aim of this retrospective study was to analyze the outcome of patients with locally advanced cervical carcinoma treated by adjuvant radiochemotherapy and to determine risk factors for local and distant relapse. Furthermore, acute and late effects of treatment were recorded., Patients and Methods: A total of 72 patients with FIGO stages I-III cervical carcinoma were treated by radical hysterectomy, pelvic lymphadenectomy, and postoperative radiochemotherapy. Only patients with positive pelvic lymph nodes, parametrial involvement, positive margins, or tumor bulk were eligible. Patients were irradiated with a standard pelvic field (50.4 Gy in 28 fractions). The majority of patients received platinum-based chemotherapy., Results: After a median follow-up of 37 months, estimated 1-, 2-, and 4-year disease-free survival (DFS) and overall survival (OS) rates were 89%, 80%, 68% and 95%, 88%, 76%, respectively. Nine of the 72 patients had pelvic recurrences including only 1 isolated local failure; 23 of the 72 patients presented with distant relapse. The majority of relapses occurred within the first 3 years after adjuvant treatment. The number of positive pelvic lymph nodes (> 1) was the strongest prognostic factor for DFS. Treatment was well tolerated with transient acute hematologic (~30%) and gastrointestinal (~30%) grade 3 toxicity. Small bowel obstruction (~6%) was the only important late sequelae., Conclusion: Adjuvant radiochemotherapy in patients with advanced cervical cancer and several risk factors is highly effective to prevent local relapse. Future efforts to improve outcome should be placed on improvement of systemic control especially in subgroups with high-risk features for distant relapse. Combined treatment was well tolerated with moderate acute and late toxicity.

Background and Purpose: The goal of the present study was to comparatively assess the results of definitive chemoradiation (CRT) with or without previous macroscopically complete resection in patients with early-stage node-negative (T1-2 N0) anal carcinoma., Patients and Methods: A total of 20 patients with T1-2 N0 anal carcinoma who received radiotherapy (RT) with or without chemotherapy following incidental R0/1 tumor resection (S/CRT group) were selected. These were matched to 20 comparable patients who underwent definitive chemoradiation without previous surgery (CRT group). Major objectives of this analysis were treatment outcomes in terms of locoregional tumor control (LRC), overall survival (OS), colostomy-free survival, and toxicity., Results: Patients treated postoperatively received significantly lower RT doses (median 54.0 Gy vs. 59.7 Gy; p < 0.001) and less frequently concomitant chemotherapy than those treated definitely. The 5-year LRC and 5-year OS rates were 97.5% and 90.0%, respectively, without significant differences between the S/CRT and the CRT groups. The distribution of acute and late toxicities was comparable, and the 5-year colostomy-free survival was 95% in both groups., Conclusion: This matched-pair comparison of incidental R0/1 resection plus dose-reduced CRT with standard definitive CRT of early-stage anal cancer shows similar treatment results. Thus, dose-reduced RT with or without chemotherapy may be considered in R0/1 resected patients with T1-2 N0 anal carcinoma.

Background and Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease. Standard treatment is performed in analogy to small cell lung cancer; however, due to the differences in rates of cerebral metastases (CM), prophylactic cranial irradiation (PCI) is not routinely used. Therefore, we evaluated the characteristics of all patients developing brain metastases in a population of EPSCC patients and calculated a number needed to treat (NNT) for the prevention of cerebral metastases by PCI., Patients, Methods, and Results: Of 51 patients treated at our institution from 1999-2011 for EPSCC, 11 presented with CM, 5 at initial diagnosis, 6 in the course of their disease. Median overall survival after primary diagnosis of EPSCC was 12 months. Overall survival after diagnosis of CM was significantly in favor of primarily cerebrally metastasized patients with 9 compared to 2 months for secondary CM (p = 0.04), median survival for all patients being 4 months. The NNT calculation was based on the 6 patients with secondary brain metastases in our series and a relative risk reduction of 60% observed in the studies of PCI for small cell lung cancer (SCLC), resulting in an NNT of 13., Conclusion: Although the frequency of brain metastases in EPSCC was lower than in SCLC, the NNT of 13 for the prevention of CM, as well as the poor median survival after diagnosis of secondary brain metastases of 2 months might be a reason to discuss and evaluate PCI for EPSCC patients responding to initial therapy.

Purpose: As extra-pulmonary small cell carcinoma (EPSCC) is a rare entity of tumors, the available treatment recommendations are mainly based on retrospective analyses and deduction from treatment of small cell lung cancer. The aim of this study was to provide a detailed analysis concerning prognostic factors and treatment modalities., Patients and Methods: A total of 20 patients with limited disease (LD) of EPSCC treated at our institution from 1999–2009 were retrospectively analyzed. Data were gathered from chart review. Localization, lymph node involvement, as well as local and systemic treatment were documented and their impact on pattern of failure and survival times statistically evaluated., Results: With a median follow-up of 21 months, the estimated median overall- and disease-free survival were 59 and 25 months, respectively. Local control was excellent with 100% at 2 years. Nodal involvement was observed in 74% (n = 14/19) of evaluable patients. However, outcome was not altered by this parameter. Local treatment consisted of surgery in 10 cases, radiotherapy in 7 cases, and a combination of both in 3 cases. Only 3 patients (15%) developed hematogenous central nervous system metastases, while none of the patients received prophylactic cranial irradiation., Conclusion: Nodal involvement did not worsen prognosis. Local control was excellent irrespective of local treatment modality and the leading cause of failure was distant metastasis. Therefore, systemic treatment should not be omitted. Prophylactic cranial irradiation might be dispensable but discussed for head and neck malignancies.

Background: The purpose of the present study was to investigate outcome after whole brain radiotherapy (WBRT) alone as a palliative treatment without concomitant chemotherapy for intracranial leptomeningeal carcinomatosis (LMC)., Patients and Methods: Overall survival and treatment response were retrospectively analyzed in 27 consecutive patients with LMC from breast and lung cancer. All patients had evidence of intracranial manifestations of LMC. Seven potential prognostic factors were evaluated., Results: Median overall survival (OS) for the entire group was 8.1 weeks. OS rates after 6 and 12 months were 26% and 15%, respectively. Improvement of neurological deficits was observed in 3 patients. In 3 of 4 patients with follow-up MRI studies, a decreased size of contrast-enhanced lesions was observed. Prognostic factors for improved OS on univariate analysis were absence of cranial nerve dysfunction, Karnofsky Performance Score (KPS) > 60%, and time interval > 35 months between the initial diagnosis of malignant disease and development of LMC. On multivariate analysis, absence of cranial nerve dysfunction remained the only significant prognosticator for OS (median 3.7 vs. 19.4 weeks, p < 0.001)., Conclusion: WBRT alone is an effective palliative treatment for patients unfit/unsuitable for chemotherapy and low performance status suffering from intracranial LMC. However, prognostic factors should be considered in order to identify patients who are likely to benefit from WBRT.

Background and Purpose: Multimodality treatment approaches provide high local control and satisfying overall survival (OS) for children with localized bladder and/or prostate rhabdomyosarcoma (BP-RMS). However, current strategies including surgery and conventional radiotherapy are compromised by high rates of long-term genitourinary adverse effects. Therefore, a planning study combining organ preserving surgery with three different innovative adjuvant radiotherapy approaches was performed., Patients and Methods: A case of a 21-month-old boy with BP-RMS treated with polychemotherapy according to the CWS 2002-P protocol, prostatectomy, partial cystectomy, and adjuvant high dose rate brachytherapy (HDR-BT) was used to perform a planning study comparing HDR-BT with intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) planning., Results: All modalities provide good coverage of the target volume and spare critical normal tissues. Rectum doses could be reduced by 2/3 using IMPT and by 1/3 using BT compared to IMRT. In terms of sparing the pelvis growth plates, BT and IMPT are also superior to IMRT., Conclusion: All modalities provide good sparing of normal tissue. BT and IMPT are superior to IMRT with regard to doses on rectum and growth plates. BT is equivalent to IMPT in adequately selected tumors.

Purpose: A voluntary, external, science-based benchmarking program was established in Germany in 2003 to analyze and improve the quality of breast cancer (BC) care. Based on recent data from 2009, we aim to show that such analyses can also be performed for individual interdisciplinary specialties, such as radiation oncology (RO)., Methods: Breast centers were invited to participate in the benchmarking program. Nine guideline-based quality indicators (QIs) were initially defined, reviewed annually, and modified, expanded, or abandoned accordingly. QI changes over time were analyzed descriptively, with particular emphasis on relevance to radiation oncology., Results: During the 2003-2009 study period, there were marked increases in breast center participation and postoperatively confirmed primary BCs. Starting from 9 process QIs, 15 QIs were developed by 2009 as surrogate indicators of long-term outcome. During 2003-2009, 2/7 RO-relevant QIs (radiotherapy after breast-conserving surgery or after mastectomy) showed considerable increases (from 20 to 85% and 8 to 70%, respectively). Another three, initially high QIs practically reached the required levels., Conclusion: The current data confirm proof-of-concept for the established benchmarking program, which allows participating institutions to be compared and changes in quality of BC care to be tracked over time. Overall, marked QI increases suggest that BC care in Germany improved from 2003-2009. Moreover, it has become possible for the first time to demonstrate improvements in the quality of BC care longitudinally for individual breast centers. In addition, subgroups of relevant QIs can be used to demonstrate the progress achieved, but also the need for further improvement, in specific interdisciplinary specialties.

Purpose: The purpose of this study was to analyze the probability and time course of fibrotic changes in breast reconstruction before or after postmastectomy radiotherapy (PMRT)., Materials and Methods: Between 1995 and 2004, 109 patients were treated with PMRT at Tübingen University and underwent heterologous (HL) or autologous (AL) breast reconstruction prior or subsequent to radiation therapy. Fibrosis of the reconstructed breast after radiotherapy was assessed using the Baker score for HL reconstructions and the Common Terminology Criteria for Adverse Events (CTCAE) for all patients. Actuarial rates of fibrosis were calculated for the maximum degree acquired during follow- up and at the last follow-up visit documented., Results: Median time to follow-up was 34 months (3-227 months). Radiotherapy was applied with a median total dose of 50.4 Gy. A total of 44 patients (40.4%) received a boost treatment with a median dose of 10 Gy. Breast reconstruction was performed with AL, HL, or combined techniques in 20, 82, and 7 patients, respectively. The 3-year incidence of ≥ grade III maximum fibrosis was 20% and 43% for Baker and CTCAE scores, respectively. The corresponding figures for fibrosis at last follow-up visit were 18% and 2%. The 3-year rate of surgical correction of the contralateral breast was 30%. Initially unplanned surgery of the reconstructed breast was performed in 39 patients (35.8%). Boost treatment and type of cosmetic surgery (HL vs. AL) were not significantly associated with the incidence of fibrosis., Conclusions: We found severe fibrosis to be a frequent complication after PMRT radiotherapy and breast reconstruction. However, surgical intervention can ameliorate the majority of high grade fibrotic events leading to acceptable long-term results. No treatment parameters associated with the rate of fibrosis could be identified.

Background and Purpose: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up., Case Report: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/ etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival., Conclusion: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC.

Purpose: To report follow-up data and results of a dose escalation within a prospective phase II protocol scheduling alternating chemoreirradiation for patients with unresectable locoregional recurrence of head and neck cancer after previous curative-intent radiotherapy., Patients and Methods: Chemoreirradiation was initially performed in 27 patients by 40.0 Gy split-course reirradiation (re-RT) alternating with three cycles of docetaxel 50 mg/m(2) day 1 and cisplatin 15 mg/m(2) days 2-5 (first cohort). From 2002 onward, 30 consecutively treated patients received a late-course concomitant boost to 49.6 Gy (second cohort). In July 2008, the survival outcome was analyzed separately for both cohorts and the entire collective (n = 57)., Results: The Kaplan-Meier estimates for 1- and 2-year overall survival (OS) were 52% and 24%, respectively (median OS 13.4 months). The median time of locoregional control was 9.6 months, and the actuarial 2-year freedom from distant metastasis rate was 55%. The re-RT dose escalation led to a significant improvement of the median OS (17.4 vs. 9.4 months; p = 0.039). Irrespective of the cohort, severe treatment-related toxicities occurred in about one third of patients., Conclusion: The treatment results confirm the efficacy and the safety of escalated re-RT doses in this chemoreirradiation protocol.

Background: In patients with advanced-stage III/IV follicular lymphoma (FL), there are many treatment options available. The current challenge is to choose the optimal strategy for the individual patient., Methods: The literature was reviewed with respect to treatment strategies in patients with advanced FL by screening the PubMed databank., Results: In advanced-stage III/IV FL, median survival may approach 8-10 years. Treatment strategies include a watch-and-wait strategy, chemoimmunotherapy, monotherapy with rituximab, and - as an experimental approach so far - radioimmunotherapy. The use of autologous hematopoietic stem cell transplantation (HSCT) for patients in first remission or chemosensitive relapse prolongs progression-free survival while the effect on overall survival remains unclear compared to standard chemotherapy. However, long-term results are flawed by high relapse rates and risk of secondary malignancies. In patients with relapsed/chemoresistant disease, allogeneic HSCT constitutes the only curative approach but is associated with high treatment-related mortality. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response., Conclusion: In case of advanced-disease FL, asymptomatic patients can be managed expectantly. In symptomatic patients, chemoimmunotherapy is regarded as standard therapy. In symptomatic elderly patients with relevant comorbidities, rituximab +/- single-agent chemotherapy, or low-dose involved-field radiotherapy might be appropriate. For younger patients with chemoresistant/relapsed disease, allogeneic HSCT might be considered, since advances in supportive care and better patient selection have resulted in improved outcomes.

Purpose: To clarify the role of external-beam radiotherapy (RT) in patients with stage I and II nodal follicular lymphoma (FL)., Methods: The literature was reviewed with respect to different treatment strategies in patients with stage I and II nodal FL by screening the PubMed databank., Results: In patients with stage I and II nodal FL, RT alone with different irradiation techniques (involved-field [IFI]/extended-field [EFI]/total nodal [TNI]/total lymphoid irradiation [TLI]) produces excellent local disease control (approximately 95%) resulting in disease-free survival and overall survival (OS) rates of 37-94% and 40-93% at 5-15 years, respectively. The main cause of failure is out-of-field recurrence. In nonrandomized trials, IFI led to higher relapse rates, but larger irradiation volumes failed to show an impact on OS and were associated with increased toxicity. Additional chemotherapy mostly failed to improve treatment results achieved with RT alone., Conclusion: Since there is no evidence so far that the prognosis of stage I and II nodal FL can be improved by the use of EFI/TNI/TLI, IFI is recommended internationally. Adequate irradiation doses range between 25-30 Gy to subclinical disease and 36-40 Gy to involved sites. To further improve the curative potential of RT in early-stage FL, novel combined approaches (e.g., RT + immunotherapy with rituximab) are under investigation.

Background: Permanent interstitial brachytherapy is--in certain cases--a very successful therapeutic option, but application of radioactive implants always results in only gradually diminishing radiation exposure of persons in the patient's immediate surroundings., Material and Methods: Using patients with clinically localized prostate cancer treated with iodine-125 ((125)I) or palladium-103 ((103)Pd) as an example, it is shown how a patient, if necessary or wished by him, can, by wearing commercially available X-ray protection shorts, reduce radiation exposure of family members in such a way that at a distance r from the patient a given dose per year is not exceeded., Results: The computational procedures necessary for the determination of the individual periods of wearing X-ray protection clothing are provided in the form of formulae and graphics. All considerations and calculations can also be applied to other radiotherapeutic interventions involving the use of (125)I, (103)Pd or other gamma-sources., Conclusion: If necessary, a patient with permanent radioactive implants can reduce radiation exposure of family members by wearing special X-ray protection clothing for a limited period of time. This kind of radiation protection is very efficient and considerably simpler to accomplish than a reduction of exposure time or an increase of the distance between the patient and family members.

Background and Purpose: Routine posttreatment surveillance is recommended after adjuvant radiotherapy for stage I seminoma. However, systematic studies on the value of follow-up in these patients are missing. This report addresses the efficiency of routine follow-up in stage I seminoma with particular reference to the mode of detection of relapse and the costs of posttreatment screening., Patients and Methods: All follow-up investigations of a prospectively followed cohort of 675 patients with stage I seminoma treated with PA radiotherapy were analyzed with respect to the first indications of relapse, patterns of recurrence, risk factors of relapse, and cost-efficiency of the different technical examinations of the follow-up schedule over a 10-year period., Results: With a median time to follow-up of 61 months, recurrence was diagnosed by symptoms or physical examination in 14 out of 26 relapsing patients. Among the technical follow-up investigations abdominopelvic imaging had the highest detection rate for relapse, while thoracic imaging and marker analysis were inefficient. Abdominal sonography had the highest cost-efficiency of all technical follow-up investigations, while computed tomography (CT) scans were responsible for approximately 60% of all costs. The authors failed to identify risk factors predictive of relapse after adjuvant irradiation., Conclusion: Routine technical investigations during follow-up after PA radiotherapy for stage I seminoma yield only a low detection rate of relapse from cancer. The data presented here provide no evidence for the value of technical follow-up beyond the 3rd year after treatment or routine screening of the chest. Thorough physical examination of the patients should be encouraged. Patients should be informed about potential symptoms indicative of recurrence. Restrictive use of abdominopelvic CT scans will reduce exposure to ionizing radiation and considerably increase the cost-efficiency of follow-up.

Purpose: Evaluation of late side effects and biochemical control (bNED) 5 years after three-dimensional radiotherapy with moderate, risk-adapted dose escalation., Patients and Methods: From 03/1999 to 07/2002, 486 patients have been registered in the prospective Austrian-German multicenter phase II trial (AUGE). 399 (82%) localized prostate cancer patients (T1-3 Nx/N0 M0) were evaluated. The low- and intermediate-risk groups were treated with 70 Gy, the high-risk group with 74 Gy, respectively. Additional hormonal therapy (HT) was recommended for intermediate- and high-risk group patients. Late toxicity (EORTC/RTOG) and bNED (ASTRO and Phoenix) were prospectively assessed., Results: Median follow-up was 65 months. Distribution concerning risk groups (low-, intermediate-, high-risk group) showed 29%, 50% and 21% of patients, respectively. HT was given in 87% of patients. The 5-year actuarial rates of late side effects grade > or = 2 for 70 Gy/74 Gy were 28%/30% (gastrointestinal; p = 0.73) and 19%/34% (urogenital; p = 0,06). The 5-year actuarial bNED rate stratified by risk groups (low-, intermediate-, high-risk group) was 74%, 66% and 50% (ASTRO), and 81%, 80% and 60% (Phoenix), respectively. Within multivariate analysis T-stage and initial prostate specific antigen were significant factors influencing bNED (ASTRO) whereas Gleason Score and duration of HT were not., Conclusion: Dose escalation within standard three-dimensional conformal radiotherapy (3D-CRT) up to a level of 74 Gy did not result in significantly increased gastrointestinal side effects, whereas urogenital side effects showed an increase close to significance. However, the total number of patients with severe toxicity was low. To achieve high tumor control rates with acceptable treatment-related morbidity, local doses of at least 74 Gy should be considered, in particular for intermediate- or high-risk patients applying 3D-CRT.

Background and Purpose: Treatment options for recurrent high-grade glioma after a complete course of radiotherapy comprise surgery, reirradiation and chemotherapy but the efficacy of any of the given salvage treatments is limited. In order to further define the role of short-term radiotherapy as retreatment option for selected patients, we analyzed outcomes after treatment with a hypofractionated radiation., Patients and Methods: Treatment outcomes (overall survival and treatment-associated toxicity) were analyzed retrospectively in 31 patients treated between 1994 and 2007. Hypofractionated radiotherapy was performed after three-dimensional CT planning with a median total dose of 20 Gy in a single department., Results: With a median interval of 20 months from primary radiotherapy, two grade III and 29 grade IV tumors were reirradiated. Pretreatment consisted of surgery and involved-field radiotherapy (median 59 Gy). 77% of the patients received additional chemotherapy before the second course of radiotherapy, and 48% were treated after secondary resection. The median overall survival after hypofractionated radiotherapy was 10.2 months, and the median overall survival time after primary diagnosis 30.9 months. No severe toxicity was observed., Conclusion: Hypofractionated reirradiation with 20 Gy given over 1 week is a practicable and well-tolerated treatment option for patients with recurrent malignant glioma. The overall survival was comparable to the reported outcomes from other series including those with longer treatment protocols.

Purpose: Measurement of the radiation dose of different radiotherapy techniques with a phantom at the position of the uterus of a pregnant patient with and without a special radiation shielding., Material and Methods: A special radiation shielding for the radiation therapy of a pregnant patient was constructed in the shape of a tunnel over the abdomen from 1 cm thick lead to reduce scatter radiation to the uterus and the fetus therein. The reduction of the scatter radiation to the lower abdomen was measured for three typical cases (cerebrum with lateral opposed fields, 6-MV photons; tangential fields for mamma irradiation, 6 MV; and anteroposterior-posteroanterior [AP-PA] opposed fields of 15 MV for treatment of the mediastinum) at an anthropomorphic Alderson phantom with thermoluminescence dosimeters in different depths and with an ionization chamber positioned in an RW3 solid water phantom. In the case of lateral opposed fields, a movable lead wall was additionally positioned next to the accelerator's head to reduce the scatter radiation from this source., Results: Depending on the geometry of the radiation fields and on the photon energy, a reduction of the dose to the lower abdomen averaged over the depths of 6, 9, and 12 cm from 16% (15 MV, mediastinum case) to 51% (6 MV, cerebrum with additional lead wall) was achieved. The absolute scattered dose with shielding in place for a 2-Gy fraction dose results to 3.85 mGy and 0.27 mGy, respectively., Conclusion: National and international recommendations on the radiation dose to a fetus of a pregnant patient state limits of 200 mSv (DGMP report no. 7) and 100 mGy (ICRP 84), below which an abortion should not be considered and above which an indication for termination of the pregnancy could be given, respectively. The dose to the fetus can be kept below these limits with the shielding described in this work. Therefore, a radiation therapy of a pregnant patient is possible when these special precautions to reduce the scatter radiation to the fetus are met.

Purpose: Several recent SEER- (Surveillance, Epidemiology and End Results-) analyses gave rise to a highly controversial discussion in how far radiotherapy for prostate cancer is associated with an increased risk of secondary neoplasms., Material and Methods: In order to enable a rational discussion, the available literature was reviewed covering all publications from the mid 80s to January 2007., Results: The reported numbers of secondary cancer (bladder, rectum, lung cancer and sarcoma) after irradiation were found to be increased in some publications. However, after age adjustment and correction for follow-up duration no clear increase was detectable., Discussion: Up to now, all available data are highly heterogeneous. Thus, a low risk for secondary cancer cannot be ruled out completely. Nevertheless, it seems very unlikely that there is a relevant risk for secondary cancer since the largest of the published series did not document an increased risk for any secondary cancer., Conclusion: Only very large prospective studies which are designed to minimize the influence of possible confounders will be able to address the real risk of prostate irradiation-related cancer induction. The available data are clearly not valid and helpful for guiding any treatment decision.

Background: Positron emission tomography/computed tomography (PET/CT) is composed of modern CT and PET technology in one machine enabling examinations of patients in one session in the same position. Its value for modern radiation treatment planning is under investigation., Methods: In 53 patients with head-and-neck (n = 11), non-small cell lung (n = 16), prostate (n = 14) and other cancers (n = 12), a PET/CT investigation was performed. During the diagnostic examination process an integrated scan under radiation treatment-planning conditions was included. Interpretation and delineation of macroscopic tumor were done in an interdisciplinary approach. Treatment changes occurred after critical interpretation of the PET/CT findings by the responsible radiotherapist. Analysis is descriptive with regard to changes in treatment intention, mode, radiation volumes and doses., Results: Examinations were well tolerated. CT datasets in treatment position could be used for planning. Delineation of macroscopic tumor led to changes of the planning target volume after PET/CT 15 times, total dose was modified twelve times. PET/CT examinations led to changes of the general treatment mode in 19 cases. Using the separate CT and PET datasets, fusion in the planning software was easily performed in all patients due to the use of the same positioning and immobilization devices in PET/CT., Conclusion: Despite the low number of patients and an expected bias of selection, the first results are encouraging to perform more extended and detailed trials of this technology in radiotherapy planning. Whether PET/CT is superior to PET alone is part of ongoing investigations.

Purpose: In Germany a new casemix-related reimbursement system with "diagnosis related groups" (DRGs) for inpatient treatment was started in 2003. The first German system G-DRG 1.0 was developed on the basis of the Australian AR-DRG version 4.1. German inpatient treatment in radiation oncology was not specifically represented in this system due to the very different health care systems. As the DRG system was planned as a pricing system with severe effects on the funding of radiation oncology departments, an adjustment was urgently needed. For the modification, national data about pattern of care and economic relevance were needed., Methods: For 3,689 cases treated in radiation oncology departments from eleven hospitals data were collected prospectively concerning diagnosis, length of stay, procedures and high-cost drugs and treatments. The DRGs were analyzed for homogeneity in length of stay and costs. Readmission frequency and interval were analyzed and the relevance of existing reimbursement regulations for this situation was evaluated., Results: It could be shown, that radiation therapy implicated additional expenses for oncologic inpatients. These additional costs were not represented in the G-DRG 1.0 reimbursement system. Chemotherapy was an additional cause for economically inhomogeneous oncologic DRGs. The complex sequence of cases for the same patient could be shown, and that the rules for reimbursement of readmissions have to take these sequential treatments into account. Based on these data, modifications of the reimbursement system were suggested. In the following G-DRG version for the year 2004, 21 DRGs were designed for patients receiving radiation therapy. The regulations concerning the readmission of oncologic patients were modified. The correlation between the number of radiation therapy fractions and the total expense was acknowledged in the following year (G-DRG system 2005) and resulted in 35 DRGs. The version for 2006 showed the solidity of these solutions with almost unchanged definitions of these DRGs., Conclusion: This evaluation revealed the deficits in the G-DRG system 1.0 (and the AR-DRG system 4.1) related to the inpatient treatment in radiation oncology departments. Modifications could be proposed for following years. In 2004-2006, the regulatory boards adopted several implications of these data for the improvement of the German casemix-based hospital-financing system.

Background and Purpose: Total-body irradiation (TBI) is a key part of the conditioning regimen before hematopoietic stem cell transplantation (HSCT). The exact role of TBI as part of the conditioning regimen is largely unclear. In order to determine the relevance of TBI, the status of TBI utilization was analyzed on the basis of a nationwide registry., Material and Methods: 14,371 patients (1998-2002) documented in the German Stem Cell Transplantation Registry (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic transplantation, underlying disorder, type of donor, stem cell source, and size of the treatment center., Results: For autologous HSCT approximately 10% of the patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL, approximately 80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL, approximately 35%, 330/929) being the most important disorders. In the allogeneic setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The type of donor, stem cell source and center size did not strongly influence the use of TBI., Conclusion: TBI has only a limited role for the conditioning prior to autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes over the observation time. The use of TBI is generally accepted for ALL, whereas approximately half of the patients with CML or AML received TBI. Although a considerably large database was analyzed, no clear determinants for the use of TBI could be distinguished.

Background and Purpose: Different radiotherapy techniques are being used for postmastectomy irradiation. A retrospective analysis of patterns of locoregional failure (LRF) after modified radical mastectomy and axillary lymph node dissection followed by locoregional radiotherapy with or without systemic treatment was performed. Main emphasis was focused on the comparison of two postmastectomy radiotherapy techniques., Patients and Methods: 287 evaluable patients with locally advanced disease and/or adverse pathologic features (pT3 17% of patients, pT4 35%, multicentricity 25%, pN more than three positive nodes and/or pN1biii 70%, "close margins" 29%, infiltration of pectoral fascia 20%) with or without adjuvant chemo-hormonal treatment were included between 1989 and 2000. Median age was 61 years (range 24-88 years). All patients had modified radical mastectomy and axillary lymphonodectomy level I-II(III) for primary breast cancer. Median total dose of conventionally fractionated radiotherapy to the chest wall was 50 Gy (range 46-56 Gy). A local boost to the tumor bed of 10 Gy was applied in 72 patients. 80% of the patients received supraclavicular and 60% ipsilateral internal mammary lymph node irradiation of 50 Gy. 19% of the patients received adjuvant chemo-hormonal therapy, 38% hormonal therapy, and 27% chemotherapy. The median follow-up of patients at risk was 43 months (average 54 months)., Results: The 5-year locoregional tumor control (LRC), LRC first event, disease-free, and overall survival were 85%, 91%, 61%, and 70% (Kaplan-Meier analysis), respectively. Cox regression analysis showed that stage III (relative risk [RR] 1.7), more than three involved axillary lymph nodes (RR 5.1), and infiltration of the pectoral fascia (RR 3.2) increased the risk of locoregional failure, while positive estrogen receptor status (RR 0.3) was associated with a reduced risk. No statistically significant differences in LRC were observed for patients treated either with the electron-rotation technique (LRC 92%) or with the photon-based technique (LRC 89%; p = 0.9). A subgroup analysis of tumors resected with "close margins" showed a higher LRF rate of 25% after electronbeam-rotation irradiation (n = 180) compared to an LRF of 13% with tangential opposed 6-MV photon fields (n = 107; p < 0.05). Large primary tumors of > or = 5 cm developed LRF in 29% of patients treated with electron-beam-rotation irradiation and in 17% of patients with photon-based irradiation (p = 0.1)., Conclusion: In locally advanced breast cancer, the LRC after postmastectomy irradiation with both techniques is comparable with published data from randomized studies. The tangential opposed photon field technique seems to be beneficial after marginal resection (histopathologic "close margins") of the primary tumor.

Background: The EORTC Trial 22845 on the role of immediate postoperative radiotherapy in patients with supratentorial lowgrade glioma revealed an advantage of immediate postoperative radiotherapy for progression-free survival, but not for overall survival. It is still an open question in which clinical setting immediate radiotherapy should be considered and whether chemotherapy may become a useful alternative., Material and Methods: Reports in the literature spanning 60 years of radiation therapy were reviewed with respect to timing of radiotherapy, prognostic factors, dose prescriptions, modern treatment techniques, and late effects. Data on chemotherapy were also reviewed. Based on these data, the role of immediate postoperative radiotherapy or chemotherapy in adult low-grade glioma is presented., Results: Radiotherapy is able to control symptoms in up to 80% of cases. Malignant transformation occurs in 36-86% of cases upon progressive disease. Long-term median survival crucially depends on prognostic factors and ranges between 12 months and 10 years. Radiotherapy does not cause neurocognitive deficits, provided that modern treatment techniques and moderate dose prescriptions are used. Recent series with small patient numbers indicate that chemotherapy using PCV or temozolomide may prolong median survival and induces response rates of 50% in oligodendroglial tumors., Conclusion: The arguments for immediate postoperative irradiation include: low-grade gliomas respond to radiotherapy; the tumors often display an aggressive pathobiological behavior; patients with high risk profile may benefit from immediate radiotherapy in terms of progression-free and overall survival; modern focal radiotherapy is far less toxic than feared; radiotherapy might be more effective at diagnosis than at progression. Chemotherapy might be an alternative in immediate postoperative treatment. Its role, however, is unclear. The forthcoming prospective trial of the EORTC will address this issue in a randomized setting.

Background: In radiotherapy of intraocular tumors, e. g., in the case of malign choroid melanomas, episcleral brachytherapy with (106)Ru ophthalmic plaques has proven to be successful. In a study, the authors reported on the discovery of the following shortcomings in industrial quality assurance, which are relevant to therapy, during the course of an internal clinical acceptance test of (106)Ru ophthalmic plaques, manufactured by the company Bebig from Berlin, Germany. This consisted of inconsistent dose rate specifications in the manufacturer's certificate, covering a range of 111% and with the risk of leakage of the plaques. Bebig was called upon to adapt state-of-the-art production methods with regard to (106)Ru ophthalmic plaques., Material and Methods: In the meantime, Bebig has modernized production of (106)Ru ophthalmic plaques and adopted all the quality assurance procedures proposed by the authors. Moreover, the requested traceability of the calibration of activity and dose rate of the (106)Ru ophthalmic plaques to standards of the federal authorities in charge of measurement procedures has been implemented., Results: In the year 2002, Bebig updated, among other things, the ASMW (GDR) calibration of the dose rate of the (106)Ru ophthalmic plaques from the years 1987-1989 by a calibration of the NIST (USA). The current NIST calibration, together with the new equipment for the measurement of the depth dose curves, led to the consequence that the new NIST 2001 dose rate values show, in the mean, a deviation of 0.75 times (plaque type CCC) up to 2.06 times (plaque types CCX, CCY, and CCZ) compared to the dose rate values that had been indicated so far in Bebig's certificate, based on the ASMW 1987 calibration. For the 95% confidence interval, Bebig estimated the measurement uncertainty to be +/- 25%. If one takes into consideration the minimal and maximal values in such 95% confidence intervals, it follows that the new NIST 2001 dose rate values deviate between 0.56 times (plaque type CCC) and 2.58 times (plaque types CCX, CCY, and CCZ) from the Bebig certificate (ASMW calibration 1987). As regards leakage, no objections arose in the case of the (106)Ru ophthalmic plaques produced according to the new quality standards., Conclusion: Legislation has to make sure that the use of radioactive material on humans be, among other things, permitted as a matter of principle only, if the dose rate calibration can be traced to standards of a federal authority of measurement procedures. Furthermore, special leakage tests for radiation sources which come into direct contact with body fluids should be established. A historical retrospect reveals that the greatest changes have taken place in the indication of the dose rates of (125)I sources. Since the beginning of the use of (125)I sources in brachytherapy in the late 1960s, the dose rate indications, so far, have had to be reduced in small steps over a period of about 35 years by nearly a factor of 2. As regards the (106)Ru ophthalmic plaques, the NIST 2001 calibration has resulted in a comparable reduction of the dose rate indications of up to a factor of 2 within the period of about several months. Thus, in the previous history of radiotherapy this case must be regarded as unique, because for the first time ever, an urgently needed recalibration has been protracted for such an unduly long period of time.

Background: For more than 60 years, radiation therapy has been an integral part in the management of childhood low-grade glioma. As this tumor carries an excellent long-term prognosis, the risk of late effects is of particular clinical importance and impinges upon radiotherapeutic treatment strategies., Material and Methods: Studies on the use of radiation therapy in children with low-grade glioma were systematically reviewed for data on radiotherapy-induced side effects on brain parenchyma, endocrine dysfunction, growth retardation, neurocognitive dysfunction, vasculopathy, and secondary neoplasms., Results: Data on late effects are scarce and heterogeneous. Past reports included only retrospective series from the 1930s to present days, a time during which treatment policies and radiation techniques widely varied and considerably changed in recent years. Often, considerable uncertainty existed regarding pretreatment health status and radiotherapy-related factors (e.g., total dose, dose per fraction, treatment fields). In spite of these shortcomings and often conflicting observations, it appears that especially younger children and children with neurofibromatosis (NF) are at risk of endocrinopathies in terms of growth retardation and developmental abnormalities, as well as neurocognitive dysfunction expressed as problems in the psychosocial environment such as in education and occupation. However, both observations may be attributed to the higher proportion of NF in the very young who frequently develop large tumors spreading along the entire supratentorial midline. The risk of radiation-induced disturbances in visual function is low (no case reported). Young children with NF appear to have an increased risk of vasculopathies. 33 cases of moyamoya disease were found (preferably in the very young), 18 of whom were NF-positive. Other cerebrovascular accidents (24 cases, of whom 14 were NF-positive) and secondary neoplasms (15 cases, of whom only five occurred in field--four were high-grade astrocytomas) are a rare condition. The latter cannot be distinguished from late relapses with malignant transformation. Modern treatment techniques appear to reduce the risk of radiation-induced late effects., Conclusions: More studies and clear definitions of clinical endpoints such as neurocognitive and endocrinological outcome are needed in order to clarify the impact of radiation therapy on the risk of late sequelae. Presently, the strategy to postpone radiotherapy in the younger children, especially with NF, is justified to reduce the risk of late effects. These information and the contribution of tumor, surgery and chemotherapy will help to define the role of radiation therapy in the future management of childhood low-grade glioma and whether the use of highly sophisticated and expensive treatment techniques is justifiable. The recently initiated prospective study of the APRO (Pediatric Radiooncology Working Party) on documentation of dose prescription to organs at risk and the network of the GPOH to explore late effects as well as the forthcoming prospective SIOP/GPOH (International Society of Pediatric Oncology/German Society of Pediatric Oncology and Hematology) LGG 2003 trial are addressing these issues.

Background: Treatment of childhood low-grade gliomas is a challenging issue owing to their low incidence and the lack of consensus about "optimal" treatment approach., Material and Methods: Reports in the literature spanning 60 years of radiation therapy, including orthovoltage, megavoltage and recently modern high-precision treatments, were reviewed with respect to visual function, survival, prognostic factors, dose prescriptions, target volumes, and treatment techniques. Based on these experiences, future strategies in the management of childhood low-grade glioma are presented., Results: Evaluation of published reports is difficult because of inconsistencies in data presentation, relatively short follow-up in some series and failure to present findings and results in a comparable way. Even with the shortcomings of the reports available in the literature, primarily concerning indications, age at treatment, dose response, timing and use of "optimal" treatment fields, radiation therapy continues to play an important role in the management of these tumors achieving long-term survival rates up to 80% or more. Particularly in gliomas of the visual pathway, high local tumor control and improved or stable visual function is achieved in approximately 90% of cases. Data on dose-response relationships recommend dose prescriptions between 45 and 54 Gy with standard fractionation. There is consensus now to employ radiation therapy in older children in case of progressive disease only, regardless of tumor location and histologic subtype. In younger children, the role of radiotherapy is unclear. Recent advances in treatment techniques, such as 3-D treatment planning and various "high-precision" treatments achieved promising initial outcome, however with limited patient numbers and short follow-ups., Conclusions: Radiation therapy is an effective treatment modality in children with low-grade glioma regarding tumor control and improvement and/or preservation of neurologic function or vision, respectively. More prospective studies are needed to address the impact of modern radiation therapy technologies (including intensity-modulated radiotherapy) on outcome especially in the very young and to define the role of radiation therapy as a part of a comprehensive treatment approach. The forthcoming prospective trial SIOP/GPOH LGG RT 2003 is addressing this issue.

Background: Standard treatment in patients with malignant glioma consists of surgery and postoperative radiotherapy. A high early recurrence rate, particularly in glioblastoma, has led to the investigation of additional chemotherapy., Material and Methods: Recent results of radiochemotherapy published in the literature were reviewed with respect to outcome in phase II and III trials. Based on these experiences, aspects of future strategies were discussed., Results: 3 decades of intensive research had, unfortunately, little impact on the overall results. While early prospective studies established adjuvant nitrosoureas, particularly BCNU, as suitable adjuvant to surgery and postoperative radiotherapy, further studies largely concentrated on combined chemotherapeutic protocols, mostly procarbazine, CCNU and vincristine (PCV), which was shown to prolong survival in anaplastic astrocytoma. The recent MRC study, however, showed no effect for adjuvant PCV in grade III and IV malignant glioma. Only in high-grade glioma with an oligodendroglial component, additional chemotherapy may be of a decisive benefit. The introduction of newer drugs such as paclitaxel, temozolomide, or gemcitabine demonstrated no decisive advantage. Different modes of application and sequencing of radiotherapy and chemotherapy are presently actively investigated, but failed to substantially improve outcome., Conclusions: Therefore, search for newer and more effective drugs continues, as well as for "optimal" administration and sequencing, especially from the standpoint of accompanying acute and late toxicity. Finally, recent endeavors focused on basic research such as angiogenesis, migration and invasion, or induction of cell differentiation, but these strategies are still away from broader clinical investigation.

Background: Apart from optimization of the radiation technology, future new strategies in radiation oncology will focus on the biological optimisation leading to improved adaptation of the tumor therapy on each tumor entity. In this regard, different areas of biological research may be distinguished: prediction, development of new cytotoxic agents, improvement of the tolerance of normal tissue and the optimisation of radiochemotherapy., Material and Method: For the development of new strategies the knowledge of molecular mechanisms of radiation induced cell death is essential. In the present article a novel biological strategy for optimisation of radiotherapy is introduced., Results: Distinct pathways mediate apoptosis in response to death receptor stimulation and ionizing radiation although an overlapping set of molecules is involved. TRAIL (TNF alpha-related apoptosis inducing ligand) is a type-II membrane protein belonging to the TNF family, which preferentially induces apoptotic cell death in a wide variety of tumor cells but not in normal cells. Based on the assumption of distinct signalling pathways, combination of TRAIL and ionizing radiation seems ideal to increase the therapeutic efficacy. Our study presents the rationale, own data, data of other groups as well as the current status of the latest findings regarding the function and physiological role of the TRAIL death ligand., Conclusions: Apoptosis resistance towards ionising radiation is not associated with a general apoptosis resistance. Death ligands, for example TRAIL trigger apoptosis even in cells not undergoing apoptosis in response to radiation. A combination of both modalities induces additive or synergistic effects in regard to apoptosis induction and eradication of clonogenic tumor cells. Thus, the combination of TRAIL with radiation proofs that novel treatment strategies may be developed on the basis of molecular or cell biological research.

Background: Radical surgery is the treatment of first choice for retroperitoneal sarcoma. However, locoregional relapse is frequently observed leading to death in the majority of patients. The role of radiotherapy is not well defined in the management of retroperitoneal sarcoma. Yet, there is evidence that adjuvant irradiation does improve local tumor control., Material and Methods: In order to deliver sufficiently high radiation doses to the retroperitoneum, different techniques for application of a local tumor boost dose in addition to external beam treatment have been proposed. We present a technique of hyperfractionated (192)Ir brachytherapy (HFIR) of the tumor bed via intraoperatively implanted plastic catheters. Postoperative CT-based image-guided brachytherapy was performed. In two consecutive patients with recurrent retroperitoneal sarcoma, treatment was delivered twice daily with single doses of 1.5-2.0 Gy in 5-10 mm tissue depth up to a total dose of 18-32.5 Gy., Results: HFIR of the tumor bed was easily accomplished facilitating delivery of high radiation doses to the retroperitoneum. No major late effects of treatment have been observed with a follow-up of 15 and 28 months, respectively. Details of the brachytherapy procedure are presented., Conclusion: HFIR via intraoperatively implanted catheters in the retroperitoneum is a technique suitable for application of a local tumor boost dose. Thus, sufficiently high doses of radiation mandatory for long-lasting local tumor control can be delivered in the tumor bed of the retroperitoneum without exceeding normal tissue radiotolerance in this unfavorable disease.

Background: Early stage prostate cancer can be treated successfully by interstitial brachytherapy with 125-iodine seeds. A quality-assurance programme is presented that was designed for this purpose for internal clinical use. Furthermore the requirements of the new German Ordinance Governing Radiation Protection (StrlSchV) that came into force on August 1, 2001, are taken into account., Material and Methods: For the 125-iodine monotherapy of the prostate we used RAPID STRANDS (Amersham Health, Braunschweig, Germany). According to the guidelines of the new Ordinance Governing Radiation Protection, the determination of the body dose of the staff is made to rely on the new measurement quantities H(p) (10) and H(p) (0.07). The nominal air kerma rate of the seeds is measured with a calibrated well-chamber of the type HDR 1000 Plus and an electrometer of the type MAX 4000 (Standard Imaging Inc., USA). The ultrasound images of the prostate are produced by an ultrasound device of the type Falcon 2101 (B-K Medical, Denmark). For treatment planning the programme VariSeed (Varian, Darmstadt, Germany) was employed. Correct loading of the needles is controlled by autoradiography before implantation. After the implantation radiation-protection measurements in the operating room are carried out., Results: As regards the personnel, for the depth personal dose equivalent Hp(10) and relating to two applications each, measurement values between 0 microSv and 14 microSv resulted. The control of the radiation exposure of the hands revealed superficial personal dose values H(p) (0.07) of up to 1 mSv. The nominal air kerma rates of the RAPID STRANDS were all lying within the 95% confidence interval guaranteed by the producer. The autoradiographs documented -- except for one case -- the correct loading of the needles. The interstitial transperineal prostate implantation of the 125-iodine seeds succeeded as planned with all patients. Until now no contamination of the operating room was detected by the radiation-protection measurements., Conclusion: The physical-technical quality assurance programme presented here covers the whole physical-technical range of the internal clinical quality assurance and could be integrated into the course of the treatment without any problems. It has th following advantages: The autoradiographic documentation of the correctly loaded needles serves as proof that the prerequisite for the production of the prescribed physical dose distribution is fulfilled. The internal clinical determination of the nominal air kerma rate is the basis for a correct dose application.

Background: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control., Patients and Methods: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement., Results: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control., Conclusion: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.

Background: Interstitial brachytherapy with I-125 seeds can be used for successful treatment of early stage prostate cancer. There is presented the technique of permanent transperineal implantation of I-125 seeds with intraoperative treatment planning which is suited for the treatment of prostate cancer up to the clinical stage of T2a., Material and Methods: Some weeks before the implantation of the seeds the prostate volume is determined using transrectal ultrasound (TRUS) so as to estimate the required number of I-125 seeds. At the outset of the treatment the prostate is stabilized by two perineally inserted needles. Subsequently there is carried out an ultrasound guided treatment planning that allows to optimize the distribution of the seeds within the prostate. In interstitial brachytherapy we use RAPID STRANDS((R)), i. e. the I-125 seeds are embedded in vicryl suture at distances of 1 cm. During implantation of the I-125 seeds the transversal placement of the applicator needles is controlled by TRUS and the cranio-caudal placement of the applicator needles is controlled using the fluoroscopic unit as well as TRUS. About 4 weeks after the implantation of the seeds there is carried out a postoperative computation of the dose distribution of the implant using CT imaging., Results: The procedure possesses the advantage that ultrasound imaging, treatment planning and seed implantation are carried out with the prostate remaining in an unaltered position. During implantation the combined imaging of TRUS and fluoroscopy allows a safe placement of the seeds with in the prostate., Conclusion: The methods for the calculation of the actually attained dose distribution must still be optimized, because the postoperative examination of the individual results has so far been possible only with difficulties resulting from methodological inconveniences.

Background: Ependymomas represent about 10% of CNS tumors in children. The proportion of cases defined as anaplastic is about 25%. Prognosis depends on extent of resection, and postoperative radiotherapy, the overall survival rate is 30-60%. Further investigations should clarify the impact of chemotherapy, histological grading, dose, and volume of radiotherapy., Material and Method: Based on historical reports, the recent literature, present guidelines, and ongoing trials an overview is provided for the management of ependymomas in childhood., Results: Local tumor control is the most important aim. Recurrences occur predominantly at the primary tumor region. The main instrument is surgery to effect maximal tumor resection. The addition of radiotherapy could improve survival significantly from 10% to 50%. Regarding the volume of irradiation there is confidence today that local fields are sufficient for all non-disseminated ependymomas. Local dose escalation has been introduced using hyperfractionated schedules. In recent studies this has been shown to increase local control up to 70%. Regarding chemotherapy in ependymomas trials have shown limited efficacy to date. For metastatic disease standard treatment has shown to be insufficient and high dose chemotherapy regimens to increase survival are in study. In younger children radiotherapy should be delayed using early chemotherapy. With pre-irradiation chemotherapy survival rates of 63.3% for children under age of 3 were achieved., Conclusions: At present the cooperating clinicians are optimizing treatment procedures to improve results and to reduce toxicity. In radiotherapy reduction of target volume to the involved field for all non-disseminated ependymomas as well as the introduction of hyperfractionated schedules and conformal therapy with dose escalation are important developments.

Background: 2-year results of a German multicenter randomized trial showed that accelerated chemoradiation with MMC/5-FU to 70.6 Gy is more effective than accelerated radiation to 77.6 Gy alone at equivalent levels of acute and late radiation morbidity. Frequency, histopathology and impact on local tumor control of selective lymph node dissection were analyzed., Patients and Methods: Between February 1996 and October 2000 at Tübingen University 42 randomized patients plus 45 non-randomized patients with stage III/IV MO head and neck cancer were treated according to this protocol. After completion of hyperfractionated accelerated (chemo-)radiation a selective lymph node dissection was performed, if the primary tumor was in complete remission and clinical plus computed tomography proved residual lymph node disease. 17 of 38 patients with residual node metastasis underwent uni- or bilateral selective node dissection, the remaining patients had residual primary tumors, clinical deterioration or refused neck dissection., Results: After a median follow-up of 26 months, the Kaplan-Meier analysis showed a 2-year overall survival of 49%, disease-specific survival of 64% and loco-regional tumor control of 60%, respectively. 3-year loco-regional tumor control in randomized patients was 52% compared to 58% in non-randomized patients (log rank p = 0.23). 2-year loco-regional tumor control in stage cT4cN0 was 76% compared to 57% in cT2-4 cN1-3 tumors. Subgroup analysis of patients with involved nodes revealed a 2-year loco-regional tumor control of 74% after complete remission of primary tumor and neck disease, 53% after complete remission of primary tumor and partial remission of neck disease. In patients with selective lymph node dissection loco-regional tumor control was 62%. Histopathological examination showed viable tumor in eight of 17 patients., Conclusions: Selective lymph node dissection of residual neck masses after completion of hyperfractionated accelerated radio-(chemo-)therapy is likely to contribute to loco-regional tumor control in advanced head and neck cancer.

Objectives: This study evaluated for the first time in intraindividual comparison the conception of care with creme or powder. Acute skin reactions on the left and right side of the neck during symmetrically performed radiotherapy and subjective impairment were assessed., Patients and Methods: Twelve patients receiving radiotherapy of the head-and-neck region up to 50, 60, 66 and 72 Gy, respectively, were asked to treat one side of the neck with creme, the contralateral side with powder after random assignment. Objective and subjective assessment and photodocumentation were performed at therapy onset and weekly during therapy. The photodocumentation provides an impressive course of acute skin reactions under these care concepts., Results: Altogether we saw no relevant difference in favor of care with creme or powder according to objective as well as subjective assessment criteria (Figure 2 and 3). In this intraindividual comparison the results are independent from interindividual different sensitivity to radiotherapy, total dose or fractionation. Therefore the small patient number is a minor limitation for evidence. Our results are in accordance to trials comparing other care concepts., Conclusions: A relevant effect concerning onset and degree of acute skin reactions or differences in symptom relief could not be demonstrated. Both conceptions are to be regarded equal in terms of subjective symptom relief and in extent of acute skin reactions. The lack of differences may be explained by the fact that the underlying pathophysiological processes cannot be influenced by topical agents.

Background: Pituitary tumors are relatively uncommon, comprising 10-12% of all intracranial tumors. The treatment consisting of surgery, radiotherapy and drug therapy or a combination of these modalities is aimed at the control of tumor cell proliferation and--in endocrine active tumors--the reduction of hormone secretion. However, the slow proliferation characteristics of pituitary tumors necessitate long-term studies for the evaluation of the treatment results. In the last decade there has been continuous improvement in surgical procedures, radiotherapy techniques and drug generation. In this paper, literature will be reviewed to assess the role of modern radiotherapy and radiosurgery in the management of pituitary adenomas., Material and Methods: Nowadays, magnetic resonance imaging for the definition of the target volume and a real three-dimensional (3-D) treatment planning with field conformation and the possibility for non-coplanar irradiation has to be recommended. Most groups irradiate these benign tumors with single doses of 1.8-2.0 Gy up to a total dose of 45 Gy or 50.4 Gy in extensive parasellar adenomas. Adenomas are mostly small, well circumscribed lesions, and have, therefore, attracted the use of stereotactically guided high-precision irradiation techniques which allow extreme focussing and provide steep dose gradients with selective treatment of the target and optimal protection of the surrounding brain tissue., Results: Radiation therapy controls tumor growth in 80-98% of patients with non-secreting adenomas and 67-89% for endocrine active tumors. Reviewing the recent literature including endocrine active and non-secreting adenomas, irradiated postoperatively or in case of recurrence the 5-, 10- and 15-year local control rates amount 92%, 89% and 79%. In cases of microprolactinoma primary therapy consists of dopamine agonists. Irradiation should be preferred in patients with macroprolactinomas, when drug therapy and/or surgery failed or for patients medically unsuitable for surgery. Reduction and control of prolactin secretion can be achieved in 44-70% of patients. After radiotherapy in acromegaly patients somatomedin-C and growth hormone concentrations decrease to normal levels in 70-90%, with a decrease rate of 10-30% per year. Hypercortisolism is controlled in 50-83% of adults and 80% of children with Cushing's disease, generally in less than 9 months. Hypopituitarism is the most common side effect of pituitary irradiation with an incidence of 13-56%. Long-term overall risk for brain necrosis in a total of 1,388 analyzed patients was estimated to be 0.2%. Other side effects are rare too, and do also depend on the damage produced by tumor itself or preceding surgery. They include deterioration of vision in 1.7% of all cases, vascular changes in 6.3%, neuropsychological disorders such as dementia in 0.7% and secondary malignancies in 0.8%, if single doses of 2.0 Gy and total doses of 50 Gy are not exceeded., Conclusion: Conventional radiation therapy of pituitary adenoma is highly effective. It is recommended after subtotal resection of primary tumors such as macroadenomas, after gross total resection from endocrine active adenomas with postsurgical hormone secretion and for recurrent tumors. Radiosurgery seems to be a possible treatment alternative in experienced centers, and only in patients with adenomas smaller than 25-30 mm with a minimum distance of 2-3 mm to the chiasm.

Background: Conformal radiotherapy techniques as used in prostate treatment allow to spare normal tissue by conforming the radiation fields to the shape of the planning target volume (PTV). To be able to fully utilize the advantages of these techniques correct patient positioning is an important prerequisite. This study employing an electronic portal imaging device (EPID) investigated the positioning uncertainties that occur in the pelvic region for different patient positioning devices., Patients and Methods: 15 patients with prostate cancer were irradiated with or without rectal balloon/pelvic mask at a linear accelerator with multileaf collimator (MLC). For each patient multiple portal images were taken from different directions and compared to the digitally reconstructed radiographs (DRRs) of the treatment planning system and to simulation films (Table 1, Figure 1)., Results: In spite of different positioning devices, all patients showed comparable total positioning uncertainties of 4.0 mm (lateral), 4.5 mm (cranio-caudal) and 1.7 mm (dorso-ventral). The lateral positioning error was reduced for the pelvic mask patients while the cranio-caudal error increased (Table 2, Figure 2). A systematic and a random component sum up to the total positioning error, and a good estimate of the magnitudes of the two is possible from six to eight portal images (Figure 3)., Conclusions: With a small number of portal images it is possible to find out the systematic and random positioning error of a patient. Knowledge of the random error can be used to resize the treatment margin which is clinically relevant since this error differs greatly for different patients (Figure 4). Image analysis with EPID is convenient, yet has some problems. For example, one only gets indirect information on the movement of the ventral rectum wall (Figure 5). The successful operation of positioning devices, although, needs further improvement--especially if one focuses on IMRT.

Background: Beta emitting 106Ru applicators manufactured by Bebig GmbH (Berlin, Germany) are widely used to treat intraocular tumors. The applicators are fixed to the bulbus and removed after several days. The following therapy relevant defects have been detected by an internal clinical acceptance test: risk of leakage and inconsistent dose-rate specifications by the manufacturer. In the meantime, components of the internal clinical acceptance test have been adopted successfully by the manufacturer of the 106Ru ophthalmic plaques., Material and Method: 106Ru ophthalmic plaques were tested with the following internal clinical acceptance tests: visual inspection, surface contamination, leakage, and dose-rate verification. The surface contamination test consists of a wet wipe test at moderate pressure. For the leakage test of the 106Ru ophthalmic plaques a clinically relevant scenario was developed in which the contact of the applicator with human tissue is simulated. In the course of it the applicator is inserted into Ringer's solution for several days. The certified energy dose-rate statements of the manufacturer are examined with a 1 mm3 plastic scintillator for consistency., Results: During the internal clinically acceptance tests of 106Ru ophthalmic plaques of different size the following results were obtained: The leakage test was performed with seven applicators and yielded measurements for two 106Ru ophthalmic plaques that were significantly higher than those of a dummy sample. The highest value of a wipe test was 57 Bq (Figure 1). The highest value in Ringer's solution was 520 Bq (Figure 2). During the dosimetry consistency checks of the certified dose-rate specifications for 14 applicators, six applicators were in good agreement with a variation coefficient of 2.6%. For the other eight applicators the deviations were between -37% and +74% (Figure 3), i.e. the range of the unaccepted applicators amounts to 111%. The results were representatively verified through external assessment., Conclusion: Grave therapy relevant shortcomings of the industrial quality assurance of ophthalmic plaques were uncovered by experimental cross-checks. It is necessary that every radioactive device is internally examined before its use. The internal clinical acceptance test of the 106Ru ophthalmic plaques can easily be adopted by other hospitals.

Background: The chances for cure in medulloblastoma, supratentorial primitive neuroectodermal tumors (stPNET) and intracranial germ cell tumors have decisively improved within the last decades. Today long-term survival in the range between 60% and 80% and more than 90%, respectively, can be achieved. The low incidence of brain tumors in childhood and the necessity for optimal patient care has led to the fact that more than 90% of children are treated within national and international controlled studies today in order to assure a constant improvement of therapeutic outcome. Recent developments in neurosurgery achieved complete tumor resections in the majority of children at a low risk for morbidity and mortality., Methods: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival., Results: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ cell tumors cisplatin containing chemotherapies in conjunction with radiotherapy achieve a long-term survival rate of 80% today. Especially in high risk medulloblastoma and secreting germ cell tumors chemotherapies are playing an increasingly important role in the interdisciplinary management. It can be expected that future developments of chemotherapeutic protocols and the introduction of new cytostatic substances will further improve the therapeutic outcome., Conclusions: The therapeutic endeavors of all those caring for children are aiming to study modifications of the therapeutic components in the interdisciplinary approach in order to optimize the therapeutic strategies. In future the affected children and young adolescents should be accrued for the forthcoming cooperative, prospective trial HIT 2000 and ongoing trial SIOP CNS GCT 96, respectively, in order to provide the body of data supporting the selection of novel and optimized approaches for future treatment strategies.