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Purpose: Purpose of this study is to evaluate plan quality on the MRIdian (Viewray Inc., Oakwood Village, OH, USA) system for head and neck cancer (HNC) through comparison of planning approaches of several centers., Methods: A total of 14 planners using the MRIdian planning system participated in this treatment challenge, centrally organized by ViewRay, for one contoured case of oropharyngeal carcinoma with standard constraints for organs at risk (OAR). Homogeneity, conformity, sparing of OARs, and other parameters were evaluated according to The International Commission on Radiation Units and Measurements (ICRU) recommendations anonymously, and then compared between centers. Differences amongst centers were assessed by means of Wilcoxon test. Each plan had to fulfil hard constraints based on dose-volume histogram (DVH) parameters and delivery time. A plan quality metric (PQM) was evaluated. The PQM was defined as the sum of 16 submetrics characterizing different DVH goals., Results: For most dose parameters the median score of all centers was higher than the threshold that results in an ideal score. Six participants achieved the maximum number of points for the OAR dose parameters, and none had an unacceptable performance on any of the metrics. Each planner was able to achieve all the requirements except for one which exceeded delivery time. The number of segments correlated to improved PQM and inversely correlated to brainstem D 0.1cc and to Planning Target Volume1 (PTV) D 0.1cc . Total planning experience inversely correlated to spinal canal dose., Conclusion: Magnetic Resonance Image (MRI) linac-based planning for HNC is already feasible with good quality. Generally, an increased number of segments and increasing planning experience are able to provide better results regarding planning quality without significantly prolonging overall treatment time., (© 2021. The Author(s).)

The International Commission on Radiation Units and Measurements (ICRU) report 91 with the title "prescribing, recording, and reporting of stereotactic treatments with small photon beams" was published in 2017. This extensive publication covers different relevant aspects of stereotactic radiotherapy such as small field dosimetry, accuracy requirements for volume definition and planning algorithms, and the precise application of treatment by means of image guidance. Finally, recommendations for prescribing, recording and reporting are given.

Background: Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel., Methods: The analysis was performed within the "Stereotactic Radiotherapy" working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch., Results: The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT., Conclusion: The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

Purpose: This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer., Methods: A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation., Results: Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities., Conclusion: SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT.

Purpose: The purpose of this work is to analyze patterns of care and outcome after stereotactic body radiotherapy (SBRT) for centrally located, early-stage, non-small cell lung cancer (NSCLC) and to address the question of potential risk for increased toxicity in this entity., Methods and Materials: A total of 90 patients with centrally located NSCLC were identified among 613 cases in a database of 13 German and Austrian academic radiotherapy centers. The outcome of centrally located NSCLC was compared to that of cases with peripheral tumor location from the same database., Results: Patients with central tumors most commonly presented with UICC stage IB (50 %), while the majority of peripheral lesions were stage IA (56 %). Average tumor diameters were 3.3 cm (central) and 2.8 cm (peripheral). Staging PET/CT was available for 73 and 74 % of peripheral and central tumors, respectively. Biopsy was performed in 84 % (peripheral) and 88 % (central) of cases. Doses varied significantly between central and peripheral lesions with a median BED10 of 72 Gy and 84 Gy, respectively (p < 0.001). Fractionation differed as well with medians of 5 (central) and 3 (peripheral) fractions (p < 0.001). In the Kaplan-Meier analysis, 3-year actuarial overall survival was 29 % (central) and 51 % (peripheral; p = 0.004) and freedom from local progression was 52 % (central) and 84 % (peripheral; p < 0.001). Toxicity after treatment of central tumors was low with no grade III/IV and one grade V event. Mortality rates were 0 and 1 % after 30 and 60 days, respectively., Conclusion: Local tumor control in patients treated with SBRT for centrally located, early-stage NSCLC was favorable, provided ablative radiation doses were prescribed. This was, however, not the case in the majority of patients, possibly due to concerns about treatment-related toxicity. Reported toxicity was low, but prospective trials are needed to resolve the existing uncertainties and to establish safe high-dose regimens for this cohort of patients.

This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft für Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy.

Purpose: To evaluate the diagnostic value of positron-emission tomography/computed tomography (PET/CT) in stage I lung cancer patients treated with stereotactic body radiation therapy (SBRT), who have suspicious or unclear local recurrence findings in CT 1 year after treatment., Patients and Methods: A group of 29 patients with unclear or suspicious CT findings 1 year after SBRT were examined with PET/CT. The ability of standard uptake values (SUVmax, SUVmean and posttherapeutic reduction in SUV) to detect local failure and identify patients at a high risk of disease-specific death was evaluated using logrank statistics. Histology and clinical follow-up were the gold standards for local recurrence., Results: SUVmean greater than 3.44 (p = 0.001); SUVmax greater than 5.48 (p = 0.009) or a relative reduction in SUVmean or SUVmax of less than 43 (p = 0.030) or 52 % (p = 0.025), respectively, was indicative of local recurrence. These parameters also correlated with an increased risk of disease-specific death: SUVmean greater than 2.81 (p = 0.023); SUVmax greater than 3.45 (p = 0.007) or a relative reduction in SUVmean or SUVmax of less than 32 (p = 0.015) or 52 % (p = 0.013), respectively, was indicative of an increased risk of disease-specific death., Conclusion: PET/CT performed 1 year after SBRT can reliably identify local recurrence and therefore help to clarify unclear CT findings. As posttherapeutic glucose metabolism also correlates with disease-specific survival, PET/CT may help to stratify lung cancer patients for additional treatment 1 year after SBRT.

Background and Purpose: Assessment of prognostic factors might influence treatment decisions in patients with brain metastases. Based on large studies, the diagnosis-specific graded prognostic assessment (GPA) score is a useful tool. However, patients with unknown or rare primary tumours are not represented in this model. A pragmatic approach might be use of the first GPA version which is not limited to specific primary tumours., Patients and Methods: This retrospective analysis examines for the first time whether the GPA is a valid score in patients not eligible for the diagnosis-specific GPA. It includes 71 patients with unknown primary tumour, bladder cancer, ovarian cancer, thyroid cancer or other uncommon primaries. Survival was evaluated in uni- and multivariate tests., Results: The GPA significantly predicted survival. Moreover, improved survival was seen in patients treated with surgical resection or radiosurgery (SRS) for brain metastases. The older recursive partitioning analysis (RPA) score was significant in univariate analysis. However, the multivariate model with RPA, GPA and surgery or SRS versus none showed that only GPA and type of treatment were independent predictors of survival., Conclusion: Ideally, cooperative research efforts would lead to development of diagnosis-specific scores also for patients with rare or unknown primary tumours. In the meantime, a pragmatic approach of using the general GPA score appears reasonable.

Purpose: The use of 4D-[(18)F]fluorodeoxyglucose (FDG) PET/CT in combination with respiratory gated magnet resonance imaging (MRI) in target volume definition for stereotactic radiation of liver metastases was investigated., Methods and Materials: A total of 18 patients received respiration gated FDG-PET/CT and MRI. Data were fused using a rigid co-registration algorithm. The quality of the co-registration was rated on a scale from 1 (excellent) to 5 (poor) for co-registration of MRI with gated PET and ungated PET. Gross tumor volume (GTV) was delineated in CT (GTV (CT)), MRI (GTV(MRI)), and PET (GTV(PET)). MRI- and PET-based GTVs were defined by three observers each. Interobserver variability was calculated for all patients as well as for subgroups with and without previous treatment of liver metastases. All GTVs were compared for all patients and separately for patients with previous local therapy. In addition, a semiautomatic segmentation algorithm was applied on the PET images., Results: Co-registration  between MR and PET images was rated with 3.3 in average when non-gated PET was used and improved significantly (p < 0.01) to 2.1 using gated PET. The average GTV(CT)  was 51.5 ml, GTV(MRI)  51.8 ml, and the average GTV(PET)  48.1 ml. Volumes delineated in MRI were 9.9% larger compared to those delineated in CT. Volumes delineated in PET were 13.8% larger than in MRI. The differences between the GTVs were more pronounced in patients with previous treatment. The GTVs defined in MRI showed an interobserver variability of 47.9% (84.1% with previous treatment and 26.2% without previous treatment). The PET-defined GTVs showed an interobserver variability of 21% regardless of previous treatment. Semiautomatic segmentation did not provide satisfying results., Conclusion: FDG-PET can distinguish vital tumor tissue and scar tissue, and therefore alters the GTV especially in patients with previous local treatment. In addition, it reduces the interobserver variability significantly compared to MRI. However, respiratory gated PET is necessary for good co-registration of PET and MRI.

Purpose: To evaluate residents' satisfaction with their training in radiation oncology, the first nationwide survey was done in 2006. Results were presented at the 2006 annual meeting of the German Society of Radiation Oncology (DEGRO)., Material and Methods: A questionnaire with 39 questions regarding training in radiation oncology in Germany was developed and sent by e-mail. Questionnaires were returned by mail and analyzed anonymously., Results: 96 questionnaires were received. A total of 88% of respondents are pleased with their decision of training in radiation oncology. Residents are strongly motivated by their interest in oncology. Quality of training is heterogeneous and not optimal. Training in three-dimensional treatment planning, radiochemotherapy and intracavitary brachytherapy is judged adequate, whereas special techniques such as intensity-modulated radiotherapy (IMRT) and permanent prostate implants are not covered by the majority of institutions. Organization of training in the departments is often judged insufficient., Conclusion: Radiation oncology is attractive for young doctors. However, training quality for radiation oncologists in Germany was judged to be heterogeneous and needs to be optimized. For this, results of this survey may be helpful. The overall positive judgment may help to attract more students into the field of radiation oncology, an issue that becomes increasingly important given the shortage of doctors and the strong competition with other disciplines. Modern techniques, such as IMRT, need to be integrated into training programs in order to maintain the high standard of radiation oncology in Germany.

Purpose: To examine experimental strategies for prevention of radiation-induced late spinal cord damage., Material and Methods: The effects of treatment with high, proliferation-stimulating doses of platelet-derived growth factor (PDGF) administered at various times after radiotherapy of rat spinal cord, and aiming at increased tissue regeneration, were studied in an established model. Animals were followed and monitored for expression of radiation myelopathy (RM), which was confirmed by histopathologic diagnosis., Results: High doses of PDGF given 8 weeks after radiotherapy significantly accelerated the development of RM compared to control animals (Figure 1). Such effects were observed also for concomitant treatment, but not for PDGF administration after 12 or 15 weeks (Figure 2). On the microscopic level, the spinal cord showed more pronounced vascular damage with vessel necroses and hemorrhages (Figure 3)., Conclusion: These data suggest that the vascular system plays an important role during development of RM and that early stimulation of cell proliferation negatively influences the time course of spinal cord damage. Further experiments should address different concepts of tissue regeneration or damage prevention.

Purpose: To test whether insulin-like growth factor-1 (IGF-1) and amifostine modulate the reirradiation tolerance of rat cervical spinal cord. Initial experiments by the authors' group suggested that administration of each agent alone significantly increased the median latent time to radiation myelopathy (RM) in previously unirradiated animals but did not change the dose-response relationship. Because of different modes of action, a follow-up study was undertaken to test the combined treatment., Material and Methods: The cervical spinal cord of 51 adult Fisher F-344 rats received a single fraction of 16 Gy, which corresponds to approximately 75% of the median paresis dose (ED(50)), followed 5 months later by a second radiation dose, which ranged from 17 to 21 Gy. The study animals received a single intrathecal injection of 0.3 mg amifostine into the cisterna magna 30-60 min before reirradiation plus three subcutaneous doses of IGF-1 (700 microg) starting from 24 h before to 24 h after reirradiation. Control animals received saline injections via the same routes. Animals were followed until RM developed or until 12 months from reirradiation. Histopathologic examinations were performed post mortem., Results: No animals showed any neurologic abnormalities before reirradiation. RM occurred in controls versus treated rats after a mean latency of 218 versus 314 days (19 Gy; p = 0.11) and 104 versus 186 days (21 Gy; p = 0.002) from second dose (Figure 1). ED(50) was 18.2 versus 19.4 Gy (p = 0.15; Figure 2). Treatment with IGF-1 and amifostine did not significantly influence the rates of tumor induction or intercurrent death., Conclusion: IGF-1 and amifostine significantly reduced RM rates after 21 Gy. The shift of the dose-response curve suggests an increase of the ED(50) for single-dose treatment by approximately 7%. Thus, brief therapeutic intervention might slightly decrease radiation-induced neurotoxicity in a retreatment situation.

Background and Purpose: The publication of Radiation Therapy Oncology Group (RTOG) Study 83-02 in 1996 stimulated further investigations of altered fractionation, i. e., application of more than one fraction per day, in high-grade gliomas. This review summarizes the results of trials published between January 1997 and June 2002., Material and Methods: To identify suitable trials, a Medline search was performed by use of the following key words: brain tumors/astrocytoma/glioma/high-grade glioma/malignant glioma/glioblastoma multiforme and accelerated radiotherapy/hyperfractionated radiotherapy/altered fractionation. In addition, the search was extended to reference lists of articles and textbooks. Whenever possible, data were extracted from the original papers on an intention-to-treat basis, i. e., patients with protocol violations were not excluded for the purpose of this analysis. Studies in brain stem gliomas, pediatric patients and studies which achieved acceleration by radiosurgery, stereotactic radiotherapy, or brachytherapy rather than conventional external-beam treatment were not included. An exploratory analysis of 2-year survival was also performed. For this purpose, the 2-year survival rate was extracted from each individual study. The total number of 2-year survivors was then calculated for each treatment strategy and compared by use of the chi(2)-test., Results: The authors identified 1,414 patients from 21 studies; two of these were randomized phase III studies. In seven studies (658 patients), chemotherapy or radiosensitizers were not administered in addition to radiotherapy. The others provide a very heterogeneous set of data, because a large variety of drugs and administration schedules was used. Seven studies included patients with glioblastoma multiforme only, two were limited to patients with anaplastic gliomas. Dose per fraction was 1.2-1.8 Gy in 17 studies and 1.9-2.65 Gy in four. Overall treatment time was 12-31 days, except for one study. Three out of five studies where three fractions per day were administered, included a 2-week break (split-course studies). None of the studies reported a significant improvement in survival by altered fractionation in comparison to either institutional historical controls or their respective randomized control arm. Doses of 60-70 Gy do not appear to improve survival compared to 50-60 Gy. The current data provide no arguments for use of three instead of two fractions per day. Median survival was 10 months after radiotherapy alone (658 patients) and 11 months after combined treatment (756 patients). Regarding 2-year survival rates, radiotherapy alone resulted in 13%, combined chemoradiation or use of sensitizers in 23% (p < 0.0001). However, prognostic factors such as tumor histology were not equally distributed and favor the combined-treatment group. Evaluation of six studies of conventional radiotherapy alone resulted in data from 571 patients. Their median survival was 10.8 months. Cumulative 2-year survival amounted to 15%. The studies of conventional radiotherapy plus chemotherapy or sensitizers included 1,115 patients with a median survival of 11 months (2-year survival rate 18.5%)., Conclusion: Altered fractionation shortens the overall treatment time for adult patients with supratentorial high-grade gliomas. However, there is no significant survival improvement.

Background: We evaluated prognostic factors for survival in patients with four or more brain metastases in order to determine whether intense local treatment might be justified for some of them. If up to three brain metastases are present, surgical resection or radiosurgery are currently being considered in case of favorable prognostic factors., Patients and Methods: Retrospective intention-to-treat analysis of 113 patients who underwent whole-brain radiotherapy without surgical resection or radiosurgery at a single institution. Standard treatment was given with ten fractions of 3 Gy. Higher total doses were administered in 13% of patients. Recursive partitioning analysis (RPA) prognostic classes have been described by the Radiation Therapy Oncology Group (RTOG) in 1997 (class I: Karnofsky performance status [KPS] > or = 70%, age < or = 65 years, no extracranial metastases, controlled primary tumor; class III: KPS < 70%; class II: others)., Results: Median number of brain metastases was six (four to 50). Most patients (69%) had extracranial metastases as well. Criteria of RPA Class I (II) were met in 4% (41%), whereas 56% had KPS < 70% and thus were grouped into class III (Tables 1 and 2). Complete or partial remission of brain metastases was found in 46% of patients who underwent computed tomography. Median survival was 4 months, 1-years survival rate 15%. Only age was a borderline significant prognostic factor in univariate analysis (< or = 50 years vs > 50 years, p = 0.05). Strong trends were found for KPS, extracranial metastases, control of the primary tumor, and breast primary tumor. Number of brain metastases, RPA class and treatment-related factors such as total dose or remission of brain metastases had no appreciable influence on survival (Figure 1). Multivariate analysis failed to identify any significant prognostic factor., Conclusions: Patients with four or more brain metastases seem to represent a group with unfavorable prognosis where remission of brain metastases or administration of more than 30 Gy were not associated with increased survival. The number of patients in RPA class I was too small to draw final conclusions. However, there was absolutely no survival difference between patients in class II (median survival 3.6 months) and III (median 4.2 months).

Background: Current models of radiation myelopathy provide a rationale for growth factor-based prevention strategies. Thus, we tested whether insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) alone or in combination modulate radiation tolerance of the rat cervical spinal cord., Materials and Methods: The cervical spinal cord of 68 adult Fisher F344 rats received a total dose of 30-36 Gy, given as a single fraction of 16 Gy followed by a second radiation dose of 14-20 Gy. Continuous intrathecal infusion of bFGF (44 rats) or saline (24 rats) into the cisterna magna was given concomitantly. A further experiment included 14 additional rats which were treated with subcutaneous injection of IGF-1 parallel to irradiation with a total dose of 34 Gy or 36 Gy. 20 rats received combined treatment, i.e. intrathecal infusion of bFGF plus subcutaneous injection of IGF-1, starting 24 hours before irradiation (total dose 33 Gy or 36 Gy) for a total of 4 days. Animals were followed until myelopathy developed or for a maximum of 12 months. Histopathologic examinations were performed post mortem., Results: Treatment with bFGF alone or IGF-1 alone increased the median time to myelopathy significantly. In the 36-Gy group, after combination treatment a comparable prolongation of latency was seen. Moreover, rats treated with 33 Gy and combined bFGF plus IGF-1 showed a significantly reduced risk of myelopathy, too (p = 0.0015, Figures 1 and 2)., Conclusion: Combination of IGF-1 and bFGF was more potent than single agent treatment. We observed a significantly reduced myelopathy rate at an intermediate radiation dose level and a longer time to myelopathy at a high-dose level. This finding strengthens the evidence that brief therapeutic intervention can decrease radiation-induced neurotoxicity. Further studies will be undertaken to optimize this strategy.