Comparison of two optimization algorithms (VOLOTM , SEQU) for CyberKnife® treatment of acoustic neuromas, lung metastases, and liver metastases.

INTRODUCTION: Two optimization algorithms VOLO™ and sequential optimization algorithm (SEQU) are compared in the Precision® treatment planning system from Accuray® for stereotactic radiosurgery and stereotactic body radiotherapy (SBRT) treatment plans. The aim is to compare the two algorithms to assess if VOLO™ is better of SEQU in certain treatment site. MATERIALS AND METHODS: Sixty clinical treatment cases were compared. Entities include Acoustic neuroma (AN), lung metastases, and liver metastases. In each entity, 10 SEQU and 10 VOLO™ treatment plans were optimized. The Ray-Tracing calculation algorithm was used for all treatment plans and the treatments were planned exclusively with fixed cones (5-50 mm). The number of nodes, beams, total MU, and treatment time were compared. Conformity index (CI), new conformity index (nCI), homogeneity index (HI), gradient index (GI), and target coverage were examined for agreement. Dmin , Dmean , Dmax , D100%, D98%, and D2% dose in the target volume as well as exposure to organs at risk was checked. To determine peripheral doses, the isodose volumes from V10% to V98% were evaluated. RESULTS: AN treatment plans showed significant differences for the number of nodes, beams, total MU, treatment time, D98%, D100% for the target volume, and the doses for all organs at risk. VOLO™ achieved better results on average. Total MU, treatment time, coverage, and D98% are significantly better for VOLO™ for lung metastases. For liver metastases, a significant reduction in number of nodes, total MU, and treatment time was observed for VOLO™ plans. The mean target coverage increased slightly with VOLO™, while the mean CI deteriorated slightly. The averages of Dmin , Dmean , D98%, D100%, and V80% resulted in a significant increase for VOLO™. CONCLUSION: The results of the present study indicate that VOLO™ should be used in place of SEQU as a standard for AN cases moving forward. Despite the lack of significance in the lung and liver cases, VOLO™ optimization is recommended because OAR sparing was similar, but coverage, Dmin , and Dmean were increased, and thus better tumor control can be expected.

Development of a LINAC head model for the CyberKnife VSI-System using EGSnrc Monte Carlo system.

INTRODUCTION: In order to understand the interaction processes of photons and electrons of the CyberKnife VSI-System, a modeling of the LINAC head must take place. Here, a Monte Carlo simulation can help. By comparing the measured data with the simulation data, the agreement can be checked. MATERIALS AND METHODS: For the Monte Carlo simulations, the toolkit EGSnrc with the user codes BEAMnrc and DOSXZYnrc was used. The CyberKnife VSI-System has two collimation systems to define the field size of the beam. On the one hand, it has 12 circular collimators and, on the other, an IRIS-aperture. The average energy, final source width, dose profiles, and output factors in a voxel-based water phantom were determined and compared to the measured data. RESULTS: The average kinetic energy of the electron beam for the CyberKnife VSI LINAC head is 6.9 MeV, with a final source width of 0.25 cm in x-direction and 0.23 cm in y-direction. All simulated dose profiles for both collimation systems were able to achieve a global gamma criterion of 1%/1 mm to the measured data. For the output factors, the deviation from simulated to measured data is < 1% from a field size of 12.5 mm for the circular collimators and from a field size of 10 mm for the IRIS-aperture. CONCLUSION: The beam characteristics of the CyberKnife VSI LINAC head could be exactly simulated with Monte Carlo simulation. Thus, in the future, this model can be used as a basis for electronic patient-specific QA or to determine scattering processes of the LINAC head.

Data-driven gating in PET: Influence of respiratory signal noise on motion resolution.

PURPOSE: Data-driven gating (DDG) approaches for positron emission tomography (PET) are interesting alternatives to conventional hardware-based gating methods. In DDG, the measured PET data themselves are utilized to calculate a respiratory signal, that is, subsequently used for gating purposes. The success of gating is then highly dependent on the statistical quality of the PET data. In this study, we investigate how this quality determines signal noise and thus motion resolution in clinical PET scans using a center-of-mass-based (COM) DDG approach, specifically with regard to motion management of target structures in future radiotherapy planning applications. METHODS: PET list mode datasets acquired in one bed position of 19 different radiotherapy patients undergoing pretreatment [18 F]FDG PET/CT or [18 F]FDG PET/MRI were included into this retrospective study. All scans were performed over a region with organs (myocardium, kidneys) or tumor lesions of high tracer uptake and under free breathing. Aside from the original list mode data, datasets with progressively decreasing PET statistics were generated. From these, COM DDG signals were derived for subsequent amplitude-based gating of the original list mode file. The apparent respiratory shift d from end-expiration to end-inspiration was determined from the gated images and expressed as a function of signal-to-noise ratio SNR of the determined gating signals. This relation was tested against additional 25 [18 F]FDG PET/MRI list mode datasets where high-precision MR navigator-like respiratory signals were available as reference signal for respiratory gating of PET data, and data from a dedicated thorax phantom scan. RESULTS: All original 19 high-quality list mode datasets demonstrated the same behavior in terms of motion resolution when reducing the amount of list mode events for DDG signal generation. Ratios and directions of respiratory shifts between end-respiratory gates and the respective nongated image were constant over all statistic levels. Motion resolution d/dmax could be modeled as d/dmax=1-e-1.52(SNR-1)0.52, with dmax as the actual respiratory shift. Determining dmax from d and SNR in the 25 test datasets and the phantom scan demonstrated no significant differences to the MR navigator-derived shift values and the predefined shift, respectively. CONCLUSIONS: The SNR can serve as a general metric to assess the success of COM-based DDG, even in different scanners and patients. The derived formula for motion resolution can be used to estimate the actual motion extent reasonably well in cases of limited PET raw data statistics. This may be of interest for individualized radiotherapy treatment planning procedures of target structures subjected to respiratory motion.

Planning benchmark study for SBRT of early stage NSCLC : Results of the DEGRO Working Group Stereotactic Radiotherapy.

PURPOSE: The aim was to evaluate stereotactic body radiation therapy (SBRT) treatment planning variability for early stage nonsmall cell lung cancer (NSCLC) with respect to the published guidelines of the Stereotactic Radiotherapy Working Group of the German Society for Radiation Oncology (DEGRO). MATERIALS AND METHODS: Planning computed tomography (CT) scan and the structure sets (planning target volume, PTV; organs at risk, OARs) of 3 patients with early stage NSCLC were sent to 22 radiotherapy departments with SBRT experience: each department was asked to prepare a treatment plan according to the DEGRO guidelines. The prescription dose was 3 fractions of 15 Gy to the 65% isodose. RESULTS: In all, 87 plans were generated: 36 used intensity-modulated arc therapy (IMAT), 21 used three-dimensional conformal radiation therapy (3DCRT), 6 used static field intensity-modulated radiation therapy (SF-IMRT), 9 used helical radiotherapy and 15 used robotic radiosurgery. PTV dose coverage and simultaneously kept OARs doses were within the clinical limits published in the DEGRO guidelines. However, mean PTV dose (mean 58.0 Gy, range 52.8-66.4 Gy) and dose conformity indices (mean 0.75, range 0.60-1.00) varied between institutions and techniques (p ≤ 0.02). OARs doses varied substantially between institutions, but appeared to be technique independent (p = 0.21). CONCLUSION: All studied treatment techniques are well suited for SBRT of early stage NSCLC according to the DEGRO guidelines. Homogenization of SBRT practice in Germany is possible through the guidelines; however, detailed treatment plan characteristics varied between techniques and institutions and further homogenization is warranted in future studies and recommendations. Optimized treatment planning should always follow the ALARA (as low as reasonably achievable) principle.

Influence of Institutional Experience and Technological Advances on Outcome of Stereotactic Body Radiation Therapy for Oligometastatic Lung Disease.

PURPOSE: Many technological and methodical advances have made stereotactic body radiotherapy (SBRT) more accurate and more efficient during the last years. This study aims to investigate whether experience in SBRT and technological innovations also translated into improved local control (LC) and overall survival (OS). METHODS AND MATERIALS: A database of 700 patients treated with SBRT for lung metastases in 20 German centers between 1997 and 2014 was used for analysis. It was the aim of this study to investigate the impact of fluorodeoxyglucose positron-emission tomography (FDG-PET) staging, biopsy confirmation, image guidance, immobilization, and dose calculation algorithm, as well as the influence of SBRT experience, on LC and OS. RESULTS: Median follow-up time was 14.3 months (range, 0-131.9 months), with 2-year LC and OS of 81.2% (95% confidence interval [CI] 75.8%-85.7%) and 54.4% (95% CI 50.2%-59.0%), respectively. In multivariate analysis, all treatment technologies except FDG-PET staging did not significantly influence outcome. Patients who received pre-SBRT FDG-PET staging showed superior 1- and 2-year OS of 82.7% (95% CI 77.4%-88.6%) and 64.8% (95% CI 57.5%-73.3%), compared with patients without FDG-PET staging resulting in 1- and 2-year OS rates of 72.8% (95% CI 67.4%-78.8%) and 52.6% (95% CI 46.0%-60.4%), respectively (P=.012). Experience with SBRT was identified as the main prognostic factor for LC: institutions with higher SBRT experience (patients treated with SBRT within the last 2 years of the inclusion period) showed superior LC compared with less-experienced centers (P≤.001). Experience with SBRT within the last 2 years was independent from known prognostic factors for LC. CONCLUSION: Investigated technological and methodical advancements other than FDG-PET staging before SBRT did not significantly improve outcome in SBRT for pulmonary metastases. In contrast, LC was superior with increasing SBRT experience of the individual center.

Stereotactic body radiotherapy (SBRT) for medically inoperable lung metastases-A pooled analysis of the German working group "stereotactic radiotherapy".

OBJECTIVES: The current literature on stereotactic body radiotherapy (SBRT) for oligometastatic disease is characterized by small patient cohorts with heterogeneous primary tumors, metastases location and dose regimes. Hence, this study established a multi-institutional database of 700 patients treated with SBRT for pulmonary metastases to identify prognostic factors influencing survival and local control. MATERIALS AND METHODS: All German radiotherapy departments were contacted and invited to participate in this analysis. A total number of 700 patients with medically inoperable lung metastases treated with SBRT in 20 centers between 1997 and 2014 were included in a database. Primary and metastatic tumor characteristics, treatment characteristics and follow-up data including survival, local control, distant metastases, and toxicity were evaluated. Lung metastases were treated with median PTV-encompassing single doses of 12.5Gy (range 3.0-33.0Gy) in a median number of 3 fractions (range 1-13). RESULTS: After a median follow-up time of 14.3 months, 2-year local control (LC) and overall survival (OS) were 81.2% and 54.4%, respectively. In multivariate analysis, OS was most significantly influenced by pretreatment performance status, maximum metastasis diameter, primary tumor histology, time interval between primary tumor diagnosis and SBRT treatment and number of metastases. For LC, independent prognostic factors were pretreatment performance status, biological effective dose (BED) at PTV isocenter (BEDISO) and single fraction (PTV-encompassing) dose in multivariate analysis. Radiation-induced pneumonitis grade 2 or higher was observed in 6.5% of patients. The only factor significantly influencing toxicity was BEDISO (p=0.006). CONCLUSION: SBRT for medically inoperable patients with pulmonary metastases achieved excellent local control and promising overall survival. Important prognostic factors were identified for selecting patients who might benefit most from this therapy approach.

Bayesian Cure Rate Modeling of Local Tumor Control: Evaluation in Stereotactic Body Radiation Therapy for Pulmonary Metastases.

PURPOSE: Most radiobiological models for prediction of tumor control probability (TCP) do not account for the fact that many events could remain unobserved because of censoring. We therefore evaluated a set of TCP models that take into account this censoring. METHODS AND MATERIALS: We applied 2 fundamental Bayesian cure rate models to a sample of 770 pulmonary metastasis treated with stereotactic body radiation therapy at German, Austrian, and Swiss institutions: (1) the model developed by Chen, Ibrahim and Sinha (the CIS99 model); and (2) a mixture model similar to the classic model of Berkson and Gage (the BG model). In the CIS99 model the number of clonogens surviving the radiation treatment follows a Poisson distribution, whereas in the BG model only 1 dominant recurrence-competent tissue mass may remain. The dose delivered to the isocenter, tumor size and location, sex, age, and pretreatment chemotherapy were used as covariates for regression. RESULTS: Mean follow-up time was 15.5 months (range: 0.1-125). Tumor recurrence occurred in 11.6% of the metastases. Delivered dose, female sex, peripheral tumor location and having received no chemotherapy before RT were associated with higher TCP in all models. Parameter estimates of the CIS99 were consistent with the classical Cox proportional hazards model. The dose required to achieve 90% tumor control after 15.5 months was 146 (range: 114-188) Gy10 in the CIS99 and 133 (range: 101-164) Gy10 in the BG model; however, the BG model predicted lower tumor control at long (≳20 months) follow-up times and gave a suboptimal fit to the data compared to the CIS99 model. CONCLUSIONS: Biologically motivated cure rate models allow adding the time component into TCP modeling without being restricted to the follow-up period which is the case for the Cox model. In practice, application of such models to the clinical setting could allow for adaption of treatment doses depending on whether local control should be achieved in the short or longer term.

Cone-beam CT-guided radiotherapy in the management of lung cancer: Diagnostic and therapeutic value.

BACKGROUND: Recent studies have demonstrated an increase in the necessity of adaptive planning over the course of lung cancer radiation therapy (RT) treatment. In this study, we evaluated intrathoracic changes detected by cone-beam CT (CBCT) in lung cancer patients during RT. METHODS AND MATERIALS: A total of 71 lung cancer patients treated with fractionated CBCT-guided RT were evaluated. Intrathoracic changes and plan adaptation priority (AP) scores were compared between small cell lung cancer (SCLC, n = 13) and non-small cell lung cancer (NSCLC, n = 58) patients. RESULTS: The median cumulative radiation dose administered was 54 Gy (range 30-72 Gy) and the median fraction dose was 1.8 Gy (range 1.8-3.0 Gy). All patients were subjected to a CBCT scan at least weekly (range 1-5/week). We observed intrathoracic changes in 83 % of the patients over the course of RT [58 % (41/71) regression, 17 % (12/71) progression, 20 % (14/71) atelectasis, 25 % (18/71) pleural effusion, 13 % (9/71) infiltrative changes, and 10 % (7/71) anatomical shift]. Nearly half, 45 % (32/71), of the patients had one intrathoracic soft tissue change, 22.5 % (16/71) had two, and three or more changes were observed in 15.5 % (11/71) of the patients. Plan modifications were performed in 60 % (43/71) of the patients. Visual volume reduction did correlate with the number of CBCT scans acquired (r = 0.313, p = 0.046) and with the timing of chemotherapy administration (r = 0.385, p = 0.013). CONCLUSION: Weekly CBCT monitoring provides an adaptation advantage in patients with lung cancer. In this study, the monitoring allowed for plan adaptations due to tumor volume changes and to other anatomical changes.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. MATERIALS AND METHODS: A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. RESULTS: After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. CONCLUSIONS: Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.

A case of radiotherapy for an advanced bronchial carcinoma patient with implanted cardiac rhythm machines as well as heart assist device.

We present a case of radiotherapy for a 66-year-old patient with squamous cell carcinoma on the left main bronchus undergoing implantation of pacemaker, implantable cardioverter defibrillator (ICD) as well as cardiopulmonary support (CPS) device. The radiation area was determined according to 4D List Mode positron emission tomography-computed tomography (PET-CT) data. Planning Target Volume (PTV) included a part of the active ICD. For the optimal tumor coverage and sparing of both the implantable cardiac devices and organs at risk, we combined the conformal radiotherapy with stereotactic body radiotherapy (SBRT) using helical tomotherapy. The prescription dose of 25.2Gy was applied by conventional radiotherapy. SBRT was performed hypofractionated with a prescription dose of 35Gy in 5 fractions. A dynamic electrocardiogram was performed during every radiation fraction. The implanted aggregates were checked three times a week. Despite partial localization of the active ICD in the radiation field, the tumor was treated without inappropriate shock delivery during radiation treatment and over twelve months afterwards. The reduced tumor size as well as tumor metabolic activity were observed by PET-CT three months after radiation treatment. The patient exhibited no signs of pneumonitis on the last radiological follow-up examination six months after radiotherapy. The reduced dyspnea and cough over the first four months after treatment were observed.In conclusion, tumor shrinkage and temporary clinical improvement of the patient as well as no technical complications of implanted cardiac devices were achieved by the radiation treatment.

Stereotactic body radiotherapy for centrally located stage I NSCLC: a multicenter analysis.

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.

Stereotactic body radiotherapy for liver tumors: principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy.

PURPOSE: This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a practical guideline for safe and effective stereotactic body radiotherapy (SBRT) of liver tumors. METHODS: The literature on the clinical evidence of SBRT for both primary liver tumors and liver metastases was reviewed and analyzed focusing on both physical requirements and special biological characteristics. RESULTS: Recommendations were developed for patient selection, imaging, planning, treatment delivery, motion management, dose reporting, and follow-up. Radiation dose constraints to critical organs at risk are provided. CONCLUSION: SBRT is a well-established treatment option for primary and secondary liver tumors associated with low morbidity.

Evaluation of time, attendance of medical staff and resources for radiotherapy in pediatric and adolescent patients. The DEGRO-QUIRO trial.

BACKGROUND: The German Society of Radiation Oncology (DEGRO) initiated a multicenter trial to develop and evaluate adequate modules to assert core procedures in radiotherapy. The aim of this prospective evaluation was to methodical assess the required resources for radiotherapy in pediatric and adolescent patients. MATERIAL AND METHODS: At three radiotherapy centers of excellence (University Hospitals of Heidelberg and Münster, the Medical School of Hannover), the manpower and time required for radiotherapy in pediatric and adolescent patients was prospectively documented consistently over a 2-year period. The data were collected using specifically developed standard forms and were evaluated using specific process analysis tools. RESULTS: A total number of 1914 data sets were documented and carefully analyzed. The personnel time requirements for all occupational groups were calculated as total time needed for a specific procedure and mean time per person. Regarding radiotherapy in general anesthesia, the required manpower was higher. The personnel time requirements in these cases were also longer, mainly due to longer room occupancy. Overall, the required resources were remarkably similar between the three different departments and may, therefore, be considered as representative. CONCLUSION: For the first time, the personnel time requirements of a radiotherapy department for the maintenance, protection, and optimization of operational readiness for radiotherapy in pediatric and adolescent patients with and without general anesthesia were determined methodically.

Support vector machine-based prediction of local tumor control after stereotactic body radiation therapy for early-stage non-small cell lung cancer.

BACKGROUND: Several prognostic factors for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) have been described, but no attempts have been undertaken to explore whether a nonlinear combination of potential factors might synergistically improve the prediction of local control. METHODS AND MATERIALS: We investigated a support vector machine (SVM) for predicting TCP in a cohort of 399 patients treated at 13 German and Austrian institutions. Among 7 potential input features for the SVM we selected those most important on the basis of forward feature selection, thereby evaluating classifier performance by using 10-fold cross-validation and computing the area under the ROC curve (AUC). The final SVM classifier was built by repeating the feature selection 10 times with different splitting of the data for cross-validation and finally choosing only those features that were selected at least 5 out of 10 times. It was compared with a multivariate logistic model that was built by forward feature selection. RESULTS: Local failure occurred in 12% of patients. Biologically effective dose (BED) at the isocenter (BED(ISO)) was the strongest predictor of TCP in the logistic model and also the most frequently selected input feature for the SVM. A bivariate logistic function of BED(ISO) and the pulmonary function indicator forced expiratory volume in 1 second (FEV1) yielded the best description of the data but resulted in a significantly smaller AUC than the final SVM classifier with the input features BED(ISO), age, baseline Karnofsky index, and FEV1 (0.696 ± 0.040 vs 0.789 ± 0.001, P<.03). The final SVM resulted in sensitivity and specificity of 67.0% ± 0.5% and 78.7% ± 0.3%, respectively. CONCLUSIONS: These results confirm that machine learning techniques like SVMs can be successfully applied to predict treatment outcome after SBRT. Improvements over traditional TCP modeling are expected through a nonlinear combination of multiple features, eventually helping in the task of personalized treatment planning.

Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer.

BACKGROUND AND PURPOSE: To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose dT) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1-8) and median single fraction dose was 12.5 Gy (2.9-33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60-100%). Assuming an α/ß-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs). RESULTS: There was strong evidence for a dose-response relationship in the total patient cohort (BFs>20), which was lacking in single-fraction SBRT (BFs<3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (dT) at 11 Gy (68% CI 8-14 Gy) or 22 Gy (14-42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the dT parameter (p=0.07, BF=2.1 and p=0.86, BF=0.8, respectively). Generally, isocentric doses resulted in much better dose-response relationships than PTV encompassing doses (BFs>20). CONCLUSION: Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism.

Safety and efficacy of stereotactic body radiotherapy for stage 1 non-small-cell lung cancer in routine clinical practice: a patterns-of-care and outcome analysis.

INTRODUCTION: To evaluate safety and efficacy of stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) in a patterns-of-care and patterns-of-outcome analysis. METHODS: The working group "Extracranial Stereotactic Radiotherapy" of the German Society for Radiation Oncology performed a retrospective multicenter analysis of practice and outcome after SBRT for stage I NSCLC. Sixteen German and Austrian centers with experience in pulmonary SBRT were asked to participate. RESULTS: Data of 582 patients treated at 13 institutions between 1998 and 2011 were collected; all institutions, except one, were academic hospitals. A time trend to more advanced radiotherapy technologies and escalated irradiation doses was observed, but patient characteristics (age, performance status, pulmonary function) remained stable over time. Interinstitutional variability was substantial in all treatment characteristics but not in patient characteristics. After an average follow-up of 21 months, 3-year freedom from local progression (FFLP) and overall survival (OS) were 79.6% and 47.1%, respectively. The biological effective dose was the most significant factor influencing FFLP and OS: after more than 106 Gy biological effective dose as planning target volume encompassing dose (N = 164), 3-year FFLP and OS were 92.5% and 62.2%, respectively. No evidence of a learning curve or improvement of results with larger SBRT experience and implementation of new radiotherapy technologies was observed. CONCLUSION: SBRT for stage I NSCLC was safe and effective in this multi-institutional, academic environment, despite considerable interinstitutional variability and time trends in SBRT practice. Radiotherapy dose was identified as a major treatment factor influencing local tumor control and OS.

External radioactive markers for PET data-driven respiratory gating in positron emission tomography.

PURPOSE: Respiratory gating is an established approach to overcoming respiration-induced image artefacts in PET. Of special interest in this respect are raw PET data-driven gating methods which do not require additional hardware to acquire respiratory signals during the scan. However, these methods rely heavily on the quality of the acquired PET data (statistical properties, data contrast, etc.). We therefore combined external radioactive markers with data-driven respiratory gating in PET/CT. The feasibility and accuracy of this approach was studied for [(18)F]FDG PET/CT imaging in patients with malignant liver and lung lesions. METHODS: PET data from 30 patients with abdominal or thoracic [(18)F]FDG-positive lesions (primary tumours or metastases) were included in this prospective study. The patients underwent a 10-min list-mode PET scan with a single bed position following a standard clinical whole-body [(18)F]FDG PET/CT scan. During this scan, one to three radioactive point sources (either (22)Na or (18)F, 50-100 kBq) in a dedicated holder were attached the patient's abdomen. The list mode data acquired were retrospectively analysed for respiratory signals using established data-driven gating approaches and additionally by tracking the motion of the point sources in sinogram space. Gated reconstructions were examined qualitatively, in terms of the amount of respiratory displacement and in respect of changes in local image intensity in the gated images. RESULTS: The presence of the external markers did not affect whole-body PET/CT image quality. Tracking of the markers led to characteristic respiratory curves in all patients. Applying these curves for gated reconstructions resulted in images in which motion was well resolved. Quantitatively, the performance of the external marker-based approach was similar to that of the best intrinsic data-driven methods. Overall, the gain in measured tumour uptake from the nongated to the gated images indicating successful removal of respiratory motion was correlated with the magnitude of the respiratory displacement of the respective tumour lesion, but not with lesion size. CONCLUSION: Respiratory information can be assessed from list-mode PET/CT through PET data-derived tracking of external radioactive markers. This information can be successfully applied to respiratory gating to reduce motion-related image blurring. In contrast to other previously described PET data-driven approaches, the external marker approach is independent of tumour uptake and thereby applicable even in patients with poor uptake and small tumours.

Retrospective, monocentric analysis of late effects after Total Body Irradiation (TBI) in adults.

PURPOSE: Total body irradiation (TBI) is a standard treatment modality within the multidisciplinary approach for allogeneous stem cell or bone marrow transplantation. However, surviving patients are at risk for developing a variety of late sequelae. This analysis aimed to retrospectively characterize late effects after TBI in adults treated in a single center. PATIENTS AND METHODS: Patients ≥ 18 years treated with fractionated TBI (4-12 Gy) between 1996 and 2008 were included in this study. Treatment data were collected retrospectively from the treating departments. Late effects were evaluated using the clinic charts and/or were obtained from the general practitioners using a standardized questionnaire. Analyses were performed by calculation of the cumulative incidences using the Kaplan-Meier method and the log rank test. RESULTS: A total of 308 patients ≥ 18 years were treated including a TBI of whom 78 patients were excluded from further analysis due to death within less than 1 year after TBI. Patients suffered from leukemia in most cases. Late toxicity follow-up was available in 120 patients (mean age 46.1 years; range, 18-70 years) after a mean follow-up of 23 months (range, 12-96 months). The cumulative incidences (CI) at 3 years were 28% for pulmonary event, 8% for pulmonary toxicity, 25% for kidney toxicity, 8% for cataract, 17% for bone toxicity, and 10% for secondary malignancy. The CI of bone toxicity was higher in female than in male patients (p = 0.019). CONCLUSION: Late effects after TBI in the context of allogeneous stem cell or bone marrow transplantation can frequently be observed. Regular follow-up examinations are advised for the early registration and treatment of adverse effects.

Dose-volume analysis of radiation nephropathy in children: preliminary report of the risk consortium.

PURPOSE: To characterize kidney function in children and adolescents who had undergone radiation treatment that included parts of the kidney. METHODS AND MATERIALS: Patients receiving radiotherapy during childhood or adolescence were prospectively registered in Germany's Registry for the Evaluation of Side Effects after Radiation in Childhood and Adolescence (RiSK). Detailed information was recorded regarding radiation doses at the organs at risk since 2001 all over Germany. Toxicity evaluation was performed according to standardized Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. RESULTS: Up to May 2009, 1086 patients from 62 centers were recruited, including 126 patients (median age, 10.2 years) who underwent radiotherapy to parts of the kidneys. Maximal late toxicity (median follow-up 28.5 months in 74 patients) was characterized as Grade 0 (n = 65), 1 (n = 7) or 2 (n = 2). All patients with late effects had received potentially nephrotoxic chemotherapy. A statistically significant difference between patients with and without Grade 1 toxicity, revealing higher exposed kidney volumes in patients with toxicity, was seen for the kidney volume exposed to 20 Gy (V20; p = 0.031) and 30 Gy (V30; p = 0.003). CONCLUSIONS: Preliminary data indicate that radiation-induced kidney function impairment is rare in current pediatric multimodal treatment approaches. In the future, RiSK will be able to provide further detailed data regarding dose-volume effect relationships of radiation-associated side effects in pediatric oncology patients.