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Purpose To show the feasibility of 3D-printed fixation masks for whole brain radiation therapy in a clinical setting and perform a first comparison to an established thermoplastic mask system. Methods Six patients were irradiated with whole brain radiotherapy using individually 3D-printed masks. Daily image guidance and position correction were performed prior to each irradiation fraction. The vectors of the daily position correction were compared to two collectives of patients, who were irradiated using the standard thermoplastic mask system (one cohort with head masks; one cohort with head and neck masks). Results The mean systematic errors in the experimental cohort ranged between 0.59 and 2.10 mm which is in a comparable range to the control groups (0.18 mm–0.68 mm and 0.34 mm–2.96 mm, respectively). The 3D-printed masks seem to be an alternative to the established thermoplastic mask systems. Nevertheless, further investigation will need to be performed. Conclusion The prevailing study showed a reliable and reproducible interfractional positioning accuracy using individually 3D-printed masks for whole brain irradiation in a clinical routine. Further investigations, especially concerning smaller target volumes or other areas of the body, need to be performed before using the system on a larger basis.

Highlights • Carbon-photon radiotherapy requires an elaborate and time-consuming planning process. • An established planning workflow includes independent optimization stages. • A bias-dose strategy may yield favorable cumulative dose distributions. • Follow-up studies will assess robustness and impact on tumor control., Background and purpose Combined photon intensity-modulated radiotherapy (IMRT) and sequential dose-escalated carbon ion beam therapy (IBT) is a technically advanced treatment option for head and neck malignancies. We proposed and evaluated an integrated planning strategy as opposed to an established and largely separated planning workflow. Materials and methods Ten patients with representative malignancies of the head and neck region underwent combined carbon-photon radiotherapy (RT) in our facilities. Clinical plans were created according to the separated workflow with independent optimization stages for both modalities. Experimental plans incorporated the existing carbon IBT dose distribution into the optimization stage of a step-and-shoot photon IMRT (bias dose planning). Results Cumulative dose distributions showed statistically significant differences between the two planning strategies and were predominantly in favor of the integrated approach. As such, target irradiation was generally maintained or even improved in a subset of metrics, while normal tissue sparing was widely enhanced; for instance, in the ipsilateral temporal lobe with median Dmean of −16% (p

Background: Patients with multiple brain metastases (BMs) from malignant melanoma have a poor prognosis. Recent developments in radiation techniques allow simultaneous integrated boost (SIB) concepts while sparing organs at risk. Data on conventional versus dose-escalated radiation approaches in multiple BMs from malignant melanoma are warranted. Methods: In this prospective, single-center, randomized two-armed study (trial ID: DRKS00005127), patients with multiple BMs from malignant melanoma were treated with either conventional whole-brain radiotherapy (WBRT) applying 30 Gy in 10 fractions (standard arm) or helical tomotherapy applying 30 Gy to the whole brain with an integrated boost to metastases of 50 Gy in 10 fractions and sparing of the hippocampus (HA-WBRT, experimental arm). The primary endpoint was treatment-related toxicity, while secondary endpoints were imaging response, intracerebral progression-free survival (PFS), overall survival (OS) and quality of life. Results: The study was stopped early due to slow patient recruitment. A total number of 7 patients were enrolled (standard arm n=3, experimental arm n=4), and were followed-up for a median time of 5 months between August 2013 and July 2017. All patients were treated according to protocol. The median OS, intracerebral PFS and follow-up time were 5 months, 2 months and 5 months, respectively. The local control in every individual BM was significantly longer in the experimental versus the standard arm. No patient developed radiation-related high-grade toxicities. Conclusion: HA-WBRT with SIB results in improved local control in the individual melanoma BMs without radiation-associated high-grade toxicities. Survival times were comparable to published data.

Background Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10-15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. Patients and methods Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45-59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0-2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival. Results Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3-34.0, 95% CI: 11.0-32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein

Background To date, only limited magnetic resonance imaging (MRI) data are available concerning tumor regression during neoadjuvant radiochemotherapy (RCT) of rectal cancer patients, which is a prerequisite for adaptive radiotherapy (RT) concepts. This exploratory study prospectively evaluated daily fractional MRI during neoadjuvant treatment to analyze the predictive value of MR biomarkers for treatment response. Methods Locally advanced rectal cancer patients were examined with daily MRI during neoadjuvant RCT. Contouring of the tumor volume was performed for each MRI scan by using T2- and diffusion-weighted-imaging (DWI)-sequences. The daily apparent-diffusion coefficient (ADC) was calculated. Volumetric and functional tumor changes during RCT were analyzed and correlated with the pathological response after surgical resection. Results In total, 171 MRI scans of eight patients were analyzed regarding anatomical and functional dynamics during RCT. Pathological complete response (pCR) could be achieved in four patients, and four patients had a pathological partial response (pPR) following neoadjuvant treatment. T2- and DWI-based volumetry proved to be statistically significant in terms of therapeutic response, and volumetric thresholds at week two and week four during RCT were defined for the prediction of pCR. In contrast, the average tumor ADC values widely overlapped between both response groups during RCT and appeared inadequate to predict treatment response in our patient cohort. Conclusion This prospective exploratory study supports the hypothesis that MRI may be able to predict pCR of rectal cancers early during neoadjuvant RCT. Our data therefore provide a useful template to tailor future MR-guided adaptive treatment concepts.

Background/aim Carbon ion radiotherapy (CIRT) offers high conformality and ability to dose-escalate skull base chordomas, with promising clinical data. However, it is an imperative measure to economically justify the use of such high-priced new technologies. Herein, we investigated the cost-effectiveness of CIRT compared to photon radiotherapy (PRT) using 10-year outcome data extrapolated to a 34-year time frame. Materials and methods Data regarding costs of PRT, as well as 10-year outcomes were obtained from published sources. Corresponding figures for CIRT were acquired from institutional and published sources. Adjustment was made in order to compare both cost figures, including elimination of additional financing and follow-up, so that only direct costs of treatment and the cost of progression were compared between both modalities. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in cost between both modalities divided by the difference in 34-year quality-adjusted life-year (QALY) outcomes. The annual gross domestic product per capita cost-effectiveness threshold definition (as recommended by the WHO) was employed. Results The total cost of a complete course of CIRT (20-22 fractions) was €31,538.21. After removal of financing and follow-up costs, the adjusted direct cost of CIRT utilized for comparison was €18,957.78. In a previous publication, the cost of PRT was €4,700.00. ICERs were based upon these direct cost figures and the average of reported 10-year progression-free survival (PFS) values with PRT (41.1%) and CIRT (54%), as well as gained PFS years (10.66 years CIRT, 8.58 years PRT). QALYs were 6.65 for photon RT and 8.26 for CIRT, a difference of 1.61 discounted lifetime QALYs for patients treated with CIRT. The overall ICER was €8,855.76/QALY. If the cost of progression/recurrence treated with imatinib were included into the calculation, the total ICER was €170.61/QALY. Conclusion CIRT is a highly cost-effective option to treat chordoma.

The present work aimed to analyze the feasibility of a shuttle-based MRI-guided radiation therapy (MRgRT) in the treatment of pelvic malignancies. 20 patients with pelvic malignancies were included in this prospective feasibility analysis. Patients underwent daily MRI in treatment position prior to radiotherapy at the German Cancer Research Center. Positional inaccuracies, time and patient compliance were assessed for the application of off-line MRgRT. In 78% of applied radiation fractions, MR imaging for position verification could be performed without problems. Additionally, treatment-related side effects and reduced patient compliance were only responsible for omission of MRI in 9% of radiation fractions. The study workflow took a median time of 61 min (range 47–99 min); duration for radiotherapy alone was 13 min (range 7–26 min). Patient positioning, MR imaging and CT imaging including patient repositioning and the shuttle transfer required median times of 10 min (range 7–14 min), 26 min (range 15–60 min), 5 min (range 3–8 min) and 8 min (range 2–36 min), respectively. To assess feasibility of shuttle-based MRgRT, the reference point coordinates for the x, y and z axis were determined for the MR images and CT obtained prior to the first treatment fraction and correlated with the coordinates of the planning CT. In our dataset, the median positional difference between MR imaging and CT-based imaging based on fiducial matching between MR and CT imaging was equal to or less than 2 mm in all spatial directions. The limited space in the MR scanner influenced patient selection, as the bore of the scanner had to accommodate the immobilization device and the constructed stereotactic frame. Therefore, obese, extremely muscular or very tall patients could not be included in this trial in addition to patients for whom exposure to MRI was generally judged inappropriate. This trial demonstrated for the first time the feasibility and patient compliance of a shuttle-based off-line approach to MRgRT of pelvic malignancies.

// Matthias Felix Haefner 1, 2, * , Frederik Lars Giesel 3, * , Matthias Mattke 1, 2 , Daniel Rath 3 , Moritz Wade 3, 4 , Jacob Kuypers 3, 4 , Alan Preuss 3, 4 , Hans-Ulrich Kauczor 5 , Jens-Peter Schenk 5 , Juergen Debus 1, 2 , Florian Sterzing 2, 6 and Roland Unterhinninghofen 4, 7 1 Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany 2 National Center for Radiation Research in Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), 69120 Heidelberg, Germany 3 Department of Nuclear Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany 4 Institute of Antropomatics and Robotics, Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany 5 Department of Diagnostic and Interventional Radiology, Heidelberg University Hospital, 69120 Heidelberg, Germany 6 Department of Radiation Oncology Kempten, 87439 Kempten, Germany 7 Institute of Robotics and Mechatronics, German Aerospace Center, 82234 Oberpfaffenhofen-Wesling, Germany * These authors contributed equally to the manuscript and share the first authorship Correspondence to: Matthias Felix Haefner, email: matthias.haefner@med.uni-heidelberg.de Keywords: immobilization; radiotherapy; 3D-printing; setup accuracy; head mask Received: October 07, 2017 Accepted: January 02, 2018 Published: January 08, 2018 ABSTRACT We developed a new approach to produce individual immobilization devices for the head based on MRI data and 3D printing technologies. The purpose of this study was to determine positioning accuracy with healthy volunteers. 3D MRI data of the head were acquired for 8 volunteers. In-house developed software processed the image data to generate a surface mesh model of the immobilization mask. After adding an interface for the couch, the fixation setup was materialized using a 3D printer with acrylonitrile butadiene styrene (ABS). Repeated MRI datasets (n=10) were acquired for all volunteers wearing their masks thus simulating a setup for multiple fractions. Using automatic image-to-image registration, displacements of the head were calculated relative to the first dataset (6 degrees of freedom). The production process has been described in detail. The absolute lateral (x), vertical (y) and longitudinal (z) translations ranged between −0.7 and 0.5 mm, −1.8 and 1.4 mm, and −1.6 and 2.4 mm, respectively. The absolute rotations for pitch (x), yaw (y) and roll (z) ranged between −0.9 and 0.8°, −0.5 and 1.1°, and −0.6 and 0.8°, respectively. The mean 3D displacement was 0.9 mm with a standard deviation (SD) of the systematic and random error of 0.2 mm and 0.5 mm, respectively. In conclusion, an almost entirely automated production process of 3D printed immobilization masks for the head derived from MRI data was established. A high level of setup accuracy was demonstrated in a volunteer cohort. Future research will have to focus on workflow optimization and clinical evaluation.

Purpose To assess treatment tolerance and toxicity rates of consolidative whole-abdominal radiation therapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high-risk patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III) using intensity modulated radiation therapy. Methods and Materials The OVAR-IMRT-02 study is a multicenter, single-arm, phase 2 trial. Twenty patients with optimally debulked ovarian cancer (International Federation of Gynecology and Obstetrics stage III) with complete remission after chemotherapy were treated with intensity modulated WART as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy was applied to the entire peritoneal cavity. The primary endpoint was treatment tolerability, defined as lack of any Common Terminology Criteria for Adverse Events grade 4 toxicity within 10 weeks after start of treatment; secondary objectives were acute and chronic toxicity, quality of life, rates of therapy disruption and abortion, and progression-free and overall survival. Results Intensity modulated WART resulted in excellent coverage of the whole peritoneal cavity, with effective sparing of all organs at risk. The primary analysis included all 20 enrolled patients, of whom 19 did not experience Common Terminology Criteria for Adverse Events grade 4 toxicity. Only 1 patient experienced acute grade 4 hematologic toxicity. Thus, the tolerability rate of intensity modulated WART was significantly higher than 70%. No gastrointestinal acute toxicities higher than grade 2 have been observed. During WART, mean global health status decreased by 18.1 points (95% confidence interval 7.1, 29.0). Six weeks after WART, global health status had already increased, with a mean score difference of 4.6 (95% confidence interval −11.1, 20.4) compared with baseline. Similar characteristics were observed for all function scale scores. Conclusion Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute toxicity and a treatment tolerability rate significantly higher than 70%. Together with our knowledge about clinical feasibility, meaning excellent coverage of the planning target volume and effective sparing of organs at risk, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.

Background Malignant pleural mesothelioma (MPM) is a rare and aggressive disease that poses a treatment challenge in spite of recent technical developments. The aim of this retrospective analysis is to assess the feasibility of administering intensity-modulated radiotherapy (IMRT) to the pleural cavity using helical tomotherapy in patients who had undergone pleurectomy/decortication (P/D) and also the resulting toxicity levels. Patients and methods Ten patients who had MPM and had undergone P/D were treated with pleural cavity irradiation that included a median dose of 52.2 Gy using helical tomotherapy. The median age of the patients was 53 years (31–74). In addition to clinical and diagnostic findings from regular follow-up examinations, we evaluated the dose distribution for other organs at risk to assess treatment in relation to toxicity, with special regard for the underlying intact lung. Results The mean lung dose on the treatment site was 32.8 Gy (±6.8). The V20 Gy was 71.7% (±17.2). No treatment-related toxicity that exceeded grade III according to common toxicity criteria (CTC) was observed. Median progression-free survival (PFS) was 13 months with a median overall survival (OAS) of 19 months. Conclusion The findings of this analysis provide data indicating that sparing the underlying lung in patients with MPM after P/D is not only feasible with helical tomotherapy, but that this treatment also causes reasonably few side effects.

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). 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. 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). 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.

Xerostomia is a common side effect of radiotherapy resulting from excessive irradiation of salivary glands. Typically, xerostomia is modeled by the mean dose-response characteristic of parotid glands and prevented by mean dose constraints to either contralateral or both parotid glands. The aim of this study was to investigate whether normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands are suitable for the prediction of xerostomia in a highly conformal low-dose regime of modern intensity-modulated radiotherapy (IMRT) techniques.We present a retrospective analysis of 153 head and neck cancer patients treated with radiotherapy. The Lyman Kutcher Burman (LKB) model was used to evaluate predictive power of the parotid gland mean dose with respect to xerostomia at 6 and 12 months after the treatment. The predictive performance of the model was evaluated by receiver operating characteristic (ROC) curves and precision-recall (PR) curves.Average mean doses to ipsilateral and contralateral parotid glands were 25.4 Gy and 18.7 Gy, respectively. QUANTEC constraints were met in 74% of patients. Mild to severe (G1+) xerostomia prevalence at both 6 and 12 months was 67%. Moderate to severe (G2+) xerostomia prevalence at 6 and 12 months was 20% and 15%, respectively. G1 + xerostomia was predicted reasonably well with area under the ROC curve ranging from 0.69 to 0.76. The LKB model failed to provide reliable G2 + xerostomia predictions at both time points.Reduction of the mean dose to parotid glands below QUANTEC guidelines resulted in low G2 + xerostomia rates. In this dose domain, the mean dose models predicted G1 + xerostomia fairly well, however, failed to recognize patients at risk of G2 + xerostomia. There is a need for the development of more flexible models able to capture complexity of dose response in this dose regime.

Purpose Leptomeningeal metastasis (LM) is an increasingly common complication of late-stage systemic cancer, for which there is no standard treatment. We analyzed outcome and toxicity in patients with LM undergoing craniospinal irradiation via helical tomotherapy (HT-CSI) at our institution. Patients and methods The charts of 15 patients diagnosed with LM and undergoing HT-CSI between 2006 and 2014 were retrospectively assessed. Main neoplasms included breast cancer, lung cancer, and lymphoma. All patients presented with cranial neuropathy due to LM. Follow-up was performed regularly. Survival analysis was performed by the Kaplan–Meier method, and prognostic factors were tested using the COX-regression model. Results Median survival by cancer type was 6 (breast cancer), 1 (lung cancer), and 2 months (lymphoma), respectively. Median overall survival and relapse-free survival were calculated to be between 2 and 3 months. Six- and 12-month survival was 30% (95% CI 0.08–0.5) and 20% (95% CI 0.05–0.4), respectively. Symptom palliation occurred in 53% of patients in general, but in 67% of breast cancer patients, in particular. Patients with lung cancer experienced no improvement. Most common acute treatment-related toxicity at different levels were hematological toxicity, multiple cranial neuropathy, fatigue, infections, nausea, and headache. Conclusion HT-CSI can help meet the challenge of treating patients with LM, especially because it can palliate symptoms and improve neurological functions. One-year survival remains as disappointing as before.

Denise Bernhardt,1–3 Florian Sterzing,1–4,5 Sebastian Adeberg,1–4 Klaus Herfarth,1–3 Sonja Katayama,1,3 Robert Foerster,1,3,6Juliane Hoerner-Rieber,1,3 Laila König,1,3 Juergen Debus,1–4 Stefan Rieken1,3 1Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany; 2Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; 3Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany; 4Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5Department of Radiation Oncology, Klinikum Kempten, Kempten, Germany; 6Department of Radiation Oncology, University Hospital of Zürich, Zürich, Switzerland Background: Treatment of patients with pelvic adenoid cystic carcinoma (ACC) remains a challenge owing to the rarity of the disease, the lack of data, and the relative radioresistance of these tumors.Case reports: This case series presents the results of three patients with recurrent or inoperable pelvic ACC treated with intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost. Patients received C12 therapy at a dose of 3Gray equivalents (GyE) (relative biological effectiveness [RBE]) per fraction up to 24GyE RBE, followed by 50GyE of photon IMRT in 25 fractions.Conclusion: IMRT plus C12 ion boost as a definitive or adjuvant treatment for pelvic ACCs seems to be a promising therapeutic option. No unexpected toxicity was detected and the observed toxicity remained consistently low. The initial treatment response is promising and similar to that experienced for head and neck ACCs. Keywords: ACC of Bartholin’s gland, adenoid cystic carcinoma, ACC of the prostate, ion therapy, IMRT, tomotherapy, particle irradiation, carbon ion

Purpose Radiotherapy is the main therapeutic approach besides surgery of localized prostate cancer. It relies on risk stratification and exact staging. This report analyses the potential of [68Ga]Glu-urea-Lys(Ahx)-HBED-CC (68Ga-PSMA-11), a new positron emission tomography (PET) tracer targeting prostate-specific membrane antigen (PSMA) for prostate cancer staging and individualized radiotherapy planning. Methods A cohort of 57 patients with prostate cancer scanned with 68Ga-PSMA-11 PET/CT for radiotherapy planning was retrospectively reviewed; 15 patients were at initial diagnosis and 42 patients at time of biochemical recurrence. Staging results of conventional imaging, including bone scintigraphy, CT or MRI, were compared with 68Ga-PSMA ligand PET/CT results and the influence on radiotherapeutic management was quantified. Results 68Ga-PSMA ligand PET/CT had a dramatic impact on radiotherapy application in the presented cohort. In 50.8 % of the cases therapy was changed. Conclusion The presented imaging technique of 68Ga-PSMA PET/CT could be a key technology for individualized radiotherapy management in prostate cancer.

Purpose: Fluoroscopic imaging is a well-suited technique for online visualization of tumor motion in the thoracic region. Template-based approaches for tumor tracking in such images are commonly used. However, overlapping of different structures, mainly bones, can lead to limited visibility of the projected tumor shape, which in turn can negatively affect the performance of the tracking method. In this study, a method based on multiple-template matching was developed, providing fast and robust detection of tumor motion even under the influence of occurring tumor overlaps. Methods: A cohort of 14 patients with varying tumor sizes and locations was investigated. Image data from eight of these patients were used for evaluation. Based on the requirement of tumor visibility, the remaining datasets did not qualify for tracking. Generation of multiple templates was improved by implementation of an algorithm for automated selection of reference images containing the most characteristic tumor appearances. Various measures were taken to ensure real-time capability of the algorithm. A prematching step was introduced in order to reduce dispensable comparison operations by selecting the most appropriate template. Subsequent matching was further optimized by using prior knowledge about likely tumor motion to effectively limit necessary matching tasks. Results: Tracking accuracy of the developed multiple-template method was compared with that of single-template. Mean errors of the multiple-template approach were 0.6 ± 0.6 mm in left–right and 0.9 ± 0.9 mm in superior–inferior direction in the isocenter plane. The single-template approach achieved mean errors of 0.7 ± 0.7 mm in left–right and 1.5 ± 1.3 mm in superior–inferior direction. These results derive from evaluation against manual tumor tracking performed by four expert observers. Computational times needed for tumor detection in a single fluoroscopic frame ranged between 1 and 29 ms depending on the tumor size and motion amplitude. Conclusions: This study shows that in case of tumor overlapping with dense structures, multiple-template tracking provides more accurate results than a single-template approach. The developed algorithm shows promising results in terms of suitability for real-time application and robustness against frequently changing overlapping.

TomoEDGE is an advanced delivery form of tomotherapy which uses a dynamic secondary collimator. This plan comparison study describes the new features, their clinical applicability, and their effect on plan quality and treatment speed. For the first 45 patients worldwide that were scheduled for a treatment with TomoEdge, at least two plans were created: one with the previous “standard”mode with static jaws and 2.5 cm field width (Reg 2.5) and one with TomoEdge technique and 5 cm field width (Edge 5). If, after analysis in terms of beam on time, integral dose, dose conformity, and organ at risk sparing the treating physician decided that the Edge 5 plan was not suitable for clinical treatment, a plan with TomoEdge and 2.5 cm field width was created (Edge 2.5) and used for the treatment. Among the 45 cases, 30 were suitable for Edge 5 treatment, including treatments of the head and neck, rectal cancer, anal cancer, malignancies of the chest, breast cancer, and palliative treatments. In these cases, the use of a 5 cm field width reduced beam on time by more than 30% without compromising plan quality. The 5 cm beam could not be clinically applied to treatments of the pelvic lymph nodes for prostate cancer and to head and neck irradiations with extensive involvement of the skull, as dose to critical organs at risk such as bladder (average dose 28 Gy vs. 29 Gy, Reg 2.5 vs. Edge 5), small bowel (29% vs. 31%, Reg 2.5 vs. Edge 5) and brain (average dose partial brain 19 Gy vs. 21 Gy, Reg 2.5 vs. Edge 5) increased to a clinically relevant, yet not statistically significant, amount. TomoEdge is an advantageous extension of the tomotherapy technique that can speed up treatments and thus increase patient comfort and safety in the majority of clinical settings. PACS numbers: 87.55.de, 87.55ne

Background Salvage surgery as an additional therapy option is currently discussed for an increasing number of patients with esophageal cancer after definitive radio(chemo)therapy after tumor progression, recurrence or on explicit request of the patient. Objectives The objective of this study was an analysis of the surgical option of salvage esophagectomy after definitive radiation in patients with esophageal cancer. Additionally the current literature on this topic was evaluated. Material and methods A total of 92 patients with esophageal cancer from a prospective database were included in this study who underwent esophagectomy either after neoadjuvant radio(chemo)therapy ( 50 Gy) between 2002 and 2012. The analysis was performed retrospectively. Results The median survival of the two groups of patients was not significantly different after initial diagnosis with 24.2 months (95 % CI 0.0-51.93) for patients undergoing definitive radio(chemo)therapy and 30.7 months (95 % CI 9.3-52.2) for patients after neoadjuvant therapy (p = 0.96). Both patient groups showed no differences in pretherapeutic characteristics and response to radio(chemo)therapy. Postoperative complications and perioperative mortality were not different. Discussion Salvage esophagectomy is now an additional treatment option after definitive radio(chemo)therapy in patients with esophageal cancer. In preselected patients with tumor recurrence, progression or with a strong wish for surgical therapy, salvage surgery should be discussed in interdisciplinary tumor boards after exclusion of distant metastases.

Purpose Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.

In radiotherapy, in vivo measurement of dose distribution within patients' lymphocytes can be performed by detecting gamma-H2AX foci in lymphocyte nuclei. This method can help in determining the whole-body dose. Options for risk estimations for toxicities in normal tissue and for the incidence of secondary malignancy are still under debate. In this investigation, helical tomotherapy (TOMO) is compared with step-and-shoot IMRT (SSIMRT) of the prostate gland by measuring the dose distribution within patients' lymphocytes. In this prospective study, blood was taken from 20 patients before and 10 min after their first irradiation fraction for each technique. The isolated leukocytes were fixed 2 h after radiation. DNA double-stranded breaks in lymphocyte nuclei were stained immunocytochemically using anti-gamma-H2AX antibodies. Gamma-H2AX foci distribution in lymphocytes was determined for each patient. Using a calibration line, dose distributions in patients' lymphocytes were determined by studying the gamma-H2AX foci distribution, and these data were used to generate a cumulative dose–lymphocyte histogram (DLH). Measured in vivo (DLH), significantly fewer lymphocytes indicated low-dose exposure (

Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009. Local control and survival were analyzed. Chronic adverse effects for 154 patients without local relapse were evaluated according to the NCI-CTCAE version 4.0 classification, with a median follow-up of 48 months. We found a 5-year disease-free survival (DFS) and overall survival (OS) of 71%. The 5-year estimated local control (LC) rate was 94%. A positive resection margin was found in 4% of the patients and was significantly correlated with decreased DFS, OS and LC. Chronic adverse effects were reported by 58% of the patients, of which 10% were Grade 3 toxicities. The most frequent Grade 2 toxicity was stool incontinence (13%). Sexual dysfunction was found in 36% of the patients (31% Grade 1 or 2, and only 5% Grade 3). SCPRT combined with TME produced excellent LC rates together with a low rate of high-grade chronic adverse effects.

BACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases. PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases. RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all pBACKGROUND: Radical local treatment of pulmonary metastases is practiced with increasing frequency due to acknowledgment and better understanding of oligo-metastatic disease. This study aimed to develop a nomogram predicting overall survival (OS) after stereotactic body radiotherapy (SBRT) for pulmonary metastases.PATIENTS AND METHODS: A multi-institutional database of 670 patients treated with SBRT for pulmonary metastases was used as training cohort. Cox regression analysis with bidirectional variable elimination was performed to identify factors to be included into the nomogram model to predict 2-year OS. The calibration rate of the nomogram was assessed by plotting the actual Kaplan-Meier 2-year OS against the nomogram predicted survival. The nomogram was externally validated using two separate monocentric databases of 145 and 92 patients treated with SBRT for pulmonary metastases.RESULTS: The median follow up of the trainings cohort was 14.3months, the 2-year and 5-year OS was 52.6% and 23.7%, respectively. Karnofsky performance index, type of the primary tumor, control of the primary tumor, maximum diameter of the largest treated metastasis and number of metastases (1 versus >1) were significant prognostic factors in the Cox model (all pCONCLUSIONS: A nomogram for prediction of OS after SBRT for pulmonary metastases was generated and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.KEY MESSAGE: A nomogram for prediction of overall survival after stereotactic body radiotherapy (SBRT) for pulmonary metastases was developed and externally validated. This tool might be helpful for interdisciplinary discussion and evaluation of local and systemic treatment options in the oligo-metastatic setting.

Purpose To investigate the extent of MR image distortions in the pelvis caused by susceptibility-induced field inhomogeneities in MR images in the context of a study on MR-guided radiotherapy. Methods Using a high-bandwidth double-echo gradient echo sequence, field maps and distortion maps of the pelvis were calculated and evaluated for 219 exams (92 of female and 127 of male patients) to investigate patient-related image distortions caused by susceptibility differences in an ongoing study on MR-guided radiotherapy. The evaluation of distortions in the regions "rectum", "prostate", "cervix", and in a reference region in the gluteus maximus was based on masks drawn by two readers. Results Distortions in the prostate and cervix were smaller than 0.03 px (0.1 mm) for 99% of voxels, and reached a maximum value of 0.09 px (0.3 mm). In the reference region, maximum distortions were smaller than in the prostate and cervix. Conclusions Using a geometric uncertainty of 0.2 px (0.6 mm) in margin definition for organs that are close to the rectum like the prostate and the cervix would be a cautious choice to account for susceptibility-induced distortions that can arise during MR-based treatment guidance for the imaging setting used in this study. Since distortions are inversely proportional to the readout bandwidth of the sequence, safety margins need to be adapted adequately. Additional sources of image distortions like gradient nonlinearities are not included in our margin recommendations and should be considered separately.

Randomized trials examining neoadjuvant chemoradiotherapy followed by surgical resection (nCRT-S) and definitive CRT (dCRT) for esophageal cancer (EC) patients are hampered by use of nonstandard treatment paradigms. Outcomes of nCRT-S versus dCRT in a more common patient population are lacking. We investigated local control and survival, evaluated clinical factors associated with endpoints, and assessed patterns of failure between these cohorts. We retrospectively analyzed 130 patients with locally advanced EC receiving either dCRT or nCRT-S at our institution from 2000–2012. Inclusion criteria were curatively treated nonmetastatic EC, Karnofsky performance status ≥70%, and receipt of concomitant CRT. Patients were excluded if receiving

Purpose: The radiation therapy treatment outcome of human papillomavirus–negative anal carcinoma may be improved by the biological effectiveness of carbon ions. However, abdominal tissue motion can compromise the precision of carbon ion therapy. This work aims to evaluate the dosimetric feasibility of carbon ion boost (CIB) therapy for anal carcinoma. Materials and Methods: An algorithm to generate computed tomographies based on daily magnetic resonance imaging data and deformable image registration was developed. By means of this algorithm, fractional computed tomography data for 54 treatment fractions for 3 different patients with anal carcinoma were derived. The dose for a sequential CIB (CIBseq) treatment plan was recalculated on the fractional computed tomography data and accumulated over the number of fractions. The resulting dose distributions were compared to standard intensity-modulated radiation therapy treatment with an integrated photon boost. Results: For the investigated patient cases, similar dosimetric results for CIBseq treatment and for intensity-modulated radiation therapy with an integrated photon boost were found. For CIBseq treatment, bladder-filling variation had the strongest influence on the dose distribution. However, the detrimental effects on the mean target dose remained below 1 Gy (RBE) as compared to photon therapy. Conclusion: This study shows the dosimetric feasibility of CIB therapy for anal carcinoma for the first time and gives reason for clinical exploitation of the enhanced biological effect of carbon ions for patients with human papillomavirus–negative anal cancer.