TY - JOUR A1 - Tamihardja, Jörg A1 - Lawrenz, Ingulf A1 - Lutyj, Paul A1 - Weick, Stefan A1 - Guckenberger, Matthias A1 - Polat, Bülent A1 - Flentje, Michael T1 - Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer JF - Strahlentherapie und Onkologie N2 - Purpose Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. Methods From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (D\(_{Mean}\)). Combined treatment was delivered as 46 Gy (D\(_{Mean}\)) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D\(_{90\%}\)). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). Results The estimated 10-year bRFS was 82.0% vs. 76.4% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9% vs. 87.0% (p = 0.195) and the 10-year OS was 65.7% vs. 68.9% (p = 0.303), respectively. Cumulative 5‑year late GU ≥ grade 2 toxicities were seen in 23.6% vs. 19.2% (p = 0.086) and 5‑year late GI ≥ grade 2 toxicities in 11.1% vs. 5.0% of the patients (p = 0.002); cumulative 5‑year late grade 3 GU toxicity occurred in 4.2% vs. 3.6% (p = 0.401) and GI toxicity in 1.0% vs. 0.3% (p = 0.249), respectively. Conclusion Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity. KW - long-term outcome KW - dose escalation KW - high-dose-rate brachytherapy boost KW - propensity score matching KW - toxicity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325055 VL - 198 IS - 8 ER - TY - JOUR A1 - Tamihardja, Jörg A1 - Schortmann, Max A1 - Lawrenz, Ingulf A1 - Weick, Stefan A1 - Bratengeier, Klaus A1 - Flentje, Michael A1 - Guckenberger, Matthias A1 - Polat, Bülent T1 - Moderately hypofractionated radiotherapy for localized prostate cancer: updated long-term outcome and toxicity analysis JF - Strahlentherapie und Onkologie N2 - Purpose Evaluation of long-term outcome and toxicity of moderately hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost treatment planning and cone beam CT-based image guidance for localized prostate cancer. Methods Between 2005 and 2015, 346 consecutive patients with localized prostate cancer received primary radiotherapy using cone beam CT-based image-guided intensity-modulated radiotherapy (IG-IMRT) and volumetric modulated arc therapy (IG-VMAT) with a simultaneous integrated boost (SIB). Total doses of 73.9 Gy (n = 44) and 76.2 Gy (n = 302) to the high-dose PTV were delivered in 32 and 33 fractions, respectively. The low-dose PTV received a dose (D95) of 60.06 Gy in single doses of 1.82 Gy. The pelvic lymph nodes were treated in 91 high-risk patients to 45.5 Gy (D95). Results Median follow-up was 61.8 months. The 5‑year biochemical relapse-free survival (bRFS) was 85.4% for all patients and 93.3, 87.4, and 79.4% for low-, intermediate-, and high-risk disease, respectively. The 5‑year prostate cancer-specific survival (PSS) was 94.8% for all patients and 98.7, 98.9, 89.3% for low-, intermediate-, and high-risk disease, respectively. The 5‑year and 10-year overall survival rates were 83.8 and 66.3% and the 5‑year and 10-year freedom from distant metastasis rates were 92.2 and 88.0%, respectively. Cumulative 5‑year late GU toxicity and late GI toxicity grade ≥2 was observed in 26.3 and 12.1% of the patients, respectively. Cumulative 5‑year late grade 3 GU/GI toxicity occurred in 4.0/1.2%. Conclusion Moderately hypofractionated radiotherapy using SIB treatment planning and cone beam CT image guidance resulted in high biochemical control and survival with low rates of late toxicity. KW - simultaneous integrated boost KW - cone beam CT KW - hypofractionation KW - intensity-modulated radiation therapy KW - image-guided radiation therapy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232509 SN - 0179-7158 VL - 197 ER - TY - JOUR A1 - Colvill, Emma A1 - Booth, Jeremy A1 - Nill, Simeon A1 - Fast, Martin A1 - Bedford, James A1 - Oelfke, Uwe A1 - Nakamura, Mitsuhiro A1 - Poulsen, Per A1 - Worm, Esben A1 - Hansen, Rune A1 - Ravkilde, Thomas A1 - Rydhög, Jonas Scherman A1 - Pommer, Tobias A1 - af Rosenschold, Per Munck A1 - Lang, Stephanie A1 - Guckenberger, Matthias A1 - Groh, Christian A1 - Herrmann, Christian A1 - Verellen, Dirk A1 - Poels, Kenneth A1 - Wang, Lei A1 - Hadsell, Michael A1 - Sothmann, Thilo A1 - Blanck, Oliver A1 - Keall, Paul T1 - A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: a multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking JF - Radiotherapy and Oncology N2 - Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for gamma-tests recorded. Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm gamma-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm gamma-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm gamma-fail rate of <3% for all systems with adaptation for lung and prostate. Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods. KW - Robotic tracking KW - Gimbaled tracking KW - MLC tracking KW - Couch tracking KW - Organ motion Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189605 VL - 119 IS - 1 ER - TY - JOUR A1 - Hardcastle, Nicholas A1 - Tomé, Wolfgang A. A1 - Cannon, Donald M. A1 - Brouwer, Charlotte L. A1 - Wittendorp, Paul W. H. A1 - Dogan, Nesrin A1 - Guckenberger, Matthias A1 - Allaire, Stéphane A1 - Mallya, Yogish A1 - Kumar, Prashant A1 - Oechsner, Markus A1 - Richter, Anne A1 - Song, Shiyu A1 - Myers, Michael A1 - Polat, Bülent A1 - Bzdusek, Karl T1 - A multi-institution evaluation of deformable image registration algorithms for automatic organ delineation in adaptive head and neck radiotherapy JF - Radiation Oncology N2 - Background: Adaptive Radiotherapy aims to identify anatomical deviations during a radiotherapy course and modify the treatment plan to maintain treatment objectives. This requires regions of interest (ROIs) to be defined using the most recent imaging data. This study investigates the clinical utility of using deformable image registration (DIR) to automatically propagate ROIs. Methods: Target (GTV) and organ-at-risk (OAR) ROIs were non-rigidly propagated from a planning CT scan to a per-treatment CT scan for 22 patients. Propagated ROIs were quantitatively compared with expert physician-drawn ROIs on the per-treatment scan using Dice scores and mean slicewise Hausdorff distances, and center of mass distances for GTVs. The propagated ROIs were qualitatively examined by experts and scored based on their clinical utility. Results: Good agreement between the DIR-propagated ROIs and expert-drawn ROIs was observed based on the metrics used. 94% of all ROIs generated using DIR were scored as being clinically useful, requiring minimal or no edits. However, 27% (12/44) of the GTVs required major edits. Conclusion: DIR was successfully used on 22 patients to propagate target and OAR structures for ART with good anatomical agreement for OARs. It is recommended that propagated target structures be thoroughly reviewed by the treating physician. KW - intensity-modulated radiotherapy KW - megavoltage computed-tomography KW - cancer KW - variability KW - strategies KW - risk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134756 VL - 7 IS - 90 ER - TY - JOUR A1 - Toussaint, André A1 - Richter, Anne A1 - Mantel, Frederick A1 - Flickinger, John C. A1 - Grills, Inga Siiner A1 - Tyagi, Neelam A1 - Sahgal, Arjun A1 - Letourneau, Daniel A1 - Sheehan, Jason P. A1 - Schlesinger, David J. A1 - Gerszten, Peter Carlos A1 - Guckenberger, Matthias T1 - Variability in spine radiosurgery treatment planning – results of an international multi-institutional study JF - Radiation Oncology N2 - Background The aim of this study was to quantify the variability in spinal radiosurgery (SRS) planning practices between five international institutions, all member of the Elekta Spine Radiosurgery Research Consortium. Methods Four institutions provided one representative patient case each consisting of the medical history, CT and MR imaging. A step-wise planning approach was used where, after each planning step a consensus was generated that formed the basis for the next planning step. This allowed independent analysis of all planning steps of CT-MR image registration, GTV definition, CTV definition, PTV definition and SRS treatment planning. In addition, each institution generated one additional SRS plan for each case based on intra-institutional image registration and contouring, independent of consensus results. Results Averaged over the four cases, image registration variability ranged between translational 1.1 mm and 2.4 mm and rotational 1.1° and 2.0° in all three directions. GTV delineation variability was 1.5 mm in axial and 1.6 mm in longitudinal direction averaged for the four cases. CTV delineation variability was 0.8 mm in axial and 1.2 mm in longitudinal direction. CTV-to-PTV margins ranged between 0 mm and 2 mm according to institutional protocol. Delineation variability was 1 mm in axial directions for the spinal cord. Average PTV coverage for a single fraction18 Gy prescription was 87 ± 5 %; Dmin to the PTV was 7.5 ± 1.8 Gy averaged over all cases and institutions. Average Dmax to the PRV_SC (spinal cord + 1 mm) was 10.5 ± 1.6 Gy and the average Paddick conformity index was 0.69 ± 0.06. Conclusions Results of this study reflect the variability in current practice of spine radiosurgery in large and highly experienced academic centers. Despite close methodical agreement in the daily workflow, clinically significant variability in all steps of the treatment planning process was demonstrated. This may translate into differences in patient clinical outcome and highlights the need for consensus and established delineation and planning criteria. KW - planning variability KW - spine radiosurgery KW - vertebral metastases KW - delineation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146687 VL - 11 IS - 57 ER - TY - JOUR A1 - Guckenberger, Matthias A1 - Sweeney, Reinhart A. A1 - Flickinger, John C. A1 - Gerszten, Peter C. A1 - Kersh, Ronald A1 - Sheehan, Jason A1 - Sahgal, Arjun T1 - Clinical practice of image-guided spine radiosurgery - results from an international research consortium JF - Radiation Oncology N2 - Background Spinal radiosurgery is a quickly evolving technique in the radiotherapy and neurosurgical communities. However, the methods of spine radiosurgery have not been standardized. This article describes the results of a survey about the methods of spine radiosurgery at five international institutions. Methods All institutions are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided radiosurgery. The questionnaire consisted of 75 items covering all major steps of spine radiosurgery. Results Strong agreement in the methods of spine radiosurgery was observed. In particular, similarities were observed with safety and quality assurance playing an important role in the methods of all institutions, cooperation between neurosurgeons and radiation oncologists in case selection, dedicated imaging for target- and organ-at-risk delineation, application of proper safety margins for the target volume and organs-at-risk, conformal planning and precise image-guided treatment delivery, and close clinical and radiological follow-up. In contrast, three major areas of uncertainty and disagreement were identified: 1) Indications and contra-indications for spine radiosurgery; 2) treatment dose and fractionation and 3) tolerance dose of the spinal cord. Conclusions Results of this study reflect the current practice of spine radiosurgery in large academic centers. Despite close agreement was observed in many steps of spine radiosurgery, further research in form of retrospective and especially prospective studies is required to refine the details of spinal radiosurgery in terms of safety and efficacy. KW - vertebral metastases KW - spine radiosurgery KW - methods KW - questionnaire Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-138006 VL - 6 IS - 172 ER - TY - JOUR A1 - Gerszten, Peter C. A1 - Sahgal, Arjun A1 - Sheehan, Jason P. A1 - Kersh, Ronald A1 - Chen, Stephanie A1 - Flickinger, John C. A1 - Quader, Mubina A1 - Fahim, Daniel A1 - Grills, Inga A1 - Shin, John H. A1 - Winey, Brian A1 - Oh, Kevin A1 - Sweeney, Reinhart A. A1 - Guckenberger, Matthias T1 - A multi-national report on methods for institutional credentialing for spine radiosurgery JF - Radiation Oncology N2 - Background: Stereotactic body radiotherapy and radiosurgery are rapidly emerging treatment options for both malignant and benign spine tumors. Proper institutional credentialing by physicians and medical physicists as well as other personnel is important for the safe and effective adoption of spine radiosurgery. This article describes the methods for institutional credentialing for spine radiosurgery at seven highly experienced international institutions. Methods: All institutions (n = 7) are members of the Elekta Spine Radiosurgery Research Consortium and have a dedicated research and clinical focus on image-guided spine radiosurgery. A questionnaire consisting of 24 items covering various aspects of institutional credentialing for spine radiosurgery was completed by all seven institutions. Results: Close agreement was observed in most aspects of spine radiosurgery credentialing at each institution. A formal credentialing process was believed to be important for the implementation of a new spine radiosurgery program, for patient safety and clinical outcomes. One institution has a written policy specific for spine radiosurgery credentialing, but all have an undocumented credentialing system in place. All institutions rely upon an in-house proctoring system for the training of both physicians and medical physicists. Four institutions require physicians and medical physicists to attend corporate sponsored training. Two of these 4 institutions also require attendance at a non-corporate sponsored academic society radiosurgery course. Corporate as well as non-corporate sponsored training were believed to be complimentary and both important for training. In 5 centers, all cases must be reviewed at a multidisciplinary conference prior to radiosurgery treatment. At 3 centers, neurosurgeons are not required to be involved in all cases if there is no evidence for instability or spinal cord compression. Backup physicians and physicists are required at only 1 institution, but all institutions have more than one specialist trained to perform spine radiosurgery. All centers believed that credentialing should also be device specific, and all believed that professional societies should formulate guidelines for institutions on the requirements for spine radiosurgery credentialing. Finally, in 4 institutions radiation therapists were required to attend corporate-sponsored device specific training for credentialing, and in only 1 institution were radiation therapists required to also attend academic society training for credentialing. Conclusions: This study represents the first multi-national report of the current practice of institutional credentialing for spine radiosurgery. Key methodologies for safe implementation and credentialing of spine radiosurgery have been identified. There is strong agreement among experienced centers that credentialing is an important component of the safe and effective implementation of a spine radiosurgery program. KW - cyberknife radiosurgery KW - advanced technology KW - conformal radiotherapy KW - clinical trials KW - quality assurance KW - credentialing KW - spine tumors KW - stereotactic body radiotherapy KW - spine Radiosurgery KW - paraspinal tumors KW - intensity modulated radiotherapy KW - ACR practice guidelines KW - radiation therapy Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131485 VL - 8 IS - 158 ER - TY - JOUR A1 - Guckenberger, Matthias A1 - Mantel, Frederick A1 - Gerszten, Peter C. A1 - Flickinger, John C. A1 - Sahgal, Arjun A1 - Létourneau, Daniel A1 - Grills, Inga S. A1 - Jawad, Maha A1 - Fahim, Daniel K. A1 - Shin, John H. A1 - Winey, Brian A1 - Sheehan, Jason A1 - Kersh, Ron T1 - Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis N2 - Purpose To evaluate patient selection criteria, methodology, safety and clinical outcomes of stereotactic body radiotherapy (SBRT) for treatment of vertebral metastases. Materials and methods Eight centers from the United States (n = 5), Canada (n = 2) and Germany (n = 1) participated in the retrospective study and analyzed 301 patients with 387 vertebral metastases. No patient had been exposed to prior radiation at the treatment site. All patients were treated with linac-based SBRT using cone-beam CT image-guidance and online correction of set-up errors in six degrees of freedom. Results 387 spinal metastases were treated and the median follow-up was 11.8 months. The median number of consecutive vertebrae treated in a single volume was one (range, 1-6), and the median total dose was 24 Gy (range 8-60 Gy) in 3 fractions (range 1-20). The median EQD210 was 38 Gy (range 12-81 Gy). Median overall survival (OS) was 19.5 months and local tumor control (LC) at two years was 83.9%. On multivariate analysis for OS, male sex (p < 0.001; HR = 0.44), performance status <90 (p < 0.001; HR = 0.46), presence of visceral metastases (p = 0.007; HR = 0.50), uncontrolled systemic disease (p = 0.007; HR = 0.45), >1 vertebra treated with SBRT (p = 0.04; HR = 0.62) were correlated with worse outcomes. For LC, an interval between primary diagnosis of cancer and SBRT of ≤30 months (p = 0.01; HR = 0.27) and histology of primary disease (NSCLC, renal cell cancer, melanoma, other) (p = 0.01; HR = 0.21) were correlated with worse LC. Vertebral compression fractures progressed and developed de novo in 4.1% and 3.6%, respectively. Other adverse events were rare and no radiation induced myelopathy reported. Conclusions This multi-institutional cohort study reports high rates of efficacy with spine SBRT. At this time the optimal fractionation within high dose practice is unknown. KW - Medizin Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110638 ER - TY - JOUR A1 - Mantel, Frederick A1 - Flentje, Michael A1 - Guckenberger, Matthias T1 - Stereotactic body radiation therapy in the re-irradiation situation – a review JF - Radiation Oncology N2 - Although locoregional relapse is frequent after definitive radiotherapy (RT) or multimodal treatments, re-irradiation is only performed in few patients even in palliative settings like e.g. vertebral metastasis. This is most due to concern about potentially severe complications, especially when large volumes are exposed to re-irradiation. With technological advancements in treatment planning the interest in re-irradiation as a local treatment approach has been reinforced. Recently, several studies reported re-irradiation for spinal metastases using SBRT with promising local and symptom control rates and simultaneously low rates of toxicity. These early data consistently indicate that SBRT is a safe and effective treatment modality in this clinical situation, where other treatment alternatives are rare. Similarly, good results have been shown for SBRT in the re-irradiation of head and neck tumors. Despite severe late adverse effects were reported in several studies, especially after single fraction doses >10 Gy, they appear less frequently compared to conventional radiotherapy. Few studies with small patient numbers have been published on SBRT re-irradiation for non-small cell lung cancer (NSCLC). Overall survival (OS) is limited by systemic progression and seems to depend particularly on patient selection. SBRT re-irradiation after primary SBRT should not be practiced in centrally located tumors due to high risk of severe toxicity. Only limited data is available for SBRT re-irradiation of pelvic tumors: feasibility and acceptable toxicity has been described, suggesting SBRT as a complementary treatment modality for local symptom control. KW - Stereotactic body radiotherapy KW - Radiosurgery KW - Re-irradiation KW - Locoregional recurrence KW - Normal tissue tolerance KW - Spinal metastases KW - NSCLC KW - Head and neck cancer KW - Pelvic tumors Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96346 UR - http://www.ro-journal.com/content/8/1/7 ER - TY - JOUR A1 - Guckenberger, Matthias A1 - Hawkins, Maria A1 - Flentje, Michael A1 - Sweeney, Reinhart A. T1 - Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial N2 - Background One third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70 % of these patients. Conventional radiotherapy with of 1–10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3–6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology – intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery – have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1) A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3) Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept. Methods / Design It is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this two-centre phase II trial. Conclusions Results of this study will refine the methods of patient selection, target volume definition, treatment planning and delivery as well as quality assurance for radiosurgery. It is the intention of this study to form the basis for a future randomized controlled trial comparing conventional radiotherapy with fractionated radiosurgery for palliation of painful vertebral metastases. Trial registration ClinicalTrials.gov Identifier: NCT01594892 KW - Medizin KW - Phase II trial KW - Spinal metastasis KW - Pain KW - Radiosurgery KW - Stereotactic body radiotherapy Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75853 ER -