@article{GuckenbergerMantelGersztenetal.2014,
  author    = {Guckenberger, Matthias and Mantel, Frederick and Gerszten, Peter C. and Flickinger, John C. and Sahgal, Arjun and L{\´e}tourneau, Daniel and Grills, Inga S. and Jawad, Maha and Fahim, Daniel K. and Shin, John H. and Winey, Brian and Sheehan, Jason and Kersh, Ron},
  title     = {Safety and efficacy of stereotactic body radiotherapy as primary treatment for vertebral metastases: a multi-institutional analysis},
  doi       = {10.1186/s13014-014-0226-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110638},
  year      = {2014},
  abstract  = {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.},
  language  = {en}
}
@article{GuckenbergerAlexandrowFlentje2012,
  author    = {Guckenberger, Matthias and Alexandrow, Nikolaus and Flentje, Michael},
  title     = {Radiotherapy alone for stage I-III low grade follicular lymphoma: long-term outcome and comparison of extended field and total nodal irradiation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75702},
  year      = {2012},
  abstract  = {Background: To analyze long-term results of radiotherapy alone for stage I-III low grade follicular lymphoma and to compare outcome after extended field irradiation (EFI) and total nodal irradiation (TNI). Methods and materials: Between 1982 and 2007, 107 patients were treated with radiotherapy alone for low grade follicular lymphoma at Ann Arbor stage I (n = 50), II (n = 36) and III (n = 21); 48 and 59 patients were treated with EFI and TNI, respectively. The median total dose in the first treatment series of the diaphragmatic side with larger lymphoma burden was 38 Gy (25 Gy - 50 Gy) and after an interval of median 30 days, a total dose of 28 Gy (12.6 Gy - 45 Gy) was given in the second treatment series completing TNI. Results: After a median follow-up of 14 years for living patients, 10-years and 15-years overall survival (OS) were 64\% and 50\%, respectively. Survival was not significantly different between stages I, II and III. TNI and EFI resulted in 15-years OS of 65\% and 34\% but patients treated with TNI were younger, had better performance status and higher stage of disease compared to patients treated with EFI. In multivariate analysis, only age at diagnosis (p<0.001, relative risk [RR] 1.06) and Karnofsky performance status (p = 0.04, RR = 0.96) were significantly correlated with OS. Freedom from progression (FFP) was 58\% and 56\% after 10-years and 15-years, respectively. Recurrences outside the irradiated volume were significantly reduced after TNI compared to EFI; however, increased rates of in-field recurrences and extra-nodal out-of-field recurrence counterbalanced this effect resulting in no significant difference in FFP between TNI and EFI. In univariate analysis, FFP was significantly improved in stage I compared to stage II but no differences were observed between stages I/II and stage III. In multivariate analysis no patient or treatment parameter was correlated with FFP. Acute toxicity was significantly increased after TNI compared to EFI with a trend to increased late toxicity as well. Conclusions: Radiotherapy alone for stage I and II follicular lymphoma resulted in long-term OS with high rates of disease control; no benefit of TNI over EFI was observed. For stage III follicular lymphoma, TNI achieved promising OS and FFP and should be considered as a potentially curative treatment option.},
  subject      = {Medizin},
  language  = {en}
}
@article{GuckenbergerRoeschBaieretal.2012,
  author    = {Guckenberger, Matthias and Roesch, Johannes and Baier, Kurt and Sweeney, Reinhart A. and Flentje, Michael},
  title     = {Dosimetric consequences of translational and rotational errors in frame-less image-guided radiosurgery},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75669},
  year      = {2012},
  abstract  = {Background: To investigate geometric and dosimetric accuracy of frame-less image-guided radiosurgery (IG-RS) for brain metastases. Methods and materials: Single fraction IG-RS was practiced in 72 patients with 98 brain metastases. Patient positioning and immobilization used either double- (n = 71) or single-layer (n = 27) thermoplastic masks. Pre-treatment set-up errors (n = 98) were evaluated with cone-beam CT (CBCT) based image-guidance (IG) and were corrected in six degrees of freedom without an action level. CBCT imaging after treatment measured intra-fractional errors (n = 64). Pre- and posttreatment errors were simulated in the treatment planning system and target coverage and dose conformity were evaluated. Three scenarios of 0 mm, 1 mm and 2 mm GTV-to-PTV (gross tumor volume, planning target volume) safety margins (SM) were simulated. Results: Errors prior to IG were 3.9 mm± 1.7 mm (3D vector) and the maximum rotational error was 1.7° ± 0.8° on average. The post-treatment 3D error was 0.9 mm± 0.6 mm. No differences between double- and single-layer masks were observed. Intra-fractional errors were significantly correlated with the total treatment time with 0.7mm±0.5mm and 1.2mm±0.7mm for treatment times ≤23 minutes and >23 minutes (p<0.01), respectively. Simulation of RS without image-guidance reduced target coverage and conformity to 75\% ± 19\% and 60\% ± 25\% of planned values. Each 3D set-up error of 1 mm decreased target coverage and dose conformity by 6\% and 10\% on average, respectively, with a large inter-patient variability. Pre-treatment correction of translations only but not rotations did not affect target coverage and conformity. Post-treatment errors reduced target coverage by >5\% in 14\% of the patients. A 1 mm safety margin fully compensated intra-fractional patient motion. Conclusions: IG-RS with online correction of translational errors achieves high geometric and dosimetric accuracy. Intra-fractional errors decrease target coverage and conformity unless compensated with appropriate safety margins.},
  subject      = {Medizin},
  language  = {en}
}
@article{GuckenbergerHawkinsFlentjeetal.2012,
  author    = {Guckenberger, Matthias and Hawkins, Maria and Flentje, Michael and Sweeney, Reinhart A.},
  title     = {Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75853},
  year      = {2012},
  abstract  = {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},
  subject      = {Medizin},
  language  = {en}
}