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  • 1
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; tumor ; carcinoma ; THERAPY ; RISK ; CONFORMAL RADIOTHERAPY ; EXPERIENCE ; head and neck ; IMRT ; ACCELERATED FRACTIONATION ; ADENOID CYSTIC CARCINOMA ; intensity modulated radiation therapy ; inverse treatment planning ; NASOPHARYNGEAL CARCINOMA ; PAROTID-GLAND ; SALIVARY-GLAND CARCINOMA
    Abstract: Purpose/Objective: The aim of this analysis is to evaluate the feasibility of inverse treatment planning and intensity modulated radiation therapy (IMRT) for head and neck cancer in daily clinical routine. A step and shoot IMRT approach was developed which allows the treatment of large target volumes without the need to use a split beam technique. By using the INIRT approach better protection of different organs at risk in the head and neck region may be achieved and an escalation of the dose in the tumor should be possible. We evaluated the feasibility of the treatment technique and the patient tolerance to the treatment. First clinical results are reported. Materials and Methods: Between 1999 and 2002, 48 patients with a carcinoma of the head and neck region were treated with curative intention. All patients were treated in a patient-specific Scotch-Cast mask. Patients who required treatment of the lymph node levels I-VI, were additionally positioned by a vacuum pillow in order to immobilize the upper part of the thorax. For inverse treatment planning, the software module KonRad was used which was integrated into the VIRTUOS planning system. Each treatment plan was verified using quantitative film dosimetry in a head and neck phantom. The step and shoot IMRT technique with a multileaf collimator integrated in a Primus (Siemens(R)) accelerator was used for treatment. For all target volumes the whole target including the lymph nodes were covered completely by the INIRT treatment. Results: The mean total dose for the target volumes of macroscopic disease ranged between 63.0 and 64.1 Gy. The mean total dose of microscopic disease ranged between 55.2 and 60.1 Gy. The mean percentage of planning target volume receiving 〈 90% of the prescribed dose ranged between 3.0 and 11.5%. For the treatment, the median number of beams was seven (range: five to nine). The time to deliver the treatment ranged between 9 and 18 min. The results of the verification revealed a mean deviation between measured and calculated absolute doses for the 48 patients of 0.1 +/- 1.4%. Including the phantom verification the IMRT treatment of the patients could be started approximately after five working days. The treatment was well tolerated by all patients. The 2-year actuarial overall survival was 92% and the 2-year actuarial local control rate was 93%. According to the Radiation Therapy Oncology Group (RTOG), no higher acute toxicity than Grade 3 was seen. Observation of the late effects revealed only one transient Grade 4 toxicity of the bone and only four patients had a xerostomia higher than Grade 1. Conclusion: The use of an inversely-planned and intensity-modulated step and shoot approach is feasible in clinical routine for head and neck tumors. Treatment could be applied as planned and no increased toxicity was found. Compared to other IMRT approaches for the head and neck region the used technique allows the treatment of the primary tumor and the lymph nodes level I-VI with only one intensity modulated treatment volume. The presented technique avoids to match conventional radiotherapy fields and INIRT fields, and therefore, reduce the risk of overdosage or underdosage at the matching line. Compared to conventional treatment techniques INIRT shows advantages in tumor dose and dose at the organs at risk. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 12742271
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  • 2
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; IONIZING-RADIATION ; IRRADIATION ; PROTECTION ; radiotherapy ; tumor ; TUMOR-CELLS ; carcinoma ; CELL ; Germany ; human ; LUNG ; THERAPY ; SYSTEM ; SYSTEMS ; GENE ; GENES ; PROTEIN ; TISSUE ; TRANSDUCTION ; INDEX ; TISSUES ; MR ; SUSCEPTIBILITY ; virus ; NO ; VECTORS ; ASSAY ; resistance ; VECTOR ; DAMAGE ; CANCER-CELLS ; CARCINOMA-CELLS ; LOCALIZATION ; SAFETY ; NORMAL TISSUE ; OVEREXPRESSION ; mutagenesis ; RECOMBINANT ADENOASSOCIATED VIRUS ; adeno-associated virus ; ADENOASSOCIATED VIRUS ; TUMOR CELLS ; RECOMBINANT ; adeno-associated virus 2 ; cervical carcinoma cells ; CANDIDATE GENES ; SUPEROXIDE-DISMUTASE ; HIGH-TITER ; INTRATRACHEAL INJECTION ; MNSOD-PL
    Abstract: Background and purpose: The success rate of any therapeutic approach depends on the therapeutic window, which can be increased by either raising the resistance of the normal tissue without protecting the tumor cells or by sensitizing the tumor cells but not the normal cells. Two promising candidate genes for normal tissue protection against radiation-induced damage may be the copper-zinc (CuZnSOD) and manganese superoxide-dismutase genes (MnSOD). The recombinant adeno-associated virus 2 (rAAV-2) offers attractive advantages over other vector systems: low immunogenicity, ability to infect dividing and non-dividing tissues and a low chance of insertional mutagenesis, due to extra-chromosomal localization. We report the production of novel rAAV-2-SOD vectors and the investigation of their modulating effects on HeLa-RC cells after irradiation. Material and methods: rAAV-2 vectors were cloned containing the human CuZnSOD or MnSOD as transgene and vector stocks were produced. In the initial experiments human cervix carcinoma (HeLa-RC) cells were chosen for their susceptibility to rAAV-2. On day 0, cells were seeded and transduced with the rAAV-2-SOD vectors. On day 3, cells were harvested, irradiated (0.5-8 Gy) and reseeded in different assays (FACS, SOD, MTT and colony assays). Results: Although 〉 70% of all cells expressed SOD and significant amounts Of functional SOD protein were detected, no radioprotective effect of SOD was observed after transduction of HeLa-RC cells. Conclusions: Novel rAAV-2-SOD vectors that could be produced at high titer, were able to efficiently infect cells and express the SOD genes. The absence of a radioprotective effect in HeLa-RC cancer cells indicates an additional safety feature and suggests that rAAV-mediated MnSOD overexpression might contribute to increasing the therapeutic index when applied for normal tissue protection. (C) 2004 Elsevier Ireland Ltd, All rights reserved
    Type of Publication: Journal article published
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  • 3
    Keywords: measurement ; CANCER ; radiotherapy ; tumor ; Germany ; LUNG ; IMAGES ; lung cancer ; LUNG-CANCER ; TISSUE ; TUMORS ; PATIENT ; MRI ; CYCLE ; SEQUENCE ; STAGE ; RADIATION-THERAPY ; MOBILITY ; REGION ; REGIONS ; WALL ; CURVES ; MOTION ; FUTURE ; LINEAR-ACCELERATOR ; LOCATION ; dynamic MRI ; TRUEFISP ; PULMONARY-FUNCTION ; EXTERNAL-BEAM RADIOTHERAPY ; breathing cycle ; CT SCANS ; DIAPHRAGM ; HEALTHY-SUBJECTS ; lung MRL radiotherapy ; tumor diameter
    Abstract: Background and purpose: To assess the influence of tumor diameter on tumor mobility and motion of the tumor bearing hemithorax during the whole breathing cycle in patients with stage I non-small-cell lung cancer (NSCLC) using dynamic MRI. Patients and methods: Breathing cycles of thirty-nine patients with solitary NSCLCs were examined using a trueFISP sequence (three images per second). Patients were divided into three groups according to the maximal tumor diameter in the transverse plane ( 〈3, 3-5 and 〉5 cm). Continuous time-distance curves and deep inspiratory and expiratory positions of the chest wall, the diaphragm and the tumor were measured in three planes. Motion of tumor-bearing and corresponding contralateral non-tumor bearing regions was compared. Results: Patients with a tumor 〉3 cm showed a significantly lower diaphragmatic motion of the tumor bearing compared with the non-tumor bearing hemithorax in the craniocaudal (CC) directions (tumors 3-5 cm: 23.4 +/- 1.2 vs 21.1 +/- 1.5 cm (P 〈0.05); tumors 〉5 cm: 23.4 +/- 1.2 vs 20.1 +/- 1.6 cm (P 〈0.01). Tumors 〉5 cm in the lower lung region showed a significantly lower mobility compared with tumors 〈3 cm (1.8 +/- 1.0 vs 3.8 +/- 0.7 cm, P 〈0.01) in the CC directions. Conclusions: Dynamic MRI is a simple non-invasive method to differentiate mobility of tumors with different diameters and its influence on the surrounding tissue. Tumor diameter has a significant influence on tumor mobility and this might be taken into account in future radiotherapy planning, (C) 2004 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15588881
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  • 4
    Keywords: CANCER ; radiotherapy ; MODEL ; THERAPY ; NETWORK ; PATIENT ; treatment ; HEALTH ; FRANCE ; PROJECT ; EUROPE ; STANDARD ; FRAMEWORK ; THERAPIES ; LIGHT ; TASK ; PROTOCOL ; ISSUES ; cost ; innovation ; light ion therapy ; RADIATION ONCOLOGY
    Abstract: In the framework of the European Network for Research in Light Ion Hadron Therapy (ENLIGHT), the health economics group develops a methodology for assessing important investment and operating costs of this innovative treatment against its expected benefits. The main task is to estimate the cost per treated patient. The cost analysis is restricted to the therapeutic phase from the hospital point of view. An original methodology for cost assessment per treatment protocol is developed based on standard costs. Costs related to direct medical activity are based on the production process analysis, whereas indirect and non direct medical costs are allocated to each protocol using relevant cost-drivers. The resulting cost model will take into account the specificities of each therapeutic protocol as well as the particularities of each of the European projects
    Type of Publication: Journal article published
    PubMed ID: 15971339
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  • 5
    Keywords: brain ; Germany ; CLASSIFICATION ; FOLLOW-UP ; VOLUME ; RISK ; SURGERY ; PATIENT ; radiosurgery ; DOSE-RESPONSE ; COMPLICATIONS ; STEREOTAXIC RADIOSURGERY ; SINGLE ; MULTIVARIATE-ANALYSIS ; IV ; arteriovenous malformation ; GENDER ; SIZE ; RETROSPECTIVE ANALYSIS ; AVM ; GRADING SYSTEM ; HEMORRHAGE ; obliteration rate
    Abstract: Purpose: We investigated patient outcome and factors affecting obliteration rate after radiosurgery in cerebral arteriovenous malformations (AVM). Material and Methods: We have treated 110 patients with cerebral AVM with linac-based radiosurgery (IRS). AVM classification according Spetzler-Martin was 17 patients grade I (15%), 39 grade II (36%), 41 grade III (37%), 12 grade IV (11%) and 1 grade V (1%). Median single dose was 18 Gy. Mean treatment volume was 4.7 cc (range, 0.1-24.0 cc). Fifty-two patients experienced hemorrhage prior to IRS. Median follow-up was 2.5 years. Results: Actuarial complete obliteration rate (CO) was 51% after 3 years and 67% after 4 years. CO rate was significantly higher in AVM 〈3 cm (64% vs. 43%, P〈0.04) and in patients with grade I/II vs. III-V (71% vs. 33%, P〈0.001). CO was significantly improved after doses 〉18 Gy (P〈0.02) and in male gender (P〈0.04). In multivariate analysis Spetzler-Martin grade remained significant. Intracranial hemorrhage after IRS occurred in 9 patients 13.9 months median after IRS. Neurological dysfunction improved/completely dissolved or remained stable in 95% of patients. No new onset of neurological dysfunction was seen. No significant adverse effects after RS were seen. Conclusions: The rate of obliteration after IRS in AVM depends on applied single dose as well as size and Spetzler-Martin grade. RS is an alternative to neurosurgery, especially in patients with small or surgically inaccesible AVM. (C) 2005 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15893833
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  • 6
    Keywords: CANCER ; Germany ; LUNG ; THERAPY ; chest ; CT ; IMAGES ; imaging ; SYSTEM ; computed tomography ; NUCLEAR-MEDICINE ; TIME ; QUALITY ; MEMBRANE ; COMPUTED-TOMOGRAPHY ; SERIES ; MOTION ; ARTIFACTS ; nuclear medicine ; dynamic MRI ; HELICAL CT ; radiology ; ONCOLOGY ; RE ; EX-VIVO ; DIAPHRAGM ; methods ; PHASE ; NUCLEAR ; IMAGE QUALITY ; respiration ; lungs ; RESPIRATORY MOTION ; phantom ; tumor motion ; MEDICINE ; NOV ; comparison ; DETECTOR CT ; PORCINE LUNGS ; ex-vivo study ; GUIDED RADIOTHERAPY ; retrospective gating
    Abstract: Purpose: To analyse the image quality of retrospectively gated helical CT using controlled respiratory motion of porcine lung explants. Materials and methods: Five porcine lungs were examined inside a chest phantom. A silicone membrane was rhythmically inflated and deflated to simulate diaphragmatic respiration. Dynamic images (regular respiration at 8/min) and static scans (w/o respiration) at 0/25/50/75 and 100% of maximum inspiration were acquired with a 40-row detector CT scanner (rotation time 1 s, pitch 0.1). Image quality on multi-planar reformations was evaluated by two observers. Partial projection artifacts, step ladder-artifacts and noise were compared for upper, middle and lower parts of the lung and different respiratory phases (scores 0-3 for absent, minimal, moderate and diagnostically relevant artifacts). Results: Partial projection effects were limited to dynamic scans (mean score 1.33). Stepladder artifacts predominated in dynamic series compared to static series (mean score 0.55 versus 0.1; p 〈 0.001). Image noise was not related to lung motion (mean scores 0.68-0.81). All artifacts predominated close to the diaphragm compared to the upper and middle parts of the lung (p 〈 0.001 to p = 0.02, respectively). Partial projection and stepladder artifacts were less in end-inspiration and end-expiration than within the respiration (p 〈 0.001 and p = 0.17, respectively). Diagnostically relevant artifacts were noted 9 times (9/9 close to diaphragm, 7/9 partial-projection). Conclusions: Even in ideal realistic conditions, helical 4D-CT produced tolerable artifacts which could be overcome by radiologists. (c) 2007 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17923161
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  • 7
    Keywords: radiotherapy ; SURVIVAL ; tumor ; Germany ; THERAPY ; imaging ; SUPPORT ; SAMPLE ; TUMORS ; NUCLEAR-MEDICINE ; radiation ; PATIENT ; primary ; BASE ; treatment ; CARBON ; EXPERIENCE ; RADIATION-THERAPY ; COST-EFFECTIVENESS ; RATES ; SKULL BASE ; local control ; side effects ; RECURRENT ; nuclear medicine ; ION RADIOTHERAPY ; radiology ; ONCOLOGY ; THERAPIES ; INCREASE ; LIFE ; chordoma ; radiation therapy ; cost ; CHONDROSARCOMAS ; SKULL-BASE ; methods ; NUCLEAR ; carbon ion radiotherapy ; carbon ion radiation therapy ; PHOTON ; BENEFITS ; carbon ion
    Abstract: Aim: The cost-effectiveness of Carbon ion radiotherapy (RT) for patients with skull base chordoma is analyzed. Materials and Methods: Primary treatment costs and costs for recurrent tumors are estimated. The costs for treatment of recurrent tumors were estimated using a sample of 10 patients presenting with recurrent chordoma at the base of skull at DKFZ. Using various scenarios for the local control rate and reimbursements of Carbon ion therapy the cost-effectiveness of ion therapy for these tumors is analyzed. Results: If local control rate for skull base chordoma achieved with carbon ion therapy exceeds 70.3%, the overall treatment costs for carbon RT are lower than for conventional RTI. The cost-effectiveness ratio for carbon RT is 2539 Euro per 1% increase in survival, or 7692 Euro per additional life year. Conclusion: Current results support the thesis that Carbon ion RT, although more expensive, is at least as cost-effective as advanced photon therapies for these patients. Ion RT, however, offers substantial benefits for the patients such as improved control rates and less severe side effects. 0 2007 Elsevier Ireland Ltd. AR rights reserved
    Type of Publication: Journal article published
    PubMed ID: 17490770
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  • 8
    Keywords: ENERGIES ; OPTIMIZATION ; CELLS ; radiotherapy ; CELL ; Germany ; MODEL ; THERAPY ; imaging ; VOLUME ; NUCLEAR-MEDICINE ; radiation ; TIME ; recombination ; IONS ; BASE ; CARBON ; NUCLEI ; PARTICLES ; TARGET ; TRANSPORT ; RADIATION-THERAPY ; ENERGY ; REGION ; BEAM ; RBE ; treatment planning ; nuclear medicine ; IMRT ; radiology ; ONCOLOGY ; THERAPIES ; NUCLEAR ; POWER ; carbon ions ; BEAMS ; HEAVY-ION RADIOTHERAPY ; Protons ; MEDICINE ; comparison ; EMISSION ; carbon ion ; antiproton ; particle irradiation
    Abstract: Antiprotons are interesting as a possible future modality in radiation therapy for the following reasons: When fast antiprotons penetrate matter, protons and antiprotons have near identical stopping powers and exhibit equal radiobiology well before the Bragg-peak. But when the antiprotons come to rest at the Bragg-peak, they annihilate, releasing almost 2 GeV per anti proton-proton annihilation. Most of this energy is carried away by energetic pions, but the Bragg-peak of the antiprotons is still locally augmented with similar to 20-30 MeV per antiproton. Apart from the gain in physical dose, an increased relative biological effect also has been observed, which can be explained by the fact that some of the secondary particles from the antiproton annihilation exhibit high-LET properties. Finally, the weakly interacting energetic pions, which are leaving the target volume, may provide a real time feedback on the exact location of the annihilation peak. We have performed dosimetry experiments and investigated the radiobiological properties using the antiproton beam available at CERN, Geneva. Dosimetry experiments were carried out with ionization chambers, alanine pellets and radiochromic film. Radiobiological experiments were done with V79 WNRE Chinese hamster cells. The radiobiological experiments were repeated with protons and carbon ions at TRIUMF and GSI, respectively, for comparison. Several Monte Carlo particle transport codes were investigated and compared with our experimental data obtained at CERN. The code that matched our data best was used to generate a set of depth dose data at several energies, including secondary particle-energy spectra. This can be used as base data for a treatment planning software such as TRiP. Our findings from the CERN experiments indicate that the biological effect of antiprotons in the plateau region may be reduced by a factor of 4 for the same biological target dose in a spread-out Bragg-peak, when comparing with protons. The extension of TRiP to handle antiproton beams is currently in progress. This will enable us to perform planning studies, where the potential clinical consequences can be examined, and compared to those of other beam modalities such as protons, carbon ions, or IMRT photons. (C) 2007 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18158194
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  • 9
    Keywords: ENERGIES ; radiotherapy ; evaluation ; Germany ; CT ; imaging ; SYSTEM ; TISSUE ; computed tomography ; NUCLEAR-MEDICINE ; PATIENT ; INDEX ; DIFFERENCE ; ENERGY ; BEAM ; PARAMETERS ; COMPUTED-TOMOGRAPHY ; treatment planning ; nuclear medicine ; radiology ; ONCOLOGY ; RE ; LEVEL ; methods ; NUCLEAR ; IMAGE QUALITY ; phantom ; MEDICINE ; comparison ; quantitative ; GUIDED RADIOTHERAPY ; TOMOTHERAPY ; CONE-BEAM-CT ; kVCBCT ; MVCBCT
    Abstract: Purpose: A study to quantitatively compare the image quality of four different image guided radiotherapy (IGRT) devices based on phantom measurements with respect to the additional dose delivered to the patient. Methods: Images of three different head-sized phantoms (diameter 16-18 cm) were acquired with the following four IGRT-CT solutions: (i) the Siemens Primatom (R) single slice fan beam computed tomography (CT) scanner with an acceleration voltage of 130 kV, (ii) a Tomotherapy HI-ART II (R) unit using a fan beam scanner with an energy of 3.5 MeV and (iii) the Siemens Artiste (R) prototype, providing the possibility to perform W (121 kV) and MV (6 MV) cone beam (CB) CTs. For each device three scan protocols (named low, normal, high) were selected to yield the same weighted computed tomography dose index (CTDIw). Based on the individual inserts of the different phantoms the image quality achieved with each device at a certain dose level was characterized in terms of homogeneity, spatial resolution, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and electron density-to-CT-number conversion. Results: Based on the current findings for head-sized phantoms all devices show an electron density-to-CT-number conversion almost independent of the imaging parameters and hence can be suited for treatment planning purposes. The evaluation of the image quality, however, points out clear differences due to the different energies and geometries. The Primatom standard CT scanner shows throughout the best performance, especially for soft tissue contrast and spatial resolution with low imaging doses. Reasonable soft tissue contrast can be obtained with slightly higher doses compared to the CT scanner with the kVCB and the Tomotherapy unit. In order to get similar results with the MVCB system a much higher dose needs to be applied to the patient. Conclusion: Considering the entire investigations, especially in terms of contrast and spatial resolution, a rough tendency for decreasing image quality can be given: Primatom, Artiste prototype kVCB, Tomotherapy, Artiste prototype MVCB. (C) 2007 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 18031854
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  • 10
    Keywords: brain ; radiotherapy ; SURVIVAL ; Germany ; THERAPY ; DIAGNOSIS ; FOLLOW-UP ; imaging ; VOLUME ; LONG-TERM ; POPULATION ; radiation ; TIME ; PATIENT ; IMPACT ; TARGET ; RADIATION-THERAPY ; AGE ; MALES ; RATES ; PROGNOSTIC-FACTORS ; RESECTION ; PROGNOSTIC FACTORS ; LOW-GRADE ASTROCYTOMAS ; CHILDREN ; MR imaging ; GLIOMAS ; THERAPIES ; GLIOMA ; radiation therapy ; fractionated stereotactic radiotherapy ; LOW-GRADE GLIOMA ; HIGH-GRADE GLIOMAS ; SYMPTOMS ; PEDIATRIC-ONCOLOGY-GROUP ; NERVOUS-SYSTEM TUMORS ; EXTENT ; GLIOBLASTOMA ; PHASE-I/II TRIAL ; PROGRESSION-FREE SURVIVAL ; outcome ; WELL ; BEAM IRRADIATION ; Brain stem gliomas ; HYPERFRACTIONATED RADIATION-THERAPY ; MEDICAL-CENTER ; PONTINE GLIOMAS
    Abstract: Introduction: To assess long-term outcome in 85 patients with brain stem gliomas treated with fractionated stereotactic radiation therapy (FSRT). Patient and methods: Thirty-nine patients were females, and 46 were males. Median age at primary diagnosis was 26 years. Thirty-one patients were younger than 18 years. Histopathological examination confirmed a low-grade glioma in 57 patients. Of the group of high-grade gliomas, six were anaplastic astrocytomas, and two were classified as glioblastoma. Patient and methods: Radiation therapy was performed as FSRT. The median target volume was 101 nil. We applied a median dose of 54 Gy in conventional fractionation of 1.8 Gy. In seven of 85 patients (8%) FSRT was performed as re-irradiation. Results: The median follow-up time was 42 months. Median overall survival (OS) was 81 months. OS rates were 77% at 12 months, 70% at 24 months, and 63% at 36 months. Significant impact on OS could be shown for pilocytic histology, age, neurosurgical resection as well as for the presence of cyst on MR-imaging. Results: Median progression-free survival (PFS) after FSRT was 52 months. PFS rates at 12 months were 70%, and 63% and 58% at 24 and 36 months. respectively. Results: Histology, partial neurosurgical resection and the duration of symptoms could be identified as significant prognostic factors. Conclusion: Long-term outcome of FSRT in patients with brain stem gliomas is acceptable with low rates of side effects. Significant impact on outcome could be shown for histology. age, extent of neurosurgical resection as well as for cyst formation. No dose-response relationship could be observed. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 91 (2009) 60-66
    Type of Publication: Journal article published
    PubMed ID: 19285356
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