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  • 1
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; tumor ; Germany ; LUNG ; THERAPY ; CT ; liver ; ACCURACY ; stereotactic ; CONFORMAL RADIOTHERAPY ; RADIATION-THERAPY ; ESCALATION ; MOTION ; TARGETS ; BREATH-HOLD TECHNIQUE ; IMMOBILIZATION ; TUMOR MOVEMENT ; multislice CT,lung tumors,stereotactic radiation therapy,respiratory movement
    Type of Publication: Journal article published
    PubMed ID: 14509953
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  • 2
    Keywords: brain ; CANCER ; IRRADIATION ; radiotherapy ; Germany ; MODEL ; FOLLOW-UP ; VOLUME ; incidence ; RISK ; TISSUE ; radiation ; PATIENT ; MECHANISM ; MR ; treatment ; magnetic resonance ; MAGNETIC-RESONANCE ; TARGET ; stereotactic ; radiosurgery ; RATES ; metastases ; CANCER-RESEARCH ; CURVES ; GAMMA-KNIFE RADIOSURGERY ; COMPLICATIONS ; MULTIVARIATE-ANALYSIS ; arteriovenous malformation ; ARTERIOVENOUS-MALFORMATION ; late radiation effects ; dose/volume response ; late radiation effect ; volume effect
    Abstract: Purpose: To evaluate late radiation effects in the brain after radiosurgery of patients with cerebral arteriovenous malformations (AVMs) and to quantify dose/volume-response relations for radiation-induced changes of brain tissue identified on follow-up neuroimaging. Patients and Methods: Data from 73 AVM patients who had stereotactic Linac radiosurgery at DKFZ (German Cancer Research Center), Heidelberg, Germany, were retrospectively analyzed. The endpoint of radiation-induced changes of brain tissue on follow-up magnetic resonance (MR) neuroimaging (i.e., edema and blood-brain-barrier breakdown [BBBB]) was evaluated. Each endpoint was further differentiated into three Levels with respect to the extent of the image change (small, intermediate, and Large). A previous analysis of the data found correlation of the endpoints with several dose/volume variables (DV) derived from each patient's dose distribution in the brain, including the mean dose in a volume of 20 cm(3) (Dmean(20)) and the absolute brain volume (including the AVM target) receiving a dose of at least 12 Gy (V12). To quantify dose/volume-response relations, patients were ranked according to DV (i.e., Dmean(20) and V12) and classified into four groups of equal size. For each group, the actuarial rates of developing the considered endpoints within 2.5 years after radiosurgery were determined from Kaplan-Meier estimates. The dose/volume-response curves were fitted with a sigmoid-shape Logistic function and characterized by DV50, the dose for a 50% incidence, and the slope parameter k. Results: Dose/volume-response relations, based on two alternative, but correlated, dose distribution variables that are a function of both dose and volume, were observed for radiation-induced changes of brain tissue. DV50 values of fitted dose/volume-response curves for tissue changes of Large extent (e.g., V12(50) = 22.0 +/- 2.6 cm(3) and Dmean20(50) =17.8 +/- 2.0 Gy for the combined endpoint of edema and/or BBBB) were significantly higher than those for small tissue changes (V12(50) = 4.0 0.3 cm(3) and Dmean20(50) 7.6 +/- 0.3 Gy). Conclusion: The derived dose/volume-response relations allow to quantitatively assess the risk of radiation-induced changes of brain tissue after radiosurgery in AVM patients. However, further understanding of the mechanism leading to brain tissue changes and their correlation with the desired obliteration is required. This knowledge will eventually help to optimize radiosurgical treatments in AVM patients
    Type of Publication: Journal article published
    PubMed ID: 15592695
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  • 3
    Keywords: OPTIMIZATION ; radiotherapy ; tumor ; Germany ; ALGORITHM ; TOOL ; TIME ; MARKER ; PROSTATE-CANCER ; MARKERS ; DELIVERY ; PARAMETERS ; CARCINOMAS ; INTENSITY-MODULATED RADIOTHERAPY ; SEGMENTS ; IMRT ; MULTILEAF COLLIMATORS ; VARIANCE ; SINGLE ; FRACTION ; SOFTWARE ; ISSUES ; dosimetry ; INTERVAL ; PROFILES ; dose rate ; dose rates ; HYPERSENSITIVITY ; MODULATED RADIATION-THERAPY ; PULSES ; step and shoot ; step-and-shoot
    Abstract: Background and Purpose: Although intensity-modulated radiotherapy (IMRT) has already shown its clinical benefit, there are some issues which are not yet fully understood. Among these is the question whether the protracted dose delivery due to the lowered dose rate has any radiobiological consequences. To investigate this question, an exact characterization of dose rate profiles in typical clinical plans is needed. Furthermore, such a characterization may lead to an increased knowledge how to improve IMRT technically. Material and Methods: A new IMRT phantom which allows precise measurement of up to nine points of interest simultaneously with pin-point ionization chambers was developed. To examine dose rates, a new software tool (GRAYHOUND) was developed which can measure doses in short time intervals of up to 0.5 s. 250 points in four clinical IMRT plans were examined. A set of parameters was defined to describe the dose rate profiles including the effective fraction time (eft, which is the percentage of the fraction time in which any dose is delivered to a specific point), and a quotient of the percentage of dose delivered in high dose pulses (〉 0.01 Gy/s) divided by the percentage of fraction time needed to deliver this dose (d(HD)/t(HD)). Results: These quotients are excellent markers for the inhomogeneity of dose rate delivery in IMRT. In both parameters a wide variance in points of the same plan and between different plans was found. For example, eft ranged between 11.6% and 37.3% in high dose points and the time in which high dose rates are delivered to a single high dose point ranged between 3.6% and 10.1% of total fraction time. Conclusions: These data show a great inhomogeneity of dose rates not only between different plans but also between different points in the same plan. Biological investigations are needed to quantify the relevance of these inhomogeneities. The parameters which are introduced in this work may be suitable to compare different optimization algorithms in IMRT
    Type of Publication: Journal article published
    PubMed ID: 16170486
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  • 4
    Keywords: RECEPTOR ; ANGIOGENESIS ; CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; proliferation ; radiotherapy ; SURVIVAL ; tumor ; TUMOR-CELLS ; carcinoma ; CELL-PROLIFERATION ; FACTOR RECEPTOR ; Germany ; human ; IN-VIVO ; KINASE ; MODEL ; MODELS ; THERAPY ; TOXICITY ; TYROSINE KINASE ; VITRO ; VIVO ; VOLUME ; DRUG ; TUMORS ; MICE ; radiation ; REDUCTION ; SKIN ; treatment ; ALPHA ; MOUSE ; MALIGNANCIES ; ASSAY ; leukemia ; DIET ; RECEPTORS ; BEHAVIOR ; CHRONIC MYELOGENOUS LEUKEMIA ; imatinib ; TUMOR CELLS ; radiosensitivity ; MALIGNANCY ; RE ; CONCURRENT ; TUMOR-GROWTH ; WEIGHT ; cell proliferation ; IMATINIB MESYLATE ; KINASE INHIBITORS ; TUMOR-CELL ; ASSAYS ; function ; STI571 ; CANCER-TREATMENT ; in vivo ; GLIOBLASTOMA ; GROWTH-FACTOR-RECEPTOR ; MONOTHERAPY ; Gleevec (R) ; GROWTH-FACTOR RECEPTORS
    Abstract: Background and Purpose: Imatinib (Gleevec (R), GLivec (R)) is an inhibitor of alpha- add beta-platelet-derived growth factor receptors and other tyrosine kinases, that are also associated with the function of growth factors. Imatinib has been approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors and is under investigation for the therapy of several other malignant tumors. Since radiotherapy is an important treatment option in many tumors, combined effects of imatinib and radiation were analyzed here. Material and Methods: In vitro, U87 cells (human glioblastoma), A431 cells (human epidermoid carcinoma), and HUVECs (human umbilical venous endothetial cells) were treated with imatinib atone and in combination with radiation. Clonogenic survival and cell proliferation were determined with and without additional radiation (0-10 Gy). In vivo, U87 and A431 cells (5 x 101) were subcutaneously injected into hind Limbs of balb c nu/u mice. Drug and radiation treatments started on day 0 when tumor volumes were approximately 400-500 mm(3). Tumors were treated with 5 x 5 Gy (U87) or 6 x 5 Gy (A431) on consecutive days from day 0. Imatinib was administered orally via the mouse diet starting on day 0 until the end of observation. Tumor growth and microvessel density (CD31 IHC) were analyzed. Results: In vitro, imatinib increased radiosensitivity of U87 and A431 tumor cells as well as HUVECs in both clonogenic and cell number/proliferation assays. The enhancement of radiosensitivity in HUVECs was comparable to that observed in the tumor cells. In vivo, the concurrent and continuous administration of imatinib increased tumor growth delay of fractionated radiotherapy in the carcinoma and the glioblastoma models at reduced microvessel densities. No apparent additional toxicity by the combination of radiation and imatinib versus monotherapies was observed in terms of weight, skin, or general behavior. Conclusion: Imatinib (GLeevec (R)), a "molecular targeted" approved drug for human malignancies, can enhance the tumor growth reduction induced by fractionated radiotherapy in glioblastoma and carcinoma models. The data provides a rationale to further investigate the combination
    Type of Publication: Journal article published
    PubMed ID: 16826359
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  • 5
    Keywords: CANCER ; radiotherapy ; carcinoma ; Germany ; imaging ; DRUG ; NUCLEAR-MEDICINE ; PATIENT ; MRI ; treatment ; metastases ; chemotherapy ; CERVICAL-CARCINOMA ; UTERINE CERVIX ; cervical carcinoma ; CISPLATIN ; nuclear medicine ; radiology ; ONCOLOGY ; SEIZURES ; NUCLEAR ; DRUGS ; UNIT ; RARE ; BRACHYTHERAPY ; MEDICINE ; intracranial ; medical imaging ; RADIOCHEMOTHERAPY ; cervix carcinoma ; leukoencephalopathy ; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME ; toxic encephalopathy
    Abstract: Case Report: A 45-year-old patient with cervix carcinoma received combined radiochemotherapy including cisplatin. After a cumulative dose of 240 mg/m(2)supercript stop the patient suddenly became somnolent and developed a severe tetraparesis and generalized seizures. After ruling out intracranial bleeding, cerebral metastases as well as infectious and metabolic causes of this condition, a severe toxic encephalopathy was diagnosed based on the clinical findings and MRI scans. After symptomatic treatment on the intensive care unit all symptoms were completely reversible. Conclusion: Toxic encephalopathy is a rare but dramatic complication of various cytostatic drugs. With the widespread use of cisplatin this rare disorder should be kept in mind
    Type of Publication: Journal article published
    PubMed ID: 17762922
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  • 6
    Keywords: carcinoma ; COMBINATION ; RISK ; chemotherapy ; CARCINOMAS ; INCREASE ; INCREASES
    Type of Publication: Journal article published
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  • 7
    Keywords: CANCER ; radiotherapy ; tumor ; carcinoma ; Germany ; THERAPY ; CT ; FOLLOW-UP ; imaging ; SURGERY ; radiation ; PATIENT ; prognosis ; CONTRAST ; RADIATION-THERAPY ; chemotherapy ; DELIVERY ; AD ; ESOPHAGUS ; RANDOMIZED-TRIAL ; IMRT ; radiology ; GUIDANCE ; THERAPIES ; LIBRARIES ; chemoradiation ; radiation therapy ; CT SCANS ; LIBRARY ; ESOPHAGEAL CANCER ; IMAGE GUIDANCE ; JUNCTION ; ATRIAL-FIBRILLATION ; outcome ; GUIDED RADIOTHERAPY ; RADIOCHEMOTHERAPY ; POSITION ; SCAN ; STRATEGY ; LIMITATIONS ; Esophageal carcinoma
    Abstract: Background: Despite maximum therapy the prognosis of esophageal carcinoma still remains extremely poor. New treatment strategies including improved radiation therapy techniques promise better outcome by improving local control through precise dose delivery due to higher conformality. Case Report: A 62-year-old patient with locally advanced carcinoma of the gastroesophageal junction underwent definitive radiochemotherapy with intensity-modulated radiation therapy (IMRT). On positioning control with the in-room CT, the distal. esophagus, and hence the tumor, was found to be highly mobile exhibiting changes in position of up to 4 cm from fraction to fraction. Result: IMRT plans were created for various positions establishing a plan library to choose from as appropriate. CT scans were performed prior to each treatment fraction to clarify esophagus position in order to choose the adequate treatment plan. Conclusion. Image guidance was crucial in this unusual case of esophageal carcinoma. Without the information from position control CTs, the tumor would have received only about half the prescribed dose due to variations in position. For this specific case, in-room CT scans are probably superior to kilo- or megavoltage CTs due to the higher soft-tissue contrast enabling detection of positioning variation of the organ and offering the possibility to use the CT for treatment planning
    Type of Publication: Journal article published
    PubMed ID: 19714309
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  • 8
    Keywords: CANCER ; radiotherapy ; Germany ; IMPACT ; QUALITY ; MALIGNANCIES ; CONFORMAL RADIOTHERAPY ; RADIATION-THERAPY ; HEAD ; SKULL BASE ; IMRT ; CONE-BEAM CT ; Image-guided radiotherapy ; Mega-voltage cone beam CT ; Radiation Dosage calculation ; Radiotherapy,intensity-modulated
    Abstract: PURPOSE: The goal of this work was to compare different methods of incorporating the additional dose of mega-voltage cone-beam CT (MV-CBCT) for image-guided intensity modulated radiotherapy (IMRT) of different tumor entities. MATERIAL AND METHODS: The absolute dose delivered by the MV-CBCT was calculated and considered by creating a scaled IMRT plan (scIMRT) by renormalizing the clinically approved plan (orgIMRT) so that the sum with the MV-CBCT dose yields the same prescribed dose. In the other case, a newly optimized plan (optIMRT) was generated by including the dose distribution of the MV-CBCT as pre-irradiation. Both plans were compared with the orgIMRT plan and a plan where the last fraction was skipped. RESULTS: No significant changes were observed regarding the 95% conformity index of the target volume. The mean dose of the organs at risk (OAR) increased by approx. 7% for the scIMRT plan and 5% for the optIMRT plan. A significant increase of the mean dose to the outline contour was observed, ranging from 3.1 +/- 1.3% (optIMRT) to 13.0 +/- 6.1% (scIMRT) for both methods over all entities. If the dose of daily MV-CBCT would have been ignored, the additional dose accumulated to nearly a whole treatment fraction with a general increase of approx. 10% to the OARs and approx. 4% to the target volume. CONCLUSION: Both methods of incorporating the additional MV-CBCT dose into the treatment plan are suitable for clinical practice. The dose distribution of the target volume could be achieved as conformal as with the orgIMRT plan, while only a moderate increase of mean dose to OAR was observed.
    Type of Publication: Journal article published
    PubMed ID: 22215128
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  • 9
    Keywords: CELL LUNG-CANCER ; RADIATION-THERAPY ; LONG-TERM SURVIVAL ; PHASE-II ; proton therapy ; DNA-CONTENT ; GEMCITABINE ; DISTAL ESOPHAGEAL CANCER ; CONCURRENT CAPECITABINE ; RESECTED ADENOCARCINOMA
    Abstract: BACKGROUND: To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV_baseplan and 54 Gy to the PTV_boost in single doses of 1.8 Gy for the PTV_baseplan and median single doses of 2.2 Gy in the PTV_boost were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT. RESULTS: Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5-37.5 months). Actuarial overall survival at 12 and 24 months was 36 % and 8 %, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79 % after 6 months, 39 % after 12 months, and 13 % after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26 % vs. 28 %). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy. CONCLUSION: IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome.
    Type of Publication: Journal article published
    PubMed ID: 23896630
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  • 10
    Keywords: EXPRESSION ; tumor ; CELL-LINES ; p53 ; acetylation ; DNA-DAMAGE ; HDAC inhibitors ; CANCER-THERAPY ; valproic acid ; RECEPTOR-MEDIATED APOPTOSIS
    Abstract: BACKGROUND: Osteosarcomas (OS) are highly malignant and radioresistant tumors. Histone deacetylase inhibitors (HDACi) constitute a novel class of anticancer agents. We sought to investigate the effect of combined treatment with suberoylanilide hydroxamic acid (SAHA) and radiotherapy in OS in vivo. METHODS: Clonogenic survival of human OS cell lines as well as tumor growth delay of OS xenografts were tested after treatment with either vehicle, radiotherapy (XRT), SAHA, or XRT and SAHA. Tumor proliferation, necrosis, microvascular density, apoptosis, and p53/p21 were monitored by immunohistochemistry. The CD95 pathway was performed by flow cytometry, caspase (3/7/8) activity measurements, and functional inhibition of CD95 death signaling. RESULTS: Combined treatment with SAHA and XRT markedly reduced the surviving fraction of OS cells as compared to XRT alone. Likewise, dual therapy significantly inhibited OS tumor growth in vivo as compared to XRT alone, reflected by reduced tumor proliferation, impaired angiogenesis, and increased apoptosis. Addition of HDACi to XRT led to elevated p53, p21, CD95, and CD95L expression. Inhibition of CD95 signaling reduced HDACi- and XRT-induced apoptosis. CONCLUSION: Our data show that HDACi increases the radiosensitivity of osteosarcoma cells at least in part via ligand-induced apoptosis. HDACi thus emerge as potentially useful treatment components of OS.
    Type of Publication: Journal article published
    PubMed ID: 23801068
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