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  • TOXICITY  (13)
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  • 1
    Keywords: CANCER ; radiotherapy ; SURVIVAL ; tumor ; Germany ; TOXICITY ; FOLLOW-UP ; imaging ; DISEASE ; LONG-TERM ; SURGERY ; PATIENT ; RESPONSES ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; TARGET ; NO ; stereotactic radiotherapy ; PROGRESSION ; MALIGNANCIES ; EXPERIENCE ; RADIATION-THERAPY ; TUMOR PROGRESSION ; EFFICACY ; RATES ; local control ; CHILDREN ; GLIOMAS ; MANAGEMENT ; MALIGNANCY ; ONCOLOGY ; CHILDHOOD ; RE ; CRANIOPHARYNGIOMAS ; development ; IMPAIRMENT ; methods ; fractionated stereotactic radiotherapy ; USA ; survival rate ; RESONANCE ; PRECISION ; COMBINED SURGERY ; Rathke pouch
    Abstract: BACKGROUND. The long-term outcome in patients with craniopharyngiomas treated with fractionated stereotactic radiotherapy (FSRT) was evaluated. METHODS. A total of 40 patients with craniopharyngiomas were treated between May 1989 and July 2006 with FSRT. Most patients were treated for tumor progression after surgery. A median target dose of 52.2 grays (Gy) (range, 50.4-56 Gy) was applied in a median conventional fractionation of 5 x 1.8 Gy per week. Follow-up examinations included thorough clinical assessment as well as contrast-enhanced magnetic resonance imaging scans. RESULTS. After a median follow-up of 98 months (range, 3-326 months), local control was 100% at both 5 years and 10 years. Overall survival rates at 5 years and 10 years were 97% and 139%, respectively. A complete response was observed in 4 patients and partial responses were noted in 25 patients. Eleven patients presented with stable disease during follow-up. Acute toxicity was mild in all patients. Long-term toxicity included enlargement of cysts requiring drainage 3 months after FSRT. No visual impairment, radionecrosis, or development of secondary malignancies were observed. CONCLUSIONS. The long-term outcome of FSRT for craniopharyngiomas is excellent with regard to local control as well as treatment-related side effects
    Type of Publication: Journal article published
    PubMed ID: 17469176
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  • 2
    Keywords: OPTIMIZATION ; CANCER ; IRRADIATION ; radiotherapy ; SURVIVAL ; tumor ; Germany ; THERAPY ; TOXICITY ; FOLLOW-UP ; imaging ; SYSTEM ; TUMORS ; radiation ; PATIENT ; treatment ; TARGET ; EXPERIENCE ; RADIATION-THERAPY ; RATES ; RECURRENCE ; SKULL BASE ; local control ; ORGANIZATION ; PROTON RADIATION-THERAPY ; ONCOLOGY ; INCREASE ; GRADE ; CHONDROSARCOMAS ; CHORDOMAS ; SKULL-BASE ; methods ; NUCLEAR ; technique ; USA ; carbon ion radiotherapy ; BEAMS ; carbon ion radiation therapy ; EVALUATE ; survival rate ; NECROSIS ; PHOTON ; NEUROPATHIES ; particle therapy ; active beam delivery ; skull-base chordoma
    Abstract: Purpose: The aim of this study was to evaluate the effectiveness and toxicity of carbon ion radiotherapy in chordomas of the skull base. Methods and Materials: Between November 1998 and July 2005, a total of 96 patients with chordomas of the skull base have been treated with carbon ion radiation therapy (RT) using the raster scan technique at the Gesellschaft fur Schwerionenforschung (GSI) in Darmstadt, Germany. All patients had gross residual tumors. Median total dose was 60 CGE (range, 60-70 CGE) delivered in 20 fractions within 3 weeks. Local control and overall survival rates were calculated using the Kaplan-Meier method. Toxicity was assessed according to the Common Terminology Criteria (CTCAE v.3.0) and the Radiation Therapy Oncology Group (RTOG) / European Organization for Research and Treatment of Cancer EORTC) score. Results: Mean follow-up was 31 months (range, 3-91 months). Fifteen patients developed local recurrences after carbon ion RT. The actuarial local control rates were 80.6% and 70.0% at 3 and 5 years, respectively. Target doses in excess of 60 CGE and primary tumor status were associated with higher local control rates. Overall survival was 94.8% and 88.5% at 3 and 5 years, respectively. Late toxicity consisted of optic nerve neuropathy RTOG/EORTC Grade 3 in 4.1% of the patients and necrosis of a fat plomb in 1 patient. Minor temporal lobe injury (RTOG/EORTC Grade 1-2) occurred in 7 patients (7.2%). Conclusions: Carbon ion RT offers an effective treatment option for skull-base chordomas with acceptable toxicity. Doses in excess of 75 CGE with 2 CGE per fraction are likely to increase local control probability. (C) 2007 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 17363188
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  • 3
    Keywords: brain ; IRRADIATION ; radiotherapy ; SURVIVAL ; tumor ; Germany ; PATHWAY ; TOXICITY ; FOLLOW-UP ; TISSUE ; TIME ; PATIENT ; TOLERANCE ; LESIONS ; PROGRESSION ; MALIGNANCIES ; RADIATION-THERAPY ; TUMOR PROGRESSION ; CHILDREN ; MANAGEMENT ; MALIGNANCY ; CHILDHOOD ; overall survival ; GLAND ; fractionated stereotactic radiotherapy ; FUTURE STRATEGIES ; LOW-GRADE GLIOMA ; NERVE ; NEUROFIBROMATOSIS TYPE-1 ; optic glioma
    Abstract: Purpose: To evaluate the effectiveness and toxicity of fractionated stereotactically guided radiotherapy (FSRT) in the management of optic glioma. Methods and Materials: Fifteen patients with optic pathway gliomas were treated with FSRT at our institution between 1990 and 2003. A median target dose of 52.2 Gy (range, 45.2-57.6 Gy) was applied using a median fractionation of 5 fractions of 1.8 Gy weekly using a linear accelerator. Results: The median follow-up time was 97 months (range, 8-151 months). Of the 15 patients, I died of tumor progression during the follow-up period. The progression-free survival rate at 3 and 5 years was 92% and 72%, respectively. The median overall survival after FSRT was 90 months (range, 8-151 months). The 5-year survival rate after FSRT was 90%. We did not observe secondary malignancies. Conclusion: Fractionated stereotactic radiotherapy was safe and well tolerated in all patients. The good tumor control and the potential of sparing normal brain tissue, especially the pituitary gland in lesions involving the optic chiasm, permit effective treatment of patients with optic nerve gliomas. Longer follow-up is needed to assess the incidence of late effects fully. (c) 2005 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 15936565
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  • 4
    Keywords: IRRADIATION ; radiotherapy ; SURVIVAL ; tumor ; COMBINATION ; Germany ; THERAPY ; TOXICITY ; SURGERY ; radiation ; TIME ; PATIENT ; TRIAL ; RADIATION-THERAPY ; AGE ; chemotherapy ; Jun ; PHARMACOKINETICS ; RECURRENT ; ADULTS ; overall survival ; radiation therapy ; INTERVAL ; PHASE ; ADJUVANT TEMOZOLOMIDE ; ANTITUMOR IMIDAZOTETRAZINES ; DIAGNOSED MALIGNANT GLIOMA ; glioblastoma multiforme ; HIGH-GRADE GLIOMA ; temozolomide
    Abstract: Background and Purpose: The role of radiochemotherapy in the treatment of primary glioblastoma multiforme is still discussed controversially. To evaluate the feasibility and toxicity of irradiation and concomitant administration of 50 mg/ml temozolomide in patients with primary malignant glioma, this phase I/II study was conducted. Patients and Methods: 53 Patients with histologically confirmed WHO grade IV malignant glioma were enrolled into the study. All patients were treated with radiation therapy up to a total dose of 60 Gy using conventional fractionation of 5 x 2.0 Gy/week. Temozolomide was administered orally each therapy day at a dose of 50 mg/ml. Results: Prior to radiochemotherapy, complete resection (n = 14), subtotal resection (n = 22) or a biopsy (n = 17) of the tumor was performed. The median time interval between surgery and radiochemotherapy was 21 days. Treatment-related toxicity was very mild. Acute toxicity 〉 grade 2 was observed in one patient who developed grade 4 hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting. No severe Late effects were observed. Median progression-free and overall survival were 8 and 19 months, respectively. The overall survival rate was 72% at 1 and 26% at 2 years. Age and extent of surgery significantly influenced survival. Conclusion: The combination of temozolomide plus radiation therapy is feasible and safe in terms of toxicity. Overall survival times were relatively long compared to survival times reported for radiotherapy atone. The application of 50 mg/ml of temozolomide can be performed throughout the whole time course without interruption due to side effects and might largely contribute to the prolonged overall survival. Further evaluation is warranted as to which dose of temozolomide is optimal with regard to tumor response and toxicity
    Type of Publication: Journal article published
    PubMed ID: 15925979
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  • 5
    Keywords: radiotherapy ; tumor ; Germany ; THERAPY ; TOXICITY ; DIAGNOSIS ; FOLLOW-UP ; VOLUME ; SURGERY ; radiation ; TIME ; PATIENT ; RADIATION-THERAPY ; PROGNOSTIC FACTORS ; local control ; COMPLICATIONS ; INITIATION ; MANAGEMENT ; SINGLE ; FRACTION ; LINEAR-ACCELERATOR RADIOSURGERY ; fractionated stereotactic radiotherapy ; NERVE ; HEARING PRESERVATION ; POTENTIAL BENEFITS ; PRESERVATION ; SURGICAL-MANAGEMENT ; vestibular schwannoma
    Abstract: Purpose: To assess the long-term outcome and toxicity of fractionated stereotactic radiotherapy for acoustic neuromas in 106 patients treated in a single institution. Patients and Methods: Between October 1989 and January 2004, fractionated stereotactic radiotherapy (FSRT) was performed in 106 patients with acoustic neuroma (AN). The median total dose applied was 57.6 Gy in median single fractions of 1.8 Gy in five fractions per week. The median irradiated tumor volume was 3.9 mL (range, 2.7-30.7 mL). The median follow-up time was 48.5 months (range, 3-172 months). Results: Fractionated stereotactic radiotherapy was well tolerated in all patients. Actuarial local tumor control rates at 3- and 5-years after FSRT were 94.3% and 93%, respectively. Actuarial useful hearing preservation was 94% at 5 years. The presence of neurofibromatosis (NF-2) significantly adversely influenced hearing preservation in patients that presented with useful hearing at the initiation of RT (p = 0.00062). Actuarial hearing preservation without the diagnosis of NF-2 was 98%. In cases with NF-2, the hearing preservation rate was 64%. Cranial nerve toxicity other than hearing impairment was rare. The rate of radiation induced toxicity to the trigeminal and facial nerve was 3.4% and 2.3%, respectively. Conclusion: Fractionated stereotactic radiotherapy is safe and efficacious for the treatment of AN, with mild toxicity with regard to hearing loss and cranial nerve function. FSRT might be considered as an equieffective treatment modality compared to neurosurgery and therefore represents an interesting alternative therapy for patients with AN. (c) 2005 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 16111574
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  • 6
    Keywords: IRRADIATION ; radiotherapy ; SURVIVAL ; Germany ; THERAPY ; TOXICITY ; POPULATION ; radiation ; TIME ; PATIENT ; RADIATION-THERAPY ; EFFICACY ; chemotherapy ; RECURRENCE ; RESECTION ; RECURRENT ; relapse ; ASTROCYTOMAS ; MALIGNANT GLIOMAS ; overall survival ; radiation therapy ; PHASE-II TRIAL ; INTERVAL ; PART ; fractionated stereotactic radiotherapy ; glioblastoma multiforme ; temozolomide ; GLIOBLASTOMA-MULTIFORME ; IMPLANT BOOST ; POSTOPERATIVE TREATMENT ; recurrent glioblastoma multiforme ; stereotactic fractionated radiotherapy
    Abstract: Purpose. To assess the feasibility, efficacy and toxicity of fractionated stereotactic radiotherapy in the treatment of recurrent glioblastoma multiforme. Patients and Methods. From January 1995 to July 2003, 53 patients with histologically proven glioblastoma multiforme were treated at recurrence with fractionated stereotactic radiation therapy. A median dose of 36 Gy using a median fractionation of 5 x 2 Gy/week was applied. Results. Median overall survival was 21 months, and median overall survival from the time point of re-irradiation was 8 months. The median time interval between primary and secondary radiation therapy was 10 months. In this patient population, no variables predicting longer overall survival could be determined. However, neurosurgical resection at relapse was associated with increased survival after re-irradiation (p=0.04), but left progression-free survival unaltered. Treatment was well-tolerated and no severe toxicities developed. Conclusion. Stereotactically guided fractionated re-irradiation is a safe and effective treatment modality in selected cases of recurring glioblastoma multiforme. Since this is not a randomized study, further evaluation in larger patient collectives is warranted. Also, based on recent results of radiochemotherapy in the treatment of primary glioblastoma multiforme, concomitant chemotherapy at relapse might be considered in the future
    Type of Publication: Journal article published
    PubMed ID: 16193388
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  • 7
    Keywords: radiotherapy ; SURVIVAL ; tumor ; Germany ; TOXICITY ; VOLUME ; TISSUE ; PATIENT ; treatment ; TARGET ; CONFORMAL RADIOTHERAPY ; RADIATION-THERAPY ; MELANOMA ; MALIGNANT-MELANOMA ; INTENSITY-MODULATED RADIOTHERAPY ; IMRT ; OF-THE-LITERATURE ; SKULL-BASE ; methods ; survival analysis ; carbon ion radiotherapy ; EVALUATE ; TUMOR-CONTROL ; LOW-GRADE CHONDROSARCOMAS ; ETHMOID SINUS ; intensity-modulated radiotherapy (IMRT) ; paranasal sinus carcinoma ; PROGRESSION-FREE SURVIVAL ; SPHENOID SINUSES
    Abstract: Purpose: To evaluate the clinical outcome of intensity-modulated radiotherapy (IMRT) in patients with mucosal melanoma (MM) of the nasal cavity and paranasal sinuses. Patients and Methods: Between January 1999 and September 2004, eight patients with histologically proven MM of the nasal cavity and paranasal sinuses were treated with IMRT. A median dose of 66 Gy was applied to the macroscopic tumor (gross tumor volume [GTV]; range, 60-68 Gy) as an integrated boost and a median dose of 59 Gy (range, 54-64 Gy) to the clinical target volume (CTV) with IMRT. Results: Treatment-related toxicity was very mild in most patients. Overall survival was 80% at 5 years. Calculated from treatment with IMRT as primary radiotherapy, survival was 100% at 1 year and 75% at 3 years. After IMRT, local progression-free survival was 71.4% at 1 year and 57.1% at 3 years, respectively. Distant progression-free survival after IMRT was 57.1% at 1 year and 28.6% at 3 years. Conclusion: Local dose escalation with IMRT yields good treatment results with respect to local and distant tumor control as well as survival, while treatment-related toxicity can be minimized
    Type of Publication: Journal article published
    PubMed ID: 17294109
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  • 8
    Keywords: CANCER ; radiotherapy ; SURVIVAL ; Germany ; THERAPY ; TOXICITY ; DIAGNOSIS ; FOLLOW-UP ; VOLUME ; incidence ; TISSUE ; TUMORS ; radiation ; TIME ; PATIENT ; primary ; treatment ; NO ; stereotactic radiotherapy ; RADIATION-THERAPY ; AGE ; metastases ; chemotherapy ; REGION ; local control ; CHILDREN ; side effects ; IMRT ; ONCOLOGY ; THERAPIES ; GRADE ; radiation therapy ; intensity modulated radiotherapy ; INTERVAL ; methods ; SIZE ; fractionated stereotactic radiotherapy ; EVALUATE ; survival rate ; ADOLESCENCE ; SARCOMAS ; systemic ; CHILDHOOD RHABDOMYOSARCOMA ; EMBRYONAL RHABDOMYOSARCOMA ; FRACTIONATION ; INTERGROUP RHABDOMYOSARCOMA ; LOCAL-CONTROL ; PARAMENINGEAL RHABDOMYOSARCOMA ; study protocol
    Abstract: Background: The present study evaluates the outcome of 19 children with rhabdomyosarcoma of the head-and-neck region treated with Intensity Modulated Radiotherapy (IMRT) or Fractionated Stereotactic Radiotherapy (FSRT) between August 1995 and November 2005. Methods: We treated 19 children with head-and-neck rhabdomyosarcoma with FSRT (n = 14) or IMRT (n = 5) as a part of multimodal therapy. Median age at the time of radiation therapy was 5 years (range 2-15 years). All children received systemic chemotherapy according to the German Soft Tissue Sarcoma Study protocols. Median size of treatment volume for RT was 93,4 ml. We applied a median total dose of 45 Gy (range 32 Gy-54 Gy) using a median fractionation of 5 x 1,8 Gy/week (range 1,6 Gy-1,8 Gy). The median time interval between primary diagnosis and radiation therapy was 5 months (range 3-9 months). Results: After RT, the 3- and 5-year survival rate was 94%. The 3- and 5-year actuarial local control rate after RT was 89%. The actuarial freedom of distant metastases rate at 3- and 5-years was 89% for all patients. Radiotherapy was well tolerated in all children and could be completed without interruptions 〉 4 days. No toxicities 〉 CTC grade 2 were observed. The median follow-up time after RT was 17 months. Conclusion: IMRT and FSRT lead to excellent outcome in children with head-and-neck RMS with a low incidence of treatment-related side effects
    Type of Publication: Journal article published
    PubMed ID: 17854490
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  • 9
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; radiotherapy ; SURVIVAL ; CELL ; COMBINATION ; FACTOR RECEPTOR ; Germany ; human ; INHIBITION ; TOXICITY ; VITRO ; imaging ; NEW-YORK ; cell line ; MONOCLONAL-ANTIBODY ; LINES ; NUCLEAR-MEDICINE ; radiation ; MECHANISM ; MARKER ; mechanisms ; CELL-LINES ; treatment ; antibodies ; antibody ; NO ; CELL-LINE ; LINE ; gene amplification ; cell lines ; nuclear medicine ; protein expression ; EPIDERMAL-GROWTH-FACTOR ; CROSS-TALK ; radiology ; ONCOLOGY ; RE ; BRAIN-TUMORS ; INCREASE ; GLIOMA ; GLIOMA-CELLS ; MALIGNANT GLIOMAS ; EGFR ; KINASE INHIBITORS ; methods ; NUCLEAR ; temozolomide ; USA ; EVALUATE ; epidermal growth factor receptor ; GLIOBLASTOMA ; GROWTH-FACTOR-RECEPTOR ; PROGNOSTIC RELEVANCE ; MEDICINE ; in combination ; ANTAGONISM ; human glioma cells ; PRIMARY GLIOBLASTOMA-MULTIFORME ; SECONDARY GLIOBLASTOMAS ; TARGETED THERAPIES
    Abstract: Background: The majority of glioblastoma multiforme (GBM) cells express the epidermal growth factor receptor (EGFR). The present study evaluates the combination of temozolomide (TMZ), EGFR inhibition, and radiotherapy (RT) in GBM cell lines. Methods and Materials: Human GBM cell lines U87, LN229, LN18, NCH 82, and NCH 89 were treated with various combinations of TMZ, RT, and the monoclonal EGFR antibody cetuximab. Responsiveness of glioma cells to the combination treatment was measured by clonogenic survival. Results: Overall, double and triple combinations of RT, TMZ, and cetuximab lead to additive cytotoxic effects (independent toxicity). A notable exception was observed for U87 and LN 18 cell lines, where the combination of TMZ and cetuximab showed substantial antagonism. Interestingly, in these two cell lines, the combination of RT with cetuximab resulted in a substantial increase in cell killing over that expected for independent toxicity. The triple combination with RT, cetuximab, and TMZ was nearly able to overcome the antagonism for the TMZ/cetuximab combination in U87, however only marginally in LN18, GBM cell lines. Conclusion: It appears that EGFR expression is not correlated with cytotoxic effects exerted by cetuximab. Combination treatment with TMZ, cetuximab and radiation resulted in independent toxicity in three out of five cell lines evaluated, the antagonistic effect of the TMZ/cetuximab combination in two cell lines could indicate that TMZ preferentially kills cetuximab-resistant cells, suggesting for some cross-talk between toxicity mechanisms. Expression of EGFR was no surrogate marker for responsiveness to cetuximab, alone or in combination with RT and TMZ. (c) 2007 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 17544000
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  • 10
    Keywords: radiotherapy ; tumor ; Germany ; TOXICITY ; RISK ; PATIENT ; LESIONS ; PROGRESSION ; radiosurgery ; STEREOTACTIC RADIOSURGERY ; TUMOR PROGRESSION ; RATES ; local control ; TYPE-2 ; LINEAR-ACCELERATOR RADIOSURGERY ; HEARING PRESERVATION ; SURGICAL-MANAGEMENT ; vestibular schwannoma ; CEREBELLOPONTINE ANGLE TUMORS ; GAMMA-KNIFE ; MIDDLE FOSSA ; RADIOTHERAPY FSRT ; RETROSIGMOID APPROACH ; SINGLE-INSTITUTION
    Abstract: Purpose: To evaluate the effectiveness and long-term outcome of stereotactic radiosurgery (SRS) for acoustic neuromas (AN). Patients and Methods: Between 1990 and 2001, we treated 26 patients with 27 AN with SRS. Two patients suffered from neurofibromatosis type 2. Before SRS, a subtotal or total resection had been performed in 3 and in 5 patients, respectively. For SRS, a median single dose of 13 Gy/80% isodose was applied. Results: The overall actuarial 5-year and 10-year tumor control probability in all patients was 91%. Two patients developed tumor progression after SRS at 36 and 48 months. Nineteen patients (73%) were at risk of treatment-related facial nerve toxicity; of these, 1 patient developed a complete facial nerve palsy after SRS (5%). A total of 93% of the lesions treated were at risk of radiation-induced trigeminal neuralgia. Two patients (8%) developed mild dysesthesia of the trigeminal nerve after SRS. The hearing preservation rate in patients with useful hearing before SRS was 55% at 9 years. Conclusion: Stereotactic radiosurgery results in good local control rates of AN and the risk of cranial nerve toxicities is acceptable. As toxicity is lower with fractionated stereotactic radiotherapy, SRS should be reserved for smaller lesions. (c) 2006 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 16464537
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