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  • radiotherapy  (20)
  • NUCLEAR-MEDICINE  (7)
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  • 1
    Keywords: RECEPTOR ; ANGIOGENESIS ; APOPTOSIS ; CANCER ; CELLS ; ENDOTHELIAL-CELLS ; GROWTH ; GROWTH-FACTOR ; IN-VITRO ; IONIZING-RADIATION ; IRRADIATION ; proliferation ; radiotherapy ; SURVIVAL ; tumor ; AGENTS ; CELL ; CELL-PROLIFERATION ; COMBINATION ; FACTOR RECEPTOR ; Germany ; human ; IN-VIVO ; INHIBITION ; KINASE ; PATHWAY ; PROSTATE ; THERAPY ; tumor growth ; VITRO ; DENSITY ; DRUG ; TUMORS ; MICE ; radiation ; PATIENT ; MECHANISM ; INDEX ; TYROSINE KINASE INHIBITOR ; DESIGN ; UP-REGULATION ; prostate cancer ; PROSTATE-CANCER ; DAMAGE ; MUSCLE ; MIGRATION ; experimental design ; CELL-MIGRATION ; TUMOR ANGIOGENESIS ; VEGF ; signaling ; AGENT ; ONCOLOGY ; RE ; antiangiogenesis ; SU5416 ; TUMOR-GROWTH ; THERAPIES ; INCREASE ; cell proliferation ; cell migration ; USA ; vascular endothelial growth factor ; cancer research ; GLIOBLASTOMA ; GROWTH-FACTOR-RECEPTOR ; SMOOTH-MUSCLE-CELLS ; ENDOTHELIAL GROWTH ; MUSCLE-CELLS ; tumor therapy ; radiation dose ; FRACTIONATED-IRRADIATION ; SU6668
    Abstract: Purpose: Investigations on the combination of radiotherapy with vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) antiangiogenic agents, which has the potential to improve the clinical outcome in cancer patients. Experimental Design: Here, we analyze the combined VEGF (SU5416) and PDGF (SU6668) receptor tyrosine kinase inhibition with irradiation in human endothelium (HUVEC), prostate cancer (PC3), and glioblastoma (U87) in vitro and in vivo. Results: Combined inhibition of VEGF and PDGF signaling resulted in enhanced apoptosis, reduced cell proliferation, and clonogenic survival as well as reduced endothelial cell migration and tube formation compared with single pathway inhibition. These effects were further enhanced by additional irradiation. Likewise, in PC3 and U87 tumors growing s.c. on BALB/c nu/nu mice, dual inhibition of VEGF and PDGF signaling significantly increased tumor growth delay versus each monotherapy. Interestingly, radiation at similar to 20% of the dose necessary to induce local tumor control exerts similar tumor growth-inhibitory effects as the antiangiogenic drugs given at their maximum effective dose. Addition of radiotherapy to both mono- as well as dual-antiangiogenic treatment markedly increased tumor growth delay. With respect to tumor angiogenesis, radiation further decreased microvessel density (CD31 count) and tumor cell proliferation (Ki-67 index) in all drug-treated groups. Of note, the slowly growing PC3 tumor responded better to the antiangiogenic drug treatments than the faster-growing U87 tumor. In addition to the beneficial effect of abrogating VEGF survival signaling when combined with radiation, we identified here a novel mechanism for the tumor escape from radiation damage. We found that radiation induced up-regulation of all four isoforms of PDGF (A-D) in endothelial cells supporting adjacent smooth muscle cells resulting in a prosurvival effect of radiation. The addition of SU6668 attenuated this undesirable paracrine radiation effect, which may rationalize the combined application of radiation with PDGF signaling inhibition to increase antitumor effects. Conclusion: A relative low radiation dose markedly enhances local antitumor effects of combined VEGF and PDGF signaling inhibition, suggesting a promising combination regimen for local tumor treatment with radiotherapy remaining an essential element
    Type of Publication: Journal article published
    PubMed ID: 18381963
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  • 2
    Keywords: radiotherapy ; TUMORS ; RADIATION-THERAPY ; chemotherapy ; SQUAMOUS-CELL CARCINOMA ; INTENSITY-MODULATED RADIOTHERAPY ; CISPLATIN ; IMRT ; reirradiation ; NASOPHARYNGEAL CARCINOMA ; ONCOLOGY-GROUP ; head and neck cancer ; XEROSTOMIA ; Recurrent head and neck cancer ; late toxicity ; UNRESECTABLE HEAD
    Abstract: Background In this retrospective investigation we analyzed outcome and toxicity after intensity-modulated reirradiation of recurrent head and neck cancer. Results Median overall survival was 17 months, and the 1- and 2-year overall survival rates were 63% and 34%. The 1- and 2-year local control rates were 57% and 53%. Distant spread occurred in 34%, and reirradiation induced considerable late toxicity in 21% of the patients. Thirty-two percent showed increased xerostomia after reirradiation. The risk for xerostomia was significantly higher for cumulative mean doses of greater-than-or-equal 45 Gy to parotid glands. Considering median cumulative maximum doses of 53 Gy to the spinal cord and 63 Gy to the brainstem, no late toxicities were observed. Conclusions Reirradiation with intensity-modulated radiotherapy in recurrent head and neck cancer is feasible with acceptable toxicity and yields encouraging rates of local control and overall survival.
    Type of Publication: Journal article published
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  • 3
    Keywords: radiotherapy ; COMBINATION ; STEREOTACTIC RADIOSURGERY ; adenocarcinoma ; GEMCITABINE ; CURATIVE RESECTION ; PHASE-III TRIAL ; BEAM IRRADIATION ; CHEMORADIOTHERAPY ; EXTERNAL-BEAM
    Abstract: ABSTRACT: BACKGROUND: To evaluate the use of intraoperative radiation therapy (IORT) in the multimodality treatment of patients with isolated local recurrences of pancreatic cancer. METHODS: We retrospectively analyzed 36 patients with isolated local recurrences of pancreatic cancer who have been treated with a combination of surgery, IORT and EBRT. Median time from initial treatment to recurrence was 20 months. All patients were surgically explored. In 18 patients a gross total resection was achieved, whereas the other half received only debulking or no resection at all. All patients received IORT with a median dose of 15 Gy. Additional EBRT was applied to 31 patients with a median dose of 45 Gy, combined with concurrent, mainly gemcitabine-based chemotherapy. RESULTS: Median follow-up in surviving patients was 23 months. Local progression was found in 6 patients after a median time of 17 months, resulting in estimated 1- and 2-year local control rates of 91% and 67%, respectively. Distant failure was observed in 23 patients, mainly in liver or peritoneal space. The median estimated progression-free survival was 9 months with 1- and 2-year rates of 40% and 26%, respectively. We found an encouraging estimated median overall survival of 19 months, transferring into 1- and 2-year rates of 66% and 45%. Notably 6 of 36 patients (17%) lived for more than 3 years. Severe postoperative complications were found in 3 and chemoradiation-related grade III toxicity in 6 patients. No severe IORT related toxicity was observed. CONCLUSION: Combination of surgery, IORT and EBRT in patients with isolated local recurrences of pancreatic cancer resulted in encouraging local control and overall survival in our cohort with acceptable toxicity. Our approach seems to be superior to palliative chemotherapy or chemoradiation alone and should be further investigated in a prospective setting specifically addressing isolated local recurrences of pancreatic cancer.
    Type of Publication: Journal article published
    PubMed ID: 22809267
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  • 4
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; SURVIVAL ; Germany ; LUNG ; THERAPY ; TOXICITY ; lung cancer ; LUNG-CANCER ; SURGERY ; radiation ; PATIENT ; CYCLE ; treatment ; antibodies ; antibody ; STAGE ; TRIAL ; RADIATION-THERAPY ; RATES ; metastases ; chemotherapy ; RESECTION ; CARCINOMAS ; OVEREXPRESSION ; IMRT ; FEASIBILITY ; PHASE-II ; NECK-CANCER ; SUBSET ; CONCURRENT ; ADVANCED HEAD ; INFUSION ; PHASE ; REMISSION ; prospective ; NSCLC ; C225 ; FACTOR RECEPTOR BLOCKADE ; stage III ; surgical resection
    Abstract: Background: Even today, treatment of Stage III NSCLC still poses a serious challenge. So far, surgical resection is the treatment of choice. Patients whose tumour is not resectable or who are unfit to undergo surgery are usually referred to a combined radio-chemotherapy. However, combined radio-chemotherapeutic treatment is also associated with sometimes marked side effects but has been shown to be more efficient than radiation therapy alone. Nevertheless, there is a significant subset of patients whose overall condition does not permit administration of chemotherapy in a combined-modality treatment. It could be demonstrated though, that NSCLCs often exhibit over-expression of EGF-receptors hence providing an excellent target for the monoclonal EGFR-antagonist cetuximab (Erbitux(R)) which has already been shown to be effective in colorectal as well as head-and-neck tumours with comparatively mild side-effects. Methods/design: The NEAR trial is a prospective phase II feasibility study combining a monoclonal EGF-receptor antibody with loco-regional irradiation in patients with stage III NSCLC. This trial aims at testing the combination's efficacy and rate of development of distant metastases with an accrual of 30 patients. Patients receive weekly infusions of cetuximab (Erbitux(R)) plus loco-regional radiation therapy as intensity-modulated radiation therapy. After conclusion of radiation treatment patients continue to receive weekly cetuximab for 13 more cycles. Discussion: The primary objective of the NEAR trial is to evaluate toxicities and feasibility of the combined treatment with cetuximab (Erbitux(R)) and IMRT loco-regional irradiation. Secondary objectives are remission rates, 3-year-survival and local/systemic progression-free survival
    Type of Publication: Journal article published
    PubMed ID: 16681848
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  • 5
    Keywords: IRRADIATION ; radiotherapy ; SURVIVAL ; tumor ; Germany ; THERAPY ; TOXICITY ; FOLLOW-UP ; DEATH ; SURGERY ; radiation ; TIME ; PATIENT ; prognosis ; treatment ; MALIGNANCIES ; AGE ; RATES ; chemotherapy ; local control ; ORGANIZATION ; MANAGEMENT ; ONCOLOGY-GROUP ; POSTOPERATIVE RADIOTHERAPY ; GRADE ; LIFE ; SIZE ; function ; TREATMENT TIME ; soft-tissue sarcoma ; ADJUVANT BRACHYTHERAPY ; electron boost radiation ; external beam radiotherapy ; limb-sparing treatment ; PROSPECTIVE RANDOMIZED TRIAL
    Abstract: Purpose: To analyze long-term prognosis and morbidity after limb-sparing treatment of patients with extremity soft-tissue sarcoma, with intraoperative electron boost radiotherapy (IOERT) followed by a moderate dose of external beam radiotherapy (EBRT). Methods and Materials: A total of 153 patients who were treated in a single center from 1991 to 2004 were ovaluated. Median IOERT dose was 15 Gy, mean EBRT dose 43 Gy (range, 40-50.4 Gy) in conventional fractionation (1.8-2 Gy). Median duration of follow-up was 33 months. Acute toxicity was assessed with Common Toxicity Criteria; late toxic effects were scored according to European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group criteria. Results: Five-year overall survival and 5-year local control rates were 77% and 78%.. respectively. Whereas tumor size, patient age, and EBRT dose did not significantly affect outcome, resection status and grading were significant for survival; resection status and IOERT dose were significant for local control. Extremity salvage until death or time of follow-up was achieved in 90% of our patients, 86% of whom showed excellent limb function without impairment in activities of daily life. Acute toxicity Grade 2-4 was observed in 23% and late toxicity Grade 2-4 in 17% of patients. Conclusions: Treatment with IOERT combined with moderate doses of external beam irradiation yields high local control and extremity preservation rates in resected extremity soft-tissue sarcoma. (c) 2006 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 16413697
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  • 6
    Keywords: CANCER ; radiotherapy ; SURVIVAL ; carcinoma ; COMBINATION ; Germany ; FOLLOW-UP ; imaging ; NEW-YORK ; RISK ; SITE ; SURGERY ; NUCLEAR-MEDICINE ; PATIENT ; treatment ; FIELD ; TARGET ; PATTERNS ; DECREASE ; chemotherapy ; RECURRENCE ; PROGNOSTIC-FACTORS ; RESECTION ; BEAM ; INVOLVEMENT ; local control ; FAILURE ; nuclear medicine ; POSTOPERATIVE RADIOTHERAPY ; radiology ; ONCOLOGY ; PATTERN ; PREOPERATIVE RADIOTHERAPY ; ADJUVANT THERAPY ; methods ; NUCLEAR ; USA ; rectal cancer ; EVALUATE ; soft-tissue sarcoma ; MEDICINE ; medical imaging ; in combination ; FIELDS ; LOCAL-CONTROL ; outcome ; REGIMEN ; BEAM RADIATION-THERAPY ; IOERT ; multimodality treatment ; neoadjuvant ; patterns of failure ; RECURRENT COLORECTAL-CANCER ; total mesorectal excision
    Abstract: Purpose: To evaluate local control and patterns of failure in patients treated with intraoperative electron beam radiotherapy (IOERT) after total mesorectal excision (TME), to appraise the effectiveness of intraoperative target definition. Methods and Materials: We analyzed the outcome of 243 patients with rectal cancer treated with IOERT (median dose, 10 Gy) after TME. Eighty-eight patients received neoadjuvant and 122 patients adjuvant external beam radiotherapy (EBRT) (median dose, 41.4 Gy), and in 88% simultaneous chemotherapy was applied. Median follow-up was 59 months. Results: Local failure was observed in 17 patients (7%), resulting in a 5-year local control rate of 92%. Only complete resection and absence of nodal involvement correlated positively with local control. Considering IOERT fields, seven infield recurrences were seen in the presacral space, resulting in a 5-year local control rate of 97%. The remaining local relapses were located as follows: retrovesical/retroprostatic (5), anastomotic site (2), promontorium (1), ileocecal (1), and perineal (1). Conclusion: Intraoperative electron beam radiotherapy as part of a multimodal treatment approach including TME is a highly effective regimen to prevent local failure. The presacral space remains the site of highest risk for local failure, but IOERT can decrease the percentage of relapses in this area. (c) 2007 Elsevier Inc
    Type of Publication: Journal article published
    PubMed ID: 17275208
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  • 7
    Keywords: CELLS ; radiotherapy ; SURVIVAL ; tumor ; CELL ; Germany ; neoplasms ; THERAPY ; TOXICITY ; FOLLOW-UP ; DISEASE ; TUMORS ; SURGERY ; radiation ; MRI ; PROGRESSION ; CONFORMAL RADIOTHERAPY ; EXPERIENCE ; RADIATION-THERAPY ; AGE ; EFFICACY ; REGION ; HEAD ; NECK ; local control ; ONCOLOGY ; overall survival ; radiation therapy ; MENINGIOMAS ; BONE ; SCAN ; INSTITUTION ; CASE SERIES
    Abstract: Background: Giant cell tumors are rare neoplasms, representing less than 5% of all bone tumors. The vast majority of giant cell tumors occurs in extremity sites and is treated by surgery alone. However, a small percentage occurs in pelvis, spine or skull bones, where complete resection is challenging. Radiation therapy seems to be an option in these patients, despite the lack of a generally accepted dose or fractionation concept. Here we present a series of five cases treated with high dose IMRT. Patients and Methods: From 2000 and 2006 a total of five patients with histologically proven benign giant cell tumors have been treated with IMRT in our institution. Two patients were male, three female, and median age was 30 years (range 20 - 60). The tumor was located in the sacral region in four and in the sphenoid sinus in one patient. All patients had measurable gross disease prior to radiotherapy with a median size of 9 cm. All patients were treated with IMRT to a median total dose of 64 Gy (range 57.6 Gy to 66 Gy) in conventional fractionation. Results: Median follow up was 46 months ranging from 30 to 107 months. Overall survival was 100%. One patient developed local disease progression three months after radiotherapy and needed extensive surgical salvage. The remaining four patients have been locally controlled, resulting in a local control rate of 80%. We found no substantial tumor shrinkage after radiotherapy but in two patients morphological signs of extensive tumor necrosis were present on MRI scans. Decline of pain and/or neurological symptoms were seen in all four locally controlled patients. The patient who needed surgical salvage showed markedly reduced pain but developed functional deficits of bladder, rectum and lower extremity due to surgery. No severe acute or late toxicities attributable to radiation therapy were observed so far. Conclusion: IMRT is a feasible option in giant cells tumors not amendable to complete surgical removal. In our case series local control was achieved in four out of five patients with marked symptom relief in the majority of cases. No severe toxicity was observed
    Type of Publication: Journal article published
    PubMed ID: 20187955
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  • 8
    Keywords: radiotherapy ; REGISTRATION ; UNCERTAINTIES ; MUTUAL INFORMATION ; Image-guided radiotherapy ; Head-and-neck cancer ; Setup uncertainties
    Abstract: PURPOSE: To evaluate the local positioning uncertainties during fractionated radiotherapy of head-and-neck cancer patients immobilized using a custom-made fixation device and discuss the effect of possible patient correction strategies for these uncertainties. METHODS AND MATERIALS: A total of 45 head-and-neck patients underwent regular control computed tomography scanning using an in-room computed tomography scanner. The local and global positioning variations of all patients were evaluated by applying a rigid registration algorithm. One bounding box around the complete target volume and nine local registration boxes containing relevant anatomic structures were introduced. The resulting uncertainties for a stereotactic setup and the deformations referenced to one anatomic local registration box were determined. Local deformations of the patients immobilized using our custom-made device were compared with previously published results. Several patient positioning correction strategies were simulated, and the residual local uncertainties were calculated. RESULTS: The patient anatomy in the stereotactic setup showed local systematic positioning deviations of 1-4 mm. The deformations referenced to a particular anatomic local registration box were similar to the reported deformations assessed from patients immobilized with commercially available Aquaplast masks. A global correction, including the rotational error compensation, decreased the remaining local translational errors. Depending on the chosen patient positioning strategy, the remaining local uncertainties varied considerably. CONCLUSIONS: Local deformations in head-and-neck patients occur even if an elaborate, custom-made patient fixation method is used. A rotational error correction decreased the required margins considerably. None of the considered correction strategies achieved perfect alignment. Therefore, weighting of anatomic subregions to obtain the optimal correction vector should be investigated in the future.
    Type of Publication: Journal article published
    PubMed ID: 20934279
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  • 9
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; tumor ; CELL ; Germany ; LUNG ; THERAPY ; TOXICITY ; lung cancer ; LUNG-CANCER ; COHORT ; DISEASE ; HISTORY ; RISK ; radiation ; ASSOCIATION ; CONFORMAL RADIOTHERAPY ; AGE ; smoking ; chemotherapy ; LOCALIZATION ; PREDICTION ; ESCALATION ; ONCOLOGY ; small cell lung cancer ; REGRESSION ; development ; NSCLC ; RADIATION PNEUMONITIS ; MODALITY ; CONCURRENT CHEMOTHERAPY ; Dose-volume constraints
    Abstract: Purpose: To analyze the association of patient- and treatment-related factors with the onset of radiation pneumonitis in a homogeneously treated cohort of patients suffering from small cell Lung cancer (SCLC). Patients and Methods: 242 patients with SCLC staged as limited disease, who had been treated with chemotherapy and three-dimensional conformal radiotherapy, were retrospectively analyzed. Pneumonitis was defined by typical symptoms and radiographic findings and judged clinically relevant, if drug administration and hospitalization were necessary. Patient- (age, gender, smoking history, performance status, tumor Localization, benign lung disease) and treatment-related parameters (V-10-V-40, mean lung dose [MLD]) were analyzed using chi(2)-tests for categorical parameters and Logistic regression for continuous variables. Results: 33 patients (13.6%) developed a clinically relevant pneumonitis, of whom three patients died. ALL cases of pneumonitis developed within 120 days. None of the patient-related parameters correlated significantly with the onset of pneumonitis. Considering treatment-related parameters, a significant correlation of V-30 in regard to total lung and V-40 in regard to ipsilateral, contralateral and total Lung to the risk of pneumonitis was found. So, the estimated risk of a clinically relevant pneumonitis increased from 10% given a V-30 of 13% to 30% given a V-30 of 35%. In contrast, no significant correlation was found for V-10 and V-20 and only a trend for MLD. Conclusion: In this series, high-dose radiation volume parameters, i.e., V-30 and especially V-40, were identified as the most important factors for the development of radiation pneumonitis. Low-dose radiation volume parameters and clinical parameters played an inferior role in predicting the pneumonitis risk
    Type of Publication: Journal article published
    PubMed ID: 20165822
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  • 10
    Keywords: CANCER ; CELLS ; radiotherapy ; SURVIVAL ; INHIBITION ; MORTALITY ; radiation ; T-CELLS ; RESECTION ; PHENOTYPE ; SAFETY ; adenocarcinoma ; microenvironment ; radiosensitivity ; endothelium ; stellate cells ; low dose radiation ; pancreatic cancer immune therapy
    Abstract: Background: The efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer. Methods/Design: This trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrolment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrolment. Discussion: This trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome
    Type of Publication: Journal article published
    PubMed ID: 21489291
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