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  • ONCOLOGY  (16)
  • imaging  (15)
  • radiation  (11)
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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: 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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  • 3
    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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  • 4
    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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  • 5
    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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  • 6
    Keywords: CANCER ; CELLS ; EXPRESSION ; GROWTH ; INVASION ; SURVIVAL ; VITRO ; DENSITY ; MICE ; radiation ; MIGRATION ; GROWTH-FACTOR-BETA ; CELL-MIGRATION ; human glioma ; antiangiogenic therapy ; GLIOBLASTOMA ; VESSEL NORMALIZATION
    Abstract: Here we investigate the effects of the novel transforming growth factor-beta receptor I (TGF-beta RI) serine/threonine kinase inhibitor LY2109761 on glioblastoma when combined with the present clinical standard combination regimen radiotherapy and temozolomide (TMZ). Human GBM U87 (methylated MGMT promoter), T98 (unmethylated MGMT promoter), and endothelial cells (HUVECs) were treated with combinations of LY2109761, TMZ, and radiation. We found that LY2109761 reduced clonogenic survival of U87 and T98 cells and further enhanced the radiation-induced anticlonogenicity. In addition, LY2109761 had antimigratory and antiangiogenic effects in Matrigel migration and tube formation assays. In vivo, in human xenograft tumors growing subcutaneously on BALB/c nu/nu mice, LY2109761 delayed tumor growth alone and in combination with fractionated radiation and TMZ. Interestingly, as expected, the methylated U87 model was more sensitive to TMZ than the unmethylated T98 model in all experiments, whereas the opposite was found for LY2109761. Moreover, with respect to tumor angiogenesis, while LY2109761 decreased the glioblastoma proliferation index (Ki-67) and the microvessel density (CD31 count), the relative pericyte coverage (alpha-SMA/CD31 ratio) increased in particular after triple therapy, suggesting a vascular normalization effect induced by LY2109761. This normalization could be attributed in part to a decrease in the Ang-2/Ang-1 messenger RNA ratio. LY2109761 also reduced tumor blood perfusion as quantified by noninvasive dynamic contrast-enhanced magnetic resonance imaging. Together, the data indicate that the addition of a TGF-beta RI kinase inhibitor to the present clinical standard (radiation plus TMZ) has the potential to improve clinical outcome in human glioblastoma, especially in patients with unmethylated MGMT promoter status
    Type of Publication: Journal article published
    PubMed ID: 21677877
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  • 7
    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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  • 8
    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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  • 9
    Keywords: pancreatic cancer ; nuclear medicine ; PANCREATIC-CANCER ; ONCOLOGY ; radiology ; PATIENT ; NUCLEAR-MEDICINE ; BLOOD ; CANCER ; imaging ; Germany ; NUCLEAR ; MEDICINE
    Type of Publication: Meeting abstract published
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  • 10
    Keywords: ONCOLOGY ; GEMCITABINE ; PANCREATIC-CANCER ; radiology ; CANCER PATIENTS ; CANCER-PATIENTS ; PREDICTION ; IMRT ; nuclear medicine ; pancreatic cancer ; CANCER ; BLOOD ; NEW-YORK ; imaging ; PATIENT ; NUCLEAR-MEDICINE ; USA ; MEDICINE ; biomarker ; NUCLEAR ; outcome ; cetuximab
    Type of Publication: Meeting abstract published
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