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  • 1
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    Keywords: ANGIOGENESIS ; CANCER ; CELLS ; GROWTH ; IRRADIATION ; proliferation ; tumor ; TUMOR-CELLS ; carcinoma ; COMBINATION ; Germany ; MICROVESSEL DENSITY ; MODEL ; THERAPY ; DENSITY ; VOLUME ; gene therapy ; radiation ; ACTIVATION ; RAT ; immunohistochemistry ; RADIATION-THERAPY ; PLASMA ; EFFICACY ; CELL THERAPY ; IMPLANTATION ; adenocarcinoma ; IMMUNE-RESPONSE ; VASCULATURE ; CYCLOPHOSPHAMIDE ; pancreatic cancer ; pancreatic carcinoma ; TNF-ALPHA ; CYP2B1 ; ifosfamide ; INTRATUMORAL ACTIVATION ; ELISA ; INFILTRATION ; RE ; PANCREATIC-CANCER ; TUMOR-GROWTH ; radiation therapy ; PLUS ; lymphocyte infiltration ; COMBINED THERAPY ; COMBINED CHEMOTHERAPY
    Abstract: Local therapy of pancreatic cancer with microencapsulated CYP2B1-producing cells and ifosfamide showed an effect both on the primary tumor and on distant metastatases. This possibly represents a consequence of the activation of immune response. Other studies have demonstrated that local tumor irradiation leads to the activation of the intratumoral lymphocyte infiltration. The aim of our study was to investigate the efficacy of the combined therapy with low-dose irradiation, ifosfamide and CYP2B1-producing cells. Syngenic pancreatic cancer was induced in 38 Lewis-rats by subcutaneous inoculation of 1 X 10(6) (DSL6A) tumor cells. Microencapsulated CYP2B1-producing cells were injected peritumorally 10-12 weeks after tumor implantation. Animals were randomized to the following groups: 1) control (NaCl, 1 ml i.p.), 2) ifosfamide (50 mg/kg, i.p., (3x/week), 3) local irradiation with 5 Gy and 4) ifosfamide plus irradiation. The tumor growth was monitored for 3 weeks. The tumor infiltration with CD4+, CD8+, NK-cells, microvessel density and proliferation rates were investigated by immunohistochemistry. Cytokine plasma level for TNF-alpha were measured by ELISA. Seven of 9 animals in the group of combined therapy showed an objective response to the therapy. The therapy with ifosfamide or radiation alone showed 5 and 3 responders, respectively. The mean tumor volume was significantly reduced after combined ifosfamide plus radiation therapy in the first week, whereas monotherapy with ifosfamide or radiation significantly decreased tumor growth earliest after 2 and 3 weeks, respectively. The high plasma level of TNF-alpha in the control group was significantly reduced after combined ifosfamide/irradiation treatment. The lymphocyte infiltration and tumor proliferation were not significantly different between the groups. Microvascular density was significantly increased after ifosfamide and ifosfamide plus irradiation therapy. The combination of ifosfamide/CYP2B1-producing cells and irradiation showed an earlier therapeutical effect on the growth of rat pancreatic cancer than the irradiation or ifosfamide alone. There was no evidence of late activation of lymphocyte infiltration and PCNA-positive tumor cells. (C) 2004 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 15455374
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  • 3
    Keywords: CELLS ; GROWTH ; IRRADIATION ; carcinoma ; Germany ; MODEL ; SYSTEM ; EXPOSURE ; radiation ; TIME ; DNA ; INDUCTION ; RAT ; RATS ; FLOW ; cell cycle ; CYCLE ; treatment ; BREAST-CANCER ; PROGRESSION ; CARCINOMAS ; DOSE-RATE BRACHYTHERAPY ; INITIATION ; CYCLE ARREST ; cell cycle progression ; animal model ; DOSE-RATE ; low dose rate brachytherapy ; prostate Dunning tumour ; pulsed dose rate brachytherapy ; RATE INTERSTITIAL BRACHYTHERAPY
    Abstract: Purpose: The study consisted of two treatment arms comparing the effects of CLDR (continuous low dose rate) and PDR ( pulsed dose rate) brachytherapy on cell cycle progression in a radioresistant rat prostate tumour model. Materials and methods: Interstitial PDR and CLDR brachytherapy ( both 192-Ir, 0.75 Gy/h) were administered to Dunning prostate R3327-AT1 carcinomas transplanted subcutaneously into the thigh of Copenhagen rats. Increasing doses of up to 20 as well as up to 40 Gy were applied. Cell cycle distributions of the aneuploid tumour cell subpopulations were determined at 4 h ( 3 Gy), 24 h ( 18 Gy), 48 h ( 20 and 36 Gy), as well as during the subsequent redistribution period ( 20 and 40 Gy) at 72, 96, and 120 h. Tumours either implemented with an empty tubing system (n = 5) or under undisturbed growth (n = 5) served as controls. Three animals were irradiated per time point and exposure condition. At least two flow cytometrical analyses were carried out per animal. Results: The aneuploid cells possessed a constant DNA-Index of 1.9 +/- 0.06. In contrast to sham-treated controls, the aneuploid cell fraction with G2/M DNA content was significantly increased (p 〈 0.05) after initiation of both, CLDR and PDR brachytherapy. However, CLDR resulted in an earlier accumulation of tumour cells in G2/M (24 h: 28% CLDR vs. 19% PDR, p 〈 0.05) with a concomitant reduction of cells in G1, whereas PDR yielded delayed, but then more pronounced cell cycle changes, particularly expressed during the redistribution period after both 20 and 40 Gy. Conclusion: CLDR and PDR brachytherapy showed differential effects on cell cycle progression. The induction of a significantly earlier but also less persistent G2/M cell cycle arrest after CLDR compared to PDR brachytherapy implies that a substantially higher fraction of tumour cells are irradiated in G2/M after CLDR
    Type of Publication: Journal article published
    PubMed ID: 16638716
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  • 4
    Keywords: CANCER ; radiotherapy ; Germany ; MODEL ; imaging ; SYSTEM ; ACCURACY ; PATIENT ; treatment ; BREAST ; breast cancer ; BREAST-CANCER ; stereotactic radiotherapy ; EFFICIENT ; STABILITY ; TRANSFORMATION ; CANCER-PATIENTS ; CANCER PATIENTS ; FRACTIONATED RADIOTHERAPY ; RE ; HEALTHY-VOLUNTEERS ; NUCLEAR ; EVALUATE ; phantom ; HOLD ; comparison ; SETUP ; ERRORS ; BREAST IRRADIATION ; FIXATION
    Abstract: Accurate and reproducible patient setup is a prerequisite to fractionated radiotherapy. To evaluate the applicability and technical performance of a commercial 3D surface imaging system for repositioning of breast cancer patients, measurements were performed in a rigid anthropomorphic phantom as well as in healthy volunteers. The camera system records a respiration-gated surface model of the imaged object, which may be registered to a previously recorded reference model. A transformation is provided, which may be applied to the treatment couch to correct the setup of the patient. The system showed a high stability and detected pre-defined shifts of phantoms and healthy volunteers with an accuracy of 0.40 +/- 0.26 mm and 1.02 +/- 0.51 mm, respectively (spatial deviation between pre-defined shift and suggested correction). The accuracy of the suggested rotational correction around the vertical axis was always better than 0.3. in phantom measurements and 0.8. in volunteers, respectively. Comparison of the suggested setup correction with that detected by a second and independently operated marker-based optical system provided consistent results. The results demonstrate that the camera system provides highly accurate setup corrections in a phantom and healthy volunteers. The most efficient use of the system for improving the setup accuracy in breast cancer patients has to be investigated in routine patient treatments
    Type of Publication: Journal article published
    PubMed ID: 17664587
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  • 5
    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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  • 6
    Keywords: CANCER ; radiotherapy ; tumor ; carcinoma ; Germany ; THERAPY ; DIAGNOSIS ; QUANTIFICATION ; DISEASE ; METABOLISM ; radiation ; PATIENT ; primary ; TRIAL ; TRIALS ; chemotherapy ; positron emission tomography ; POSITRON-EMISSION-TOMOGRAPHY ; tomography ; SQUAMOUS-CELL CARCINOMA ; GLUCOSE ; PET ; sensitivity ; laryngeal carcinoma ; RECONSTRUCTION ; NECK-CANCER ; THERAPIES ; ADVANCED HEAD ; chemoradiation ; FDG PET ; hypopharyngeal carcinoma ; larynx organ preservation ; ORGAN PRESERVATION ; RESIDUAL DISEASE
    Abstract: Patients and methods. In a group of 20 patients undergoing chemoradiation for larynx organ preservation after diagnosis of laryngeal and hypopharyngeal carcinoma, F-18-fluordeoxyglucose positron emission tomography (F-18-FDG-PET) was performed before the start of therapy. After i.v.application of 240 MBq FDG, a dynamic PET in 3-D-mode was performed over 90 min (Siemens CTI ECAT EXACT HR+). Analysis was done visually and semiquantitatively (60-90 min p.i.) following iterative reconstruction. Additional F-18-FDG-PET investigations were done and correlated with the clinical outcome in 16/20 patients at 3 months and in 14/20 patients at 6 months after the end of therapy. Results. In 17/20 patients (85%), the preclinical F-18-FDG-PET correlated well with the histologically confirmed primary tumor. Three cases were false negatives. In one case this was due to an increased glucose value (203 mg%). After 3 months, 8/13 (62%) patients showed a positive correlation between clinical and PET results (sensitivity 100%, specificity 70%). After 6 months, 9/11 (82%) patients presented clinically normal PET results. PET results were false negative in one case (sensitivity 67%, specificity 88%). Conclusion. The data of our trial slightly reduce the enthusiasm of early F-18-FDG-PET detection of residual disease after chemoradiation in resectable laryngeal or hypopharyngeal cancer. Further trials should optimize the calculation integrating the exact quantification of glucose metabolism with the aim of improving sensitivity and specificity
    Type of Publication: Journal article published
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  • 7
    Keywords: CANCER ; chest ; BREAST ; breast cancer ; BREAST-CANCER ; RECURRENCE ; WALL ; F ; CHEST-WALL
    Type of Publication: Journal article published
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  • 8
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; carcinoma ; CLINICAL-TRIAL ; Germany ; PROSTATE ; THERAPY ; imaging ; SYSTEM ; VOLUME ; liver ; RISK ; ACCURACY ; computed tomography ; NUCLEAR-MEDICINE ; PATIENT ; kidney ; BONE-MARROW ; TARGET ; NO ; TRIAL ; OVARIAN-CANCER ; chemotherapy ; COMPUTED-TOMOGRAPHY ; treatment planning ; MOTION ; nuclear medicine ; IMRT ; FEASIBILITY ; radiology ; BODIES ; ONCOLOGY ; THERAPIES ; methods ; NUCLEAR ; technique ; MODULATED RADIATION-THERAPY ; BONE ; MEDICINE ; clinical trial ; TOMOTHERAPY ; advanced ovarian cancer ; ADVANCED OVARIAN-CANCER ; helical tomotherapy ; IMRT.4D-CT ; PLATINUM-BASED CHEMOTHERAPY ; TOTAL-BODY ; whole abdominal irradiation
    Abstract: Purpose: To describe a new intensity-modulated radiotherapy (IMRT) technique using helical tomotherapy for whole abdominal irradiation (WAI) in patients with advanced ovarian cancer. Material and Methods: A patient with radically operated ovarian cancer FIGO stage IIIc was treated in a prospective clinical trial with WAI to a total dose of 30 Gy in 1.5-Gy fractions as an additional therapy after adjuvant platinum-based chemotherapy. The planning target volume (PTV) included the entire peritoneal cavity. PTV was adapted according to breathing motion as detected in a four-dimensional respiratory-triggered computed tomography (4D-CT). Inverse treatment planning was done with the Hi-Art tomotherapy planning station. Organs at risk (OARs) were kidneys, liver, bone marrow, spinal cord, thoracic and Lumbosacral vertebral bodies, and pelvic bones. Daily control of positioning accuracy was performed with megavoltage computed tomography (MV-CT). Results: Helical tomotherapy enabled a very homogeneous dose distribution with excellent sparing of OARs and coverage of the PTV (V 90 of 93.1%, V 95 of 86.9%, V-105 of 1.9%, and V-110 of 0.01%). Mean Liver dose was 21.57 Gy and mean kidney doses were 9.75 Gy and 9.14 Gy, respectively. Treatment could be performed in 18.1 min daily and no severe side effects occurred. Conclusion: Helical tomotherapy is feasible and fast for WAI. Tomotherapy enabled excellent coverage of the PTV and effective sparing of Liver, kidneys and bone marrow
    Type of Publication: Journal article published
    PubMed ID: 18330510
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  • 9
    Keywords: 3, A, Abdominal, ADHESION, ADHESIONS, ADJUVANT, ADJUVANT CHEMOTHERAPY, BONE, CANCER, carcinoma, chem
    Abstract: PURPOSE: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. METHODS AND MATERIALS: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. RESULTS: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. CONCLUSIONS: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment
    Type of Publication: Journal article published
    PubMed ID: 19628341
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  • 10
    Keywords: CANCER ; IRRADIATION ; radiotherapy ; SURVIVAL ; carcinoma ; TISSUE ; TRIAL ; RADIATION-THERAPY ; ovarian cancer ; COMPLICATIONS ; FEASIBILITY ; INDUCTION CHEMOTHERAPY ; DOSE DISTRIBUTION ; DEBULKING SURGERY ; Large-field IMRT ; Planning study ; Whole-abdominal irradiation
    Abstract: Introduction: Despite enormous efforts to improve therapeutic strategies for patients with advanced ovarian carcinoma, outcome remains poor even with the advent cisplatinum-based chemotherapy regimen or taxanes with over 70% of patients developing local failure. Several trials were able to establish the potential benefit of adjuvant whole abdominal RT (WAI) though at the cost of sometimes marked side-effects. New technologies like IMRT have the potential of sparing normal tissues thus also potentially limiting treatment-related toxicity, hence a phase I trial was initiated to evaluate potential clinical benefit of WAI with IMRT. We intended to demonstrate that whole-abdominal IMRT is feasible and can be used in a routine clinical setting. Methods: A water-equivalent phantom containing OARs was created simulating organ shape of the upper abdomen to investigate the necessary number of beams for the upper abdominal target irrespective of the number of segments and hence treatment times. We prescribed a total dose of 30 Gy in 1.5 Gy fractions to the median of the target. IMRT treatment plans for three patients with advanced ovarian cancer were created using 2 isocentres and between 12 and 14 beams while restricting the number of segments so as to restrict treatment times to less than 45 min. Dose to OARs such as kidneys and liver was strictly limited even below established maxima. Results: In the phantom plans, no clear indication as to the optimum number of beams could be shown though there seems to be a slight trend toward a higher number of beams yielding better results. Examples demonstrating clinically inacceptable dose distributions for plans using only 9 beams. Acceptable treatment plans for real patients could be achieved using 12-14 beams and 2 iso-centres. Treatment plans consisted of 264-286 segments resulting in an overall treatment time of approximately 37-45 min. Mean doses to the kidneys could be limited to 29.3% [23.1-33.2%] (right), and 26.8% [21-30.4%] (left). 50% of the liver received less than 72.4% [61-83%]. Conclusion: IMRT for whole abdominal irradiation in patients with advanced ovarian carcinoma is applicable and feasible though treatment planning is complex and time-consuming. There is a significant reduction of dose to critical organs by using IMRT while maintaining target volume coverage.
    Type of Publication: Journal article published
    PubMed ID: 21215671
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