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1.
Radiat Oncol ; 16(1): 145, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348765

RESUMO

BACKGROUND: Hypofractionation is increasingly being applied in radiotherapy for prostate cancer, requiring higher accuracy of daily treatment deliveries than in conventional image-guided radiotherapy (IGRT). Different adaptive radiotherapy (ART) strategies were evaluated with regard to dosimetric benefits. METHODS: Treatments plans for 32 patients were retrospectively generated and analyzed according to the PACE-C trial treatment scheme (40 Gy in 5 fractions). Using a previously trained cycle-generative adversarial network algorithm, synthetic CT (sCT) were generated out of five daily cone-beam CT. Dose calculation on sCT was performed for four different adaptation approaches: IGRT without adaptation, adaptation via segment aperture morphing (SAM) and segment weight optimization (ART1) or additional shape optimization (ART2) as well as a full re-optimization (ART3). Dose distributions were evaluated regarding dose-volume parameters and a penalty score. RESULTS: Compared to the IGRT approach, the ART1, ART2 and ART3 approaches substantially reduced the V37Gy(bladder) and V36Gy(rectum) from a mean of 7.4cm3 and 2.0cm3 to (5.9cm3, 6.1cm3, 5.2cm3) as well as to (1.4cm3, 1.4cm3, 1.0cm3), respectively. Plan adaptation required on average 2.6 min for the ART1 approach and yielded doses to the rectum being insignificantly different from the ART2 approach. Based on an accumulation over the total patient collective, a penalty score revealed dosimetric violations reduced by 79.2%, 75.7% and 93.2% through adaptation. CONCLUSION: Treatment plan adaptation was demonstrated to adequately restore relevant dose criteria on a daily basis. While for SAM adaptation approaches dosimetric benefits were realized through ensuring sufficient target coverage, a full re-optimization mainly improved OAR sparing which helps to guide the decision of when to apply which adaptation strategy.

2.
Radiother Oncol ; 158: 230-236, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33667585

RESUMO

BACKGROUND: Local treatment of metastases in combination with systemic therapy can prolong survival of oligo-metastasized patients. To fully exploit this potential, safe and effective treatments are needed to ensure long-term metastases control. Stereotactic body radiotherapy (SBRT) is one means, however, for moving liver tumors correct delivery of high doses is challenging. After validating equal in-vivo treatment accuracy, we analyzed a pooled multi-platform liver-SBRT-database for clinical outcome. METHODS: Local control (LC), progression-free interval (PFI), overall survival (OS), predictive factors and toxicity was evaluated in 135 patients with 227 metastases treated by gantry-based SBRT (deep-inspiratory breath-hold-gating; n = 71) and robotic-based SBRT (fiducial-tracking, n = 156) with mean gross tumor volume biological effective dose (GTV-BEDα/ß=10Gy) of 146.6 Gy10. RESULTS: One-, and five-year LC was 90% and 68.7%, respectively. On multivariate analysis, LC was significantly predicted by colorectal histology (p = 0.006). Median OS was 20 months with one- and two-year OS of 67% and 37%. On multivariate analysis, ECOG-status (p = 0.003), simultaneous chemotherapy (p = 0.003), time from metastasis detection to SBRT-treatment (≥2months; p = 0.021) and LC of the treated metastases (≥12 months, p < 0.009) were significant predictors for OS. One- and two-year PFI were 30.5% and 14%. Acute toxicity was mild and rare (14.4% grade I, 2.3% grade II, 0.6% grade III). Chronic °III/IV toxicities occurred in 1.1%. CONCLUSIONS: Patient selection, time to treatment and sufficient doses are essential to achieve optimal outcome for SBRT with active motion compensation. Local control appears favorable compared to historical control. Long-term LC of the treated lesions was associated with longer overall survival.


Assuntos
Radiocirurgia , Seguimentos , Humanos , Fígado , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
3.
Int J Radiat Oncol Biol Phys ; 110(3): 745-756, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33508373

RESUMO

PURPOSE: Cardiac radioablation is a novel treatment option for therapy-refractory ventricular tachycardia (VT) ineligible for catheter ablation. Three-dimensional clinical target volume (CTV) definition is a key step, and this complex interdisciplinary procedure includes VT-substrate identification based on electroanatomical mapping (EAM) and its transfer to the planning computed tomography (PCT). Benchmarking of this process is necessary for multicenter clinical studies such as the RAVENTA trial. METHODS AND MATERIALS: For benchmarking of the RAVENTA trial, patient data (epicrisis, electrocardiogram, high-resolution EAM, contrast-enhanced cardiac computed tomography, PCT) of 3 cases were sent to 5 university centers for independent CTV generation, subsequent structure analysis, and consensus finding. VT substrates were first defined on multiple EAM screenshots/videos and manually transferred to the PCT. The generated structure characteristics were then independently analyzed (volume, localization, surface distance and conformity). After subsequent discussion, consensus structures were defined. RESULTS: VT substrate on the EAM showed visible variability in extent and localization for cases 1 and 2 and only minor variability for case 3. CTVs ranged from 6.7 to 22.9 cm3, 5.9 to 79.9 cm3, and 9.4 to 34.3 cm3; surface area varied from 1087 to 3285 mm2, 1077 to 9500 mm2, and 1620 to 4179 mm2, with a Hausdorff-distance of 15.7 to 39.5 mm, 23.1 to 43.5 mm, and 15.9 to 43.9 mm for cases 1 to 3, respectively. The absolute 3-dimensional center-of-mass difference was 5.8 to 28.0 mm, 8.4 to 26 mm, and 3.8 to 35.1 mm for cases 1 to 3, respectively. The entire process resulted in CTV structures with a conformity index of 0.2 to 0.83, 0.02 to 0.85, and 0.02 to 0.88 (ideal 1) with the consensus CTV as reference. CONCLUSIONS: Multicenter efficacy endpoint assessment of cardiac radioablation for therapy-refractory VT requires consistent CTV transfer methods from the EAM to the PCT. VT substrate definition and CTVs were comparable with current clinical practice. Remarkable differences regarding the degree of agreement of the CTV definition on the EAM and the PCT were noted, indicating a loss of agreement during the transfer process between EAM and PCT. Cardiac radioablation should be performed under well-defined protocols and in clinical trials with benchmarking and consensus forming.


Assuntos
Radiocirurgia , Taquicardia Ventricular/radioterapia , Benchmarking , Humanos
4.
Phys Med ; 80: 308-316, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33246190

RESUMO

PURPOSE: Image-guided radiation therapy could benefit from implementing adaptive radiation therapy (ART) techniques. A cycle-generative adversarial network (cycle-GAN)-based cone-beam computed tomography (CBCT)-to-synthetic CT (sCT) conversion algorithm was evaluated regarding image quality, image segmentation and dosimetric accuracy for head and neck (H&N), thoracic and pelvic body regions. METHODS: Using a cycle-GAN, three body site-specific models were priorly trained with independent paired CT and CBCT datasets of a kV imaging system (XVI, Elekta). sCT were generated based on first-fraction CBCT for 15 patients of each body region. Mean errors (ME) and mean absolute errors (MAE) were analyzed for the sCT. On the sCT, manually delineated structures were compared to deformed structures from the planning CT (pCT) and evaluated with standard segmentation metrics. Treatment plans were recalculated on sCT. A comparison of clinically relevant dose-volume parameters (D98, D50 and D2 of the target volume) and 3D-gamma (3%/3mm) analysis were performed. RESULTS: The mean ME and MAE were 1.4, 29.6, 5.4 Hounsfield units (HU) and 77.2, 94.2, 41.8 HU for H&N, thoracic and pelvic region, respectively. Dice similarity coefficients varied between 66.7 ± 8.3% (seminal vesicles) and 94.9 ± 2.0% (lungs). Maximum mean surface distances were 6.3 mm (heart), followed by 3.5 mm (brainstem). The mean dosimetric differences of the target volumes did not exceed 1.7%. Mean 3D gamma pass rates greater than 97.8% were achieved in all cases. CONCLUSIONS: The presented method generates sCT images with a quality close to pCT and yielded clinically acceptable dosimetric deviations. Thus, an important prerequisite towards clinical implementation of CBCT-based ART is fulfilled.


Assuntos
Processamento de Imagem Assistida por Computador , Planejamento da Radioterapia Assistida por Computador , Algoritmos , Tomografia Computadorizada de Feixe Cônico , Humanos , Masculino , Radiometria , Dosagem Radioterapêutica
5.
Strahlenther Onkol ; 196(5): 421-443, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32211939

RESUMO

This review details and discusses the technological quality requirements to ensure the desired quality for stereotactic radiotherapy using photon external beam radiotherapy as defined by the DEGRO Working Group Radiosurgery and Stereotactic Radiotherapy and the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The covered aspects of this review are 1) imaging for target volume definition, 2) patient positioning and target volume localization, 3) motion management, 4) collimation of the irradiation and beam directions, 5) dose calculation, 6) treatment unit accuracy, and 7) dedicated quality assurance measures. For each part, an expert review for current state-of-the-art techniques and their particular technological quality requirement to reach the necessary accuracy for stereotactic radiotherapy divided into intracranial stereotactic radiosurgery in one single fraction (SRS), intracranial fractionated stereotactic radiotherapy (FSRT), and extracranial stereotactic body radiotherapy (SBRT) is presented. All recommendations and suggestions for all mentioned aspects of stereotactic radiotherapy are formulated and related uncertainties and potential sources of error discussed. Additionally, further research and development needs in terms of insufficient data and unsolved problems for stereotactic radiotherapy are identified, which will serve as a basis for the future assignments of the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. The review was group peer-reviewed, and consensus was obtained through multiple working group meetings.


Assuntos
Consenso , Garantia da Qualidade dos Cuidados de Saúde/normas , Radiocirurgia/normas , Alemanha , Doses de Radiação , Sociedades Médicas
6.
Sci Rep ; 9(1): 15489, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664066

RESUMO

A long-standing hypothesis in radiotherapy is that intensity-modulated radiotherapy (IMRT) increases the risk of second cancer due to low-dose exposure of large volumes of normal tissue. Therefore, young patients are still treated with conventional techniques rather than with modern IMRT. We challenged this hypothesis in first-of-its-kind experiments using an animal model. Cancer-prone Tp53+/C273X knockout rats received mediastinal irradiation with 3 × 5 or 3 × 8 Gy using volumetric-modulated arc therapy (VMAT, an advanced IMRT) or conventional anterior-posterior/posterior-anterior (AP/PA) beams using non-irradiated rats as controls (n = 15/group, ntotal = 90). Tumors were assigned to volumes receiving 90-107%, 50-90%, 5-50%, and <5% of the target dose and characterized by histology and loss-of-heterozygosity (LOH). Irradiated rats predominantly developed lymphomas and sarcomas in areas receiving 50-107% (n = 26) rather than 5-50% (n = 7) of the target dose. Latency was significantly shortened only after 3 × 8 Gy vs. controls (p < 0.0001). The frequency (14/28 vs. 19/29; p = 0.29) and latency (218 vs. 189 days; p = 0.17) of radiation-associated tumors were similar after VMAT vs. AP/PA. LOH was strongly associated with sarcoma but not with treatment. The results do not support the hypothesis that IMRT increases the risk of second cancer. Thus the current practice of withholding dose-sparing IMRT from young patients may need to be re-evaluated.


Assuntos
Modelos Animais de Doenças , Mediastino/efeitos da radiação , Neoplasias Induzidas por Radiação/epidemiologia , Radioterapia de Intensidade Modulada/métodos , Animais , Feminino , Masculino , Órgãos em Risco , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Ratos , Ratos Transgênicos , Fatores de Risco , Proteína Supressora de Tumor p53/genética
7.
Phys Med ; 65: 46-52, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31430586

RESUMO

AIM: Ultrasound-based repositioning and real-time-monitoring aim at the improvement of the precision of SBRT in deep inspiration breath-hold (DIBH). Accuracy of ultrasound-based daily repositioning was estimated by comparison with DIBH-cone-beam-CT. Intrafraction motion during beam-delivery was assessed by ultrasound-real-time-monitoring. PATIENTS/METHODS: Residual error after ultrasound-based interfractional repositioning (85 fractions, 16 SBRT-series; 14 patients) was assessed by marker-based (7 series) or liver-contour-based (9 series) matching in DIBH-CBCT. During beam-delivery, the percentage of 3D misalignment vector below 2 mm, between 2 and 5 mm, 5-7 mm and over 7 mm was estimated. Percentage of relevant target-displacements was analyzed as a function of DIBH-duration. RESULTS: Residual error after ultrasound-based positioning was 0.4 ±â€¯3.3 mm in LR (left-right), 0.2 ±â€¯4.3 mm in CC (cranio-caudal) and 1.0 ±â€¯3.0 mm in AP (anterior-posterior) directions (vector magnitude 5.4 ±â€¯3.3 mm, MV ±â€¯SD). Over 544 DIBHs, target displacement was 1.3 ±â€¯0.5 mm, 0.7 ±â€¯0.3 mm, 1.6 ±â€¯0.6 mm for CC, LR and AP directions, respectively (3D-vector 2.5 ±â€¯0.7 mm). 3D misalignment vector length was below 2 mm in 49.8%, between 2 and 7 mm in 46.3%, and over 7 mm in 3.9% of the beam-delivery-time. During the first 5 s of the DIBH, 3D-misalignment vector length was always below 10 mm. Percentage of target displacements over 10 mm was 0.2%, 0.5% and 0.8% for 10 s, 15 s and 20 s DIBH-duration. CONCLUSIONS: Ultrasound-based interfractional repositioning is an accurate method for daily localization of abdominal DIBH-SBRT targets. Residual motion is <7 mm in 96% of the beam-delivery-time. Deviations >10 mm occur rarely and can be avoided by gating the beam at a predefined threshold. Ideal DIBH-duration should not exceed 15 s.


Assuntos
Abdome/diagnóstico por imagem , Abdome/efeitos da radiação , Suspensão da Respiração , Posicionamento do Paciente/métodos , Doses de Radiação , Radiocirurgia/métodos , Cirurgia Assistida por Computador/métodos , Idoso , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Movimento , Fatores de Tempo , Ultrassonografia
8.
Radiother Oncol ; 135: 78-85, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015174

RESUMO

PURPOSE: Lung tumors treated with hypo-fractionated deep-inspiration breath-hold stereotactic body radiotherapy benefit from fast imaging and treatment. Single breath-hold cone-beam-CT (CBCT) could reduce motion artifacts and improve treatment precision. Thus, gantry speed was accelerated to 18°/s, limiting acquisition time to 10-20 s. Image quality, dosimetry and registration accuracy were compared with standard-CBCT (3°/s). METHODS AND MATERIALS: For proof-of-concept, image quality was analyzed following customer acceptance tests, CT-dose index measured, and registration accuracy determined with an off-centered ball-bearing-phantom. A lung-tumor patient was simulated with differently shaped tumor-mimicking inlays in a thorax-phantom. Signal-to-noise-ratio, contrast-to-noise-ratio and geometry of the inlays quantified image quality. Dose was measured in representative positions. Registration accuracy was determined with inlays scanned in pre-defined positions. Manual, automatic (clinical software) and objective-automatic (in-house-developed) registration was performed on planning-CT, offsets between results and applied shifts were compared. RESULTS: Image quality of ultrafast-CBCT was adequate for high-contrast areas, despite contrast-reduction of ∼80% due to undersampling. Dose-output was considerably reduced by 60-83% in presented setup; variations are due to gantry-braking characteristics. Registration accuracy was maintained better than 1 mm, mean displacement errors were 0.0 ±â€¯0.2 mm with objective-automatic registration. Ultrafast-CBCT showed no significant registration differences to standard-CBCT. CONCLUSIONS: This study of first tests with faster gantry rotation of 18°/s showed promising results for ultrafast high-contrast lung tumor CBCT imaging within single breath-hold of 10-20 s. Such fast imaging times, in combination with fast treatment delivery, could pave the way for intra-fractional combined imaging and treatment within one breath-hold phase, and thus mitigate residual motion and increase treatment accuracy and patient comfort. Even generally speaking, faster gantry rotation could set a benchmark with immense clinical impact where time matters most: palliative patient care, general reduction in uncertainty, and increase in patient throughput especially important for emerging markets with high patient numbers.


Assuntos
Suspensão da Respiração , Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Pulmonares/radioterapia , Radioterapia Guiada por Imagem/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Aceleradores de Partículas , Imagens de Fantasmas , Dosagem Radioterapêutica , Rotação
9.
J Reconstr Microsurg ; 35(1): 46-56, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29996155

RESUMO

BACKGROUND: Regenerative medicine is still deficient in the reconstruction after cancer due to impaired vascularization after radiotherapy and due to the need to substitute larger defects after tumor excision. Aiming at introducing regenerative medicine for reconstruction after cancer, we tested an axially vascularized bone construct in an experimental setting that mimics the clinical situation after tumor resection and adjuvant radiotherapy. METHODS: Twenty bone constructs were axially vascularized using microsurgically created arteriovenous loops and were implanted subcutaneously in Lewis rats. After 2 weeks, the animals were randomly allocated either to receive a clinically relevant single dose of external beam irradiation or not (n = 10 for each group). The animals were sacrificed either after 1 week or 10 weeks after irradiation (n = 5 for each time point). The constructs were tested for vascularization, tissue growth, cellular proliferation, cellular apoptosis, and osteogenic differentiation via histomorphometric, immunohistochemical, and polymerase chain reaction (PCR) analysis. One construct per group was subjected at 10 weeks to qualitative micro-computed tomography (CT) imaging. RESULTS: Tissue generation and cellular proliferation were significantly reduced at 1 week after irradiation, but no longer significantly different after 10 weeks.No significant differences in vascularization were detected at any time point. Apoptosis did not show any statistically significant differences between both groups at both time points. At the late time point, mature bone was considerably more in the irradiated group, but the results were not statistically significant. PCR analysis showed a significantly enhanced expression of osteocalcin in the irradiated group at 1 week. Micro-CT imaging showed that both constructs were adequately vascularized with no evident morphologic differences regarding vascular density or vascular distribution. CONCLUSIONS: Axially vascularized bone constructs can withstand clinically relevant doses of irradiation and retain their angiogenic and osteogenic potential in the long term. Irradiation led to a delayed tissue generation with a comparatively enhanced osteogenic differentiation within the constructs.


Assuntos
Derivação Arteriovenosa Cirúrgica/métodos , Microcirurgia , Neovascularização Fisiológica/efeitos da radiação , Osteogênese/efeitos da radiação , Medicina Regenerativa , Microtomografia por Raio-X/efeitos adversos , Animais , Transplante Ósseo , Modelos Animais , Distribuição Aleatória , Ratos , Ratos Endogâmicos Lew
10.
Anticancer Res ; 38(8): 4789-4796, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30061250

RESUMO

BACKGROUND/AIM: Metastases involving the adrenal glands can be treated surgically or with radiation therapy. Retrospective studies indicate that radiotherapy for this indication is safe, well-tolerated and associated with symptom palliation and good local control. We conducted this analysis to report on patterns and outcomes of patients with adrenal metastases treated with hypo- or conventionally fractionated image-guided radiotherapy. PATIENTS AND METHODS: Patients with adrenal metastases from solid tumors treated at our department between 01/2010-12/2017 were reviewed. A total of 22 lesions were treated in 18 patients with a median dose of 35 Gy (20-60 Gy) in a median number of 7 (4-25) fractions. RESULTS: No grade ≥3 toxicity occurred. Median overall survival was 11.9 months. Five local failures occurred (22.7%). Lesion sizes or radiation dose were not correlated with local control. Patients treated for oligometastatic and oligoprogressive disease had a median overall survival of 33 and 6.5 months, respectively (palliative/polymetastatic: 1.6 months). Symptoms improved in all patients treated for clinically apparent lesions. CONCLUSION: Stereotactic radiotherapy of adrenal metastases was safe and effective in patients with oligometastases or oligoprogression. In palliative patients, short-course radiotherapy complemented with supportive care should be preferred.


Assuntos
Neoplasias das Glândulas Suprarrenais , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/métodos , Neoplasias das Glândulas Suprarrenais/mortalidade , Neoplasias das Glândulas Suprarrenais/radioterapia , Neoplasias das Glândulas Suprarrenais/secundário , Fracionamento da Dose de Radiação , Humanos , Resultado do Tratamento
11.
Strahlenther Onkol ; 194(9): 815-823, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29802434

RESUMO

BACKGROUND AND PURPOSE: In this retrospective treatment planning study, the effect of a uniform and non-uniform planning target volume (PTV) dose coverage as well as a coplanar and non-coplanar volumetric modulated arc therapy (VMAT) delivery approach for lung stereotactic body radiation therapy (SBRT) in deep inspiration breath-hold (DIBH) were compared. MATERIALS AND METHODS: For 46 patients with lesions in the peripheral lungs, three different treatment plans were generated: First, a coplanar 220° VMAT sequence with a uniform PTV dose prescription (UC). Second, a coplanar 220° VMAT treatment plan with a non-uniform dose distribution in the PTV (nUC). Third, a non-coplanar VMAT dose delivery with four couch angles (0°, ±35°, 90°) and a non-uniform prescription (nUnC) was used. All treatment plans were optimized for pareto-optimality with respect to PTV coverage and ipsilateral lung dose. Treatment sequences were delivered on a flattening-filter-free linear accelerator and beam-on times were recorded. Dosimetric comparison between the three techniques was performed. RESULTS: For the three scenarios (UC, nUC, nUnC), median gross tumor volume (GTV) doses were 63.4 ± 2.5, 74.4 ± 3.6, and 77.9 ± 3.8 Gy, and ipsilateral V10Gy lung volumes were 15.7 ± 6.1, 13.9 ± 4.7, and 12.0 ± 5.1%, respectively. Normal tissue complication probability of the ipsilateral lung was 3.9, 3.1, and 2.8%, respectively. The number of monitor units were 5141 ± 1174, 4104 ± 786, and 3657 ± 710 MU and the corresponding beam-on times were 177 ± 54, 143 ± 29, and 148 ± 26 s. CONCLUSION: For SBRT treatments in DIBH, a non-uniform dose prescription in the PTV, combined with a non-coplanar VMAT arc arrangement, significantly spares the ipsilateral lung while increasing dose to the GTV without major treatment time increase.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Adulto , Idoso , Suspensão da Respiração , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Pulmão/efeitos da radiação , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Taxa de Sobrevida , Carga Tumoral/efeitos da radiação
12.
PLoS One ; 13(1): e0190183, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29346397

RESUMO

Localization microscopy has shown to be capable of systematic investigations on the arrangement and counting of cellular uptake of gold nanoparticles (GNP) with nanometer resolution. In this article, we show that the application of specially modified RNA targeting gold nanoparticles ("SmartFlares") can result in ring like shaped GNP arrangements around the cell nucleus. Transmission electron microscopy revealed GNP accumulation in vicinity to the intracellular membrane structures including them of the endoplasmatic reticulum. A quantification of the radio therapeutic dose enhancement as a proof of principle was conducted with γH2AX foci analysis: The application of both-SmartFlares and unmodified GNPs-lead to a significant dose enhancement with a factor of up to 1.2 times the dose deposition compared to non-treated breast cancer cells. This enhancement effect was even more pronounced for SmartFlares. Furthermore, it was shown that a magnetic field of 1 Tesla simultaneously applied during irradiation has no detectable influence on neither the structure nor the dose enhancement dealt by gold nanoparticles.


Assuntos
Neoplasias da Mama/patologia , Ouro/química , Nanopartículas Metálicas , RNA Neoplásico/efeitos dos fármacos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Humanos , Nanopartículas Metálicas/química
13.
J Tissue Eng Regen Med ; 12(2): e657-e668, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-27696709

RESUMO

In order to introduce bone tissue engineering to the field of oncological reconstruction, we are investigating for the first time the effect of various doses of ionizing irradiation on axially vascularized bone constructs. Synthetic bone constructs were created and implanted in 32 Lewis rats. Each construct was axially vascularized through an arteriovenous loop made by direct anastomosis of the saphenous vessels. After 2 weeks, the animals received ionizing irradiation of 9 Gy, 12 Gy and 15 Gy, and were accordingly classified to groups I, II and III, respectively. Group IV was not irradiated and acted as a control. Tissue generation, vascularity, cellular proliferation and apoptosis were investigated either 2 or 5 weeks after irradiation through micro-computed tomography, histomorphometry and real-time polymerase chain reaction (PCR). At 2 weeks after irradiation, tissue generation and central vascularity were significantly lower and apoptosis was significantly higher in groups II and III than group IV, but without signs of necrosis. Cellular proliferation was significantly lower in groups I and II. After 5 weeks, the irradiated groups showed improvement in all parameters in relation to the control group, indicating a retained capacity for angiogenesis after irradiation. PCR results confirmed the expression of osteogenesis-related genes in all irradiated groups. Dense collagen was detected 5 weeks after irradiation, and one construct showed discrete islands of bone indicating a retained osteogenic capacity after irradiation. This demonstrates for the first time that axial vascularization was capable of supporting a synthetic bone construct after a high dose of irradiation that is comparable to adjuvant radiotherapy. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Osso e Ossos/irrigação sanguínea , Osso e Ossos/efeitos da radiação , Neovascularização Fisiológica , Osteogênese , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Apoptose/efeitos da radiação , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Osso e Ossos/diagnóstico por imagem , Proliferação de Células/efeitos da radiação , Relação Dose-Resposta à Radiação , Regulação da Expressão Gênica/efeitos da radiação , Implantes Experimentais , Masculino , Osteogênese/efeitos da radiação , Ratos Endogâmicos Lew , Microtomografia por Raio-X
14.
PLoS One ; 12(11): e0187710, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29125857

RESUMO

PURPOSE: Combined ultrafast 90°+90° kV-MV-CBCT within single breath-hold of 15s has high clinical potential for accelerating imaging for lung cancer patients treated with deep inspiration breath-hold (DIBH). For clinical feasibility of kV-MV-CBCT, dose exposure has to be small compared to prescribed dose. In this study, kV-MV dose output is evaluated and compared to clinically-established kV-CBCT. METHODS: Accurate dose calibration was performed for kV and MV energy; beam quality was determined. For direct comparison of MV and kV dose output, relative biological effectiveness (RBE) was considered. CT dose index (CTDI) was determined and measurements in various representative locations of an inhomogeneous thorax phantom were performed to simulate the patient situation. RESULTS: A measured dose of 20.5mGE (Gray-equivalent) in the target region was comparable to kV-CBCT (31.2mGy for widely-used, and 9.1mGy for latest available preset), whereas kV-MV spared healthy tissue and reduced dose to 6.6mGE (30%) due to asymmetric dose distribution. The measured weighted CTDI of 12mGE for kV-MV lay in between both clinical presets. CONCLUSIONS: Dosimetric properties were in agreement with established imaging techniques, whereas exposure to healthy tissue was reduced. By reducing the imaging time to a single breath-hold of 15s, ultrafast combined kV-MV CBCT shortens patient time at the treatment couch and thus improves patient comfort. It is therefore usable for imaging of hypofractionated lung DIBH patients.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Imagens de Fantasmas , Relação Dose-Resposta à Radiação , Humanos
15.
PLoS One ; 12(9): e0183486, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28886048

RESUMO

PURPOSE: To introduce a new method of deriving a virtual source model (VSM) of a linear accelerator photon beam from a phase space file (PSF) for Monte Carlo (MC) dose calculation. MATERIALS AND METHODS: A PSF of a 6 MV photon beam was generated by simulating the interactions of primary electrons with the relevant geometries of a Synergy linear accelerator (Elekta AB, Stockholm, Sweden) and recording the particles that reach a plane 16 cm downstream the electron source. Probability distribution functions (PDFs) for particle positions and energies were derived from the analysis of the PSF. These PDFs were implemented in the VSM using inverse transform sampling. To model particle directions, the phase space plane was divided into a regular square grid. Each element of the grid corresponds to an area of 1 mm2 in the phase space plane. The average direction cosines, Pearson correlation coefficient (PCC) between photon energies and their direction cosines, as well as the PCC between the direction cosines were calculated for each grid element. Weighted polynomial surfaces were then fitted to these 2D data. The weights are used to correct for heteroscedasticity across the phase space bins. The directions of the particles created by the VSM were calculated from these fitted functions. The VSM was validated against the PSF by comparing the doses calculated by the two methods for different square field sizes. The comparisons were performed with profile and gamma analyses. RESULTS: The doses calculated with the PSF and VSM agree to within 3% /1 mm (>95% pixel pass rate) for the evaluated fields. CONCLUSION: A new method of deriving a virtual photon source model of a linear accelerator from a PSF file for MC dose calculation was developed. Validation results show that the doses calculated with the VSM and the PSF agree to within 3% /1 mm.


Assuntos
Método de Monte Carlo , Aceleradores de Partículas , Fótons , Algoritmos
16.
Phys Med ; 37: 82-87, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28535919

RESUMO

BACKGROUND: To the present date, IORT has been eye and hand guided without treatment planning and tissue heterogeneity correction. This limits the precision of the application and the precise documentation of the location and the deposited dose in the tissue. Here we present a set-up where we use image guidance by intraoperative cone beam computed tomography (CBCT) for precise online Monte Carlo treatment planning including tissue heterogeneity correction. MATERIALS AND METHODS: An IORT was performed during balloon kyphoplasty using a dedicated Needle Applicator. An intraoperative CBCT was registered with a pre-op CT. Treatment planning was performed in Radiance using a hybrid Monte Carlo algorithm simulating dose in homogeneous (MCwater) and heterogeneous medium (MChet). Dose distributions on CBCT and pre-op CT were compared with each other. Spinal cord and the metastasis doses were evaluated. RESULTS: The MCwater calculations showed a spherical dose distribution as expected. The minimum target dose for the MChet simulations on pre-op CT was increased by 40% while the maximum spinal cord dose was decreased by 35%. Due to the artefacts on the CBCT the comparison between MChet simulations on CBCT and pre-op CT showed differences up to 50% in dose. CONCLUSIONS: igIORT and online treatment planning improves the accuracy of IORT. However, the current set-up is limited by CT artefacts. Fusing an intraoperative CBCT with a pre-op CT allows the combination of an accurate dose calculation with the knowledge of the correct source/applicator position. This method can be also used for pre-operative treatment planning followed by image guided surgery.


Assuntos
Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem , Algoritmos , Artefatos , Tomografia Computadorizada de Feixe Cônico , Humanos , Método de Monte Carlo
17.
Strahlenther Onkol ; 193(7): 578-588, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28220185

RESUMO

BACKGROUND: This treatment planning study analyzes dose coverage and dose to organs at risk (OAR) in intensity-modulated radiotherapy (IMRT) of rectal cancer and compares prone vs. supine positioning as well as the effect of dose optimization for the small bowel (SB) by additional dose constraints in the inverse planning process. PATIENTS AND METHODS: Based on the CT datasets of ten male patients in both prone and supine position, a total of four different IMRT plans were created for each patient. OAR were defined as the SB, bladder, and femoral heads. In half of the plans, two additional SB cost functions were used in the inverse planning process. RESULTS: There was a statistically significant dose reduction for the SB in prone position of up to 41% in the high and intermediate dose region, compared with the supine position. Furthermore, the femoral heads showed a significant dose reduction in prone position in the low dose region. Regarding the additional active SB constraints, the dose in the high dose region of the SB was significantly reduced by up to 14% with the additional cost functions. There were no significant differences in the dose distribution of the planning target volume (PTV) and the bladder. CONCLUSION: Prone positioning can significantly reduce dose to the SB in IMRT for rectal cancer and therefore should not only be used in 3D conformal radiotherapy but also in IMRT of rectal cancer. Further protection of the SB can be achieved by additional dose constraints in inverse planning without jeopardizing the homogeneity of the PTV.


Assuntos
Neoplasias Colorretais/radioterapia , Intestino Delgado/efeitos da radiação , Posicionamento do Paciente , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Proteção Radiológica , Radiometria , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Cabeça do Fêmur/efeitos da radiação , Humanos , Masculino , Órgãos em Risco/efeitos da radiação , Decúbito Ventral , Decúbito Dorsal , Bexiga Urinária/efeitos da radiação
18.
Z Med Phys ; 27(1): 56-64, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27320149

RESUMO

PURPOSE: In radiation therapy of small animals treatment depths range from a few millimetres to several centimetres. In order to spare surrounding organs at risk steep dose gradients are necessary. To minimize the treatment time, and therefore the strain to the animals, a high dose rate is required. A description how these parameters can be optimized through an appropriate choice of collimators with different source surface distances (SSD) as well as different materials and geometries is presented. MATERIAL AND METHODS: An industrial micro-CT unit (Y.Fox, YXLON GmbH, Hamburg, Germany) was converted into a precision irradiator for small animals. Different collimators of either stainless steel (Fe) with cylindrical bores (SSD=42mm) or tungsten (W) with conical bores (SSD=14mm) were evaluated. The dosimetry of very small radiation fields presents a challenge and was performed with GafChromic EBT3 films (Ashland, Vayne, KY, USA) in a water phantom. The films were calibrated with an ionization chamber in the uncollimated field. Treatments were performed via a rotation of the objects with a fixed radiation source. RESULTS: As expected, the shorter SSD of the W-collimators resulted in a (4.5±1.6)-fold increase of the dose rates compared to the corresponding Fe-collimators. The ratios of the dose rates at 1mm and 10mm depth in the water phantom was (2.6±0.2) for the Fe- and (4.5±0.1) for the W-collimators. For rotational treatments in a cylindrical plastic phantom maximum dose rates of up to 1.2Gy/min for Fe- and 5.1Gy/min for W-collimators were measured. CONCLUSION: Choosing the smallest possible SSD leads to a high dose rate and a high surface dose, which is of advantage for the treatment of superficial target volumes. For larger SSD the dose rate is lower and the depth dose curve is shallower. This leads to a reduction of the surface dose and is best suited for treatments of deeper seated target volumes. Divergent collimator bores have, due to the reduced scatter within the collimators, a steeper penumbra. The dosimetry of small kilovoltage beams with Gafchromic EBT3 films in a water phantom has proven successful.


Assuntos
Microtomografia por Raio-X/instrumentação , Animais , Calibragem , Alemanha , Imagens de Fantasmas , Exposição à Radiação/prevenção & controle , Radiometria , Dosagem Radioterapêutica
19.
Radiother Oncol ; 119(2): 351-6, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27090736

RESUMO

BACKGROUND AND PURPOSE: Since IMRT-techniques lead to an increasingly complicated environment, a patient specific IMRT-plan verification is recommended. Furthermore, verifications during patient irradiation and 3D dose reconstruction have the potential to improve treatment delivery, accuracy and safety. This study provides a detailed investigation of the new transmission detector (DTD) Dolphin (IBA Dosimetry, Germany) for online dosimetry. MATERIALS AND METHODS: The clinical performance of the DTD was tested by dosimetric plan verification in 2D and 3D for 18 IMRT-sequences. In 2D, DTD measurements were compared to a pre-treatment verification method and a treatment planning system by gamma index and dose difference evaluations. In 3D, dose-volume-histogram (DVH) indices and gamma analysis were evaluated. Furthermore, the error detection ability was tested with leaf position uncertainties and deviations in the linear accelerator (LINAC) output. RESULTS: The DTD measurements were in excellent agreement to reference measurements in both 2D (γ3%,3mm=(99.7±0.6)% <1, ΔD±5%=(99.5±0.5)%) and 3D. Only a small dose underestimation (<2%) within the target volume was observed when analyzing DVH-indices. Positional errors of the leaf banks larger than 1mm and errors in LINAC output larger than 2% were identified with the DTD. CONCLUSIONS: The DTD measures the delivered dose with sufficient accuracy and is therefore suitable for clinical routine.


Assuntos
Neoplasias/radioterapia , Radiometria/instrumentação , Planejamento da Radioterapia Assistida por Computador/instrumentação , Raios gama , Humanos , Aceleradores de Partículas , Garantia da Qualidade dos Cuidados de Saúde , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos
20.
Strahlenther Onkol ; 192(5): 312-21, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26864049

RESUMO

PURPOSE: Combined kV-MV cone-beam CT (CBCT) is a promising approach to accelerate imaging for patients with lung tumors treated with deep inspiration breath-hold. During a single breath-hold (15 s), a 3D kV-MV CBCT can be acquired, thus minimizing motion artifacts and increasing patient comfort. Prior to clinical implementation, positioning accuracy was evaluated and compared to clinically established imaging techniques. METHODS AND MATERIALS: An inhomogeneous thorax phantom with four tumor-mimicking inlays was imaged in 10 predefined positions and registered to a planning CT. Novel kV-MV CBCT imaging (90° arc) was compared to clinically established kV-chest CBCT (360°) as well as nonclinical kV-CBCT and low-dose MV-CBCT (each 180°). Manual registration, automatic registration provided by the manufacturer and an additional in-house developed manufacturer-independent framework based on the MATLAB registration toolkit were applied. RESULTS: Systematic setup error was reduced to 0.05 mm by high-precision phantom positioning with optical tracking. Stochastic mean displacement errors were 0.5 ± 0.3 mm in right-left, 0.4 ± 0.4 mm in anteroposterior and 0.0 ± 0.4 mm in craniocaudal directions for kV-MV CBCT with manual registration (maximum errors of no more than 1.4 mm). Clinical kV-chest CBCT resulted in mean errors of 0.2 mm (other modalities: 0.4-0.8 mm). Similar results were achieved with both automatic registration methods. CONCLUSION: The comparison study of repositioning accuracy between novel kV-MV CBCT and clinically established volume imaging demonstrated that registration accuracy is maintained below 1 mm. Since imaging time is reduced to one breath-hold, kV-MV CBCT is ideal for image guidance, e.g., in lung stereotactic ablative radiotherapy.


Assuntos
Tomografia Computadorizada de Feixe Cônico/instrumentação , Imageamento Tridimensional/instrumentação , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Radioterapia Guiada por Imagem/instrumentação , Técnica de Subtração , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Imagens de Fantasmas , Intensificação de Imagem Radiográfica/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Integração de Sistemas
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