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1.
Cancers (Basel) ; 13(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668646

RESUMO

Infection with the human papillomavirus (HPV) has been identified as a major risk factor for oropharyngeal cancer (OPC). HPV-related OPCs have been shown to be more radiosensitive and to have a reduced risk for cancer related death. Hence, the histological determination of HPV status of cancer patients depicts an essential diagnostic factor. We investigated the ability of deep learning models for imaging based HPV status detection. To overcome the problem of small medical datasets, we used a transfer learning approach. A 3D convolutional network pre-trained on sports video clips was fine-tuned, such that full 3D information in the CT images could be exploited. The video pre-trained model was able to differentiate HPV-positive from HPV-negative cases, with an area under the receiver operating characteristic curve (AUC) of 0.81 for an external test set. In comparison to a 3D convolutional neural network (CNN) trained from scratch and a 2D architecture pre-trained on ImageNet, the video pre-trained model performed best. Deep learning models are capable of CT image-based HPV status determination. Video based pre-training has the ability to improve training for 3D medical data, but further studies are needed for verification.

2.
Phys Med ; 81: 102-113, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33445122

RESUMO

PURPOSE: To predict the impact of optimization parameter changes on dosimetric plan quality criteria in multi-criteria optimized volumetric-modulated-arc therapy (VMAT) planning prior to optimization using machine learning (ML). METHODS: A data base comprising a total of 21,266 VMAT treatment plans for 44 cranial and 18 spinal patient geometries was generated. The underlying optimization algorithm is governed by three highly composite parameters which model a combination of important aspects of the solution. Patient geometries were parametrized via volume- and shape properties of the voxel objects and overlap-volume histograms (OVH) of the planning-target-volume (PTV) and a relevant organ-at-risk (OAR). The impact of changes in one of the three optimization parameters on the maximally achievable value range of five dosimetric properties of the resulting dose distributions was studied. To predict the extent of this impact based on patient geometry, treatment site, and current parameter settings prior to optimization, three different ML-models were trained and tested. Precision-recall curves, as well as the area-under-curve (AUC) of the resulting receiver-operator-characteristic (ROC) curves were analyzed for model assessment. RESULTS: Successful identification of parameter regions resulting in a high variability of dosimetric plan properties depended on the choice of geometry features, the treatment indication and the plan property under investigation. AUC values between 0.82 and 0.99 could be achieved. The best average-precision (AP) values obtained from the corresponding precision/recall curves ranged from 0.71 to 0.99. CONCLUSIONS: Machine learning models trained on a database of pre-optimized treatment plans can help finding relevant optimization parameter ranges prior to optimization.

3.
Eur Radiol ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33211140

RESUMO

OBJECTIVE: Assessing the advantage of x-ray dark-field contrast over x-ray transmission contrast in radiography for the detection of developing radiation-induced lung damage in mice. METHODS: Two groups of female C57BL/6 mice (irradiated and control) were imaged obtaining both contrasts monthly for 28 weeks post irradiation. Six mice received 20 Gy of irradiation to the entire right lung sparing the left lung. The control group of six mice was not irradiated. A total of 88 radiographs of both contrasts were evaluated for both groups based on average values for two regions of interest, covering (irradiated) right lung and healthy left lung. The ratio of these average values, R, was distinguished between healthy and damaged lungs for both contrasts. The time-point when deviations of R from healthy lung exceeded 3σ was determined and compared among contrasts. The Wilcoxon-Mann-Whitney test was used to test against the null hypothesis that there is no difference between both groups. A selection of 32 radiographs was assessed by radiologists. Sensitivity and specificity were determined in order to compare the diagnostic potential of both contrasts. Inter-reader and intra-reader accuracy were rated with Cohen's kappa. RESULTS: Radiation-induced morphological changes of lung tissue caused deviations from the control group that were measured on average 10 weeks earlier with x-ray dark-field contrast than with x-ray transmission contrast. Sensitivity, specificity, and accuracy doubled using dark-field radiography. CONCLUSION: X-ray dark-field radiography detects morphological changes of lung tissue associated with radiation-induced damage earlier than transmission radiography in a pre-clinical mouse model. KEY POINTS: • Significant deviations from healthy lung due to irradiation were measured after 16 weeks with x-ray dark-field radiography (p = 0.004). • Significant deviations occur on average 10 weeks earlier for x-ray dark-field radiography in comparison to x-ray transmission radiography. • Sensitivity and specificity doubled when using x-ray dark-field radiography instead of x-ray transmission radiography.

4.
Int J Radiat Biol ; : 1-11, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33211606

RESUMO

PURPOSE: The MSc Radiation Biology course is a highly interdisciplinary degree program placing radiation biology at the interface between biology, medicine, and physics, as well as their associated technologies. The goal was to establish an internationally acknowledged program with diverse and heterogeneous student cohorts, who benefit from each other academically as well as culturally. We have completed a Five-Year evaluation of the program to assess our qualification profile and the further direction we want to take. MATERIALS AND METHODS: We evaluated the student cohort's data from the last 5 years regarding gender, age, and nationality as well as the highest degree before applying and career path after graduation. RESULTS: Data shows a great diversity regarding nationalty as well as undergraduate background. Cohort sizes could be increased and future prospects mainly aimed to a PhD. Measures after regular quality meetings and students' feedback led to improving the curriculum and workload, teacher's training, and changes to examination regulations. CONCLUSIONS: After 5 years, statistics show that our expectations have been met exceedingly. All graduates had excellent career opportunities reflecting the necessity of this MSc and its topics. We are continuously working on improving the program and adapting the curriculum to the requirements in radiation sciences. The future vision includes an expansion of the program as well as undergraduate education opportunities in this field.

5.
Radiat Oncol ; 15(1): 253, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33138837

RESUMO

BACKGROUND: The ESCALOX trial was designed as a multicenter, randomized prospective dose escalation study for head and neck cancer. Therefore, feasibility of treatment planning via different treatment planning systems (TPS) and radiotherapy (RT) techniques is essential. We hypothesized the comparability of dose distributions for simultaneous integrated boost (SIB) volumes respecting the constraints by different TPS and RT techniques. METHODS: CT data sets of the first six patients (all male, mean age: 61.3 years) of the pre-study (up to 77 Gy) were used for comparison of IMRT, VMAT, and helical tomotherapy (HT). Oropharynx was the primary tumor location. Normalization of the three step SIB (77 Gy, 70 Gy, 56 Gy) was D95% = 77 Gy. Coverage (CVF), healthy tissue conformity index (HTCI), conformation number (CN), and dose homogeneity (HI) were compared for PTVs and conformation index (COIN) for parotids. RESULTS: All RT techniques achieved good coverage. For SIB77Gy, CVF was best for IMRT and VMAT, HT achieved highest CN followed by VMAT and IMRT. HT reached good HTCI value, and HI compared to both other techniques. For SIB70Gy, CVF was best by IMRT. HTCI favored HT, consequently CN as well. HI was slightly better for HT. For SIB56Gy, CVF resulted comparably. Conformity favors VMAT as seen by HTCI and CN. Dmean of ipsilateral and contralateral parotids favor HT. CONCLUSION: Different TPS for dose escalation reliably achieved high plan quality. Despite the very good results of HT planning for coverage, conformity, and homogeneity, the TPS also achieved acceptable results for IMRT and VMAT. Trial registration ClinicalTrials.gov Identifier: NCT01212354, EudraCT-No.: 2010-021139-15. ARO: ARO 14-01.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33038461

RESUMO

PURPOSE: Microbeam radiation therapy is a preclinical concept in radiation oncology. It spares normal tissue more effectively than conventional radiation therapy at equal tumor control. The radiation field consists of peak regions with doses of several hundred gray, whereas doses between the peaks (valleys) are below the tissue tolerance level. Widths and distances of the beams are in the submillimeter range for microbeam radiation therapy. A similar alternative concept with beam widths and distances in the millimeter range is presented by minibeam radiation therapy. Although both methods were developed at large synchrotron facilities, compact alternative sources have been proposed recently. METHODS AND MATERIALS: A small-animal irradiator was fitted with a special 3-layered collimator that is used for preclinical research and produces microbeams of flexible width of up to 100 µm. Film dosimetry provided measurements of the dose distributions and was compared with Monte Carlo dose predictions. Moreover, the micronucleus assay in Chinese hamster CHO-K1 cells was used as a biological dosimeter. The focal spot size and beam emission angle of the x-ray tube were modified to optimize peak dose rate, peak-to-valley dose ratio (PVDR), beam shape, and field homogeneity. An equivalent collimator with slit widths of up to 500 µm produced minibeams and allowed for comparison of microbeam and minibeam field characteristics. RESULTS: The setup achieved peak entrance dose rates of 8 Gy/min and PVDRs >30 for microbeams. Agreement between Monte Carlo simulations and film dosimetry is generally better for larger beam widths; qualitative measurements validated Monte Carlo predicted results. A smaller focal spot enhances PVDRs and reduces beam penumbras but substantially reduces the dose rate. A reduction of the beam emission angle improves the PVDR, beam penumbras, and dose rate without impairing field homogeneity. Minibeams showed similar field characteristics compared with microbeams at the same ratio of beam width and distance but had better agreement with simulations. CONCLUSION: The developed setup is already in use for in vitro experiments and soon for in vivo irradiations. Deviations between Monte Carlo simulations and film dosimetry are attributed to scattering at the collimator surface and manufacturing inaccuracies and are a matter of ongoing research.

7.
Med Phys ; 47(10): 5183-5193, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32757280

RESUMO

PURPOSE: X-ray microbeam radiation therapy is a preclinical concept for tumor treatment promising tissue sparing and enhanced tumor control. With its spatially separated, periodic micrometer-sized pattern, this method requires a high dose rate and a collimated beam typically available at large synchrotron radiation facilities. To treat small animals with microbeams in a laboratory-sized environment, we developed a dedicated irradiation system at the Munich Compact Light Source (MuCLS). METHODS: A specially made beam collimation optic allows to increase x-ray fluence rate at the position of the target. Monte Carlo simulations and measurements were conducted for accurate microbeam dosimetry. The dose during irradiation is determined by a calibrated flux monitoring system. Moreover, a positioning system including mouse monitoring was built. RESULTS: We successfully commissioned the in vivo microbeam irradiation system for an exemplary xenograft tumor model in the mouse ear. By beam collimation, a dose rate of up to 5.3 Gy/min at 25 keV was achieved. Microbeam irradiations using a tungsten collimator with 50 µm slit size and 350 µm center-to-center spacing were performed at a mean dose rate of 0.6 Gy/min showing a high peak-to-valley dose ratio of about 200 in the mouse ear. The maximum circular field size of 3.5 mm in diameter can be enlarged using field patching. CONCLUSIONS: This study shows that we can perform in vivo microbeam experiments at the MuCLS with a dedicated dosimetry and positioning system to advance this promising radiation therapy method at commercially available compact microbeam sources. Peak doses of up to 100 Gy per treatment seem feasible considering a recent upgrade for higher photon flux. The system can be adapted for tumor treatment in different animal models, for example, in the hind leg.

8.
Z Med Phys ; 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32576410

RESUMO

PURPOSE: To approximate dose-volume histogram (DVH) based quality indicators in volumetric modulated arc therapy (VMAT) planning using multi-criteria optimization (MCO) with a low number of composite optimization parameters. METHODS: The solution space for VMAT optimization with a low number of composite optimization parameters is approximated by trilinear dose inter- polation and prediction of dose-volume-histogram (DVH) based plan quality indicator values. To assess the approximation quality a diverse dataset of 44 cranial and 18 spine patient geometries was chosen. Optimization results are governed by three composite parameters focusing on target-organ-at-risk- (OAR)-trade-off, overall healthy tissue sparing, and delivery/quality assurance complexity. 21,266 optimized dose distributions were pre-calculated and the numerical values for a choice of 10 DVH points, referred to as plan quality indicators, were stored to serve as ground truth. Using a subset of 8 and 27 pre-calculated optimization results, dose distributions for unknown parameter values were approximated by trilinear interpolation. The resulting quality indicator values were compared to the previously obtained exact solutions. RESULTS: The magnitude of the deviation between exact and approximated values varied largely with respect to patient geometry and the criterion under investigation. Approximation with 27 pre-calculated results yielded lower deviations than approximation with 8 results, at the cost of a higher pre-calculation workload. CONCLUSIONS: Solution space approximation via trilinear dose interpolation in VMAT treatment planning governed by composite optimization parameters is possible without further knowledge of the internal implementation of the underlying optimizer. Maximum average deviations between approxi- mation and actual values of characteristic dose quality indicators below 1% (cranial) and 8% (spine) allow for a quick qualitative assessment of the possible solution landscape.

9.
Phys Med ; 75: 77-82, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32559648

RESUMO

Microbeam radiation therapy (MRT), a so far preclinical method in radiation oncology, modulates treatment doses on a micrometre scale. MRT uses treatment fields with a few ten micrometre wide high dose regions (peaks) separated by a few hundred micrometre wide low dose regions (valleys) and was shown to spare tissue much more effectively than conventional radiation therapy at similar tumour control rates. While preclinical research focused primarily on tumours of the central nervous system, recently also lung tumours have been suggested as a potential target for MRT. This study investigates the effect of the lung microstructure, comprising air cavities of a few hundred micrometre diameter, on the microbeam dose distribution in lung. In Monte Carlo simulations different models of heterogeneous lung tissue are compared with pure water and homogeneous air-water mixtures. Experimentally, microbeam dose distributions in porous foam material with cavity sizes similar to the size of lung alveoli were measured with film dosimetry at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Simulations and experiments show that the microstructure of the lung has a huge impact on the local doses in the microbeam fields. Locally, material inhomogeneities may change the dose by a factor of 1.7, and also average peak and valley doses substantially differ from those in homogeneous material. Our results imply that accurate dose prediction for MRT in lung requires adequate models of the lung microstructure. Even if only average peak and valley doses are of interest, the assumption of a simple homogeneous air-water mixture is not sufficient. Since anatomic information on a micrometre scale are unavailable for clinical treatment planning, alternative methods and models have to be developed.

10.
BMC Cancer ; 20(1): 501, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487151

RESUMO

BACKGROUND: The aim of our study was to assess the feasibility and oncologic outcomes in patients treated with spinal (SI) or craniospinal irradiation (CSI) in patients with leptomeningeal metastases (LM) and to suggest a prognostic score as to which patients are most likely to benefit from this treatment. METHODS: Nineteen patients treated with CSI at our institution were eligible for the study. Demographic data, primary tumor characteristics, outcome and toxicity were assessed retrospectively. The extent of extra-CNS disease was defined by staging CT-scans before the initiation of CSI. Based on outcome parameters a prognostic score was developed for stratification based on patient performance status and tumor staging. RESULTS: Median follow-up and overall survival (OS) for the whole group was 3.4 months (range 0.5-61.5 months). The median overall survival (OS) for patients with LM from breast cancer was 4.7 months and from NSCLC 3.3 months. The median OS was 7.3 months, 3.3 months and 1.5 months for patients with 0, 1 and 2 risk factors according to the proposed prognostic score (KPS < 70 and the presence of extra-CNS disease) respectively. Nonhematologic toxicities were mild. CONCLUSION: CSI demonstrated clinically meaningful survival that is comparable to the reported outcome of intrathecal chemotherapy. A simple scoring system could be used to better select patients for treatment with CSI in this palliative setting. In our opinion, the feasibility of performing CSI with modern radiotherapy techniques with better sparing of healthy tissue gives a further rationale for its use also in the palliative setting.

11.
J Appl Clin Med Phys ; 21(8): 6-14, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32476247

RESUMO

BACKGROUND: Throughout the last years, carbon-fibre-reinforced PEEK (CFP) pedicle screw systems were introduced to replace standard titanium alloy (Ti) implants for spinal instrumentation, promising improved radiotherapy (RT) treatment planning accuracy. We compared the dosimetric impact of both implants for intensity modulated proton (IMPT) and volumetric arc photon therapy (VMAT), with the focus on uncertainties in Hounsfield unit assignment of titanium alloy. METHODS: Retrospective planning was performed on CT data of five patients with Ti and five with CFP implants. Carbon-fibre-reinforced PEEK systems comprised radiolucent pedicle screws with thin titanium-coated regions and titanium tulips. For each patient, one IMPT and one VMAT plan were generated with a nominal relative stopping power (SP) (IMPT) and electron density (ρ) (VMAT) and recalculated onto the identical CT with increased and decreased SP or ρ by ±6% for the titanium components. RESULTS: Recalculated VMAT dose distributions hardly deviated from the nominal plans for both screw types. IMPT plans resulted in more heterogeneous target coverage, measured by the standard deviation σ inside the target, which increased on average by 7.6 ± 2.3% (Ti) vs 3.4 ± 1.2% (CFP). Larger SPs lead to lower target minimum doses, lower SPs to higher dose maxima, with a more pronounced effect for Ti screws. CONCLUSIONS: While VMAT plans showed no relevant difference in dosimetric quality between both screw types, IMPT plans demonstrated the benefit of CFP screws through a smaller dosimetric impact of CT-value uncertainties compared to Ti. Reducing metal components in implants will therefore improve dose calculation accuracy and lower the risk for tumor underdosage.

12.
Neuro Oncol ; 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32369601

RESUMO

BACKGROUND: Because of the increased risk in cancer patients of developing complications caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), physicians have to balance the competing risks of the negative impact of the pandemic and the primary tumor. In this consensus statement, an international group of experts present mitigation strategies and treatment guidance for patients suffering from high grade gliomas (HGG) during the coronavirus disease 2019 (COVID-19) pandemic. METHOD / RESULTS: 16 international experts in the treatment of HGG contributed to this consensus-based practice recommendation including neuro-oncologists, neurosurgeons, radiation -oncologists and a medical physicist. Generally, treatment of neuro-oncological patients cannot be significantly delayed and initiating therapy should not be outweighed by COVID-19. We present detailed interdisciplinary treatment strategies for molecular subgroups in two pandemic scenarios, a scale-up phase and a crisis phase. CONCLUSION: This practice recommendation presents a pragmatic framework and consensus-based mitigation strategies for the treatment of HGG patients during the SARS-CoV-2 pandemic.

13.
Med Phys ; 47(7): 2768-2778, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32162332

RESUMO

PURPOSE: To model four-dimensional (4D) relative biological effectiveness (RBE)-weighted dose variations in abdominal lesions treated with scanned carbon ion beam in case of irregular breathing motion. METHODS: The proposed method, referred to as bioWED method, combines the simulation of tumor motion in a patient- and beam-specific water equivalent depth (WED)-space with RBE modeling, aiming at the estimation of RBE-weighted dose changes due to respiratory motion. The method was validated on a phantom, simulating gated and free breathing dose delivery, and on a patient case, for which free breathing irradiation was assumed and both amplitude and baseline breathing irregularities were simulated through a respiratory motion model. We quantified (a) the effect of motion on the equivalent uniform dose (EUD) and the RBE-weighted dose-volume histograms (DVH), by comparing the planned dose distribution with "ground truth" 4D RBE-weighted doses computed using 4D computed tomography data, and (ii) the estimation error, by comparing the doses estimated with the bioWED method to "ground truth" 4D RBE-weighted doses. RESULTS: In the phantom validation, the estimation error on the EUD was limited with respect to the motion effect and the median estimation error on relevant RBE-weighted DVH metrics remained within 5%. In the patient study, the estimation error as computed on the EUD was smaller than the corresponding motion effect, exhibiting the largest values in the baseline irregularity simulation. However, the median estimation error over all simulations was below 3.2% considering relevant DVH metrics. CONCLUSIONS: In the evaluated cases, the bioWED method showed proper accuracy when compared to deformable image registration-based 4D dose calculation. Therefore, it can be seen as a tool to test treatment plan robustness against irregular breathing motion, although its accuracy decreases as a function of increasing soft tissue deformation and should be evaluated on a larger patient dataset.

14.
Radiat Environ Biophys ; 59(1): 111-120, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31655869

RESUMO

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 Gy or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 Gy or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

15.
Radiat Oncol ; 14(1): 198, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711524

RESUMO

BACKGROUND: Adjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome. METHODS: We evaluated 253 patients treated with postoperative RT with a median age of 66 years (range 42-85 years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level <0.1 ng/mL were excluded. Hence, data of 179 patients was evaluated. We used propensity score matching to build homogenous groups. A Cox regression model was used to determine differences between treatment options. Median follow-up was 32.5 months (range 1.4-128.0 months). RESULTS: Early SRT at PSA levels <0.3 ng/mL was associated with significant longer BCRFS than late SRT (HR: 0.32, 95%-CI: 0.14-0.75, p = 0.009). Multiple Cox regression showed pre-RT PSA level, tumor stage, and Gleason score as predictive factors for biochemical relapse. In the overall group, patients treated with either ART or early SRT showed no significant difference in BCRFS (HR: 0.17, 95%-CI: 0.02-1.44, p = 0.1). In patients with locally advanced PC (pT3/4) BCRFS was similar in both groups as well (HR: 0.21, 95%-CI:0.02-1.79, p = 0.15). CONCLUSION: For patients with PSA-triggered follow-up, close observation is essential and early initiation of local treatment at low PSA levels (<0.3 ng/mL) is beneficial. Our data suggest, that SRT administered at early PSA rise might be equieffective to postoperative ART in patients with locally advanced PC. However, the individual treatment decision must be based on any adverse risk factors and the patients' postoperative clinical condition. STUDY REGISTRATION: The present work is approved by the Ethics Commission of the Technical University of Munich (TUM) and is registered with the project number 320/14.


Assuntos
Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Radioterapia/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Período Pós-Operatório , Pontuação de Propensão , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/análise , Radioterapia Adjuvante , Estudos Retrospectivos , Resultado do Tratamento
16.
Cancer Commun (Lond) ; 39(1): 73, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706337

RESUMO

BACKGROUND: More than 25% of patients with solid cancers develop intracerebral metastases. Aside of surgery, radiation therapy (RT) is a mainstay in the treatment of intracerebral metastases. Postoperative fractionated stereotactic RT (FSRT) to the resection cavity of intracerebral metastases is a treatment of choice to reduce the risk of local recurrence. However, FSRT has to be delayed until a sufficient wound healing is attained; hence systemic therapy might be postponed. Neoadjuvant stereotactic radiosurgery (SRS) might offer advantages over adjuvant FSRT in terms of better target delineation and an earlier start of systemic chemotherapy. Here, we conducted a study to find the maximum tolerated dose (MTD) of neoadjuvant SRS for intracerebral metastases. METHODS: This is a single-center, phase I dose escalation study on neoadjuvant SRS for intracerebral metastases that will be conducted at the Klinikum rechts der Isar Hospital, Technical University of Munich. The rule-based traditional 3 + 3 design for this trial with 3 dose levels and 4 different cohorts depending on lesion size will be applied. The primary endpoint is the MTD for which no dose-limiting toxicities (DLT) occur. The adverse events of each participant will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 continuously during the study until the first follow-up visit (4-6 weeks after surgery). Secondary endpoints include local control rate, survival, immunological tumor characteristics, quality of life (QoL), CTCAE grade of late clinical, neurological, and neurocognitive toxicities. In addition to the intracerebral metastasis which is treated with neoadjuvant SRS and resection up to four additional intracerebral metastases can be treated with definitive SRS. Depending on the occurrence of DLT up to 72 patients will be enrolled. The recruitment phase will last for 24 months. DISCUSSION: Neoadjuvant SRS for intracerebral metastases offers potential advantages over postoperative SRS to the resection cavity, such as better target volume definition with subsequent higher efficiency of eliminating tumor cells, and lower damage to surrounding healthy tissue, and much-needed systemic chemotherapy could be initiated more rapidly. Trial registration The local ethical review committee of Technical University of Munich (199/18S) approved this study on September 05, 2018. This trial was registered on German Clinical Trials Register (DRKS00016613; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016613) on January 29, 2019.


Assuntos
Neoplasias Encefálicas/radioterapia , Terapia Neoadjuvante , Radiocirurgia , Neoplasias Encefálicas/secundário , Ensaios Clínicos Fase I como Assunto , Humanos , Dose Máxima Tolerável , Terapia Neoadjuvante/efeitos adversos , Qualidade de Vida , Radiocirurgia/efeitos adversos
17.
PLoS One ; 14(9): e0221454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31483811

RESUMO

Side effects caused by radiation are a limiting factor to the amount of dose that can be applied to a tumor volume. A novel method to reduce side effects in radiotherapy is the use of spatial fractionation, in which a pattern of sub-millimeter beams (minibeams) is applied to spare healthy tissue. In order to determine the skin reactions in dependence of single beam sizes, which are relevant for spatially fractionated radiotherapy approaches, single pencil beams of submillimeter to 6 millimeter size were applied in BALB/c mice ears at a Small Animal Radiation Research Platform (SARRP) with a plateau dose of 60 Gy. Radiation toxicities in the ears were observed for 25 days after irradiation. Severe radiation responses were found for beams ≥ 3 mm diameter. The larger the beam diameter the stronger the observed reactions. No ear swelling and barely reddening or desquamation were found for the smallest beam sizes (0.5 and 1 mm). The findings were confirmed by histological sections. Submillimeter beams are preferred in minibeam therapy to obtain optimized tissue sparing. The gradual increase of radiation toxicity with beam size shows that also larger beams are capable of healthy tissue sparing in spatial fractionation.


Assuntos
Orelha/efeitos da radiação , Raios gama/efeitos adversos , Pele/patologia , Animais , Orelha/fisiologia , Eritema/etiologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Dosímetros de Radiação , Pele/metabolismo , Pele/efeitos da radiação
18.
Radiat Oncol ; 14(1): 170, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533742

RESUMO

PURPOSE: Pathogenesis of brain metastases/meningeal cancer and the emotional and neurological outcomes are not yet well understood. The hypothesis of our study is that patients with leptomeningeal cancer show volumetric differences in brain substructures compared to patients with cerebral metastases. METHODS: Three groups consisting of female breast cancer patients prior to brain radiotherapy were compared. Leptomeningeal cancer patients (LMC Group), oligometastatic patients (1-3 brain metastases) prior to radiosurgery (OMRS Group) and patients prior to whole brain radiation (WB Group) were included. All patients had MRI imaging before treatment. T1 MRI sequences were segmented using automatic segmentation. For each patient, 14 bilateral and 11 central/median subcortical structures were tested. Overall 1127 structures were analyzed and compared between groups using age matched two-sided t-tests. RESULTS: The average age of patients in the OMRS group was 60.8 years (± 14.7), 65.3 (± 10.3) in the LMC group and 62.6 (± 10.2) in the WB group. LMC patients showed a significantly larger fourth ventricle compared to OMRS (p = 0.001) and WB (p = 0.003). The central corpus callosum appeared smaller in the LMC group (LMC vs OMRS p = 0.01; LMC vs WB p = 0.026). The right amygdala in the WB group appeared larger compared with the OMRS (p = 0.035). CONCLUSIONS: Differences in the size of brain substructures of the three groups were found. The results appear promising and should be taken into account for further prospective studies also involving healthy controls. The volumetrically determined size of the fourth ventricle might be a helpful diagnostic marker in the future.


Assuntos
Mapeamento Encefálico/métodos , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Imagem por Ressonância Magnética/métodos , Carcinomatose Meníngea/secundário , Idoso , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Carcinomatose Meníngea/diagnóstico por imagem , Carcinomatose Meníngea/cirurgia , Pessoa de Meia-Idade , Técnicas de Rastreamento Neuroanatômico , Prognóstico , Radiocirurgia , Estudos Retrospectivos
19.
Top Magn Reson Imaging ; 28(2): 49-61, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31022048

RESUMO

Radiation therapy (RT) is a mainstay in the interdisciplinary treatment of brain tumors of the skull base and brain. Technical innovations during the past 2 decades have allowed for increasingly precise treatment with better sparing of adjacent healthy tissues to prevent treatment-related side effects that influence patients' quality of life. Particle therapy with protons and charged ions offer favorable kinetics with sharp dose deposition in a well-defined depth (Bragg-Peak) and a steep radiation fall-off beyond that maximum. This review highlights the role of particle therapy in the management of primary brain tumors and tumors of the skull base.


Assuntos
Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias da Base do Crânio/radioterapia , Humanos , Íons , Prótons
20.
Radiat Oncol ; 14(1): 2, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626408

RESUMO

BACKGROUND: Advanced radiotherapy (RT) techniques allow normal tissue to be spared in patients with extremity soft tissue sarcoma (STS). This work aims to evaluate toxicity and outcome after neoadjuvant image-guided radiotherapy (IGRT) as helical intensity modulated radiotherapy (IMRT) with reduced margins based on MRI-based target definition in patients with STS. METHODS: Between 2010 to 2014, 41 patients with extremity STS were treated with IGRT delivered as helical IMRT on a tomotherapy machine. The tumor site was in the upper extremity in 6 patients (15%) and lower extremity in 35 patients (85%). Reduced margins of 2.5 cm in longitudinal direction and 1.0 cm in axial direction were used to expand the MRI-defined gross tumor volume, including peritumoral edema, to the clinical target volume. An additional margin of 5 mm was added to receive the planning target volume. The full total dose of 50 Gy in 2 Gy fractions was sucessfully applied in 40 patients. Two patients received chemotherapy instead of surgery due to systemic progression. All patients were included into a strict follow-up program and were seen interdisciplinarily by the Departments of Orthopaedic Surgery and Radiation Oncology. RESULTS: Thirty eight patients that received total RT total dose and subsequent resection were analyzed for outcome. After a median follow-up of 38.5 months cumulative OS, local PFS and systemic PFS at 2 years were determined at 78.2, 85.2 and 54.5%, respectively. Two of 6 local recurrences were proximal marginal misses. Negative resection margins were achieved in 84% of patients. The rate of major wound complications was comparable to previous IMRT studies with 36.8%. RT was overall tolerable with low toxicity rates. CONCLUSIONS: IMRT-IGRT offers neoadjuvant treatment for extremity STS with reduced safety margins and thus low toxicity rates. Wound complication rates were comparable to previously reported frequencies. Two reported marginal misses suggest a word of caution for reduction of longitudinal safety margins.


Assuntos
Extremidades/efeitos da radiação , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/radioterapia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Sarcoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Extremidades/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Adjuvante , Sarcoma/patologia , Taxa de Sobrevida , Adulto Jovem
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