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2.
Br J Radiol ; 93(1107): 20190573, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31778315

RESUMO

OBJECTIVE: Classical robust optimization (cRO) in intensity-modulated proton therapy (IMPT) considers isocenter position and particle range uncertainties; anatomical robust optimization (aRO) aims to consider additional non-rigid positioning variations. This work compares the influence of different uncertainty sources on the robustness of cRO and aRO IMPT plans for head and neck squamous cell carcinoma (HNSCC). METHODS: Two IMPT plans were optimized for 20 HNSCC patients who received weekly control CTs (cCT): cRO, using solely the planning CT, and aRO, including 2 additional cCTs. The robustness of the plans in terms of clinical target volume (CTV) coverage and organ at risk (OAR) sparing was analyzed considering stepwise the influence of (1) non-rigid anatomical variations given by the weekly cCT, (2) with fraction-wise added rigid random setup errors and (3) additional systematic proton range uncertainties. RESULTS: cRO plans presented significantly higher nominal CTV coverage but are outperformed by aRO plans when considering non-rigid anatomical variations only, as cRO and aRO plans presented a median target coverage (D98%) decrease for the low-risk/high-risk CTV of 1.8/1.1 percentage points (pp) and -0.2 pp/-0.3 pp, respectively. Setup and range uncertainties had larger influence on cRO CTV coverage, but led to similar OAR dose changes in both plans. Considering all error sources, 10/2 cRO/aRO patients missed the CTV coverage and a limited number exceeded some OAR constraints in both plans. CONCLUSION: Non-rigid anatomical variations are mainly responsible for critical target coverage loss of cRO plans, whereas the aRO approach was robust against such variations. Both plans provide similar robustness of OAR parameters. ADVANCES IN KNOWLEDGE: The influence of different uncertainty sources was quantified for robust IMPT HNSCC plans.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Incerteza , Humanos , Órgãos em Risco/efeitos da radiação , Posicionamento do Paciente , Lesões por Radiação/prevenção & controle , Erros de Configuração em Radioterapia , Radioterapia de Intensidade Modulada/normas , Estudos Retrospectivos
3.
Radiother Oncol ; 131: 127-134, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30773179

RESUMO

BACKGROUND AND PURPOSE: Classical robust optimization considers uncertainties in patient setup and particle range. However, anatomical changes occurring during the treatment are neglected. Our aim was to compare classical robust optimization (cRO) with anatomical robust optimization (aRO), to quantify the influence of anatomical variations during the treatment course, and to assess the need of adaptation. MATERIALS AND METHODS: Planning CT and weekly control CTs (cCTs) from 20 head and neck patients were analysed. Three intensity-modulated proton therapy (IMPT) plans were compared: conventional PTV-based plan; cRO, using solely the planning CT, and aRO, including additionally the first 2 cCTs in the optimization. Weekly and total cumulative doses, considering anatomical variations during the treatment, were calculated and compared with the nominal plans. RESULTS: Nominal plans fulfilled clinical specifications for target coverage (D98% ≥95% of prescribed dose). The PTV-based and cRO approaches were not sufficient to account for anatomical changes during the treatment in 10 and 5 patients, respectively, resulting in the need of plan adaptation. With the aRO approach, in all except one patient the target coverage was conserved, and no adaptations were necessary. CONCLUSION: In 25% of the investigated cases, classical robust optimization is not sufficient to account for anatomical changes during the treatment. Adding additional information of random anatomical variations in the optimization improves plan robustness.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Cabeça/anatomia & histologia , Cabeça/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Pescoço/anatomia & histologia , Pescoço/diagnóstico por imagem , Órgãos em Risco/anatomia & histologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Incerteza
4.
Radiat Oncol ; 13(1): 228, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30466468

RESUMO

BACKGROUND: Neoadjuvant radio(chemo)therapy of non-metastasized, borderline resectable or unresectable locally advanced pancreatic cancer is complex and prone to cause side-effects, e.g., in gastrointestinal organs. Intensity-modulated proton therapy (IMPT) enables a high conformity to the targets while simultaneously sparing the normal tissue such that dose-escalation strategies come within reach. In this in silico feasibility study, we compared four IMPT planning strategies including robust multi-field optimization (rMFO) and a simultaneous integrated boost (SIB) for dose-escalation in pancreatic cancer patients. METHODS: For six pancreatic cancer patients referred for adjuvant or primary radiochemotherapy, four rMFO-IMPT-SIB treatment plans each, consisting of two or three (non-)coplanar beam arrangements, were optimized. Dose values for both targets, i.e., the elective clinical target volume [CTV, prescribed dose Dpres = 51Gy(RBE)] and the boost target [Dpres = 66Gy(RBE)], for the organs at risk as well as target conformity and homogeneity indexes, derived from the dose volume histograms, were statistically compared. RESULTS: All treatment plans of each strategy fulfilled the prescribed doses to the targets (Dpres(GTV,CTV) = 100%, D95%,(GTV,CTV) ≥ 95%, D2%,(GTV,CTV) ≤ 107%). No significant differences for the conformity index were found (p > 0.05), however, treatment plans with a three non-coplanar beam strategy were most homogenous to both targets (p < 0.045). The median value of all dosimetric results of the large and small bowel as well as for the liver and the spinal cord met the dose constraints with all beam arrangements. Irrespective of the planning strategies, the dose constraint for the duodenum and stomach were not met. Using the three-beam arrangements, the dose to the left kidney could be significant decreased when compared to a two-beam strategy (p < 0.045). CONCLUSION: Based on our findings we recommend a three-beam configuration with at least one non-coplanar beam for dose-escalated SIB with rMFO-IMPT in advanced pancreatic cancer patients achieving a homogeneous dose distribution in the target while simultaneously minimizing the dose to the organs at risk. Further treatment planning studies on aspects of breathing and organ motion need to be performed.


Assuntos
Quimiorradioterapia Adjuvante , Órgãos em Risco/efeitos da radiação , Neoplasias Pancreáticas/terapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Pancreáticas/patologia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos
5.
Int J Radiat Oncol Biol Phys ; 99(3): 738-749, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29280468

RESUMO

PURPOSE: To compare the difference in robustness of single-field optimized (SFO) and robust multifield optimized (rMFO) proton plans for oropharynx carcinoma patients by an improved robustness analysis. METHODS AND MATERIALS: We generated rMFO proton plans for 11 patients with oropharynx carcinoma treated with SFO intensity modulated proton therapy with simultaneous integrated boost prescription. Doses from both planning approaches were compared for the initial plans and the worst cases from 20 optimization scenarios of setup errors and range uncertainties. Expected average dose distributions per range uncertainty were obtained by weighting the contributions from the respective scenarios with their expected setup error probability, and the spread of dose parameters for different range uncertainties were quantified. Using boundary dose distributions created from 56 combined setup error and range uncertainty scenarios and considering the vanishing influence of setup errors after 30 fractions, we approximated realistic worst-case values for the total treatment course. Error bar metrics derived from these boundary doses are reported for the clinical target volumes (CTVs) and organs at risk (OARs). RESULTS: The rMFO plans showed improved CTV coverage and homogeneity while simultaneously reducing the average mean dose to the constrictor muscles, larynx, and ipsilateral middle ear by 5.6 Gy, 2.0 Gy, and 3.9 Gy, respectively. We observed slightly larger differences during robustness evaluation, as well as a significantly higher average brainstem maximum and ipsilateral parotid mean dose for SFO plans. For rMFO plans, the range uncertainty-related spread in OAR dose parameters and many error bar metrics were found to be superior. The SFO plans showed a lower global maximum dose for single-scenario worst cases and a slightly lower mean oral cavity dose throughout. CONCLUSIONS: An enhanced robustness analysis has been proposed and implemented into clinical systems. The benefit of better CTV coverage and OAR dose sparing in oropharynx carcinoma patients by rMFO compared with SFO proton plans is preserved in a robustness analysis with consideration of setup error and range uncertainty.


Assuntos
Carcinoma/radioterapia , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco , Neoplasias Orofaríngeas/radioterapia , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Algoritmos , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/efeitos da radiação , Carcinoma/diagnóstico por imagem , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Neoplasias Orofaríngeas/diagnóstico por imagem , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Erros de Configuração em Radioterapia , Incerteza
6.
Radiat Oncol ; 12(1): 190, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29183377

RESUMO

BACKGROUND: Proton beam therapy is promising for the treatment of head and neck cancer (HNC), but it is sensitive to uncertainties in patient positioning and particle range. Studies have shown that the planning target volume (PTV) concept may not be sufficient to ensure robustness of the target coverage. A few planning studies have considered irradiation of unilateral HNC targets with protons, but they have only taken into account the dose on the nominal plan, without considering anatomy changes occurring during the treatment course. METHODS: Four pencil beam scanning (PBS) proton therapy plans were calculated for 8 HNC patients with unilateral target volumes: single-field (SFO) and multi-field optimized (MFO) plans, either using the PTV concept or clinical target volume (CTV)-based robust optimization. The dose was recalculated on computed tomography (CT) scans acquired during the treatment course. Doses to target volumes and organs at risk (OARs) were compared for the nominal plans, cumulative doses considering anatomical changes, and additional setup and range errors in each fraction. If required, the treatment plan was adapted, and the dose was compared with the non-adapted plan. RESULTS: All nominal plans fulfilled the clinical specifications for target coverage, but significantly higher doses on the ipsilateral parotid gland were found for both SFO approaches. MFO PTV-based plans had the lowest robustness against range and setup errors. During the treatment course, the influence of the anatomical variation on the dose has shown to be patient specific, mostly independent of the chosen planning approach. Nine plans in four patients required adaptation, which led to a significant improvement of the target coverage and a slight reduction in the OAR dose in comparison to the cumulative dose without adaptation. CONCLUSIONS: The use of robust MFO optimization is recommended for ensuring plan robustness and reduced doses in the ipsilateral parotid gland. Anatomical changes occurring during the treatment course might degrade the target coverage and increase the dose in the OARs, independent of the chosen planning approach. For some patients, a plan adaptation may be required.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Algoritmos , Feminino , Humanos , Masculino , Órgãos em Risco/efeitos da radiação , Prognóstico , Terapia com Prótons/métodos , Dosagem Radioterapêutica
7.
Radiother Oncol ; 125(3): 526-533, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29050953

RESUMO

BACKGROUND AND PURPOSE: To reduce range uncertainty in particle therapy, an accurate computation of stopping-power ratios (SPRs) based on computed tomography (CT) is crucial. Here, we assess range differences between the state-of-the-art CT-number-to-SPR conversion using a generic Hounsfield look-up table (HLUT) and a direct patient-specific SPR prediction (RhoSigma) based on dual-energy CT (DECT) in 100 proton treatment fields. MATERIAL AND METHODS: For 25 head-tumor and 25 prostate-cancer patients, the clinically applied treatment plan, optimized using a HLUT, was recalculated with RhoSigma as CT-number-to-SPR conversion. Depth-dose curves in beam direction were extracted for both dose distributions in a regular grid and range deviations were determined and correlated to SPR differences within the irradiated volume. RESULTS: Absolute (relative) mean water-equivalent range shifts of 1.1mm (1.2%) and 4.1mm (1.7%) were observed in the head-tumor and prostate-cancer cohort, respectively. Due to the case dependency of a generic HLUT, range deviations within treatment fields strongly depend on the tissues traversed leading to a larger variation within one patient than between patients. CONCLUSIONS: The magnitude of patient-specific range deviations between HLUT and the more accurate DECT-based SPR prediction is clinically relevant. A clinical application of the latter seems feasible as demonstrated in this study using medically approved systems from CT acquisition to treatment planning.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Pélvicas/radioterapia , Terapia com Prótons/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto Jovem
8.
J Appl Clin Med Phys ; 18(6): 104-113, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28921843

RESUMO

PURPOSE: Evaluation of dose degradation by anatomic changes for head-and-neck cancer (HNC) intensity-modulated proton therapy (IMPT) relative to intensity-modulated photon therapy (IMRT) and identification of potential indicators for IMPT treatment plan adaptation. METHODS: For 31 advanced HNC datasets, IMPT and IMRT plans were recalculated on a computed tomography scan (CT) taken after about 4 weeks of therapy. Dose parameter changes were determined for the organs at risk (OARs) spinal cord, brain stem, parotid glands, brachial plexus, and mandible, for the clinical target volume (CTV) and the healthy tissue outside planning target volume (PTV). Correlation of dose degradation with target volume changes and quality of rigid CT matching was investigated. RESULTS: Recalculated IMPT dose distributions showed stronger degradation than the IMRT doses. OAR analysis revealed significant changes in parotid median dose (IMPT) and near maximum dose (D1ml ) of spinal cord (IMPT, IMRT) and mandible (IMPT). OAR dose parameters remained lower in IMPT cases. CTV coverage (V95% ) and overdose (V107% ) deteriorated for IMPT plans to (93.4 ± 5.4)% and (10.6 ± 12.5)%, while those for IMRT plans remained acceptable. Recalculated plans showed similarly decreased PTV conformity, but considerable hotspots, also outside the PTV, emerged in IMPT cases. Lower CT matching quality was significantly correlated with loss of PTV conformity (IMPT, IMRT), CTV homogeneity and coverage (IMPT). Target shrinkage correlated with increased dose in brachial plexus (IMRT, IMPT), hotspot generation outside the PTV (IMPT) and lower PTV conformity (IMRT). CONCLUSIONS: The study underlines the necessity of precise positioning and monitoring of anatomy changes, especially in IMPT which might require adaptation more often. Since OAR doses remained typically below constraints, IMPT plan adaptation will be indicated by target dose degradations.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Órgãos em Risco/efeitos da radiação , Fótons/uso terapêutico , Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Radiometria/métodos , Dosagem Radioterapêutica
9.
Z Med Phys ; 27(4): 285-299, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28676371

RESUMO

PURPOSE: Objectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation. METHODS AND MATERIALS: The approach divides the target volume into sub-volumes according to retrospectively observed spatial failure patterns. The product of all sub-volume TCPi values reproduces the observed TCP for the total tumor. The derived formalism provides for each target sub-volume i the tumor control dose (D50,i) and slope (γ50,i) parameters at 50% TCPi. For a simultaneous integrated boost (SIB) prescription for 45 advanced head and neck cancer patients, TCP values for photon and proton irradiation were calculated and compared. The target volume was divided into gross tumor volume (GTV), surrounding clinical target volume (CTV), and elective CTV (CTVE). The risk of a local failure in each of these sub-volumes was taken from the literature. RESULTS: Convenient expressions for D50,i and γ50,i were provided for the Poisson and the logistic model. Comparable TCP estimates were obtained for photon and proton plans of the 45 patients using the sub-volume model, despite notably higher dose levels (on average +4.9%) in the low-risk CTVE for photon irradiation. In contrast, assuming a homogeneous dose response in the entire target volume resulted in TCP estimates contradicting clinical experience (the highest failure rate in the low-risk CTVE) and differing substantially between photon and proton irradiation. CONCLUSIONS: The presented method is of practical value for three reasons: It (a) is based on empirical clinical outcome data; (b) can be applied to non-uniform dose prescriptions as well as different tumor entities and dose-response models; and (c) is provided in a convenient compact form. The approach may be utilized to target spatial patterns of local failures observed in patient cohorts by prescribing different doses to different target regions. Its predictive power depends on the uncertainty of the employed established TCP parameters D50 and γ50 and to a smaller extent on that of the clinically observed pattern of failure risk.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Modelos Teóricos , Dosagem Radioterapêutica , Humanos , Probabilidade , Terapia com Prótons , Estudos Retrospectivos
10.
Med Phys ; 44(2): 703-712, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28133755

RESUMO

PURPOSE: To determine whether individual liver tumor patients can be safely treated with pencil beam scanning proton therapy. This study reports a planning preparation workflow that can be used for beam angle selection and the evaluation of the efficacy of abdominal compression (AC) to mitigate motion. METHODS: Four-dimensional computed tomography scans (4DCT) with and without AC were available from 10 liver tumor patients with fluoroscopy-proven motion reduction by AC, previously treated using photons. For each scan, the motion amplitudes and the motion-induced variation of water-equivalent thickness (ΔWET) in each voxel of the target volume were evaluated during treatment plan preparation. Optimal proton beam angles were selected after volume analysis of the respective beam-specific planning target volume (BSPTV). M⊥80 and ΔWET80 derived from the 80th percentiles of perpendicular motion amplitude (M⊥ ) and ΔWET were compared with and without AC. Proton plans were created on the average CT to achieve target coverage similar to that of the conventional photon treatments. 4D dynamic dose calculation was performed postplan by synchronizing proton beam delivery timing patterns to the 4DCT phases to assess interplay and fractionation effects, and to determine motion criteria for subsequent patient treatment. RESULTS: Selected coplanar beam angles ranged between 180° and 39°, primarily from right lateral (oblique) and posterior (oblique) directions. While AC produced a significant reduction in mean Liver-GTV dose, any reduction in mean heart dose was patient dependent and not significant. Similarly, AC resulted in reductions in M⊥ , ΔWET, and BSPTV volumes and improved dose degradation (ΔD95 and ΔD1 ) within the CTV. For small motion (M⊥80 < 7 mm and ΔWET80 < 5 mm), motion mitigation was not needed. For moderate motion (M⊥80 7-10 mm or ΔWET80 5-7 mm), AC produced a modest improvement. For large motion (M⊥80 > 10 mm or ΔWET80 > 7 mm), AC and/or some other form of mitigation strategies were required. CONCLUSION: A workflow for screening patients' motion characteristics and optimizing beam angle selection was established for the pencil beam scanning proton therapy treatment of liver tumors. Abdominal compression was found to be useful at mitigation of moderate and large motion.


Assuntos
Abdome , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/radioterapia , Movimento , Terapia com Prótons , Fracionamento da Dose de Radiação , Feminino , Fluoroscopia , Tomografia Computadorizada Quadridimensional , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Planejamento da Radioterapia Assistida por Computador , Respiração
11.
Trials ; 17(1): 543, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27846903

RESUMO

BACKGROUND: Primary radiochemotherapy with photons is the standard treatment for locally advanced-stage non-small cell lung cancer (NSCLC) patients. Acute radiation-induced side effects such as oesophagitis and radiation pneumonitis limit patients' quality of life, and the latter can be potentially life-threatening. Due to its distinct physical characteristics, proton therapy enables better sparing of normal tissues, which is supposed to translate into a reduction of radiation-induced side effects. METHODS/DESIGN: This is a single-centre, prospective, randomised controlled, phase II clinical trial to compare photon to proton radiotherapy up to 66 Gy (RBE) with concomitant standard chemotherapy in patients with locally advanced-stage NSCLC. Patients will be allocated in a 1:1 ratio to photon or proton therapy, and treatment will be delivered slightly accelerated with six fractions of 2 Gy (RBE) per week. DISCUSSION: The overall aim of the study is to show a decrease of early and intermediate radiation-induced toxicity using proton therapy. For the primary endpoint of the study we postulate a decrease of radiation-induced side effects (oesophagitis and pneumonitis grade II or higher) from 39 to 12%. Secondary endpoints are locoregional and distant failure, overall survival and late side effects. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with Identifier NCT02731001 on 1 April 2016.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Protocolos Clínicos , Neoplasias Pulmonares/radioterapia , Terapia com Prótons , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade , Estudos Prospectivos , Terapia com Prótons/efeitos adversos
12.
Med Phys ; 43(9): 5028, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27587033

RESUMO

PURPOSE: Rating both a lung segmentation algorithm and a deformable image registration (DIR) algorithm for subsequent lung computed tomography (CT) images by different evaluation techniques. Furthermore, investigating the relative performance and the correlation of the different evaluation techniques to address their potential value in a clinical setting. METHODS: Two to seven subsequent CT images (69 in total) of 15 lung cancer patients were acquired prior, during, and after radiochemotherapy. Automated lung segmentations were compared to manually adapted contours. DIR between the first and all following CT images was performed with a fast algorithm specialized for lung tissue registration, requiring the lung segmentation as input. DIR results were evaluated based on landmark distances, lung contour metrics, and vector field inconsistencies in different subvolumes defined by eroding the lung contour. Correlations between the results from the three methods were evaluated. RESULTS: Automated lung contour segmentation was satisfactory in 18 cases (26%), failed in 6 cases (9%), and required manual correction in 45 cases (66%). Initial and corrected contours had large overlap but showed strong local deviations. Landmark-based DIR evaluation revealed high accuracy compared to CT resolution with an average error of 2.9 mm. Contour metrics of deformed contours were largely satisfactory. The median vector length of inconsistency vector fields was 0.9 mm in the lung volume and slightly smaller for the eroded volumes. There was no clear correlation between the three evaluation approaches. CONCLUSIONS: Automatic lung segmentation remains challenging but can assist the manual delineation process. Proven by three techniques, the inspected DIR algorithm delivers reliable results for the lung CT data sets acquired at different time points. Clinical application of DIR demands a fast DIR evaluation to identify unacceptable results, for instance, by combining different automated DIR evaluation methods.


Assuntos
Algoritmos , Quimiorradioterapia , Processamento de Imagem Assistida por Computador/métodos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/efeitos da radiação , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Fatores de Tempo
13.
Phys Med ; 32(7): 874-82, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27328991

RESUMO

Since 2009, a 4D treatment planning workshop has taken place annually, gathering researchers working on the treatment of moving targets, mainly with scanned ion beams. Topics discussed during the workshops range from problems of time resolved imaging, the challenges of motion modelling, the implementation of 4D capabilities for treatment planning, up to different aspects related to 4D dosimetry and treatment verification. This report gives an overview on topics discussed at the 4D workshops in 2014 and 2015. It summarizes recent findings, developments and challenges in the field and discusses the relevant literature of the recent years. The report is structured in three parts pointing out developments in the context of understanding moving geometries, of treating moving targets and of 4D quality assurance (QA) and 4D dosimetry. The community represented at the 4D workshops agrees that research in the context of treating moving targets with scanned ion beams faces a crucial phase of clinical translation. In the coming years it will be important to define standards for motion monitoring, to establish 4D treatment planning guidelines and to develop 4D QA tools. These basic requirements for the clinical application of scanned ion beams to moving targets could e.g. be determined by a dedicated ESTRO task group. Besides reviewing recent research results and pointing out urgent needs when treating moving targets with scanned ion beams, the report also gives an outlook on the upcoming 4D workshop organized at the University Medical Center Groningen (UMCG) in the Netherlands at the end of 2016.


Assuntos
Tomografia Computadorizada Quadridimensional , Planejamento da Radioterapia Assistida por Computador , Relatório de Pesquisa , Pesquisa Médica Translacional , Humanos , Processamento de Imagem Assistida por Computador , Terapia com Prótons , Radiometria
14.
Front Oncol ; 5: 256, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26636038

RESUMO

INTRODUCTION: Presently used radiochemotherapy regimens result in moderate local control rates for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Dose escalation (DE) may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT) or proton therapy (IMPT). MATERIALS AND METHODS: For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB) in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP). RESULTS: An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences <2%) in all models, except for the risk of aspiration, which increased on average by 8 and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence. CONCLUSION: Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose-response description, e.g., ulcers.

15.
Acta Oncol ; 54(9): 1355-63, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26398663

RESUMO

BACKGROUND: Tumour hypoxia can be measured by FMISO-PET and negatively impacts local tumour control in patients with head and neck squamous cell carcinoma (HNSCC) undergoing radiotherapy. The aim of this post hoc analysis of a prospective clinical trial was to investigate the spatial variability of FMISO hypoxic subvolumes during radio-chemotherapy and the co-localisation of these volumes with later recurrences as a basis for individualised dose prescription trials with dose escalation defined by FMISO-PET. METHODS: Sequential FMISO scans of 12 (of 25) patients presenting residual hypoxia taken before (FMISOpre) and during (FMISOw1-FMISOw5) radio-chemotherapy were analysed regarding the stability of the FMISO subvolumes and, in case of local failure, their correlation to local relapse. RESULTS: Consecutive FMISO-PET positive volumes could be classified as moderately stable with Dice conformity indices of 62% and 58% up to the second week of treatment. Substantial volumetric variation during treatment was observed, with more than 20% geographic miss in all patients and more than 40% in half of the patients. The localisation of the maximum standardised uptake value (SUVmax) differed with a mean distance of 7.0 mm and 13.5 mm between the pre-therapeutic and first or second FMISO-PET during treatment. A stable hypoxic consensual volume (i.e. overlap of pre-therapeutic FMISO and intra-treatment FMISO subvolumes up to week two, generated by different contouring methods) was determined for six patients with imaging information of local recurrence. Three of these six local recurrences were located within this consensual volume. CONCLUSIONS: Our data suggest that selective dose painting to hypoxic tumour subvolumes requires adaptation during treatment and sufficient margins. An alternative strategy is to escalate the dose to the gross tumour volume, accepting lesser escalation of dose outside hypoxic areas if indicated by constraints for organs at risk.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Hipóxia/diagnóstico por imagem , Misonidazol/análogos & derivados , Compostos Radiofarmacêuticos/farmacocinética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Misonidazol/farmacocinética , Imagem Multimodal , Tomografia por Emissão de Pósitrons/métodos , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas de Cabeça e Pescoço , Tomografia Computadorizada por Raios X
16.
Acta Oncol ; 54(9): 1658-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26340301

RESUMO

BACKGROUND: To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only. MATERIALS AND METHODS: For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (∆NTCPIMXT-IMPT) as well as between IMXT and the mixed modality treatment (∆NTCPIMXT-Mix) were calculated. RESULTS: Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, ∆NTCPIMXT-Mix values were a factor 2-10 smaller than ∆NTCPIMXT-IMPT. Assuming a threshold of ≥ 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, ∆NTCP ≥ 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost. CONCLUSIONS: The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering the toxicities xerostomia and dysphagia, if a feasible strategy for patient anatomy changes is implemented.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Modelos Estatísticos , Fótons/efeitos adversos , Terapia com Prótons/efeitos adversos , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada/efeitos adversos , Transtornos de Deglutição/etiologia , Edema/etiologia , Humanos , Doenças da Laringe/etiologia , Mucosite/etiologia , Órgãos em Risco , Fótons/uso terapêutico , Probabilidade , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Aspiração Respiratória/etiologia , Trismo/etiologia , Xerostomia/etiologia
17.
Phys Med Biol ; 60(16): 6227-46, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26237315

RESUMO

At the Heidelberg Ion-Beam Therapy Center, patient irradiation with scanned proton and carbon ion beams is verified by offline positron emission tomography (PET) imaging: the ß+-activity measured within the patient is compared to a prediction calculated on the basis of the treatment planning data in order to identify potential delivery errors. Currently, this monitoring technique is limited to the treatment of static target structures. However, intra-fractional organ motion imposes considerable additional challenges to scanned ion beam radiotherapy. In this work, the feasibility and potential of time-resolved (4D) offline PET-based treatment verification with a commercial full-ring PET/CT (x-ray computed tomography) device are investigated for the first time, based on an experimental campaign with moving phantoms. Motion was monitored during the gated beam delivery as well as the subsequent PET acquisition and was taken into account in the corresponding 4D Monte-Carlo simulations and data evaluation. Under the given experimental conditions, millimeter agreement between the prediction and measurement was found. Dosimetric consequences due to the phantom motion could be reliably identified. The agreement between PET measurement and prediction in the presence of motion was found to be similar as in static reference measurements, thus demonstrating the potential of 4D PET-based treatment verification for future clinical applications.


Assuntos
Tomografia Computadorizada Quadridimensional/métodos , Tomografia por Emissão de Pósitrons/métodos , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Imagens de Fantasmas
18.
Int J Radiat Oncol Biol Phys ; 92(5): 1165-1174, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26194685

RESUMO

PURPOSE: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. METHODS AND MATERIALS: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. RESULTS: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. CONCLUSIONS: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Órgãos em Risco/efeitos da radiação , Seleção de Pacientes , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas/patologia , Transtornos de Deglutição/prevenção & controle , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Edema Laríngeo/prevenção & controle , Masculino , Mucosite/prevenção & controle , Órgãos em Risco/diagnóstico por imagem , Pneumonia Aspirativa/prevenção & controle , Radiografia , Trismo/prevenção & controle , Carga Tumoral , Xerostomia/prevenção & controle
19.
Z Med Phys ; 25(2): 146-55, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25193358

RESUMO

INTRODUCTION: Particle Therapy Positron Emission Tomography (PT-PET) is currently the only clinically applied method for in vivo verification of ion-beam radiotherapy during or close in time to the treatment. Since a direct deduction of the delivered dose from the measured activity is not feasible, images are compared to a reference distribution. The achievable accuracy of two image analysis approaches was investigated by means of reproducible phantom benchmark tests. This is an objective method that excludes patient related factors of influence. MATERIAL AND METHODS: Two types of phantoms were designed to produce well defined deviations in the activity distributions. Pure range differences were simulated using the first phantom type while the other emulated cavity structures. The phantoms were irradiated with (12)C-ions. PT-PET measurements were performed by means of a camera system installed at the beamline. Different measurement time scenarios were investigated, assuming a PET scanner directly at the irradiation site or placed within the treatment room. The images were analyzed by means of the Pearson Correlation Coefficient (PCC) and a range calculation algorithm combined with a dedicated cavity filling detection method. RESULTS: Range differences could be measured with an error of less than 2 mm. The range comparison algorithm yielded slightly better results than the PCC method. The filling of a cavity structure could be safely detected if its inner diameter was at least 5 mm. CONCLUSION: Both approaches evaluate the PT-PET data in an objective way and deliver promising results for in-beam and in-room PET for clinical realistic dose rates.


Assuntos
Radioterapia com Íons Pesados/métodos , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Radioterapia Guiada por Imagem/métodos , Simulação por Computador , Humanos , Modelos Biológicos , Imagens de Fantasmas , Radiometria/métodos , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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