RESUMO
Most radiotherapy treatments are nowadays delivered with linear accelerators producing photons. This robust radiation technique improved outstandingly during the last three decades, allowing treatments for most tumoural indications with an exquisite accuracy, a formidable effectiveness, a low toxicity, and a very low cost for the society. Therefore, the reasons for using and developing the more expensive hadron therapy and more particularly proton therapy may seem futile. In the current article targeting the general practitioners readership, we look at the principles of this innovative technique, its inherent advantages and limitations, the current and future indications, the challenges and perspectives for the future. We conclude with an overview of the Belgian landscape in terms of installation, operation, access and reimbursement procedures.
L'essentiel des traitements de radiothérapie sont délivrés à l'aide d'accélérateurs linéaires produisant des photons. La technique est robuste et a connu une évolution fulgurante ces trois dernières décennies, apportant une efficacité redoutable et une extrême précision dans de nombreuses indications tumorales, avec les avantages d'un risque de toxicité réduit et d'un coût sociétal extrêmement faible. Dès lors, quel intérêt y aurait-il à utiliser et développer des traitements de radiothérapie par hadrons, et plus particulièrement par protons, sachant que les coûts d'installation et de production sont, au bas mot, décuplés par rapport aux photons ? Dans cet article destiné en première intention aux praticiens de santé généralistes, nous abordons les principes de fonctionnement, les avantages et limitations inhérents à la technique, les indications actuelles et celles qui se profilent, les défis et perspectives à venir. Nous terminons, enfin, par un tour d'horizon du paysage belge en termes d'installation, de fonctionnement, d'accès et de modalités de remboursement.
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Neoplasias , Terapia com Prótons , Humanos , Bélgica , Terapia com Prótons/métodos , Neoplasias/radioterapiaRESUMO
Stereotactic body radiotherapy (SBRT) for patients with metastatic cancer, especially when characterised by a low tumour burden (ie, oligometastatic disease), receiving targeted therapy or immunotherapy has become a frequently practised and guideline-supported treatment strategy. Despite the increasing use in routine clinical practice, there is little information on the safety of combining SBRT with modern targeted therapy or immunotherapy and a paucity of high-level evidence to guide clinical management. A systematic literature review was performed to identify the toxicity profiles of combined metastases-directed SBRT and targeted therapy or immunotherapy. These results served as the basis for an international Delphi consensus process among 28 interdisciplinary experts who are members of the European Society for Radiotherapy and Oncology (ESTRO) and European Organisation for Research and Treatment of Cancer (EORTC) OligoCare consortium. Consensus was sought about risk mitigation strategies of metastases-directed SBRT combined with targeted therapy or immunotherapy; a potential need for and length of interruption to targeted therapy or immunotherapy around SBRT delivery; and potential adaptations of radiation dose and fractionation. Results of this systematic review and consensus process compile the best available evidence for safe combination of metastases-directed SBRT and targeted therapy or immunotherapy for patients with metastatic or oligometastatic cancer and aim to guide today's clinical practice and the design of future clinical trials.
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Neoplasias , Radioterapia (Especialidade) , Radiocirurgia , Humanos , Consenso , Imunoterapia , OncologiaRESUMO
PURPOSE: Defining dosimetric rules to automatically detect patients requiring adaptive radiotherapy (ART) is not straightforward, and most centres perform ad-hoc ART with no specific protocol. This study aims to propose and analyse different steps to design a protocol for dosimetrically triggered ART of head and neck (H&N) cancer. As a proof-of-concept, the designed protocol was applied to patients treated in TomoTherapy units, using their available software for daily MVCT image and dose accumulation. METHODS: An initial protocol was designed by a multidisciplinary team, with a set of flagging criteria based only on dose-volume metrics, including two action levels: (1) surveillance (orange flag), and (2) immediate verification (red flag). This protocol was adapted to the clinical needs following an iterative process. First, the protocol was applied to 38 H&N patients with daily imaging. Automatic software generated the daily contours, recomputed the daily dose and flagged the dosimetric differences with respect to the planning dose. Second, these results were compared, by a sensitivity/specificity test, to the answers of a physician. Third, the physician, supported by the multidisciplinary team, performed a self-analysis of the provided answers and translated them into mathematical rules in order to upgrade the protocol. The upgraded protocol was applied to different definitions of the target volume (i.e. deformed CTV + 0, 2 and 4 mm), in order to quantify how the number of flags decreases when reducing the CTV-to-PTV margin. RESULTS: The sensitivity of the initial protocol was very low, specifically for the orange flags. The best values were 0.84 for red and 0.15 for orange flags. After the review and upgrade process, the sensitivity of the upgraded protocol increased to 0.96 for red and 0.84 for orange flags. The number of patients flagged per week with the final (upgraded) protocol decreased in median by 26% and 18% for red and orange flags, respectively, when reducing the CTV-to-PTV margin from 4 to 2 mm. This resulted in only one patient flagged at the last fraction for both red and orange flags. CONCLUSION: Our results demonstrate the value of iterative protocol design with retrospective data, and shows the feasibility of automatically-triggered ART using simple dosimetric rules to mimic the physician's decisions. Using a proper target volume definition is important and influences the flagging rate, particularly when decreasing the CTV-to-PTV margin.
Assuntos
Neoplasias de Cabeça e Pescoço , Radioterapia de Intensidade Modulada , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Radioterapia de Intensidade Modulada/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Protocolos ClínicosRESUMO
BACKGROUND: Definitive external beam radiotherapy (EBRT) is an unusual treatment of unresectable soft-tissue sarcomas (STS). Recent technical innovations and physical advantages of particle therapies may improve results of this therapeutic option. The role of this review was to report the clinical results of photon- and particle-based EBRT in unresectable STS. MATERIAL AND METHODS: We performed a systematic review of the literature on Pubmed database to identify studies investigating the efficacy and safety of EBRT. The primary endpoint was local control (LC) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and adverse events in a subset of patients with gross disease STS. RESULTS: We identified 29 studies involving 1409 patients (pts) evaluating photon (n = 18; 956 pts), proton (n = 1; 21 pts), carbon ion (n = 2; 152 pts), neutron (n = 7; 259 pts) or pion (n = 1; 21 pts) therapy. Definitive EBRT achieves valuable 5-year LC rates of 28-73% with photon and 52-69% with particle therapies. Most local failures (66-100%) occurred within 3 years. Long-term disease control can be achieved in a fraction of patients, with 5-year PFS and OS of 0-39% and 24.7-63%, respectively. The rate of severe adverse events was highly variable with photons, <15% in proton and carbon ion therapy, whereas 25 to 50% of patients treated with neutrons and pions presented severe AE. While a dose higher or equal 64 Gy seem to improve the prognosis, delivering a dose higher or equal 68 Gy dramatically increases severe adverse events. CONCLUSION: Definitive EBRT with dose 64-66 Gy seems to be a safe and efficient treatment for unresectable STS. Future clinical trials should assess the potential of biomarkers of response, thus identifying patients that could benefit from local treatment.
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Sarcoma , Neoplasias de Tecidos Moles , Humanos , Prótons , Dosagem Radioterapêutica , Radioterapia Adjuvante , Sarcoma/radioterapiaRESUMO
Background: There has been growing evidence of the benefits of high-intensity aerobic interval training (HIIT) and resistance training (RES) for populations with cancer. However, these two modalities have not yet been performed alone in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACR T). Therefore, this study aimed to determine the feasibility of HIIT and RES in rectal cancer patients undergoing NACR T. Materials and methods: Rectal cancer patients set to undergo NACRT were randomly assigned to HIIT intervention, RES intervention, or the usual care. Feasibility of HIIT and RES was assessed by measuring recruitment rate, adherence (retention rate, attendance rate, and exercise sessions duration and intensity), and adverse events. Endpoints (changes in fatigue, health-related quality of life, depression, daytime sleepiness, insomnia, sleep quality, functional exercise capacity, and executive function) were assessed at baseline and at week 5. Results: Among the 20 eligible patients, 18 subjects were enrolled and completed the study, yielding a 90% recruitment rate and 100% retention rate. Attendance at exercise sessions was excellent, with 92% in HIIT and 88% in RES. No exercise-related adverse events occurred. Conclusion: This study demonstrated that HIIT and RES are feasible in rectal cancer patients undergoing NACR T. Trial registration: www.clinicaltrials.gov, NCT03252821 (date of registration: March 30, 2017).
RESUMO
BACKGROUND: About 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR). METHODS: This investigator-initiated, multicentric, randomised controlled open-label phase II clinical trial will test the hypothesis that the combination of SABR and L19-IL2 increases progression free survival (PFS) in patients with limited metastatic NSCLC. One hundred twenty-six patients will be stratified according to their metastatic load (oligo-metastatic: ≤5 or poly-metastatic: 6 to 10) and randomised to the experimental-arm (E-arm) or the control-arm (C-arm). The C-arm will receive SOC, according to the local protocol. E-arm oligo-metastatic patients will receive SABR to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consists of irradiation of one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). The accrual period will be 2.5-years, starting after the first centre is initiated and active. Primary endpoint is PFS at 1.5-years based on blinded radiological review, and secondary endpoints are overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, immune monitoring, CT-based radiomics, stool collection, iRECIST and tumour growth rate will be performed. DISCUSSION: The combination of SABR with or without ICI and the immunocytokine L19-IL2 will be tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients in 14 centres located in 6 countries. This bimodal and trimodal treatment approach is based on the direct cytotoxic effect of radiotherapy, the tumour selective immunocytokine L19-IL2, the abscopal effect observed distant from the irradiated metastatic site(s) and the memory effect. The first results are expected end 2023. TRIAL REGISTRATION: ImmunoSABR Protocol Code: NL67629.068.18; EudraCT: 2018-002583-11; Clinicaltrials.gov: NCT03705403; ISRCTN ID: ISRCTN49817477; Date of registration: 03-April-2019.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Radiocirurgia/métodos , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Quimiorradioterapia/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Intervalo Livre de Progressão , Qualidade de Vida , Radiocirurgia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes de Fusão/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Padrão de CuidadoRESUMO
PURPOSE: The purpose of this study was to address the dosimetric accuracy of synthetic computed tomography (sCT) images of patients with brain tumor generated using a modified generative adversarial network (GAN) method, for their use in magnetic resonance imaging (MRI)-only treatment planning for proton therapy. METHODS: Dose volume histogram (DVH) analysis was performed on CT and sCT images of patients with brain tumor for plans generated for intensity-modulated proton therapy (IMPT). All plans were robustly optimized using a commercially available treatment planning system (RayStation, from RaySearch Laboratories) and standard robust parameters reported in the literature. The IMPT plan was then used to compute the dose on CT and sCT images for dosimetric comparison, using RayStation analytical (pencil beam) dose algorithm. We used a second, independent Monte Carlo dose calculation engine to recompute the dose on both CT and sCT images to ensure a proper analysis of the dosimetric accuracy of the sCT images. RESULTS: The results extracted from RayStation showed excellent agreement for most DVH metrics computed on the CT and sCT for the nominal case, with a mean absolute difference below 0.5% (0.3 Gy) of the prescription dose for the clinical target volume (CTV) and below 2% (1.2 Gy) for the organs at risk (OARs) considered. This demonstrates a high dosimetric accuracy for the generated sCT images, especially in the target volume. The metrics obtained from the Monte Carlo doses mostly agreed with the values extracted from RayStation for the nominal and worst-case scenarios (mean difference below 3%). CONCLUSIONS: This work demonstrated the feasibility of using sCT generated with a GAN-based deep learning method for MRI-only treatment planning of patients with brain tumor in intensity-modulated proton therapy.
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Neoplasias Encefálicas , Terapia com Prótons , Radioterapia de Intensidade Modulada , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Humanos , Imageamento por Ressonância Magnética , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: By increasing lung volume and decreasing respiration-induced tumour motion amplitude, administration of continuous positive airway pressure (CPAP) during stereotactic ablative radiotherapy (SABR) could allow for better sparing of the lungs and heart. In this study, we evaluated the effect of CPAP on lung volume, tumour motion amplitude and baseline shift, as well as the dosimetric impact of the strategy. METHODS: Twenty patients with lung tumours referred for SABR underwent 4D-computed tomography (CT) scans with and without CPAP (CPAP/noCPAP) at two timepoints (T0/T1). First, CPAP and noCPAP scans were compared for lung volume, tumour motion amplitude, and baseline shift. Next, CPAP and noCPAP treatment plans were computed and compared for lung dose parameters (mean lung dose (MLD), lung volume receiving 20 Gy (V20Gy), 13 Gy (V13Gy), and 5 Gy (V5Gy)) and mean heart dose (MHD). RESULTS: On average, CPAP increased lung volume by 8.0% (pâ¯< 0.001) and 6.3% (pâ¯< 0.001) at T0 and T1, respectively, but did not change tumour motion amplitude or baseline shift. As a result, CPAP administration led to an absolute decrease in MLD, lung V20Gy, V13Gy and V5Gy of 0.1â¯Gy (pâ¯= 0.1), 0.4% (pâ¯= 0.03), 0.5% (pâ¯= 0.04) and 0.5% (pâ¯= 0.2), respectively, while having no significant influence on MHD. CONCLUSIONS: In patients referred for SABR for lung tumours, CPAP increased lung volume without modifying tumour motion or baseline shift. As a result, CPAP allowed for a slight decrease in radiation dose to the lungs, which is unlikely to be clinically significant.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Movimentos dos Órgãos/fisiologia , Radiometria , Tomografia Computadorizada por Raios XRESUMO
AIM: The aim of the study was to assess the feasibility of an individualized 18F fluorodeoxyglucose positron emission tomography (FDG-PET)-guided dose escalation boost in non-small cell lung cancer (NSCLC) patients and to assess its impact on local tumor control and toxicity. PATIENTS AND METHODS: A total of 13 patients with stage II-III NSCLC were enrolled to receive a dose of 62.5 Gy in 25 fractions to the CT-based planning target volume (PTV; primary turmor and affected lymph nodes). The fraction dose was increased within the individual PET-based PTV (PTVPET) using intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) until the predefined organ-at-risk (OAR) threshold was reached. Tumor response was assessed during follow-up by means of repeat FDG-PET/computed tomography. Acute and late toxicity were recorded and classified according to the CTCAE criteria (Version 4.0). Local progression-free survival was determined using the Kaplan-Meier method. RESULTS: The average dose to PTVPET reached 89.17 Gy for peripheral and 75 Gy for central tumors. After a median follow-up period of 29 months, seven patients were still alive, while six had died (four due to distant progression, two due to grade 5 toxicity). Local progression was seen in two patients in association with further recurrences. One and 2-year local progression free survival rates were 76.9% and 52.8%, respectively. Three cases of acute grade 3 esophagitis were seen. Two patients with central tumors developed late toxicity and died due to severe hemoptysis. CONCLUSION: These results suggest that a non-uniform and individualized dose escalation based on FDG-PET in IMRT delivery is feasible. The doses reached were higher in patients with peripheral compared to central tumors. This strategy enables good local control to be achieved at acceptable toxicity rates. However, dose escalation in centrally located tumors with direct invasion of mediastinal organs must be performed with great caution in order to avoid severe late toxicity.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Idoso , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/métodos , Compostos Radiofarmacêuticos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Resultado do TratamentoRESUMO
BACKGROUND: PET-guided dose painting (DP) aims to target radioresistant tumour regions in order to improve radiotherapy (RT) outcome. Besides the well-known [18F]fluorodeoxyglucose (FDG), the hypoxia positron emission tomography (PET) tracer [18F]fluoroazomycin arabinoside (FAZA) could provide further useful information to guide the radiation dose prescription. In this study, we compare the spatial distributions of FDG and FAZA PET uptakes in lung tumours. MATERIAL AND METHODS: Fourteen patients with unresectable lung cancer underwent FDG and FAZA 4D-PET/CT on consecutive days at three time-points: prior to RT (pre), and during the second (w2), and the third (w3) weeks of RT. All PET/CT were reconstructed in their time-averaged midposition (MidP). The metabolic tumour volume (MTV: FDG standardised uptake value (SUV) > 50% SUVmax), and the hypoxic volume (HV: FAZA SUV > 1.4) were delineated within the gross tumour volume (GTVCT). FDG and FAZA intratumoral PET uptake distributions were subsequently pairwise compared, using both volume-, and voxel-based analyses. RESULTS: Volume-based analysis showed large overlap between MTV and HV: median overlapping fraction was 0.90, 0.94 and 0.94, at the pre, w2 and w3 time-points, respectively. Voxel-wise analysis between FDG and FAZA intratumoral PET uptake distributions showed high correlation: median Spearman's rank correlation coefficient was 0.76, 0.77 and 0.76, at the pre, w2 and w3 time-points, respectively. Interestingly, tumours with high FAZA uptake tended to show more similarity between FDG and FAZA intratumoral uptake distributions than those with low FAZA uptake. CONCLUSIONS: In unresectable lung carcinomas, FDG and FAZA PET uptake distributions displayed unexpectedly strong similarity, despite the distinct pathways targeted by these tracers. Hypoxia PET with FAZA brought very little added value over FDG from the perspective of DP in this population.
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Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Fluordesoxiglucose F18/metabolismo , Neoplasias Pulmonares/metabolismo , Nitroimidazóis/metabolismo , Compostos Radiofarmacêuticos/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Idoso , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Carcinoma de Pequenas Células do Pulmão/diagnóstico por imagem , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapiaRESUMO
BACKGROUND: Dose painting (DP) aims to improve radiation therapy (RT) outcome by targeting radioresistant tumour regions identified through functional imaging, e.g., positron emission tomography (PET). Importantly, the expected benefit of DP relies on the ability of PET imaging to identify tumour areas which could be consistently targeted throughout the treatment. In this study, we analysed the spatial stability of two potential DP targets in lung cancer patients undergoing RT: the tumour burden surrogate [18F]fluorodeoxyglucose (FDG) and the hypoxia surrogate [18F]fluoroazomycin arabinoside (FAZA). MATERIALS AND METHODS: Thirteen patients with unresectable lung tumours underwent FDG and FAZA 4D-PET/CT before (pre), and during the second (w2) and third (w3) weeks of RT. All PET/CT were reconstructed in their time-averaged midposition (MidP) for further analysis. The metabolic tumour volume (MTV: FDG standardised uptake value (SUV) > 50% SUVmax) and the hypoxic volume (HV: FAZA SUV >1.4) were delineated within the gross tumour volume (GTVCT). The stability of FDG and FAZA PET uptake distributions during RT was subsequently assessed through volume-overlap analysis and voxel-based correlation analysis. RESULTS: The volume-overlap analysis yielded median overlapping fraction (OF) of 0.86 between MTVpre and MTVw2 and 0.82 between MTVpre and MTVw3. In patients with a detectable HV, median OF was 0.82 between HVpre and HVw2 and 0.90 between HVpre and HVw3. The voxel-based correlation analysis yielded median Spearman's correlation coefficient (rS) of 0.87 between FDGpre and FDGw2 and 0.83 between FDGpre and FDGw3. Median rS was 0.78 between FAZApre and FAZAw2 and 0.79 between FAZApre and FAZAw3. CONCLUSIONS: FDG and FAZA PET uptake distributions were spatially stable during the 3 first weeks of RT in patients with unresectable lung cancer, both based on volume- and voxel-based indicators. This might allow for a consistent targeting of high FDG or FAZA PET uptake regions as part of a DP strategy.
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Fluordesoxiglucose F18/farmacocinética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Nitroimidazóis/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Idoso , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioterapia/métodos , Dosagem RadioterapêuticaRESUMO
BACKGROUND: In the context of dose painting by numbers delivered with intensity-modulated radiotherapy, the robustness of dose distributions against geometric uncertainties can be ensured by robust optimization. As robust optimization is seldom available in treatment planning systems (TPS), we propose an alternative method that reaches the same goal by modifying the heterogeneous dose prescription (based on (18)FDG-PET) and guarantees coverage in spite of systematic and random errors with known standard deviations Σ and σ, respectively. MATERIAL AND METHODS: The objective was that 95% of all voxels in the GTVPET received at least 95% of the prescribed dose despite geometric errors. The prescription was modified by a geometric dilation of αΣ for systematic errors and a deconvolution by a Gaussian function of width σ for random errors. For a 90% confidence interval, α = 2.5. Planning was performed on a TomoTherapy system, such that 95% of the voxels received at least 95% of the modified prescription and less than 5% of the voxels received more than 105% of the modified prescription. The applicability of the method was illustrated for two head-and-neck tumors. RESULTS: Systematic and random displacements larger than αΣ and σ degraded coverage. Down to 62.8% of the points received at least 95% of prescribed dose for the largest considered displacements (5 mm systematic translation and 3 mm standard deviation for random errors). When systematic and random displacements were smaller than αΣ and σ, no degradation of target coverage was observed. CONCLUSIONS: The method led to treatment plans with target coverage robust against geometric uncertainties without the need to incorporate these in the optimizer of the TPS. The methodology was illustrated for head-and-neck cancer but can be potentially extended to all treatment sites.
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Algoritmos , Neoplasias de Cabeça e Pescoço/radioterapia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/radioterapia , Intervalos de Confiança , Fluordesoxiglucose F18 , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Neoplasias/radioterapia , Distribuição Normal , Tomografia por Emissão de Pósitrons , Prescrições , Compostos Radiofarmacêuticos , IncertezaRESUMO
This study aimed to compare combined audio-visual coaching with audio coaching alone and assess their respective impact on the reproducibility of external breathing motion and, one step further, on the internal lung tumor motion itself, through successive sessions. Thirteen patients with NSCLC were enrolled in this study. The tumor motion was assessed by three to four successive 4D CT sessions, while the breathing signal was measured from magnetic sensors positioned on the epigastric region. For all sessions, the breathing was regularized with either audio coaching alone (AC, n = 5) or combined with a real-time visual feedback (A/VC, n = 8) when tolerated by the patients. Peak-to-peak amplitude, period and signal shape of both breathing and tumor motions were first measured. Then, the correlation between the respiratory signal and internal tumor motion over time was evaluated, as well as the residual tumor motion for a gated strategy. Although breathing and tumor motions were comparable between AC and AV/C groups, A/VC approach achieved better reproducibility through sessions than AC alone (mean tumor motion of 7.2 mm ± 1 vs. 8.6 mm ± 1.8 mm, and mean breathing motion of 14.9 mm ± 1.2 mm vs. 13.3mm ± 3.7 mm, respectively). High internal/external correlation reproducibility was achieved in the superior-inferior tumor motion direction for all patients. For the anterior posterior tumor motion direction, better correlation reproducibility has been observed when visual feedback has been used. For a displacement-based gating approach, A/VC might also be recommended, since it led to smaller residual tumor motion within clinically relevant duty cycles. This study suggests that combining real-time visual feedback with audio coaching might improve the reproducibility of key characteristics of the breathing pattern, and might thus be considered in the implementation of lung tumor radiotherapy.
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Recursos Audiovisuais , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Tomografia Computadorizada Quadridimensional , Neoplasias Pulmonares/radioterapia , Educação de Pacientes como Assunto/métodos , Respiração , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Movimento , Prognóstico , Lesões por Radiação/prevenção & controle , Dosagem RadioterapêuticaRESUMO
Objective. Radio-opaque markers are recommended for image-guided radiotherapy in liver stereotactic ablative radiotherapy (SABR), but their implantation is invasive. We evaluate in thisin-silicostudy the feasibility of cone-beam computed tomography-guided stereotactic online-adaptive radiotherapy (CBCT-STAR) to propagate the target volumes without implanting radio-opaque markers and assess its consequence on the margin that should be used in that context.Approach. An emulator of a CBCT-STAR-dedicated treatment planning system was used to generate plans for 32 liver SABR patients. Three target volume propagation strategies were compared, analysing the volume difference between the GTVPropagatedand the GTVConventional, the vector lengths between their centres of mass (lCoM), and the 95th percentile of the Hausdorff distance between these two volumes (HD95). These propagation strategies were: (1) structure-guided deformable registration with deformable GTV propagation; (2) rigid registration with rigid GTV propagation; and (3) image-guided deformable registration with rigid GTV propagation. Adaptive margin calculation integrated propagation errors, while interfraction position errors were removed. Scheduled plans (PlanNon-adaptive) and daily-adapted plans (PlanAdaptive) were compared for each treatment fraction.Main results.The image-guided deformable registration with rigid GTV propagation was the best propagation strategy regarding tolCoM(mean: 4.3 +/- 2.1 mm), HD95 (mean 4.8 +/- 3.2 mm) and volume preservation between GTVPropagatedand GTVConventional. This resulted in a planning target volume (PTV) margin increase (+69.1% in volume on average). Online adaptation (PlanAdaptive) reduced the violation rate of the most important dose constraints ('priority 1 constraints', 4.2 versus 0.9%, respectively;p< 0.001) and even improved target volume coverage compared to non-adaptive plans (PlanNon-adaptive).Significance. Markerless CBCT-STAR for liver tumours is feasible using Image-guided deformable registration with rigid GTV propagation. Despite the cost in terms of PTV volumes, daily adaptation reduces constraints violation and restores target volumes coverage.
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Tomografia Computadorizada de Feixe Cônico , Estudos de Viabilidade , Neoplasias Hepáticas , Fígado , Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Radioterapia Guiada por Imagem , Humanos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagemRESUMO
AIMS: The effects of isolated contemporary low-dose breast cancer (BC) radiotherapy (RT) on the heart remain poorly understood. This study aims to assess the long-term impacts of BC-RT on cardiac structure and function. METHODS AND RESULTS: Seventy-six women (62 ± 7 years) without history of prior heart disease, who had undergone RT for either first left (n = 36) or right (n = 40) BC, without additional medical oncology therapy apart from hormonal treatment 11 ± 1 years earlier, underwent transthoracic echocardiography, cardiac magnetic resonance imaging (CMR), computed tomography coronary angiography (CTCA), NT-proBNP, and a 6-min walk test (6MWT). They were compared with 54 age-matched healthy female controls. By CTCA, 68% of BC patients exhibited no or very mild coronary disease, while only 11% had moderate stenosis (50-69%) and 3% had significant stenosis (>70%). Despite slightly reduced regional echocardiographic midventricular strains, BC patients exhibited similar global left and right ventricular volumes, ejection fractions, and global strains by echocardiography and CMR as controls. Mitral E/e' ratios were slightly higher, and mitral deceleration times were slightly lower, but NT-proBNP was similar to controls. Also, 6MWT was normal. None had late gadolinium enhancement, and extracellular volume fraction was similar in BC (28 ± 3 vs. 29 ± 3, P = 0.15) and controls. No differences were observed relative to dose or side of RT. CONCLUSION: Aside from minor alterations of regional strains and diastolic parameters, women who received isolated RT for BC had low prevalence of coronary disease, normal global systolic function, NT-proBNP, and exercise capacity and showed no structural changes by CMR, refuting significant long-term cardiotoxicity in such low-risk patients.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/radioterapia , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Radioterapia Adjuvante , Estudos de Casos e Controles , Angiografia Coronária , Idoso , Ecocardiografia , Imagem Cinética por Ressonância Magnética/métodos , Medição de Risco , Angiografia por Tomografia Computadorizada/métodos , Fragmentos de Peptídeos/sangue , Peptídeo Natriurético Encefálico/sangue , Seguimentos , Fatores de TempoRESUMO
Background: Although stereotactic body radiotherapy (SBRT) was progressively adopted in clinical practice in Belgium, a reimbursement request in 2011 was not granted because of remaining clinical and economic uncertainty. A coverage with evidence development (CED) program on SBRT started in 2013, with the aim to assess clinical and technical patterns-of-care in Belgium and monitor survival per indication, in view of supporting inclusion in the reimbursement system. Methods: The Belgian National Institute for Health and Disability Insurance (NIHDI) initiated this prospective observational registry. Participating departments, using SBRT in clinical practice, signed the 'NIHDI convention'. Eligible patients had a primary tumour (PT) or oligometastatic disease (OMD). Patient, tumour, and treatment characteristics were collected through an online module of the Belgian Cancer Registry, prerequisite for financing. Five-year overall survival (5YOS) and 30- and 90-days mortality were primary outcomes, derived from vital status information. Findings: Between 10/2013 and 12/2019, 20 of the 24 accredited radiotherapy departments participated, 6 were academic. Registered cases per department ranged from 21 to 867. Of 5675 registrations analysed, the majority had good performance status and limited number of lesions. Enrolment of PTs remained stable over time, OMDs almost doubled. Peripheral lung lesions dominated in PTs as in OMDs. Other metastases were (para)spinal, 'non-standard' and hepatic. Thirty- and 90-days mortalities remained below 0.5% [95% CI 0.3%-0.8%] respectively 2.1% [95% CI 1.6%-2.7%]. 5YOS varied by indication, primary prostate patients performing best (85%, 95% CI [76%, 96%]), those with liver metastases worst (19%, 95% CI [15%, 24%]). Better OS was observed in academic departments, department size did not significantly impact survival. OMD survival was better in 2018-19. Interpretation: CED can be used to define patterns-of-care and real-life outcome of innovative radiotherapy. As the observed survival for different indications was in line with outcome in emerging literature, SBRT was included in the Belgian reimbursement system as of January 2020. Funding: NIHDI financed participating departments per registered case.
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INTRODUCTION: The international phase II single-arm LungTech trial 22113-08113 of the European Organization for Research and Treatment of Cancer assessed the safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage NSCLC. METHODS: Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance for any eligible patient, SBRT (8 × 7.5 Gy) was delivered. The primary endpoint was freedom from local progression probability three years after the start of SBRT. RESULTS: The trial was closed early due to poor accrual related to repeated safety-related pauses in recruitment. Between August 2015 and December 2017, 39 patients from six European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Six patients (19.4%) had an ultracentral tumor location. The median follow-up was 3.6 years. The rates of 3-year freedom from local progression and overall survival were 81.5% (90% confidence interval [CI]: 62.7%-91.4%) and 61.1% (90% CI: 44.1%-74.4%), respectively. Cumulative incidence rates of local, regional, and distant progression at three years were 6.7% (90% CI: 1.6%-17.1%), 3.3% (90% CI: 0.4%-12.4%), and 29.8% (90% CI: 16.8%-44.1%), respectively. SBRT-related acute adverse events and late adverse events ≥ G3 were reported in 6.5% (n = 2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4% (n = 6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively. CONCLUSIONS: The LungTech trial suggests that SBRT with 8 × 7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after a thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints, and post-SBRT interventions is crucial.
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AIM: To evaluate acute toxicity at 6 months after stereotactic body radiotherapy (SBRT) in patients with oligometastatic cancer within the OligoCare cohort. MATERIAL AND METHODS: OligoCare is a prospective, registry-based, single-arm, observational study that aims to report prospective real-world data of patients with oligometastases from solid cancer treated with SBRT (NCT03818503). Primary tumor included non-small cell lung cancer (NSCLC), breast cancer (BC), colorectal cancer (CRC), and prostate cancer (PC). This analysis addresses a secondary endpoint of the trial, acute toxicity within 6 months after SBRT. RESULTS: Out of 1,597registered patients, 1'468 patients were evaluated for acute toxicity. Globally, 290 (20 %) had NSCLC primary disease, 227 (16 %) had BC, 293 (20 %) had CRC, and 658 (45 %) had PC. Concomitant systemic treatment was administered in 527 (35.9 %) patients. According to the EORTC/ESTRO oligometastatic disease (OMD) classification, 828 (56 %) patients had de novo OMD, 464 (32 %) repeat OMD, and 176 (12 %) induced OMD. Acute grade ≥ 3 SBRT related adverse events were reported in 8 (0.5 %) patients, including 2 (0.1 %) fatal AEs. In particular, 6 (0.4 %) grade 3 events were: 1 empyema, 1 pneumonia, 1 radiation pneumonitis, 1 radiation skin injury, 1 decreased appetite, and 1 bone pain. Among those 2 occurred in NSCLC patients, 2 in BC patients, and 1 in CRC and PC patients each. The two (0.1 %) grade 5 toxicity were represented by: pneumonitis and cerebral hemorrhage. CONCLUSION: OligoCare is the largest prospective registry cohort on oligometastatic disease. Acute toxicity within 6 months was low, confirming the safety of SBRT in the treatment of oligometastases.
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BACKGROUND AND INTRODUCTION: Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation. MATERIALS AND METHODS: Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/ß of 10 Gy for all primaries, and cancer-specific α/ß of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC). RESULTS: Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions. CONCLUSION: This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).
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Fracionamento da Dose de Radiação , Radiocirurgia , Humanos , Radiocirurgia/métodos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Dosagem Radioterapêutica , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Idoso de 80 Anos ou mais , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Neoplasias/radioterapia , Neoplasias/patologiaRESUMO
PURPOSE: Ethos proposes a template-based automatic dose planning (Etb) for online adaptive radiotherapy. This study evaluates the general performance of Etb for prostate cancer, as well as the ability to generate patient-optimal plans, by comparing it with another state-of-the-art automatic planning method, i.e., deep learning dose prediction followed by dose mimicking (DP + DM). MATERIALS: General performances and capability to produce patient-optimal plan were investigated through two studies: Study-S1 generated plans for 45 patients using our initial Ethos clinical goals template (EG_init), and compared them to manually generated plans (MG). For study-S2, 10 patients which showed poor performances at study-S1 were selected. S2 compared the quality of plans generated with four different methods: 1) Ethos initial template (EG_init_selected), 2) Ethos updated template-based on S1 results (EG_upd_selected), 3) DP + DM, and 4) MG plans. RESULTS: EG_init plans showed satisfactory performance for dose level above 50 Gy: reported mean metrics differences (EG_init minus MG) never exceeded 0.6 %. However, lower dose levels showed loosely optimized metrics, mean differences for V30Gy to rectum and V20Gy to anal canal were of 6.6 % and 13.0 %. EG_init_selected showed amplified differences in V30Gy to rectum and V20Gy to anal canal: 8.5 % and 16.9 %, respectively. These dropped to 5.7 % and 11.5 % for EG_upd_selected plans but strongly increased V60Gy to rectum for 2 patients. DP + DM plans achieved differences of 3.4 % and 4.6 % without compromising any V60Gy. CONCLUSION: General performances of Etb were satisfactory. However, optimizing with template of goals might be limiting for some complex cases. Over our test patients, DP + DM outperformed the Etb approach.