RESUMO
PURPOSE: For many thoracic tumors, patient respiration can introduce a significant amount of variability in tumor position that must be accounted for during radiotherapy. Of all existing techniques, real-time dynamic tumor tracking (DTT) represents the most ideal motion management strategy but can be limited by the treatment delivery technique. Our objective was to analyze the dosimetric performance of a dynamic conformal arc (DCA) approach to tumor tracking on standard linear accelerators that may offer similar dosimetric benefit, but with less complexity compared to intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT). METHODS: Ten patients who previously received free-breathing VMAT for lung cancer were retrospectively analyzed. Patient 4D-CT and respiratory traces were simultaneously acquired prior to treatment and re-planned with DCA and VMAT using the Eclipse v15.6 Treatment Planning System with gated, deep inspiration breath hold (DIBH), and motion encompassment techniques taken into consideration, generating seven new plans per patient. DTT with DCA was simulated using an in-house MATLAB script to parse the radiation dose into each phase of the 4D-CT based on the patient's respiratory trace. Dose distributions were normalized to the same prescription and analyzed using dose volume histograms (DVHs). DVH metrics were assessed using ANOVA with subsequent paired t-tests. RESULTS: The DCA-based DTT plans outperformed or showed comparable performance in their DVH metrics compared to all other combinations of treatment techniques while using motion management in normal lung sparing (p < 0.05). Normal lung sparing was not significantly different when comparing DCA-based DTT to gated and DIBH VMAT (p > 0.05), while both outperformed the corresponding DCA plans (p < 0.05). Simulated treatment times using DCA-based DTT were significantly shorter than both gating and DIBH plans (p < 0.05). CONCLUSIONS: A DCA-based DTT technique showed significant advantages over conventional motion encompassment treatments in lung cancer radiotherapy, with comparable performance to stricter techniques like gating and DIBH while conferring greater time-saving benefits.
Assuntos
Neoplasias Pulmonares , Radioterapia de Intensidade Modulada , Humanos , Estudos Retrospectivos , Planejamento da Radioterapia Assistida por Computador/métodos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Neoplasias Pulmonares/radioterapia , Órgãos em RiscoRESUMO
Positron emission tomography with x-ray computed tomography (PET/CT) is increasingly being utilized for radiation treatment planning (RTP). Accurate delivery of RT therefore depends on quality PET/CT data. This study covers quality control (QC) procedures required for PET/CT for diagnostic imaging and incremental QC required for RTP. Based on a review of the literature, it compiles a list of recommended tests, performance frequencies, and tolerances, as well as references to documents detailing how to perform each test. The report was commissioned by the Canadian Organization of Medical Physicists as part of the Canadian Partnership for Quality Radiotherapy initiative.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Planejamento da Radioterapia Assistida por Computador , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Física Médica , Canadá , Controle de Qualidade , Tomografia por Emissão de PósitronsRESUMO
PURPOSE: For lung and liver tumors requiring radiotherapy, motion artifacts are common in 4D-CT images due to the small axial field-of-view (aFOV) of conventional CT scanners. This may negatively impact contouring and dose calculation accuracy and could lead to a geographic miss during treatment. Recent advancements in volumetric CT (vCT) enable an aFOV up to 160 mm in a single rotation, which may reduce motion artifacts. However, the impact of large aFOV on CT number required for dose calculation needs to be evaluated before clinical implementation. The objective of this study was to determine the utility of a 256-slice vCT scanner for 4D-CT simulation by evaluating image quality and generating relative electron density (RED) curves. METHODS: Images were acquired on a 256-slice GE Revolution CT scanner with 40 mm, 80 mm, 120 mm, 140 mm, and 160 mm aFOV. Image quality was assessed by evaluating CT number linearity, uniformity, noise, and low-contrast resolution. The relationship between each quality metric and aFOV was assessed. RESULTS: CT number linearity, uniformity, noise, and low-contrast resolution were within the expected range for each image set, except CT number in Teflon and Delrin, which were underestimated. Spearman correlation coefficient (ρ) showed that the CT number for Teflon (ρ = 1.0, p = 0.02), Delrin (ρ = 1.0, p = 0.02), and air (ρ = 1.0, p = 0.02) was significantly related to aFOV, while all other measurements were not. The measured deviations from expected values were not clinically significant. CONCLUSION: These results suggest that vCT can be used for CT simulation for radiation treatment planning.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Radioterapia (Especialidade) , Simulação por Computador , Humanos , Imagens de Fantasmas , Dosagem Radioterapêutica , Tomógrafos ComputadorizadosRESUMO
BACKGROUND: The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions. METHODS: This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744. FINDINGS: 99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group. INTERPRETATION: SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit. FUNDING: Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.
Assuntos
Metástase Neoplásica/radioterapia , Cuidados Paliativos , Radiocirurgia , Idoso , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/terapia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Radiocirurgia/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: A recent randomized phase II trial evaluated stereotactic ablative radiotherapy (SABR) in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with a significant improvement in progression-free survival and a trend to an overall survival benefit, supporting progression to phase III randomized trials. METHODS: Two hundred and ninety-seven patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care [SOC] palliative-intent treatments), and the SABR arm (consisting of SOC treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (prostate, breast, or renal vs. all others), and disease-free interval (defined as time from diagnosis of primary tumor until first detection of the metastases being treated on this trial; divided as ≤2 vs. > 2 years). The primary endpoint is overall survival, and secondary endpoints include progression-free survival, cost effectiveness, time to development of new metastatic lesions, quality of life (QoL), and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. DISCUSSION: This study will provide an assessment of the impact of SABR on survival, QoL, and cost effectiveness to determine if long-term survival can be achieved for selected patients with 1-3 oligometastatic lesions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03862911. Date of registration: March 5, 2019.
Assuntos
Tomografia Computadorizada Quadridimensional/métodos , Neoplasias/cirurgia , Células Neoplásicas Circulantes/patologia , Seleção de Pacientes , Radiocirurgia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase III como Assunto , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Metástase Neoplásica , Neoplasias/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
We quantitatively investigate the influence of image registration, using open-source software (3DSlicer), on kinetic analysis (Tofts model) of dynamic contrast enhanced MRI of early-stage breast cancer patients. We also show that registration computation time can be reduced by reducing the percent sampling (PS) of voxels used for estimation of the cost function. DCE-MRI breast images were acquired on a 3T-PET/MRI system in 13 patients with early-stage breast cancer who were scanned in a prone radiotherapy position. Images were registered using a BSpline transformation with a 2 cm isotropic grid at 100, 20, 5, 1, and 0.5PS (BRAINSFit in 3DSlicer). Signal enhancement curves were analyzed voxel-by-voxel using the Tofts kinetic model. Comparing unregistered with registered groups, we found a significant change in the 90th percentile of the voxel-wise distribution of Ktrans. We also found a significant reduction in the following: (1) in the standard error (uncertainty) of the parameter value estimation, (2) the number of voxel fits providing unphysical values for the extracellular-extravascular volume fraction (ve > 1), and (3) goodness of fit. We found no significant differences in the median of parameter value distributions (Ktrans, ve) between unregistered and registered images. Differences between parameters and uncertainties obtained using 100PS versus 20PS were small and statistically insignificant. As such, computation time can be reduced by a factor of 2, on average, by using 20PS while not affecting the kinetic fit. The methods outlined here are important for studies including a large number of post-contrast images or number of patient images.
Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste , Humanos , Cinética , Imageamento por Ressonância Magnética , IncertezaRESUMO
Radiotherapy for the treatment of left-sided breast cancer increases the long-term risk of cardiovascular disease. The purpose of the present study was to noninvasively image the progression of radiation-induced cardiac inflammation in a large animal model using a hybrid PET and MRI system. Five canines were imaged using [18F]fluorodeoxyglucose PET to assess changes in myocardial inflammation. All animals were imaged at baseline, 1 wk, and 1, 3, 6, and 12 mo after focused cardiac external beam irradiation with image guidance. Radiation was delivered in a single fraction. The linear quadratic model was used to convert a typical multifractionated heart dose to a corrected single-fraction biologically equivalent dose. Immunohistochemistry was performed on excised left ventricular tissue samples from all five irradiated canines and one nonirradiated control canine to confirm the presence of inflammation. The mean doses delivered to the entire heart, left ventricle, left anterior descending artery, and left circumflex artery were 1.7 ± 0.2, 2.7 ± 0.2, 5.5 ± 0.9, and 1.1 ± 0.4 Gy, respectively. FDG standard uptake values remained persistently elevated compared with baseline (1.1 ± 0.03 vs. 2.6 ± 0.19, P < 0.05). The presence of myocardial inflammation was confirmed histologically and correlated with myocardial dose. This study suggests a global inflammatory response that is persistent up to 12 mo postirradiation. Inflammation PET imaging should be considered in future clinical studies to monitor the early changes in cardiac function that may play a role in the ultimate development of radiation-induced cardiac toxicity. NEW & NOTEWORTHY Using advanced cardiac PET imaging, we have shown the spatial and quantitative relationship between radiation dose deposition and temporal changes in inflammation. We have shown that the progression of radiation-induced cardiac inflammation is immediate and does not subside for up to 1 yr after radiation. Results are presented in a large animal model that closely resembles the size and vessel architecture of humans. The proposed imaging protocol can be easily replicated for clinical use.
Assuntos
Neoplasias da Mama/radioterapia , Doenças Cardiovasculares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Lesões por Radiação/diagnóstico por imagem , Radioterapia/efeitos adversos , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Cães , Feminino , Fluordesoxiglucose F18 , Imageamento por Ressonância Magnética , Imagem Multimodal , Doses de Radiação , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Stereotactic ablative radiotherapy (SABR) has become an established treatment option for medically-inoperable early-stage (Stage I-IIA) non-small cell lung cancer (ES-NSCLC). SABR is able to obtain high rates of local control with low rates of symptomatic toxicity in this patient population. However, in a subset of patients with fibrotic interstitial lung disease (ILD), elevated rates of SABR-related toxicity and mortality have been described. The Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD) study will conduct a thorough prospective evaluation of the clinical outcomes, toxicity, changes in diagnostic test parameters and patient-related outcomes following SABR for ES-NSCLC for patients with fibrotic ILD. METHODS: ASPIRE-ILD is a single-arm Phase II prospective study. The accrual target is 39 adult patients with T1-2N0M0 non-small cell lung cancer with co-existing ILD who are not candidates for surgical excision. Pathological confirmation of diagnosis is strongly recommended but not strictly required. Enrolled patients will be stratified by ILD-related mortality risk. The starting SABR dose will be 50 Gy in 5 fractions every other day (biologically effective dose: 100 Gy10 or 217 Gy3), but the radiation dose can be de-escalated up to two times to 50 Gy in 10 fractions daily (75 Gy10 or 133 Gy3) and 45 Gy in 15 fractions daily (58 Gy10 or 90 Gy3). Dose de-escalation will occur if 2 or more of the first 7 patients in a cohort experiences grade 5 toxicity within 6 months of treatment. Similarly, dose de-escalation can also occur if 2 or more of the first 7 patients with a specific subtype of ILD experiences grade 5 toxicity within 6 months of treatment. The primary endpoint is overall survival. Secondary endpoints include toxicity (CTC-AE 4.0), progression-free survival, local control, patient-reported outcomes (cough severity and quality of life), rates of ILD exacerbation and changes in pulmonary function tests/high-resolution computed tomography findings post-SABR. DISCUSSION: ASPIRE-ILD will be the first prospective study specifically designed to comprehensively evaluate the effectiveness and safety of SABR for ES-NSCLC in patients with co-existing ILD. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03485378. Date of registration: April 2, 2018.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Doenças Pulmonares Intersticiais/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Doenças Pulmonares Intersticiais/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions. METHODS: One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. DISCUSSION: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4-10 oligometastatic lesions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03721341 . Date of registration: October 26, 2018.
Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Células Neoplásicas Circulantes/efeitos da radiação , Radiocirurgia , Biomarcadores Tumorais/sangue , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias/sangue , Seleção de Pacientes , Prognóstico , Intervalo Livre de Progressão , Qualidade de Vida , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
The Canadian Organization of Medical Physicists (COMP), in close partnership with the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series of Technical Quality Control (TQC) guidelines for radiation treatment equipment. These guidelines outline the performance objectives that equipment should meet in order to ensure an acceptable level of radiation treatment quality. The TQC guidelines have been rigorously reviewed and field tested in a variety of Canadian radiation treatment facilities. The development process enables rapid review and update to keep the guidelines current with changes in technology (the most updated version of this guideline can be found on the CPQR website). This particular TQC details recommended quality control testing of CT simulators.
Assuntos
Simulação por Computador , Física Médica , Guias de Prática Clínica como Assunto/normas , Garantia da Qualidade dos Cuidados de Saúde/normas , Controle de Qualidade , Relatório de Pesquisa , Tomografia Computadorizada por Raios X/normas , Canadá , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/instrumentação , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Volumetric-modulated arc therapy (VMAT) delivery for stereotactic ablative radiotherapy (SABR) of multiple lung tumors allows for faster treatments. We report on clinical outcomes and describe a general approach for treatment planning. MATERIAL AND METHODS: Patients undergoing multi iso-center VMAT-based SABR for ≥2 lung lesions between 2009 and 2014 were identified from the VU University Medical Center and London Health Sciences Centre. Patients were eligible if the start date of the SABR treatment for the different lesions was within a time range of 30 days. SABR was delivered using separate iso-centers for lesions at a substantial distance from each other. Tumors were either treated with a single fraction of 34 Gy, or using three risk-adapted dose-fractionation schemes, namely three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, depending on the tumor size and the location. Multivariable analysis was performed to assess factors predictive of clinical outcomes. RESULTS: Of 84 patients (188 lesions) identified, 46% were treated for multiple metastases and 54% for multiple primary NSCLC. About 97% were treated for two or three lesions, and 56% had bilateral disease. After a median follow-up of 28 months, median overall survival (OS) for primary tumors was 27.6 months, and not reached for metastatic lesions (p = .028). Grade ≥3 toxicity was observed in 2% of patients. Multivariable analysis showed that grade 2 or higher radiation pneumonitis (n = 9) was best predicted by a total lung V35Gy of ≥6.5% (in 2Gy/fraction equivalent) (p = .007). CONCLUSION: Severe toxicity was uncommon following SABR using VMAT for up to three lung tumors. Further investigations of planning parameters are needed in patients presenting with more lesions.
Assuntos
Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: New parameters that correlate with overall survival were identified in patients with liver lesions treated with radiation therapy. METHODS: Pretreatment information and parameters of radiation treatment plans for 129 metastatic and 66 hepatocellular carcinoma liver cancer patients were analyzed. Study end points included overall survival collected from patient charts and electronic records. RESULTS: Two practical nomograms were constructed for primary hepatocellular carcinoma and liver metastasis patients. For patients with a Child-Pugh A, radiation dose escalation provided a significant survival benefit. However, for those with Child-Pugh B or C, increasing dose does not impact on survival. CONCLUSION: The developed models can potentially guide dose selection and provide prognostic information but still require external validation.
Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/radioterapia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Carcinoma Hepatocelular/diagnóstico , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Nomogramas , Prognóstico , Carga TumoralRESUMO
Volumetric-modulated arc therapy (VMAT) is emerging as a leading technology in treating early-stage, non-small cell lung cancer (NSCLC) with stereotactic ablative radiotherapy (SABR). However, two other modalities capable of deliver-ing intensity-modulated radiation therapy (IMRT) include fixed-beam and helical TomoTherapy (HT). This study aims to provide an extensive dosimetric compari-son among these various IMRT techniques for treating early-stage NSCLC with SABR. Ten early-stage NSCLC patients were retrospectively optimized using three fixed-beam techniques via nine to eleven beams (high and low modulation step-and-shoot (SS), and sliding window (SW)), two VMAT techniques via two partial arcs (SmartArc (SA) and RapidArc (RA)), and three HT techniques via three different fan beam widths (1 cm, 2.5 cm, and 5 cm) for 80 plans total. Fixed-beam and VMAT plans were generated using flattening filter-free beams. SS and SA, HT treatment plans, and SW and RA were optimized using Pinnacle v9.1, Tomoplan v.3.1.1, and Eclipse (Acuros XB v11.3 algorithm), respectively. Dose-volume histogram statistics, dose conformality, and treatment delivery efficiency were analyzed. VMAT treatment plans achieved significantly lower values for contralat-eral lung V5Gy (p ≤ 0.05) compared to the HT plans, and significantly lower mean lung dose (p < 0.006) compared to HT 5 cm treatment plans. In the comparison between the VMAT techniques, a significant reduction in the total monitor units (p = 0.05) was found in the SA plans, while a significant decrease was observed in the dose falloff parameter, D2cm, (p = 0.05), for the RA treatments. The maximum cord dose was significantly reduced (p = 0.017) in grouped RA&SA plans com-pared to SS. Estimated treatment time was significantly higher for HT and fixed-beam plans compared to RA&SA (p < 0.001). Although, a significant difference was not observed in the RA vs. SA (p = 0.393). RA&SA outperformed HT in all parameters measured. Despite an increase in dose to the heart and bronchus, this study demonstrates that VMAT is dosimetrically advantageous in treating early-stage NSCLC with SABR compared to fixed-beam, while providing significantly shorter treatment times.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Órgãos em Risco/efeitos da radiação , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Seleção de Pacientes , Dosagem Radioterapêutica , Estudos RetrospectivosRESUMO
BACKGROUND: Accurate target volume segmentation is crucial for success in image-guided radiotherapy. However, variability in anatomical segmentation is one of the most significant contributors to uncertainty in radiotherapy treatment planning. This is especially true for lung cancer where target volumes are subject to varying magnitudes of respiratory motion. MATERIAL AND METHODS: This study aims to analyze multiple observer target volume segmentations and subsequent intensity-modulated radiotherapy (IMRT) treatment plans defined by those segmentations against a reference standard for lung cancer patients imaged with four-dimensional computed tomography (4D-CT). Target volume segmentations of 10 patients were performed manually by six physicians, allowing for the calculation of ground truth estimate segmentations via the simultaneous truth and performance level estimation (STAPLE) algorithm. Segmentation variability was assessed in terms of distance- and volume-based metrics. Treatment plans defined by these segmentations were then subject to dosimetric evaluation consisting of both physical and radiobiological analysis of optimized 3D dose distributions. RESULTS: Significant differences were noticed amongst observers in comparison to STAPLE segmentations and this variability directly extended into the treatment planning stages in the context of all dosimetric parameters used in this study. Mean primary tumor control probability (TCP) ranged from (22.6±11.9)% to (33.7±0.6)%, with standard deviation ranging from 0.5% to 11.9%. However, mean normal tissue complication probabilities (NTCP) based on treatment plans for each physician-derived target volume well as the NTCP derived from STAPLE-based treatment plans demonstrated no discernible trends and variability appeared to be patient-specific. This type of variability demonstrated the large-scale impact that target volume segmentation uncertainty can play in IMRT treatment planning. CONCLUSIONS: Significant target volume segmentation and dosimetric variability exists in IMRT treatment planning amongst experts in the presence of a reference standard for 4D-CT-based lung cancer radiotherapy. Future work is needed to mitigate this uncertainty and ensure highly accurate and effective radiotherapy for lung cancer patients.
Assuntos
Algoritmos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Tomografia Computadorizada Quadridimensional/métodos , Neoplasias Pulmonares/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Movimento , Variações Dependentes do Observador , Órgãos em Risco/diagnóstico por imagem , Radioterapia (Especialidade)/normas , Respiração , Carga Tumoral , IncertezaRESUMO
BACKGROUND: Although radiotherapy is a key component of curative-intent treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC), it can be associated with substantial pulmonary toxicity in some patients. Current radiotherapy planning techniques aim to minimize the radiation dose to the lungs, without accounting for regional variations in lung function. Many patients, particularly smokers, can have substantial regional differences in pulmonary ventilation patterns, and it has been hypothesized that preferential avoidance of functional lung during radiotherapy may reduce toxicity. Although several investigators have shown that functional lung can be identified using advanced imaging techniques and/or demonstrated the feasibility and theoretical advantages of avoiding functional lung during radiotherapy, to our knowledge this premise has never been tested via a prospective randomized clinical trial. METHODS/DESIGN: Eligible patients will have Stage III NSCLC with intent to receive concurrent chemoradiotherapy (CRT). Every patient will undergo a pre-treatment functional lung imaging study using hyperpolarized 3He MRI in order to identify the spatial distribution of normally-ventilated lung. Before randomization, two clinically-approved radiotherapy plans will be devised for all patients on trial, termed standard and avoidance. The standard plan will be designed without reference to the functional state of the lung, while the avoidance plan will be optimized such that dose to functional lung is as low as reasonably achievable. Patients will then be randomized in a 1:1 ratio to receive either the standard or the avoidance plan, with both the physician and the patient blinded to the randomization results. This study aims to accrue a total of 64 patients within two years. The primary endpoint will be a pulmonary quality of life (QOL) assessment at 3 months post-treatment, measured using the functional assessment of cancer therapy-lung cancer subscale. Secondary endpoints include: pulmonary QOL at other time-points, provider-reported toxicity, overall survival, progression-free survival, and quality-adjusted survival. DISCUSSION: This randomized, double-blind trial will comprehensively assess the impact of functional lung avoidance on pulmonary toxicity and quality of life in patients receiving concurrent CRT for locally advanced NSCLC. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02002052.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/radioterapia , Pulmão/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/efeitos adversos , Método Duplo-Cego , Humanos , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética/métodos , Medicina de Precisão , Estudos Prospectivos , Qualidade de Vida , Análise de SobrevidaRESUMO
Importance: Patients with interstitial lung disease (ILD) and early-stage non-small cell lung cancer (NSCLC) have been reported to be at high risk of toxic effects after stereotactic ablative radiotherapy (SABR), but for many patients, there are limited alternative treatment options. Objective: To prospectively assess the benefits and toxic effects of SABR in this patient population. Design, Setting, and Participants: This prospective cohort study was conducted at 6 academic radiation oncology institutions, 5 in Canada and 1 in Scotland, with accrual between March 7, 2019, and January 12, 2022. Patients aged 18 years or older with fibrotic ILD and a diagnosis of T1-2N0 NSCLC who were not candidates for surgical resection were enrolled. Intervention: Patients were treated with SABR to a dose of 50 Gy in 5 fractions every other day. Main Outcomes and Measures: The study prespecified that SABR would be considered worthwhile if median overall survival-the primary end point-was longer than 1 year, with a grade 3 to 4 risk of toxic effects less than 35% and a grade 5 risk of toxic effects less than 15%. Secondary end points included toxic effects, progression-free survival (PFS), local control (LC), quality-of-life outcomes, and changes in pulmonary function. Intention-to-treat analysis was conducted. Results: Thirty-nine patients enrolled and received SABR. Median age was 78 (IQR, 67-83) years and 59% (n = 23) were male. At baseline, 70% (26 of 37) of patients reported dyspnea, median forced expiratory volume in first second of expiration was 80% (IQR, 66%-90%) predicted, median forced vital capacity was 84% (IQR, 69%-94%) predicted, and median diffusion capacity of the lung for carbon monoxide was 49% (IQR, 38%-61%) predicted. Median follow-up was 19 (IQR, 14-25) months. Overall survival at 1 year was 79% (95%, CI 62%-89%; P < .001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Median PFS was 19 months (95% CI, 13-28 months), and 2-year LC was 92% (95% CI, 69%-98%). Adverse event rates (highest grade per patient) were grade 1 to 2: n = 12 (31%), grade 3: n = 4 (10%), grade 4: n = 0, and grade 5: n = 3 (7.7%, all due to respiratory deterioration). Conclusions and Relevance: In this trial, use of SABR in patients with fibrotic ILD met the prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT03485378.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Doenças Pulmonares Intersticiais/etiologia , Masculino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patologia , Feminino , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Qualidade de Vida , CanadáRESUMO
PURPOSE: This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of stereotactic ablative radiotherapy (SABR) to standard of care (SOC) systemic therapy. METHODS: We enrolled patients with 1-5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs. non-cytotoxic), randomized 1:2 between continued SOC treatment vs. SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all non-hematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events (AEs), and duration of systemic therapy post-randomization. RESULTS: Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. Median age was 67 years and 39 (43%) were female. The most common primary sites were lung (44%), genitourinary (23%) and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. Median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs. 4.3 months in the SOC arm but curves cross and 2-year PFS was 9% vs. 24% respectively, p=0.91). Median OS was 31.2 months vs. 27.4 months, respectively (p=0.22). Lesional control was superior with SABR (70% vs. 38% respectively, p=0.0015). There were 2 (3.4%) grade 3 and no grade 4/5 AEs attributable to SABR. CONCLUSION: SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).
RESUMO
Tumor motion during radiation treatment on a helical tomotherapy unit may create problems due to interplay with motion of the multileaf collimator, gantry rotation, and patient couch translation through the gantry. This study evaluated this interplay effect for typical clinical parameters using a cylindrical phantom consisting of 1386 diode detectors placed on a respiratory motion platform. All combinations of radiation field widths (1, 2.5, and 5 cm) and gantry rotation periods (16, 30, and 60 s) were considered for sinusoidal motions with a period of 4 s and amplitudes of 5, 6, 7, 8, 9, and 10 mm, as well as real patient breathing pattern. Gamma comparisons with 2% dose difference and 2 mm distance to agreement and dose profiles were used for evaluation. The required motion margins were determined for each set of parameters. The required margin size increased with decreasing field width and increasing tumor motion amplitude, but was not affected by rotation period. The plans with the smallest field width of 1 cm have required motion margins approximately equal to the amplitude of motion (± 25%), while those with the largest field width of 5 cm had required motion margins approximately equal to 20% of the motion amplitude (± 20%). For tumor motion amplitudes below 6 mm and field widths above 1 cm, the required additional motion margins were very small, at a maximum of 2.5 mm for sinusoidal breathing patterns and 1.2 mm for the real patient breathing pattern.
Assuntos
Artefatos , Neoplasias/radioterapia , Radiometria/instrumentação , Radiometria/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Mecânica Respiratória , Humanos , Movimento (Física) , Dosagem Radioterapêutica , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Our purpose was to investigate the utility of 18F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18F-FDG SUVmean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUVmean in left anterior descending segments (P = 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P ≤ 0.02). Further, a significant reduction in left ventricular stroke volume (-7%) was seen (P < 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.
Assuntos
Neoplasias da Mama , Neoplasias Unilaterais da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Fluordesoxiglucose F18 , Coração/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Arritmias Cardíacas , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured. METHOD: In five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method. RESULTS: MBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories. CONCLUSION: In this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.