RESUMO
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a novel non-invasive alternative for patients with primary renal cell cancer who do not undergo surgical resection. The FASTRACK II clinical trial investigated the efficacy of SABR for primary renal cell cancer in a phase 2 trial. METHODS: This international, non-randomised, phase 2 study was conducted in seven centres in Australia and one centre in the Netherlands. Eligible patients aged 18 years or older had biopsy-confirmed diagnosis of primary renal cell cancer, with only a single lesion; were medically inoperable, were at high risk of complications from surgery, or declined surgery; and had an Eastern Cooperative Oncology Group performance status of 0-2. A multidisciplinary decision that active treatment was warranted was required. Key exclusion criteria were a pre-treatment estimated glomerular filtration rate of less than 30 mL/min per 1·73 m2, previous systemic therapies for renal cell cancer, previous high-dose radiotherapy to an overlapping region, tumours larger than 10 cm, and direct contact of the renal cell cancer with the bowel. Patients received either a single fraction SABR of 26 Gy for tumours 4 cm or less in maximum diameter, or 42 Gy in three fractions for tumours more than 4 cm to 10 cm in maximum diameter. The primary endpoint was local control, defined as no progression of the primary renal cell cancer, as evaluated by the investigator per Response Evaluation Criteria in Solid Tumours (version 1.1). Assuming a 1-year local control of 90%, the null hypothesis of 80% or less was considered not to be worthy of proceeding to a future randomised controlled trial. All patients who commenced trial treatment were included in the primary outcome analysis. This trial is registered with ClinicalTrials.gov, NCT02613819, and has completed accrual. FINDINGS: Between July 28, 2016, and Feb 27, 2020, 70 patients were enrolled and initiated treatment. Median age was 77 years (IQR 70-82). Before enrolment, 49 (70%) of 70 patients had documented serial growth on initial surveillance imaging. 49 (70%) of 70 patients were male and 21 (30%) were female. Median tumour size was 4·6 cm (IQR 3·7-5·5). All patients enrolled had T1-T2a and N0-N1 disease. 23 patients received single-fraction SABR of 26 Gy and 47 received 42 Gy in three fractions. Median follow-up was 43 months (IQR 38-60). Local control at 12 months from treatment commencement was 100% (p<0·0001). Seven (10%) patients had grade 3 treatment-related adverse events, with no grade 4 adverse events observed. Grade 3 treatment-related adverse events were nausea and vomiting (three [4%] patients), abdominal, flank, or tumour pain (four [6%]), colonic obstruction (two [3%]), and diarrhoea (one [1%]). No treatment-related or cancer-related deaths occurred. INTERPRETATION: To our knowledge, this is the first multicentre prospective clinical trial of non-surgical definitive therapy in patients with primary renal cell cancer. In a cohort with predominantly T1b or larger disease, SABR was an effective treatment strategy with no observed local failures or cancer-related deaths. We observed an acceptable side-effect profile and renal function after SABR. These outcomes support the design of a future randomised trial of SABR versus surgery for primary renal cell cancer. FUNDING: Cancer Australia Priority-driven Collaborative Cancer Research Scheme.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Idoso , Feminino , Humanos , Masculino , Carcinoma de Células Renais/radioterapia , Neoplasias Renais/radioterapia , Neoplasias Renais/patologia , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Padrão de Cuidado , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Radiocirurgia/métodos , Estudos Prospectivos , Masculino , Feminino , Estadiamento de Neoplasias , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Idoso , AdultoRESUMO
PURPOSE: Patient-specific quality assurance (PSQA) for vertebra stereotactic body radiation therapy (SBRT) presents challenges due to highly modulated small fields with high-dose gradients between the target and spinal cord. This study aims to explore the use of the SRS MapCHECK® (SRSMC) for vertebra SBRT PSQA. METHODS: Twenty vertebra SBRT treatment plans including prescriptions 20 Gy/1 fraction and 24 Gy/2 fractions were selected for each of Millennium (M)-Multileaf Collimator (MLC), and high-definition (HD)-MLC. All 40 plans were measured using Gafchromic EBT3 film (film) and SRSMC, using the StereoPHAN phantom. Plan complexity was assessed using modulation complexity score (MCS), edge metric (EM) (mm-1), modulation factor (MU/cGy), and average leaf pair opening (ALPO) (mm) and its correlation with gamma-pass rate was investigated. The high dose gradient between the target and the spinal cord was analyzed for film and SRSMC and compared against the treatment planning system (TPS). Applying the methodology proposed by AAPM TG-218, action and tolerance values specific to the SRSMC for vertebra SBRT were determined for ß values ranging from 5 to 8. RESULTS: Film and SRSMC gamma-pass rates showed no correlation (p > 0.05). A moderate negative correlation (R = -0.57, p = 0.01) is present between EM and SRSMC 3%/1 mm gamma-pass rate for HD-MLC plans. Both film and SRSMC accurately measured high dose gradients between the target and the spinal cord (R2 > 0.86, p ≤ 0.05). Notably, dose-gradient of HD-MLC plans is 22% steeper and has a smaller standard deviation to M-MLC plans (p ≤ 0.05). Applying TG-218, the film tolerance limit was 96% with action limit 95% for 5%/1 mm (ß = 6) and for the SRSMC tolerance limit was 97% with an action limit of 96% for 4%/1 mm (ß = 6). CONCLUSION: Our findings suggest that universal TG-218 limits may not be suitable for vertebra SBRT PSQA. This study demonstrates that SRSMC is a viable tool for vertebra SBRT PSQA, supported by TG-218 implementation of process-based tolerance and action limits.
Assuntos
Órgãos em Risco , Imagens de Fantasmas , Garantia da Qualidade dos Cuidados de Saúde , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Garantia da Qualidade dos Cuidados de Saúde/normas , Órgãos em Risco/efeitos da radiação , Neoplasias da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/radioterapiaRESUMO
BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .
Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Movimentos dos Órgãos , Radiocirurgia/métodos , Radioterapia Guiada por Imagem/métodos , Austrália , Carcinoma Hepatocelular/secundário , Dinamarca , Marcadores Fiduciais , Humanos , Neoplasias Hepáticas/secundário , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radiocirurgia/instrumentação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Respiração , Resultado do TratamentoRESUMO
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) of primary kidney cancers is confounded by motion. There is a risk of interplay effect if the dose is delivered using volumetric modulated arc therapy (VMAT) and flattening filter-free (FFF) dose rates due to target and linac motion. This study aims to provide an efficient way to generate plans with minimal aperture complexity. METHODS: In this retrospective study, 62 patients who received kidney SABR were reviewed. For each patient, two plans were created using internal target volume based motion management, on the average intensity projection of a four-dimensional CT. In the first plan, optimization was performed using a knowledge-based planning model based on delivered clinical plans in our institution. In the second plan, the optimization was repeated, with a maximum monitor unit (MU) objective applied in the optimization. Dose-volume, conformity, and complexity metric (with the field edge metric and the modulation complexity score) were compared between the two plans. Results are shown in terms of median (first quartile - third quartile). RESULTS: Similar dosimetry was obtained with and without the utilization of an objective on the MU. However, complexity was reduced by using the objective on the MUs (modulation complexity score = 0.55 (0.50-0.61) / 0.33 (0.29-0.36), P-value < 10-10 , with/without the MU objective). Reduction of complexity was driven by a larger aperture area (area aperture variability = 0.68 (0.64-0.73) / 0.42 (0.37-0.45), P-value < 10-10 , with/without the MU objective). Using the objective on the MUs resulted in a more spherical dose distribution (sphericity 50% isodose = 0.73 (0.69-0.75) / 0.64 (0.60-0.68), P-value < 10-8 , with/without the MU objective) reducing dose to organs at risk given respiratory motion. CONCLUSIONS: Aperture complexity is reduced in kidney SABR by using an objective on the MU delivery with VMAT and FFF dose rate.
Assuntos
Radiocirurgia , Radioterapia de Intensidade Modulada , Humanos , Rim/diagnóstico por imagem , Rim/cirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos RetrospectivosRESUMO
PURPOSE: This study aimed to develop a physical geometric phantom for the deformable image registration (DIR) credentialing of radiotherapy centers for a clinical trial and tested the feasibility of the proposed phantom at multiple domestic and international institutions. METHODS AND MATERIALS: The phantom reproduced tumor shrinkage, rectum shape change, and body shrinkage using several physical phantoms with custom inserts. We tested the feasibility of the proposed phantom using 5 DIR patterns at 17 domestic and 2 international institutions (21 datasets). Eight institutions used the MIM software (MIM Software Inc, Cleveland, OH); seven used Velocity (Varian Medical Systems, Palo Alto, CA), and six used RayStation (RaySearch Laboratories, Stockholm, Sweden). The DIR accuracy was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). RESULTS: The mean and one standard deviation (SD) values (range) of DSC were 0.909 ± 0.088 (0.434-0.984) and 0.909 ± 0.048 (0.726-0.972) for tumor and rectum proxies, respectively. The mean and one SD values (range) of the HD value were 5.02 ± 3.32 (1.53-20.35) and 5.79 ± 3.47 (1.22-21.48) (mm) for the tumor and rectum proxies, respectively. In three patterns evaluating the DIR accuracy within the entire phantom, 61.9% of the data had more than a DSC of 0.8 in both tumor and rectum proxies. In two patterns evaluating the DIR accuracy by focusing on tumor and rectum proxies, all data had more than a DSC of 0.8 in both tumor and rectum proxies. CONCLUSIONS: The wide range of DIR performance highlights the importance of optimizing the DIR process. Thus, the proposed method has considerable potential as an evaluation tool for DIR credentialing and quality assurance.
Assuntos
Algoritmos , Processamento de Imagem Assistida por Computador , Credenciamento , Humanos , Planejamento da Radioterapia Assistida por Computador , Suécia , Tomografia Computadorizada por Raios XRESUMO
Peripheral lung lesions treated with a single fraction of stereotactic ablative body radiotherapy (SABR) utilizing volumetric modulated arc therapy (VMAT) delivery and flattening filter-free (FFF) beams represent a potentially high-risk scenario for clinically significant dose blurring effects due to interplay between the respiratory motion of the lesion and dynamic multi-leaf collimators (MLCs). The aim of this study was to determine an efficient means of developing low-modulation VMAT plans in the Eclipse treatment planning system (v15.5, Varian Medical Systems, Palo Alto, USA) in order to minimize this risk, while maintaining dosimetric quality. The study involved 19 patients where an internal target volume (ITV) was contoured to encompass the entire range of tumor motion, and a planning target volume (PTV) created using a 5-mm isotropic expansion of this contour. Each patient had seven plan variations created, with each rescaled to achieve the clinical planning goal for PTV coverage. All plan variations used the same field arrangement, and consisted of one dynamic conformal arc therapy (DCAT) plan, and six VMAT plans with varying degrees of modulation restriction, achieved through utilizing different combinations of the aperture shape controller (ASC) in the calculation parameters, and monitor unit (MU) objective during optimization. The dosimetric quality was assessed based on RTOG conformity indices (CI100/CI50), as well as adherence to dose-volume metrics used clinically at our institution. Plan complexity was assessed based on the modulation factor (MU/cGy) and the field edge metric. While VMAT plans with the least modulation restriction achieved the best dosimetry, it was found that there was no clinically significant trade-off in terms of dose to organs at risk and conformity by reducing complexity. Furthermore, it was found that utilizing the ASC and MU objective could reduce plan complexity to near-DCAT levels with improved dosimetry, which may be sufficiently robust to overcome the interplay effect.
Assuntos
Neoplasias Pulmonares , Radiocirurgia , Radioterapia de Intensidade Modulada , Humanos , Pulmão , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
PURPOSE: The aim of this study was to provide a comprehensive assessment of patient intrafraction motion in linac-based frameless stereotactic radiosurgery (SRS) and radiotherapy (SRT). METHODS: A retrospective review was performed on 101 intracranial SRS/SRT patients immobilized with the Klarity stereotactic thermoplastic mask (compatible with the Brainlab frameless stereotactic system) and aligned on a 6 Degree of Freedom (DoF) couch with the Brainlab ExacTrac image guidance system. Both pretreatment and intrafraction correction data are provided as observed by the ExacTrac system. The effects of couch angle and treatment duration on positioning outcomes are also explored. RESULTS: Initial setup data for patients is shown to vary by up to ±4.18 mm, ±2.97°, but when corrected with a single x-ray image set with ExacTrac, patient positions are corrected to within ±2.11 mm, ±2.27°. Intrafraction patient motion is shown to be uniformly random and independent of both time and couch angle. Patient motion was also limited to within approximately 3 mm, 3° by the thermoplastic mask. CONCLUSIONS: Our results indicate that since patient intrafraction motion is unrelated to couch rotation and treatment duration, intrafraction patient monitoring in 6 DoF is required to minimize intracranial SRS/SRT margins.
Assuntos
Neoplasias Encefálicas , Radiocirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Humanos , Imageamento Tridimensional , Aceleradores de Partículas , Posicionamento do Paciente , Planejamento da Radioterapia Assistida por Computador , Erros de Configuração em Radioterapia/prevenção & controle , Estudos Retrospectivos , RotaçãoRESUMO
Four-dimensional computerized tomography (4DCT) is required for stereotactic ablative body radiotherapy (SABR) of mobile targets to account for tumor motion during treatment planning and delivery. In this study, we report on the impact of an image review quality assurance process performed prior to treatment planning by medical physicists for 4DCT scans used for SABR treatment. Reviews were performed of 211 4DCT scans (193 patients) over a 3-yr period (October 2014 to October 2017). Treatment sites included lung (n = 168), kidney/adrenal/adrenal gland (n = 12), rib (n = 4), mediastinum (n = 10), liver (n = 2), T-spine (n = 1), and other abdominal sites (n = 14). It was found that in 23% (n = 49) of cases patient management was altered due to the review process. The most frequent intervention involved patient-specific contouring advice (n = 35 cases, 17%) including adjustment of internal target volume (ITV) margins. In 13 cases (6%) a rescan was requested due to extensive motion artifact rendering the scan inadequate for SABR treatment planning. 4DCT review by medical physicists was found to be an effective method to improve plan quality for SABR.
Assuntos
Tomografia Computadorizada Quadridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias/cirurgia , Órgãos em Risco/efeitos da radiação , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Respiração , Estudos RetrospectivosRESUMO
PURPOSE: This study focused on determining risks from stereotactic radiotherapy using flattening filter-free (FFF) beams for patients with cardiac implantable electronic device (CIEDs). Two strategies were employed: a) a retrospective analysis of patients with CIEDs who underwent stereotactic radiosurgery (SRS)/SBRT at the Peter MacCallum Cancer Centre between 2014 and 2018 and b) an experimental study on the impact of FFF beams on CIEDs. METHODS: A retrospective review was performed. Subsequently, a phantom study was performed using 30 fully functional explanted CIEDs from two different manufacturers. Irradiation was carried out in a slab phantom with 6-MV and 10-MV FFF beams. First, a repetition-rate test (RRT) with a range of beam pulse frequencies was conducted. Then, multifraction SBRT (48 Gy/4 Fx) and single-fraction SBRT (28 Gy/1 Fx) treatment plans were used for lung tumors delivered to the phantom. RESULTS: Between 2014 and 2018, 13 cases were treated with an FFF beam (6 MV, 1400 MU/min or 10 MV, 2400 MU/min), and 15 cases were treated with a flattening filter (FF) beam (6 MV, 600 MU/min). All the devices were positioned outside the treatment field at a distance of more than 5 cm, except for one case, and no failures were reported due to SBRT/SRS. In the phantom rep-rate tests, inappropriate sensing occurred, starting at a rep-rate of 1200 MU/min. Cardiac implantable electronic device anomalies during and after delivering VMAT-SBRT with a 10-MV FFF beam were observed. CONCLUSIONS: The study showed that caution should be paid to managing CIED patients when they undergo SBRT using FFF beams, as it is recommended by AAPM TG-203. Correspondingly, it was found that for FFF beams although there is small risk from dose-rate effects, delivering high dose of radiation with beam energy greater than 6 MV and high-dose rate to CIEDs positioned in close vicinity of the PTV may present issues.
Assuntos
Radiocirurgia , Radioterapia de Intensidade Modulada , Eletrônica , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos RetrospectivosRESUMO
OBJECTIVES: Rigid image registration (RIR) and deformable image registration (DIR) are widely used in radiotherapy. This project aims to capture current international approaches to image registration. METHODS: A survey was designed to identify variations in use, resources, implementation, and decision-making criteria for clinical image registration. This was distributed to radiotherapy centers internationally in 2018. RESULTS: There were 57 responses internationally, from the Americas (46%), Australia/New Zealand (32%), Europe (12%), and Asia (10%). Rigid image registration and DIR were used clinically for computed tomography (CT)-CT registration (96% and 51%, respectively), followed by CT-PET (81% and 47%), CT-CBCT (84% and 19%), CT-MR (93% and 19%), MR-MR (49% and 5%), and CT-US (9% and 0%). Respondent centers performed DIR using dedicated software (75%) and treatment planning systems (29%), with 84% having some form of DIR software. Centers have clinically implemented DIR for atlas-based segmentation (47%), multi-modality treatment planning (65%), and dose deformation (63%). The clinical use of DIR for multi-modality treatment planning and accounting for retreatments was considered to have the highest benefit-to-risk ratio (69% and 67%, respectively). CONCLUSIONS: This survey data provides useful insights on where, when, and how image registration has been implemented in radiotherapy centers around the world. DIR is mainly in clinical use for CT-CT (51%) and CT-PET (47%) for the head and neck (43-57% over all use cases) region. The highest benefit-risk ratio for clinical use of DIR was for multi-modality treatment planning and accounting for retreatments, which also had higher clinical use than for adaptive radiotherapy and atlas-based segmentation.
Assuntos
Processamento de Imagem Assistida por Computador , Planejamento da Radioterapia Assistida por Computador , Algoritmos , Humanos , Dosagem Radioterapêutica , Inquéritos e Questionários , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.
Assuntos
Carcinoma de Células Renais/radioterapia , Neoplasias Renais/radioterapia , Radiocirurgia/efeitos adversos , Adulto , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/fisiopatologia , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/fisiopatologia , Estudos Multicêntricos como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases. METHODS/DESIGN: The TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study. Eligible patients have up to three metastases to the lung from any non-haematological malignancy, each < 5 cm in size, non-central targets, and have all primary and extrathoracic disease controlled with local therapies. Patients are randomised 1:1 to a single fraction of 28Gy versus 48Gy in four fractions of SABR. The primary objective is to assess the safety of each treatment arm, with secondary objectives including assessment of quality of life, local efficacy, resource use and costs, overall and disease free survival and time to distant failure. Outcomes will be stratified by number of metastases and origin of the primary disease (colorectal versus non-colorectal primary). Planned substudies include an assessment of the impact of online e-Learning platforms for lung SABR and assessment of the effect of SABR fractionation on the immune responses. A total of 84 patients are required to complete the study. DISCUSSION: Fractionation schedules have not yet been investigated in a randomised fashion in the setting of oligometastatic disease. Assuming the likelihood of similar clinical efficacy in both arms, the present study design allows for exploration of the hypothesis that cost implications of managing potentially increased toxicities from single fraction SABR will be outweighed by costs associated with delivering multiple-fraction SABR. TRIALS REGISTRATION: ACTRN12613001157763 , registered 17th October 2013.
Assuntos
Fracionamento da Dose de Radiação , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Radiocirurgia , Radioterapia/métodos , Custos de Cuidados de Saúde , Recursos em Saúde , Humanos , Neoplasias Pulmonares/diagnóstico , Qualidade de Vida , Radiocirurgia/economia , Radiocirurgia/métodos , Radioterapia/economia , Tomografia Computadorizada por Raios X , Carga TumoralRESUMO
Stereotactic body radiation therapy (SBRT) aims to deliver a highly conformal ablative dose to a small target. Dosimetric verification of SBRT for lung tumors presents a challenge due to heterogeneities, moving targets, and small fields. Recent software (M3D) designed for dosimetric verification of lung SBRT treatment plans using an advanced convolution-superposition algorithm was evaluated. Ten lung SBRT patients covering a range of tumor volumes were selected. 3D CRT plans were created using the XiO treatment planning system (TPS) with the superposition algorithm. Dose was recalculated in the Eclipse TPS using the AAA algorithm, M3D verification software using the collapsed-cone-convolution algorithm, and in-house Monte Carlo (MC). Target point doses were calculated with RadCalc software. Near-maximum, median, and near-minimum target doses, conformity indices, and lung doses were compared with MC as the reference calculation. M3D 3D gamma passing rates were compared with the XiO and Eclipse. Wilcoxon signed-rank test was used to compare each calculation method with XiO with a threshold of significance of p < 0.05. M3D and RadCalc point dose calculations were greater than MC by up to 7.7% and 13.1%, respectively, with M3D being statistically significant (s.s.). AAA and XiO calculated point doses were less than MC by 11.3% and 5.2%, respectively (AAA s.s.). Median and near-minimum and near-maximum target doses were less than MC when calculated with AAA and XiO (all s.s.). Near-maximum and median target doses were higher with M3D compared with MC (s.s.), but there was no difference in near-minimum M3D doses compared with MC. M3D-calculated ipsilateral lung V20 Gy and V5 Gy were greater than that calculated with MC (s.s.); AAA- and XiO-calculated V20 Gy was lower than that calculated with MC, but not statistically different to MC for V5 Gy. Nine of the 10 plans achieved M3D gamma passing rates greater than 95% and 80%for 5%/1 mm and 3%/1 mm criteria, respectively. M3D typically calculated a higher target and lung dose than MC for lung SBRT plans. The results show a range of calculated doses with different algorithms and suggest that M3D is in closer agree-ment with Monte Carlo, thus discrepancies between the TPS and M3D software will be observed for lung SBRT plans. M3D provides a useful supplement to verification of lung SBRT plans by direct measurement, which typically excludes patient specific heterogeneities.
Assuntos
Algoritmos , Neoplasias Pulmonares/cirurgia , Imagens de Fantasmas , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Simulação por Computador , Humanos , Método de Monte Carlo , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Carga TumoralRESUMO
BACKGROUND: Auto-segmentation of organs-at-risk (OARs) in the head and neck (HN) on computed tomography (CT) images is a time-consuming component of the radiation therapy pipeline that suffers from inter-observer variability. Deep learning (DL) has shown state-of-the-art results in CT auto-segmentation, with larger and more diverse datasets showing better segmentation performance. Institutional CT auto-segmentation datasets have been small historically (n < 50) due to the time required for manual curation of images and anatomical labels. Recently, large public CT auto-segmentation datasets (n > 1000 aggregated) have become available through online repositories such as The Cancer Imaging Archive. Transfer learning is a technique applied when training samples are scarce, but a large dataset from a closely related domain is available. PURPOSE: The purpose of this study was to investigate whether a large public dataset could be used in place of an institutional dataset (n > 500), or to augment performance via transfer learning, when building HN OAR auto-segmentation models for institutional use. METHODS: Auto-segmentation models were trained on a large public dataset (public models) and a smaller institutional dataset (institutional models). The public models were fine-tuned on the institutional dataset using transfer learning (transfer models). We assessed both public model generalizability and transfer model performance by comparison with institutional models. Additionally, the effect of institutional dataset size on both transfer and institutional models was investigated. All DL models used a high-resolution, two-stage architecture based on the popular 3D U-Net. Model performance was evaluated using five geometric measures: the dice similarity coefficient (DSC), surface DSC, 95th percentile Hausdorff distance, mean surface distance (MSD), and added path length. RESULTS: For a small subset of OARs (left/right optic nerve, spinal cord, left submandibular), the public models performed significantly better (p < 0.05) than, or showed no significant difference to, the institutional models under most of the metrics examined. For the remaining OARs, the public models were inferior to the institutional models, although performance differences were small (DSC ≤ 0.03, MSD < 0.5 mm) for seven OARs (brainstem, left/right lens, left/right parotid, mandible, right submandibular). The transfer models performed significantly better than the institutional models for seven OARs (brainstem, right lens, left/right optic nerve, left/right parotid, spinal cord) with a small margin of improvement (DSC ≤ 0.02, MSD < 0.4 mm). When numbers of institutional training samples were limited, public and transfer models outperformed the institutional models for most OARs (brainstem, left/right lens, left/right optic nerve, left/right parotid, spinal cord, and left/right submandibular). CONCLUSION: Training auto-segmentation models with public data alone was suitable for a small number of OARs. Using only public data incurred a small performance deficit for most other OARs, when compared with institutional data alone, but may be preferable over time-consuming curation of a large institutional dataset. When a large institutional dataset was available, transfer learning with models pretrained on a large public dataset provided a modest performance improvement for several OARs. When numbers of institutional samples were limited, using the public dataset alone, or as a pretrained model, was beneficial for most OARs.
Assuntos
Neoplasias de Cabeça e Pescoço , Processamento de Imagem Assistida por Computador , Órgãos em Risco , Tomografia Computadorizada por Raios X , Órgãos em Risco/efeitos da radiação , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Aprendizado Profundo , Conjuntos de Dados como AssuntoRESUMO
BACKGROUND: The use of modulated techniques for intra-cranial stereotactic radiosurgery (SRS) results in highly modulated fields with small apertures, which may be susceptible to uncertainties in the delivery device. PURPOSE: This study aimed to quantify the impact of simulated delivery errors on treatment plan dosimetry and how this is affected by treatment planning system (TPS), plan geometry, delivery technique, and plan complexity. A beam modelling error was also included as context to the dose uncertainties due to treatment delivery errors. METHODS: Delivery errors were assessed for multiple-target brain SRS plans obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets, each with a prescription of 20 Gy. Of the final dataset of 54 plans, 51 were created using the volumetric modulated arc therapy (VMAT) technique and three used intensity modulated arc therapy (IMRT). Thirty-five plans were from the Varian Eclipse TPS, 17 from Elekta Monaco TPS, and one plan each from RayStation and Philips Pinnacle TPS. The errors introduced included: monitor unit calibration errors, multi-leaf collimator (MLC) bank offset, single MLC leaf offset, couch rotations, and collimator rotations. Dosimetric leaf gap (DLG) error was also included as a beam modelling error. Dose to targets was assessed via dose covering 98% of planning target volume (PTV) (D98%), dose covering 2% of PTV (D2%), and dose covering 99% of gross tumor volume (GTV) (D99%). Dose to organs at risk (OARs) was assessed using the volume of normal brain receiving 12 Gy (V12Gy), mean dose to normal brain, and maximum dose covering 0.03cc brainstem (D0.03cc). Plan complexity was also assessed via edge metric, modulation complexity score (MCS), mean MLC gap, mean MLC speed, and plan modulation (PM). RESULTS: PTV D98% showed high robustness on average to most errors with the exception of a bank shift of 1.0 mm and large rotational errors ≥1.0° for either the couch or collimator. However, in some cases, errors close to or within generally accepted machine tolerances resulted in clinically relevant impacts. The greatest impact upon normal brain V12Gy, mean dose to normal brain, and D0.03cc brainstem was found for DLG error in alignment with other recent studies. All delivery errors had on average a minimal impact across these parameters. Comparing plans from the Monaco TPS and the Eclipse TPS, showed a lesser increase to V12Gy, mean dose to normal brain, and D0.03cc brainstem for Monaco plans (p < 0.01) when DLG error was simulated. Monaco plans also correlated to lower plan complexity. Using Spearman's correlation coefficient (r) a strong negative correlation (r ≤ -0.8) was found between the mean MLC gap and dose to OARs for DLG errors. CONCLUSIONS: Reducing MLC complexity and using larger mean MLC gaps is recommended to improve plan robustness and reduce sensitivity to delivery and modelling errors. For cases in which the calculated dose distribution or dose indices are close to the clinically acceptable limits, this is especially important.
Assuntos
Neoplasias Encefálicas , Radiocirurgia , Radioterapia de Intensidade Modulada , Humanos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Radiometria , Neoplasias Encefálicas/cirurgia , Órgãos em Risco , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
PURPOSE: Radiation therapy treatment for non-small cell lung cancer (NSCLC) may result in radiation damage to the perfused lung. The loss in perfusion may be measured from positron tomography emission (PET) perfusion imaging; however, this modality may not be widely available. Dual-energy computed tomography (DECT) with contrast may be an alternative to PET/CT. The purpose of this work is to investigate the equivalence of dose-response curves (DRCs) determined from PET and DECT in NSCLC. METHODS AND MATERIALS: PET and DECT data sets from the prospective clinical trial HI-FIVE (NTC03569072) were included in this preplanned trial analysis. Patients underwent 68Ga-macroaggregated albumin PET/CT examination and DECT with contrast on the same day at baseline and at 3 and 12 months after treatment. The perfused lung was defined from a threshold based on the maximum standardized uptake value (%SUVmax)/iodine concentration (%IoMax) in PET/DECT. The equivalence between PET and DECT DRC was established by comparing (1) the average of the normalized overlap of the 2 DRCs ranging from 0 (no overlap) to 1 (perfect overlap) and (2) the slope of a linear model applied to DRCs. RESULTS: Of the 19 patients enrolled in the clinical trial, 14/10 patients had a posttreatment imaging session at a median of 4.5/13.5 months, respectively. With 30%SUVmax/35%IoMax, the average normalized overlap was maximized, and the difference between PET and DECT slopes of the linear model was minimized at each time point (slope = 0.76%/Gy / 0.75%/Gy at 3 months and 0.86%/Gy / 0.87%/Gy at 12 months determined from PET/DECT). CONCLUSIONS: The dose-response relationship determined from DECT was comparable to that from PET at 3 and 12 months after treatment in patients with NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Pulmão/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Perfusão , Fluordesoxiglucose F18RESUMO
BACKGROUND: Lattice radiation therapy (LRT) alternates regions of high and low doses within the target. The heterogeneous dose distribution is delivered to a geometrical structure of vertices segmented inside the tumor. LRT is typically used to treat patients with large tumor volumes with cytoreduction intent. Due to the geometric complexity of the target volume and the required dose distribution, LRT treatment planning demands additional resources, which may limit clinical integration. PURPOSE: We introduce a fully automated method to (1) generate an ordered lattice of vertices with various sizes and center-to-center distances and (2) perform dose optimization and calculation. We aim to report the dosimetry associated with these lattices to help clinical decision-making. METHODS: Sarcoma cancer patients with tumor volume between 100 cm3 and 1500 cm3 who received radiotherapy treatment between 2010 and 2018 at our institution were considered for inclusion. Automated segmentation and dose optimization/calculation were performed by using the Eclipse Scripting Application Programming Interface (ESAPI, v16, Varian Medical Systems, Palo Alto, USA). Vertices were modeled by spheres segmented within the gross tumor volume (GTV) with 1 cm/1.5 cm/2 cm diameters (LRT-1 cm/1.5 cm/2 cm) and 2 to 5 cm center-to-center distance on square lattices alternating along the superior-inferior direction. Organs at risk were modeled by subtracting the GTV from the body structure (body-GTV). The prescription dose was that 50% of the vertice volume should receive at least 20 Gy in one fraction. The automated dose optimization included three stages. The vertices optimization objectives were refined during optimization according to their values at the end of the first and second stages. Lattices were classified according to a score based on the minimization of body-GTV max dose and the maximization of GTV dose uniformity (measured with the equivalent uniform dose [EUD]), GTV dose heterogeneity (measured with the GTV D90%/D10% ratio), and the number of patients with more than one vertex inserted in the GTV. Plan complexity was measured with the modulation complexity score (MCS). Correlations were assessed with the Spearman correlation coefficient (r) and its associated p-value. RESULTS: Thirty-three patients with GTV volumes between 150 and 1350 cm3 (median GTV volume = 494 cm3 , IQR = 272-779 cm3 were included. The median time required for segmentation/planning was 1 min/21 min. The number of vertices was strongly correlated with GTV volume in each LRT lattice for each center-to-center distance (r > 0.85, p-values < 0.001 in each case). Lattices with center-to-center distance = 2.5 cm/3 cm/3.5 cm in LRT-1.5 cm and center-to-center distance = 4 cm in LRT-1 cm had the best scores. These lattices were characterized by high heterogeneity (median GTV D90%/D10% between 0.06 and 0.19). The generated plans were moderately complex (median MCS ranged between 0.19 and 0.40). CONCLUSIONS: The automated LRT planning method allows for the efficacious generation of vertices arranged in an ordered lattice and the refinement of planning objectives during dose optimization, enabling the systematic evaluation of LRT dosimetry from various lattice geometries.
Assuntos
Neoplasias , Radioterapia Conformacional , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Dosagem RadioterapêuticaRESUMO
PURPOSE: This study aimed to analyse correlations between planning factors including plan geometry and plan complexity with robustness to patient setup errors. METHODS: Multiple-target brain stereotactic radiosurgery (SRS) plans were obtained through the Trans-Tasman Radiation Oncology Group (TROG) international treatment planning challenge (2018). The challenge dataset consisted of five intra-cranial targets with a 20 Gy prescription. Setup error was simulated using an in-house tool. Dose to targets was assessed via dose covering 99 % (D99 %) of gross tumour volume (GTV) and 98 % of planning target volume (PTV). Dose to organs at risk was assessed using volume of normal brain receiving 12 Gy and maximum dose covering 0.03 cc of brainstem. Plan complexity was assessed via edge metric, modulation complexity score, mean multi-leaf collimator (MLC) gap, mean MLC speed and plan modulation. RESULTS: Even for small (0.5 mm/°) errors, GTV D99 % was reduced by up to 20 %. The strongest correlation was found between lower complexity plans (larger mean MLC gap and lower edge metric) and higher robustness to setup error. Lower complexity plans had 1 %-20 % fewer targets/scenarios with GTV D99 % falling below the specified tolerance threshold. These complexity metrics correlated with 100 % isodose volume sphericity and dose conformity, though similar conformity was achievable with a range of complexities. CONCLUSIONS: A higher level of importance should be directed towards plan complexity when considering plan robustness. It is recommended when planning multi-target SRS, larger MLC gaps and lower MLC aperture irregularity be considered during plan optimisation due to higher robustness should patient positioning errors occur.
Assuntos
Radiocirurgia , Planejamento da Radioterapia Assistida por Computador , Erros de Configuração em Radioterapia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Erros de Configuração em Radioterapia/prevenção & controle , Dosagem Radioterapêutica , Órgãos em Risco/efeitos da radiação , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgiaRESUMO
PURPOSE: Lattice radiation therapy (LRT) alternates regions of high and low doses inside the tumour. Whilst this technique reported positive results in tumour size reduction, optimal lattice parameters are still unknown. We introduce an automated LRT planning method personalised to tumour shape and designed to allow investigation of lattice geometry. METHODS: Patients with retroperitoneal sarcoma were considered for inclusion. Automation was performed with the Eclipse Scripting Application Interface (v16, Varian Medical Systems, Palo Alto). By iterating over vertex size (V) and centre-to-centre distance (D), vertices were segmented within the gross tumour volume (GTV) in an alternating square pattern. Iterations stopped when the number of inserted vertices was contained between a prespecified lower and upper bound. Forty sets of lattices were considered, produced by varying V and D in five lower/upper bound pairs. Best-scoring sets were determined with a score favouring the maximization of GTV dose uniformity and heterogeneity whilst minimizing the maximum dose to organs at risk. RESULTS: Fifty patients with tumour volumes between 150 cm3 and 10,000 cm3 were included. Best-scoring sets were characterised by a low number of vertices (<15). Based on the best-scoring set, the predicted parameters to use for new patients were V = 0.19 (GTV volume)1/3 and D = 2V, in centimetres. The number of vertices (N) to insert in the GTV can be estimated with N ≤ (24 × 3% GTV volume)/(4πV3). CONCLUSIONS: The automated LRT treatment planning personalised to tumour size allows investigation of lattice geometry over a large range of GTV volumes.