Optimization of stereotactic ablative radiation therapy of malignant lung nodules presented as ground-glass opacities
[eng] INTRODUCTION Lung cancer is the most common and lethal cancer worldwide. Patients with early-stage, inoperable non-small cell lung cancer are treated with high-precision radiotherapy, known as extracranial ablative stereotactic radiotherapy (SABR). A small percentage of tumors treated with SAB...
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| Tipo de documento: | tese |
| Estado: | Versão publicada |
| Data de publicação: | 2025 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositório: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/223869 |
| Acesso em linha: | https://hdl.handle.net/2445/223869 http://hdl.handle.net/10803/695574 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Radioteràpia Càncer de pulmó Metàstasi Dosimetria (Radiació) Efectes secundaris Radiotherapy Lung cancer Metastasis Radiation dosimetry Side effects |
| Resumo: | [eng] INTRODUCTION Lung cancer is the most common and lethal cancer worldwide. Patients with early-stage, inoperable non-small cell lung cancer are treated with high-precision radiotherapy, known as extracranial ablative stereotactic radiotherapy (SABR). A small percentage of tumors treated with SABR have frosted glass opacities (GGOs). This treatment has two main problems. First, the calculation algorithms used clinically tend to be inaccurate for GGO SABR, which can lead to excessive irradiation of healthy tissues. Second, GGOs are treated encompassing the entire suspicious volume (which includes the solid part and the GGO component), although they tend to be multifocal and present an evolution with a better prognosis than solid lesions. In addition, an increase in the number of patients with GGO tumors is expected thanks to screening programs, so it is important to optimize SABR treatment for these nodules. HYPOTHESIS With the current methodology, GGO's SABR treatments have excellent local control at the expense of excessive irradiation to healthy tissues. By using a correct dose calculation and adapting the administration of the treatment to cases with GGO, we will be able to reduce the toxicity of the treatment, while maintaining local control. OBJECTIVES In the first part, the observed toxicity has been evaluated with the objectives of: • To analyze and quantify the changes in the lung parenchyma after treatment with extracranial fractional stereotactic radiotherapy. • To correlate grade 1 pulmonary toxicity with the dose administered to the patient. In a second part, this treatment has been optimized for lesions with a frosted glass component with the sub-objectives of: • To evaluate the accuracy of clinical dose calculation algorithms in pulmonary nodules in the presence of opacities in frosted glass. • Define an approach to optimize stereotactic pulmonary treatments for lesions with opacities component in ground glass that maintains the expected local control while reducing the risk of associated toxicity. METHODS The first step was to retrospectively analyse the radiological toxicity observed in patients treated at Hospital Clinic Barcelona between 2017 and 2021, with a total of 102 patients and 118 lesions. We correlated this toxicity with the dose calculated with the clinically used planning systems (8Eclipse, Varian). To do this, we have defined criteria to assess radiological toxicity based on the computerized axial tomography (CT) images of the patients, correlating this toxicity with the dose received. At the same time, we have evaluated the uncertainties of dosimetric calculation in different planning systems used in clinical practice for different degrees of GGO, both in real cases of patients and in an anthropomorphic mannequin. We correlated these differences with the amount of GGO present in the lesion for the different cases. Regarding the calculation algorithms, a type B algorithm (AAA, Eclipse) has been used and compared with a type C algorithm, which solves the linear transport equation of Boltzman (Accuros, Eclipse). Finally, we recalculated the treatment plan using the two available dose calculation models, both for the original approach, consisting of giving a single dose level to the entire lesion, and using two different dose levels depending on whether the treated area corresponds to the solid part of the lesion or to the part with a GGO component. In the selection of these two dose levels, the effective biological dose of 100 GyBED10 has been chosen as the lower threshold, as it is the value recommended in the literature to achieve acceptable local control for this type of lesion. This dose level has been given to the GGO component of the lesion while the prescription to the solid part of the lesion has remained the same as in the original treatment. We have analysed the differences in terms of lung dose and robustness of the two approaches to treatment. MAIN RESULTS We found a correlation between the volume of lung receiving effective biological doses greater than 300 GyBED3 with the onset and magnitude of the radiological toxicities observed. It has also been observed that changes in the lung parenchyma tend to be maintained or worsen in those cases where the volume with D>300 GyBED3 is greater than 20 cm³. In the second part of the study, a positive correlation was found between the presence of GGO and dose calculation errors in the case of dummy calculations. These differences decrease in patients, especially in the presence of respiratory movement. When a treatment is proposed by applying dose de-escalation to the GGO area, significant reductions in the mean dose in the lung, V20 and V300GyBED3, are achieved. Finally, it has also been observed that, by optimizing using lower doses in the GGO area, more stable creep patterns are achieved, increasing the robustness of the treatment. CONCLUSIONS From the results of this thesis, a clear correlation is observed between effective biological doses above 300 Gy and both short- and long-term radiological changes. If confirmed in an independent cohort of patients, these findings could lead to the first radiation therapy dose restrictions for grade 1 lung toxicity. This study lays the groundwork for dose de-escalation in SABR treatment of lung lesions with GGO, which could lead to equivalent local control while reducing associated toxicities. These findings lay the groundwork for future clinical trials. |
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