SC03.01 Advances in Stereotactic Body Radiotherapy

Abstract

Advances in Stereotactic Body Radiotherapy Matthias Guckenberger, Switzerland Stereotactic Body Radiotherapy (SBRT) has become the guideline-recommended treatment of choice for patients with early stage NSCLC, who are medically inoperable because of their comorbidities. This reflects that SBRT has transformed from an emerging technology practiced only by few and highly experienced centres to a mature treatment practice broadly in the radiation oncology community setting. Nevertheless, the methodology of SBRT has continuously evolved covering all aspects of patient selection, practice of SBRT planning and delivery and follow-up assessment. In many centers, SBRT has been introduced as a replacement for conventionally fractionated radiotherapy in patients considered fit enough for a six weeks long radical treatment but unfit for surgical resection. Recent data have demonstrated that SBRT is also well tolerated in very old (> 80 years) patients and patients suffering from severe comorbidities.1 Simultaneously, the patient characteristics of age, performance status and patients comorbidities are not suitable to accurately predict a high risk of early non-cancer death such that these patients could be offered best supportive care and they would not benefit from SBRT as a curative treatment approach.2 However, several studies have identified interstitial lung disease as a highly significant factor for severe post-SBRT radiation induced pneumonitis; these patients should be treated only with caution.3 On the other end of the patient spectrum, there is an increasing amount of data comparing SBRT with surgical resection, lobectomy and sublobar resection: despite a growing evidence suggests equivalent outcome, lobectomy remains the standard of care for properly selected patients.4,5 Multiple advanced radiotherapy treatment planning and treatment delivery technologies as well as dedicated SBRT delivery machines have been developed and have become clinically available within the last years. Despite simulations studies showed a benefit for most these technologies, it remains unclear whether small improvements in accuracy and dosimetry will translate into a clinically meaningful improvements of patient outcome. The upcoming ESTRO ACROP practice guideline has therefore only identified few technologies as mandatory components of up-to-date SBRT practice (e.g. type B dose calculation algorithm, image guidance, 4D motion compensation strategy). SBRT dose and fractionation has been one of the most controversially discussed topics in lung SBRT and patterns-of-practice analyses reported a large variability between institutions. Comparison of different fractionation schedules requires radiobiological modelling and several recent studies suggested that the traditional linear-quadratic model (LQ-model) describes the observed outcome with sufficient accuracy.6 Consequently, biological effective doses (BED) or 2-Gy equivalent doses are used by most studies for dose-effect modelling. Several studies consistently showed that a threshold dose of minimum 100Gy BED (alpha/beta ratio 10Gy) is required for a local tumor control probability of >90%. Furthermore, not only the minimum dose at the PTV edge but also the maximum dose within the GTV was shown as important predictor for local tumor control supporting the traditional SBRT concept of inhomogeneous dose distributions within the PTV. After central tumor location has been called a no-fly-zone for SBRT based on studies with “excessive” toxicity of very high dose SBRT, recent retrospective and prospective data suggest that lower total doses combined with more fractionated SBRT protocols improve the therapeutic ratio. Nevertheless, our understanding of the radiation tolerance of critical central structures is still insufficient and further research is necessary. The development of radiation induced fibrosis in the high dose region is well documented following SBRT. Only recently, algorithms for differentiation between local tumor recurrence and fibrosis have been developed and validated7,8: CT features of bulging margin and cranio-caudal growth appear to best differentiate between fibrosis and tumor recurrence. More advanced studies evaluate the value of mathematical image analysis methods, radiomics, but such studies strongly require external validation. 1. Takeda A, Sanuki N, Eriguchi T, et al: Stereotactic ablative body radiation therapy for octogenarians with non-small cell lung cancer. Int J Radiat Oncol Biol Phys 86:257-63, 2013 2. Klement RJ, Belderbos J, Grills I, et al: Prediction of Early Death in Patients with Early-Stage NSCLC-Can We Select Patients without a Potential Benefit of SBRT as a Curative Treatment Approach? J Thorac Oncol, 2016 3. Ueki N, Matsuo Y, Togashi Y, et al: Impact of pretreatment interstitial lung disease on radiation pneumonitis and survival after stereotactic body radiation therapy for lung cancer. J Thorac Oncol 10:116-25, 2015 4. Chang JY, Senan S, Paul MA, et al: Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomized trials. Lancet Oncol 16:630-7, 2015 5. Nagata Y, Hiraoka M, Shibata T, et al: Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys 93:989-96, 2015 6. Guckenberger M, Klement RJ, Allgauer M, et al: Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer. Radiother Oncol 109:13-20, 2013 7. Huang K, Dahele M, Senan S, et al: Radiographic changes after lung stereotactic ablative radiotherapy (SABR) - Can we distinguish recurrence from fibrosis? A systematic review of the literature. Radiother Oncol 102:335-42, 2012 8. Peulen H, Mantel F, Guckenberger M, et al: Validation of High-Risk Computed Tomography Features for Detection of Local Recurrence After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 96:134-41, 2016. stereotactic body radiotherapy, non-small cell lung cancer, early stage