LungTech: Stereotactic Body Radiotherapy (SBRT) of Inoperable Centrally Located NSCLC

Conventionally fractionated radiotherapy (RT) has been the standard of care for medically inoperable NSCLC with prescribed doses of usually 60 - 66 Gy.This moderate irradiation regimen resulted in a local failure rate of approximately 50% and local failure- not distant - has been shown to be the most frequent pattern of disease recurrence. Still, conventional RT resulted in overall survival (OS) and cancer specific survival (CSS) superior to best supportive care, though it is clearly an insufficient treatment with CSS rates of only about 30% after 5 years. Retrospective studies reported a dose-response relationship for local tumor control: higher irradiation doses resulted in improved rates of local tumor control which was found to translate into improved OS. Simultaneously, a dose- response relationship with a volume-effect relation has been demonstrated for radiation induced pneumonitis, being the most relevant toxicity after RT. These relations are known to apply to other organs at risk (OAR)including esophagus and spinal cord. Consequently, traditional target volume concepts conducting nodal irradiation in clinically node negative patients and traditional RT- planning and delivery techniques, with low accuracy and broad safety margins, do not allow the routine application of sufficient irradiation doses due to high toxicity rates. In the mid-90s, after encouraging success in the treatment of cerebral malignancies, the concept of stereotactic RT was taken over from the cranium to the body. Only the primary tumor was targeted and precise stereotactic tumor localization combined with techniques reducing breathing- induced target motion allowed small safety margins. These small volumes were treated with hypo-fractionated, escalated irradiation doses. Since then, the technique of image guided (IG) -stereotactic body RT (SBRT) also known as Stereotactic Ablative Body Radiotherapy (SABR) was further developed in multiple clinical and technological aspects e.g. Fluorine-18 Fluorodeoxyglucose positron emission tomography / computed tomography (FDG-PET/CT) based nodal staging, respiration correlated CT-imaging for target volume definition and image-guided treatment delivery. Safety and efficacy has been demonstrated in a large series of patients with stage I NSCLC. The majority of patients were medically inoperable and SBRT was practiced instead of conventionally fractionated RT. However, safety of SBRT has been demonstrated even in high risk patients with advanced age, severe COPD and very poor pulmonary function, which would have made any curative approach except SBRT difficult or even impossible. On the other side of the patient spectrum, retrospective studies suggested equivalent outcome compared to sub-lobar resection, which is confirmed by Markov modelling studies.