LungTech, an EORTC Phase II trial of stereotactic body radiotherapy for centrally located lung tumours: a clinical perspective

Abstract

Evidence supports stereotactic body radiotherapy (SBRT) as a curative treatment option for inoperable early stage nonsmall-cell lung cancer (NSCLC) resulting in high rates of tumour control and low risk of toxicity. However, promising results are mainly derived from SBRT of peripheral pulmonary lesions, whereas SBRT for the central tumours can lead to severe radiation sequelae owing to the spatial proximity to the serial organs at risk. Robust data on the tolerance of mediastinal structures to high-dose hypofractionated radiation are limited; furthermore, there are many open questions regarding the efficiency, safety and response assessment of SBRT in inoperable, centrally located early stage NSCLC, which are addressed in a prospective multicentre study [sponsored by the European Organization for Research and Treatment of Cancer (EORTC 22113-08113-LungTech)]. In this review, we summarize the current status regarding SBRT for centrally located early stage NSCLC that leads to the rationale of the LungTech trial. Outline and some essential features of the study with focus on a summary of current experiences in dose/fraction-toxicity coherences after SBRT to the mediastinal structures that lead to LungTech normal tissue constraints are provided.Stereotactic body radiotherapy (SBRT) is a technique in which high doses of radiotherapy are very precisely delivered with steep dose gradients and a short overall treatment time (OTT). This achieves a very high biological dose.1 Evidence supports SBRT as a curative treatment option for inoperable early stage non-small-cell-lung cancer (NSCLC).2-5 Highprecision, hypofractionated dose delivery enables a significant reduction in both target volume size and exposure of normal tissue (NT) to high doses, resulting in a decreased toxicity risk and high rates of local control.6-8 However, promising results are mainly derived from the SBRT of small peripheral pulmonary lesions with low risk of treatment-related toxicity, as these tumours are surrounded by parallel organs at risk (OARs), specifically lung tissue. In contrast, the SBRT for central tumours can lead to severe, potentially life-threatening radiation sequelae owing to the spatial proximity to serial OARs. As robust, prospective and multicentre data on the tolerance of mediastinal structures to high-dose hypofractionated radiation is limited, there is generally caution in implementing SBRT for central lung tumours. Current published data are rather inconsistent regarding the definition of "central tumour", SBRT techniques, dose prescription and reporting, calculation algorithms, image guidance and evaluation of outcome. A recent systematic review has summarized the current limited evidence on this topic, mainly from singlecentre experiences, 9 but there are still many open questions

A systematic review of outcomes following stereotactic ablative radiotherapy in the treatment of early-stage primary lung cancer

“…88 This should hopefully provide high-quality data on the efficacy and safety of this regimen for central tumours.…”

Respiratory motion-management in stereotactic body radiation therapy for lung cancer – A dosimetric comparison in an anthropomorphic lung phantom (LuCa)

“…Lung, heart and spinal cord were contoured as organs at risk (OAR) and spared as much as possible in the optimization process. The spinal cord was constrained to a dose maximum below 32 Gy [21]. All treatment plans consisted of four co-planar, full arcs with an avoidance sector to spare the contralateral side of the lung.…”

Stereotactic body radiotherapy for central lung tumours:Author reply

“…adjacent to the oesophagus or overlapping the central airways and for whom dose constraints cannot be achieved, are explicitly excluded. 2 The dose and fractionation used in the LungTech trial is derived from the important and promising data from VU University Medical Center, Amsterdam, Netherlands. 3 Implementing the dose constraints in our trial, those routinely used at the VU University Medical Center have been considered; however, not all of their constraints have been adopted.…”

“…We apologize for the misunderstanding and that the constraint for the central airway was not clearly quoted in table 1 of our review. 2 One of the aims of LungTech is to define the therapeutic limits for moderately central lung tumours. Therefore, details as to how the organs at risk are defined and delineated and which dose-volume histogram parameters are used may have a large influence on local control and toxicity.…”