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 non-small-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.

Figure 1.

(a) An 81-year-old patient with centrally located non-small-cell lung cancer (NSCLC), T1N0M0, meeting the eligibility criteria for inclusion in the LungTech trial. Delineation of tumour: gross tumour volume (GTV) (purple), internal target volume (ITV) (red), planning target volume (PTV) (pink) and organs at risk. (b) The proximity to the right central bronchus (cyan) does not allow planning according to the LungTech protocol without exceeding the dose constraint for the proximal bronchus tree (prox BT) 44 Gy [equivalent dose in 2 Gy fractions (EqD2), 74.8 Gy]—maximum dose for prox BT here 66.76 Gy (EqD2, 151.3 Gy)—leading to secondary exclusion from the trial.

Figure 2.

Local progression evaluation based on modified Huang et al criteria. ¹⁸F-FDG, fluorine-18 fludeoxyglucose; PET, positron emission tomography. yr, year. ^a Repeat imaging should be performed no later than 3 months after the first abnormal CT. ^b Biopsy should be considered to confirm outcome if patient is fit enough and in particular if radical treatment remains an option should isolated local progression be confirmed.

Figure 3.

A 54-year-old patient with centrally located non-small-cell lung cancer, T1N0M0, meeting the eligibility criteria for inclusion in the LungTech trial (benchmark case). (a) Delineation of tumour: gross tumour volume (GTV) (purple), internal target volume (red), planning target volume (pink), brachiocephalic vein (orange), superior trachea (pink), chest wall (green), vertebral body (blue), oesophagus (orange) and lungs-GTV (cyan). (b) Stereotactic body radiotherapy planning with dose prescription and adherence of organ at risk dose constraints according to LungTech protocol, isodoses: 64.2 Gy (red), 57.0 Gy (yellow), 48.0 Gy (green), 30.0 Gy (blue) and 15.0 Gy (cyan).

Figure 4.

Design of the LungTech trial [European Organization for Research and Treatment of Cancer (EORTC) 22113-08113]. 3D, three dimensional; 4D-CT, four-dimensional CT; ¹⁸F-FDG, Fluorine-18 Fludeoxyglucose; CBCT, cone beam CT; fr, fractions; NSCLC, non-small-cell lung cancer; ORTA, online randomized trials access; PET, position emission tomography; RT, radiotherapy; RTQA, radiation therapy quality assurance; SBRT, stereotactic body radiotherapy; yrs, years.

Figure 5.

European organization for research and treatment of cancer (EORTC) infrastructure to support new generation clinical trials. ORTA (online randomized trials access), web-based application designed to facilitate the registration and randomization of patients in EORTC clinical trials; RTQA, radiation therapy quality assurance; VISTA, web-based application designed for the completion of most case report forms; PRISMA (protocol repository and integrated project management application), the EORTC clinical trial management system provides a global overview of all projects and also very detailed information about specific protocols.