Sublobar Wedge Resection or Stereotactic Radiotherapy Treatment of High-risk Patients With Early-stage Lung Cancer

In low-risk patients with stage I non-small cell lung cancer (NSCLC) surgical treatment with an anatomical resection is currently the standard of care. For medically inoperable patients with stage I NSCLC, radiation therapy is currently the standard treatment. The latest generation of radiation therapy modalities is Stereotactic Body Radiation Therapy (SBRT). In high-risk patients, minimal invasive surgery in terms of sublobar resection (wedge resection) with lymph node sampling is currently the recommended treatment approach for these patients, even though the evidence is limited. Additionally, SBRT is an alternative treatment option but the use in these patients is also based on weak evidence. So, it is highly warranted to compare these two treatment options in this group of patients in a randomized, controlled trial where selection bias can be eliminated. It is the specific aim of this study to provide such a trial allowing an evidence-based approach when deciding between surgery and SBRT as treatment for NSCLC in high-risk patients. The STRADOS study (STereotactic RADiotherapy Or Surgery) is an open randomized, controlled national multicenter study in which high-risk patients with stage I non-small-cell lung cancer (NSCLC) are randomized to receive either surgical treatment with minimal invasive wedge resection with lymph node sampling, or SBRT. The overall purpose of the study is to investigate the disease-free survival (DFS) after surgical treatment when compared to SBRT. The primary endpoint is DFS after 3 years. Secondary endpoint is quality of life after 1, 3, 6, 12 and 36 months. Tertiary endpoints are overall survival (OS) after 3 and 5 years; DFS after 5 years; re-admission adverse events and complications after 1, 3, 6, 12 and 36 months; health-care related costs within 12 and 36 months; PRO data - other than quality of life (QoL) (health condition, symptoms and functional level) after 1, 3, 6, 12 and 36 months and lung function test after 12 month.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Age ≥ 18 years
* Biopsy-proven NSCLC
* Diagnostic codes: DC34, DC 34.1, DC 34.2, DC 34.3 or DC 34.9
* Clinical stage I NSCLC according to the 9th edition of TNM
* Performed diagnostic PET-CT and supplementary invasive procedures for staging purposes in accordance with the Danish national reference program for the staging and treatment of lung cancer (30)
* 9th edition TNM staging: cT1aN0M0, cT1b-cN0M0, cT1cN0M0 and cT2aN0M0 (clinical stage I)
* Tumor is localized in the outer third of the lung and considered technically resectable by SWR, as well as treatable with peripheral SBRT when assessed during MDT conference
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0-2.
* Preoperative pulmonary function test according to national guidelines performed within 6 weeks before the MDT conference
* Patient fulfills the "high-risk patient" criteria outlined:

A high-risk patient is a patient that fulfills at minimum one of the main-risk criteria and/or two of the secondary criteria:

Main criteria:

* FEV-1 ≤ 50% and/or
* DLCO ≤ 50%

Secondary criteria:

* Age ≥ 80
* FEV-1 = 51-60% and/or DLCO = 51-60%
* Known pulmonary hypertension with PAP ≥40 mm Hg diagnosed \< 6 months before inclusion
* Known LVEF ≤ 40% diagnosed \< 6 months before inclusion

Exclusion Criteria:

* Declared terminally ill or life expectancy shorter than one year.
* Multifocal disease
* PS ≥ 3
* Centrally located tumors not eligible to SBRT
* Previous ipsilateral lung surgery
* Pregnancy or breastfeeding.
* Inability to understand oral and written informed consent
* Intravenous substance abuse or severe alcohol abuse (\> 25 units per week)
* Not amendable for surgery in general anesthetic
* Previous radiotherapy to the thorax, which may limit the feasibility or increase the risk of stereotactic reirradiation due to cumulative dose constraints and potential toxicity
* Diagnosed with Interstitial lung disease (ILD)