Upfront Resection of Locally Advanced NSCLC Followed by Chemoradiotherapy

For patients with irresectable locally advanced non-small cell lung cancer (NSCLC) (e.g. multilevel or bulky N2 disease or presence of N3 lymph node metastases), current guidelines recommend treatment with chemoradiotherapy (CRT) followed by immune checkpoint inhibition (ICI, durvalumab). Chances of sterilization of a large (e.g. clinically staged T3 or T4 tumor) tumor volume by CRT alone are relatively small and these tumors are associated with a high local recurrence rate. Moreover, necrosis and cavitation of these tumors puts these patients at risk of fatal bleeding and might cause infectious complications, which lead to subsequent impaired quality of life (QoL) and to interruption of, or the need for postponing, (systemic) treatment.Upfront resection of the tumor in the lung, followed by postoperative CRT in patients who have a (potentially) resectable tumor could be a strategy to prevent complications of CRT in large volume and/or cavitating tumors with extensive mediastinal disease.

Inclusion Criteria:Provision of signed, written and dated IC prior to any study specific procedures.Male or female aged at least 18 years.Eastern Cooperative Oncology Group (ECOG)/WHO performance status of 0 or 1.A pretreatment PET/CT scan (of the thorax and upper abdomen) and an MRI (or CT scan) of the brain is considered SoC and must be done prior to start of treatment.Pathologically proven NSCLC, staged according to the 8th edition of the AJCC Staging Manual, with a clinical indication for concurrent CRT (according to current guidelines).Pathology proven N2 or N3 lymph node metastasis.Patients should be able to receive concurrent CRT.Patients should be operable to the discretion of the treating pulmonary physician, surgeon and anesthesiologist, based on lung function testing and performance scoring.EGFR/ALK mutations and never-smokers may be included in the study (since endpoints are settled after finishing CRT and before starting adjuvant systemic treatment).Exclusion Criteria:Irresectable primary lung tumor before start of concurrent CRT.Pneumonectomy deemed necessary (by the treating surgeon) to achieve a complete resection (R0).Sulcus superior tumor with invasion of the thoracic wall.cT3-4 based on satellite nodus/lesion in the ipsilateral lung.Patients with a locoregional recurrence or a second primary lung cancer.Patients with prior treatment with radiotherapy on the lung.Patients with a history of other malignancies, except:adequately treated non-melanoma skin cancercuratively treated in-situ cancer, orother malignancies curatively treated with no evidence of disease for >5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy.Small cell lung cancer or a pulmonary carcinoid tumor.