Lung cancer is the first cause of death among cancer patients. Non Small Cell lung cancer (NSCLS) represents about 80-85% of the cases. Of this, about 80% presents with locally advanced or metastatic disease. Important to mention the number of patients that progress or recur in central nervous system (CNS). It has been reported that patients with adenocarcinoma, who are under 60 years and with elevated carcinoembryonic antigen (CEA) are in the highest risk to develop brain metastasis. In small cell lung cancer, treatment with prophylactic cranial irradiation (PCI) is the standard of care in patients without progression after locoregional or systemic treatment because the proven benefit in overall survival (OS) and progression free survival (PFS). However, in NSCLC PCI has not been able to prove any survival benefit, only in CNS PFS, probably because there is no trial, to our knowledge, of PCI in NSCLC that include only the specific group of patients considered in high risk of developing brain metastasis.

Objectives:

1. To obtain a greater PFS and CNS PFS in patients with NSCLC treated with PCI after locoregional or systemic treatment.
2. Evaluate the benefit in OS in the specific group of patients who are at increased risk of developing brain metastasis
3. Evaluate quality of life and mental function before and after treatment with PCI and compare it with patients in the observation group.

Methods: One hundred and twenty eight patients with locally advanced or metastatic (except CNS metastasis) NSCLC will be included and randomized to receive either observation or PCI 25 Gy in 10 fractions Whole Brain Radiotherapy (WBRT) once the initial treatment has been completed and progression of the disease ruled out.

Inclusion Criteria:

• Patients with histologically proven advanced NSCLC (Stage IIIB or IV) including wild-type, EGFR-mutated or ALK-rearrangements who received treatment and were without progression at the end.
• Above 18 years
• General status with a Karnofsky >80%
• Eastern Cooperative Group (ECOG) ≤2
• Negative CNS MRI at the beginning of any treatment
• Carcinoembryonic antigen > 20 pg
• Hepatic and hematic cytology test within normal range
• Adequate renal function
• Those who accepted to participate in the study and who sign the letter of informed consent.

Exclusion Criteria:

• Patients with another type of cancer
• Patients who refuse participate in the protocol
• General status with a Karnofsky <80%
• Eastern Cooperative Group (ECOG) >2
• Previous treatment with WBRT
• Previous treatment with chemotherapy
• Disease progression after initial treatment, either chemotherapy or chemoradiotherapy depending the case.
• CNS metastasis at diagnosis
• Abnormal laboratory test that interfere with chemotherapy or TKI administration