Thoracic radiotherapy (TRT) is a standard curative treatment for locally advanced, unresectable non-small cell lung cancer (NSCLC) and limited stage small cell lung cancer (SCLC). TRT has been recognized to cause moderate to severe lung injury in a substantial portion of patients. Conventional standard curative TRT planning techniques minimize the radiation dose to the anatomical lungs, without adaption of regional pulmonary function variations. The principal investigator hypothesized that preferential avoidance of functional lung during curative TRT may decrease the risk of pulmonary toxicity. Functional lung regions are identified using four- dimensional computed tomography for ventilation imaging. This randomized, single-blind trial will comprehensively assess the impact of functional lung avoidance on pulmonary toxicity, quality of life, and clinical outcome in patients receiving curative TRT for locally advanced NSCLC and SCLC.

Inclusion criteria:

1. Patients with a histologic diagnosis of non-small cell carcinoma or small cell carcinoma of lung
2. Locally advanced stage III A or III B lung carcinoma according to American Joint Committee on Cancer (AJCC) 7th edition or highly selected patients with oligo-metastatic disease amendable for thoracic radiotherapy with curative intent
3. Not undergoing radical surgical resection
4. Patients do not have prior radiotherapy to the thorax
5. Age ≥ 20 years
6. Karnofsky performance status (KPS) ≥ 60%.
7. Women of childbearing potential and male participants must practice adequate contraception
8. Patients must be able to comply with the study protocol and follow-up schedules and provide study-specific informed consent

Exclusion criteria:

1. Prior radiotherapy to thorax

2. Unable to receive assigned radiation dose due to normal lung constraint

3. Inability to attend full course of radiotherapy or follow-up visits

4. Presence of metastatic disease. Patients who present with oligo-metastatic disease where all metastases have been ablated (with surgery or radiotherapy) or in complete remission after systemic therapy are candidates if they are receiving radiotherapy to the thoracic disease with curative intent

5. Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:

   • Uncontrolled active infection requiring intravenous antibiotics at the time of registration
   • Transmural myocardial infarction ≤ 6 months prior to registration.
   • Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration.
   • Life-threatening uncontrolled clinically significant cardiac arrhythmias.
   • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
   • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration.
   • Uncontrolled psychiatric disorder.

6. Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic.

7. Pregnant or lactating women