Insufficient accrual

Concurrent chemoradiotherapy is the standard treatment for locally advanced, unresectable non-small cell lung cancer, but carries a risk of radiation pneumonitis of approximately 30%, and is associated with a decline in pulmonary quality of life.

Standard radiation planning aims to optimize dose to the anatomic lung volume, without consideration of the differences in regional lung function. Functional lung avoidance radiotherapy aims to reduce radiotherapy dose to regions of functioning lung, instead depositing dose in areas of lung that are not well-ventilated. Functional lung regions are determined using noble-gas MRI and co-registered to the radiotherapy planning CT scans. Functional lung avoidance radiotherapy has been demonstrated to be feasible, and this trial aims to compare outcomes between standard radiotherapy (with concurrent chemotherapy) vs. functional lung avoidance radiotherapy (with concurrent chemotherapy).

All consenting patients will undergo hyperpolarized noble gas MRI using 3-He for definition of functional lung volumes. Two radiotherapy treatment plans will be generated prior to randomization: one standard plan using anatomical lung avoidance, and one functional lung avoidance plan. After approval of both plans, patients will be randomized, and both patients and physicians will be blinded to treatment allocation.

Inclusion Criteria:

• Age 18 or older
• Willing to provide informed consent
• ECOG performance status 0-2
• Histologically confirmed non-small cell lung carcinoma
• Locally advanced Stage IIIA or IIIB lung carcinoma according to AJCC 7th edition
• History of at least 10-pack-years of smoking
• Not undergoing surgical resection
• Assessment by medical oncologist and radiation oncologist, with adequate bone marrow, hepatic and renal function for administration of platinum-based chemotherapy

Exclusion Criteria:

• Contraindications to MRI
• Serious medical comorbidities (such as unstable angina, sepsis) or other contraindications to radiotherapy or chemotherapy
• Prior history of lung cancer within 5 years
• Prior thoracic radiation at any time
• Metastatic disease. Patients who present with oligometastatic disease where all metastases have been ablated (with surgery or radiotherapy) are candidates if they are receiving chemoradiotherapy to the thoracic disease with curative intent.
• Inability to attend full course of radiotherapy or follow-up visits
• Pregnant or lactating women