How important is a severely diminished diffusion capacity in determining whether to offer a lung cancer patient radiotherapy?

Conventionally, Pulmonary function tests (PFTs) are considered essential before considering thoracic surgery and by extension this rule has applied to definitive radiation. This is because baseline pulmonary function (PF) can predict the risk of pulmonary complications after thoracotomy, and patients with very poor PF are generally considered unfit for surgery. Similarly, impairment in PF is often considered a contraindication to definitive radiation therapy in clinical practice and often limits participation of patients in clinical trials.

The role of diminished diffusion capacity (DLCO) specifically in radiation treatment decision making for patients is easiest when SBRT is employed. SBRT typically is used for early stage lung cancer patients, the preponderance of whom are medically inoperable by virtue of impaired pulmonary function, both clinical and objective. Essentially there is no lower DLCO limit established that would preclude such a patient from receiving SBRT, as long as the patient is medically stable, though of course chronically impaired.

On the other hand, the role of diminished PF in decision making for locally advanced disease is not clear. For patients treated according to clinical trial criteria, there are typically spirometry and/or DLCO values which exclude participation in the trial. Thus clinicians can use these in practice to assist in their treatment decision making, i.e., concurrent chemoradiotherapy might not be offered to a patient based on their abnormal PF. The literature unfortunately is not clear. For example, two recent papers draw opposite conclusions on the importance of impaired PF in decision making: "Poor Baseline Pulmonary Function May Not Increase the Risk of Radiation-Induced Lung Toxicity". Int J Radiat Oncol Biol Phys. 2013 Mar 1;85(3):798-804; compared to "Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer." Respir Res. 2018 Apr 24;19(1):72

In general, appropriate clinical assessment of the pt, consideration of clinical and objective findings, while incorporating tumor characteristics such as tumor size and GTV volume, lobar location of the tumor, relation to central airways, bulk and number of mediastinal nodal stations can all factor in to make the interpretation of and weighting of the impaired PF most relevant in the appropriateness of radiotherapy and its use in conjunction with other factors that may increase lung injury risk, such as concurrent chemotherapy. Unfortunately, there are no well tested, hard and fast "rules" on what the lowest acceptable critical values are.