Biochemical markers as predictors for pulmonary effects of radiation
Authors: McDonald Sandra , Rubin Philip , Constine Louis , Williams Jacky , Finkelstein Jacob , Smudzin Therese 
Published: February 2007

The delay in onset of clinical/radiological expression of pulmonary radiation toxicity precludes modification of radiation factors during treatment. Early detection of normal lung damage by biochemical markers that would predict for pneumonitis and/or fibrosis could allow for timely intervention. This study was undertaken to analyze changes in blood levels of surfactant apoprotein, procollagen III, and transforming growth factor β (TGF‐β) in patients undergoing pulmonary radiation therapy (RT) and to determine if a correlation exists between early changes of these biochemical markers and subsequent radiographic and clinical evidence of pneumonitis and/or fibrosis. Sixteen patients with primary lung cancer undergoing thoracic irradiation were enrolled in this study and blood samples were obtained pretreatment, weekly during treatment, and at follow‐up. At the same time points, patients underwent physical examination, chest X‐rays, and computerized tomographic (CT) scans. Surfactant apoprotein was determined by immunodot blot analysis, procollagen III levels were determined by radioimmunoassay (RIA), and TGF‐β was determined by an enzyme‐linked immunosorbent assay (ELISA) kit. Radiographically, 9 of 16 patients entered developed moderate to severe evidence of acute radiation injury; 6 had mild or no changes. The mean increase in surfactant apoprotein level during treatment was different (P = 0.074) between the two groups: 6% in the moderate/severe group vs. 42% in the mild/no change group. The inverse correlation for surfactant apoprotein levels during treatment relative to radiographic changes at 2 months was statistically significant (R = −0.59, P < 0.05). Clinically, 5 of 16 developed pneumonitis. Lack of increase in surfactant apoprotein levels during treatment similarly corresponded to clinical pneumonitis. During treatment 50% (8 of 16) of the patients had procollagen III levels above the upper limit of normal. This group had increased radiographic evidence at 4–6 months posttreatment of radiation late effects (fibrosis) compared to the group with normal procollagen levels during treatment. TGF‐β values pretreatment were elevated for patients developing pneumonitis and moderate to severe radiological changes, but this did not have statistical significance. Analysis of preliminary data suggests that an increase in surfactant apoprotein levels during thoracic irradiation is associated with a decreased probability of clinical and radiographic evidence of radiation‐induced lung injury. Furthermore, an elevated procollagen III level during treatment may be useful in predicting the development of late radiographic evidence of more severe fibrosis than patients with normal values during treatment. The role of TGF‐β as a predictor of fibrosis needs to be further investigated. These biochemical markers may prove useful as short‐term endpoints to evaluate toxicity at a time when treatment factors could be modified (e.g., volume or dose) and particularly with the assessment of new modalities such as three‐dimensional treatment planning. © 1995 Wiley‐Liss, Inc.