Transforming growth factor-beta plasma dynamics and post-irradiation lung injury in lung cancer patients.
OBJECTIVE
To investigate the relevance of transforming growth factor-beta (TGF-beta) dynamics in plasma for identification of patients at low risk for developing pneumonitis as a complication of thoracic radiotherapy (RT).


METHODS
Non-small cell lung cancer patients undergoing conventional RT were included in the prospective study. Concentrations of TGF-beta were measured in the patients' plasma prior to and weekly during 6 weeks of RT. The incidence of symptoms of early post-irradiation lung injury, i.e. symptomatic radiation pneumonitis, was correlated with TGF-beta parameters.


RESULTS
Forty-six patients were included in the study. Eleven patients (24%) developed symptomatic radiation pneumonitis. Absolute TGF-beta plasma levels did not differ between the groups of patients without or with pneumonitis. However, patients who developed pneumonitis tended to show increases in TGF-beta levels in the middle of the RT course relative to their pre-treatment levels while TGF-beta plasma levels of patients who did not develop pneumonitis tended to decrease over the RT treatment. The difference in the relative TGF-beta dynamics between the groups reached marginal significance in the third week of the treatment (P = 0.055) but weakened towards the end of the RT course. The utility of TGF-beta testing was evaluated at each RT week based on the test's ability to yield more accurate estimate of complication probability in an individual patient compared to empirically expected probability in similar group of patients. The ratio of TGF-beta level at week 3/week 0 being <1 showed an ability to improve the prediction of freedom from pneumonitis, yet with a large degree of uncertainty (wide confidence intervals). The accuracy of prediction deteriorated at later time points (weeks 4, 5 and 6) rendering the end-RT ratios without predictive power.


CONCLUSIONS
We observed a trend of plasma TGF-beta concentration to decrease below the pre-treatment value during the RT treatment in patients who did not develop pulmonary complications after the RT treatment. However, this trend was not consistent enough to warrant safe decision-making in clinical setting.
Novakova-Jiresova
Alena
A
Department of Radiation and Stress Cell Biology, Faculty of Medical Sciences, University of Groningen, Ant. Deusinglaan 1, bldg 3215, 9713 AV Groningen, The Netherlands.
Van Gameren
Mieke M
MM
Coppes
Rob P
RP
Kampinga
Harm H
HH
Groen
Harry J M
HJ
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D016022:Case-Control Studies; D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D017564:Radiation Pneumonitis / Q000097:blood* / Q000209:etiology; D011879:Radiotherapy Dosage; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000097:blood*
D014408:Biomarkers, Tumor; D016212:Transforming Growth Factor beta