Predictors Of Radiation Pneumonitis Research Articles

Circulating IL-6 as a predictor of radiation pneumonitis

Purpose: We report results from a clinical research protocol investigating circulating pro-inflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor α [TNFα]) in relation to radiation pulmonary injury. Methods and Materials: In a protocol for cytokine measurement, 25 patients had clinical follow-up longer than 12 months, and 24 had serial cytokine data. Serial plasma specimens before, during, and after thoracic radiotherapy were analyzed for IL-6 and TNFα using enzyme-linked immunosorbent assay (ELISA). Radiation pulmonary injury was defined using National Cancer Institute Common Toxicity Criteria. Results: Of the 24 patients, 6 had Grade 1 pneumonitis, and 13 had Grade 2 pneumonitis. There was no Grade 3/4 pneumonitis. Median time of radiation pneumonitis was between 8 and 12 weeks post-therapy. IL-6 levels before, during, and after thoracic radiation therapy were significantly higher in those who developed pneumonitis. In contrast, we did not detect a significant correlation between plasma TNFα and radiation pneumonitis. Conclusions: High pretreatment plasma levels of IL-6 predisposed patients to the risk of radiation pneumonitis. Pretreatment IL-6 level may serve as a predictor for radiation pneumonitis. Serial plasma IL-6 was consistently higher for the pneumonitis group. The role of IL-6 in the cytokine cascades that promote radiation pulmonary injury deserves further investigation.

Serum markers for the prediction of radiation pneumonitis: Pulmonary surfactant protein A and D

Serum markers for the prediction of radiation pneumonitis: Pulmonary surfactant protein A and D

Changes in plasma transforming growth factor β1 during radiotherapy: an independent predictor of radiation pneumonitis

Changes in plasma transforming growth factor β1 during radiotherapy: an independent predictor of radiation pneumonitis

Plasma transforming growth factor β1 as a predictor of radiation pneumonitis

Purpose: To investigate prospectively the utility of plasma transforming growth factor β1 (TGFβ1) as a marker for the development of symptomatic radiation pneumonitis. Materials and Methods: Seventy-three patients with lung cancer treated with curative intent are reported herein. Plasma TGFβ1 samples were obtained before, weekly during, and at each follow-up after radiation therapy (RT). TGFβ1 was extracted using an acid/ethanol method. An enzyme-linked immunosorbent assay was used to quantify plasma TGFβ1 concentrations. The TGFβ1 level at the end of RT was considered “normal” if it was both ≤ 7.5 ng/ml and less than the pretreatment value. All patients were followed for at least 6 months, unless symptomatic pneumonitis developed sooner. Pneumonitis was defined by National Cancer Institute (NCI) common toxicity criteria. Results: Fifteen of the 73 patients (21%) developed symptomatic pneumonitis and the remaining 58 (79%) did not. A normal plasma TGFβ1 by the end of RT, as defined above, was more common in patients who did not develop pneumonitis. A return of the plasma TGFβ1 to normal accurately identified patients who would not develop pneumonitis with both a sensitivity and positive predictive value of 90%. Conclusion: Plasma TGFβ1 levels appear to be a useful means to identify patients at low risk for the development of pneumonitis from thoracic RT. Thus, monitoring of plasma TGFβ1 levels may identify candidates for dose escalation studies in the treatment of lung cancer.

Evaluation of two dose–volume histogram reduction models for the prediction of radiation pneumonitis

Purpose: To evaluate the similarities between the mean lung dose and two dose–volume histogram (DVH) reduction techniques of 3D dose distributions of the lung. Patients and methods: DVHs of the lungs were calculated from 3D dose distributions of patients treated for malignant lymphoma (44), breast cancer (42) and lung cancer (20). With a DVH reduction technique, a DVH is summarized by the equivalent uniform dose (EUD), a quantity which is directly related to the normal tissue complication probability (NTCP). Two DVH reduction techniques were used. The first was based on an empirical model proposed by Kutcher et al. (Kutcher, G.J., Burman, C., Brewster, M.S., Goitein, M. and Mohan, R. Histogram reduction method for calculating complication probabilities for three-dimensional treatment planning evaluations. Int. J. Radiat. Oncol. Biol. Phys. 21: 137–146, 1991), which needs a volume exponent n. Several values for n were tested. The second technique was based on a radiobiological model, the parallel functional subunit model developed by Niemierko et al. (Niemierko, A. and Goitein, M. Modeling of normal tissue response to radiation: the critical volume model. Int. J. Radiat. Oncol. Biol. Phys. 25: 135–145, 1993) and Jackson et al. (Jackson, A., Kutcher, G.J. and Yorke, E.D. Probability of radiation-induced complications for normal tissues with parallel architecture subject to non-uniform irradiation. Med. Phys. 20: 613–625, 1993), for which a local dose–effect relation needed to be specified. This relation was obtained from an analysis of perfusion and ventilation SPECT data. Results: It can be shown analytically that the two DVH reduction techniques are identical, if the local dose–effect relation obeys a power-law relationship in the clinical dose range. Local dose–effect relations based on perfusion and ventilation SPECT data can indeed be fitted with a power-law relationship in the range 0–80 Gy, from which values of n=0.8–0.9 were deduced. These correspond to the commonly used value of n=0.87 for lung tissue and yielded EUD n=0.87 values which were almost identical to the mean lung doses. For other n values, for which no experimental data are present, differences exist between EUD and mean dose values. Six patients with malignant lymphoma (6/44) and none of the breast cancer patients (0/42) developed radiation pneumonitis. These cases occurred only at high values for the mean lung dose. Conclusion: The two DVH reduction techniques are identical for lung and are very similar to mean dose calculations. The two techniques are also relatively similar for other model parameter values.

124 Plasma transforming growth factor β1 as a predictor of radiation pneumonitis

124 Plasma transforming growth factor β1 as a predictor of radiation pneumonitis

Von Willebrand factor levels do not predict or diagnose radiation pneumonitis

In search for an index of endothelial injury that would provide an early diagnosis of radiation pneumonitis, we investigated the plasma levels of von Willebrand Factor (Factor VIII Related Antigen, FVIII:RAg) in 14 patients undergoing pulmonary irradiation. This study was based on observations indicating that damage to the endothelium-rich pulmonary parenchyma may produce alterations in the synthesis, storage or release of FVIII:RAg, detectable in plasma. There was no correlation between FVIII:RAg levels and radiation pneumonitis, radiation dose, volume of irradiated lung, tumor burden, or time-interval between exposure and sampling. The heterogeneity of the neoplasms and the inconstant effects of radiation in the tumor vasculature are among several variables that may explain this lack of correlation. The plasma levels of FVIII:RAg cannot be used to diagnose or predict radiation pneumonitis.