A new Method of Quantitative Estimation of Radiation-Induced Lung Damage in Oncological Patients on the CT in Dynamics

Objective: to develop a methodology for quantitative assessment of changes in density parameters of pulmonary tissue on the basis of  dynamic CT data, which makes it possible to assess the presence of  the dependence of changes in lung tissue on the time elapsed after  radiation therapy (RT), the dose and volume of irradiated pulmonary tissue.

Materials and methods. Using the data collected by 11 patients  with malignant lymphomas, we developed a new diagnostic  technique for quantitative analysis, which is based on the analysis of the density of pulmonary tissue before and after RT in areas with a  selected range of doses throughout the lung volume. All selected  patients received LT in the chest region, using 3D-planning, fractions of 2Gy and total focal doses of 13–56 Gy. Also, each patient had at least two CT examinations (a total of 25 studies in the Dicom- format). The first CT scan was performed before LT, repeated –  within 2–7 months after the end of RT.

Results. In 6 patients, control CT examinations were performed  2.1–2.8 months after RT. As a result, a quantitative increase in the  density indices in the range from +12 to +62 HU in regions of the  lungs irradiated at a dose of more than 19 Gy was noted, different  from the control areas. The volume of these areas of the lungs was  from 16% to 30% of the total lung volume, and the volume of  regions with the maximum values of density growth – from 7% to  14%. These changes in density are below the “visual” threshold. In  control areas, the density change varied from −15 HU (increased airiness) to + 8 HU. According to the data of other CT  studies performed later than 3 months after RT, the reverse  development of changes characterizing the early radiation reaction was observed.

Conclusions. A series of CT studies performed before and at various intervals after RT allows quantitative assessment of the dynamics of the indices of the density of irradiated pulmonary tissue, which is  necessary for an objective assessment of the severity of early  radiation-induced injuries of pulmonary tissue sites, depending on  the dose. A study of the dynamics of these changes in pulmonary  tissue density over time with RT and the connection of this indicator  with the baseline data may allow one to predict radiation-induced damage to the lungs on the one hand, and on the other, to evaluate individual radiosensitivity.

1. Kwa S.L., Lebesque J.V., Theuws J.C., Marks L.B., Munley M.T., Bentel G., Oetzel D., Spahn U., Graham M.V., Drzymala R.E., Purdy J.A., Lichter A.S., Martel M.K., Ten Haken R.K.. Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients. Int. J. Radiat. Oncol. Biol. Phys. 1998; 42 (1): 1–9. DOI: 10.1016/S0360-3016(98)00196-5.

2. Yarmonenko S.P., Vaynson A.A. Radiobiology of humans and animals. M.: Vishaya shkola, 2004: 173–209. (In Russian)

3. Joiner M.S., van der Kogel A. Basic clinical radiobiology. M.: BINOM. Laboratoriya znaniy, 2015: 430–441. (In Russian)

4. McDonald S., Rubin P., Phillips T.L., Marks L.B. Injury to the lung from cancer therapy: clinical syndromes, measurable endpoints, and potential scoring systems. Int. J. Radiat. Oncol. Biol. Phys. 1995; 31 (5): 1187–1203. DOI: 10.1016/0360-3016(94)00429-о.

5. MacKenzie R.G., Franssen E., Wong R., Sawka C., Berinstein N., Cowan D.H., Senn J., Poldre P. Riskadapted therapy for clinical stage I-II Hodgkin's disease: 7-years results of radiotherapy alone for low-risk disease, and ABVD and radiotherapy for high-risk disease. Clin. Oncol. (R. Coll. Radiol). 2000; 12 (5): 278–288. DOI: 10.1053/clon.2000.9174.

6. Afanasyev B.P., Akimov A.A., Nikolaev E.N., Kozlov A.P., Il'in N.V. Radiobiological analysis of the frequency of the radial light damage after mediastinal irradiation in patients with Hodgkin's lymphoma. Medical Radiology and Radiation Safety. 2005; 2: 34–40. (In Russian)

7. Nudnov N.V., Sotnikov V.M., Ledenev V.V., BaryshnikovaD. V. Quantitative estimation of radiation-induced lung damage by CT. Medical Visualization. 2016; 1: 39–47. (In Russian)

8. Nudnov N.V., Sotnikov V.M., Ledenev V.V., Baryshnikova D.V. Quantitative estimation of radiation-induced lung damage by CT. Medical Visualization. 2016; 3: 85–94. (In Russian)

9. Distel L.V., Neubauer S., Keller U., Sprung C.N., Sauer R., Grabenbauer G.G. Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients. Radiother. Oncol. 2006; 81 (3): 257–263. DOI: 10.1016/j.radonc.2006.10.012.

10. De Ruysscher D., Sharifi H., Defraene G., Kerns S.L., Christiaens M., De Ruyck K., Peeters S., Vansteenkiste J., Jeraj R., Van Den Heuvel F., van Elmpt W.. Quantification of radiation-induced lung damage with CT scans: the possible benefit for radiogenomics. Acta Oncol. 2013; 52 (7): 1405–1410. DOI: 10.3109/0284186X.2013.813074.

11. Defraene G., van Elmpt W., Crijns W., Slagmolen P., De Ruysscher D. CT characteristics allow identification of patient-specific susceptibility for radiation-induced lung damage. Radiother. Oncol. 2015; 117 (1): 29–35. DOI: 10.1016/j.radonc.2015.07.033.

12. Lobachevsky P., Leong T., Daly P., Smith J., Best N., Tomaszewski J., Thompson E.R., Li N., Campbell I.G., Martin R.F., Martin O.A. Compromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity. Cancer Lett. 2016; 383 (2): 212–219. DOI: 10.1016/j.canlet.2016.09.010.

13. Palma D.A., van Sörnsen de Koste J., Verbakel W.F., Vincent A., Senan S. Lung density changes after stereotactic radiotherapy: a quantitative analysis in 50 patients. Int. J. Radiat. Oncol. Biol. Phys. 2011; 81 (4): 974–978. DOI: 10.1016/j.ijrobp.2010.07.025.

14. Phernambucq E.C., Palma D.A., Vincent A., Smit E.F., Senan S. Time and dose- related changes in radiological lung density after concurrent chemoradiotherapy for lung cancer. Lung. Cancer. 2011; 74 (3): 451–456. DOI: 10.1016/j.lungcan.2011.05.010.

15. Diot Q., Marks L.B., Bentzen S.M., Senan S., Kavanagh B.D., Lawrence M.V., Miften M., Palma D.A. Comparison of radiation-induced normal lung tissue density changes for patients from multiple institutions receiving conventional or hypofractionated treatments. Int. J. Radiat. Oncol. Biol. Phys. 2014; 89 (3): 626– 632. DOI:10.1016/j.ijrobp.2014.03.022.

16. Sharifi H., van Elmpt W., Oberije C., Nalbantov G., Das M., Öllers M., Lambin P., Dingmans A.C., De Ruysscher D. Quantification of CT-assessed radiation-induced lung damage in lung cancer patients treated with or without chemotherapy and cetuximab. Acta Oncol. 2015; 23: 1–7. DOI: 10.3109/0284186X.2015.1080856

17. Ghobadi G., Wiegman E.M., Langendijk J.A., Widder J., Coppes R.P., van Luijk P. A new CT-based method to quantify radiation-induced lung damage in patients. Radiother. Oncol. 2015; 117 (1): 4–8. DOI: 10.1016/j.radonc.2015.07.017.