LONG-TERM OUTCOMES OF INTRAOPERATIVE RADIATION THERAPY FOR NON-SMALL CELL LUNG CANCER

The purpose of the study was to analyze long-term outcomes of intraoperative radiation therapy (IORT) in patients with stage III non-small cell lung cancer (NS CLC).

Material and Methods. The study included 103 patients with stage III NS CLC treated at the Cancer Research Institute (Tomsk, Russia). All patients were divided into two groups. Group I consisted of 51 patients, who underwent radical surgery and IORT at a single dose of 15 Gy. Group II (control group) comprised 52 patients, who underwent radical surgery alone. There were 34 (33 %) pneumonectomies, 39 (37.9 %) lob-, bilobectomies, 9 (8.7 %) reconstructive surgeries and 21 (20.4 %) combined surgeries. A compact pulsed betatron MIB-6E with the average electron energy of 6 MeV, located directly in the operating unit, was used for performing IORT. The Kaplan-Meier method was used for survival analysis. The significance of differences in survival between groups was assessed using the log rank test.

Results. Excluding the cases lost to follow-up and deaths from concomitant non-malignant diseases, treatment outcomes were followed up in 97 of 103 patients with NS CLC for 3, 5, and 10 years. The 3-year and disease-free survival rates were significantly higher in the IORT group than in the control group (p<0.05). The IORT reduced the frequency of locoregional recurrence from 28.6 % to 20.8 % and increased recurrence-free survival from 12 to 17.1 months. In patients with stage III NS CLC, who received combined modality treatment including IORT, the 5and 10-year disease-free survival rates were 18.7 % and 12.5 %, respectively. In the control group patients, the corresponding values were 14.3 % and 6.1 %, respectively (р<0.05). The 5and 10-year overall survival rates were 29.2 % and 18.7 % versus 20.4 % and 8.2 %, respectively (р<0.05).

Conclusion. In patients with stage III NS CLC, combined modality treatment, including radical surgery and IORT, results in a better local control and higher long-term survival rates compared to surgery alone.

non-small cell lung cancer, surgical treatment, combined modality treatment, intraoperative radiation therapy (IORT), survival

1. Kaprin A.D., Starinskii V.V., Petrova G.V. Malignant neoplasms in Russia in 2015 (morbidity and mortality). M., 2017. 250. (in Russian).

2. Sakaeva D.D. Practical Oncology. 2013; 14(1): 59–67. (in Russian).

3. Vinogradov V.M. The main directions of development of radiation therapy of malignant tumors. Practical Oncology. 2013; 14(1): 33–42. (in Russian).

4. Chen F., Okubo K., Sonobe M., Shibuya K., Matsuo Y., Kim Y.H., Yanagihara K., Bando T., Date H. Hyperfractionated Irradiation with 3 Cycles of Induction Chemotherapy in Stage IIIA-N2 Lung Cancer. World J Surg. 2012 Dec; 36(12): 2858–64. doi: 10.1007/s00268-012-1747-1.

5. Daly B.D., Cerfolio R.J., Krasna M.J. Role of surgery following induction therapy for stage III non-small cell lung cancer. Surg Oncol Clin N Am. 2011 Oct; 20(4): 721–32. doi: 10.1016/j.soc.2011.07.006.

6. Koshy M., Goloubeva O., Suntharalingam M. Impact of neoadjuvant radiation on survival in stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011 Apr 1; 79(5): 1388–94. doi: 10.1016/j.ijrobp.2009.12.066.

7. Matsuguma H., Nakahara R., Ishikawa Y., Suzuki H., Inoue K., Katano S., Yokoi K. Postoperative radiotherapy for patients with completely resected pathological stage III A-N2 non-small cell lung cancer: focusing on an effect of the number of mediastinal lymph node stations involved. Interact Cardiovasc Thorac Surg. 2008 Aug; 7(4): 573–7. doi: 10.1510/icvts.2007.174342.

8. Ilin M.A., Sotnikov V.M., Panshin G.A., Kotliarov P.M., Kharchenko V.P., Solodki V.A. Hypofractionated radiation therapy of peripheral non-small cell lung cancer with the increase of the equvivalent summary dose. Russian Scientific Center of Roentgenoradiology. 2011; 4(11): 25–38. (in Russian).

9. Mardynsky Yu.S., Gulidov I.A., Ivanova I.N., Kursova L.V., Zolotkov A.G., Kudryavtsev D.V., Ragulin Yu. A., Gogolin D.V. Results of continuous hyperfractionated radiotherapy in treatment of non-small cell lung cancer. Siberian Journal of Oncology. 2010; 2: 11–14. (in Russian).

10. Calvo F.A., Sole C.V., Herranz R., Lopez-Bote M., Pascau J., Santos A., Muñoz-Calero A., Ferrer C., Garcia-Sabrido J.L. Intraoperative Radiotherapy in Lung Cancer: Methodology (Electrons or Brachytherapy), Clinical Experiences and Long-Term Institutional Results. Advances in Radiation Oncology in Lung Cancer. Springer, Heidelberg. 2011; 461–476.

11. Gunderson L.L., Willett C.G., Calvo F.A., Harrison L.B. Intraoperative Irradiation – Techniques and Results. Humana Press/Springer. 529.

12. Zhou G., Zeng T., Wang L., Ma L. Analysis of the Long-term Effect of Intraoperative Radiotherapy (IORT) for Non-Small Cell Lung Carcinoma (NSCLC). Chinese Journal of Clinical Oncology. 2007 Feb; 4(1): 65–70.

13. Zav’yalov A.A., Musabaeva L.I., Lisin V.A., Choinzonov E.L., Novikov V.A., Kolomiets L.A., Tuzikov S.A., Afanas’ev S.G., Dubskii S.V., Anisenya I.I., Tyukalov Yu.I., Miller S.V., Dobrodeev A.Yu., Chivchish L.N., Nechitailo M.N., Zheravin A.A. Fifteen years of experience in the use of intraoperative radiotherapy. Siberian Journal of Oncology. 2004; 2–3(10–11): 75–84. (in Russian).

14. Calvo F.A., Hoekstra H.J., Lehnert T. Intraoperative radiotherapy: 20 years of clinical experience, technological development and consolidation of results. Eur J Surg Oncol. 2000 Nov; 26 Suppl A: S1–4.

15. Carter Y.M., Jablons D.M., DuBois J.B., Thomas C.R.Jr. Intraoperative radiation therapy in the multimodality approach to upper aerodigestive tract cancer. Surg Oncol Clin N Am. 2003 Oct; 12(4): 1043–63.

16. Aristu J., Arbea L., Calvo F.A. Intraoperative Electron Beam Radiotherapy in Lung Cancer: Methodology, Clinical Experience, and Long-Term Institutional Results. Advances in Radiation Oncology in Lung Cancer. Springer, Heidelberg. 2005; 255–268.