Proton beam therapy in repeat irradiation of recurrent head and neck tumors: analysis of short-term results

Introduction. Recurrence of head and neck tumors occurs in 50 % of cases and usually has locoregional character. Due to the characteristics of dose distribution, proton beam therapy is a promising treatment option for patients with recurrences of tumors in this location who previously underwent radiation therapy.

Aim. To evaluate the effectiveness and tolerability of repeat irradiation using active scanning proton beam therapy in patients with recurrent head and neck tumors who previously underwent radiation therapy.

Materials and methods. Between November of 2015 and December of 2020, 40 patients with locoregional recurrence of head and neck tumors underwent treatment using active scanning proton beam therapy at the A. F . Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center. Median cumulative dose of primary irradiation was 64.5 Gy. Median time between primary and repeat irradiation was 35.7 months, mean irradiated volume of the repeat course was 94.5 cm³. Proton beam therapy was performed using standard mode (2 isoGy) and accelerated hypofractionation (2.4 isoGy / 3 isoGy) with mean equivalent cumulative dose of 56.4 Gy (α / β = 10). Radiation toxicity was evaluated using the Radiation Therapy Oncology Group European (RTOG) / Organization for Research and Treatment of Cancer (EORTC) scale.

Results. Treatment response was achieved in 34 (85 %) patients: in 17 (42.5 %) patients, stable disease was observed; in 10 (25 %) patients, partial response was observed; and in 7 (17.5 %) patients, complete response was observed. In 6 (15 %) cases, disease progression was diagnosed at first follow-up examination. One- and two-year locoregional control, progression-free survival and overall survival were 58.4 / 19.8; 44.5 / 19.8 and 82.3 / 38.8 % respectively with median follow-up duration of 14.2 months. Median survival was 19.5 months. Grade III and above early radiation toxicity was observed in 3 (7.5 %) patients. In total, 6 (15 %) cases of grade III complications and 2 (5 %) episodes of carotid artery rupture leading to death were observed. Overall frequency of complications of grade III and higher was 20 %.

Conclusion. Repeat irradiation using proton beam therapy can be considered an effective and safe treatment method for patients with recurrent head and neck tumors. Dosimetric and radiobiological benefits of proton beams allow to achieve balance between high doses and radiation exposure in previously irradiated tissues.

1. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study. JAMA Oncol 2017;3(4):524–48. DOI: 10.1001/jamaoncol.2016.5688

2. Malignant neoplasms in Russia in 2019. Ed. by A.D. Kaprin, V.V. Starinsky, G.V. Petrov. Moscow: P.A. Herzen Moscow State Medical Research Institute – branch of the Federal State Budgetary Institution “NMIC of Radiology” of the Ministry of Health of Russia, 2020. 239 p. (In Russ.).

3. Morris L.G., Sikora A.G., Patel S.G. et al. Second primary cancers after an index head and neck cancer: subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 2011;29(6):739–46. DOI: 10.1200/JCO.2010.31.8311

4. Bachar G.Y., Goh C., Goldstein D.P. et. al. Long-term outcome analysis after surgical salvage for recurrent tonsil carcinoma following radical radiotherapy. Eur Arch Otorhinolaryngol 2010;267(2):295–301. DOI: 10.1007/s00405-009-1070-0

5. Vermorken J.B., Mesia R., Rivera F. et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359(11):1116–27. DOI: 10.1056/NEJMoa0802656

6. Karabajakian A., Toussaint P., Neidhardt E.M. et al. Chemotherapy for recurrent/metastatic head and neck cancers. Anticancer Drugs 2017;28(4):357–61. DOI: 10.1097/CAD.0000000000000473

7. Rozhnov V.A., Andreev V.G., Gordon K.B. et al. Modern methods of treatment of recurrent inoperable squamous cell carcinoma of the larynx. (Literature review). Sibirskij onkologicheskij zhurnal = Siberian Journal of Oncology 2016;15(2):90–100. (In Russ.). DOI: 10.21294/1814-4861-2016-15-2-90-100

8. Kim Y.S. Reirradiation of head and neck cancer in the era of intensity-modulated radiotherapy: patient selection, practical aspects, and current evidence. Radiat Oncol J 2017;35(1):1–15. DOI: 10.3857/roj.2017.00122

9. Phan J., Sio T.T., Nguyen T.P. et al. Reirradiation of head and neck cancers with proton therapy: outcomes and analyses. Int J Radiat Oncol Biol Phys 2016;96(1):30–41. DOI: 10.1016/j.ijrobp.2016.03.053

10. Pfister D., Spencer S., Adelstein D. et al. Head and Neck Cancers, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020;18(7):873–98. DOI: 10.6004/jnccn.2020.0031

11. Doyen J., Falk A.T., Floquet V. et al. Proton beams in cancer treatments: clinical outcomes and dosimetric comparisons with photon therapy. Cancer Treat Rev 2016;43:104–12. DOI: 10.1016/j.ctrv.2015.12.007

12. McDonald M.W., Zolali-Meybodi O., Lehnert S.J. et al. Reirradiation of recurrent and second primary head and neck cancer with proton therapy. Int J Radiat Oncol Biol Phys 2016;96(4):808–19. DOI: 10.1016/j.ijrobp.2016.07.037

13. Gordon K., Gulidov I., Semenov A. et al. Proton re-irradiation of unresectable recurrent head and neck cancers. Rep Pract Oncol Radiother 2021;26(2):203–10. DOI: 10.5603/RPOR.a2021.0029

14. Sokurenko V.P., Mikhailov A.V., Vorobyev N.A. et al. The possibility of repeated radiation therapy in patients with recurrent squamous cell carcinoma of the head and neck. Luchevaya diagnostika i terapiya = Radiation diagnostics and therapy 2017;1:82–7. (In Russ.). DOI: 10.22328/2079-5343-2017-1-82-87

15. Ang K.K., Price R.E., Stephens L.C. et al. The tolerance of the primate spinal cord to re-irradiation. Int J Radiat Oncol Biol Phys 1993;25(3):459–64. DOI: 10.1016/0360-3016(93)90067-6

16. Spencer S.A., Harris J., Wheeler R.H. et al. Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck. Head Neck 2008;30(3):281–8. DOI: 10.1002/hed.20697

17. Langer C.J., Harris J., Horwitz E.M. et al. Phase II study of low-dose paclitaxel and cisplatin in combination with split-course concomitant twice-daily reirradiation in recurrent squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Protocol 9911. J Clin Oncol 2007;25(30):4800–5. DOI: 10.1200/JCO.2006.07.9194

18. Yamazaki H., Ogita M., Himei K. et al. Carotid blowout syndrome in pharyngeal cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife: a multi-institutional matched-cohort analysis. Radiother Oncol 2015;115(1):67–71. DOI: 10.1016/j.radonc.2015.02.021

19. Gogineni E., Zhang I., Rana Z. et al. Quality of life outcomes following organ-sparing SBRT in previously irradiated recurrent head and neck cancer. Front Oncol 2019;9:836. DOI: 10.3389/fonc.2019.00836

20. Choe K.S., Haraf D.J., Solanki A. et al. Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation. Cancer 2011;117(20):4671–8. DOI: 10.1002/cncr.26084

21. Takiar V., Garden A.S., Ma D. et al. Reirradiation of head and neck cancers with intensity modulated radiation therapy: outcomes and analyses. Int J Radiat Oncol Biol Phys 2016;95(4):1117–31. DOI: 10.1016/j.ijrobp.2016.03.01