Efficacy of Boron Neutron Capture Therapy for Head and Neck Cancer: Systematic Review
https://doi.org/10.37174/2587-7593-2025-8-3-18-26
Abstract
Introduction. Head and neck cancer is characterized by a high rate of locoregional relapses. Treatment of progressive disease is ineffective, which significantly reduces the prognosis. The importance to study boron neutron capture therapy (BNCT) as a promising method capable of providing selective destruction of tumor cells with minimal damage to surrounding tissues.
The aim of this systematic review was to comprehensively evaluate the efficacy and safety of BNCT in locally advanced recurrent head and neck cancer.
Materials and methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic search of PubMed for all articles up to January 2025.
Results: 22 studies were included in the systematic review: 8 phase I/II studies and one phase II study, as well as 11 retrospective studies. The search identified 680 patients with recurrent or locally advanced unresectable head and neck cancer. The analysis showed that BNCT demonstrates promising efficacy in various cancer types with a manageable safety profile. Conclusions: BNCT shows significant promise as a treatment modality, offering potential benefits with acceptable safety. However, further research is needed to improve its clinical application and ensure its safety and efficacy.
About the Authors
B. B. Vyzhigina
Oncology Center No. 1 of S.S. Yudin City Clinical Hospital of the Department of Health
Russian Federation
Competing Interests:
Russian Federation
Bella B. Vyzhigina
117152 Moscow, Zagorodnoye Shosse, 18A
Competing Interests:
Not declared.
B. I. Dolgushin
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation
Competing Interests:
Russian Federation
24 Kashirskoye Shosse, Moscow, 115478
Competing Interests:
Not declared.
M. A. Kropotov
A.F. Tsyb Medical Radiological Research Centre — branch of the National Medical Research Radiological Centre
Russian Federation
Competing Interests:
Russian Federation
249031, Obninsk, 10 Zhukova str.
Competing Interests:
Not declared.
References
1. Bray F, Laversanne M, Sung H. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwidefor 36 cancers in 185 countries. Cancer J Clin. 2024;74(3):229- 63. https://doi.org/10.3322/caac.21834
2. Dong L, Xue L, Cheng W, et al. Comprehensive survival analysis of oral squamous cell carcinoma patients undergoing initial radical surgery. BMC Oral Health. 2024;24(1):919. https://doi.org/10.1186/s12903-024-04690-z
3. Guntinas-Lichius O, Kreppel MP, Stuetzer H, et al. Single modality and multimodality treatment of nasal and paranasal sinuses cancer: a single institution experience of 229 patients. Eur J Surg Oncol. 2007;33(2):222-28. https://doi.org/10.1016/j.ejso.2006.10.033
4. Yang KL, Chi MS, Hao CY, et al. Phase II clinical trial assessing the addition of hyperthermia to salvage concurrent chemoradiotherapy for unresectable recurrent head and neck cancer. Radiat Oncol. 2025;20(1):21. https://doi.org/10.1186/s13014-025-02585-z
5. Lee N, Chan K, Bekelman JE, et al. Salvage re-irradiation for recurrent head and neck cancer. Int J Radiat Oncol Biol Phys. 2007;68(3):731-40. https://doi.org/10.1016/j.ijrobp.2006.12.055
6. Baselga J, Trigo JM, Bourhis J, et al. Phase II study of cetuximab plus platinum-based chemotherapy in platinum-refractory metastatic head and neck cancer. J Clin Oncol. 2005;23(24):5568-77. https://doi.org/10.1200/JCO.2005.07.119
7. Ferris RL, Blumenschein GJ, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856-67. https://doi.org/10.1056/NEJMoa1602252
8. Vermorken JB, 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. https://doi.org/10.1056/NEJMoa0802656
9. Salama JK, Vokes EE, Chmura SJ, et al. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head and neck cancer. Int J Radiat Oncol Biol Phys. 2006;64(2):382-91. https://doi.org/10.1016/j.ijrobp.2005.07.005
10. Sewnaik A, Keereweer S, Al-Mamgani A, et al. High complication risk of salvage surgery after chemoradiation failures. Acta Otolaryngol. 2012;132:96-100. https://doi.org/10.3109/00016489.2011.617779
11. Dionisi F, Fiorica F, D’Angelo E, et al. Organs at risk’s tolerance and dose limits for head and neck cancer re-irradiation: a literature review. Oral Oncol. 2019;98:35-47. https://doi.org/10.1016/j.oraloncology.2019.08.017
12. Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy vs cetuximab with chemotherapy in recurrent/metastatic head and neck cancer (KEYNOTE-048). Lancet. 2019;394:1915-28. https://doi.org/10.1016/S0140-6736(19)32591-7
13. Patachi B, Jensen KH, Gothelf A, et al. Pembrolizumab as firstline treatment for recurrent/metastatic head and neck cancer: single-centre data. Acta Oncol. 2025;64:143-46. https://doi.org/10.2340/1651-226X.2025.42128
14. Zhou T, Igawa K, Kasai T, et al. The current status and novel advances of boron neutron capture therapy clinical trials. Am J Cancer Res. 2024;14(2):429-47. https://doi.org/10.62347/HBBE6868
15. Moher MD, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097
16. Wittig A, Collette L, Appelman K, et al. EORTC Trial 11001: distribution of two 10B-compounds in patients with squamous cell carcinoma of head and neck. J Cell Mol Med. 2009;13:1653-65. https://doi.org/10.1111/j.1582-4934.2009.00856.x
17. Hirose K, Konno A, Hiratsuka J, et al. BNCT using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): an open-label phase II trial. Radiother Oncol. 2021;155:182-87. https://doi.org/10.1016/j.radonc.2020.11.001
18. Aihara T, Morita N, Kamitani N, et al. Boron neutron capture therapy for advanced salivary gland carcinoma in head and neck. Int J Clin Oncol. 2014;19:437-44. https://doi.org/10.1007/s10147-013-0580-3
19. Aihara T, Morita N. BNCT for advanced or recurrent head and neck cancer. Neutron Capture Therapy: Principles and Applications. Springer; 2012:417-24. https://doi.org/10.1016/j.apradiso.2014.04.007
20. Kankaanranta L, Seppälä T, Koivunoro H, et al. BNCT for locally recurred head and neck cancer: final analysis of a phase I/II trial. Int J Radiat Oncol Biol Phys. 2012;82:e67-e75. https://doi.org/10.1016/j.ijrobp.2010.09.057
21. Kankaanranta L, Seppälä T, Koivunoro H, et al. BNCT in the treatment of locally recurred head and neck cancer. Int J Radiat Oncol Biol Phys. 2007;69:475-82. https://doi.org/10.1016/j.ijrobp.2007.03.039
22. Wang LW, Chen YW, Ho CY, et al. Fractionated BNCT in locally recurrent head and neck cancer: a prospective phase I/II trial. Int J Radiat Oncol Biol Phys. 2016;95:396-403. https://doi.org/10.1016/j.ijrobp.2016.02.028
23. Wang LW, Chen YW, Ho CY, et al. Fractionated BNCT for locally recurrent head and neck cancer: experience from a phase I/II trial at Tsing Hua Open-Pool Reactor. Appl Radiat Isot. 2014;88:23-27. https://doi.org/10.1016/j.apradiso.2013.11.134
24. Lee JC, Chuang KS, Liu YW, et al. Comparison of dose distributions in gross tumor volume between BNCT alone and BNCT plus IMRT for head and neck cancer. PLoS One. 2019;14:e0210626. https://doi.org/10.1371/journal.pone.0210626
25. Wang LW, Liu YH, Chu PY, et al. BNCT followed by image-guided IMRT for locally recurrent head and neck cancer: a prospective phase I/II trial. Cancers (Basel). 2023;15(10):2762. https://doi.org/10.3390/cancers15102762
26. Koivunoro H, Kankaanranta L, Seppälä T, et al. BNCT for locally recurrent head and neck squamous cell carcinoma: an analysis of dose response and survival. Radiother Oncol. 2019;137:153-58. https://doi.org/10.1016/j.radonc.2019.04.033
27. Haapaniemi A, Kankaanranta L, Saat R, et al. BNCT in the treatment of recurrent laryngeal cancer. Int J Radiat Oncol Biol Phys. 2016;95:404-10. https://doi.org/10.1016/j.ijrobp.2015.11.010
28. Higashino M, Aihara T, Takeno S, et al. BNCT as a larynx-preserving treatment for locally recurrent laryngeal carcinoma after conventional radiation therapy: a preliminary report. Auris Nasus Larynx. 2024;51(4):792-96. https://doi.org/10.1016/j.anl.2024.06.007
29. Sato M, Hirose K. Efficacy and safety of BNCT for hypopharyngeal/laryngeal cancer in previously irradiated patients. Radiother Oncol. 2024;198:110382. https://doi.org/10.1016/j.radonc.2024.110382
30. Kikuoka Y, Aihara T, Higashino M, et al. LAT1 expression in high-grade parotid carcinoma and potential of BNCT as a treatment option. Appl Radiat Isot. 2025;218:111657. https://doi.org/10.1016/j.apradiso.2024.111657
31. Suzuki M, Kato I, Aihara T, et al. BNCT outcomes for advanced or recurrent head and neck cancer. J Radiat Res. 2014;55(1):146-53. https://doi.org/10.1093/jrr/rrt098
32. Wang LW, Wang SI, Chu PY, et al. BNCT for locally recurrent head and neck cancer: preliminary clinical experience from a phase I/II trial. Appl Radiat Isot. 2011;69:1803-06. https://doi.org/10.1016/j.apradiso.2011.03.008
33. Kimura Y, Ariyoshi Y, Shimahara M, et al. BNCT for recurrent oral cancer and cervical lymph node metastasis. Appl Radiat Isot. 2009;67(Suppl 7-8):S47-49. https://doi.org/10.1016/j.apradiso.2009.03.019
34. Lan TL, Chang FC, Wang CW, et al. Prevention and early management of carotid blowout syndrome in patients receiving salvage BNCT. J Dent Sci. 2021;16(3):854-60. https://doi.org/10.1016/j.jds.2020.12.013
35. Sato M, Hirose K, Takeno S, et al. Safety and efficacy of BNCT with Borofalan (10B) for recurrent head and neck cancer: real-world post-marketing outcomes. Cancers (Basel). 2024;16(5):869. https://doi.org/10.3390/cancers16050869
36. Takeno S, Yoshino Y, Aihara T, et al. Preliminary outcomes of BNCT for head and neck cancers under public insurance in Japan: real-world experiences. Cancer Med. 2024;13(11):e7250. https://doi.org/10.1002/cam4.7250
37. Suzuki M, Sakurai Y, Nagata Y, et al. Impact of intra-arterial boron administration on dose-volume histograms in BNCT for recurrent head and neck tumors. Int J Radiat Oncol Biol Phys. 2006;66:1523-27. https://doi.org/10.1016/j.ijrobp.2006.07.1373
38. Ariyoshi Y, Miyatake SI, Kimura Y, et al. BNCT using epithermal neutrons for recurrent cancer in oral cavity and cervical lymph nodes. Oncol Rep. 2007;18(4):861-66. https://doi.org/10.3892/or.18.4.861
39. Agra IM, Carvalho AL, Ulbrich FS, et al. Prognostic factors in salvage surgery for recurrent oral and oropharyngeal cancer. Head Neck. 2006;28:107-13. https://doi.org/10.1002/hed.20309
40. Rivera F, García-Castaño A, Vega N, et al. Cetuximab in metastatic/recurrent head and neck cancer: the EXTREME trial. Expert Rev Anticancer Ther. 2009;9(10):1421-28. https://doi.org/10.1586/era.09.113.
Review
For citations:
Vyzhigina B.B., Dolgushin B.I., Kropotov M.A. Efficacy of Boron Neutron Capture Therapy for Head and Neck Cancer: Systematic Review. Journal of oncology: diagnostic radiology and radiotherapy. 2025;8(3):18-26. (In Russ.) https://doi.org/10.37174/2587-7593-2025-8-3-18-26
Views:
18
Email this article 