Clinical trials for treating recurrent head and neck cancer with boron neutron capture therapy using the Tsing-Hua Open Pool Reactor

Abstract

Head and neck (HN) cancer is an endemic disease in Taiwan, China. Locally recurrent HN cancer after full-dose irradiation poses a therapeutic challenge, and boron neutron capture therapy (BNCT) may be a solution that could provide durable local control with tolerable toxicity. The Tsing-Hua Open Pool Reactor (THOR) at National Tsing-Hua University in Hsin-Chu, provides a high-quality epithermal neutron source for basic and clinical BNCT research. Our first clinical trial, entitled "A phase I/II trial of boron neutron capture therapy for recurrent head and neck cancer at THOR", was carried out between 2010 and 2013. A total of 17 patients with 23 recurrent HN tumors who had received high-dose photon irradiation were enrolled in the study. The fructose complex of L-boronophenylalanine was used as a boron carrier, and a two-fraction BNCT treatment regimen at 28-day intervals was used for each patient. Toxicity was acceptable, and although the response rate was high (12/17), re-recurrence within or near the radiation site was common. To obtain better local control, another clinical trial entitled "A phase I/II trial of boron neutron capture therapy combined with image-guided intensity-modulated radiotherapy (IG-IMRT) for locally recurrent HN cancer" was initiated in 2014. The first administration of BNCT was performed according to our previous protocol, and IG-IMRT was initiated 28 days after BNCT. As of May 2017, seven patients have been treated with this combination. The treatment-related toxicity was similar to that previously observed with two BNCT applications. Three patients had a complete response, but locoregional recurrence was the major cause of failure despite initially good responses. Future clinical trials combining BNCT with other local or systemic treatments will be carried out for recurrent HN cancer patients at THOR.

Keywords: Boron neutron capture therapy; Boronophenylalanine; Head and neck cancer; Tsing-Hua Open Pool Reactor.

Fig. 1

A view of the Tsing-Hua Open Pool Reactor (THOR) and a photo of the treatment room. a An image of THOR; the treatment room for boron neutron capture therapy (BNCT) is at the lower right corner. b The treatment couch and polyethylene extension collimator in the THOR irradiation room for maintaining treatment position during epithermal neutron irradiation

Fig. 2

Dose distribution and dose volume histogram (DVH) calculated by THORplan for one patient treated with fractionated boron neutron capture therapy. a Three-dimensional dose distribution for a man with recurrent buccal cancer by THORplan. b DVH for the same case by THORplan. The gross tumor volume (light blue, right) received far more of the dose than normal tissues (other colors)

Fig. 3

[18]-Fluoro-boronophenylalanine positron emission tomography (¹⁸F-BPA-PET) of the patient in Fig. 2. The tumor is indicated with an arrow to determine the tumor/normal tissue BPA ratio

Fig. 4

Photos of a recurrent buccal cancer patient before and after boron neutron capture therapy (BNCT). a A photo taken before BNCT (recurrent left buccal tumor indicated by arrows). b A partial response was found 2 months following two-fraction BNCT. His pain symptoms and quality of life improved significantly

Fig. 5

^[18]F-BPA PET images of a patient with recurrent nasopharyngeal cancer in the auditory canal after two courses of radical radiotherapy and surgery. a Before boron neutron capture therapy (BNCT), the bright area anterior to the cerebellum showed the recurrent tumor (arrow head). b Five months after two applications of BNCT, the tumor in the auditory canal shrank completely