In recent years, a number of "black technologies" have emerged in the field of oncology. First, immunotherapy and its combination therapy are widely used in clinical practice, bringing new choices to tumor patients, and then CAR-T therapy, which can clear tumor cells with a single injection of 1.2 million, exploded in the circle of friends at the end of last year, bringing new hope to tumor patients.
Today, we are going to talk about another black technology of tumor treatment - "boron neutron capture therapy". About boron neutron capture therapy, we have mentioned in our previous article - no surgery! Is this cancer treatment really that amazing? After the article was published, we found that people were very interested in it and raised many questions, so we will come back today to explain this "black technology" in depth to answer your questions.
I. Who is "boron neutron capture therapy"?
Boron Neutron Capture Therapy (BNCT) is an emerging and rapidly developing precision therapy in the field of international cancer treatment in recent years, which is known as the fifth therapy after surgery, radiotherapy, drug therapy and immunotherapy.
Boron neutron capture therapy is to inject a boron-containing drug into the patient first, which has a very strong affinity with tumor cells in the body and will rapidly and specifically gather in the tumor cells, which is equivalent to putting a "bad guy" mark on the tumor cells, and then irradiate the tumor site with a low-energy superheated neutron beam. When the irradiated neutrons are captured by the boron in the tumor cells, it will produce highly lethal alpha particles and 7Li particles (the damage size is about one tumor cell size nuclear reaction), which can make the tumor cells die completely due to the DNA breakage, so as to kill the tumor cells precisely without damaging the normal tissues.
The whole process takes about 30 minutes to an hour, hence the saying "30 minutes to zero tumor cells".
Second, "boron neutron capture therapy" has many advantages
Compared to other conventional treatments, boron neutron capture therapy has unique advantages.
①Good targeting effect and high safety
Boron has a high affinity for tumor cells and can only be absorbed and aggregated by tumor cells, which can precisely target the positioning of tumor cells and produce high-energy particles with a range of only one tumor cell size, without harming the surrounding normal cells. Therefore, the whole treatment process realizes the precise killing of tumor cells without affecting normal cells, with high safety and little harm to patients.
②Short duration and high compliance
No incisions are required and the treatment can be completed in a short time. Each irradiation takes only 30 minutes to an hour, and only 1-2 irradiation sessions are required, resulting in relatively high patient compliance.
(iii) Predictable efficacy
After boron injection and before neutron beam irradiation, the degree of boron aggregation in cancer cells can be observed by FBPA-PET nuclear medicine examination, which can be used to determine the uptake of tumor cells and thus predict the efficacy of treatment. Problems can also be intervened in time to ensure the best treatment effect.
④Good treatment effect and low recurrence rate
There are two types of cells in tumor tissues, aerobic type and oxygen-depleted type. Among them, traditional radiotherapy has obvious effect on aerobic tumor cells, but not on oxygen-depleted type, which leads to the existence of oxygen-depleted tumor cells cells in the body after traditional radiotherapy, and it is very easy to lead to recurrence. In contrast, boron neutron capture therapy is effective for both types of tumor cells, which can "eliminate the root of the problem" and reduce the risk of recurrence.
Since boron neutron capture therapy is so effective, which tumors is it applicable to?
Which tumors are suitable for boron neutron capture therapy?
①Head and neck tumors
From October 2003 to September 2007, clinical data from a Japanese institution showed that after boron neutron capture treatment in 20 patients with advanced/recurrent head and neck tumors, 11 patients were in complete remission and 7 patients were in partial remission, with an efficiency rate of (CR+PR) 90% [1].
②Brain tumors
Brain tumors are currently a relatively mature area for BNCT research, and BNCT has shown extraordinary potential both in glioblastoma and meningioma.
a Glioblastoma
After BNCT treatment of 23 patients with glioblastoma, the median survival time was 19.5 months and the survival rates at 2, 3 and 5 years were 26.1%, 17.4% and 5.8%, respectively, which showed significantly better clinical outcomes compared to conventional single radiotherapy [2]. And after BNCT treatment of 38 patients with glioblastoma multiforme, the median time to tumor progression was found to be 31.6 months and the median survival time was 13.0 months, with no serious toxic effects detected [3].
b Meningioma
A retrospective study investigated at Osaka Medical University in Japan found that among 31 patients with recurrent meningioma treated with BNCT, all patients showed tumor shrinkage with a median survival time of 24.6 months [4].
③Lung cancer
Two patients with lung cancer treated with BNCT were reported to have stable or shrinking tumors with no significant serious toxicities at the 6-month follow-up. However, further research is needed in the field of lung cancer treatment with BNCT [5].
④Breast cancer
Tumor models have shown that BNCT has great therapeutic potential in breast cancer patients with HER2 overexpression [6]; trial analysis has also shown that BNCT can be used to treat patients with recurrent breast cancer, but these need to be confirmed by further clinical studies [7].
⑤ Liver cancer
The first case of a patient with liver cancer who underwent BNCT was first reported in Japan, and after treatment, his tumor size remained stable, but the disease progressed after 3-5 months [8], while in another 63-year-old patient with liver cancer who underwent BNCT, the patient also had initially more stable disease, but later developed metastasis. Liver cancer needs to be studied more thoroughly [9].
(6) Melanoma
Several studies have confirmed that BNCT has great therapeutic potential for the treatment of cutaneous melanoma, with safe and controlled adverse effects and no significant serious adverse effects, and can also be used to control recurrence and lymphoma metastasis in cutaneous melanoma [10].
In addition, BNCT in colon cancer, urological tumors, and osteosarcoma, promising results and acceptable toxic reactions have been found, but these require further studies to determine the role involved [11].
In general, boron neutron capture therapy is relatively well researched in the field of head and neck tumors and brain tumors, and the results are very clear, among which, Japan has included BNCT in the medical coverage of recurrent head and neck cancer. The areas such as lung cancer, liver cancer, breast cancer, and colon cancer have also shown great therapeutic potential, but further research is needed.
Ltd. announced last November 23 that it has successfully developed the first anti-cancer boron drug, which is expected to be used in the clinic in 2023, so everyone will be able to use this anti-cancer black technology by then.
In addition, some patients may be concerned that BNCT is a new type of therapy and will be expensive. Considering other factors such as the economic development level of China and Japan, it is expected that the treatment cost in China will be around 100,000 RMB, and if it is included in medical insurance, according to 60% reimbursement, individuals only need to pay 40,000 RMB. This means that most tumor patients can enjoy the black technology of "30 minutes to clear tumor cells" to fight against cancer.
We believe that BNCT can bring us more surprises in the near future, and we hope it can be put into the clinic and enter the medical insurance soon. It will benefit the majority of tumor patients.
Reference.
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[2]Kageji T, Mizobuchi Y, Nagahiro S,Nakagawa Y, Kumada H. 硼中子捕获疗法（BNCT）治疗胶质母细胞瘤的临床结果。Appl Radiat Isot. doi:10.1016/j.apradiso.2011.05.029. Epub 2011 Jun 12. pmid: 21684170.
[3]Chanana AD, Capala J, Chadha M, CoderreJA, Diaz AZ, Elowitz EH, et al. 硼中子捕获疗法治疗多形性母细胞瘤：I/II期剂量递增研究的中期结果。神经外科（1999）44（6）：1182-92；讨论92-3。10.1097/00006123-199906000-00013
[4]Takeuchi K, Kawabata S, Hiramatsu R,Matsushita Y, Tanaka H, Sakurai Y, et al. Boron Neutron Capture Therapyfor High-Grade Skull-Base Meningioma. J Neurol Surg B SkullBase (2018) 79(Suppl 4):S322-s7. 10.1055/s-0038-1666837.
[5] Suzuki M, Endo K, Satoh H, Sakurai Y,Kumada H, Kimura H, et al. 硼中子捕获疗法（BNCT）治疗弥漫性或多发性胸膜肿瘤的新概念。RadiotherOncol（2008）88（2）：192-5。10.1016/j.radonc.2008.06.009
[6]Gadan MA, Gonzalez SJ, Batalla M, Olivera MS, Policastro L, Sztejnberg ML. 应用BNCT治疗HER2+乳腺癌的复发。在阿根廷的研究和发展。Appl Radiat Isot (2015) 104:155-9. 10.1016/j.apradiso.2015.07.006
[7] Yanagie H, Kumada H, Sakurai Y, NakamuraT, Furuya Y, Sugiyama H, et al. 中子俘获疗法对局部晚期乳腺癌的剂量学评价。Appl RadiatIsot (2009) 67(7-8 Suppl):S63-6. 10.1016/j.apradiso.2009.03.110
[8] Suzuki M, Sakurai Y, Hagiwara S,Masunaga S, Kinashi Y, Nagata K, et al. 硼中子俘获疗法（BNCT）治疗肝细胞癌的首次尝试。Jpn J ClinOncol（2007）37（5）：376-81。10.1093/jjco/hym039
[9]Yanagie H, Higashi S, Seguchi K, Ikushima I, Fujihara M, Nonaka Y, et al. 复发性肝癌硼烷捕获疗法的试验性临床研究，包括动脉内注射含（10）BSH的WOW乳液。Appl RadiatIsot (2014) 88:32-7. 10.1016/j.apradiso.2014.01.014
[10] Omori M, Fujiwara S, Shimizu H, IkedaT, Bito T, Suzuki M, et al. 使用反应堆热中子束的硼中子俘获疗法可以有效控制源于皮肤恶性黑色素瘤的在途和淋巴结转移。JDermatol（2018）45（4）：e90-e1. 10.1111/1346-8138.14134
[11]Malouff TD, Seneviratne DS, Ebner DK,Stross WC, Waddle MR, Trifiletti DM, Krishnan S. Boron Neutron Capture Therapy: A Review of Clinical Applications. Front Oncol. 2021年2月26日；11:601820.DOI:10.3389/fonc.2021.601820. pmid: 33718149; pmcid: pmc7952987.
