Neutron capture therapy of cancer

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Neutron capture therapy ( NCT ) is a non-invasive treatment modality for treating invasive local malignant tumors such as primary brain tumors and recurrent head and neck cancers. In summary, this is a two-step procedure: first , the patient is injected with a tumor localization drug containing the high-tendency or cross-sectional isotope of boron-10 ( ¹⁰ B) ?) to capture slow neutrons. Cross section ¹⁰ B is many times larger than other elements present in tissues such as hydrogen, oxygen, and nitrogen. At the sec step, the patient is emitted with an epithermal neutron, the source is a nuclear reactor or, more recently, an accelerator. After losing energy as they penetrate the network, the neutrons are absorbed by the arresting agent, which then emits high-energy-charged particles that can selectively kill tumor cells that have taken enough amount of ¹⁰ B (Fig 1).

All clinical experience to date with NCT is with the non-radioactive isotope boron-10, and this is known as boron neutron retention therapy (BNCT ). At present, the use of other non-radioactive isotopes, such as gadolinium, has been limited, and to date, has not been used clinically. BNCT has been clinically evaluated as an alternative to conventional radiation therapy for the treatment of malignant (glioma) brain tumors, and recurrent, forward head and neck localized cancer and skin melanoma and extrasutane.

Video Neutron capture therapy of cancer

Boron neutron capture therapy

History

After the early discovery of neutrons in 1932 by Sir James Chadwick, H. J. Taylor in 1935 showed that boron-10 nuclei have a tendency to capture thermal neutrons. This results in nuclear splitting from the boron-11 core to helium-4 (alpha particles) and lithium-7 ions. In 1936, G.L. Locher, a scientist at the Franklin Institute in Pennsylvania, recognized the therapeutic potential of this discovery and suggested that neutron capture could be used to treat cancer. WH Sweet, of Massachusetts General Hospital, first suggested techniques for treating malignant brain tumors and BNCT trials against the most violent brain tumors, glioblastoma multiforme, using borax as a shipping agent in 1951. Clinical trials began in collaboration with Brookhaven National Laboratory in Long Island, USA and Massachusetts General Hospital in Boston in 1954.

A number of research groups around the world have continued the work of early breakthroughs William Sweet and Ralph Fairchild, and in particular, pioneering clinical studies of Hiroshi Hatanaka in Japan. This was followed by clinical trials in a number of other countries including the United States, Sweden, Finland, Czech Republic, Argentina, the European Union (based in the Netherlands) and Japan. Currently, programs in Japan have switched from reactor neutron sources to accelerators, and now Phase I/II trials are underway to evaluate the security of neutron accelerator sources.

Maps Neutron capture therapy of cancer

Basic principles

Neutron capture therapy is a binary system consisting of two separate components to achieve its therapeutic effect. Each component itself is non-tumoricidal, but when combined together they are very deadly to cancer cells.

BNCT is based on nuclear capture and fission reactions that occur when non-radioactive boron-10, which forms about 20% of the boron's natural element, is irradiated with neutrons from the right energy to produce an excited (11) B *). It undergoes instant nuclear fission to produce high energy alpha particles ( ⁴ He nuclei) and high energy lithium-7 ( ^{7/li) li nuclei. The nuclear reactions are:}

¹⁰ B n _th -> [ ¹¹ B] * ->? ⁷ Li 2.31 MeV

Alpha particles and lithium ions produce close ionisation near the reaction, with a range of 5-9 μm, which is approximately close to the diameter of the target cell. The lethality of the capture reaction is limited to the boron containing cells. Therefore, BNCT can be considered as a type of radiation therapy that is biologically and physically targeted. The success of BNCT depends on selective delivery of sufficient quantities of ¹⁰ B to tumors with only small amounts localized in the surrounding normal tissue. Thus, normal tissue, if they do not take sufficient boron-10, can avoid nuclear capture and fission reactions. Normal tissue tolerance is determined by nuclear reactions that occur with normal tissues of hydrogen and nitrogen.

A wide variety of boron delivery agents have been synthesized, but only two of these are currently being used in clinical trials. The first, which has been used mainly in Japan, is the borocedral anion, sodium borokaptate or BSH (Na ₂ B ₁₁ SH), and the second is the dihydroxyboryl derivative of phenylalanine, which is referred to as boronophenylalanine or BPA. The latter has been used in clinical trials in the United States, Finland, Japan and more recently, Argentina and Taiwan. After administration of BPA or BSH through intravenous infusions, the tumor sites were irradiated with neutrons, sources that have now been specially designed nuclear reactors. Until 1994, low-energy thermal neutrons (& lt; 0.5 eV) were used in Japan and the United States, but because they had a limited penetration depth in tissue, higher energy (& gt;.5eV & lt; 10 keV) Epitermal beam neutrons, which have greater penetration depth, have been used in clinical trials in the United States, Europe, Japan, Argentina, Taiwan, and China. In theory, BNCT is a very selective type of radiation therapy that can target tumor cells without causing radiation damage to normal cells and adjacent tissues. Doses up to 60-70Ã, Gray (Gy) may be delivered to tumor cells in one or two applications compared to 6-7 weeks for conventional irradiated external radiation. However, the effectiveness of BNCT relies on a relatively homogeneous cellular distribution of ¹⁰ B in tumors, and this remains one of the major unsolved problems that has limited its success.

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Radiobiological Considerations

The radiation dose delivered to the tumor and the normal tissue during BNCT is due to energy deposition of three different types of direct ionizing radiation in linear energy transfer (LET), which is the rate of energy loss along the ionizing particles path:

1. low gamma rays, mainly generated from thermal neutron capture by normal tissue hydrogen atoms ¹ H (n ,?) ² H];

2. High LET protons, produced by rapid neutron scattering and from thermal neutron capture by nitrogen atoms [ ¹⁴ N (n, p) ¹⁴ C]; and

3. High LET, heavier charged alpha particles (helical nuclei [ ⁴ He]) and lithium-7 ions, are released as a product of thermal neutron capture and fission reactions with ¹⁰ B [ ¹⁰ B (n ,?) ⁷ Li].

Since both the tumor and surrounding normal tissue are present in the radiation field, even with ideal epithermal neutron rays, there will be an unavoidable nonspecific background dose consisting of high and low LET radiation. However, higher concentrations of ¹⁰ B in the tumor will result in receiving a higher total dose than adjacent normal tissue, which is the basis for therapeutic benefit in BNCT. The total dose of radiation in Gy delivered to any network can be expressed in equivalent units of photons as the sum of each component of the high dose LET multiplied by the weighting factor (Gy _w ), which depends on increasing the radiobiological effectiveness of each of these components.

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clinical dosimetry

Biological weighting factors have been used in all recent clinical trials in patients with high grade gliomas, using boronophenylalanine (BPA) in combination with epithermal neutron rays. The ⁷ B component of the radiation dose to the scalp has been based on boron concentrations measured in blood at BNCT, assuming blood: boron concentration ratio scalp 1.5: 1 and biological effectiveness factor (CBE) combined for BPA in skin 2.5. The relative biological effectiveness factor (RBE) of 3.2 has been used in all tissues for high LET components of rays, such as alpha particles. The RBE factor is used to compare the biological effectiveness of different types of ionizing radiation. The high LET component includes protons generated from the normal tissue nitrogen-capture reaction, and proton recoil resulting from rapid neutron collisions with hydrogen. It should be emphasized that the tissue distribution of boron delivery agents in humans should be similar to those in animal models to use experimentally obtained values ​​to estimate radiation doses for clinical radiation. For more detailed information relating to the calculation of dosimetry and treatment planning, interested readers are referred to a comprehensive review of this.

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Boron delivery agent

The development of boron delivery agencies for BNCT began about 50 years ago and is a sustainable and difficult task with high priority. A number of shipping agents containing boron-10 have been prepared for potential use in BNCT. The most important requirements for a successful boron delivery agent are:

• low systemic toxicity and normal tissue uptake with high tumor uptake and tumor high simultaneously: to brain (T: Br) and tumor: to blood (T: Bl) concentration ratio (& gt; 3-4 : 1);
• tumor concentration in the tumor range ~ 20 Âμg ¹⁰ B/g;
• rapid clearance of blood and normal tissue and persistence of tumors during BNCT.

However, it should be noted that there are currently no single boron delivery agencies that meet all of these criteria. With the development of new chemical synthesis techniques and increased knowledge of the biological and biochemical requirements required for effective agents and means of delivery, a variety of new boron agents have emerged (see example in Table 1), but only two of these, boronophenylalanine (BPA) and sodium borocaptate (BSH) has been used clinically.

* These are two clinically used delivery agents for boron.
View Barth, RF, Mi, P., and Yang, W., Boron delivery agents for neutrons capture cancer therapy, Cancer Communications, in the media (doi: 10.1186/s40880-018-0299 -7) for an updated review.

A major challenge in the development of boron delivery agents is the requirement for targeting selective tumors to achieve sufficient boron concentration to produce radiation therapy doses at tumor sites with minimal radiation delivered to normal tissues. Selective cell tumor cell damage (glioma) in the presence of normal cells represents a greater challenge than malignancy at other sites in the body, because malignant glioma is highly infiltrative of normal, histologically diverse and heterogeneous brain in their genomic profile. In principle, NCT is a radiation therapy that can selectively deliver lethal doses of radiation to tumor cells while saving normal adjacent cells.

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Gadolinium neutron capture therapy (Gd NCT)

There is also an interest in the possibility of using gadolinium-157 ( ¹⁵⁷ Gd) as an arresting agent for NCT for the following reasons: First , and most importantly, there has been a very high portion of neutron capture from 254,000 barns. Secondly, gadolinium compounds, such as Gd-DTPA (gadopentetate dimeglumine MagnevistÃ,®), have been used routinely as contrast agents for magnetic resonance imaging (MRI) from brain tumors and have demonstrated high cell uptake brain tumor. in tissue culture ( in vitro ). Third , gamma rays and Auger's internal and electron conversion are the products of the ^<157 Gd (n ,?) ¹⁵⁸ catch reaction Gd ( ¹⁵⁷ Gd n _th (0,025eV) -> [ ¹⁵⁸ Gd] -> ¹⁵⁸ Gd? 7.94 MeV). Although gamma rays have longer path lengths, the depth of penetration depth is greater than that of alpha particles, other radiation products (internal conversion and Auger electrons) have a path length of about one cell diameter and can directly damage DNA. Therefore, it would be advantageous for the production of DNA damage if ¹⁵⁷ Gd is localized in the cell nucleus. However, the possibility of combining gadolinium into biologically active molecules is very limited and only a small number of potential delivery agents for Gd NCT have been evaluated. Relatively few studies with Gd have been conducted in animal experiments compared with large numbers with boron-containing compounds (Table 1), which have been synthesized and evaluated in experimental animals ( in vivo ). Although in vitro activity has been shown using MRI contrast agents containing Gd MagnevistÃ,® as Gd shipping agents, there are very few studies showing the efficacy of GD NCT in experimental animal tumor models, and Gd NCT. until now has never been used clinically in humans.

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Neutron Source

Nuclear reactor

Until now neutron sources for NCT have been limited to nuclear reactors and in this section we will only summarize the information described in more detail in the recently published reviews. The reactor-derived neutrons are classified according to their energy as thermals (E _n & lt; 0.5 eV), epithermal (0.5 eV & lt; E _n & lt; 10 keV) or fast (E _n & gt; 10 keV). Thermal neutrons are the most important for BNCT because they usually start a reaction capture ¹⁰ B (n ,?) ⁷ Li. However, since they have limited penetration depths, epithermal neutrons, which lose energy and fall into the thermal range when they penetrate the tissue, are not used for clinical therapy other than for skin tumors such as melanoma.

A number of excellent neutron beam nuclear reactors have been developed and used clinically. These include:

1. The Kyoto University Research Reactor Institute (KURRI) in Kumatori, Japan;
2. The Massachusetts Institute of Technology Research Reactor (MITR);
3. FiR1 research reactor (Triga Mk II) at VTT Technical Research Center, Espoo, Finland;
4. the RA-6 CNEA reactor in Bariloche, Argentina;
5. High Flux Reactor (HFR) at Petten in the Netherlands; and
6. Tsing Hua Open-pool Reactor (THOR) at Tsing Hua National University, Hsinchu, Taiwan.

However, since April 2018, only RA-6 reactors in Argentina and THOR reactors in Taiwan are currently used for clinical studies.

Although not currently used for BNCT, the neutron irradiation facility at MITR represents the state of the art in epithermal beams for NCT with the ability to complete the radiation field in 10-15 minutes with close to the theoretical maximum to the normal ratio of tumors. tissue dose. Unfortunately, however, no clinical studies are being conducted in HFR and MITR. Operation of the BNCT facility at the Finnish research reactor FiR1 (Triga Mk II), treating patients since 1999, was suspended in 2012 for various reasons, one of which is finance. It is estimated that future clinical studies in Finland will utilize a source of neutron accelerators designed and manufactured in the United States by Neutron Therapeutics. Finally, the low-power "low-power" hospital nuclear reactor has been designed and built in Beijing, China, and is currently used only to treat a small number of patients with skin melanoma.

Accelerator

Accelerators can also be used to produce epithermal neutrons and accelerator-based neutron sources (ABNS) are being developed in a number of countries. Interested readers refer to Proceedings that were recently published on the 16th and abstracts of the 17th International Congress on Neutron Taking Therapy for more information on this. For ABNS, one of the more promising nuclear reactions involves bombarding the ⁷ Li target with high energy protons. An experimental BNCT facility, using solid lithium solid targets, has been in use since the early 1990s at the University of Birmingham in the UK, but to date no clinical studies have been conducted at this facility, which utilizes high currents. The dynamitron accelerator was originally supplied by Radiation Dynamics.

Recently, a cyclotron-based neutron source (C-BENS) has been developed by Sumitomo Heavy Industries (SHI) in Japan. It has been installed at the Center for Particle Radiation Oncology at Kyoto University in Kumatori, Japan. It is currently being used in Phase I clinical trials to evaluate its safety to treat patients with high-grade gliomas. The second has been built by Mitsubishi Heavy Industries for use at Tsukuba University in Japan, but due to technical problems it is unlikely that it will ever be used for clinical studies. The third is being built by Hitachi for use in Tokyo. A fourth accelerator, produced by SHI, is located at the Southern Tohoku BNCT Research Center in Fukushima prefecture in Japan and is being used in Phase II clinical trials for BNCT recurrent brain tumors and head and neck cancers. Finally, the fifth, which in Spring 2018 is being installed at Helsinki University Hospital in Finland. This accelerator is designed and manufactured by Neutron Therapeutics in Danvers, Massachusetts. It is important to determine how ABNS is compared to BNCT that has been done in the past using nuclear reactors as a source of neutrons.

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BNCT clinical studies for brain tumors

Preliminary studies in the US and Japan

It was not until 1950 that the first clinical trial was initiated by Farr at Brookhaven National Laboratory (BNL) in New York and by Sweet and Brownell at Massachusetts General Hospital (MGH) using the Massachusetts Institute of Technology (MIT) nuclear reactor and some compounds boron with different low molecular weight as boron delivery agent. However, the results of this study were disappointing, and no further clinical trials were conducted in the United States until the 1990s.

After two years of Fulbright fellowship at Sweet laboratory at MGH, a clinical study was initiated by Hiroshi Hatanaka in Japan in 1967. He used low-energy thermal neutron rays, which possessed low tissue penetration properties, and sodium borocaptate (BSH) as boron delivery agents has been evaluated as a boron delivery agent by Albert Soloway at MGH. In the Hatanaka procedure, as much as possible the tumor is surgically removed ("debulking"), and at some later time, BSH is given by slow infusion, usually intra-arterial, but then intravenously. Twelve to 14 hours later, BNCT is conducted in one of several different nuclear reactors using low-energy thermal neutrons. The less tissue-penetrating properties of the thermal neutron rays necessitate reflecting the skin and lifting the bone cover to directly illuminate the open brain, the procedure first used by Sweet and his colleagues.

About 200 patients were treated by Hatanaka, and later by his colleague Nakagawa. Due to the heterogeneity of the patient population, in terms of tumor microscopic diagnosis and grade, size, and ability of patients to perform normal daily activities (Karnofsky's performance status), it is impossible to come up with a definite conclusion about therapeutic efficacy. However, survival data were no worse than those obtained by standard therapy at the time, and there were some long-term survivors, and most likely they recovered from their brain tumors.

Latest clinical studies in the US and Japan

BNCT patients with brain tumors returned in the United States in the mid-1990s by Chanana, Diaz, and Coderre and their colleagues at the Brookhaven National Laboratory Medical Research Reactor (BMRR) and at Harvard/Massachusetts Institute of Technology (MIT)) using MIT Research Reactor (MITR). For the first time, BPA is used as a boron delivery agent, and patients are irradiated with collimator light from high-energy epithermal neutrons, which have greater tissue penetration properties than thermal neutrons. A research group led by Zamenhof at Beth Israel Deaconess Medical Center/Harvard Medical School and MIT was the first to use epithermal neutron rays for clinical trials. Initially patients with skin melanoma were treated and this was extended to include patients with brain tumors, particularly metastatic melanoma to the brain and primary glioblastoma (GBMs). Included in the research team are Otto Harling at MIT and Paul Busse's Oncologist Radiation at Beth Israel Deaconess Medical Center in Boston. A total of 22 patients were treated by the Harvard-MIT research group. Five patients with skin melanoma were treated using epithermal neutron rays at the MIT research reactor (MITR-II) and then patients with brain tumors were treated using redesigned rays at MIT reactors that had far superior characteristics with original MITR-II rays, and BPA as arresting agents. The clinical outcomes of cases treated at Harvard-MIT have been summarized by Busse. Although treatment was well tolerated, there was no significant difference in the mean survival time of patients who had received BNCT compared with those receiving conventional external X-irradiation rays.

Miyatake and Kawabata at Osaka Medical College in Japan have conducted extensive clinical studies using a combination of BPA (500 mg/kg) and BSH (100 mg/kg), infused intravenously (iv) for 2 hours, followed by neutron irradiation at Kyoto Reactor Institute Research University (KURRI). Mean Survival Time (MST) of 10 patients in their first trial was 15.6 months, with one long-term survivor (& gt; 5 years). Based on experimental animal data, which shows that BNCT in combination with X-irradiation results in improved survival compared with BNCT alone, Miyatake and Kawabata combined BNCT, as described above, with X-ray impulse. A total dose of 20 to 30 Gy is given, divided into 2 Gy daily fractions. The MST of this patient group was 23.5 months and no significant toxicity was observed, other than hair loss (alopecia). However, the vast majority of these patients, high proportions have small cell variant glioblastoma, developing a spreading of cerebrospinal fluid from their tumors. In other Japanese experiments, conducted by Yamamoto et al., BPA and BSH were infused for 1 hour, followed by BNCT in the Japanese Reactor Reactor (JRR) -4 reactor. The patient then received an X-ray enhancement after the completion of BNCT. The median overall survival time (MeST) was 27.1 months, and the survival rates of 1 year and 2 years were 87.5 and 62.5%, respectively. Based on Miyatake, Kawabata, and Yamamoto reports, it seems that combining BNCT with X-ray impulses can generate significant therapeutic benefits. However, further research is needed to optimize this combination therapy alone or in combination with other approaches including chemotherapy and immunotherapy, and to evaluate it using a larger patient population.

Clinical studies in Finland

A team of doctors led by Heikki Joensuu and Leena Kankaanranta and nuclear engineers led by Iro Auterinen at the Helsinki University Central Hospital and Finland's VTT Technical Research Center have treated approximately 200 patients with recurrent glioma glioma (glioblastoma) and head and neck cancers undergo standard therapy, relapse, and then receive BNCT at the time of their recurrence using BPA as a boron delivery agent. The median time for progression in patients with glioma is 3 months, and the overall MEST is 7 months. It is difficult to compare these results with other results reported in patients with recurrent malignant glioma, but they are a starting point for future studies using BNCT as a rescue therapy in patients with recurrent tumors. For various reasons, including finance, no further research is undertaken at this facility, which is scheduled for decommissioning. However, the new facility for BNCT treatment will be opened at Meilahti Tower Hospital in 2018 using an accelerator designed and manufactured by Neutron Therapeutics, Danvers, MA. The hospital will be the first BNCT accelerator house ever designed for hospital use, and BNCT treatment and clinical studies will continue there. Finnish and foreign patients are expected to be treated at the facility.

Clinical studies in Sweden

Finally, to summarize this section, the following is a brief summary of the clinical trials conducted by Stenstam, SkÃÆ'¶ld, Capala and their colleagues in Sweden using BPA and epithermal neutron rays in the Studsvik nuclear reactor, which has greater network penetration properties rather than the thermal block originally used in Japan. This study differed significantly from all previous clinical trials that the total amount of BPA administered increased (900 mg/kg), and it was infused i.v. more than 6 hours. This is based on research on animal experiments in glioma mice that show an increase in BPA absorption by infiltration tumor cells after a 6-hour infusion. The longer infusion time of BPA was well tolerated by the 30 patients enrolled in the study. All were treated with 2 fields, and the mean overall brain dose was 3.2-6.1 Gy (weighted), and the minimum dose for tumors ranged from 15.4 to 54.3 Gy (w). There is some disagreement among Swedish researchers regarding the evaluation of results. Based on incomplete survival data, MeST was reported as 14.2 months and the time for tumor development was 5.8 months. However, a more careful examination of complete survival data revealed that MeST was 17.7 months compared with the 15.5 months reported for patients receiving standard surgery therapy, followed by radiotherapy (RT) and temozolomide (TMZ). Furthermore, the frequency of adverse events was lower after BNCT (14%) than after radiation therapy (21%) and both were lower than those seen after RT in combination with TMZ. If this improves survival data, obtained by using higher doses of BPA and 6 hours infusion time, can be confirmed by others, preferably in randomized clinical trials, it could represent a significant step forward in brain tumor BNCT, especially if combined with photon boost.

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BNCT Clinical Study for extracranial tumors

Head and neck cancer

The single most important clinical advance over the past 13 years is the application of BNCT to treat patients with recurrent tumors in head and neck areas that have failed in all other therapies. These studies were first initiated by Kato et al. in Japan and later followed by several other Japanese groups and by Kankaanranta, Joensuu, Auterinen, Koivunoro and their co-workers in Finland. All of these studies use BPA as a boron delivery agent, either alone or in combination with BSH. A group of very heterogeneous patients with various histopathological types of tumors have been treated, the largest number of recurrent squamous cell carcinomas. Kato et al. has reported on a series of 26 patients with advanced cancer who have no further treatment options. Neither the BPA BSH or the CPA itself is managed by 1 or 2 hours i.v. infusion, and this was followed by BNCT using epithermal rays. In this series, there is complete regression in 12 cases, 10 partial regressions, and progression in 3 cases. MST is 13.6 months, and 6 years survival is 24%. Significant treatment - related complications ("harm" events) include temporary mucositis, alopecia and, rarely, brain necrosis and osteomyelitis.

Kankaanranta et al. have reported their results in a prospective Phase I/II study of 30 patients with inoperable and nonoperable recurrent squamous cell carcinoma in the head and neck region. Patients received two or, in some cases, one BNCT treatment using BPA (400 mg/kg), administered i.v. more than 2 hours, followed by irradiation of neutrons. Of the 29 patients evaluated, there were 13 complete and 9 remissions, with an overall response rate of 76%. The most common side effects are oral mucositis, oral pain, and fatigue. Based on clinical results, it was concluded that BNCT was effective for the treatment of inoperable patients, previously irradiated with head and neck cancers. Some responses last long but are common, usually in a recurrent tumor site. As mentioned earlier in the neutron source section, all clinical studies have ended in Finland, based on a variety of reasons including the economic difficulties of two directly involved companies, VTT and Boneca. However, there are plans to continue clinical studies using neutron accelerator sources designed and manufactured by Neutron Therapeutics. Finally, a group in Taiwan, led by Ling-Wei Wang and colleagues at the Taipei Veterans General Hospital, treated 17 patients with recurrent head and neck cancer at Tsing Hua Open-pool Reactor (THOR) from National University Tsinghua. The overall two-year survival was 47% and the two-year-old local controls were 28%. Further studies are underway to further optimize their treatment regimen.

Another type of tumor

Melanoma

Other treated extracranial tumors include malignant melanoma, originally performed in Japan by the late Yutaka Mishima and his clinical team at the Dermatology Department at Kobe University using BPA and thermal neutron rays. It is important to point out that it was Mishima who first used BPA as a boron delivery agent and this was later extended to other types of tumors based on the experimental study of Coderre et al. at the Brookhaven National Laboratory. Local control is achieved in almost all patients, and some recover from their melanoma. Recently, Junichi Hiratsuka and his colleagues at Kawasaki Medical School Hospital have treated patients with melanoma in the head and neck, vulva, and Paget's extramammary areas in the genital area with impressive clinical outcomes. The first clinical trial of BNCT in Argentina for melanoma treatment was conducted in October 2003 and since then some patients with skin melanoma have been treated as part of a Phase II clinical trial at the RA-6 nuclear reactor in Bariloche. The neutron beam has a thermal-hyperthermal neutron spectrum mixture that can be used to treat superficial tumors. Finally, as recently reported, Beijing's neutron irradiator (IHNI) in Beijing has been used to treat three patients with skin melanoma with a complete response of primary lesions and no evidence of delayed radiation injury over the next 24 months. up period. The main objective of the group in Beijing is to initiate multi-institutional randomized clinical trials to evaluate BNCT melanoma.

Colorectal cancer

Two patients with colon cancer, which has spread to the liver, have been treated by Zonta and colleagues at the University of Pavia in Italy. The first was admitted in 2001 and the second in mid-2003. The patients received i.v. infusion of BPA, followed by liver removal (hepatectomy), which is irradiated outside the body (extracorporeal BNCT) and then transplanted back into the patient. The first patient performed very well and survived for more than 4 years after treatment, but the second died within a month due to cardiac complications. Obviously, this is a very challenging approach to the treatment of liver metastasis, and it's unlikely that it will ever be widely used. However, a good clinical outcome in the first patient establishes the proof of principle . Finally, Yanagie and his colleagues at Meiji Pharmaceutical University in Japan have treated several patients with recurrent rectal cancer using BNCT. Although no long-term results are reported, there is evidence of short-term clinical response.

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Conclusion

BNCT is a combination of nuclear, chemical, biological, and medicinal technology to treat brain tumors, recurrent head and neck cancer, and skin melanoma and extrasutane. Unfortunately, the lack of progress in developing more effective treatments for these tumors has been part of the driving force that continues to drive research in this area. BNCT may be best suited as adjuvant treatment, used in combination with other modalities, including surgery, chemotherapy, immunotherapy, and external beam radiation therapy for malignancy, whether primary or recurrent, for which no effective therapy is possible. Clinical studies have demonstrated the safety of BNCT. The challenge facing doctors and researchers is how to move forward. A significant advantage of BNCT is the potential ability to selectively deliver doses of radiation to tumors at much lower doses to surrounding normal tissues. This is an important feature that makes BNCT very attractive for patient rescue therapy with many irradiated malignancies. Although palliative may be palliative, BNCT may produce a marked clinical response, as evidenced by the experience of some groups treating patients with recurrent and therapeutic head and neck cancers.

Challenges that need to be addressed include:

1. Optimize dosage and administration paradigms of BPA and BSH.
2. Development of more selective boron tumor-delivery agents for BNCT.
3. Accurate, real-time dosimetry to estimate the radiation dose delivered to tumors and normal tissues better.
4. Evaluation of new accelerator-based neutron sources is built as an alternative to nuclear reactors.

For a more detailed discussion of these challenges and their solutions at BNCT, readers are referred to the published abstracts of the 17th International Congress on Neutron Pick Up Therapy, two reviews of the current status of BNCT, and recent comments providing a realistic assessment of the BNCT Failure. If the above-mentioned problems can be resolved, BNCT could have an important role in the treatment of twenty-first-century cancer from loco-regional malignancies and which today can not be cured by other therapeutic modalities.

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See also

• Particle therapy, Neutrons, protons or heavy ions (eg carbon)
  • Rapid neutron therapy
  • Proton therapy

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References

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External links

• Helsinki University Central Hospital and Technical Research Center of Finland's BNCT Project
• Therapeutic Removal of Boron and Gadolinium Neutrons for Cancer Treatment
• Overview of MIT Reactor Lab from BNCT
• Nuclear Radiation Center Washington State University, BNCT Review

Source of the article : Wikipedia