BORON NEUTRON CAPTURE THERAPY (BNCT)
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JAIME G.GOMEZ,M.D.

12/1/98

NCT is an experimental form of treatment that requires the infusion of an element such as Boron or Gadolinium and exposure of the patient to a Neutron Beam from a nuclear reactor. At the present time there are two targets: Glioblastoma, a highly malignant tumor whose treatment is not satisfactory and Malignant Melanoma.

Conventional treatment includes surgical resection or biopsy, six weeks of radiotherapy and chemotherapy. Best average survival is 53 weeks. At the end of five years, only 5% survive. Glioblastoma has been chosen because it is a highly malignant tumor, of short evolution and no extracranial metastasis.

Pharmacological compounds to be administered require a high therapeutic index with affinity and selectivity for the tumor and low concentration in the normal tissue. Usually the rapidly dividing malignant cells take the pharmacological compound in greater amounts that the normal tissue. Neurons usually do not captate the drug because they do not divide.

At present time, the only source of Neutrons are modified Nuclear Reactors. Experience has shown that the use of epithermal neutrons with power between 0.5 eV and 10 LeV pass trough the scalp and skull . This avoids the need for intraoperative NCT.

When neutrons are captured by the malignant cells loaded with Boron or Gadolinium, a high energy fission reaction occurs. Fortunately it extends only five to ten microns away. In the first case the fission produces Alpha and Gamma rays, Lithium, Hydrogen and Nitrogen. When Gadolinium is used, Auger electrons and Gamma rays alter the DNA of the malignant cells. Neutrons are spared. This is particular useful for children with brain tumors. NCT does not produce mental retardation as conventional Radiotherapy.

The exposure to a beam of epithermal Neutrons 10E9 n/cm2/sec with less than 10E-13 Gy. of Gamma Rays and fast neutrons is usually given in one session of 50 minutes.

At present there are six nuclear reactors for NCT: New York, Boston, Tokyo, Kyoto, Petten in Holland and now Helsinki. In the USA plans for modification of reactors at Davis-McLlelan, New Hampshire, Columbia (Missouri) Washington y Rhode Island have been proposed. Other sites would be the Czech Republic, Italy, Portugal, Argentina, Brazil and Russia,

An interesting alternative would be the development of Neutron generators. Research on the modification of linear accelerators at Berkley ,Birmingham (UK), Texas, Italy and Japan probably could be adapted for NCT treatment of Malignant Brain Tumors, Melanoma and other form of cancer at Medical Centers.

Treatment planning is made with special computer software, in which information on the neutron beam from the nuclear reactor beam, concentration of the drug in blood and the medical images are introduced. The computer calculates the doses and recommends the treatment.

There are three types of programs:

  1. Montecarlo from los Alamos
  2. Mac-NCT from Boston MIT/Harvard and
  3. SERA, from INEL/Montana

NCT require an extensive resection of the tumor. One week later CT/MRI are repeated. These images are introduced in the computer for the treatment planning. On the ten day an intravenous infusion of the pharmacological agent is given in one or two hours. Blood samples taken every 20 minutes. After 20 minutes of radiation the reactor is shut down. A blood sample is taken to test the amount of drug in the blood. After this is accomplished and data is introduced into the computer, the irradiation is restarted. Treatment lasts about 50 minutes. It is given only once.

The patient is observed for 24 or 48 hours at the intensive care unit. Then is discharged home. Monthly medical images are taken looking for recurrence of the tumor or late toxicity from radiation,

Results

GBM cases treated in Boston and New York by Harvard Professor of Neurological Surgery, Dr William H Sweet. Results were not satisfactory. The initial pharmacological compounds were e not specific, the thermal neutrons did not have enough penetration and there was no computerized treatment planning.

Dr. Sweets'disciple, the Japanese Neurosurgeon Dr. Hiroshi Hatanaka learned the technique and modified it. He used a second generation Boron compound called BSH and performed intraoperative NCT. Thermal neutron radiation was given with the open skull.

Boron concentration of 26 ppm, were obtained and a dose of 18 Gy with a Neutron flux of 1.9x10E13 n/cm2/sec. was given, Dr. Hatanaka presented the results of his work from 1968 to 1993 at the International Congress of Neurological surgery in Acapulco, Mexico. Hatanaka died in 1994 but his disciples have continued hs work in Tokyo and Kyoto,

Nakagawa et al. reported at the 8th International seminar of NCT for cancer held in La Jolla, California, (September 13-18, 1998) the following results: 201 patients with brain tumors have received treatment. 81 Glioblastoma, 45 Anaplásic Astrocitomas , 8 Brain stem gliomas, 6 meningiomas and other tumors.

Forty out of 201 were alive at the end of three years. Ten survived more than ten years. There were 19 cases of late radiation toxicity. Three of them were patients which received previous Radiotherapy.

At Brookhaven National Laboratory, as reported By Diaz et al at the same meeting, 40 Glioblastoma patients have been treated. Phase I and II demonstrated NCT is not toxic. With low Neutron dose radiation (8-17 Gy-Eq), NCT has a similar result as conventional treatment. 12 months survival is 12.9%. New protocols to increase the dose are prepared.

Three cases were worse after NCT. Convulsions and cerebral edema required special treatment. Maximum tumor volume plus edema plus a 2 cm. zone in the periphery of the mass seen at the medical images was irradiated with an average of 29 Gy-Eq.

The European Consortium has treated the first group of ten patients in Petten, Holland. BSH four sessions of epithermal neutrons and four doses of BSH were given. The new group from Finland plans to use BPA in four sessions.

Recurrence or Radionecrosis

Symptoms appearing after NCT may due to regrowth of the tumor or to late toxicity Radionecrosis. Differentiation between these two conditions is important: PET scanner, SPECT with Gallium, Magnetic Resonance Spectroscopy may help to differentiate the culprit. Some times however, a Stereotactic biopsy may give the clue.

  1. NCT is a promising method for the treatment of cancer.
  2. Low neutron doses treatment proved similar results that conventional treatment for Glioblastoma
  3. No toxicity has been seen in experimental clinical trials in New York and Boston.
  4. Escalation with higher doses of neutrons and new pharmacological compounds may result in a cure for cancer
  5. Development of neutron generators will male NCT available at the hospital level in the near future.
  6. Research is required for other types of cancer: lung, prostate, kidney, breast, pancreas, etc. .

Index words
Glioblastoma Multiforme.
Anaplasic Astrocitoma
Neutron Capture Therapy
Neutrons
Cancer

References

Busse PM, Kaplan I, Zamenhof R, et al: BNCT for GBM and intracranial metastatic melanoma: clinical results of the Harvard-MMI, Phase I trial [Abstr V2. 8o. International Symposium on NCT for Cancer, La Jolla, Ca, Sept. 1998]

Diaz AZ, Capala J, Ma R, et al: Patterns of tumor progression following BNCT of GBM [Abstr V5. 8o. International Symposium on NCT for Cancer, La Jolla, Ca, Sept. 1998]

Elowitz EH, Capala J, Coderre JA, et al: Case studies of patients with Glioblastoma Multiforme treated with Boron Neutron Capture therapy at the Brookhaven Research Reactor. [Abstr V1. 8o. International Symposium on NCT for Cancer, La Jolla, Ca, Sept. 1998] Gomez JG: Glioblastoma Multiforme, Medico (New York) June 1995 [Sp] Gomez JG: La captura atomos Boro con neutrones Medico (New York) June, 1996 [Sp]

Gomez JG: Melanoma maligno, Medico (New York) 1997 [Sp]

Gomez JG: Tratamiento del Cancer con Captura Neutrons, Rev Medicina (Bogota) 19: 27-31, 1997 [Sp] Hatanaka, H: analysis of clinical results of long surviving brain tumor patients who underwent Boron-neutron-capture therapy with mercapto undeca hydrocarborate. {Abs; X International Congress of Neurosurgery, Acapulco Mexico 1993, pp 199

Hideghety K, Sauerwein W, Vries M, et al: Report of the first patient group of the European Phase I trial (EORTC, protocol 11961) at the high flux reactor, Petten [Abstr V3. 8o. International Symposium on NCT for Cancer, La Jolla, Ca, Sept. 1998]

Sweet WH: Practical problems in the past in the use of boron-slow neutron capture therapy in the treatment of Glioblastoma Multiforme In Fairchild et al (eds) Proceedings of the First International Symposium on Neutron Capture Therapy. Upton, Brookhaven National Laboratory 1983, pp 376-378


 

JAIME G GOMEZ, M.D. 

5353 N Federal Highway  (Suite 210) 
Ft. Lauderdale, FL 33308, USA 
Tel (954) 776-6777 
FAX (954) 776-6852 
E-mail: JIMGOM@aol.com




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