Fast neutron therapy
Overview
Fast neutron therapy utilizes high energy neutrons typically greater than 20 MeV to treat cancer. Most fast neutron therapy beams are produced from proton beams impinging upon beryllium targets.
Advantages
Radiation therapy of cancers is based upon the biological response of cells to ionizing radiation. Tumor cells typically lack effective repair mechanisms, so if radiation is delivered in small sessions, a process known as fractionation, normal tissue will have time to repair itself. This repair of normal tissue means that there is a therapeutic ratio between cancer cells and normal cells.[1]
In addition, different types of ionizing radiation will produce different effects upon cells. A comparison of neutrons with X-rays illustrates the differences. X-rays are the most common form of radiation used to treat cancer. Both neutrons and X-rays are uncharged; for this reason they are referred to as indirectly ionizing radiation. The biological effect of neutrons or X-rays is due almost completely to the secondary electrons that they produce when they interact with a patient's tissue.
LET
When therapeutic energy X-rays (1 to 25 MV) interact with cells in human tissue, they do so mainly by Compton interactions, and produce relatively high energy secondary electrons. These high energy electrons deposit their energy at about 1 KeV/µm.[2] By comparison, the charged particles produced at a site of a neutron interaction may deliver their energy at a rate of 30-80 KeV/µm. The amount of energy deposited as the particles traverse a section of tissue is referred to as the Linear Energy Transfer (LET). X-rays produce low LET radiation, and neutrons produce high LET radiation.
Because the electrons produced from X-rays have high energy and low LET, when they interact with a cell typically only a few ionizations will occur. It is likely then that the low LET radiation will cause only single strand breaks of the DNA helix. Single strand breaks of DNA molecules can be readily repaired, and so the effect on the target cell is not necessarily lethal. By contrast, the high LET charged particles produced from neutron irradiation cause many ionizations as they traverse a cell, and so double strand breaks of the DNA molecule are possible. Double strand DNA breaks are much more difficult for a cell to repair, and more likely to lead to cell death.
DNA repair mechanisms are quite efficient,[3] and during a cell's lifetime many thousands of double strand DNA breaks will be repaired. A sufficient dose of ionizing radiation, however, delivers so many DNA breaks that it overwhelms the capability of the cellular mechanisms to cope.
Heavy ion therapy (e.g. carbon ions) makes use of the similarly high LET of 12C6+ ions.[4][5] Because of the high LET, the relative radiation damage (relative biological effect or RBE) of fast neutrons is 4 times that of X-rays,[6][7]meaning 1 rad of fast neutrons is equal to 4 rads of X-rays. The RBE of neutrons is also energy dependent, so neutron beams produced with different energy spectra at different facilities will have different RBE values.
Oxygen effect
The presence of oxygen in a cell acts a radiosensitizer, making the effect of the radiation more damaging. Tumor cells typically have a lower oxygen content than normal tissue (hypoxia) and therefore the oxygen effect acts to increase the sensitivity of normal tissue.[8] Generally it is believed that neutron irradiation overcomes the effect of tumor hypoxia,[9] although there are counterarguments[10]
Clinical uses
The efficacy of neutron beams for use on prostate cancer has been shown through randomized trials.[11][12][13] Fast neutron therapy has been applied successfully against salivary gland tumors.[14][15][16][17][18][19][20] See also the NCI Salivary Cancer Page. Adenoid Cystic Carcinomas have also been treated.[21][22] Various other head and neck tumors have been examined.[23][24][25]
Fast neutron centers
Several centers around the world have used fast neutrons for treating cancer. Due to lack of funding and support, at present only 2 are active in the USA. The University of Washington and the Gershenson Radiation Oncology Center operate fast neutron therapy beams and both are equipped with a Multi-Leaf Collimator (MLC) to shape the neutron beam.[26][27][28]
University of Washington
The University of Washington operates a proton cyclotron that produces fast neutrons from directing 50.5MeV protons onto a beryllium target. The University of Washington Cyclotron is equipped with a gantry mounted delivery system an MLC to produce shaped fields. the University of Washington Neutron system is referred to as the Clinical Neutron Therapy System (CNTS).
The CNTS is typical of most neutron therapy systems. A large, well shielded building is required to cut down on radiation exposure to the general public and to house the necessary equipment.
A beamline transports the proton beam from the cyclotron to a gantry system. The gantry system contains magnets for deflecting and focusing the proton beam onto the beryllium target. The end of the gantry system is referred to as the head, and contains dosimetry systems to measure the dose, along with the MLC and other beam shaping devices. The advantage of having a beam transport and gantry are that the cyclotron can remain stationary, and the radiation source can be rotated around the patient. Along with varying the orientation of the treatment couch which the patient is positioned on, variation of the gantry position allows radiation to be directed from virtually any angle, allowing sparing of normal tissue and maximum radiation dose to the tumor.
During treatment, only the patient remains inside the treatment room (called a vault) and the therapists will remotely control the treatment via video cameras. Each delivery of a set neutron beam geometry is referred to as a treatment field or beam. The treatment delivery is planned to deliver the radiation as effectively as possible, and usually results in fields that conform to the shape of the gross target, with any extension to cover microscopic disease.
Detroit
The Gershenson Radiation Oncology Center at Harper University Hospital in Detroit is the only other neutron therapy center in the USA equipped with an MLC beam shaping device.
The WSU radiotherapy team has more experience than anyone in the world using the neutron cyclotron for prostate cancer, having treated nearly 1,000 patients during the past 10 years.
The third-generation neutron cyclotron combines three-dimensional treatment planning with a type of collimator that tailors the beam of radiation to the exact size, shape and location of each person's tumor.
FermiLab
The Fermilab neutron therapy center first treated patients in 1976,[29] and since that time has treated over 3000 patients.
External links
- University of Washington Radiation oncology department
- UWMC SCCA Site
- FermiLab Neutron Therapy
- Gershenson Radiation Oncology Center
- Michigan State Therapy NSCL
References
- ↑ Hall EJ. Radiobiology for the Radiologist. Lippincott Williams & Wilkins; 5th edition (2000)
- ↑ Johns HE and Cunningham JR. The Physics of Radiology. Charles C Thomas 3rd edition 1978
- ↑ Goodsell DS. Fundamentals of Cancer Medicine The Molecular Perspective: Double-Stranded DNA Breaks The Oncologist, Vol. 10, No. 5, 361-362, May 2005
- ↑ Kubota N, Suzuki M, Furusawa Y, Ando K, Koike S, Kanai T, Yatagai F, Ohmura M, Tatsuzaki H, Matsubara S, et al. A comparison of biological effects of modulated carbon-ions and fast neutrons in human osteosarcoma cells. International Journal of Radiation Oncology*Biology*Physics, Volume 33, Issue 1, 30 August 1995, Pages 135-141
- ↑ http://www.dkfz-heidelberg.de/index.html
- ↑ Pignol JP, Slabbert J and Binns P. Monte Carlo simulation of fast neutron spectra: Mean lineal energy estimation with an effectiveness function and correlation to RBE. International Journal of Radiation Oncology*Biology*Physics, Volume 49, Issue 1, 1 January 2001, Pages 251-260
- ↑ Theron T, Slabbert J, Serafin A and Böhm L. The merits of cell kinetic parameters for the assessment of intrinsic cellular radiosensitivity to photon and high linear energy transfer neutron irradiation. International Journal of Radiation Oncology*Biology*Physics, Volume 37, Issue 2, 15 January 1997, Pages 423-428
- ↑ Vaupel P, Harrison L. Tumor Hypoxia: Causative Factors, Compensatory Mechanisms, and Cellular Response The Oncologist 2004;9(suppl 5):4-9
- ↑ Wambersie A, Richard F, Breteau N. Development of fast neutron therapy worldwide. Radiobiological, clinical and technical aspects. Acta Oncol. 1994;33(3):261-74.
- ↑ Warenius HM, White R, Peacock JH, Hanson J, Richard A. Britten, Murray D. The Influence of Hypoxia on the Relative Sensitivity of Human Tumor Cells to 62.5 MeV (p?Be) Fast Neutrons and 4 MeV Photons. Radiation Research 154, 54-63 (2000)
- ↑ Russell KJ, Caplan RJ, Laramore GE, et al. Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial. International Journal of Radiation Oncology, Biology, Physics 28(1): 47-54, 1993.
- ↑ Haraf DJ, Rubin SJ, Sweeney P, Kuchnir FT, Sutton HG, Chodak GW and Weichselbaum RR. Photon neutron mixed-beam radiotherapy of locally advanced prostate cancer. International Journal of Radiation Oncology*Biology*Physics, Volume 33, Issue 1, 30 August 1995, Pages 3-14
- ↑ Forman J, Ben-Josef E, Bolton SE, Prokop S and Tekyi-Mensah S . A randomized prospective trial of sequential neutron-photon vs. photon-neutron irradiation in organ confined prostate cancer. International Journal of Radiation Oncology*Biology*Physics, Volume 54, Issue 2, Supplement 1, 1 October 2002, Pages 10-11
- ↑ Douglas JD, Koh WJ , Austin-Seymour, M, Laramore GE. Treatment of Salivary Gland Neoplasms with fast neutron Radiotherapy. Arch Otolaryngol Head Neck Surg Vol 129 944-948 Sep 2003
- ↑ Laramore GE, Krall JM, Griffin TW, Duncan W, Richter MP, Saroja KR, Maor MH, Davis LW. Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Int J Radiat Oncol Biol Phys. 1993 Sep 30;27(2):235-40.
- ↑ Laramore GE. Fast neutron radiotherapy for inoperable salivary gland tumors: is it the treatment of choice?Int J Radiat Oncol Biol Phys. 1987 Sep;13(9):1421-3.
- ↑ Prott FJ, Micke O, Pötter R, Haverkamp U, Schüller P and Willich N. 2137 Results of fast neutron therapy of adenoid cystic carcinoma of the salivary glands. International Journal of Radiation Oncology*Biology*Physics, Volume 39, Issue 2, Supplement 1, 1997, Page 309
- ↑ Saroja KR, Mansell J, Hendrickson FR, et al.: An update on malignant salivary gland tumors treated with neutrons at Fermilab. Int J Radiat Oncol Biol Phys 13 (9): 1319-25, 1987.
- ↑ Buchholz TA, Laramore GE, Griffin BR, et al.: The role of fast neutron radiation therapy in the management of advanced salivary gland malignant neoplasms. Cancer 69 (11): 2779-88, 1992.
- ↑ Krüll A, Schwarz R, Engenhart R, et al.: European results in neutron therapy of malignant salivary gland tumors. Bull Cancer Radiother 83 (Suppl): 125-9s, 1996
- ↑ http://www.rare-cancer.org/adenoid-cystic-carcinoma/lara.html
- ↑ Douglas JG, Laramore GE, Austin-Seymour M, Koh WJ, Lindsley KL, Cho P and Griffin TW. Neutron radiotherapy for adenoid cystic carcinoma of minor salivary glands. International Journal of Radiation Oncology*Biology*Physics, Volume 36, Issue 1, 1 August 1996, Pages 87-93
- ↑ MacDougall RH, Orr JA, Kerr GR, and Duncan W. Fast neutron treatment for squamous cell carcinoma of the head and neck: final report of Edinburgh randomised trial. BMJ. 1990 December 1; 301(6763): 1241-1242.
- ↑ Asgarali S, Errington RD, Jones AS. The treatment of recurrence following fast neutron therapy for head and neck malignancy. Clin Otolaryngol Allied Sci. 1996 Jun;21(3):274-7.
- ↑ K.J. Stelzer, K.L. Lindsley, P.S. Cho, G.E. Laramore and T.W. Griffin. Fast Neutron Radiotherapy: The University of Washington Experience and Potential Use of Concomitant Boost with Boron Neutron Capture. Radiation Protection Dosimetry 70:471-475 (1997)
- ↑ Brahme A, Eenmaa J, Lindback S, Montelius A, Wootton P. Neutron beam characteristics from 50 MeV protons on beryllium using a continuously variable multi-leaf collimator. Radiother Oncol. 1983 Aug;1(1):65-76.
- ↑ Farr JB. A compact multileaf collimator for conventional and intensity modulated fast neutron therapy Medical Physics April 2004 Volume 31, Issue 4, p. 951
- ↑ Farr JB, Maughan RL, Yudelev M, Blosser E, Brandon J, Horste T Compact multileaf collimator for conformal and intensity modulated fast neutron therapy: Electromechanical design and validation Medical Physics -- September 2006 -- Volume 33, Issue 9, pp. 3313-3320
- ↑ Cohen L and Lennox A. Midwest Institute for Neutron Therapy at Fermilab. International Journal of Radiation Oncology*Biology*Physics, Volume 34, Issue 1, 1 January 1996, Page 269