Fast neutron therapy

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.

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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.

• University of Washington Radiation oncology department
• UWMC SCCA Site
• FermiLab Neutron Therapy
  • FermiLab Neutron Therapy overview
• Gershenson Radiation Oncology Center
• Michigan State Therapy NSCL

References