Fast neutron therapy
Fast neutron therapy utilizes high energy neutrons between 50 and 70 MeV to treat cancer. Most fast neutron therapy beams are produced by reactors and linear accelerators. Neutron therapy is available in Germany, South Africa and the United States. In the United States, three treatment centers are operational in Seattle, Detroit and Batavia, Illinois; the Detroit and Seattle centers use a cyclotron which produces a proton beam impinging upon a beryllium target. Radiation therapy kills cancer cells in two ways depending on the effective energy of the radiative source; the amount of energy deposited as the particles traverse a section of tissue is referred to as the linear energy transfer. X-rays produce low LET radiation, protons and neutrons produce high LET radiation. Low LET radiation damages cells predominantly through the generation of reactive oxygen species, see free radicals; the neutron is uncharged and damages cells by direct effect on nuclear structures. Malignant tumors thus can be resistant to low LET radiation.
This gives an advantage to neutrons in certain situations. One advantage is a shorter treatment cycle. To kill the same number of cancerous cells, neutrons require one third the effective dose as protons. Another advantage is the established ability of neutrons to better treat some cancers, such as salivary gland, adenoid cystic carcinomas and certain types of brain tumors high-grade gliomas When therapeutic energy X-rays interact with cells in human tissue, they do so by Compton interactions, produce high energy secondary electrons; these high energy electrons deposit their energy at about 1 keV/µm. 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. X-rays produce low LET radiation, neutrons produce high LET radiation; because the electrons produced from X-rays have high energy and low LET, when they interact with a cell only a few ionizations will occur.
It is then that the low LET radiation will cause only single strand breaks of the DNA helix. Single strand breaks of DNA molecules can be repaired, so the effect on the target cell is not lethal. By contrast, the high LET charged particles produced from neutron irradiation cause many ionizations as they traverse a cell, so double-strand breaks of the DNA molecule are possible. DNA repair of double-strand breaks are much more difficult for a cell to repair, more to lead to cell death. DNA repair mechanisms are quite efficient, during a cell's lifetime many thousands of single strand DNA breaks will be repaired. A sufficient dose of ionizing radiation, delivers so many DNA breaks that it overwhelms the capability of the cellular mechanisms to cope. Heavy ion therapy makes use of the high LET of 12C6+ ions; because of the high LET, the relative radiation damage of fast neutrons is 4 times that of X-rays, meaning 1 rad of fast neutrons is equal to 4 rads of X-rays. The RBE of neutrons is energy dependent, so neutron beams produced with different energy spectra at different facilities will have different RBE values.
The presence of oxygen in a cell acts as a radiosensitizer, making the effects of the radiation more damaging. Tumor cells have a lower oxygen content than normal tissue; this medical condition is known as tumor hypoxia and therefore the oxygen effect acts to decrease the sensitivity of tumor tissue. The oxygen effect may be quantitatively described by the Oxygen Enhancement Ratio, it is believed that neutron irradiation overcomes the effect of tumor hypoxia, although there are counterarguments The efficacy of neutron beams for use on prostate cancer has been shown through randomized trials. Fast neutron therapy has been applied against salivary gland tumors. Adenoid cystic carcinomas have been treated. Various other head and neck tumors have been examined. No cancer therapy is without the risk of side effects. Neutron therapy is a powerful nuclear scalpel that has to be utilized with exquisite care. For instance, some of the most remarkable cures it has been able to achieve are with cancers of the head and neck.
Many of these cancers cannot be treated with other therapies. However, neutron damage to nearby vulnerable areas such as the brain and sensory neurons can produce irreversible brain atrophy, etc; the risk of these side effects can be mitigated by several techniques, but they cannot be eliminated. Moreover, some patients are more susceptible to such side effects than others and this cannot be predicted in advance; the patient must decide whether the advantages of a lasting cure outweigh the risks of this treatment when faced with an otherwise incurable cancer. Several centers around the world have used fast neutrons for treating cancer. Due to lack of funding and support, at present only three 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 to shape the neutron beam. The Radiation Oncology Department operates a proton cyclotron that produces fast neutrons from directing 50.5MeV protons onto a beryllium target.
The UW Cyclotron is equipped with a gantry mounted delivery system an MLC to produce shaped fields. The UW Neutron system is referred to as the Clinical Neutron The
The CyberKnife System is a radiation therapy device manufactured by Accuray Incorporated. The system is used to deliver radiosurgery for the treatment of benign tumors, malignant tumors and other medical conditions; the device combines a compact linear accelerator mounted on a robotic manipulator, an integrated image guidance system. The image guidance system acquires stereoscopic kV images during treatment, tracks tumor motion, guide the robotic manipulator to and align the treatment beam to the moving tumor; the system is designed for stereotactic body radiation therapy. The system is used for select 3D conformal radiotherapy and intensity modulated radiation therapy; the system was invented by John R. Adler, a Stanford University professor of neurosurgery and radiation oncology, Peter and Russell Schonberg of Schonberg Research Corporation; the first system was installed at Stanford University in 1991 and was cleared by the FDA for clinical investigation in 1994. After years of clinical investigation the FDA cleared the system for the treatment of intracranial tumors in 1999 and for the treatment of tumors anywhere in the body in 2001.
Since the original design, Accuray Incorporated released six CyberKnife System models over the years: the CyberKnife G3 System in 2005, the CyberKnife G4 System in 2007, the CyberKnife VSI System in 2009, the CyberKnife M6 System in 2012 Image-guided radiation therapy Horsley–Clarke apparatus Gamma knife Robotic surgery Kilby, W. "The CyberKnife® Robotic Radiosurgery System in 2010". TCRT. 9: 433–452. Doi:10.1177/153303461000900502. PMID 20815415. Principles and Practice of Stereotactic Radiosurgery, Lawrence Chin, MD and William Regine, MD, Editors
Iobenguane known as metaiodobenzylguanidine or mIBG, or MIBG is a radiopharmaceutical, used in a scintigraphy method called MIBG scan. Iobenguane is a radiolabeled molecule similar to noradrenaline; the radioisotope of iodine used for the label can be iodine-123 or iodine-131. It localizes to adrenergic tissue and thus can be used to identify the location of tumors such as pheochromocytomas and neuroblastomas. With I-131 it can be used to eradicate tumor cells that take up and metabolize norepinephrine. Thyroid blockade with potassium iodide is indicated for nuclear medicine scintigraphy with iobenguane/mIBG; this competitively inhibits radioiodine uptake, preventing excessive radioiodine levels in the thyroid and minimizing the risk of thyroid ablation. The minimal risk of thyroid carcinogenesis is reduced as a result; the FDA-approved dosing of potassium iodide for this purpose are as follows: infants less than 1 month old, 16 mg. Not all sources are in agreement on the necessary duration of thyroid blockade, although agreement appears to have been reached about the necessity of blockade for both scintigraphic and therapeutic applications of iobenguane.
Commercially available iobenguane is labeled with iodine-123, product labeling recommends administration of potassium iodide 1 hour prior to administration of the radiopharmaceutical for all age groups, while the European Associated of Nuclear Medicine recommends that potassium iodide administration begin one day prior to radiopharmaceutical administration, continue until the day following the injection, with the exception of newborns, who do not require potassium iodide doses following radiopharmaceutical injection. Product labeling for diagnostic iodine-131 iobenguane recommends potassium iodide administration one day before injection and continuing 5 to 7 days following. Iodine-131 iobenguane used for therapeutic purposes requires a different pre-medication duration, beginning 24–48 hours prior to iobenguane injection and continuing 10–15 days following injection; the FDOPA PET/CT scan has proven to be nearly 100% sensitive for detection of pheochromocytomas, vs. 90% for MIBG scans. Centers which offer FDOPA PET/CT, are rare.
Iobenguane I 131, marketed under the trade name Azedra, has had a clinical trial as a treatment for malignant, recurrent or unresectable pheochromocytoma and paraganglioma, the FDA approved it on July 30, 2018. The drug is developed by Progenics Pharmaceuticals. Iodine 131-metaiodobenzylguanidine at the NCI Drug Dictionary
A dose-volume histogram is a histogram relating radiation dose to tissue volume in radiation therapy planning. DVHs are most used as a plan evaluation tool and to compare doses from different plans or to structures. DVHs were introduced by Michael Goitein and Verhey in 1979. DVH summarizes 3D dose distributions in a graphical 2D format. In modern radiation therapy, 3D dose distributions are created in a computerized treatment planning system based on a 3D reconstruction of a CT scan; the "volume" referred to in DVH analysis is a target of radiation treatment, a healthy organ nearby a target, or an arbitrary structure. DVHs can be visualized in either of two ways: cumulative DVHs. A DVH is created by first determining the size of the dose bins of the histogram. Bins can be of e.g. 0 -- 1 Gy, 1.001 -- 2.000 Gy, 2.001 -- 3.000 Gy, etc.. In a differential DVH, bar or column height indicates the volume of structure receiving a dose given by the bin. Bin doses are along the horizontal axis, structure volumes are on the vertical.
The differential DVH takes the appearance of a typical histogram. It reads like the volume of the organ, it is built by the sum of the number of voxels characterized by a specified range of dosage for the organ considered. It is helpful in providing information about changes in dose within the structure considered and to visualize minimum and maximum dose; the cumulative DVH is plotted with bin doses along the horizontal axis, as well. However, the column height of the first bin represents the volume of structure receiving greater than or equal to that dose; the column height of the second bin represents the volume of structure receiving greater than or equal to that dose, etc. With fine bin sizes, the cumulative DVH takes on the appearance of a smooth line graph; the lines always start from top-left to bottom-right. For a structure receiving a homogenous dose the cumulative DVH will appear as a horizontal line at the top of the graph, at 100% volume as plotted vertically, with a vertical drop at 10 Gy on the horizontal axis.
A DVH used clinically includes all structures and targets of interest in the radiotherapy plan, each line plotted a different color, representing a different structure. The vertical axis is always plotted as percent volume, as well. Clinical studies have shown. A drawback of the DVH methodology is. DVHs from initial radiotherapy plans represent the doses to structures at the start of radiation treatment; as treatment progresses and time elapses, if there are changes, the original DVH loses its accuracy. Sambasivam, Sasikumar. "Dose Volume Histogram". Slideshare. P. 28
Strontium-89 is a radioactive isotope of strontium produced by nuclear fission, with a half-life of 50.57 days. It undergoes β− decay into yttrium-89. Strontium-89 has an application in medicine, it was used for the first time by Belgian scientist Charles Pecher. Pecher filed a patent in May 1941 for the synthesis of strontium-89 and yttrium-86 using cyclotrons and described the use of strontium for therapeutic uses. Strontium belongs to the same periodic family as calcium, is metabolised in a similar fashion. 89Sr, used in the treatment of osseous metastases preferentially targets metabolically active regions of the bone. As such, intravenous or intracavity administration of 89Sr may be helpful in the palliation of painful bony metastases, as it allows for targeted radiation to metastatic lesions, inducing apoptosis of cells and protein damage. Subsequently, bone pain resulting from cytokine release at the site of lesions, bone-associated nerve compression and stretching of the periosteum may be reduced.
Treatment with 89Sr has been effective in patients with hormonally-resistant prostate cancer leading to a decreased requirement for opioid analgesics, an increase in time until further radiation, a decrease in tumour markers. It is an artificial radioisotope, used in treatment of bone cancer. In circumstances where cancer patients have widespread and painful bony metastases, the administration of 89Sr results in the delivery of beta particles directly to the area of bony problem, where calcium turnover is greatest. Isotopes of strontium Alpharadin, Radium-223 with similar clinical use
Megavoltage X-rays are produced by linear accelerators operating at voltages in excess of 1000 kV range, therefore have an energy in the MeV range. The voltage in this case refers to the voltage used to accelerate electrons in the linear accelerator and indicates the maximum possible energy of the photons which are subsequently produced, they are used in medicine in external beam radiotherapy to treat neoplasms and tumors. Beams with the voltage range of 4-25 MV are used to treat buried cancers because radiation oncologists find that they penetrate well to deep sites within the body. Lower energy x-rays, called orthovoltage X-rays, are used to treat cancers closer to the surface. Megavoltage x-rays are preferred for treatment of deep lying tumours as they are attenuated less than lower energy photons, will penetrate further, with a lower skin dose. Megavoltage x-rays have higher relative biological effectiveness than orthovoltage x-rays; these properties help to make megavoltage x-rays the most common beam energies used for radiotherapy in modern techniques such as IMRT.
Use of megavoltage x-rays for treatment first became widespread with the use of Cobalt-60 machines in the 1950s. However prior to this other devices had been capable of producing megavoltage radiation, including the 1930s Van de Graaff generator and betatron. Orthovoltage X-rays External beam radiotherapy
Orthovoltage x-rays are produced by x-ray tubes operating at voltages in the 100–500 kV range, therefore the x-rays have a peak energy in the 100–500 keV range. Orthovoltage X-rays are sometimes termed "deep" x-rays, they cover the upper limit of energies used for diagnostic radiography, are used in external beam radiotherapy to treat cancer and tumors. They penetrate tissue to a useful depth of about 4–6 cm; this makes them useful for treating skin, superficial tissues, ribs, but not for deeper structures such as lungs or pelvic organs. The energy and penetrating ability of the x-rays produced by an x-ray tube increases with the voltage on the tube. External beam radiotherapy began around the turn of the 20th century with ordinary diagnostic x-ray tubes, which used voltages below 150 kV. Physicians found that these were adequate for treating superficial tumors, but not tumors inside the body. Since these low energy x-rays were absorbed in the first few centimeters of tissue, to deliver a large enough radiation dose to buried tumors would cause severe skin burns.
Therefore beginning in the 1920s "orthovoltage" 200–500 kV x-ray machines were built. These were found to be able to reach shallow tumors, but to treat tumors deep in the body more voltage was needed. By the 1930s and 1940s megavoltage X-rays produced by huge machines with 3-5 million volts on the tube, began to be employed. With the introduction of linear accelerators in the 1970s, which could produce 4-30 MV beams, orthovoltage x-rays are now considered quite shallow. Megavoltage X-rays