Radiation therapy is the main treatment modality for diseases like lung cancer19 and is used in over half of cancer patients as part of their treatment. The goal of RT is to have a have therapeutic ratio – the ratio of cancer tissue vs healthy tissue damaged by the
radiation. It has been shown that a higher dose results in an improved local control of the tumor19 but the higher dose increases toxicity to the healthy tissue surrounding it. This brought on the idea of 3D conformal radiation therapy which targets the tumor by using multiple entrance angles of radiation to ensure that the tumor receives the maximal dose and greatly dropping the dose after crossing the boundary to the surrounding tissue. The hypothesis behind this technique was that conformal radiation would allow for a higher local dose which would translate into an improvement in local control.
The next step up from 3D-CRT is intensity modulated RT (IMRT), which divides each large CRT beam into numerous small ‘beamlets’, and adjusts the intensity of each one
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individually to achieve complex dose distributions that further conform to the tumor shape. IMRT requires a larger amount of beams, generally 5 to 9, for each fraction20.
IMRT makes it possible to increase the dose gradient at the tumor boundary. The strategy is to treat the tumor region with increase dose volumes but also to “carve out” dose-limiting regions around sensitive structures where there is little chance of tumor expansion21. This was not possible with other modalities because of the difficulty of producing specific treatment volumes with uniform irradiation fields. Examples of conformation avoidance include sparing uninvolved parotid glands, auditory apparatus, mucosa and larynx in head and neck radiotherapy21.
There are several drawbacks to IMRT. The first is that the treatment plans are more complex and take longer to deliver. Alongside that, the accuracy without any image guidance or patient immobilization, physiological motion ruins the dose distribution. To account for motion and uncertainty, an increased integral dose is delivered. The lengthy treatment may also cause an increased tumor cell repair during the radiation delivery20. Lastly, IMRT increases the monitor units– amount of radiation produced by the linac which are associated with an increase in scatter radiation, which would increase the total-body dose22.
The development of image guided therapy and hypofractionation improved upon the problems of fixed field radiation treatment. IGRT ensured that the treatment was
delivered to the correct location after positioning the patient. This also lead to the decrease of the ‘safety margin’ which was set around the tumor to account for positioning errors20. An issue that arouse was the increased total treatment time as a result of this added imaging benefit. Hypofractionation is the delivery of much larger daily doses than the
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standard 2Gy per day. An example would be for stereotactic lung radiotherapy, where three fractions of 20 Gy are delivered with excellent local control results. Fixed field delivery, however, increases the radiation time greatly as well.
To counter these problems, arc therapy became a treatment option. Arc therapy rotates the radiation beam while it is on, treating the patient from all angles. The idea behind its improvement over IMRT is that it not only covers all angles and provides a better conformal shape, but also it being on while moving speeds up the treatment process. While the selection of the 5-9 beam angles is difficult and time consuming for IMRT, arc therapy removes the necessity of that calculation.
There are two types of arc therapy: tomotherapy and volumetric modulate arc therapy. Tomotherapy is the RT version of CT imaging where a thin radiation beam treats axial slices of the patient by rotating around them as they moves through the machine longitudinally. It order to avoid ‘hot’ or ‘cold’ spots between the slices, some system move the beam helically around the patient. This geometry also allows for CT imaging prior to treatment and an accurate dose distribution to be made from knowing the exit dose. Tomotherapy has been implemented in many tumor regions and in a study of effectiveness between it and 3D-CRT in 60 patients, it was found that tomotherapy plans were
equivalent or superior to 3D-CRT in 95% of cases20. Compared to IMRT, tomotherapy was shown to provide an equivalent or slightly improved dose distribution but no treatment time comparisons have been reported.
In 2007, a new form of arc therapy called volumetric modulated arc therapy was introduced. In this RT modality, the dose rate, beam shape, and rotation speed are altered as the on beam is rotated. It differs from tomotherapy in that in can treat the entire tumor
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at once in one rotation, making the treatment time independent on the tumor size20. Compared to IMRT, VMAT produced similar or improved dose distributions along with a reduced treatment time of 1.5-3 mins. It also showed a reduction in monitor units by about 50%20. An extension to this system would be to use multiple arcs to improve dose
distributions.
With these advancements in ionizing radiation therapy, another treatment method that is becoming more common and gaining a lot of popularity in research is proton and heavy ion therapy. The premise of proton therapy is the Bragg peak which creates a favorable depth–dose distributionfor tumor treatment. Since the Bragg peak for particles of a single energy is very narrow, a combination of beams of varying energies can be
superimposed to produce a spread-out Bragg peak that conforms to the tumor shape, which looks very favorable to tumors with proximity of critical dose-limiting normal tissue. The Bragg curve characteristics indicate that proton therapy can rival with the most advanced X-ray methods, including IMRT23.
There are twenty centers in the world that use protons therapy, and three use12C ions. About 5,000 patients have been treated with12C ions and 50,000 with protons23. Proton therapy has been used to treat a wide variety of areas, including the head and neck, liver, brain, upper abdomen, pelvis, lung cancer, and in the vicinity of the spinal cord. It is particularly a favorable option for pediatric tumors where more complications are expected from stray radiation due to the increased inherent tissue sensitivity23.
Due to the lack of phase III clinical trials, it is hard to firmly compare the success of proton therapy, C-ion therapy, IMRT and conventional conformal. There are simply not enough centers and patients to state the clinical effectiveness of particle-based therapy.
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However, Durante 2009 claims that there is enough evidence to conclude that proton or C- ion therapies are superior to IMRT for the “most favorable tumor sites and subtypes, in particular ocular melanoma, adenoid cystic carcinoma and chordomas or chondrosarcomas of the base of the skull”23.