Radiation Therapies in Oncology

Siobhan Haney, VMD, MS, DACVR (RO), Hope Veterinary Specialists and the Veterinary CyberKnife Cancer Center, Malvern, Pennsylvania

March 2018|Oncology|Peer Reviewed|Web-Exclusive

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Radiation Therapies in Oncology

Linear accelerators provide external beam radiation therapy. Advances in radiation planning and technology have improved targeting of tumors and avoidance of surrounding critical tissues and organs, as seen with intensity-modulated radiation therapy (IMRT) and stereotactic radiation therapy (SRT). This article reviews use of fractionated external beam radiation therapy, IMRT, and SRT in veterinary patients.

Radiation Therapy

Radiation therapy for cancer treatment relies on localizing radiation to a target, whether microscopic cancer cells (eg, an incompletely excised skin tumor) or visible target (eg, brain or nasal tumor). Most cytotoxic damage caused by radiation affects cellular DNA. Interaction of radiation with intracellular water creates free oxygen radicals, which can cause strand breaks and other damage to DNA. A lesser amount of DNA damage is done through direct effects of radiation on DNA strands. Small daily radiation doses will allow normal tissues to repair, thus reducing potential toxicity. Cancer cells have a decreased ability to repair DNA damage as compared with normal cells; therefore, fractionated radiation protocols allow normal tissue to repair while cancer cells accumulate DNA damage and, ultimately, die.1 Thus, the biologic rationale for fractionation (ie, dividing a total dose of radiation into multiple smaller doses) is to spare the healthy, sensitive tissue surrounding a tumor.

Conventional Radiation Therapy

Conventional (or standard) radiation therapy protocols deliver a total radiation dose divided into multiple small daily doses (ie, fractions) that may span 3 to 4 weeks (16-20 fractions).2-4 Older techniques that do not involve the use of advanced imaging for 3D radiation treatment planning purposes involve the use of bony or other anatomic landmarks to “manually plan” a radiation protocol. In this scenario, the radiation oncologist chooses the angle and number of radiation beams and size of the radiation field based on the appearance and/or location of the tumor and proximity of the tumor to sensitive surrounding anatomy. In some cases, flat radiographic films may be used to create a 2D plan. Benefits of this approach include speed and simplicity and, in some cases, lower cost. In contrast to the aforementioned planning techniques, 3D-conformal or Intensity Modulated Radiation Therapy (IMRT) planning involve advanced imaging techniques such as CT or MRI and use either forward planning in the case of 3D-conformal planning or inverse planning in the case of IMRT.

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Forward planning involves tumor/target delineation, typically using axial CT and/or MRI images. Healthy, critical surrounding structures are also contoured on each axial image and a plan is created by selecting the number of beams, beam weights, and the radiation field sizes. A trial-and-error plan is then created based on the dose delivery to the tumor and surrounding structures (Figure 1). Beam weights, angles, and field sizes can be adjusted to deliver appropriate doses to the tumor while attempting to avoid normal tissue. Radiation beams can be shaped by collimator use. Standard (or primary) collimators can form squares and rectangles. Beams can also be shaped using lead or other heavy alloy blocks, which can be molded to conform closely to tumor shape and size. Recently, the use of multileaf collimators, composed of thin individual leaves of metal that can be moved in and out of a beam of radiation, have enabled even more efficiency in beam shaping without the use of cumbersome lead blocks.5 Despite these advances, the normal tissue surrounding a tumor limits the use of conventional radiation therapy. However, developments in the field of radiation may allow for more conformal dosing and less normal-tissue exposure. 

3-D conformal radiation plan for a dog with a nasal tumor. The prescribed dose of radiation therapy is being delivered to the tissue inside the thick red line. In this particular case, wedges of metal are inserted into the beams of radiation, which progressively attenuate a dose of radiation across a field.
3-D conformal radiation plan for a dog with a nasal tumor. The prescribed dose of radiation therapy is being delivered to the tissue inside the thick red line. In this particular case, wedges of metal are inserted into the beams of radiation, which progressively attenuate a dose of radiation across a field.

FIGURE 1 3-D conformal radiation plan for a dog with a nasal tumor. The prescribed dose of radiation therapy is being delivered to the tissue inside the thick red line. In this particular case, wedges of metal are inserted into the beams of radiation, which progressively attenuate a dose of radiation across a field.

FIGURE 1 3-D conformal radiation plan for a dog with a nasal tumor. The prescribed dose of radiation therapy is being delivered to the tissue inside the thick red line. In this particular case, wedges of metal are inserted into the beams of radiation, which progressively attenuate a dose of radiation across a field.

It is important to note that the above described planning techniques are independent of a radiation oncologist’s prescription for radiation dose, which is defined by the number and frequency of treatments and dose per treatment. A radiation oncologist’s prescription for radiation may also be dependent on the tumor size, invasiveness, anatomic location, proximity to surrounding critical organs and tissue, and pet owner’s goals for therapy. Radiation may be delivered using larger doses per fraction with fewer number of fractions in a process that may be considered a hypofractionated or “palliative” protocol. (The alternative would be a more finely fractionated protocol, considered “full course” or “definitive-intent” radiation therapy, in which smaller fractions may be delivered on a daily basis for several weeks.) 

Hypofractionated protocols employ larger doses per treatment. These protocols typically deliver a lower cumulative radiation dose than does full-course or definitive-intent radiation therapy but with higher doses per treatment. This generally results in fewer acute radiation side effects but lower rates of long-term tumor control. Hypofractionated radiation may be used for palliative purposes, as this course of radiation may successfully confer pain relief, decrease tumor bleeding, or slow/stabilize tumor growth for a finite period of time, thus effectively improving an animal’s quality of life. Many hypofractionated protocols have been described in veterinary medicine and typically entail one to 2 treatments per week for 4 to 6 weeks; however, some protocols require 2 to 5 treatments administered in one week, and some hypofractionated protocols may be delivered in an accelerated fashion (ie, 2 doses of radiation per day for 2 or more days). 6-11

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Intensity-Modulated Radiation Therapy

IMRT uses multileaf collimators in a field of radiation. Collimator leaves can be moved during radiation treatment, thereby allowing the radiation oncologist to deliver a variable dose of radiation in a treatment field and to modify intensity for different areas. Radiation dose intensity should be elevated near the gross tumor volume, whereas the dose to surrounding healthy tissue should be decreased or avoided. Radiation intensity may also be varied across a field by using custom-made compensators or helical tomotherapy. These methods may cause fewer side effects and may allow for dose escalation in some circumstances, which could lead to improved treatment outcomes as compared with conventional radiation therapy.12,13 

IMRT can improve the ability to create complex treatment volumes and conform radiation to concave tumor shapes. Specifically, this allows tumors that may be wrapped around or near sensitive structures (eg, spinal cord, urethra, eyes, brain) to be treated more effectively with a lower dose delivered to nearby tissue (Figure 2).13-16 IMRT necessitates the use of inverse planning, which is independent of radiation prescription (ie, dose per fraction, frequency of treatments, and total dose). Inverse planning involves the definition of the area to be treated with radiation as well as organs at risk (OAR). Radiation delivery is optimized to maximize the dose of radiation to the target and minimize the dose to the OAR. This is accomplished by assigning dose constraints to the OAR prior to optimization and dose calculation. IMRT planning techniques may be used as part of a conventionally fractionated protocol or a hypofractionated protocol.

IMRT plan showing a dog with melanoma that has metastasized to the regional lymph nodes. The dose is shown in color wash, with red indicating “hotter” areas (prescription dose or slightly above) and blue areas indicating “cooler” areas receiving a much smaller dose of radiation.
IMRT plan showing a dog with melanoma that has metastasized to the regional lymph nodes. The dose is shown in color wash, with red indicating “hotter” areas (prescription dose or slightly above) and blue areas indicating “cooler” areas receiving a much smaller dose of radiation.

FIGURE 2 IMRT plan showing a dog with melanoma that has metastasized to the regional lymph nodes. The dose is shown in color wash, with red indicating “hotter” areas (prescription dose or slightly above) and blue areas indicating “cooler” areas receiving a much smaller dose of radiation.

FIGURE 2 IMRT plan showing a dog with melanoma that has metastasized to the regional lymph nodes. The dose is shown in color wash, with red indicating “hotter” areas (prescription dose or slightly above) and blue areas indicating “cooler” areas receiving a much smaller dose of radiation.

Stereotactic Radiation Therapy

Stereotactic refers to a 3-dimensional coordinate system that enables accurate correlation of a tumor visualized in diagnostic images with actual tumor position in the patient’s body. These treatment methods rely on accurate patient positioning, strict quality assurance, on-board imaging and/or rigid immobilization, and highly conformal delivery methods, which result in a steep dose gradient between the edge of the tumor and surrounding normal tissue. This results in a high dose of radiation being received by the tumor and a relatively low dose being received by surrounding healthy tissue.17,18 

SRT further minimizes the volume of normal tissue exposed to high-dose radiation by more narrowly defining the treatment volume and using beam arrangements that achieve a high degree of conformality and rapid dose falloff. Stereotactic radiation may be delivered in multiple fractionation schemes, such as a single high-dose fraction (ie, radiosurgery), or in a fractionated manner consisting of multiple treatments. Historically, the term stereotactic radiosurgery indicated treatment of intracranial location, and stereotactic body radiation therapy (SBRT) has been used for extracranial locations. Of note, the terms SRT and SBRT are sometimes used interchangeably.

The practice of SRT depends on precise target definition and radiation delivery. In human medicine, this is defined by accuracy to within 1 mm. First, the patient is immobilized in a treatment-positioning device for CT and/or MRI imaging to allow for precise definition of target and critical structures, which should be repeatable for treatment delivery. Treatment planning software is then used to create a highly conformal treatment plan that maximizes the dose to the target while minimizing dose outside the target and to critical structures. This is typically accomplished using multiple rotational arc and/or IMRT fields and/or specialized attachments to the linear accelerator that finely collimate a beam of radiation (ie, stereotactic cones). For patient setup and radiation treatment, a stereotactic coordinate system and/or on-line image-guidance is used to verify accuracy immediately before and/or during treatment delivery. There are important quality assurance techniques at each of these steps that should be overseen by a qualified medical physicist and/or radiation oncologist to ensure that the desired levels of accuracy are met.

Stereotactic radiation therapy has become more widely available in veterinary medicine and has been described for use in brain tumors, nasal tumors, osteosarcomas, feline oral squamous cell carcinomas, heart base tumors, feline injection site sarcomas, and trigeminal nerve sheath tumors (Figure 3).19-27

Stereotactic radiation plan for a left-sided trigeminal nerve sheath tumor in a dog. The prescribed dose of radiation is being delivered to the tumor inside the yellow line. Concentric lines around the tumor are isodose lines, which denote the percentage of radiation being received by surrounding tissue. Stereotactic plans are characterized by rapid dose falloff outside the target tissue. (See Figure 4)
Stereotactic radiation plan for a left-sided trigeminal nerve sheath tumor in a dog. The prescribed dose of radiation is being delivered to the tumor inside the yellow line. Concentric lines around the tumor are isodose lines, which denote the percentage of radiation being received by surrounding tissue. Stereotactic plans are characterized by rapid dose falloff outside the target tissue. (See Figure 4)

FIGURE 3 Stereotactic radiation plan for a left-sided trigeminal nerve sheath tumor in a dog. The prescribed dose of radiation is being delivered to the tumor inside the yellow line. Concentric lines around the tumor are isodose lines, which denote the percentage of radiation being received by surrounding tissue. Stereotactic plans are characterized by rapid dose falloff outside the target tissue. (See Figure 4)

FIGURE 3 Stereotactic radiation plan for a left-sided trigeminal nerve sheath tumor in a dog. The prescribed dose of radiation is being delivered to the tumor inside the yellow line. Concentric lines around the tumor are isodose lines, which denote the percentage of radiation being received by surrounding tissue. Stereotactic plans are characterized by rapid dose falloff outside the target tissue. (See Figure 4)

Stereotactic radiation plan for a large invasive nasal tumor in a dog.  Any tissue inside the white line is receiving the prescribe dose of radiation. There is a rapid decrease in dose outside of the white line. The eyes received a minimal dose of radiation due to the rapid dose falloff, despite being millimeters away from the tumor (note that concave treatment fields that were created around the eyes).
Stereotactic radiation plan for a large invasive nasal tumor in a dog.  Any tissue inside the white line is receiving the prescribe dose of radiation. There is a rapid decrease in dose outside of the white line. The eyes received a minimal dose of radiation due to the rapid dose falloff, despite being millimeters away from the tumor (note that concave treatment fields that were created around the eyes).

FIGURE 4 Stereotactic radiation plan for a large invasive nasal tumor in a dog.  Any tissue inside the white line is receiving the prescribe dose of radiation. There is a rapid decrease in dose outside of the white line. The eyes received a minimal dose of radiation due to the rapid dose falloff, despite being millimeters away from the tumor (note that concave treatment fields that were created around the eyes).

FIGURE 4 Stereotactic radiation plan for a large invasive nasal tumor in a dog.  Any tissue inside the white line is receiving the prescribe dose of radiation. There is a rapid decrease in dose outside of the white line. The eyes received a minimal dose of radiation due to the rapid dose falloff, despite being millimeters away from the tumor (note that concave treatment fields that were created around the eyes).

Conclusion

The field of radiation therapy in veterinary medicine is rapidly advancing. Available techniques enable clinicians to deliver doses of radiation with increasing accuracy and precision. Prospective studies are needed to compare radiation treatment delivery modalities to establish standards of care.

References

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