Stereotactic Radiosurgery and IMRT Update: What New Tumors can we Treat?

Stereotactic radiation (SRT) and intensity modulated radiation therapy (IMRT) are becoming more readily available for animals.  In a survey of veterinary radiation facilities performed in 2010 (Farrelly et al VRUS, 2014) approximately 1/3 of facilities had IMRT capability, SRT capability or both, and this number has been growing rapidly.

Prior to the advent of these technologies, almost any solid tumor could be treated with radiation.  The clinical problem has been that, although radiation could theoretically be used to treat any tumor,  most tumors are surrounded by normal tissues that can be adversely affected by the radiation.  This results in significant side effects in these areas and severely limits the dose that can be safely given to the tumor.  Many radiation oncologists and pet owners might decide not to pursue radiation because the side effects of treatment can result in severe negative effects on quality of life.

Probably the best example of this is nasal tumors in dogs.  Given the location of these tumors most early studies showed no significant benefit to surgery.   (Theon et al JAVMA 1993) so radiation therapy has been the focus of local therapy for these tumors.  However, side effects from conventional radiation can be severe for dogs with nasal tumors.  Short term side effects such as conjunctivitis, oral mucositis, dermatitis etc. can cause a severe impact on quality of life during the treatment.  Also, late effects, such as damage to the eyes, can lead to significant long-term health issues and even euthanasia in some cases (Pinard et al Can Vet J 2012).

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Figure 1 Acute conjunctivitis (left) and chronic cataract (right) from radiation to the eye for treatment of a nasal tumor

IMRT and SRT will allow the dose of radiation to be targeted to the tumor while minimizing the dose to the local normal tissues.

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Figure 2 Dose distribution for treatment of a nasal tumor in a dog.
The nasal cavity (red color wash) is receiving greater than 98% of the prescribed dose while the lenses receive less than 20-30% of the dose.

Being able to target the radiation better to the tumor makes it easier to deliver radiation to tumors without severe side effects.

Bone tumors

Bone tumors, such as osteosarcoma, are usually best treated with surgical removal followed by chemotherapy.  When surgery is not an option due to the location of the tumor (e.g. some axial tumors) or the ability of the patient to tolerate an amputation, stereotactic radiation may be beneficial.   In one study 11 dogs were treated with stereotactic radiation (plus or minus chemotherapy) for osteosarcoma involving the distal limbs.  These dogs had a median survival of 363 days and most of the dogs had excellent function of their limbs (Farese, et al JAVMA 2004).

This type of treatment may be an alternative to amputation in dogs where a lot of the bone has not been destroyed yet.

Adrenal Tumors

Treatment of choice for adrenal tumors is typically surgical removal.  However, when there is a significant invasion of the tumor into the nearby vessels, surgery can sometimes be dangerous.  Given the relatively stable location of the adrenal gland stereotactic radiation may be used to treat these tumors.  At the 2014 ACVR  Scientific Meeting, an abstract was presented on this type of treatment for 12 dogs (Malfassi et al ACVR Abstract 2014).  All dogs were treated with 3 large doses of radiation.  Ten dogs had partial responses and 87% of dogs were alive with a mean follow-up of 21 months.  While this data is still early, this may prove to be a possible treatment option for dogs with invasive adrenal tumors.

Brain Tumors

Brain tumors are typically best treated with surgery or surgery plus radiation, with reported survival times of 12-24 months (Rohrer-Bley et al JVIM 2005;Kyerleber et al VCO 2013).  However, some brain tumors are in locations where surgery is not possible.  For these, definitive radiation may give the best chance for long-term tumor control.  However, in cases where definitive radiation is not an option, stereotactic radiation may be an option.  In one study 51 dogs were treated with stereotactic radiation with a median survival of 399 days.  In an abstract from the 2014 ACVR Meeting 69 dogs were treated with stereotactic radiation and their outcome was compared to dogs that had surgery or palliative care alone.  Dogs that had radiation had survival times ranging from 22-26 months compared to less than 19 months for dogs with surgery alone (Malfassi et al ACVR Abstract 2014).

Nasal tumors in dogs

Nasal tumors are some of the most difficult and most frustrating tumors to treat in dogs.  Nasal tumors are very locally invasive and given their location they are often right up against the eyes, the brain the skin and the oral mucosa.  Traditional conformal radiation therapy has shown to be effective.  However, dogs treated this way often have significant short-term side effects involving their eyes, and mouth  which results in significant discomfort.  Tumor control is good, with average survival times of approximately 12-18 months.  However, long-term tumor control is not common as most dogs end up dying from their nasal tumor.

Stereotactic radiation may be a reasonable alternative for treating nasal tumors as the treatment causes much fewer side effects and only requires usually 3 anesthesias.  One study has been published so far with 19 dogs that were treated with three large doses.  Median survival time was 399 days.  This is similar to definitive radiation but with much fewer side effects short term (Glasser et al JAAHA 2014).

Now that we have the ability to focus radiation to almost any area, pretty much any solid tumor can be safely treated with radiation. 

Submitted by

Dr. John Farrelly DVM, MS, ACVIM (Oncology), ACVR (Radiation Oncology)

Radiation Oncologist/Medical Oncologist at The Veterinary Cancer Center

The Veterinary CyberKnife Cancer Center in Malvern, PA offers CyberKnife radiation therapy treatments for veterinary patients. CyberKnife is a form of stereotactic radiation therapy which allows pain-free, non-invasive precision tumor treatment with fewer visits to the hospital. For questions regarding cases that may benefit from this treatment, please contact Dr. Siobhan Haney (radiation oncologist) at Hope Veterinary Specialists 610-296-2099.

 

References

Farrelly J, McEntee MC. A survey of veterinary radiation facilities in 2010. Vet Radiol Ultrasound. 2014 Nov-Dec;55(6):638-43. http://onlinelibrary.wiley.com/doi/10.1111/vru.12161/full

Théon AP, Madewell BR, Harb MF, Dungworth DL. Megavoltage irradiation of neoplasms of the nasal and paranasal cavities in 77 dogs.  J Am Vet Med Assoc. 1993 May 1;202(9):1469-75.http://europepmc.org/abstract/med/8496103

Pinard CL, Mutsaers AJ, Mayer MN, Woods JP. Retrospective study and review of ocular radiation side effects following external-beam Cobalt-60 radiation therapy in 37 dogs and 12 cats.  Can Vet J. 2012 Dec;53(12):1301-7. Review.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500122/

Farese JP, Milner R, Thompson MS, et al. Stereotactic radiosurgery for treatment of osteosarcomas involving the distal portions of the limbs in dogs. J Am Vet Med Assoc. 2004 Nov 15;225(10):1567-72, 1548.

http://avmajournals.avma.org/doi/abs/10.2460/javma.2004.225.1567

Malfassi L, Dolera M, Marcarini S, et al Adrenal tumors with vascular invasion: stereotactic hypofractionated volume modulated arc radiotherapy (VMAT) in 12 dogs. Proceeding of the ACVR 2014 Annual Scientific Meeting

Rohrer-Bley CR, Sumova A, Roos M, et al. Irradiation of brain tumors in dogs with neurologic disease. J Vet Intern Med. 2005 Nov-Dec;19(6):849-54. http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2005.tb02776.x/abstract

Keyerleber MA, McEntee MC, Farrelly J, et al. Three-dimensional conformal radiation therapy alone or in combination with surgery for treatment of canine intracranial meningiomas. Vet Comp Oncol. 2013 Jul 19. vco.12054. [Epub ahead of print] http://onlinelibrary.wiley.com/doi/10.1111/vco.12054/full

Malfassi L, Dolera M, Marcarini S, et al.  Canine meningioma: comparison of palliative therapy , surgery and stereotactic radiosurgery. Proceeding of the ACVR 2014 Annual Scientific Meeting

Glasser SA, Charney S, Dervisis NG, et al Use of an image-guided robotic radiosurgery system for the treatment of canine nonlymphomatous nasal tumors. J Am Anim Hosp Assoc. 2014 Mar-Apr;50(2):96-104.

http://www.jaaha.org/doi/abs/10.5326/JAAHA-MS-6024

 

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