Meningioma in a 9-year-old chocolate Lab: Radiation oncology perspective

Dr. Isabella PfeifferExternal beam radiation therapy is the treatment of choice for nonresectable meningiomas, and it also has been shown to be beneficial in the postoperative setting, if surgical margins are incomplete. One study reported a significant increase in median survival time when surgery was followed by definitive radiation therapy.1 Dogs that underwent surgery alone lived a median of seven months, whereas dogs treated with surgery and radiation therapy had a median survival of 16.5 months.1 Another study reported an extended median progression-free survival of 30 months when surgery was followed by radiation therapy, but this was not compared with a control group.2 A third study reported a median survival time of 24 months for dogs treated with radiation therapy alone for extra-axial tumors.3 This study did not have a tissue diagnosis of meningioma, as the diagnosis was based on imaging characteristics alone. Neurologic status improved in about 85% of dogs during or within three weeks after completion of the radiation therapy protocol. Quality of life was deemed to be good to excellent for those dogs as determined by their owners.3

A definitive radiation therapy protocol for brain tumors usually involves daily treatments with a low dose per fraction (usually < 3 Gy) on a Monday through Friday basis over four weeks. Why do we have to treat with so many low-dose fractions when we irradiate a substantial amount of normal brain? The brain is a so-called late-responding tissue, meaning that a high radiation dose per fraction will increase the risk for nonrepairable damage. By definition, late responding tissues usually do not express that damage for at least six months or sometimes years after radiation therapy. In the case of brain tissue, this damage is usually expressed as brain necrosis or hemorrhage in the irradiated area; these effects are irreversible and may be life-threatening or cause uncontrollable clinical signs that lead to euthanasia.

In the early stages, signs may be manageable with anti-inflammatory doses of corticosteroids and antiepileptic drugs. Anecdotally, antioxidants such as vitamins E and C and pentoxifylline, a nonselective phosphodiesterase inhibitor, have been used to alleviate clinical signs due to necrosis and secondary inflammation (personal communication, Michael Kent, DVM, MS, Department of Surgical and Radiological Services, School of Veterinary Medicine, University of California, Davis, 2015).

Definitive radiation therapy protocols usually try to minimize the risk for late side effects, such as brain necrosis, to less than 5% risk. In dogs that undergo surgical debulking of a brain tumor, a large volume of normal brain has to be irradiated to effectively treat the remaining microscopic disease, and this is why we have to fractionate the dose in those cases to avoid late side effects. In one study, dogs were treated with palliative doses of radiation for their brain tumors with escalating doses (5, 7, 8, 9, and 9 Gy) once a week for five treatments.4 At least 12 of 76 dogs died of suspected late side effects (i.e. brain necrosis).4 This high dose per fraction protocol resulted in an estimated 20% to 25% risk for brain necrosis, which is unacceptably high, considering the median survival times achievable with definitive type protocols in dogs with meningiomas.

Acute radiation side effects are very rare in dogs treated for meningiomas. They rarely show any skin side effects, but depending on location we may see ocular or inner ear effects, such as keratoconjunctivitis sicca (KCS) or otitis. Uncommonly, transient neurologic deterioration, often similar to initial presenting signs, may be seen two to 12 weeks after treatment, with a peak incidence at about eight weeks after radiation therapy is completed.5 This early delayed side effect generally resolves with time, and these usually respond to anti-inflammatory doses of corticosteroids. Therefore, it is important to be aware that recurrence of initial neurologic signs may be due to this temporary radiation side effect and should not be automatically attributed to tumor recurrence.

At some veterinary schools, the practice of stereotactic radiotherapy (SRT) is used to treat nonresectable well-defined meningiomas. SRT uses few fractions of high-dose radiation that is precisely targeted to a well-defined intracranial lesion. Instead of having to fractionate over several weeks, the tumor can be targeted in a way that the late-responding normal brain tissue is spared and only receives a low to minimal radiation dose during this procedure. SRT requires image guidance to verify patient positioning, a reference frame (in most cases the bones of the skull to confirm tumor and patient position), and the ability to target the radiation dose (i.e. a well-designed planning and delivery system). For stereotactic as well as conventional radiation therapy, patients at the University of Tennessee are positioned in a Vac-Lok cushion system (CIVCO Medical Solutions) and a thermoplastic mask system attached to an indexed rigid head and neck frame. This system is used to position patients for their radiation therapy planning CT and each of their radiation treatments (Figure 9).

Figure 9. A dog (not the dog in the case described here) undergoing stereotactic radiotherapy positioned in a Vac-Lok cushion and thermoplastic mask attached to an indexed head and neck frame.

The SRT protocol for meningiomas at the University of Tennessee involves three fractions of 8 Gy on consecutive days. We usually allow a couple of days between the planning CT and the actual treatment to develop the best treatment plan, which is then verified on a phantom before the patient returns for treatment.

A median survival time of about 18.5 months with stereotactic radiotherapy for suspected meningiomas has been reported.6 About 36% of the dogs had mild to moderate exacerbation of neurologic signs three to 16 weeks after SRT that were usually well-managed with corticosteroids. An Italian group reported median survival times of two years with SRT.7 With those preliminary data and personal experience from various veterinary radiation oncologists, SRT is a viable alternative to four weeks of treatment in most of our meningioma patients in which surgery is not a viable option or owners decline surgery.

References

1. Axlund TW, McGlasson ML, Smith AN. Surgery alone or in combination with radiation therapy for treatment of intracranial meningiomas in dogs: 31 cases (1989-2002). J Am Vet Med Assoc 2002;221:1597-1600.

2. Théon AP, Lecouteur RA, Carr EA, et al. Influence of tumor cell proliferation and sex-hormone receptors on effectiveness of radiation therapy for dogs with incompletely resected meningiomas. J Am Vet Med Assoc 2000;216:701-707.

3. Bley CR, Sumova A, Roos M, et al. Irradiation of brain tumors in dogs with neurologic disease. J Vet Intern Med 2005;19:849-854.

4. Brearley MJ, Jeffery ND, Phillips SM, et al. Hypofractionated radiation therapy of brain masses in dogs: a retrospective analysis of survival of 83 cases (1991-1996). JVet Intern Med 1999;13:408-412.

5. Gillette EL, LaRue SM, Gillette SM. Normal tissue tolerance and management of radiation injury. Semin Vet Med Surg (Small Anim) 1995;10:209-213.

6. Griffin LR, Nolan MW, Selmic LE, et al. Stereotactic radiation therapy for treatment of canine intracranial meningiomas. Vet Comp Oncol 2014 Dec 18. [Epub ahead of print]

7. Malfassi L, Dolera M, Marcarini S, et al. Canine meningioma: comparison of palliative therapy, surgery and stereotactic radiosurgery (abst), in Proceedings. Am Coll Vet Radiol Congress 2014.