Survival after BNCT in Combination with Surgery for Dogs with Spontaneous Brain Tumors

Abstract

Dogs develop spontaneous brain tumors as in humans and serve as a large animal model for evaluation of BNCT for treatment of brain tumor. In this study, 13 dogs with spontaneous brain tumors were treated surgery (SX) followed by BNCT and the median survival of was determined. The median survival was also determined for a group of dogs with spontaneous brain tumors previously treated with BNCT alone (n = 20). All dogs had histologic confirmation of tumor type either at the time of surgery or at necropsy. Of the dogs treated surgically, BNCT followed 3 to 6 weeks after surgery. Dogs of each group had various tumor types, however, the majority were meningiomas (13/20 BNCT; 9/13 SX + BNCT). Of the dogs in the surgery group, all had incomplete resections of the tumor primarily due to tumor location or infiltration of surrounding brain. In both groups, BSH or p-BPA were used for the boron agent. Peak brain dose was 10 to 12.5 Gy- equivalent.

All dogs in the BNCT only group and 11/13 dogs in the SX + BNCT group diedor were euthanized due to progression of intracranial signs attributed to progressive tumor. Two dogs in the SX + BNCT group are alive at the time of this writing (540 and 660 days after therapy).

Median survival in days was determined for both groups. Dogs in the historical group receiving BNCT treatment alone had median survival of 90 days (range 1 to 1,860 days). Dogs receiving surgical biopsy/debulking had a median survival of 300 days (range 17 to 690 days). When dogs with meningiomas were analyzed independently within each group, median survivals for the BNCT group was 75 days (range 1 to 180 days) and those in the SX + BNCT group was 300 days (range 14 to 690 days). These results may suggest that BNCT used following incomplete surgical brain tumor removal may improve survival over those previously reported.

Brain tumors occur in dogs with a frequency of 14.5 per 100,000 at risk.1 Of 95 dogs with brain tumors evaluated at our hospital, the majority were older (median age 9 years; range 4 to 13 years) and had meningiomas (47%).2 Meningioma is the most common primary brain tumor in dogs and cats.3–5 The diagnosis of an intracranial mass is readily made using an advanced imaging modalities such as computed tomography (CT) or magnetic resonance (MR) imaging. Features of primary brain tumor have been reviewed.6–8

Treatments for brain tumors in dogs depend upon tumor type, tumor location, natural history of the tumor, associated morbidity/mortality of the treatment modality, and cost. Surgical removal is ideal for superficially located, encapsulated, relatively small, benign tumors of which meningiomas would be the most common example. Unfortunately, even when these tumors are histologically benign, they are often not well encapsulated and hence difficult to differentiate from surrounding non-tumorous brain. Brain damage in areas adjacent to the tumor can make gross delineation of tumor borders difficult if not impossible.

Limited studies have been published regarding survival in dogs with spontaneous brain tumors. Studies of survival after brain tumor treatment in dogs include small patient numbers and include a diverse patient population. Median survival in dogs with brain tumors treated with surgery alone vary but tend to cluster around 140 to 150 days.9,10 As an adjunctive therapy to surgery, or as a primary therapy for tumors that are difficult to access surgically, conventional radiation therapy has been shown effective for some brain tumor in animals.9,11,12 Treatment protocols and survival analysis for radiation therapy of brain tumors has been reviewed previously.11 From these limited studies, median survival in dogs treated with conventional radiation therapy survival is also between 150 and 300 days.

Boron Neutron Capture Therapy (BNCT) has been performed on dogs with spontaneous brain tumors for over 10 years at our institution. From 1988, animals with radiologic or surgically confirmed neoplasms were entered in the BNCT protocol with the client’s consent. From 1988 through 1992, dogs were treated with BNCT as the primary modality of therapy. From 1992 to the time of this writing BNCT has been used as therapy following surgical debulking. In an effort to better understand the role of surgery and BNCT therapy, median survival times were retrospectively calculated for two groups of dogs with spontaneous brain tumors. No significant numbers of control groups consisting of dogs with brain tumors not treated or dogs with brain tumors only surgically treated were available from our hospital population for statistical comparisons. The survival for the groups reported, however, provide some pilot information regarding surgery combined with BNCT for dogs with brain tumor.