Definitive‐intent intensity‐modulated radiation therapy provides similar outcomes to those previously published for definitive‐intent three‐dimensional conformal radiation therapy in dogs with primary brain tumors: A multi‐institutional retrospective study

Radiotherapy with or without surgery is a common choice for brain tumors in dogs. Although numerous studies have evaluated use of three‐dimensional conformal radiotherapy, reports of definitive‐intent, IMRT for canine intracranial tumors are lacking. Intensity‐modulated radiation therapy has the benefit of decreasing dose to nearby organs at risk and may aid in reducing toxicity. However, increasing dose conformity with IMRT calls for accurate target delineation and daily patient positioning, in order to decrease the risk of a geographic miss. To determine survival outcome and toxicity, we performed a multi‐institutional retrospective observational study evaluating dogs with brain tumors treated with IMRT. Fifty‐two dogs treated with fractionated, definitive‐intent IMRT at four academic radiotherapy facilities were included. All dogs presented with neurologic signs and were diagnosed via MRI. Presumed radiological diagnoses included 37 meningiomas, 12 gliomas, and one peripheral nerve sheath tumor. One dog had two presumed meningiomas and one dog had either a glioma or meningioma. All dogs were treated in the macroscopic disease setting and were prescribed a total dose of 45‐50 Gy (2.25‐2.5 Gy per fraction in 18‐20 daily fractions). Median survival time for all patients, including seven cases treated with a second course of therapy was 18.1 months (95% confidence of interval 12.3‐26.6 months). As previously described for brain tumors, increasing severity of neurologic signs at diagnosis was associated with a worse outcome. Intensity‐modulated radiation therapy was well tolerated with few reported acute, acute delayed, or late side effects.     

Outcome and failure patterns of localized sinonasal lymphoma in cats treated with first‐line single‐modality radiation therapy: A retrospective study

Failure rate and site are not well defined in localized sinonasal lymphoma in cats treated with radiotherapy. In this study, we describe (a) failure pattern, (b) outcome, (c) influence of previously reported prognostic variables on the outcome in cats with suspected localized sinonasal lymphoma. In this multi‐institutional retrospective study, we included 51 cats treated with single‐modality radiotherapy. Cats were irradiated using 10x4.2Gy (n = 32), 12x3Gy (n = 11) or 5x6Gy (n = 8). Regional lymph nodes were prophylactically irradiated in 24/51 cats (47.1%). Twenty‐five cats (49.0%) developed progressive disease: progression was local (nasal) in five (9.8%), locoregional (nodal) in two (3.9%), local and locoregional in three (5.9%), systemic in nine (17.6%) and both local and systemic in six cats (11.8%). No cat receiving prophylactic nodal irradiation had progression in the locoregional lymph nodes. The median time to progression was 974 days (95%CI: 283;1666), with 58% and 53% of cats free of progression at 1 and 2 years, respectively. Median overall survival was 922 days (95%CI: 66;1779) with 61% and 49% alive at 1 and 2 years, respectively. Half of the cats that died of relapse/progression (13/26) died within 6 months of treatment, suggesting possible shortcomings of staging, rapid dissemination of disease or sequential lymphomagenesis. None of the prognostic factors evaluated were predictive of outcome (prednisolone use, anaemia, nasopharyngeal involvement, modified canine Adams tumour stage, protocol, total dose). Radiotherapy is an effective treatment for localized sinonasal lymphoma with a long time to progression. However, in one‐third of the cats, systemic disease progression occurs soon after radiotherapy.     

Using biologically based objectives to optimize boost intensity‐modulated radiation therapy planning for brainstem tumors in dogs

Irradiated brain tumors commonly progress at the primary site, generating interest in focal dose escalation. The aim of this retrospective observational study was to use biological optimization objectives for a modeling exercise with simultaneously‐integrated boost IMRT (SIB‐IMRT) to generate a dose‐escalated protocol with acceptable late radiation toxicity risk estimate and improve tumor control for brainstem tumors in dogs safely. We re‐planned 20 dog brainstem tumor datasets with SIB‐IMRT, prescribing 20 × 2.81 Gy to the gross tumor volume (GTV) and 20 × 2.5 Gy to the planning target volume. During the optimization process, we used biologically equivalent generalized equivalent uniform doses (gEUD) as planning aids. These were derived from human data, calculated to adhere to normal tissue complication probability (NTCP) ≤5%, and converted to the herein used fractionation schedule. We extracted the absolute organ at risk dose‐volume histograms to calculate NTCP of each individual plan. For planning optimization, gEUD_{(a = 4)} = 39.8 Gy for brain and gEUD_{(a = 6.3)} = 43.8 Gy for brainstem were applied. Mean brain NTCP was low with 0.43% (SD ±0.49%, range 0.01‐2.04%); mean brainstem NTCP was higher with 7.18% (SD ±4.29%, range 2.87‐20.72%). Nevertheless, NTCP of < 10% in brainstem was achievable in 80% (16/20) of dogs. Spearman's correlation between relative GTV and NTCP was high (ρ = 0.798, P < .001), emphasizing increased risk with relative size even with subvolume‐boost. Including biologically based gEUD values into optimization allowed estimating NTCP during the planning process. In conclusion, gEUD‐based SIB‐IMRT planning resulted in dose‐escalated treatment plans with acceptable risk estimate of NTCP < 10% in the majority of dogs with brainstem tumors. Risk was correlated with relative tumor size.     

Laparoscopically implanted tissue expander radiotherapy in canine transitional cell carcinoma

Organ motion and injury to adjacent structures limit curative treatment of intraabdominal tumors with external beam radiotherapy. We evaluated the use of Laparoscopically Implanted Tissue Expander Radiotherapy (LITE-RT) to exclude critical structures during irradiation of the urinary bladder in two dogs with transitional cell carcinoma (TCC) using helical tomotherapy. Dogs had histologically confirmed bladder TCC with no metastasis. A custom-shaped tissue expander was placed between the colon and bladder laparoscopically in one dog and during laparotomy in the other. The prescribed radiation dose was 45 Gy to 98% volume of the bladder in 18 fractions of 2.5 Gy. Tumor response and normal tissue effects were monitored with cystoscopy and colonic biopsies before treatment and 3, 6, and 15 months after treatment. Based on treatment plans from inflated vs. deflated tissue expander CT images, there was a mean dose reduction to the colon of 53% and 31% for the two dogs. Interfractional target repositioning was possible by using volumetric megavoltage computed tomography helical tomotherapy. Both dogs had no clinical signs of chronic colitis but did experience mild cystitis during treatment. Tissue expanders became detached, requiring an additional surgery for reattachment, in both dogs. One dog developed a fibrous adhesion resulting in bladder rupture during inflation, which necessitated early device removal. One dog was euthanized for tumor-associated ureteral obstruction at 8 months while the other is alive at 21 months. We conclude that LITE-RT shows promise in treatment of canine bladder TCC due to lack of acute colitis and enteritis.     

Evaluation of mega-voltage CT images for completed radiotherapy treatments for dogs and cats reveals uncommon but potentially consequential dose deviation in thoracic and abdominal tumors

As advanced delivery techniques such as intensity-modulated radiation therapy (IMRT) become conventional in veterinary radiotherapy, highly modulated radiation delivery helps to decrease dose to normal tissues. However, IMRT is only effective if patient setup and anatomy are accurately replicated for each treatment. Numerous techniques have been implemented to decrease patient setup error, however tumor shrinkage, variations in the patient's contour and weight loss continue to be hard to control and can result in clinically relevant dose deviation in radiotherapy plans. Adaptive radiotherapy (ART) is often the most effective means to account for gradual changes such as tumor shrinkage and weight loss, however it is often unclear when adaption is necessary. The goal of this retrospective, observational study was to review dose delivery in dogs and cats who received helical radiotherapy at University of Wisconsin, using detector dose data (D2%, D50%, D98%) and daily megavoltage computed tomography (MVCT) images, and to determine whether ART should be considered more frequently than it currently is. A total of 52 treatment plans were evaluated and included cancers of the head and neck, thorax, and abdomen. After evaluation, 6% of the radiotherapy plan delivered had clinically relevant dose deviations in dose delivery. Dose deviations were more common in thoracic and abdominal targets. While adaptation may have been considered in these cases, the decision to adapt can be complex and all factors, such as treatment delay, cost, and imaging modality, must be considered when adaptation is to be pursued.     

Outcome of a dog undergoing definitive‐intent intensity‐modulated radiation therapy for an intranasal ganglioneuroma

An 11‐year‐old intact male Shiloh Shepherd was presented for evaluation of epistaxis, decreased nasal airflow, and destructive caudal nasal lesion identified using CT. Histopathologic evaluation of the nasal mass was consistent with a ganglioneuroma. The dog was treated with 10 × 4.2 Gy using IMRT technique. Post radiation therapy (RT), improvement in clinical signs were noted. Tumor progressed in size based on CT evaluation at 49 days, 3, and 6 months post‐treatment. A grade 2 oral mucositis was the only RT side effect noted. Radiation therapy as described above was completed without evidence of high‐grade radiation toxicities and has potential to improve clinical signs but failed to induce tumor response.