Development of a new methodology to induce immunological chimerism after allogeneic hematopoietic cell (HC) transplantation in a rhesus macaque model is described. The chimeric state was achieved using a non-myeloablative, helical tomotherapy-based total lymphoid irradiation (TomoTLI) conditioning regimen followed by donor HC infusions between 1-haplotype matched donor/recipient pairs. The technique was tested as a feasibility study in an experimental group of seven rhesus macaques that received the novel TomoTLI tolerance protocol and HC allo-transplants. Two tomotherapy protocols were compared: TomoTLI (n = 5) and TomoTLI/total-body irradiation (TBI) (n = 2). Five of seven animals developed mixed chimerism. Three of five animals given the TomoTLI protocol generated transient mixed chimerism with no graft-versus-host disease (GVHD) with survival of 33, 152 and >180 days. However, the inclusion of belatacept in addition to a single fraction of TBI resulted in total chimerism and fatal GVHD in both animals, indicating an unacceptable conditioning regimen.

No standard of care is currently recognized for treatment of canine prostatic carcinoma (PC). This retrospective study assesses outcome following definitive‐intent, intensity‐modulated radiation therapy (RT) in dogs with PC. Medical records review was performed, including 18 patients from four institutions undergoing definitive‐intent intensity‐modulated radiotherapy to treat PC. Diagnosis was incidental in 7/18 (39%) patients. Five dogs (28%) had evidence of metastasis to loco‐regional lymph nodes at diagnosis. Seventeen patients received concurrent non‐steroidal anti‐inflammatory drugs; 15/18 (83%) patients received maximally‐tolerated dose (MTD) chemotherapy, with variable drugs and protocols employed. Total prescribed radiation dose ranged from 48 to 54 Gy (median 50 Gy) delivered as daily doses of 2.5‐2.8 Gy. One patient was euthanized prior to completing radiotherapy. Acute toxicity was observed in nine patients; Grade 1‐2 diarrhoea was the most common toxicity observed. Suspected late toxicity (urethral stricture, ureteral stricture and hindlimb oedema) was observed in three patients. Median event‐free survival (EFS) following RT was 220 days, and median overall survival was 563 days. Local progression occurred in seven patients at a median of 241 days. Median overall survival was significantly longer in incidentally diagnosed dogs (581 vs 220 days in symptomatic dogs, P = .042). EFS was significantly longer in patients treated with MTD chemotherapy (241 vs 25 days, P < .001), and significantly shorter in patients presenting with evidence of metastatic disease (109 days) vs those without (388 days, P = .008). These findings suggest that definitive‐intent radiotherapy is a valuable treatment option for local control of canine PC with moderate risk of toxicity.

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 definitiveintent, intensity modulated radiation therapy (IMRT) for canine intracranial tumors are lacking. IMRT 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 evaluation of 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 magnetic resonance imaging. Presumed radiological diagnoses included 37 meningiomas, 12 gliomas, and 1 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% CI 12.3-26.6 months). As previously described for brain tumors, increasing severity of neurologic signs at diagnosis was associated with a worse outcome. IMRT was well tolerated with few reported acute, acute delayed or late side effects.

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.

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