Solitary intraventricular tumors in dogs and cats treated with radiotherapy alone or combined with ventriculoperitoneal shunts: A retrospective descriptive case series

Background: Intraventricular tumors are rare, optimal treatment is not defined. Symptomatic patients often exhibit life-threatening hydrocephalus. With several months time-to-effect after radiotherapy (RT), increased intracranial pressure is concerning. This increase in pressure can be overcome by ventriculoperitoneal shunting (VPS). Objectives: Retrospective evaluation of outcome and complications in dogs and cats with intracranial tumors treated with either RT or VPS/RT. Animals: Twelve client-owned cats and dogs. Methods: Dogs and cats with symptomatic intraventricular tumors treated with definitive-intent RT or VPS/RT were included in a retrospective, descriptive case series. Complications, tumor volume evolution, time-to-progression, and survival time were determined. Results: Twelve animals were included: 1 cat and 5 dogs treated with single-modality RT and 4 cats and 2 dogs treated with VPS/RT. Neurological worsening seen in 4/6 animals during single-modality RT and 2/6 died during RT (suspected brain herniation). All dogs with VPS normalized clinically by the end of RT or earlier. Complications occurred in 4/6 animals, all but 1 were successfully managed surgically. Imaging follow-up in 8 animals surviving RT showed a marked decrease in tumor volume. Median survival time was 162 days (95% confidence interval [CI]: 16; infinity) for animals treated with RT and 1103 days (95%CI: 752; infinity) for animals treated with VPS/RT. Median time-to-progression was 71 days (95%CI: 7; infinity) and 895 days (95%CI: 704; infinity) for each group, respectively. Two dogs died because of intraventricular metastasis 427 and 461 days after single-modality RT. Conclusions and clinical importance: Ventriculoperitoneal shunting led to rapid normalization of neurological signs and RT had a measurable effect on tumor volume. Combination of VPS/RT seems to be beneficial

Indocyanine-based near-infrared lymphography for real-time detection of lymphatics in a cat with multiple mast cell tumours

Case summary An 11-year-old female domestic shorthair cat was presented with cutaneous mast cell tumours (MCTs) localised at the right temporal region, the left buccal region and on the third digit of the right thoracic limb. Staging was negative and locoregional lymph nodes appeared normal, based on clinical findings. During surgery, real-time indocyanine green (ICG)-based lymphography was performed to detect the cutaneous draining pattern of all the primary MCTs. ICG was injected intracutaneously in four quadrants around each tumour, and a clear lymphogram was visible shortly after injection. Using near-infrared lymphography (NIR-L) for guidance, all lymphadenectomies were performed in 12 mins or less, with a maximal incision length of 3.5 cm. The smallest resected node was 0.9 cm in diameter. All MCTs were classified as low-grade cutaneous MCT. All four ICG-positive lymph nodes were considered premetastatic or metastatic. The only ICG-negative resected node was also negative for tumour cells. No complications related to NIR-L were recorded. Relevance and novel information This is the first description of NIR-L in a cat with MCT. Application was straightforward and ICG enrichment only occurred in the metastatic nodes, suggesting correct identification of lymphatic draining patterns. Of note, as previously described in dogs, we did detect nodal metastasis, despite low-grade primary tumours. The clinical relevance should be evaluated in future studies

Lymph node metastasis in feline cutaneous low-grade mast cell tumours

Objectives This retrospective study aimed to determine the incidence of nodal metastatic disease in cats affected by low-grade cutaneous mast cell tumours (MCTs) in our study population. Methods The clinical records of two centres were retrospectively searched for cats with cutaneous MCTs that had undergone lymphadenectomy of enlarged and non-enlarged lymph nodes. All primary tumours were histologically reviewed by two experienced pathologists and graded as high- or low-grade based on the grading system for feline cutaneous MCT. We graded the lymph nodes based on the grading scheme used for canine MCTs and considered HN2 and HN3 nodes to be metastatic. The number of patients with nodal metastasis was calculated. Results We identified 17 cats with cutaneous MCT resection and concurrent lymphadenectomy. All 21 MCTs were graded as low grade and 30 nodes were removed, with 12 being considered early or overtly metastatic (HN2 or HN3, respectively). Based on nodal status, 10/17 (59%) cats were affected by nodal metastasis in our population. Conclusions and relevance In contrast to previous reports, high percentage of cats with cutaneous MCTs in which lymphadenectomy was performed were presented with metastatic lymph nodes. The clinical relevance of this finding and a potential benefit of lymphadenectomy must be determined in future studies

Treatment of intracranial neoplasia in dogs using higher doses: A randomized controlled trial comparing a boosted to a conventional radiation protocol

Background: Local progression of intracranial tumors can be the consequence of insufficient radiation dose delivered. Dose increases in the brain must be made carefully so as not to risk debilitating adverse effects such as radiation necrosis. Hypothesis: A new protocol with 10 × 4 Gy + 11% physical dose increase limited to the macroscopic tumor volume results in a clinically better outcome compared to a 10 × 4 Gy protocol. Animals: Fifty-seven client-owned dogs with primary intracranial neoplasia. Methods: Randomized controlled trial. Twenty-eight dogs were assigned to the control protocol (10 × 4 Gy) and 29 to the simultaneous integrated boost (SIB) protocol with 4.45 Gy dose increase. Treatment groups were compared for outcome and signs of toxicity. Results: Mild, transient acute or early-delayed adverse radiation effects were observed in 5 dogs. Severe late adverse effects were not seen. Between the protocols, no significant differences were found for outcome (intention-to-treat analysis): overall time to progression (TTP) was 708 days (95% confidence interval (95% CI) [545,872]), in the control group it was 828 days (95% CI [401,1256]), and in the SIB group 627 days (95% CI [282,973]; P = .07). Median overall survival (OS) was 684 days (95% CI [516,853]), in the control group it was 724 days (95% CI [623,826]), and in the SIB group 557 days (95% CI [95,1020]; P = .47). None of the tested variables was prognostic in terms of outcome. Conclusion and clinical importance: The dose escalation used with an 11% physical dose increase did not result in better outcome

A concept for anisotropic PTV margins including rotational setup uncertainties and its impact on the tumor control probability in canine brain tumors

Objective. In this modelling study, we pursued two main goals. The first was to establish a new CTV-to-PTV expansion which considers the closest and most critical organ at risk (OAR). The second goal was to investigate the impact of the planning target volume (PTV) margin size on the tumor control probability (TCP) and its dependence on the geometrical setup uncertainties. The aim was to achieve a smaller margin expansion close to the OAR while allowing a moderately larger expansion in less critical areas further away from the OAR and whilst maintaining the TCP. Approach. Imaging data of radiation therapy plans from pet dogs which had undergone radiation therapy for brain tumor were used to estimate the clinic specific rotational setup uncertainties. A Monte-Carlo methodology using a voxel-based TCP model was used to quantify the implications of rotational setup uncertainties on the TCP. A combination of algorithms was utilized to establish a computational CTV-to-PTV expansion method based on probability density. This was achieved by choosing a center of rotation close to an OAR. All required software modules were developed and integrated into a software package that directly interacts with the Varian Eclipse treatment planning system. Main results. Several uniform and non-isotropic PTVs were created. To ensure comparability and consistency, standardized RT plans with equal optimization constraints were defined, automatically applied and calculated on these targets. The resulting TCPs were then computed, evaluated and compared. Significance. The non-isotropic margins were found to result in larger TCPs with smaller margin excess volume. Further, we presented an additional application of the newly established CTV-to-PTV expansion method for radiation therapy of the spinal axis of human patients

Definitive-intent radiotherapy for sinonasal carcinoma in cats: a multicenter retrospective assessment

Treatment of epithelial sinonasal tumors in cats is not commonly reported. Palliative radiation protocols have been described more often than definitive-intent protocols. In this multi-institutional retrospective study, we included 27 cats treated with single-modality radiotherapy. Cats were irradiated using 10 daily fractions of 4.2Gy. Three cats (11.1%) experienced a complete clinical response and 17 (63%) had a partial clinical response. Stable clinical disease was noted in three cats (11.1%). Four cats (14.8%) showed progression within 3 months following treatment. The median time to progression for all cases was 269 days (95% CI: 225;314). The proportion of cats free of progression at 1 and 2 years was 24% (95%CI: 22%;26%) and 5% (95%CI: 5%;6%), respectively. None of the prognostic factors evaluated were predictive of outcome (anemia, tumor volume at the time of staging, modified Adams stage, intracranial involvement, facial deformity, epistaxis, inappetence or weight loss). Median overall survival (OS) for all deaths was 452 days (95%CI: 334;571). The proportion of cats alive at 1 and 2 years was 57% (95%CI: 37%;77%) and 27% (95%CI: 25%;29%), respectively. Surprisingly, cats with epistaxis had a longer median OS of 828 days (95%CI: 356;1301) compared to 296 days (95%CI: 85;508) in cats without epistaxis, (p=0.04, Breslow). Radiation therapy used as a single modality for the treatment of feline sinonasal carcinoma improved clinical signs and was well tolerated

Strahlentherapie zur Behandlung makroskopischer Analbeuteltumoren des Hundes – eine retrospektive Studie

Canine anal gland tumors are locally invasive and early metastasize to the loco-regional pelvic lymph nodes. Radiation therapy is a good method for loco-regional tumor control, especially in inoperable tumors. Since the organs in the pelvic area are sensitive to both acute and late radiation damage (chronic diarrhea, bleeding, strictures or intestinal perforations) and such damage mainly depends on the fraction size, we examined the radiation protocol used in this study with a reduced number of fractions (hypofractionated) regarding effectiveness and side effects. This retrospective study describes 13 dogs with macroscopic anal gland carcinoma that were irradiated with imaging-guided, intensity-modulated radiation therapy with a hypofractionated curative protocol of 12 × 3,8 Gy. Gross pathology was either in the region of the anal gland and/or in the sublumbar lymph nodes. Ten of the 13 dogs had advanced tumor diseases (stage 3a or 3b). The acute radiation reactions were mild to moderate and had been reported for some of the dogs in a previous study. The mean study time was 572 days (range 105–1292 days). Disease progression was observed or suspected in 7/13 dogs during the study period: local or loco-regional progression occurred in 3 dogs (23 %) and distant metastases in 4 dogs (31 %). Median progression-free survival was 480 days (95 %CI, 223–908), median survival was 597 days (95 %CI, 401–908). One year after treatment, 76,9 % (95 %CI, 53,5–100) of the dogs were still alive. The likelihood of tumor progression was lower with increasing age, otherwise none of the examined tumor or patient factors showed a prognostic influence on progression or survival time. No clinically relevant late side effects were observed apart from slight alopecia, pigmentation changes or dry, scaly skin, Medium to long-term tumor control can be expected in dogs with macroscopic anal gland tumors treated with a moderately hypofractionated radiation therapy protocol (12 × 3,8 Gy). During long-term monitoring no serious side effects or side effects requiring treatment were observed

Dose- and Volume-Limiting Late Toxicity of FLASH Radiotherapy in Cats with Squamous Cell Carcinoma of the Nasal Planum and in Mini Pigs

Purpose: The FLASH effect is characterized by normal tissue sparing without compromising tumor control. Although demonstrated in various preclinical models, safe translation of FLASH-radiotherapy stands to benefit from larger vertebrate animal models. Based on prior results, we designed a randomized phase III trial to investigate the FLASH effect in cat patients with spontaneous tumors. In parallel, the sparing capacity of FLASH-radiotherapy was studied on mini pigs by using large field irradiation. Experimental Design: Cats with T1-T2, N0 carcinomas of the nasal planum were randomly assigned to two arms of electron irradiation: arm 1 was the standard of care (SoC) and used 10 × 4.8 Gy (90% isodose); arm 2 used 1 × 30 Gy (90% isodose) FLASH. Mini pigs were irradiated using applicators of increasing size and a single surface dose of 31 Gy FLASH. Results: In cats, acute side effects were mild and similar in both arms. The trial was prematurely interrupted due to maxillary bone necrosis, which occurred 9 to 15 months after radiotherapy in 3 of 7 cats treated with FLASH-radiotherapy (43%), as compared with 0 of 9 cats treated with SoC. All cats were tumor-free at 1 year in both arms, with one cat progressing later in each arm. In pigs, no acute toxicity was recorded, but severe late skin necrosis occurred in a volume-dependent manner (7–9 months), which later resolved. Conclusions: The reported outcomes point to the caveats of translating single-high-dose FLASH-radiotherapy and emphasizes the need for caution and further investigations. See related commentary by Maity and Koumenis, p. 363