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

Radiation toxicity grading after chemoradiotherapy of canine urinary tract carcinomas: Comparing VRTOG to VRTOG_v2.0

Radiation toxicities may be underestimated after treatment of transitional cell carcinoma in dogs' lower urinary tract. Assessing acute and late toxicities and differentiating them from progressive disease (PD) impacts further therapeutic approach. We retrospectively assessed dogs treated with definitive‐intent chemoradiotherapy (12 × 3.8 Gy, various first‐line chemotherapeutics). Local tumour control, radiation toxicities and survival were evaluated. We classified radiation toxicities according to the previously published radiation toxicity scheme “VRTOG” as well as the updated version, “VRTOG_v2.0”. Fourteen dogs with transitional cell carcinoma of bladder ± urethra (n = 8), +prostate (n = 3) or solely urethra (n = 3), were included. Median follow‐up was 298 days (range 185–1798 days), median overall survival 305 days (95%CI = 209;402) and 28.6% deaths were tumour‐progression‐related. Acute radiation toxicity was mild and self‐limiting with both classification systems: In VRTOG, 5 dogs showed grade 1, and 1 dog grade 2 toxicity. In VRTOG_v2.0, 2 dogs showed grade 1, 3 dogs grade 2, and 3 dogs grade 3 toxicity. Late toxicity was noted in 14.2% of dogs (2/14) with the VRTOG, both with grade 3 toxicity. With VRTOG_v2.0, a larger proportion of 42.9% of dogs (6/14) showed late toxicities: Four dogs grade 3 (persistent incontinence), 2 dogs grade 5 (urethral obstructions without PD resulting in euthanasia). At time of death, 5 dogs underwent further workup and only 3 were confirmed to have PD. With the updated VRTOG_v2.0 classification system, more dogs with probable late toxicity are registered, but it is ultimately difficult to distinguish these from disease progression as restaging remains to be the most robust determinant

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

Risk adaptive planning with biology-based constraints may lead to higher tumor control probability in tumors of the canine brain: A planning study

Background: Classical radiation protocols are guided by physical dose delivered homogeneously over the target. Protocols are chosen to keep normal tissue complication probability (NTCP) at an acceptable level. Organs at risk (OAR) adjacent to the target volume could lead to underdosage of the tumor and a decrease of tumor control probability (TCP). The intent of our study was to explore a biology-based dose escalation: by keeping NTCP for OAR constant, radiation dose was to be maximized, allowing to result in heterogeneous dose distributions. Methods: We used computed tomography datasets of 25 dogs with brain tumors, previously treated with 10x4 Gy (40 Gy to PTV D50). We generated 3 plans for each patient: A) original treatment plan with homogeneous dose distribution, B) heterogeneous dose distribution with strict adherence to the same NTCPs as in A), and C) heterogeneous dose distribution with adherence to NTCP <5%. For plan comparison, TCPs and TCP equivalent doses (homogenous target dose which results in the same TCP) were calculated. To enable the use of the generalized equivalent uniform dose (gEUD) metric of the tumor target in plan optimization, the calculated TCP values were used to obtain the volume effect parameter a. Results: As intended, NTCPs for all OARs did not differ from plan A) to B). In plan C), however, NTCPs were significantly higher for brain (mean 2.5% (SD±1.9, 95%CI: 1.7,3.3), p<0.001), optic chiasm (mean 2.0% (SD±2.2, 95%CI: 1.0,2.8), p=0.010) compared to plan A), but no significant increase was found for the brainstem. For 24 of 25 of the evaluated patients, the heterogenous plans B) and C) led to an increase in target dose and projected increase in TCP compared to the homogenous plan A). Furthermore, the distribution of the projected individual TCP values as a function of the dose was found to be in good agreement with the population TCP model. Conclusion: Our study is a first step towards risk-adaptive radiation dose optimization. This strategy utilizes a biologic objective function based on TCP and NTCP instead of an objective function based on physical dose constraints. Keywords: Biologic objective function; Biology-based; Brain tumor; Dog; IMRT; Intensity-modulated radiation therapy; NTCP; Radiation therapy; Risk-adaptive optimization; TCP

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