In radiation therapy tumor size, and thus also volume, has a significant impact on the local control of tumors. Moreover, tumor volume is a significant prognostic factor for modelling and predicting therapeutic outcomes in cancer treatment. In research, the distribution of tumor volumes in patient populations has so far remained widely unexplored. In this work, the frequency distributions of maximum diameter of tumors for various types of cancer was studied based on SEER data and it was explored if they can be modelled using Weibull distributions. Further, actual volume data were obtained directly from computer tomography (CT) datasets and the frequency distributions of tumor volumes and maximum diameters were explored and a link between them was found. In cancer research, tumors are often modelled as ellipsoids. In order to verify the appropriateness of using ellipsoids as a model, to the obtained three-dimensional data, ellipsoids were fitted and the resulting volumes and diameters analysed. Finally, NSCLC tumor diameters were Monte Carlo simulated using tumor growth and incidence models. A comparison of the simulated tumor diameter distributions with observed SEER data yielded the determination of tumor growth rates.

Dear Editor, We have read with interest the article by José-Lopez and colleagues titled “Clinical features, diagnosis, and survival analysis of dogs with glioma.” In this publication the authors characterize clinicopathologic findings, diagnostic imaging features and survival of a sample of dogs with glioma, along the Comparative Brain Tumor Consortium diagnostic classification. While we appreciate the thorough investigation of clinicopathological and imaging features, we would like to raise a few points of discussion regarding treatment and survival. Our first concern about the used terminology for “definitive” treatments. The definition of the term “definitive” treatment was based on a study of histiocytic sarcoma involving the CNS and we believe could be misleading. A systematic review of brain tumor treatment in dogs examines the scientific evidence supporting use of radiation therapy and surgery, and at the same time underlining the lack of evidence for chemotherapy in treatment of brain tumors in dogs. Since then, no additional findings have been added to the scientific literature on chemotherapy and chemotherapy is not a recommended or acceptable treatment of intracranial tumors at this time. In José-Lopez et al's study radiation therapy was acknowledged as “anecdotal” treatment. We are surprised about this, quoting Hu et al: “There has long been a suggestion that combinations of treatment, notably surgery and radiotherapy, provide the best mode of treatment for brain tumors (particularly meningiomas),(...). However, looking at the data as a whole, this conclusion appears inappropriate because the evidence would suggest that adding radiotherapy to surgery has a large impact,(...) whereas adding surgery to radiotherapy has no impact,(...) suggesting that radiotherapy is the effective modality and surgery may have little additive effect.” Also, in the meantime, several veterinary publications on outcome after radiotherapy with newer, standard-of-care irradiation devices have become available in the peer-reviewed literature. In José-Lopez et al's study, treatments seem chosen and distributed randomly, without information on dosages, dose intensity or quality of radiation therapy. This leads to a substantial lack of quality validation or standardization of the claimed “definitive” treatments and in our view could mislead the uncritical or inexperienced reader and client in regard to possible outcome of dogs with glial tumors. Such variable treatments should also not be used to make predictions on prognostic indicators. Surgery indeed often leads to subpar outcome likely because a high percentage of tumors are not amenable to an oncological definitive (clean) resection in this often highly infiltrative disease. Cytoreductive surgeries/debulking in oncology cannot be considered a stand-alone therapy for any type of tumor and in general serve only to palliate. Median survival time after surgery—often anecdotally claimed as the standard treatment by neurologists and surgeons— remains unfortunately not well described and is at best short, around 6 months. Radiation oncologists have shown various times that dogs with glioma have an excellent outcome after radiation therapy, when compared to symptomatic, palliative treatment. Using the state-of-the-art irradiation devices of the last decade, time to progression has oscillated around 18 months, with disease-specific survivals around 20 months. These dogs have a good life after treatment, even though tumors might subsequently recur or disseminate within the CNS. Of second concern is the that >50% of the 91 dogs were immediately euthanized upon diagnosis, which was based on results of imaging. While these dogs were excluded in the survival analysis, recommendations with regard to euthanasia or treatment were most likely made based on initial first diagnostic imaging. Making treatment decisions based on diagnostic imaging only is often criticized, (own experience). Noninvasive diagnosis, which is based on imaging, is often chosen by clinical radiation oncologists and neurologists because of the perceived risk of biopsy in dogs with this disease. Furthermore, it does not appear to be consistent to criticize treatmentdecision-making on imaging diagnosis, but then recommending euthanasia on the other hand directly after diagnostic imaging. Our third concern is the “main takeaway” from José-Lopez et al that no associations were found between clinicopathologic findings or survival and tumor type or grade. Unfortunately, in spite of the meticulous description of clinical and diagnostic imaging features, the tumor volume, one of the only factors so far found to possibly be of relevance with regard to outcome, was not included in the evaluation. It is surprising to us that none of the described prognostic variables were of prognostic value. This would render all the recommendations for pretreatment biopsies or advanced imaging baseless, as extensive diagnostics clinically only serve to refine the guide to treatment-decision making. It would also disqualify the valuable findings of this study, such as the description of margins, MR intensities, ventricular contact and imaging association with presumed histologic classification. We believe this perceived irrelevance of histopathological classification and imaging Received: 8 July 2022 Accepted: 8 July 2022

INTRODUCTION:This case report describes a 12-year-old female spayed mixed-breed dog referred for treatment of a large, inoperable hepatocellular carcinoma. A computed tomography (CT) scan confirmed the previous ultrasonographic and laparoscopic findings of a large, lobulated, poorly defined mass on the left and central aspect of the liver. Multiple biopsies confirmed the diagnosis of hepatocellular carcinoma. Due to the large extent of the tumor, the vascular association to the Vena cava caudalis and the associated high risk of intraoperative bleeding, a resection of the mass was refrained from and a radiotherapeutic treatment was chosen. The dog underwent radiation therapy (RT) with a 6MV linear accelerator with 5×6 Gy, total dose 30 Gy. In the follow up examinations three months and one year after therapy, the dog presented in normal condition and had normal Alanine-amino-transferase (ALT) and alkaline phosphatase (AP). The tumor size measured in the CT-examinations decreased by 61% and 90%, respectively. Two years after radiation therapy the dog has a normal general condition and liver enzymes are within the normal limits.

In order to overcome the common local treatment failure of canine sinonasal tumours, integrated boost techniques were tried in the cobalt/orthovoltage era, but dismissed because of unacceptable early (acute) toxicity. Intriguingly, a recent calculation study of a simultaneously integrated boost (SIB) technique for sinonasal irradiation using intensity‐modulated radiation therapy (IMRT) predicted theoretical feasibility. In this prospective pilot study we applied a commonly used protocol of 10 × 4.2 Gy to the planning target volume (PTV) with a 20%‐SIB dose to the gross tumour volume (GTV). Our hypothesis expected this dose escalation to be clinically tolerable if applied with image‐guided IMRT. We included 9 dogs diagnosed with sinonasal tumours without local/distant metastases. For treatment planning, organs at risk were contoured according to strict anatomical guidelines. Planning volume extensions (GTV/CTV/PTV) were standardized to minimize interplanner variability. Treatments were applied with rigid patient positioning and verified daily with image guidance. After radiation therapy, we set focus on early ophthalmologic complications as well as mucosal and cutaneous toxicity. Early toxicity was evaluated at week 1, 2, 3, 8 and 12 after radiotherapy. Only mild ophthalmologic complications were found. Three patients (33%) had self‐limiting moderate to severe early toxicity (grade 3 mucositis) which was managed medically. No patient developed ulcerations/haemorrhage/necrosis of skin/mucosa. The SIB protocol applied with image‐guided IMRT to treat canine sinonasal tumours led to clinically acceptable side effects. The suspected increased tumour control probability and the risk of late toxicity with the used dose escalation of 20% has to be further investigated.

While surgery is the treatment of choice for thymomas, complete excision is not possible in a significant proportion of cases. For these patients, radiotherapy can be used as neoadjunctive, post-operative adjunctive or sole therapy. During radiotherapy, rapid biological clearance of tumour cells is often observed, requiring adaptation of the treatment plan. Adaptive radiation therapy (RT) is a dynamic process, whereby the treatment plan is altered throughout the treatment course due to changes in morphologic, functional or positioning changes. With the hypothesis, that individually adapted replanning will massively reduce the dose to organs at risk (OAR) in a fast-changing environment such as a rapidly responding thymoma, the dosimetric impact of adaptive treatment planning in 5 patients with large thymoma was measured. In all patients rapid tumour-shrinkage of the gross tumour volume was observed after 1 week of therapy, with a mean shrinkage of 31.0% ± 15.2%, or a tumour regression of 5.2% per day. In consequence, there was a considerable change in position of organs such as heart and lung, both of them moving cranially into the high dose area upon tumour regression. After mid-therapy replanning, the dose to OAR was significantly reduced, with -18.2% in the mean heart dose and -27.9% in the V20 lung dose. Adaptive planning led to a significantly reduced radiation dose and hence protection of OAR for these patients. It can be concluded that adaptive replanning should be considered for canine and feline thymoma patients receiving fractionated RT.

Stage 3b anal sac gland carcinoma (ASGC) can be life-threatening. A surgical approach is not always possible or may be declined. Dogs with stage 3b ASGC treated with surgery or conformal radiation therapy (RT) with 8 × 3.8 Gy (total dose 30.4 Gy, over 2.5 weeks) were retrospectively evaluated. Patient characteristics, median progression-free interval (PFI) and median survival time (MST) were compared. Twenty-eight dogs were included; 15 underwent surgery, 13 underwent RT. At the time of presentation, 21% showed life-threatening obstipation and 25% showed hypercalcaemia. PFI and MST for surgery cases were 159 days (95% CI: 135-184 days) and 182 days (95% CI: 146-218 days), both significantly lower than for RT cases with 347 days (95% CI: 240-454 days) and 447 days (95% CI: 222-672 days), (P = 0.01, P = 0.019). Surgery as well as RT led to a fast relief of symptoms. PFI and survival of surgical patients were significantly inferior to that of a comparable patient group treated with conformal hypofractionated RT.

________________________________________________________________________________interview technique with an independent interviewer.The focus group was conducted shortly after the completion of the first clinical placement.The themes that came from this were then used to create a survey for group B. This was also completed shortly after their first clinical placement.Additionally this survey was also

Technical advances make it possible to deliver radiation therapy for canine intracranial tumours in fewer fractions, under the assumption of equivalent tumour control. With the aim of estimating the late toxicity risk profile for various tumour sizes and locations, the present paper evaluates the normal tissue complication probability (NTCP) values for the intracranial organs at risk. By making isoeffect calculations, a new 10-fraction radiation protocol was developed with the same tumour control probability (TCP) as a currently used 20-fraction standard protocol, and complication risk profiles for brain, brainstem and optic chiasm were modelled using a representative population of 64 dogs with brain tumours. For >59% of cases, the new 10-fraction protocol yielded an acceptable, low risk estimate of late toxicity (<10%). Our calculations suggest that it may be safe to treat small to intermediate-sized tumours that are neither located near the optic chiasm nor at the brainstem with 10 daily fractions of 4.35 Gy.

TriN 2755 is an alkylating antineoplastic agent for intravenous (IV) use, carrying the triazene group as the cytotoxic principal. Using a standard 3 + 3 design, a phase I study was performed in tumour bearing dogs to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and pharmacokinetic (PK) profile of TriN 2755. Thirty dogs were included in the study. TriN 2755 was administered over 20 min on two consecutive weeks per month for a total of three cycles. The starting dose was 25 mg kg-1 and the MTD was 74.6 mg kg-1 . Three dogs experienced DLT, which was characterized by gastrointestinal adverse events. The PKs of TriN 2755 and its main metabolites in plasma and sputum are described in a two-compartment model. The response rate for 19 of 30 dogs was 47.3% (six partial remission, three stable disease) and the median progression-free interval (PFI) for the responders was 47 days (range: 21-450 days).

BACKGROUND:The epothilones are microtubule-stabilizing agents with promising antitumor effect in refractory and metastatic tumors in humans. The toxicity profile is considered more favorable than in taxanes. The safety of epothilone B (patupilone) has not been evaluated in tumor-bearing dogs.OBJECTIVES:To evaluate the inhibition of proliferation in canine tumor cells after patupilone treatment. To assess toxicity profile and maximally tolerated dose of patupilone in dogs with refractory tumors.ANIMALS:Twenty client-owned dogs with various malignancies.METHODS:Prospective clinical study. The inhibition of proliferation was assessed with a proliferation assay in vitro in canine hemangiosarcoma and lymphoma cell lines. Dogs received patupilone IV once a week for 2 treatments (= 1 treatment cycle). Dose was escalated with 3 dogs per cohort and 20% increments. Adverse effects were graded according to the VCOG-CTCAE v1.0.RESULTS:Both canine cell lines were sensitive to patupilone with approximately 50% decrease in proliferative activity at 0.2-1 nM. In vivo, dose-limiting adverse effects occurred at 3.3 mg/m(2); main adverse effects were diarrhea, anorexia, vomiting, and nausea. Neither neutropenia nor peripheral neuropathy was observed. Maximally tolerated dose for 2 patupilone administrations once weekly IV is 2.76 mg/m(2). Three per 11 dogs receiving more than 1 treatment cycle showed partial remission in the short period of observation.CONCLUSIONS AND CLINICAL IMPORTANCE:Canine tumor cells show inhibition of proliferation to patupilone in vitro. Clinically, a dose of 2.76 mg/m(2) IV is well tolerated in dogs with spontaneously occurring tumors.