# Adaptive, Clinically Guided Multimodal Therapy with Supportive Drug Sensitivity Testing in a Dog with Hepatic Neuroendocrine Carcinoma: A Case Report

## TL;DR

This case report describes a personalized treatment approach for a dog with rare liver cancer, using drug sensitivity testing and adaptive therapy to manage the disease.

## Contribution

The paper introduces an adaptive, multimodal treatment strategy for a rare canine cancer, integrating drug sensitivity testing with clinical response monitoring.

## Key findings

- Ex vivo drug sensitivity testing provided supportive but not predictive data for treatment decisions.
- Sequential therapy transitions achieved sustained clinical stability despite early in vitro-outcome discordance.
- Adjunct immunomodulatory therapy was used, though its independent effect could not be determined.

## Abstract

This case describes a dog with advanced hepatic neuroendocrine carcinoma characterized by multifocal intrahepatic lesions and regional lymph node metastasis, for which no standardized systemic protocol has been established. An ex vivo drug sensitivity assay was performed at diagnosis as supportive, hypothesis-generating information to complement clinical decision-making. Systemic therapy was adapted sequentially based on imaging response, tolerability, and quality-of-life considerations, including doxorubicin followed by mitoxantrone with lomustine and subsequently toceranib. A cytokine-based NK cell activator was administered as an adjunct during the treatment course; however, its independent clinical contribution could not be determined in the absence of immune or pharmacodynamic monitoring. Despite early discordance between in vitro findings and in vivo response, protocol transitions achieved sustained clinical stability with acceptable tolerability, highlighting the value of response-driven treatment adaptation in rare canine hepatic malignancies.

Hepatic neuroendocrine carcinoma (NEC) in dogs is a rare malignancy with limited therapeutic guidance and no established standard of care. This report describes an adaptive, clinically guided multimodal treatment approach in a dog with advanced hepatic NEC with regional lymph node involvement. Sequential systemic therapies—including doxorubicin, mitoxantrone with lomustine and prednisolone, and subsequently toceranib—were administered based on clinical response assessment using imaging (VCOG RECIST), hematologic monitoring, and quality-of-life evaluation. Ex vivo drug sensitivity testing (DST) was performed to provide functional reference information but was interpreted as supportive rather than predictive. Notably, discordance was observed between strong in vitro sensitivity to doxorubicin and early clinical progression, underscoring the limitations of monoculture-based assays in recapitulating in vivo tumor biology. Sustained stable disease was observed following transition to toceranib with continued adjunct immunomodulatory therapy; however, the independent contribution of each treatment component cannot be determined. This case highlights the feasibility of iterative treatment refinement in rare canine malignancies and emphasizes that DST findings should be integrated cautiously within a broader clinical decision-making framework.