{
  "abstract": "Background Canine thyroid carcinomas (CTCs) are the most common endocrine malignancy in dogs. CTCs grow rapidly, often invade local tissues and vasculatures, and about 30% of CTC patients have metastasis at diagnosis. When surgical resection is not possible, radiation and radioiodine therapy results in survival times of ~30 months compared to 10 months in dogs with incompletely excised CTCs and no therapy. In this study, we evaluated efficacy, safety, and clinical response of ultrasound-guided intratumoral (US-IT) chemo-immunotherapy in a spontaneous canine follicular thyroid carcinoma (CFTC) patient. CFTCs share histologic and biologic behavior with differentiated human thyroid carcinomas (hTC), supporting CFTC patients as an optimal animal model for hTC studies.Methods A female companion pet with four large unresectable CFTC masses, a reactive submandibular lymph node (LN), and multiple lung node metastases was enrolled in the study (study approval #199). The patient’s owner signed an informed consent form. Under US-IT each tumor mass was treated on day 0 (D0) with liposomal doxorubicin, oxaliplatin, and combretastatin A4 Phosphate (CA4P) (0.125 mg, each) followed by US-IT therapy with anti-canine PD-1 (acPD-1, 0.5 mg), toll-like receptor (TLR) 7/8/9 agonists (0.125 mg, each), and CA4P (0.125 mg, each) on D2, D10, D17, D24, and D31. The LN received weekly treatments of acPD-1 (0.5 mg) and TLR7/8/9 agonists (0.125 mg, each). Safety was evaluated by blood and biochemistry assays and efficacy was evaluated by tumor reduction.Results Five weekly US-IT treatments did not cause immune-related adverse events and the patient had good quality of life. US images indicate cavitations in tumor masses and reduction in Doppler intensity induced by the vascular disruptor CA4P, suggestive of tumor necrosis and reduced tumor burden. Tumor shrinkage was observed in three out of four injected tumors (objective response of 75%; three partial response and one progressive disease). A partial response was observed in the injected LN, and a significant reduction in vascularity suggested an antitumor response. Although the number of small (<2cm) metastatic lung nodes increased from 13 to 19, it is remarkable that tumor growth in two of three large metastatic nodules (>2cm) was reduced which suggests an abscopal effect.Conclusions This multicomponent chemo-immune US-IT therapy caused no adverse effects, generated anti-tumor efficacy in treated tumor masses and reactive LN, and an abscopal effect in established large lung metastases. This novel IT chemo-immunotherapy could be a groundbreaking immunotherapy for CFTC patients and a potential future immunotherapy for hTC patients.Acknowledgements We thank the patient’s owner who has been very generous and supportive of the present study, the personnel of the Hospital Oncológico Veterinario La Rioja for their help, and the Canine Cancer Alliance (https://www.ccralliance.org/) for the generous funding support.Ethics Approval This study is approved by the Internal Committee for the Care and Use of Animals, Faculty of Veterinary Medicine and Zootechnics of the National Autonomous University of Mexico (Protocol #199).Consent The patient’s owner signed an informed consent form.",
  "authors": [
    {
      "affiliations": [
        "VETCONNECT Diagnóstico por imagen, Monterrey, NL, Mexico"
      ],
      "name": "Daniel Luna Dávalos"
    },
    {
      "affiliations": [
        "Hospital Oncológico Veterinario La Rioja, Monterrey, NL, Mexico"
      ],
      "name": "Lisa F Guerra Herrera"
    },
    {
      "affiliations": [
        "Hospital Oncológico Veterinario La Rioja, Monterrey, NL, Mexico"
      ],
      "name": "Odalys Francisca Brandi García"
    },
    {
      "affiliations": [
        "DIAGSA, Diagnóstico de Salud Animal, Naucalpan, EM, Mexico"
      ],
      "name": "Juan Carlos Pinto-Cardenas"
    },
    {
      "affiliations": [
        "Hospital Oncológico Veterinario La Rioja, Monterrey, NL, Mexico"
      ],
      "name": "Jesus Rodolfo Salazar Rivera"
    },
    {
      "affiliations": [
        "Geisel School of Medicine at Dartmouth, Lebanon, NH, USA"
      ],
      "name": "Steve Fiering"
    },
    {
      "affiliations": [
        "Geisel School of Medicine at Dartmouth, Lebanon, NH, USA",
        "Canine Cancer Alliance, Bellevue, WA, USA"
      ],
      "name": "Hugo Arias-Pulido"
    }
  ],
  "title": "618 A multicomponent intratumoral chemo-immunotherapeutic approach is effective in a canine metastatic thyroid cancer patient",
  "uid": "9a68cefb-f54e-536a-9336-2ce63d2530ea"
}