Evaluating the Impact of Elective Nodal Irradiation for Dogs With Oral Malignant Melanoma Undergoing Hypofractionated Radiotherapy

Abstract

Hypofractionated radiotherapy (hRT) is often used to treat dogs with oral malignant melanoma (OMM); however, there is no consensus as to whether clinically uninvolved regional lymph nodes should be prophylactically irradiated. The objective of this retrospective study is to compare outcomes for dogs with OMM treated with hRT+/- elective nodal irradiation (ENI). Dogs with nonmetastatic OMM undergoing hRT+/- ENI with a prescription of ≥ 30 Gy were included. Survival statistics were evaluated with Kaplan-Meier curves and log-rank testing. Univariable and multivariable Cox proportional hazard models were used to assess how survival was impacted by the use of ENI, WHO T-stage, mitotic count, RT technique, and use of Oncept melanoma vaccine. Data from four institutions and 100 dogs (80 with ENI and 20 without) were included. In the ENI group, nodal and distant metastases were documented in 4 and 30 dogs, respectively. In the non-ENI group, nodal and distant metastases were documented in 6 and 4 dogs, respectively. There was no significant difference in the 1-year nodal or distant progression-free intervals (p = 0.174, and 0.563, respectively). The only variable maintaining significance on multivariable analysis was T-stage (overall progression-free survival, HR 1.393, p = 0.006; overall survival time, HR 1.426, p = 0.005; distant progression-free interval, HR 1.521, p = 0.033). ENI did not measurably alter the oncologic outcomes in this study population. Results should be interpreted cautiously given the lack of standardised staging/restaging and the heterogenous nature of this clinical population. Future investigations are needed to clarify the role of ENI in the treatment of canine OMM.

Keywords: dog; lymph node; melanoma; radiotherapy.

FIGURE 1

Lymphatic anatomy in the head of the dog and lymph node inclusion in elective nodal irradiation for canine oral tumours. Normal anatomic drainage is complex and may vary amongst patients. The afferent drainage to the mandibular lymph nodes typically includes the upper and lower lip, tip of the tongue, gums, cheek, hard and soft palate, nose, as well as various skull bones. The efferent vessels of the mandibular lymph nodes open into the ipsilateral or contralateral medial retropharyngeal lymph node and the lateral retropharyngeal lymph node, if present. The afferent drainage to the medial retropharyngeal lymph nodes includes the mid to caudal tongue, gingiva, hard and soft palate, tonsil, parotid, mandibular and sublingual salivary glands, pharynx and oesophagus, nasal cavity, larynx, thyroid, trachea (initial part) and ear, various skull bones as well as efferent vessels from the mandibular, buccal, parotid and lateral retropharyngeal and cranial cervical lymph nodes. The efferent vessels combine to form the tracheal duct [21, 22, 23]. Elective nodal irradiation for oral tumours in dogs typically aims to include unilateral [24] or bilateral mandibular and/or retropharyngeal lymph nodes [12, 13, 25]. Other lymph nodes in the vicinity, such as the cranial cervical lymph node, may be included in the RT field. Abbreviations: LN, lymph node; ENI, elective nodal irradiation.

FIGURE 2

Outcomes of 100 dogs with oral malignant melanoma treated with hypofractionated RT with or without elective nodal irradiation, based on disease burden. (A) There was no difference in OPFS with the use of ENI when comparing dogs in the subclinical (log‐rank test, p = 0.36, 95% CI: 0.3260–2.791) and macroscopic (p = 0.20, 95% CI: 0.5121–1.659) disease settings. There was a significant difference between disease burden groups (p = 0.0004). (B) There was no difference in OST with the use of ENI when comparing dogs in the subclinical (log‐rank test, p = 0.82, 95% CI: 0.3546–4.049) and macroscopic (p = 0.83, 95% CI: 0.5551–2.068) disease settings. There was a significant difference between disease burden groups (p = 0.0006). Tick marks on the Kaplan–Meier curves represent censored patients. PD, progressive disease.