Sustained metabolic response in metastatic melanoma after intraperitoneal ozone therapy: a case report

Metastatic melanoma remains a therapeutic challenge despite major advances in immunotherapy and targeted therapies. Immune checkpoint inhibitors and BRAF/MEK inhibitors have improved survival in selected patients; however, their use may be limited by immune-related adverse events, acquired resistance, deterioration in quality of life, and economic burden. Intraperitoneal ozone therapy (IPO₃) has been described as a feasible and well-tolerated complementary approach in advanced oncologic settings, although clinical evidence remains limited. This case report describes the clinical and metabolic evolution of a patient with refractory metastatic melanoma treated with high-dose IPO₃ after progression under immunotherapy and intolerance to targeted therapy.

A 66-year-old woman with a history of cutaneous melanoma developed extensive metastatic disease involving subcutaneous, muscular, pulmonary, pleural, and left adrenal sites. Disease progression was documented after adjuvant pembrolizumab, and targeted therapy with dabrafenib plus trametinib was discontinued because of clinically significant systemic toxicity. In June 2024, the patient initiated high-dose IPO₃. Serial positron emission tomography-computed tomography (PET-CT) scans showed sustained disappearance of pathological hypermetabolic uptake in previously affected systemic sites, with isolated persistence and oscillation of metabolic activity in the left adrenal lesion. Additional IPO₃ cycles were administered, and focal radiotherapy was directed to the persistent adrenal lesion. Treatment was clinically well tolerated, with no significant adverse events. Progressive functional improvement was documented, with Karnofsky performance status increasing from 60% at treatment initiation to 90% during follow-up.

In this case, high-dose IPO₃ was temporally associated with sustained systemic metabolic remission and objective functional improvement in refractory metastatic melanoma. Although a causal relationship cannot be established from a single observation, these findings support further prospective studies to evaluate the safety, efficacy, and potential immunometabolic mechanisms of IPO₃ as a complementary strategy in selected oncologic scenarios.