Complete Response Demonstrated by [ 11 C]methionine-PET Imaging of a Patient With Squamous-cell Carcinoma of the Tongue Treated With Chemotherapy, Immunotherapy and Methionine Restriction Without Radiation or Surgery: A Potential New Low-toxicity Tre

Background/Aim: Head and neck squamous-cell carcinoma (HNSCC) is associated with substantial morbidity. Treatment of locally-advanced disease commonly involves surgery, radiotherapy, and systemic therapy, which may result in functional impairment and treatment-related toxicity. Methionine addiction, known as the Hoffman effect, is a metabolic hallmark of cancer that is targeted by methionine restriction. We report here a patient with locally-advanced HPV-positive squamous-cell carcinoma of the tongue who achieved a complete response following chemotherapy combined with methionine restriction and subsequent immunotherapy, without surgery or radiotherapy. Case Report: A 58-year-old man was diagnosed with HPV-positive squamous-cell carcinoma arising from the base of the tongue with extensive cervical lymph-node involvement (cT1N3M0). The patient elected to avoid surgery and radiotherapy because of concerns regarding functional impairment and disfigurement. Treatment consisted of seven cycles of docetaxel, cisplatinum, and 5-fluorouracil combined with a low-methionine diet and oral recombinant methioninase (o-rMETase). Pembrolizumab was initiated during the fifth chemotherapy cycle and continued as maintenance therapy. The cervical tumor rapidly regressed and became clinically undetectable after the initial treatment cycles. Follow-up [11C]methionine-PET/CT and [18F]FDG-PET/CT demonstrated no evidence of active disease, consistent with a complete response. The patient remains clinically well without evidence of recurrence and continues pembrolizumab therapy and methionine restriction. Conclusion: The present case demonstrates a complete clinical and metabolic response in a patient with locally-advanced HPV-positive tongue squamous-cell carcinoma treated with combination chemotherapy, methionine restriction, and pembrolizumab without surgery or radiotherapy. Although the present findings suggest that methionine restriction may have potential as an adjunct to systemic treatment in HNSCC, additional case series and prospective clinical studies are required to determine the efficacy, safety, and generalizability of this therapeutic approach.