Carbon Radiotherapy for Rare Tumors: Electronic Consent and Follow-up

Introduction: We propose a novel study design to address a critical gap in the treatment of unresectable adenoid cystic carcinoma (ACC) of the head and neck (H&N), a rare tumor with limited research and poor patient outcomes. Prospective clinical studies for such rare tumors are difficult to conduct due to significant costs and challenges in enrolling sufficient patient numbers. Consequently, outcomes for affected patients remain poor, with current treatments using photon/proton radiation achieving suboptimal local control rates of 50 to 60% at three years, with local recurrences being the primary cause of mortality. High linear energy transfer (LET) radiation, such as fast neutron therapy, has shown improved efficacy but poses significant toxicity risks. Carbon ion radiotherapy (CIRT), a high LET radiation with better conformality, has emerged as a preferred treatment option in Europe and Asia, achieving 2-year local control rates of 80 to 90% and is recognized by NCCN guidelines as appropriate for unresectable ACC. Mayo Clinic Florida (MCF) is pioneering the establishment of the first CIRT center in North America, expected to begin treating patients in 2028. However, North American patients currently lack access to this treatment modality.

Materials and Methods: To address this gap, we propose a prospective two-arm clinical trial to investigate the benefits of a CIRT boost combined with standard photon/proton radiation for patients with unresectable ACC of the H&N. This study will leverage novel clinical trial infrastructure designed to minimize costs and personnel requirements, enabling virtual enrollment and treatment. Patients will be referred from partnering high-volume head and neck institutions and consented through a virtual video consent process through MCF. Group 1 will receive an upfront boost of CIRT of up to eight treatments (24 GyE at 3 GyE), followed by 25 to 30 treatments of photon/proton therapy (45–50 GyRBE) at their partner institution. For those unable to travel, enrollment in a prospective registry component (Group 2) will be offered. Secondary endpoints include patient quality of life, patient-reported outcomes, progression-free survival, and overall survival. The study will be powered to detect a difference in the primary endpoint, the 2-year local control (LC) rate, between patients treated with and without CIRT. Local disease progression will be assessed using clinical or radiographic exams as per RECIST 1.1 criteria. Based on literature estimates, the 2-year LC for patients treated with photon/proton radiation is expected to be 50%, compared with 90% for those treated with the combination of CIRT and photon/proton radiation. With a two-sided α of 0.05 and desired power of 80%, 14 participants will be required in each group, totaling 28 patients.

Conclusion: This study aims to transform the therapeutic landscape for rare tumors by generating North American-based evidence for the efficacy and safety of CIRT and providing a platform for multinational, multi-institutional trials. This may not only pave the way for broader access to CIRT research in the United States but also increase study accrual for patients with other rare tumors beyond those with ACC if successful.

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Artikel online veröffentlicht:
07. Februar 2025