Combined treatment of malignant salivary gland tumours with intensity-modulated radiation therapy (IMRT) and carbon ions: COSMIC

The COSMIC trial is a prospective, mono-centric, phase II trial evaluating toxicity (primary endpoint: mucositis ≥ CTCAE°3) and efficacy (secondary endpoint: local control, disease-free survival) in the combined treatment with IMRT and carbon ion boost in 54 patients with histologically proved (≥R1-resected, inoperable or Pn+) salivary gland malignancies. Patients receive 24 GyE carbon ions (8 fractions) and IMRT (50 Gy at 2.0 Gy/fraction).The primary objective of COSMIC is to evaluate toxicity and feasibility of the proposed treatment in all salivary gland malignancies.Clinical trial identifier NCT 01154270Malignant salivary gland tumours are rare and a heterogenous group of tumours accounting for about 3-5% of head and neck cancers. High-grade tumours such as mucoepidermiod carcinoma (35%) and adenoid cystic carcinoma (25%) are the most common histological subtypes [1], characterised by a rather slow pattern of growth, perineural spread and high propensity for haematogenous metastases. So far, standard therapy of high-grade salivary gland carcinoma consists of complete surgical resection and adjuvant radiation in high-risk situations (R+ or close margin, perineural spread, neural infiltration, large tumours (T3/4), or nodal metastases [2-4]. To achieve local control, radiation doses of > 60 Gy or even 66 Gy (5) are recommended [5,6], with apparently all tumour stages profiting from postoperative radiotherapy [5,7-9].Regarding radiation therapy, local control was also significantly improved by the application of high-precision techniques, dose-escalation and high-LET radiation [9-13].Intensity-modulated radiation therapy (IMRT) as well as fractionated stereotactic RT could already improve local control as compared to conventional RT techniques achieving 3-year PFS rates of 38% [14].So far, the highest local control rates at 75 - 100% [11,13] were achieved by neutron radiation albeit at the cost of significant late toxicity.Dose escalation [12] though only in a smal