The SINTART 2 Study. A Phase II Nonrandomized Controlled Trial of Induction Chemotherapy, Photon-, Proton- And Carbon Ion-Based Radiotherapy Integration In Patients With Locally Advanced Unresectable Sinonasal Tumors
Mené sur 25 patients présentant des tumeurs épithéliales sinonasales non traitées et non résécables, cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression à 5 ans, et la sécurité d'un traitement multimodal, combinant une chimiothérapie d'induction et une radiothérapie photonique, modulé par le type histologique et la réponse à la chimiothérapie
Purpose: Unresectable, locally advanced sinonasal epithelial tumors are rare diseases with poor prognosis. Multimodal approach is widely used, although no standard therapy has been established in prospective trials. This study assessed activity and safety of an innovative integration of multimodality treatment - induction chemotherapy (ICT), surgery and radiotherapy (RT) - modulated by histology and response to ICT. Methods: Patients with untreated, unresectable sinonasal epithelial tumors with selected histotypes (squamous cell carcinoma, intestinal-type adenocarcinoma, sinonasal undifferentiated and neuroendocrine carcinoma, olfactory neuroblastoma) were enrolled in a single-arm, open-label, phase II, multicenter clinical trial. Patients were treated with up to 5 ICT cycles, whose regimen was selected according to histotype. Photon and/or proton/carbon ion-based RT was employed according to disease site, stage and ICT response. Primary endpoint was 5-years progression-free survival (PFS), secondary endpoints were overall survival (OS), ICT objective response rate (ORR) per RECIST 1.1 and safety. Results: Twenty-five patients were evaluable for primary endpoint. Five-year PFS was 26.8% (95% CI 12.6 – 57.1), with a median PFS of 18 months. Five-year OS was 23.8% (95% CI, 9.5 – 59.3), with a median OS of 27 months. The overall response rate to ICT was 40%. Three-year PFS for patients achieving major volumetric partial response (mPRv) vs non-mPRv was 40% (95%CI: 13.7% - 100%) vs 23.1% (95%CI: 8.3% - 64.7%) (P=0.318) and 3-year OS was 53.3% (95%CI:21.4% - 100%) vs 37.7% (95%CI: 20.0% - 71.0%) (P=0.114). Conclusion: Multimodal combination of ICT and innovative RT did not provide a significant improvement in survival rates with respect to previous experiences. This finding underscores the need for future research in this rare disease, still characterized by a heavy burden and poor prognosis. We observed longer survival in subjects achieving response to ICT. The overall treatment safety is acceptable.