The SINTART 1 study. A phase II non-randomised controlled trial of induction chemotherapy, surgery, photon-, proton- and carbon ion-based radiotherapy integration in patients with locally advanced resectable sinonasal tumours.

Paolo Battaglia, Lisa Licitra, Tiziana Tartaro, Carla Facco, Marco Ravanelli, Giuseppina Calareso, Nadia Facchinetti, Davide Mattavelli, Mario Turri-Zanoni, Marco Guzzo, Carlo Resteghini, Nicola Alessandro Iacovelli, Simone Gambazza, Alberto Schreiber, Barbara Vischioni, Paolo Bossi, Ester Orlandi, Piero Nicolai, Paolo Castelnuovo

Journal: European journal of cancer (Oxford, England : 1990) 2023;187():185-194

PMID: 37164774

Full Text on Elsevier Science View on PubMed

Abstract

PURPOSE

Sinonasal tumours are rare diseases with poor prognosis. Multimodal approach including surgery 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, operable sinonasal tumours with selected histotypes (squamous cell carcinoma, intestinal-type adenocarcinoma, sinonasal undifferentiated and neuroendocrine carcinoma, olfactory neuroblastoma) were enrolled in a single-arm, phase II, multicenter clinical trial. Patients were treated with up to 5 ICT cycles, whose regimen was selected according to histotype, followed either by curative chemo-RT for pts with ≥80% reduction of initial tumour diameter or surgery and adjuvant (chemo)RT. Photon and/or proton/carbon ion-based RT was employed according to the disease site and stage. Primary end-point was 5-year progression-free survival (PFS), secondary end-points were overall survival (OS), ICT objective response rate (ORR) per RECIST 1.1 and safety.

RESULTS

Thirty-five patients were evaluable for primary end-point. Fourteen patients (40%) were treated with definitive (CT)RT and 20 (57%) underwent surgery. Five-year PFS was 38% (95% confidence interval [CI], 21-69), with a median PFS of 26 months. Five-year OS was 46% (95% CI, 28-75), with a median OS of 36 months. Three-year PFS-OS for pts achieving PR/CR versus stable disease (SD)/PD to ICT were 49.8-57% versus 43.2-53%, respectively. Three-year PFS for patients achieving major volumetric partial response (≥80% reduction of initial tumour volume, major partial volumetric response [mPRv]) versus non-mPRv were 82% versus 28% and 3-year OS were 92% versus 36% (p value 0.010 and 0.029, respectively). The ORR to ICT was 54% and 60% across all histotypes and in the sinonasal undifferentiated carcinoma (SNUC) subpopulation, respectively, with 6/15 SNUCs (40%) achieving mPRv.

CONCLUSION

Treatment of advanced sinonasal cancer with histology-driven ICT followed by (CT)RT in responsive patients was feasible. Overall, these findings suggest a possible role of ICT as the primary approach in newly diagnosed, resectable sinonasal tumours-especially SNUC-to select patients with favourable prognosis. Histology heterogeneity limits generalisation of trial results.

Address: Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. Electronic address: [email protected].; Division of Otorhinolaryngology, Department of Surgical Specialties, 'ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi', Varese, Italy; Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, 'ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi', University of Insubria, Varese, Italy; Head and Neck Surgery & Forensic Dissection Research center (HNS&FDRc), Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy.; Unit of Otorhinolaryngology - Head and Neck Surgery, Department of Neurosciences, 'Azienda Ospedale Università di Padova', University of Padua, Padua, Italy.; Radiation Oncology Clinical Department, National Center for Oncological Hadrontherapy (CNAO), Pavia, Italy; Department of Radiation Oncology 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Unit of Medical Oncology, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, 'ASST Spedali Civili di Brescia', University of Brescia, Brescia, Italy.; Radiation Oncology Clinical Department, National Center for Oncological Hadrontherapy (CNAO), Pavia, Italy.; Unit of Otorhinolaryngology - Head and Neck Surgery, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, 'ASST Spedali Civili di Brescia', University of Brescia, Brescia, Italy.; Laboratory of Medical Statistics and Biometry, 'Giulio A. Maccacaro', Department of Clinical Sciences and Community Health, Campus Cascina Rosa, University of Milan, Milan, Italy.; Department of Radiation Oncology 2, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Department of Otorhinolaryngology, Maxillofacial, and Thyroid Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; Division of Otorhinolaryngology, Department of Surgical Specialties, 'ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi', Varese, Italy; Division of Otorhinolaryngology, Department of Biotechnology and Life Sciences, 'ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi', University of Insubria, Varese, Italy.; Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.; Unit of Radiology, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia - 'ASST Spedali Civili di Brescia', Brescia, Italy.; Unit of Pathology, Department of Medicine and Surgery, ASST Sette-Laghi, University of Insubria, Varese, Italy.; Department of Medical Oncology, 'ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi', Varese, Italy.; Head and Neck Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.

DOI: 10.1016/j.ejca.2023.03.033

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MeSH Terms: Cisplatin, Carbon, Maxillary Sinus Neoplasms, Prospective Studies, Humans, Carcinoma, Squamous Cell, Protons, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Induction Chemotherapy