The SINTART 1 study: A phase II trial of induction chemotherapy (IC), surgery, photon-, proton-and carbon ion-based radiotherapy (RT) integration in locally advanced operable sinonasal epithelial tumors patients (pts).

Abstract

6066 Background: Sinonasal epithelial tumors are rare diseases with several histotypes and 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 - IC, surgery and RT - modulated by histology, molecular profile and response to IC. Methods: Pts with untreated, operable squamous cell carcinoma (SCC), p53 wild type intestinal type adenocarcinoma (ITAC), sinonasal undifferentiated and neuroendocrine carcinoma (SNUC, SNEC) were enrolled in a single-arm, phase II, multicenter clinical trial from 2014 to 2018. Pts was treated with up to 5 IC cycles, whose regimen was selected according to histotype, followed either by curative radio-chemotherapy (CRT) (pts with ≥80% reduction of initial tumor volume (TV)) or surgery and adjuvant (C)RT. Photon and/or proton/carbon ion-based RT was employed according to disease site and stage. Primary endpoint was 5 years PFS, secondary endpoints were OS, IC ORR per RECIST 1.1 and safety. Results: Out of 39 enrolled pts, 35 pts were evaluable for primary endpoint. Two pts were only considered for safety analyses because definitive diagnosis on surgical specimen did not meet the study entry criteria; other two pts were screening failure due to inoperable disease. Five-year PFS was 38% (95% 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. Responses to IC are reported in table. Globally, 15 pts avoided surgery. Overall treatment safety was in line with multimodality intensive head and neck cancer treatments (5% of pts with G3-4 adverse event during IC). One sudden cardiac death was recorded. At a median follow up of 27 months, 5 G3-4 RT related late adverse events have been recorded (1 G3 neurotoxicity, 2 G3 hearing impairment, 2 G3 xerostomia). Three-year PFS - OS for pts achieving PR/CR vs SD/PD to IC were 49.8% - 56.7% vs 43.2% - 53%, respectively. Conclusions: Treatment of advanced SNC with histology-driven IC followed by locoregional therapy tailored to response to IC was safe and showed survival rate similar to surgery containing case series. In the first prospective study, a surgery sparing multimodal approach proved feasible and effective in IC responsive pts. Clinical trial information: NCT02099175. [Table: see text]

The role of induction chemotherapy for orbital invasion in sinonasal malignancies: A systematic review

“…After IC, seven out of 13 patients achieved resectability and, thus, avoided OE 22 . Last, Resteghini et al 23 . reported on 15 SNM patients with orbital invasion that initially required OE, and response to IC in seven out of 15 patients led to avoidance of OE surgery.…”

Particle Reirradiation of Malignant Epithelial and Neuroectodermal Sinonasal Tumors: A Case Series from CNAO

“…Our series is small since SNCs are rare tumors and often managed with further surgery after a first primary treatment course that most of the time includes surgery and RT. Same as for other re-RT series after photon RT in the head and neck [ 25 ] and SNCs [ 26 , 27 ], our cohort is heterogeneous for histologies, treatment sites, and modalities aiming at including bad prognosis epithelial SNCs (mainly SCC and ITAC) for which research in the primary setting is also ongoing to improve prognosis [ 28 ]. It is noteworthy that we excluded from the analysis salivary glands tumors, already presented in a previous publication from our group [ 19 ], and head and neck sarcomas and mucosal melanomas.…”

Analysis of Treatment Modalities for Advanced Stage Squamous Cell Carcinoma of the Maxillary Sinus: A National Cancer Database Study

“…Recent nonrandomized trials (SINTART 1 and SINTART 2) on induction chemotherapy for advanced sinonasal tumors didn't show significant survival improvements but suggest its potential role. 16,17 Abdelmeguid et al found improved survival with neoadjuvant chemotherapy in stable disease. 18 Farrell et al (NCDB) showed induction chemotherapy followed by surgery improved OS compared with other approaches.…”

“…Most literature on the subject to date consists of single institution experiences and retrospective analyses. Recent non-randomized trials (SINTART 1 and SINTART 2) on induction chemotherapy for advanced sinonasal tumors didn't show significant survival improvements, but suggest its potential role 14,15 . Abdelmeguid et al found improved survival with neoadjuvant chemotherapy in stable disease 16 .…”