Neoadjuvant chemoradiation for patients with resectable locally advanced oral cavity squamous cell carcinoma: Results of the prospective INVERT clinical trial

OBJECTIVE: The INVERT trial is a prospective, monocentric, proof-of-principle phase 2clinical trial evaluating the safety and efficacy of neoadjuvant chemoradiation (CRT) inpatients with resectable, locally advanced oral cavity squamous cell carcinoma (LAOCSCC). METHODS: Eligible patients received intensity-modulated radiotherapy (IMRT) to primarytumor and nodal volumes (60/54/50 Gy in 30 fractions) with concomitant platinumbasedchemotherapy. Surgery was performed 6-8 weeks after CRT. Primary endpointwas the pathological complete response (pCR = ypT0N0) rate. Secondary endpointsincluded R0 resection rate, surgical complications, oncological outcomes, and qualityof life. RESULTS: Between 02/2012 and 09/2022, 28 UICC Stage (7th edition) IVA-IVB LAOCSCCpatients were enrolled; 92.1 % showed mandibular involvement. All patientsreceived the the full IMRT dose of 60 Gy. For all cisplatin-eligible patients, the mediancumulative dose was 200 mg/m2 BSA. In the intention-to-treat population, the pCR ratewas 46.4 % (n = 13) but did not met the primary endpoint. In total, we recorded 384adverse events (AEs) of any grade and 109 AEs ≥ grade 3 according to CTCAE (nograde 5). Surgical complications were primarily wound healing disorders and postbleeding, with no grade 4 or 5 events. At a median follow-up of 28.5 months,progression-free survival (PFS), local control (LC), freedom from distant failure (DF),and overall survival (OS) were 60.7 %, 89.3 %, 82.1 %, and 64.3 %, respectively. pCRPowered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationsignificantly correlated with improved PFS (p = 0.010) and OS (p = 0.021). CONCLUSION: Neoadjuvant CRT is feasible and safe, achieving high pCR rates in LAOCSCC.pCR was associated with improved outcomes.