ESTRO 2024 - Abstract Book

S1443

Clinical - Head & neck

ESTRO 2024

Purpose/Objective:

Locally-advanced oral cavity squamous cell carcinoma (LA-OSCC) is typically managed with radical and reconstructive surgery followed by postoperative risk-adapted (chemo-)radiation (C/RT). Neoadjuvant treatment has improved efficacy and outcomes in many malignancies, its role in patients with LA-OSCC, however, is poorly explored. The INVERT trial is a prospective, monocentric, proof-of-principle phase 2 clinical trial, investigating safety and efficacy of neoadjuvant platinum-based CRT, followed by surgery in LA-OSCC.

Material/Methods:

Eligible patients with primarily resectable LA-OSCC received neoadjuvant intensity-modulated radiotherapy (IMRT) to the gross tumor volume, involved/high-risk and elective nodal volumes of the neck with 60/54/50 Gy in 30 fractions, respectively. Concurrent chemotherapy with cisplatin (20-25mg/m2 per day) and 5-fluoruracil (600mg/m2 per day) was administered at days 1-5 and days 29-34 (split course). Radical surgery was scheduled 6-8 weeks after completion of CRT. Pathologic complete response (ypT0N0) was the primary endpoint. Secondary endpoints were R0 resection rate, surgical complications according to the Clavien-Dindo Classification, survival and quality of life (QoL). Moreover, potential molecular and imaging factors for treatment response were investigated including immune contextures detected by multiplex immunofluorescence panels in pretreatment specimens and diffusion weighted magnetic resonance imaging (DW-MRI) signal changes during treatment.

Results:

Between 02/2012 and 09/2022, 28 patients with UICC Stage IVA-IVB LA-OSCC were enrolled; 92.1% (n=26) showed erosive or infiltrative mandibular or maxillary involvement. All patients received full IMRT dose of 60 Gy. For all cisplatin-eligible patients, the median cumulative dose was 200 mg/m2. In total, we recorded 384 adverse events (AEs) of any grade and 109 AEs ≥ grade 3 according to CTCAE during CRT. One patient experienced grade 4 peritonitis with consecutive pleural empyema after a severe gastric feeding tube infection. After CRT, 27 patients underwent surgery. Median time between CRT and surgery was eight weeks. Surgical complications were mostly wound healing disorders and post bleeding - no grade 4 or 5 occurred. In the intention-to-treat (IIT) population pCR rate was 46.4 % (n=13); R0 resection rate was 92.9 %. Median follow-up is 23.0 months (4-129 months). Progression free survival (PFS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS) and overall survival (OS) was 60.7 %, 89.3 %, 82.1 % and 71.4 %, respectively. pCR was significantly associated with favorable PFS (p=0.012). Within this cohort, we failed to identify potential molecular and imaging factors predicting for treatment response.

Conclusion:

Neodjuvant CRT is feasible and results in high pCR rates in patients with LA-OSCC. Adverse events and toxicity were comparable to the standard-of-care treatment algorithm. Response to neoadjuvant CRT may help further stratify patients suitable for de-escalation or in need of additional therapies, whereas predictive and prognostic molecular and imaging factors in LA-OSCC remain to be established in larger patients cohorts.

Keywords: oral cavity cancer, neoadjuvant, chemoradiation