Surgery Plus Postoperative Radiotherapy for T4 Sinonasal Adenoid Cystic Carcinoma: A Prospective Observational Study

This is a prospective, multicenter, observational cohort study of T4 stage sinonasal adenoid cystic carcinoma (SNACC) patients receiving standard treatment (surgery followed by postoperative intensity-modulated radiotherapy). No experimental intervention is assigned. Approximately 70 patients will be enrolled from six Chinese centers over 18-24 months. Key exclusions include unresectable disease (e.g., bilateral cavernous sinus or carotid artery involvement) and progressive lung metastases.

Endpoints: Primary is 3-year progression-free survival (PFS). Secondary include R0 rate, 3-year overall survival, distant metastasis-free survival, local control, postoperative complications (CTCAE v5.0), radiotherapy toxicity, quality of life (EORTC QLQ-C30/H&N35), and surgery-to-radiotherapy interval. Exploratory analyses by margin status, histologic subtype (solid ≥30%), T4a/T4b, and surgical approach.

Quality & data management: Central pathology/imaging review; EDC with range/logic checks; quarterly remote and biannual on-site monitoring with ≥20% source data verification; data dictionary; MDT requirement; independent DSMB every 6 months.

Statistical methods: Primary PFS estimated by Kaplan-Meier with 95% CI. Secondary time-to-event endpoints similarly analyzed. QoL longitudinal data using MMRM. Missing data: censoring for PFS; no imputation for safety; MMRM for QoL under MAR.

Inclusion criteria

• Age 18 80 years, any gender; ECOG performance status 0 2; life expectancy ≥6 months.
• Histologically confirmed primary sinonasal adenoid cystic carcinoma (cribriform, tubular, solid, or mixed type). Other malignancies excluded.
• T4 stage (T4a or T4b) according to AJCC 8th edition, based on contrast enhanced MRI/CT.
• N0 2 (operable lymph node metastasis allowed).
• M0 (no distant metastasis on chest CT and abdominal ultrasound) OR M1 with stable limited lung metastases; (c) stable on two CT scans ≥3 months apart; (d) no respiratory symptoms.
• Previously untreated (no radiotherapy, chemotherapy, targeted therapy, immunotherapy, or tumor resection). MDT deems technically resectable (R0/R1 achievable, not diffusely unresectable).
• Adequate organ function within 14 days before enrollment: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, Hb ≥90 g/L; ALT/AST ≤2.5×ULN, TBil ≤1.5×ULN, Cr ≤1.5×ULN or CrCl ≥50 mL/min; LVEF ≥50%, no uncontrolled arrhythmia.
• Willing and able to provide written informed consent for clinical data collection (and optional biospecimen banking). Investigator judges good compliance.

Exclusion criteria

• Progressive lung metastases within 6 months (new lesions or >20% increase); extrapulmonary metastases (liver, bone, brain); symptomatic lung metastases.
• MDT judged unresectable, e.g., bilateral cavernous sinus invasion, brain parenchyma invasion, bilateral internal carotid artery encasement.
• Primary tumor outside sinonasal cavity (e.g., major salivary glands, oropharynx); non ACC histology.
• Other active malignancy within 5 years (except cured basal cell carcinoma, cervical carcinoma in situ, etc.).
• Severe comorbidities: NYHA class III/IV heart failure, recent myocardial infarction or unstable angina, uncontrolled hypertension (≥160/100 mmHg); COPD requiring home oxygen or interstitial lung disease; decompensated cirrhosis; active hepatitis B/C without antiviral therapy; nephropathy requiring dialysis; active serious infection; active bleeding or coagulopathy (INR >1.5×ULN without anticoagulation, or platelets <50×10⁹/L).
• Special populations: pregnant or breastfeeding; unwilling to use contraception (if childbearing potential); severe allergy to medications required for surgery/radiotherapy; severe psychiatric or cognitive disorder impairing cooperation; currently participating in another interventional trial.
• Unable to undergo contrast enhanced MRI (metal implants, claustrophobia, gadolinium allergy); investigator judges inability to complete follow up (e.g., living abroad, substance abuse).