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

Official title

SPORT-SNACC: A Prospective, Multicenter, Observational Cohort Study of Surgery Plus Postoperative Radiotherapy in T4 Sinonasal Adenoid Cystic Carcinoma

Overview

This observational study follows patients with T4 stage sinonasal adenoid cystic carcinoma (a rare cancer of the nasal cavity/sinuses) who receive standard treatment: surgery followed by postoperative radiotherapy. The main goal is to measure the 3-year progression-free survival rate (the percentage of patients alive without cancer growth or spread). We will also assess overall survival, recurrence, side effects, and quality of life. This multicenter, prospective study will provide much-needed real-world data to improve patient counseling and guide future research.

Detailed description

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.

Interventions

• Procedure Surgery
  Postoperative Radiotherapy

Primary outcome measures

• 3-Year Progression-Free Survival [Time frame: Up to 3 years after enrollment]

Secondary outcome measures (6)

• R0 Resection Rate [Time frame: At time of surgery (postoperative pathological assessment)]
• 3-Year Overall Survival [Time frame: Up to 3 years after enrollment]
• 3-Year Distant Metastasis-Free Survival [Time frame: Up to 3 years after enrollment]
• 3-Year Local Control Rate [Time frame: Up to 3 years after enrollment]
• Postoperative Complication Rate (CTCAE Grade ≥3) [Time frame: Within 30 days after surgery]
• Radiotherapy Toxicity Rate (Grade ≥3) [Time frame: From start of radiotherapy up to 3 years]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 6 centers

• The Second Affiliated Hospital of Harbin Medical University — Harbin
• Third Xiangya Hospital, Central South University — Changsha
• The First Affiliated Hospital of China Medical University — Shenyang
• Eye & ENT Hospital of Fudan University — Shanghai
• The First Affiliated Hospital of Air Force Medical University — Xi’an
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou

Publications

• Jang S, Patel PN, Kimple RJ, McCulloch TM. Clinical Outcomes and Prognostic Factors of Adenoid Cystic Carcinoma of the Head and Neck. Anticancer Res. 2017 Jun;37(6):3045-3052. doi: 10.21873/anticanres.11659. PMID 28551643
• Lee TH, Kim K, Oh D, Yang K, Jeong HS, Chung MK, Ahn YC. Clinical Outcomes in Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinus: A Comparative Analysis of Treatment Modalities. Cancers (Basel). 2024 Mar 21;16(6):1235. doi: 10.3390/cancers16061235. PMID 38539566
• Song X, Sun J, Yang G, Wang X, Wang L. Long-term outcomes of platinum-based chemotherapy for T4 stage sinonasal adenoid cystic carcinoma. Front Pharmacol. 2025 Sep 29;16:1623242. doi: 10.3389/fphar.2025.1623242. eCollection 2025. PMID 41089828
• Mays AC, Hanna EY, Ferrarotto R, Phan J, Bell D, Silver N, Mulcahy CF, Roberts D, Abdelmeguid ASA, Fuller CD, Frank SJ, Raza SM, Kupferman ME, DeMonte F, Su SY. Prognostic factors and survival in adenoid cystic carcinoma of the sinonasal cavity. Head Neck. 2018 Dec;40(12):2596-2605. doi: 10.1002/hed.25335. Epub 2018 Nov 17. PMID 30447126
• Cavalieri S, Mariani L, Vander Poorten V, Van Breda L, Cau MC, Lo Vullo S, Alfieri S, Resteghini C, Bergamini C, Orlandi E, Calareso G, Clement P, Hauben E, Platini F, Bossi P, Licitra L, Locati LD. Prognostic nomogram in patients with metastatic adenoid cystic carcinoma of the salivary glands. Eur J Cancer. 2020 Sep;136:35-42. doi: 10.1016/j.ejca.2020.05.013. Epub 2020 Jul 3. PMID 32629365
• Seok J, Lee DY, Kim WS, Jeong WJ, Chung EJ, Jung YH, Kwon SK, Kwon TK, Sung MW, Ahn SH. Lung metastasis in adenoid cystic carcinoma of the head and neck. Head Neck. 2019 Nov;41(11):3976-3983. doi: 10.1002/hed.25942. Epub 2019 Aug 29. PMID 31463986
• Mavrikios A, Goudjil F, Beddok A, Zefkili S, Bolle S, Feuvret L, Le Tourneau C, Choussy O, Sauvaget E, Herman P, Dendale R, Calugaru V. Proton therapy and/or helical tomotherapy for locally advanced sinonasal skull base adenoid cystic carcinoma: Focus on experience of the Institut Curie and review of literature. Head Neck. 2023 Jul;45(7):1619-1631. doi: 10.1002/hed.27371. Epub 2023 Apr 25. PMID 37097003
• Bjorndal K, Krogdahl A, Therkildsen MH, Overgaard J, Johansen J, Kristensen CA, Homoe P, Sorensen CH, Andersen E, Bundgaard T, Primdahl H, Lambertsen K, Andersen LJ, Godballe C. Salivary gland carcinoma in Denmark 1990-2005: a national study of incidence, site and histology. Results of the Danish Head and Neck Cancer Group (DAHANCA). Oral Oncol. 2011 Jul;47(7):677-82. doi: 10.1016/j.oraloncology.2 PMID 21612974

Identifiers

NCT: NCT07652489 · 2026134

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗