Background Extranodal extension (ENE) is an established adverse prognostic factor in oral cavity squamous cell carcinoma (OCSCC), but the clinical relevance of its extent remains uncertain. This systematic review and meta-analysis evaluated the prognostic impact of quantitatively defined minor versus major ENE, with particular emphasis on the conventional 2-mm threshold. Methods PubMed, Scopus, Embase, and the Cochrane Library were searched from inception to August 2026. Studies of surgically treated OCSCC assessing pathological ENE extent and oncological outcomes were included. Random-effects meta-analyses using restricted maximum likelihood and Hartung-Knapp inference were performed when at least three compatible adjusted hazard ratios (HRs) were available. Risk of bias was assessed using QUIPS. Results Twenty-two reports representing 18 independent cohorts were included. Five studies contributed to the primary overall survival (OS) meta-analysis. Major ENE was associated with significantly worse OS than minor ENE (pooled HR 2.01, 95% CI 1.10–3.66; I2 = 60.5%). Three studies contributed to the disease-free survival (DFS) meta-analysis, showing a concordant but imprecise association (pooled HR 2.16, 95% CI 0.44–10.66; I2 = 59.3%). Alternative thresholds and morphological classifications also generally suggested poorer outcomes with increasing ENE extent. Conclusions ENE extent provides prognostic information beyond binary ENE status in OCSCC. Major ENE is associated with worse OS, while evidence for DFS is directionally consistent but less precise. The 2-mm cutoff should be considered clinically useful but not yet biologically definitive.
PURPOSE We investigated the risk and prognostic value of pre-treatment nodal progression to inform the safe de-escalation of elective nodal irradiation (ENI) in high-risk oropharyngeal squamous cell carcinoma (OPSCC). METHODS We identified patients with p16-negative, clinical T4, node-positive OPSCC treated consecutively with definitive radiotherapy between 2008 and 2021 from a prospectively maintained database. Pre-treatment diagnostic scans were compared against simulation scans to evaluate nodal disease based on pre-specified criteria, growth kinetics, and imaging-detected extranodal extension (iENE). Association of nodal factors and oncologic outcomes were assessed using regression models. RESULTS A total of 79 patients with a median 30-day interval between diagnostic and simulation scan were identified. Nodal growth was minimal with a median absolute change of + 0.5 cc and growth rate of 0.3%/day. Nodal kinetics and duration between imaging were not prognostic for treatment response. While no patients developed de novo pathological nodal disease, 14% of patients had indeterminant nodes on diagnostic scan, with 27% of these becoming pathological at time of simulation. Total nodal volume was highly correlated with presence of iENE, and was prognostic for locoregional failure (HR = 1.02, p = 0.03), distant failure (HR = 1.02, p = 0.02), and progression-free survival (HR = 1.02, p = 0.05). All regional failures were in-field of high dose treatment volumes. CONCLUSIONS Pre-treatment nodal disease volume, but not growth kinetics, was a prognostic factor in locally advanced OPSCC. While lack of new nodal disease and minimal growth over a 30-day pre-treatment interval supports the investigation of novel timing of ENI, particular care should be taken in patients to identify and appropriately manage indeterminate nodes at risk for progression.
BACKGROUND Radiotherapy induced dysphagia is a common side effect in post-operative oral cavity squamous cell carcinoma (OCSCC) patients, affecting quality of life (QOL). Dysphagia-optimized radiotherapy reduces dose to dysphagia aspiration-related structures (DARS) while maintaining oncological efficacy. This prospective study compared dysphagia outcomes between DO-VMAT and S-VMAT in resected oral cavity cancers. MATERIALS AND METHODS This was a two-arm comparative, prospective, interventional study conducted between June 2022 and December 2023 with 50 patients of OCSCC on adjuvant chemoradiation divided in 1:1 ratio to either arm. Acute and chronic toxicities were graded by RTOG criteria. Dysphagia assessment by physician-reported toxicity, 100 ml water swallow test (WST), fiberoptic endoscopic evaluation of swallowing (FEES-DIGEST), and patient-reported QOL using MD Anderson Dysphagia Inventory (MDADI) were performed. Kaplan-Meier method was used to analyze disease-free survival (DFS) and overall survival (OS). RESULTS DO-VMAT achieved significantly lower mean doses to DARS (superior constrictor p = 0.023, middle constrictor p = 0.003, inferior constrictor p = 0.001) compared with S-VMAT. Acute dysphagia rates were comparable (p = 0.238), chronic effects including dysphagia (p = 0.041) and feeding tube dependency (p = 0.041) were significantly lower with DO-VMAT. At 12 months, objective swallowing outcomes favored DO-VMAT, with lower FEES-DIGEST scores (p = 0.018) and higher MDADI composite scores (p = 0.03). 2-year OS (82% vs 78%) and DFS (74% vs 76%) were comparable between S-VMAT and DO-VMAT. CONCLUSION DO-VMAT is safe and feasible for adjuvant radiotherapy in OCSCC. It significantly reduces late dysphagia and improves patient-reported QOL without affecting disease control or survival.
