Extranodal extension linked to shorter survival in oral cavity cancer
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DALLAS — Microscopic extranodal extension appeared associated with shorter survival among patients with oral cavity squamous cell carcinoma, according to study results.
In addition, it remains unclear whether adjuvant chemoradiation therapy confers a survival benefit for patients with microscopic or macroscopic extranodal extension (ENE), findings presented at American Head & Neck Society Annual Meeting showed.
“The fact that patients with oral cavity primary cancers and microscopic ENE had worse outcomes than those without is different from the accepted thought surrounding oropharyngeal primaries in the literature,” researcher Brooke Quinton, second-year medical student at Case Western Reserve University School of Medicine, told Healio. “In addition, we need to do more research to better fine-tune adjuvant treatment paradigms for patients with microscopic and macroscopic ENE.”
Background and methods
The oral cavity is the most common primary site of head and neck cancers, and approximately 40% of these patients present with lymph node metastases at the time of diagnosis, Quinton said.
ENE — defined as spread of cancer cells beyond the lymph node capsule — is a well-known adverse prognostic factor for head and neck cancers. ENE can be categorized as microscopic ( 2 mm beyond the capsule) or macroscopic (> 2 mm beyond the capsule).
The impact of the extent of ENE on OS among patients with some head and neck cancers has not been clearly established, and reports focused on oral cavity subsites have yielded conflicting findings, Quinton said.
Quinton and colleagues aimed to evaluate the prognostic significance of microscopic vs. macroscopic ENE among patients with oral cavity squamous cell carcinoma and nodal metastasis. They also sought to assess differences in survival among patients with microscopic or macroscopic ENE based on adjuvant treatment regimen (radiation alone vs. chemoradiation).
Researchers used the National Cancer Database to identify 7,975 patients with oral cavity squamous cell carcinoma who underwent primary ablative surgery with neck dissection. Researchers collected data on several factors, including age at diagnosis, race, sex, Charlson-Deyo Comorbidity Index score, tumor size, surgical margins and adjuvant treatment.
Investigators performed univariate- and multivariate-adjusted Cox regressions, then created propensity score matched models for microscopic and macroscopic ENE cohorts to evaluate the effects of each adjuvant treatment modality on survival.
Key findings
One-quarter (25.4%) of the cohort had microscopic ENE, 5.2% had macroscopic ENE and 69.5% had positive nodal disease with no evidence of ENE.
Most patients received adjuvant chemoradiation (39.4%), whereas 32.7% received adjuvant radiation alone and 27.9% received no adjuvant therapy.
Univariate analysis showed significantly shorter survival among patients with microscopic ENE (HR = 1.67; 95% CI, 1.56-1.79) and macroscopic ENE (HR = 1.88; 95% CI, 1.66-2.14).
Analysis by primary site showed no statistically significant differences between the microscopic and macroscopic ENE groups, with the exception of the tongue. In that subgroup, patients with macroscopic ENE had significantly shorter survival than those with microscopic ENE (HR = 1.22; 95% CI, 1.01-1.49).
Multivariate analysis showed both microscopic and macroscopic ENE are associated with significantly shorter survival for all primary sites, with the exception of the lip and hard palate, Quinton said.
The addition of adjuvant therapy — radiation alone or chemoradiation — appeared associated with longer survival.
However, the propensity score matched model showed no significant difference in survival by treatment modality (radiation vs. chemoradiation) for patients with microscopic ENE (HR = 1.08; 95% CI, 0.89-1.32) or macroscopic ENE (HR = 1.37; 95% CI, 0.73-0.87).
“The finding that adjuvant chemoradiation did not necessarily improve survival for patients with macroscopic ENE definitely was surprising because there are many studies that suggest it is necessary,” Quinton said.
Implications
Quinton acknowledged study limitations, including the retrospective design, modest sample sizes for certain primary sites and the macroscopic ENE subgroup, and the lack of a standardized definition of microscopic ENE until recently.
In addition, the National Cancer Database lacks information about other metastatic nodal features such as lymph node ratio that might predict poorer prognosis.
“The practical implication is deciding whether we are overtreating some patients with microscopic ENE with adjuvant chemoradiation,” Quinton said. “Also, our finding that [survival for patients with macroscopic ENE] did not necessarily improve with chemoradiation is contrary to lot of studies in the literature. Further research with a larger sample size and a prospective arm would help us answer that question.”
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Quinton B, et al. Abstract AHNS046. Presented at: American Head & Neck Society Annual Meeting at COSM 2022; April 27-28, 2022; Dallas.
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