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Researchers identify factors associated with survival in patients with submandibular gland tumors
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Certain prognostic factors — including older age at diagnosis, high tumor grade and later stage at presentation — predicted poorer survival among patients with malignant submandibular gland tumors, according to the results of a SEER analysis.
However, female sex and surgical resection served as independent prognostic factors for prolonged survival, according to the researchers.
Because malignant tumors of the submandibular gland are uncommon, little information regarding prognostic factors exists, according to study background. This has led to difficulty in evaluating treatment modalities.
Russell E. Christensen, DDS, MS, associate professor and chair of the department of oral and maxillofacial pathology at UCLA School of Dentistry, and colleagues sought to investigate correlates of survival in this patient population.
Researchers used the SEER database to conduct a retrospective population-based cohort study. Treatment interventions evaluated in the study included surgery, radiation therapy, both or neither.
OS and disease-specific survival (DSS) served as the primary endpoints.
The study included data from 2,626 patients (mean age, 61.3 years; 52.9% male). Adenoid cystic carcinoma served as the most prevalent histologic subtype in the patient population (36%).
Approximately 87% of patients received surgical treatment, whereas 57.8% underwent radiation therapy.
Sixty-five percent of patients achieved 2-year OS, and 74% achieved 2-year DSS. The researchers observed a 5-year OS rate of 54% and 5-year DSS rate of 67%, and a 10-year OS rate of 40% and 10-year DSS rate of 60%.
In a multivariate analysis, independent prognostic factors for poorer OS and DSS included older age (OS: HR = 1.04; 95% CI, 1.03-1.04; DSS: HR = 1.02; 95% CI, 1.01-1.03), higher tumor grade (OS: HR = 1.47; 95% CI, 1.19-1.81; DSS: HR = 1.67; 95% CI, 1.25-2.25) and later stage at presentation (OS: HR = 1.56; 95% CI, 1.41-1.72; DSS: HR = 1.96; 95% CI, 1.69-2.28). However, female sex (OS: HR = 0.69; 95% CI, 0.57-0.84; DSS: HR = 0.73; 95% CI, 0.56-0.96) and surgical resection (OS: HR = 0.55; 95% CI, 0.41-0.74; DSS: HR = 0.51; 95% CI, 0.35-0.75) had a positive impact on survival.
When the researchers conducted a multivariate analysis of cohorts — separated by a tumor cutoff size of 3 cm — they found that patients with tumors larger than 3 cm had a less favorable prognosis than patients with smaller tumors (median OS, 2.8 years vs. 12.6 years). However, surgery (OS: HR = 0.57; 95% CI, 0.39-0.83) and radiation (OS: HR = 0.69; 95% CI, 0.51-0.95) appeared associated with prolonged survival among patients with tumors larger than 3 cm. Still, researchers noted that radiation therapy has only recently become commonly used in patients with submandibular gland tumors, resulting in the inclusion of a smaller number of patients in this cohort.
The researchers acknowledged the lack of available information regarding comorbidities, extant of surgical resection, margin status and chemotherapy receipt as a study limitation.
“Here we report the largest study to date [in this setting], in which we found that the correlates of survival for both OS and DSS include age at diagnoses, sex, tumor grade, stage at presentation and receipt of surgical therapy,” Christensen and colleagues wrote. “In addition, we demonstrated a 3 cm critical tumor size cutoff above which was associated with significantly worsened prognosis, as well as demonstrating that receipt of radiation therapy has mixed association with survival dependent on tumor subtype and size.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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David J. Adelstein, MD, FACP
Lee and colleagues present an analysis of submandibular gland malignancy based on SEER registry data. In a review spanning 38 years, 2,626 patients were identified, making this the largest series of patients reported with this rare diagnosis. Their study confirms the work of others demonstrating that older patients, those with a higher tumor grade and those with a higher tumor stage at presentation have a worse prognosis. Although the conclusions are not surprising, these results serve to validate our current understanding of this disease.The researchers are careful to point out some of the limitations of this analysis. Most notable is the difficulty of pathologic classification and tumor grading. There are many histologic subtypes of salivary gland cancer that have been recognized. Their distinction, and the assignment of a tumor grade, have major clinical importance and require considerable pathologic expertise. Extracting this information from tumor registry data is difficult and likely flawed. This is apparent when noting that 18% of patients were given the diagnosis of squamous cell carcinoma, a disease — as noted by the authors — that is unlikely to arise from submandibular gland. Similarly, no tumor grading was available in almost half of the cases. Nonetheless, the better prognosis of adenoid cystic carcinoma, and of low-grade tumors in general, is demonstrated again. One must also be cautious about overinterpreting the importance of an endpoint like disease-specific survival. This outcome is also a difficult data point to obtain from a tumor registry, and the importance of their reported median disease-specific survival of 23 years is limited.
I would emphasize the researchers’ conclusion that treatment recommendations cannot be made based on this kind of retrospective analysis. Surgical patients did better in this series, as would be expected. Radiation therapy did not have a consistent impact, reflecting the use of this modality for a variety of indications in these patients. Better understanding of the optimal use of surgery, radiation and chemotherapy will require careful prospective study in well-defined, prognostically similar patient populations.
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