Comparative impact of grade on mortality across salivary cancers: A novel, unifying staging system

Abstract

Background: The comparative impact of histologic variants and grade has not been well described.Methods: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival.Results: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [highgrade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73). Conclusion:Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems.

Reply to Letter to the Editor: Should there be a definite place for grade in the next TNM staging system for (major) salivary gland malignancies?

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We thank Kantamani and Thiagarajan for their interest in our study on grade and histology in salivary cancer staging. 1 We agree that a study previously published by these authors using a different dataset 2 shows parallels to our analysis, and that the findings of the two studies largely complement one another.The main analytic differences between our study and that of the Kantamani and Thiagarajan involve how histology was integrated. While the Tata Memorial paper incorporated the ASCO 2017 risk stratification of low-aggression and high-aggression salivary cancers (an amalgam of histology and grade), 2,3 we focused on grade alone.

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“…We thank Kantamani and Thiagarajan for their interest in our study on grade and histology in salivary cancer staging. 1 We agree that a study previously published by these authors using a different dataset 2 shows parallels to our analysis, and that the findings of the two studies largely complement one another.…”

Should there be a definite place for grades in the next TNM staging system for (major) salivary gland malignancies?

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Rs e e p a g e 2 7 4 2 -2 7 4 3 Should there be a definite place for grades in the next TNM staging system for (major) salivary gland malignancies?We would like to congratulate Ho et al for their article on reinforcing the importance of grade for salivary gland malignancies and also for showning that it is the primary determinant of prognosis in these malignancies. 1 We are in agreement with the authors for the inclusion of grade in the TNM staging system for salivary gland malignancies not just based on the work of the authors but also based on our work on similar lines published a year ago. 2 The authors in the introduction cited only one study and mentioned that few studies have been published that have looked into the comparative risk of mortality between salivary cancer variants.

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Translational Insights in the Landscape of Salivary Gland Cancers: Ready for a New Era?

“…ORRs ranged from 8 to 16% and PFS values were between 4.3 to 17.5 months. Sorafenib and lenvatinib show the highest ORRs for all tyrosine kinase inhibitors (sorafenib 11% and 16% respectively), and Lenvatinib also demonstrated the best PFS (17.5 months) [ 32 , 33 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ].…”

“…ORRs ranged from 8 to 16% and PFS values were between 4.3 to 17.5 months. Sorafenib and lenvatinib show the highest ORRs for all tyrosine kinase inhibitors (sorafenib 11% and 16% respectively), and Lenvatinib also demonstrated the best PFS (17.5 months) [32][33][34][36][37][38][39][40][41][42][43][44]. Tchekmedyan et al enrolled 33 patients with advanced ACC in a phase II clinical trial and used Lenvatinib 24 mg/d.…”