Postoperative Chemoradiotherapy versus Radiotherapy Alone in Major Salivary Gland Cancers: A Stratified Study Based on the External Validation of the Distant Metastasis Risk Score Model

SIMPLE SUMMARY: Postoperative radiotherapy (PORT) was strongly recommended for major salivary gland malignancies (SGM) with adverse features. However, distant metastasis (DM) remained the major failure pattern of the patients, and the role of adjuvant chemotherapy was inconclusive. This study aimed to compare the survival outcome between the patients following adjuvant CRT or RT alone based on a DM risk score model. No significant difference was revealed between the CRT and RT group in the entire cohort when matching with the IPTW. After DM risk stratification, we found inferior survival with the administration of adjuvant CRT in the low-risk subset but no significant difference in the high-risk group. Our finding provided evidence that additional chemotherapy to PORT is not well recommended in clinical practice for major SGM patients. ABSTRACT: Background: The role of additional chemoradiotherapy (CRT) for distant metastasis (DM) on the resected malignancy of the major salivary gland (SGM) remained unknown. We conducted this study to externally validate a recently reported DM risk score model and compare the survival outcome between adjuvant CRT and RT alone. Materials: We retrospectively reviewed the patients with SGM following postoperative radiotherapy (PORT). The cumulative incidence of DM was assessed using a competing risk method. Multivariate analysis was performed with Cox proportional-hazards regression to identify significant predictors for DM. Patients were classified as high- and low-risk subgroups with the cutoff value of the DM risk score model. The inverse probability of treatment weighting (IPTW) was conducted to minimize the bias of the groups. Results: A total of 586 eligible patients were analyzed and 67 cases underwent adjuvant CRT. The 5-year incidence of DM was 19.5% (95% CI 16.0–23.0%). The model reasonably discriminated the DM risk between the high- and low-risk subgroup in our cohort, and the c-index was 0.75. No survival benefit was observed for the CRT group compared with RT alone in the entire cohort after IPTW (p = 0.095). After subgroup analysis, increased mortality was identified with the administration of CRT in the low-risk subset (p = 0.002) while no significant difference in OS was illustrated in the high-risk subgroup (p = 0.98). Conclusions: This external validation provides further exploration of the DM risk score model in major SGM. Our results demonstrated no support for the utility of additional chemotherapy to PORT in the major SGM, especially in the low-risk subgroup of patients with DM.