This study revealed that aRT is significantly associated with survival benefits in patients with Stage IV SCC of the tongue. aRT is commonly used after surgery in cases of unfavorable histological findings. For large tumors, several oncologists recommend aRT if the surgical margins are close to the tumor or involved or if several positive nodes persist after neck dissection. Previous studies have indicated that early tongue cancers are associated with 5-year survival rates of at least 80% [21,31,32], although cancers of the tongue have a worse prognosis than those affecting other oral areas. Rusthoven et al. revealed that Stage I and II tongue cancers have 60.9% and 83.5% 5-year OS and cause-specific survival rates, respectively; other oral subsites had rates of 64.7% and 94.1%, respectively, according to the SEER database . Shim et al. attributed the high survival rate of tongue cancer to appropriate radiotherapy . Thus, feasible and reasonable radiation therapy regimens are important for the survival status of patients. In this study, we analyzed the survival of patients with SCC of the tongue and sought to determine the impact of aRT use on survival. We discovered that aRT confers advanced survival in Stage IV SCC of the tongue, whereas it failed to improve survival status in Stage I to Stage III SCC patients. Furthermore, aRT for Stage I cancers has a negative impact on patient survival. To unequivocally establish the association between the tumor stage and aRT, we verified the results in the original and PSM cohorts and obtained the same conclusion. Our results contribute to the growing body of knowledge related to tongue SCC-related outcomes and reveal that survival and response to aRT vary with tumor stage. In this article, we report a number of observational associations that can provide motivation and set the stage for future mechanistic studies investigating the biological mechanisms that may underlie the observed differences in tongue body SCC prognosis and response to treatment.
In our original data analysis, aRT served as a risk factor for patients with Stage I tumors in 5-year OS and DSS. In addition, it is worth noting that we could not detect any significant benefits of aRT for Stage II and Stage III patients. These results suggest that these early-stage patients do not benefit from aRT. There are reports [21–24] of findings similar to those of our study. Sandhya et al. analyzed a cohort of 103 cases and suggested that postoperative radiation therapy had no significant impact on the survival of patients with Stage I and II deep tongue cancers, with no less than a 4-mm tumor invasion depth . According to Shim et al., 86 patients with early-stage tongue cancer were enrolled in the study, but no significant differences were observed in the OS rate after surgery alone and a combination of surgery and postoperative radiation therapy . However, these studies included only a few patients, and it was difficult to adjust baselines. Focusing on oral cavity cancers generally, Luryi et al. and Sowder et al. analyzed the data from the SEER database with a large number of cases and revealed that treatment with adjuvants led to significantly worse OS and DSS than surgery alone for early-stage oral cancers [23,24]. However, they did not determine whether postoperative radiation therapy was beneficial for each subsite. Our results are consistent with those of previous studies that suggested that early-stage patients should not receive aRT after surgery. This would increase the cost of treatment and reduce the quality of life of these patients, and the radiation exposure to the oral cavity and oropharynx may lead to unfavorable complications.
In contrast, some other reports have suggested that aRT is beneficial for early-stage head and neck SCC. Tsai et al. confirmed that aRT could improve neck control and survival status in patients with early oral cancers with a single nodal status in the Taiwan Cancer Registry database . Furthermore, Schiff et al. suggested that aRT could improve regional failure in patients with pN1 tongue cancers, although the results were not significant (P=0.32) . Torrecillas et al. confirmed significant survival benefit of aRT for patients with T1N1 and T2N2 oral cavity SCC . Qian et al. suggested that aRT resulted in better survival in patients with pN0 . Shrime et al. suggested that aRT was associated with the most significant improvements in cancers of the tongue after verifying its effects on T1N1 or T2N1 oral SCCs . Several factors were responsible for these divergent conclusions: first, the sources of their data were variable, and the characteristics of patients and aRT modalities could be different; second, some studies have focused on the oral cavity or head and neck rather than a specific subsite, which may influence the survival status of patients; third, some early-stage patients may suffer from occult node metastases. We speculate that advanced benefits of aRT may be identified in larger cohorts with occult metastases.
Compared with these studies, we conducted a more accurate study based on a large number of patients in the SEER database and included SCCs of the entire tongue body (anterior 2/3 and base of tongue). We also included various patient characteristics and treatment options. Considering that patients with different tumor stages could have different characteristics, we made some adjustments to the basic characteristics of the patients to reduce bias. We performed a subgroup analysis and conducted PSM based on baseline variables. For both the original and PSM groups, we explored the effects of postoperative radiation therapy on OS and DSS. After adjustment, we did not detect any significant changes in the results compared to the original data. We used PSM to match all variables at a 1:1 ratio between aRT and non-aRT receivers; 1502 cases were included. We discovered that aRT could worsen the survival of patients with Stage I SCC, even after adjustment and matching. In addition, we found that aRT could not always extend the duration of survival for late-stage tumors. aRT can only improve the survival of patients with Stage IV SCC of the tongue and is not significantly associated with survival benefits in the original and propensity-score matching populations. Our PSM and adjusted results provide dual authentication that patients with different stages of SCC cannot always benefit from aRT after surgery. The provision of appropriate therapeutic regimens is of great importance. This should be based on several factors, including patient characteristics, disease progression, and quality of life following surgery.
Because of its retrospective nature, this study inevitably had several limitations. Due to the lack of therapeutic parameters of radiation (including definitive versus palliative intent, dose/fractionation) in the SEER database, we could not evaluate the effects of these factors on survival and prognosis. The list of variables included in our analysis was not exhaustive, and some potentially important factors (e.g., smoking status, alcohol drinking, and vascular invasion) were not available in the SEER database. Additionally, we do not have access to the information on various patient characteristics in the SEER database, including quality of life, complications, tumor resection margins, recurrence, and treatment of recurrence, all of which may have affected our aRT analysis. Advances have been made in radiotherapy technology; however, as a result of differences in selection criteria, techniques, and equipment, toxicity and quality of life within a given period of time can be compromised more than survival outcomes .
In conclusion, we suggested that there were significant survival benefits associated with aRT for Stage IV SCC of the tongue and that patients with Stage I SCC of the tongue cannot benefit from aRT. Thus, survival and other benefits of aRT for early-stage SCC need some further justification, especially for Stage I patients. Otherwise, these patients may not be subjected to unnecessary radiation and morbidity. Our results provide an orientation for research interest in the biological mechanism, and future researchers can provide reasonable explanations and feasible methods of improvements for aRT.