Tracheal cancers are uncommon malignancies, and there is a scarcity of large-scale studies to provide guidance on their management. However, preliminary investigations demonstrate that radiation therapy may improve overall survival and decrease the incidence of tracheal cancer-related mortality in patients suffering from primary malignant tracheal tumors who are medically unsuitable for surgery. Surgery is regarded as one of the best treatment options for these tumors; however, its implementation is restricted by factors such as the tumor's size, location, and extent, as well as the presence of comorbidities. While radiation therapy is an important local treatment modality, its efficacy in treating malignant tracheal tumors remains contentious. Neoadjuvant radiation therapy is not recommended, as it can hinder bronchial blood supply, causing delays in anastomotic site healing, and increasing the risk of dehiscence, especially in patients with invasive extraluminal tracheal tumors that require comprehensive treatment. Nevertheless, a study conducted by Napieralska and colleagues confirmed the potential of radiation therapy in treating malignant tracheal tumors(Napieralska, Miszczyk, & Blamek, 2016). In a retrospective analysis of 58 cases of pathologically confirmed malignant tracheal tumors, Napieralska et al found that radiation therapy (P = 0.013), performance status (PS) score (P = 0.033), and hemoptysis (P = 0.003) were independent prognostic factors that were associated with greater longterm survival in patients with tracheal malignancies. Local surgical or endoscopic resection therapy was only found to be a survival prognostic factor in the univariate analysis (P = 0.030); however, in the multivariate analysis, its impact on survival was not statistically significant (P = 0.324). Larger studies on surgical treatment of tracheal tumors indicate that 70% of patients are eligible for surgical resection, while 70% of patients with adenoid cystic carcinoma of the trachea require postoperative radiation therapy(Grillo & Mathisen, 1990). For incompletely resected moderately to poorly differentiated malignant tumors, adjuvant radiation therapy is recommended after surgery(Fields, Rigaud, & Emami, 1989). Je et al. believe that for adenoid cystic carcinoma of the trachea that has undergone surgical resection with residual lesions found under the microscope, adjuvant radiotherapy should be given(Je et al., 2017).
The management of unresectable primary tracheal tumors is not well-defined due to the scarcity of reliable data. However, for patients who are not eligible or decline surgical intervention, radical radiotherapy should be administered whenever feasible. This approach can provide a viable alternative to surgical resection, and may significantly improve the prognosis for patients with primary tracheal tumors that cannot be surgically removed(Graham MV, 1997; Thotathil, Agarwal, Shrivastava, & Dinshaw, 2004). Histology is a significant determinant in determining the outcome of radical radiotherapy, and patients with adenoid cystic carcinoma tend to have better prognoses than those afflicted with SCC(Fields et al., 1989). For adenoid cystic carcinoma of the trachea that cannot be completely resected surgically, definitive radiotherapy is an effective treatment(Je et al., 2017). Chen et al. also found that adjuvant radiotherapy significantly prolonged progression-free survival (PFS) (P = 0.027) and OS (P = 0.004) in 24 cases of incompletely resected tracheal adenoid cystic carcinoma(Chen et al., 2015). Tracheal squamous cell carcinoma has a relatively poor prognosis, and its radio-sensitivity is generally considered inferior to that of tracheal adenoid cystic carcinoma. Tracheal Squamous cell carcinoma, on the other hand, generally has a poor prognosis and is considered to be less responsive to radiotherapy than adenoid cystic carcinoma. However, SCC managed with radiotherapy in other locations has demonstrated favorable outcomes in terms of local control and survival, including in the postoperative setting among patients with lung, cervix, head, and neck cancers(Lung Cancer Study, 1986; Peters et al., 1993; Rotman et al., 2006; Trodella et al., 2002). A retrospective analysis conducted by Xie et al. on 78 patients who received radiotherapy and 78 patients who did not receive radiotherapy for tracheal SCC from the SEER database showed that overall survival was significantly prolonged in patients who received radiotherapy, with a decreased cumulative mortality rate(Xie et al., 2012).
Due to the low incidence of malignant tumors in the trachea, research on the doseresponse relationship of radiotherapy is limited. It is common to administer a dose of 54 Gy for tracheal tumors, which can be increased up to 60 Gy with the use of intensity-modulated radiotherapy (IMRT). F. Mornex et al. suggested that the dose of radiotherapy is a prognostic factor for primary tracheal tumors. The 5-year survival rate of patients who received > 56 Gy of radiotherapy was 12%, while that of patients who received low-dose radiotherapy dropped to 5%(Mornex et al., 1998). Levy et al. performed a retrospective analysis of 31 cases of tracheal adenoid cystic carcinoma that were treated at their center from 1984 to 2014. They found that whether the radiotherapy dose exceeded 60 Gy was an independent prognostic factor for progression-free survival(Levy, Omeiri, Fadel, & Le Pechoux, 2018). Similar findings were reported by Licht et al., showing that tracheal malignancies treated with a radiation dose over 60 Gy had a 2-year survival rate superior to that of patients receiving less than 40 Gy(Licht et al., 2001). High-dose radiotherapy may increase local tumor control rates and survival time. However, it also increases the risk of complications, such as tracheobronchial fistulas, airway stenosis, and tracheal necrosis(Alraiyes, Alraies, & Abbas, 2013; Kelsey et al., 2006; Miller et al., 2005). With the advancement of radiotherapy techniques, complications after high-dose radiotherapy can be minimized. However, there is currently a lack of randomized trials on curative radiotherapy for primary tracheal tumors, and the optimal dose and fractionation of radiotherapy remain uncertain.
This analysis has several limitations that should be considered. Firstly, retrospective studies and population-based studies have inherent limitations that could affect the reliability and validity of the results. Secondly, the sample size of patients with malignant tumors of the trachea (N = 360) is relatively small, which could have contributed to potential errors in the analysis. Thirdly, there are numerous factors, including tumor size and systemic treatments, that could not be taken into account due to the limitations of the SEER registry. Finally, while race does not seem to impact the prognosis of patients with malignant tumors of the trachea, it is important to note that the majority of study participants were white, so the generalizability of these models to other ethnic groups is uncertain and necessitates further investigation.
Our study has found that surgery, marital status, disease extension, pathology, and age are all independent risk factors for patients diagnosed with tracheal malignant tumors. For patients who did not undergo surgery, radiotherapy and disease extension were identified as independent prognostic factors. The development of nomograms as an intuitive graphic tool can facilitate the quantitative evaluation of risk and prognosis, and guide clinical decision-making in cases of tracheal malignant tumors.