The development of stereotactic irradiation techniques has made it possible to focus high-doses radiation on tumors without increasing the side effects. Moreover, this approach can significantly reduce the treatment schedule compared to the conventional methods. In Japan, SBRT is performed for the treatment of early-stage lung cancer, and recently, it has also been performed for inoperable and operable patients . In this study, the 5-year OS rates was 66.3% (Fig. 1), and the 5-year OS rates according to stage IA, IB, and IV were 72.7, 55.6, and 52.1%, respectively (Fig. 2). In addition, it was suggested that the 5-year LC rates was 86.0% (Fig. 1), and the 5-year LC rates according to T1 and T2 were 86.4 and 83.8%, respectively (Fig. 3). It was reported that the representative 5-year OS rates for surgery against clinical stage IA and IB NSCLC were approximately 60–75% (IA) and 40–60% (IB), respectively, and the clinical outcomes of patients with early-stage NSCLC treated with SBRT were as good as the outcomes of surgery [3, 19]. The results of this study supported these reports. Furthermore, we categorized the cause of death for patients who died within 5 years after SBRT as a result of lung cancer or other diseases. The percentages of patients who died from lung cancer vs. other diseases were 6.6 and 93.4%, respectively, indicating that the patients who died from lung cancer was small. Therefore, our results demonstrated that the 5-year OS (66.3%) and LC (86.0%) rates after SBRT treatment were superior and the prognosis was favorable.
In the multivariate analysis, SP-D and IDV showed the highest hazard ratios (HR) for OS and LC, respectively (Table 7, 8), suggesting that they influence the prognosis after SBRT. Our results suggested that the 5-year OS rates in the SP-D normal group and high group were 69.9 and 48.0%, respectively, and the high group showed a poor prognosis compared to the 5-year OS rates for all patients (66.3%) (Table 7, Fig. 4). Inn-Wen et al. reported that high expression of SP-D in NSCLC correlates with poor prognosis , which was consistent with our result. SP-D has been known as an effective diagnostic biomarker for RP [14, 18, 21–23]. Yamazaki et al. indicated the relationship between SP-D levels in serum and RP . However, our results demonstrated that 96% of the patients with RP after SBRT showed G1 and below. Furthermore, 4.65% of the patients in the SP-D high group, and 2.93% in the normal group showed G2 or higher. There was no statistically significant difference in these groups. Therefore, it was suggested that other factors besides RP may contribute to poor prognosis. Regarding histology, the patients with squamous cell carcinoma showed high SP-D rates compared to the patients with adenocarcinoma (35.3% vs. 16.8%, data not shown). The proportion of deaths in the high SP-D group were 6.4 and 20.6% for adenocarcinoma and squamous cell carcinoma, respectively. These results indicated that the cancer histology type, especially squamous cell carcinoma, was related to the poor prognosis in the SP-D high group. Thus, combining histology with SP-D may improve the accuracy of prognostic prediction although histology was not selected as an OS-related factor in multivariate analysis. However, since recent reports indicate that the SP-D low group was correlated with the poor prognosis of patients with lung cancer , further studies are necessary to use them as prognostic factors.
Our previous study demonstrated that IDV is related to LC after SBRT . This study identified that TCTV is a new factor related to both OS and LC after SBRT. Aoki et al. reported that the reduction of IDV as an index of blood flow may reflect the hypoxic cell population cause of radioresistant in the tumor . In contrast, WDV in the tumor is presumed to reflect cell density and cell necrosis. Our previous study suggested that the reduction of the WDV has a positive effect on the OS after radiotherapy . Although the correlation between WDV and IDV was not confirmed, WDV tended to decrease with increasing IDV. Thus, the combination of decreasing IDV and increasing WDV may indicate a poor prognostic index. However, there is a limitation to its use as a prognostic factor because WDV details are not fully understood. Our results indicated a positive correlation between WDV and TCTV, suggesting that using it as an alternative index to WDV and combining it with IDV may improve the accuracy of prognostic prediction. Further studies on TCTV and WDV will improve the validity of these factors.