Patients who underwent complete removal of stage IIIA (N2) NSCLC are at risk of local and distant recurrence7 Adjuvant chemotherapy has been accepted as a part of the standard postoperative treatment of patients with NSCLC, including those with N2 disease.17–20 In recent years, with the significant improvement of technology, the simulation, planning and delivery of radiotherapy have been optimized. These improved techniques are useful for adjuvant radiotherapy in patients with completely resected NSCLC. Zou et al20 believe that radiotherapy combined with chemotherapy can improve the survival rate of patients. One of the most representative articles in the previous study was that from Lally et al21, who retrospectively analyzed the treatment results of NSCLC patients over 21 years old in the US SEER database from 1988 to 2002. After excluding patients with stage I or IV disease, with an unclear disease stage, and with N3 stage disease and surgical patients who died 4 months later, a total of 7545 patients were included in the analysis; 47% of the patients received postoperative radiotherapy. The results showed that, compared to no radiotherapy, the use of radiotherapy after surgery increased the 5-year overall survival rate from 20% to 27% for patients with N2 disease and reduced the risk of death by 14.5% (p=0.007), which was statistically significant. A randomized trial from Mayer et al evaluated the role of adjuvant radiotherapy in 155 patients with completely resected stage IB to IIIA NSCLC. All patients underwent modern conformal radiation treatment, which administers 50Gy in pN0 disease and 56Gy in pN1 and pN2 disease. The results showed a significant increase in terms of local control with PORT compared to without PORT.22 However, there have been many previous studies in which the results have not been satisfactory. It has also been shown that PORT causes an increase in the number of deaths unrelated to cancer. Radiation toxicity, in the form of pneumonia, esophagitis and cardiotoxicity, is the leading cause of treatment-related mortality. This is currently believed to be due to old-fashioned radiotherapy equipment, techniques and scheduling.23 At present, with the improvements made to radiotherapy equipment and personnel technology, the number of deaths caused by radiotherapy and unrelated to cancer has been greatly reduced.
In this study, postoperative radiotherapy, younger age, lobectomy, smaller tumor diameter, and lower number of positive lymph nodes were all suggested as independent factors for better prognosis for patients who underwent removal after N2 radical surgery. Due to the large number of samples analyzed by Lally et al21, their conclusions deserve our attention, suggesting that postoperative radiotherapy can improve the survival rate of N2 patients. Recently, Corso et al24 searched the National Cancer Database to find 30,552 stage II~IIIA NSCLC patients who received postoperative treatment. The 5-year OS was significantly improved in the N2 patients, and postoperative radiotherapy had a significant impact on the OS. Patients who received 45~54Gy had a greater benefit than patients who received other doses; the 5-year OS for patients who received 45~54Gy was 38%, but patients who received higher than 54Gy had the same 5-year survival as those who did not receive PORT. The range of surgical excision, extent of lymph node dissection and dose of radiotherapy affected the curative effect of postoperative radiotherapy. The RTOG standard recommends that radiation therapy be started within 9 weeks of surgery, but the precise timing remains to be studied. Our results are consistent with the abovementioned results. Furthermore, we also analyzed the effect of EGFR mutation status on patient survival. EGFR mutation status was not an independent factor that influenced long-term survival, which is consistent with the results of previous studies.25,26 We hypothesized that EGFR activation mutations cause tumor cells to proliferate faster than normal. On the one hand, the cells with EGFR mutations are highly sensitive to treatment (including EGFR-TKIs, chemotherapy, and radiotherapy), and the treatment shows high efficacy. On the other hand, EGFR mutations make the tumor cells highly invasive and prone to metastasis, and metastases may rapidly develop once the disease progresses, thus offsetting the survival advantage.
In this study, the multifactor analysis showed that the number of chemotherapy cycles and the number of metastatic lymph nodes were independent factors that influenced long-term survival. This study suggests that postoperative radiotherapy and chemotherapy were beneficial to stage IIIA (N2) NSCLC with multistation metastasis. In terms of reducing the recurrence rate and improving the disease-free survival rate, postoperative radiotherapy was of positive value to N2 stage multistation metastasis.
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