As one of the important treatments for malignant tumors, radiotherapy plays a curative, adjuvant or life-prolonging role in 70% of lung cancer patients. In this year’s World Conference on Lung Cancer (WCLC), scholars from different countries discussed extensively on basic research of radiotherapy and its application in early, intermediate and advanced lung cancer, and their views were either close or distant, consistent or contradictory, but they expressed their views freely and straightforwardly, and argued with each other on the basis of reasoning, which was a veritable “brainstorm”. The first day of the congress was devoted to individualized therapy. In line with this, the first radiotherapy session was devoted to translational research. The presenters coincidentally focused on the combination of inhibitors of tumor signaling pathways other than the epidermal growth factor receptor (EGFR) pathway and the vascular endothelial growth factor (VEGF) pathway with radiotherapy. The following three classes of inhibitors of signaling pathways may be the first to enter clinical studies for radiotherapy in the future. Aurora kinases, an important class of serine/threonine kinases responsible for regulating cell mitosis, are highly expressed in lung cancer cells, especially in tumors that remain after neoadjuvant therapy. A preclinical study showed that its targeted inhibitors could be used in conjunction with radiotherapy to reduce radiotherapy antagonism in tumor-like stem cells. Inhibition of polyadenosine diphosphate ribose polymerase (PARP) leads to the accumulation of intracellular single-stranded DNA breaks with radiosensitizing effects. Studies reported by Stanford University scholars in this meeting demonstrate that inhibition of PARP also improves tumor oxygenation, forming a second mechanism of radiosensitization, and is therefore an experimental drug with great potential. The function of the Src proto-oncogene has long been known, but therapeutic strategies to block the Src conduction pathway have not been successful in pharmaceutical clinical studies. University of Colorado researchers did not give up and found its more role in metastatic lung cancer through research, proposing that new clinical studies should be designed to apply Src inhibitors as maintenance therapy after radical radiotherapy. Early-stage NSCLC: A stimulating debate on the future of stereotactic radiotherapy The afternoon of the first day of the conference culminated in a series of presentations and debates. Timmerman (USA) first reported the mature results of the RTOG0236 study, in which 55 patients with inoperable early-stage (T1 to 2, median age 72 years) non-small cell lung cancer (NSCLC) received stereotactic body radiotherapy (SBRT) at a dose of 54 Gy/3 doses after tissue density correction calculations. Results after a median follow-up of 24.8 months showed a 2-year local control rate of 93.7%, a 2-year progression-free survival (PFS) rate of 66.6%, and a 2-year overall survival (OS) rate of 72%, which was very encouraging. A similar study was reported by Senan (Netherlands), but with a larger number of cases (193), older patients (over 75 years, median 79 years), worse general condition, and doses of 60 Gy/3, 5, or 8 doses. Despite the numerous unfavorable factors, the 3-year local control rate was still 81%, while the 3-year OS rate was 46%. The two studies above have in common a clinical phase II study in which patients could not tolerate surgery, tolerated SBRT well, had a high local control rate, and had a higher survival rate than historical controls. This led to two debates on the agenda: (i) whether SBRT needs to be tested in a phase III randomized study as the standard of care for patients in the early stages of intolerable surgery; and (ii) whether SBRT is an option for patients in the early stages of operable disease. Ball expressed his insistence on the need for phase III randomized studies because the maturity of the technology must be subjected to a reality check, and although there are 17 relevant phase I/II studies, the dose of radiation therapy varies and the injury situation is yet to be further detailed reports, so it cannot be promoted in a hurry. New randomized studies comparing SBRT with conventional radiotherapy have been initiated. van Schil opposes SBRT as an option for operable patients because of its inability to clarify lymph node status, difficulty in assessing efficacy and deciding on adjuvant therapy, and its inability to be equated with complete anatomic resection. The audience benefited from the opposing arguments in both debates, both of which were well articulated. Locally Advanced NSCLC: Expecting Breakthroughs in Comprehensive Treatment There have been few breakthroughs in the treatment of locally advanced NSCLC in recent years, and there were no big surprises this year. On the second day of the conference, the Radiation Therapy Oncology Collaborative Group (RTOG) reported the results of RTOG 0214, a randomized study of whether to perform prophylactic brain irradiation (PCI) after radical radiotherapy for stage III NSCLC. This study was poorly enrolled from the beginning, originally hoping to randomize 1058 patients, but only 356 patients were enrolled over 5 years. the dose of PCI was 30 Gy/15 sessions. PCI significantly reduced brain metastases (7.7% vs. 18%, P=0.004), but 1-year survival rates were similar (75.6% vs. 76.9%, P=0.86), as were disease-free survival (DFS) rates ( 56.4% versus 51.2%, P=0.11). patients with PCI had no decrease in quality of life but poorer recall. RTOG0214 is consistent with the results of four previous phase III studies, and at this stage it can be considered that there is no clear indication for PCI in NSCLC patients. Concurrent radiotherapy is largely accepted as the standard of care for locally advanced NSCLC, but the most important RTOG study on this issue (RTOG 9410) has not been published for a long time. During the forum discussion on the second day of the meeting, RTOG President Curran revealed that a meta-analysis of all six randomized studies had been completed and submitted to the New England Journal of Medicine, and that the final analysis showed that concurrent radiotherapy reduced the risk of death by 16% compared to sequential radiotherapy (p=0.004). Hopefully, we will soon be able to learn this information in full. Another dilemma in locally advanced NSCLC is that only 25% to 65% of patients can tolerate concurrent radiotherapy, and Macbeth (UK) suggests that sequential accelerated hyperfractionated radiotherapy (CHART) combined with platinum-containing adjuvant chemotherapy may be a better option, if not the best option for all patients. The situation in locally advanced NSCLC is dull for now, but the academic community is still working on it. RTOG 0617 phase III randomized study is ongoing, comparing conventional radiotherapy with high-dose (60 Gy vs. 74 Gy), concurrent conventional chemotherapy with chemotherapy combined with targeted therapy (paclitaxel + carboplatin ± cetuximab). + cisplatin is superior to the etoposide + cisplatin regimen. Hopefully, we will be more encouraged at the 14th WCLC in the Netherlands in two years!