I. Chemotherapy issues In 1995, the British Medical Journal published the results of a meta-analysis covering a total of 9387 lung cancer patients in 52 RCTs, showing that chemotherapy significantly prolonged the survival of NSCLC patients compared to best supportive care (1), establishing the status of chemotherapy from an evidence-based medical perspective and showing its advantages only in patients treated with platinum-containing regimens. The The ECOG1594 study (2) compared the efficacy of four (cisplatin/paclitaxel, carboplatin/paclitaxel, cisplatin/gemcitabine, and cisplatin/doxorubicin) 3rd generation chemotherapeutic agents with platinum-based combination regimens. There were no significant differences in OS and PFS between the four chemotherapy regimens. The platinum diphasic combination was more effective than single agent chemotherapy, but adding additional drugs to this (triple or quadruple combination) did not increase efficacy but rather increased adverse effects. Currently, platinum diphasic regimens remain the standard of care for first-line treatment of lung cancer. There is no difference in efficacy between platinum diphasic regimens based on three generations of chemotherapeutic agents (vincristine, paclitaxel, gemcitabine, doxorubicin) + platinum. Results comparing the efficacy between the platinum diphasic regimen of doxorubicin + cisplatin and the triple-generation + triple-generation regimen of doxorubicin + gemcitabine suggested that the latter did not show superiority. (3) Comparing the efficacy of platinum-based chemotherapy regimens with 4 and 6 cycles for patients with stage IIIB and V NSCLC, increasing the number of chemotherapy cycles did not prolong overall survival time and one-year survival rate, but rather increased toxicities. Obviously, the continuation of first-line two-drug chemotherapy until disease progression after 4 to 6 cycles of first-line therapy is not desirable and does not benefit patients’ OS (4). This is also the rationale for “waiting” for patients to relapse or progress before starting second-line therapy. These results suggest that current chemotherapeutic agents and chemotherapy regimens have reached a plateau and that new treatment modalities and strategies must be found to improve the prognosis and outcomes of lung cancer patients. Both the ECOG 4599 and AVAiL studies have shown that the combination of the angiogenesis inhibitor bevacizumab (Avastin) and chemotherapy has a survival advantage. Studies of Endo in combination with TC regimens also showed a better clinical benefit than chemotherapy alone. none of the studies of EGFR-TKI in combination with chemotherapy showed an increase in efficacy. However, the FASTACT study (5), which included 19 research centers in seven countries and regions, suggested that the first-line application of chemotherapy (gemcitabine + platinum) sequential to troche in advanced NSCLC had a significant prognostic advantage compared with the chemotherapy alone group (gemcitabine + platinum). Its ORR and PFS were both better than those in the chemotherapy-only group. Targeted drug therapy in combination with chemotherapy in a sequential fashion may provide greater benefit to patients. Maintenance therapy is another strategy to improve the efficacy of chemotherapy. Maintenance therapy appears to be more aggressive and proactive than stopping first-line therapy after remission on first-line therapy because increasing the course of therapy only increases the adverse effects and not the efficacy, and waiting for relapse to start second-line chemotherapy. Many studies in recent years also suggest that maintenance therapy may be a clinically valuable treatment strategy. The maintenance strategy can be achieved by continuing the effective first-line two-drug regimen until disease progression, which is essentially a continuation of first-line therapy. As mentioned above, this approach does not prolong overall survival.2 Maintenance therapy with a knitted third䛣 chemotherapy drug, so-called prodrug maintenance: gemcitabine for maintenance therapy is clearly beneficial and can significantly increase the patient’s TTP. paclitaxel and vincristine increase adverse effects without benefit.3 Maintenance therapy with the second-line chemotherapy drug doxorubicin ∖ pemetrexed, so-called drug exchange, is a clinically valuable strategy. maintenance therapy with pemetrexed, so-called maintenance by drug exchange: the former is unclear. The latter efficacy was established by the JMEN study (6), in which patients in the pemetrexed group had a longer PFSDCR than in the placebo group. It was this study that led the US FDA to approve pemetrexed for maintenance therapy after first-line control of lung}.4 Targeted drug therapy G drugs for maintenance therapy: both gefitinib and erlotinib for 㻴-sustainment are supported by the literature.The WJTOG0203 study looked at patients treated with gefitinib after chemotherapy alone and 3 cycles of chemotherapy, respectively, and showed that platinum dif The SATURN study (7), involving 152 research centers in 29 countries, showed that maintenance treatment with erlotinib after chemotherapy in patients with advanced NSCLC significantly improved tumor remission rates compared to the placebo group, with significantly more patients with more than 12 weeks of disease control and well-tolerated . We should have confidence in the treatment of lung cancer, actively explore it and report an optimistic attitude. However, we must also recognize the seriousness and urgency of the problem, and have a certain sense of pessimism and crisis. The number of drugs and efficacy of first-line chemotherapy tend to enter a plateau. The development of new drugs lags behind the development of the disease, the efficacy brought by new drugs is limited, and the future of first-line chemotherapy makes people confused. Some scholars have even suggested that the ideal treatment for lung cancer must await the search for avenues other than chemotherapy. The current situation of second-line treatment is that the advanced stage of the disease and the failure of chemotherapy have made the treatment more difficult, and there are even fewer drugs to choose from, only pemetrexed and doxorubicin are available, and the current situation is that doxorubicin has been used as the first-line drug in many clinical cases. As for maintenance therapy, it is essentially an inevitable choice with little effect and controversy. Second, the issue of targeted drug therapy targeted therapy drugs are mainly divided into small molecules of TKI and large molecules of monoclonal antibodies. The two main studies confirming the efficacy of TKI are ISEL and BR-21( 8). Both of these studies enrolled patients who failed chemotherapy. Thus, TKI applications were initially introduced into lung cancer treatment as a second-line treatment measure. Initially, there was confusion as to why there was a population difference in the efficacy of TKI. Studies revealed that the efficacy of TKI depends on the mutation of EGFR. Those with the mutation had good efficacy, while those with the wild type were almost ineffective. Patients with lung cancer of yellow ethnicity have a high rate of mutations in EGFR and thus have good efficacy in this population. One of the main reasons for the early termination of the TORCH study (9) with first-line erlotinib and second-line gemcitabine/cisplatin than with first-line gemcitabine/cisplatin and second-line erlotinib was that the trial design was not genetically stratified to select patients for enrollment. Mutations in the KRAS gene are negative predictors of TKI efficacy. Targeted drug therapy is a new horizon in tumor prevention and treatment, a new pathway and an attempt with significant value after people showed concern about the status and future of chemotherapy in tumor treatment. Based on promising results in patients who have failed chemotherapy, TKI has been used for maintenance treatment of patients in remission in first-line therapy, and has also achieved better results. As mentioned earlier. In contrast to the first-line, second-line, and then maintenance strategy for chemotherapy, the TKI strategy has been reversed, with the TKI’s efficacy first being achieved in second-line therapy for patients who have failed chemotherapy, offering hope. Therefore, the intention to re-evaluate its status and expand its thinking is logical. “Would it be possible to spare patients the pain and financial expense of chemotherapy if targeted agents were given at the outset for the advantaged population, rather than second-line therapy after chemotherapy failure or maintenance therapy given to DD after chemotherapy?” The IPASS study (10) selectively used gefitinib for first-line treatment of NSCLC nooks based on EGFR gene mutation or not and found that skid-podвpang tranquilizer i.e. + carboplatin thus established the status of TKI first-line treatment. In fact, from the current research results on, targeted drug therapy can also s exist in the plateau phase. After the plateau phase of chemotherapy should we now be prepared for the possible plateau phase of targeted drug therapy? Another question of placing targeted drug therapy in the first line E is, do we then choose chemotherapy when the patient’s targeted drug fails? III. The problem of treatment and prevention The global incidence of lung cancer is on the increase, and the impression brought to us by epidemiology is that the more developed the so-called modern civilization is, the higher the incidence is. The incidence rates of lung cancer in Eastern Europe, North America, Southern Europe, Western Europe, and Northern Europe are 65.1/100,000, 61.7/100,000, 56.9/100,000, 50.9/100,000, and 44.3/100,000 for men, respectively; and 8.7/100,000, 35.6/100,000, 9.2/10, 12.0/100,000, and 21.3/100,000 for women, respectively. The incidence rates in the Asia-Pacific region were:, 42.2/100,000, 39.1/100,000, 38.1/100,000, 33.1/100,000, 27.1/100,000, and 11.9/100,000 for men in China, Australia and New Zealand, Japan, West Asia, Southeast Asia, and South Asia, respectively; and 19.0/100,000, 17.4/100,000, 12.3/100,000, 5.5/100,000, and 5.5/100,000 for women and 8.9/100,000, 2.4/100,000 for women. The incidence rates of lung cancer in Central, East and West Africa in the African region were 4.7/100,000, 3.6/100,000 and 2.4/100,000 for males and 0.7/100,000, 2.2/100,000 and 0.6/100,000 for females, respectively. (11) Such geographical distribution characteristics and epidemiological trends suggest that the incidence of lung cancer is somewhat regularly associated with the development of modern civilization. Although developed countries have enjoyed the comfortable life brought by industrialization, they have also suffered from the environmental pollution brought by it. After the pains, they have reflected, acted, alerted and curbed, adopted a series of measures to prevent air pollution and adjusted the industrial structure, but the momentum of lung cancer incidence has not been stopped at least for the time being. This raises the question: In the historical trend of justifiably accelerating our development to meet our growing material and cultural needs, how do we avoid harm and tend to benefit? Admittedly, this is not something that physicians and laboratory scientists whose horizons and thinking are inevitably confined to their own specialization can solve by devoting their interests or their life’s work exclusively to the discovery of a gene, the development of a drug, the relief of some patients. This must rely on a social thinking, an integrated action, a dispassionate analysis that incorporates philosophy and humanism to arrive at a decision. The problem can only be solved when the unintentional producers of lung cancer upstream and the exhausted and anxious people trying to end it downstream recognize the seriousness of the problem, establish a unified code of conduct at the macro level, and reach a consensus in defining the goals. While we are spending a lot of energy, manpower, material and financial resources on the treatment of lung cancer, we should not focus on another perspective. The relationship between civilization and civilizational diseases in the modernization process, and the reflection on the humanism brought by this relationship make us take a serious look at the pros and cons of civilization, the blessings and curses of development!