For thousands of years, cancer and human beings have followed each other, and so far about 8 million people die from cancer every year worldwide. In the future, we will fight against cancer more persistently and wisely! In recent years, the incidence and mortality rate of lung cancer in China has been rising rapidly. According to the World Health Organization (WHO), it is predicted that by 2025, China will have more than 1 million new lung cancer cases each year and will become the world’s number one lung cancer country.
Under such a serious situation, we have made great progress in lung cancer screening, diagnosis and treatment through decades of scientific research and clinical practice, from the continuous maturation of radiotherapy to the leap forward development of targeted and immunotherapy, and the comprehensive management mode of lung cancer has almost undergone a radical change. “This year’s theme is “Science against cancer, care for life”, and the Chinese Anti-Cancer Association calls on everyone to strengthen health education and stay away from bad habits.
Lung cancer screening, low-dose spiral CT is the best “tool”
To fight against cancer, the most important thing is early diagnosis and treatment. Therefore, for many years, scholars from different countries have done a lot of research on how to detect early lung cancer, including finding tumor cells in sputum, chest X-ray and screening with low-dose spiral CT (LDCT).
In the 1950s and 1980s, studies found that chest X-rays could detect more early lung cancers, but could not reduce the mortality rate of lung cancer. Data from the U.S. Lung Cancer Screening Study Group showed a 20% reduction in lung cancer mortality and a 6.7% reduction in all-cause mortality in the LDCT screening group compared to the chest x-ray group. Subsequently, LDCT has become an effective screening tool for large lung cancers, with a detection rate of up to 80% for early stage lung cancers, and can detect lesions less than 1cm in diameter, and almost 100% of patients can be cured by minimally invasive surgical resection without further radiotherapy and chemotherapy.
In addition, Prof. Jiang also pointed out that an important finding in the practice of lung cancer screening is that the definition of high-risk group for lung cancer in China is different from that in the United States. In recent years, the incidence of lung cancer in China has increased rapidly, including a 4-fold increase in Beijing over the past decade; the prevalence of lung cancer in rural areas is about 2 times lower than that in urban areas, even though both people smoke; many women who do not smoke also develop lung cancer; and about 50% of patients with peripheral nodules are malignant (most of them are benign abroad). From these phenomena, it seems that haze may be an important influencing factor of lung cancer, so people at high risk of lung cancer in China, except for smoking, second-hand smoke, occupational factors, repeated infections and family history of lung cancer, living in heavy air pollution for a long time should also be included.
Then, how to deal with small lung nodules found in LDCT screening?
Small pulmonary nodules are round lesions with a diameter of <1cm, which can be classified into pure solid nodules (7% probability of malignancy), pure ground glass nodules (18% probability of malignancy) and partially solid ground glass nodules (63% probability of malignancy) according to the density of nodules shown on imaging.
In the face of small pulmonary nodules, we should first clarify the qualitative diagnosis of cancer, and then consider the natural course of nodule development, develop a long-term follow-up strategy, and fully understand the patient’s medical history before making a comprehensive judgment, and avoid the misconception that “small pulmonary nodules = early lung cancer, requiring immediate surgery”. At the same time, multidisciplinary discussion is also very important to better reduce the rate of misdiagnosis.
Chemotherapy, the cornerstone status cannot be shaken
In the history of lung cancer treatment, chemotherapy was the first treatment that significantly prolonged the survival of lung cancer patients. And decades have passed, chemotherapy has become even more classical in continuous improvement. Currently, two-drug combination chemotherapy based on platinum is basically used in clinical practice, and only minor adjustments occur in comparison.
1.Drug use in different tissue types: pemetrexed drugs are more advantageous for patients with adenocarcinoma or large cell lung cancer, while gemcitabine is more therapeutic for squamous cancer.
2.Change in dosing strategy: Related studies have shown that increasing the number of chemotherapy sessions after 4-6 sessions of chemotherapy does not clearly increase the efficacy. Therefore, in the past, chemotherapy was stopped after the end of chemotherapy and continued when the tumor disease progressed, but now for patients with advanced NSCLC (CR+PR+SD) who have achieved disease control with first-line therapy, single agent maintenance therapy can be chosen.
3, chemotherapy indications: chemotherapy is the standard treatment for EGFR wild-type patients in the first line; chemotherapy is the mainstay of the whole treatment for patients without drug-resistant gene mutation after the progression of targeted therapy; chemotherapy is the standard treatment for patients with rapid progression after EGFR/ALK-TKI therapy; chemotherapy is the standard treatment for advanced NSCLC patients in the second and third line.
Targeted therapy, God’s gift to the Chinese
When it comes to targeted therapy, Prof. Jiang said that the biggest highlight of the Asian population is the high rate of EGFR mutations, and is an important reason why EGFR-TKI (tyrosine kinase inhibitor) improves the survival of patients with advanced NSCLC (especially Asian non-smoking women with lung adenocarcinoma).
The results of the IPASS study showed that in patients with positive EGFR mutations, the progression-free survival of the gefitinib group, a generation of EGFR-TKI, was significantly better than that of the paclitaxel-carboplatin group, establishing the importance of EGFR mutations as predictors of efficacy and ushering in a new era of individualized lung cancer treatment. Of course, in the clinical application of targeted therapy for more than ten years, drug resistance has become the biggest problem. Among them, EGFR20 exon T790M mutation is the first EGFR-TKI resistance mechanism identified and the most common resistance mechanism (present in 50%-60% of patients after EGFR-TKI treatment). Although tremendous progress has been made in research related to T790M resistance (in the AURA3 study, the third-generation EGFR-TKI Osimertinib was approved by the FDA for second-line treatment of NSCLC patients with T790M mutation-positive disease that progressed after first-generation EGFR-TKI therapy, with a more than two-fold survival benefit over chemotherapy), the detection of T790M resistance has been a major challenge for detection of T790M drug resistance still leaves something to be desired.
When targeting therapy, tissue biopsy to determine tissue typing, clarify the target, and detect the driver gene status to determine subsequent therapy has become the routine treatment process. For patients receiving targeted therapy, Shanghai Chest Hospital then detects changes in drug resistance in patients by ddPCR (microdrop digital polymerase chain reaction) technology at several time points before treatment, one month after treatment, and when disease progression is clinically detected. However, the greatest difficulty in performing re-biopsy after drug resistance is the difficulty in obtaining tissue specimens, when liquid biopsy can play a great role and can be used as a routine screening tool for T790M mutations, and after liquid biopsy, tissue biopsy reconfirmation has become a standard procedure. In addition, re-biopsy after re-drug resistance is a concept that we now want to emphasize.
Immunotherapy, 5-year survival for advanced lung cancer is not a dream
Immunotherapy is the latest therapy for lung cancer and has been developed by leaps and bounds in recent years (currently the FDA has approved anti-PD-1 antibodies nivolumab and pembrolizumab for second-line treatment of NSCLC; while anti-PD-L1 antibodies such as atezolizumab and durvalumab have also entered phase 3 clinical trials). At the American Association for Cancer Research (AACR) 2017 meeting this month, results from the CA209-003 Phase Ib clinical trial, the first study of a PD-1 immunodetectable site inhibitor for lung cancer, showed that immunotherapy resulted in a 16 percent 5-year survival rate, a full 3-fold improvement over the previous 4 percent overall survival rate with conventional therapy. However, in addition to this encouraging data, other studies at the AACR meeting made scholars aware of many serious realities, such as the threshold classification of PD-L1, which is not the same in the trials due to the inconsistency of detection antibodies, staining and evaluation of immune drugs, so there is still a lot of room to explore the threshold setting for the appropriate population; in addition, the tumor The survival benefit of patients with different mutational load is also different.
Therefore, for immunotherapy, it is worth exploring the question of what kind of population and what kind of markers can be selected as a guide? What kind of population is more suitable for immunotherapy? After all, immunotherapy cannot be a one-size-fits-all sword.
Finally, it is expected that the diagnosis and treatment of lung cancer will become more and more accurate, with better research data and relatively sensitive populations to guide radiotherapy; faster technology to screen lung cancer patients for targeted therapies, drug resistance detection and dosing recommendations; and more uniform markers to select populations truly suitable for immunotherapy.