Patient female, born in 1937. 1980.12, left breast cancer, surgically treated, pathology: simple cancer, no metastasis in LN. 2002.7 Chest X-ray revealed a right lower lung occupancy, so CT examination was performed (Figure 1).
Figure 1: 2002.7 CT: 1.2 X 1.5 cm nodular shadow was seen in the dorsal segment of the right lower lung lobe, slightly lobulated, with hairy margins and small burrs visible.
2002.8 A right lower lung lobectomy was performed in a teaching hospital in Shanghai. The tumor was located in the lower lobe of the right lung, about 3 X 2 X 2 cm, with a hard texture and a concave pleura on the surface.
Pathology: adenocarcinoma (right lower lung), grade II-III differentiation, no cancer involvement in bronchial margins. Four parabronchial lymph nodes were found, none of which showed cancer metastasis.
No further treatment was done after surgery.
In 2003.9 (1 year and 1 month after surgery), the CT was reviewed (Figure 2).
Figure 2: 2003.9 (1 year and 1 month after surgery) CT (Figure 2): multiple new small nodular shadows in the left lung, intrapulmonary metastases were considered.
Multiple new small nodular shadows in the left lung were considered intrapulmonary metastases. Chemotherapy was given. 2003.9 (1 year and 1 month after surgery) -2003.11, three chemotherapy regimens were given: paclitaxel 240mg ivdrip d1, cisplatin 30mg ivdrip d1-5. The fourth and fifth rounds of chemotherapy were administered from 2003.12 to 2004.1 with paclitaxel 240mg ivdrip d1 and carboplatin 600mg ivdrip d1.
In 2004.2 and 2004.5, CT was repeated: no significant change from the previous one.
2006.1 (3 years and 5 months after surgery) Patient complained of “sudden onset of pleural effusion while visiting relatives in the United States, with significant symptoms – inability to eat, sleep, chest tightness and wheezing, and sudden weight loss of 7 kg”.
2006.2 (3 years and 6 months after surgery) Patient complained: “Started taking Tarceva (150mg/day) orally, and her health was improving day by day after taking it. After returning to China in March, my daughter has been bringing back the medicine by proxy every month without fail”.
Figure 3: Screenshot of the patient’s invoice for Tarceva (Troche) in the US
You can see the price of Tarceva in the U.S. at that time: $8845.9 for 90 tablets, which translates into about 20,000 RMB per 30 tablets.
Regular review of chest X-ray after taking Troche.
Figure 4: From left to right (1) 2006.4.21 (3 years and 8 months after surgery, 2 months after taking Tarceva) Chest X-ray: bilateral pleural effusion.
(2) 2006.6.15 (3 years and 10 months after surgery, taking Troche for 4 months) Chest X-ray: bilateral pleural effusion.
(3) 2007.3.28 (4 years and 7 months after surgery, taking Troche for 13 months) Chest X-ray: left pleural effusion decreased compared with the previous one.
From the above chest film results, it can be seen that the pleural effusion gradually decreased after taking Troche.
Thereafter, the lesion continued to improve by continuing to take Troche and regularly reviewing the chest CT.
Figure 5: 2010.7.23 (7 years and 11 months after surgery, 4 years and 5 months on Troche) CT: No significant nodules were seen.
Reflections.
1. The dream is coming true! Ancient emperors sought to seek immortality and sought to refine the elixir, resulting mostly in death due to heavy metal poisoning.
Figure 6: Ancient alchemy
Before the advent of EGFR-TKI, for patients suffering from advanced lung cancer, those without contraindications to chemotherapy had to undergo painful chemotherapy with survival time basically less than two years, and those with contraindications to chemotherapy could only be given the best supportive treatment with even shorter survival time. Today, with just one pill a day, you can basically live like a normal person, and your quality of life is basically unaffected. In some patients, the dream has become a reality!
2. The era of molecular typing has arrived. This should be attributed to the identification of key tumor molecules and the successful development of corresponding targeted drugs. It also marks the advent of the era of molecular tumor typing. As long as there are specific genes and molecular alterations, good efficacy will be achieved by using specific drugs. Representative drugs: 1. small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as Gefitinib (Gefitinib, Iressa, Eressa); Erlotinib (Tarceva); 2. anti-EGFR monoclonal antibodies, such as Cetuximab (Erbitux); 3. anti-HER-2 monoclonal antibodies, such as Herceptin. monoclonal antibodies, such as Herceptin (Trastuzumab, Herceptin); 4. Bcr-Abl tyrosine kinase inhibitors, such as Imatinib; 5. Vascular endothelial growth factor receptor inhibitors, such as Bevacizumab (Avastin); 6. Anti-CD20 monoclonal antibodies, such as rituximab (Rituximab). Rituximab).
3. Thinking about tumor treatment methods: chemotherapeutic drugs kill both tumor cells and normal cells, without obvious specificity (Figure 7).
Figure 7: Lack of specificity of chemotherapy
In contrast, with targeted therapy, we can first perform testing and give targeted drugs only when we determine that the patient belongs to sensitive patients (Figure 8), which significantly improves the specificity.
Figure 8: Targeted drugs find sensitive patients through testing, which significantly improves the specificity
4. Tumor heterogeneity: further research found that not only between different tumors, even the same tumor, there is heterogeneity depending on pathological type, race, gender, smoking and other factors, a targeted drug is only effective for the corresponding patients, a key to open a lock, for example: among EGFR-TKI insensitive lung cancer patients, there is a class of patients with EML4-ALK fusion gene, research A new drug, Crizotinib, was found to have a high remission rate and a favorable safety profile in lung cancer patients carrying the EML4-ALK fusion gene, which is mutated in about 4% of lung adenocarcinomas; the EML4-ALK gene causes 3-5% of non-small cell lung cancers (about 10,000 such cases per year in the United States alone). With multiple clinical trials related to Crizotinib currently underway, we expect that humanity will hold more and more keys to unlock all lung cancer subtypes (Figure 9).
Figure 9: We expect that human beings can master more and more keys to open the locks of all lung cancer subtypes
5. Drug resistance will emerge sooner or later. Targeted drugs have such good efficacy that people are ecstatic, but so far, all patients will eventually develop drug resistance, which is one of the problems that cancer has posed to human beings, and the cunning opponent of cancer uses his versatility to escape the fatal blow once again. Humans have begun to discover several mechanisms of drug resistance in lung cancer (Figure 10), the most representative of which is the acquired drug resistance mutation T790M.
The devil is one step above the law! Humans have made great strides in the fight against cancer. Although.
it is still far from the dream.
But there is hope!