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The second Chinese chest tumor consultation
Based on the successful holding of the "Guangdong Consultation" in 2021, in order to gather the wisdom of experts on a larger scale and promote the multidisciplinary expert diagnosis and treatment model of lung cancer more widely, the Lung Oncology Branch of the Guangdong Medical Association and the Guangdong Clinical Trial Association/China Chest Oncology Research Assistance Group (GACT/CTONG) will organize the "China Chest Oncology Conference" activity from February 2022. We invite experts from all majors in the field of chest tumor treatment across the country to form a consultation and decision-making team, and conduct multidisciplinary consultations on representative difficult cases of lung cancer every month, gather the sword of everyone's wisdom, and pick up the shield of evidence-based medicine to contribute to the key tasks of lung cancer diagnosis and treatment in China.
The case of this consultation
NO.1 case introduction
▶Medical history summary
patient, female, 53 years old, PS=1 point.
patients had no obvious cause of coughing or white sticky sputum in early February 2020. 2020-03-04 CT of the chest and abdomen in our hospital showed that: considering central lung cancer in the right upper lung (67×39 mm) and multiple metastasis in both lungs and right pleura, and multiple lymph node metastasis in both hilar and mediastinal . Multiple liver metastases (24 × 20 mm) were considered (Fig. 1). Head MR enhancement: No abnormalities were seen.
Figure 1. During the initial diagnosis, the chess and abdomen CT, primary foci of the right upper lung (A), anterior vascular lymph node (B), liver metastasis (C), vertebral body (D)
2020-03-05 The right supraclavicular lymph node biopsy was performed in our hospital. The pathology showed that adenocarcinoma tissue metastasis was visible, PD-L1 (22C3) (TPS, 2%+), EGFR:21 showed L858R point mutation (+).
Diagnosis: right upper lung lung adenocarcinoma cT4N3M1c (dual lungs, pleura , liver) stage IVB.
patients started orally taking afatinib 40mg qd, PR, 1° diarrhea, 3° rash, diarrhea, diarrhea on 2020-03-20.
2021-07-22 PET/CT examination indicated that mediastinal lymph nodes were enlarged compared with the previous one, the lesions were slowly enlarged, and there was suspicious metastasis of the liver and vertebrae. It is recommended to continue taking afatinib oral (Figure 2).
Figure 2
initial diagnosis (2020-03-03), when PR is reached (2020-08-28), when suspicious progress (2021-07-22) the change trend of
lesions, primary foci (A), anterior vascular lymph nodes (B), liver (C), vertebral body (D)
department discussion evaluated as slow progress, and it was decided to continue oral afatinib, 2021-10-12 Head MR enhancement: multiple intracranial lesions, combined with the history, multiple metastatic tumors are considered, the largest located in the left caudate nucleus, about 9×6mm (Figure 3). 2021-10-13 Chest enhancement CT showed that the primary lesions and metastatic lesions were both enlarged compared with the previous one, and the number of metastatic lesions increased, evaluation progress, PFS1=16 months (Figure 4).
Figure 3.2021-10-12 Head MR shows multiple intracranial metastasis (A,B)
Figure 4
2021-07-22 and 2021-10-13 thoracic and abdomen CT comparison, indicating enlargement of the lesion, primary foci of the right upper lung lobe (A), liver (B), vertebral body (C)
2021-10-18 lumbar puncture examination, cerebrospinal fluid pressure 218mmH2O, pathology: (cerebrospinal fluid) TCT production, see lymphocyte and histocyte , and no clear malignant tumor cells were found.
2021-10-19 Right lung puncture biopsy, pathology: (right lung) invasive adenocarcinoma.
Immunohistochemistry results: PD-L1 (22C3) (about 1%+).
fluorescence in situ hybridization (FISH): negative (CMET gene has no amplification), NGS detection results are shown in Table 1.
Table 1 The evaluation progress of patients with mutation genes and abundances shown in NGS examination. Oral osimertinib 80mg was started on 2021-11-02. Regular review was conducted after treatment. The review of 2022-02-14 showed that there was no significant enlargement of the lesions in the lungs, and multiple nodules in the liver were enlarged. Evaluation progress, PSF2=3 months (Figure 5).
Figure 5.
Before treatment (2021-10-13) and after treatment (2022-02-14), there was no significant enlargement of the intrapulmonary lesions (A), and the intraliary lesions were significantly enlarged (B,C)
022-02-25 was given the first cycle of pemetrexed + carboplatin +amvitin; later, due to economic reasons, pemetrexed + carboplatin treatment was performed on 2022-03-17; 2022-4-25 performed thoracic and abdomen enhancement CT in our hospital, with mixed efficacy. At present, the lung lesions are enlarged compared with the previous period, and the liver metastasis is smaller than the previous period (Figure 6).
Figure 6. Comparison of thoracic and abdomen CT before treatment (2022-02-14) and after two cycles (2022-04-25), intrapulmonary lesions were enlarged (A), new nodules in the lung (B), and intrahepatic lesions were reduced (C, D)
▎ medical history summary :
patient, female, 53 years old, PS 1 point.
2020-3 Diagnosed stage IVB of right upper lung adenocarcinoma cT4N3M1c (dual lung, pleura, liver) and EGFR L858R mutation.
First line: afatinib, PR, PFS1=19.0m, newly developed brain and liver multiple metastasis, NGS: EGFR L858R+T790M mutation.
second line: osimertinib, SD, PFS2=3.4m, the primary lung lesion is stable, and the liver lesion is enlarged compared with the previous one.
three-line: pemetrexed + carboplatin for two cycles, bevacizumab was used once, and the mixed efficacy was effective. Currently, the lung lesions are enlarged compared with the previous one, and the liver metastasis is smaller than the previous one.
▶Diagnosis and treatment timeline
Figure 7.Diagnosis and treatment timeline
NO.2Case discussion
Question 1: When patients have previous first-line afatinib 2021.7 considering progress, should they consider changing their dressing?
A. Yes B. No C. Unsure
Voting result:
▎ Doctor Yang Jinji (host):
Please explain the reasons for your choice.
▎ Dr. Yang Xuening:
First, the patient can see clear progress in the lesions; Second, previous studies have shown that afatinib is not effective in patients with T790M mutations. For patients with T790M mutations, osimirinib is a better choice. When drugs are available, individuals consider changing the dressing.
▎ Dr. Liu Zhefeng:
combined with the patient's entire medical history, I personally think that not changing the dressing at that time is a better choice, because the patient benefits from targeted treatment and progresses slowly. If the dressing changes prematurely, it may enter the stage of chemotherapy quickly. In fact, the patient's time to benefit from osimertinib is also very short. Overall, the patient benefited greatly from targeted therapy and was in a slow progression state at that time. When the prediction of the disease has not yet progressed rapidly and has not directly threatened the patient's life safety, I personally recommend that you continue to use afatinib under effective monitoring. Assuming that once the disease progresses rapidly, you will consider using another inhibitor with better efficacy.
▎Dr. Zhao Mingfang:
This patient found an intrahepatic metastatic lesion at that time. Did the intrahepatic lesion meet the standard of slow progress? The slow progress of personal understanding is the gradual increase in the original lesions and the increase in the tumor marker , but can we define a lesion of the newly discovered organ as slow progress? Or define it as a way of progress in which the quality of life is not affected? In this case, the treatment of the original regimen can be continued. If new liver lesions appear, I personally think that T790M testing should be considered and whether there is a possibility of changing the third-generation drug? Or give puncture biopsy for new liver lesions, so the personal choice is uncertain, so improve relevant testing and then formulate the next treatment strategy. Because this research is an article published by Director Yang, you, with rapid progress, local progress, and slow progress, so how do you consider this concept?
▎Doctor Yang Jinji:
This study was published in Lung Cancer[1] in 2013 and included more than 200 patients. The second and third generation drugs were not popular at the time of the study. It summarized the first generation of TKI drugs, including gefitinib and erlotinib. The problem mentioned just now is that if a small lesion in the liver does not cause symptoms or worsens, this can be included in the broad sense of slow progress. For example, new lesions of 2mm or 3mm appear, and overall the patient's target lesions are under effective control and are asymptomatic and can still be defined as slow progress.
▎Doctor Zhao Wenhua:
People will consider more positive ways. The patient's CT in March 2021 showed that metastases were visible to the bone. At this time, I personally consider whether to perform gene detection , and blood can be drawn for genetic testing to determine whether there is a T790M mutation. A new intrahepatic lesion was seen in the CT on July 22, 2021. The lesion was further confirmed by the CT in October 2021. Therefore, when reviewing the patient's medical history, when considering whether it progressed in July 2021, I personally believe that the puncture should be re-spiked for genetic testing and then consider whether to change the dressing.
▎ Zhou Jin Doctor:
My opinions are somewhat different from several experts. I personally believe that the patient's second-generation TKI afatinib has a very good effect. In the LUX-LUNG series clinical trials, the mPFS targeted for first-line afatinib was 10-11 months, and the patient's EGFR L858R mutation can still reach 16.0 months of PFS. When the patient first showed suspicious slow progression, new vertebral metastasis and liver lesions appeared. Based on these two conditions, individuals considered actively changing the dressing and providing a pathological biopsy to support it. Looking back at the patient's medical history, the patient quickly developed brain metastasis in the future, and it is very likely that he had developed drug resistance when using afatinib in July 2021. This is the result obtained from the analysis of the patient's subsequent treatment. Overall, the patient's first-line afatinib treatment has good efficacy. I personally believe that interventional treatment can be actively carried out as soon as possible when PFS=16.0m.
▎5 Wu Yilong Doctor:
I agree with Dr. Zhou Jin's view, because the first question is retrospective. If there is no data from the patient in October 2021, the efficacy of afatinib in this patient had been using it for 16 months is very good. In July 2021, the mediastinal lymph nodes were swollen, and the liver lesions were not determined. The vertebral metastasis was osteogenic. What would you consider at this time Dr. Zhou Jin?
▎ Zhou Jindian:
people will choose to perform biopsy for genetic testing. When the patient has good compliance, communicate with the patient to try to take biopsy for genetic testing as much as possible for the next step of exploration. According to the specific situation of the patient, including financial conditions and whether the patient is willing to be strong, combined with the points mentioned by Dean Wu, I personally consider biopsy for genetic testing.
▎Doctor Zhao Mingfang:
People have some different opinions. The efficacy of this patient's initial use of afatinib was very good. During the reexamination, the imaging method considered the appearance of new bone metastasis in the vertebral body. Most of the bone metastasis in lung cancer is osteolytic changes, which is the most common. Then osteogenic changes usually occur after TKI treatment, showing no osteogenic changes in the repair process; therefore, generally speaking, after TKI treatment is effective, the occurrence of osteogenic changes often suggests that the process of bone metastasis repair, and is often easily mistaken for new bone metastasis. Therefore, at this time, I personally believe that most of the bone metastasis needs to be fully considered, and most of them show effective responses rather than progress. In clinical practice, bone metastasis in patients, especially if the patient has other lesions and control is effective and the tumor markers are reduced, it should not be judged as PD. I personally believe that vertebral metastasis is osteogenic change and is not metastasis.
▎Doctor Pan Yi:
People consider not changing the medicine. First, I personally agree with Professor Zhao's point of view that clinicians cannot judge tumor progression based on osteogenic changes. In many cases, it is actually a process of bone repair, especially simple osteogenic changes. Second, the PFS of patients using afatinib in July 2021 was 16.0m. The patients have clinical benefits, no symptoms, and other lesions are smaller. I personally choose not to change the medicine.
▎ Dr. Wu Haijun:
From an imaging perspective, the suspected lesions of the vertebral body are osteogenic metastasis. The patient's CT in March 2020 showed no clear osteogenic changes in the bone. Then, clear osteogenic metastatic lesions can be seen in patients 2021-3 and 2021-7. If there is some osteogenic changes around the lesion after treatment, imaging physicians generally consider it as metastatic repair. If the lesion begins to appear as an osteogenic lesion, and the lesion gradually increases and the growth rate is slower than the osteolytic lesion, it may be a slow increase and the number of lesions increases. The patient's vertebral lesion does not appear at baseline until March 2021, it should be considered as the repair response of the metastatic lesion after effective treatment.
Question 2: For this case, during the treatment of osimertinib, mixed efficacy of liver and lung lesions appeared:
A. No biopsy is required, and the plan is changed to
B. For progressive lesions, biopsy
C. Both lesions were biopsy
Voting results:
▎ Dr. Lei Jie:
Comprehensive the entire medical history process of the patient, the patient's first-line afatinib has good efficacy, but the patient's subsequent treatment is poor. If the patient's newly added intrahepatic lesions are punctured, this site is difficult for clinicians to perform puncture operations, and the puncture risk is greater. If the patient has a lesion in the lung, it is difficult to undergo a puncture biopsy at the location of the lesion. The efficacy of osimertinib in this patient after T790M mutation was poor, and the puncture site in the lung and liver lesions was difficult to operate, and the puncture risk was high. Individuals would consider changing the plan directly without a biopsy.
▎Doctor Yang Jinji:
Doctor Zhou Lin What do you think?
▎ Dr. Zhou Lin:
Because the patient's lesions are heterogeneous, the lung lesions are stable, and the intrahepatic lesions are progressive, I personally consider the patient's follow-up treatment mainly aims at progressive lesions biopsy. As for the stable lesions, the patient has been controlled after systemic treatment, and I personally believe that it can continue to observe.
▎Dr. Yang Zhe:
I personally agree with Dr. Zhou Lin’s point of view. During the treatment of osimertinib, the lung lesions are stable and the intrahepatic lesions progress. Osimertinib is used for a short time, and mutations or pathological changes in other pathways may occur. New lesions in the liver may better reflect heterogeneous changes. I personally recommend that biopsy be performed for progressive lesions.
▎Doctor Guo Hui:
persons support biopsy for liver progression lesions. I have always been paying attention to the research on lung cancer liver metastasis . In the early stage, the clinical data and clinical characteristics of patients with lung cancer liver metastasis were summarized. First, the OS of patients with lung cancer liver metastasis is worse than those with brain metastasis; second, whether for patients with lung cancer liver metastasis, the overall response of patients with lung cancer liver metastasis is poor and heterogeneous, so I personally believe that liver metastasis is a greater threat to patients' survival in the future; third, the location of the lesions in the lung is more difficult to puncture, but puncture should be feasible.
▎ Dr. Zhang Jian:
People consider biopsy in both lesions. If as suggested by experts above, clinicians do not know whether the original treatment plan will continue to be used. In the current clinical situation where there are many drug choices such as single targets and double targets, how should clinicians choose these drugs? I personally believe that if feasible, it is feasible to be able to obtain more specimens for more testing in the era of precise treatment.
▎Doctor Yang Jinji:
When the patient's lung lesions are stable, there may be challenges in communicating with the patient and his family. How do Dr. Zhang Jian consider it?
▎ Dr. Zhang Jian:
must have such a problem. It is only for progressing lesion biopsy, which may change the patient's subsequent treatment plan and may lose control of the primary lesion. Therefore, when considering whether subsequent treatment can cover the previous treatment, if the second generation of drugs are replaced from a third generation of drugs, the third generation of drugs also cover the second generation of drug targets. I personally believe that biopsy of stable lesion can not be performed. If other mutant targets are found and replaced with other drugs and cannot cover the original mutant target, whether two targeted drugs are needed? At this time, both lesions require biopsy.
▎Dr. Wei Li:
Personal views are the same as Dr. Zhang Jian's views, and both lesions are considered to be biopsy.
▎ Dr. Zhou Rongrong:
is a biopsy for liver progression sites. Please ask the interventional department team to evaluate the biopsy. Radiofrequency ablation is performed at the same time. Individuals will tend to conduct more active local treatment.
▎Dr. Zhao Wenhua:
people support biopsy of both lesions.
The EGFR L858R mutation in this patient has a long targeted treatment time. Currently, the progress of liver lesions has occurred. In addition to being alert to whether there are coexisting mutations, clinicians also need to consider the possibility of small cell lung cancer transformation. Therefore, I personally believe that both lesions are biopsy to determine whether the original treatment plan continues to be used and whether the liver lesions need special treatment.
Question 3: If the patient has resistant to pemetrexed + carboplatin, will immunotherapy be considered?
A. Yes B. No C. Unsure
Voting results:
▎ Dr. Chen Jianhua:
In clinical practice, it can be seen that patients with EGFR mutation have poor efficacy in using immunotherapy. Even patients with EGFR mutations with PD-L1≥50% expression, the efficacy of using immunotherapy is not good. Currently, patients have other treatment options that can be considered, and immunotherapy is not recommended for individuals.
▎ Dr. Fan Zhaohui:
Previous studies have suggested that EGFR mutations are a negative indicator of immunotherapy. Moreover, in most clinical studies in the early stage of immunotherapy, only the IMPOWER150 study suggests that patients with EGFR mutations can use Atezolizumab. However, the subgroup analysis of this study suggests that patients with mutant type have poorer efficacy than patients with wild type, and most patients with mutant type have poorer efficacy, and individuals do not consider using immunotherapy.
▎Dr. Wu Yilong:
How do experts who choose not to consider immunotherapy think about the ORIENT-31 test just reported by Professor Lu Shun obtained a positive result after resistant to EGFR mutation patients?
▎Dr. Chen Jianhua:
I think antivascular treatment is the main reason why this group of people benefit.
▎ Dr. Fan Zhaohui:
patients are not the only pemetrexed + carboplatin chemotherapy regimen, and there are still more options. There have been many clinical trials before, and the results of EGFR mutation patients have negative results with immunotherapy. The ORIENT-31 trial is a multi-drug combined treatment study, so it is difficult to determine whether immunotherapy takes effect. Clinical research is not used as a clinical diagnosis and treatment guide, but clinical research is used as a reference for clinicians without guidelines, so individuals do not consider using immunotherapy.
▎Dr. Wu Yilong:
How do experts who choose to consider immunotherapy think about the ORIENT-31 test just reported by Professor Lu Shun obtained a positive result after resistant to EGFR mutation patients?
▎ Doctor Bao Yong:
This patient is currently in fourth-line treatment. The third question is whether there is a bug. Immunotherapy requires combined chemotherapy. At present, the patient still has many backline chemotherapy options, such as gemcitabine single-drug treatment. The patient's financial conditions are not good and may not be able to use immunotherapy. For patients with rapid progress, obvious symptoms and life-threatening patients, SBRT can be considered, which may improve the efficacy of immunotherapy, which is a unique method in the radiotherapy department.
▎ Dr. Lei Jie:
This patient currently has a good PS score, and I personally consider immunotherapy. The ORIENT-31 trial just reported by Professor Lu Shun mainly included these patients after EGFR mutation resistance. The study obtained a positive result. The patient has now been to the backline for treatment and is in good condition. I personally consider trying a four-drug combination immunotherapy regimen.
▎Dr. Zhao Wenhua:
People are considering using immunotherapy. The CT18 study suggests that patients who fail to treat osimertinib, the treatment of terreprizumab combined with pemetrexed + carboplatin can benefit compared with standard chemotherapy. The ORIENT-31 trial included the patient population, which is highly consistent with the patients in this case. The study suggests that this population can still benefit from immunotherapy. Individuals tend to use immunotherapy. Because patients have liver metastasis, individuals prefer the four-drug combination model studied by Impower150, followed by immunotherapy and chemotherapy.
▎Dr. Wu Yilong:
This patient has used two cycles of pemetrexed + carboplatin for treatment. If immunotherapy is considered, how can Dr. Zhao Wenhua consider chemotherapy?
▎Dr. Zhao Wenhua:
Judge based on the patient's physical condition. If the patient is in good health, individuals choose four or three drugs combined. If the patient's physical condition is poor, individuals choose single-drug chemotherapy combined with immunotherapy.
▎ weeks into the doctor:
people choose not to be sure whether they consider immunotherapy.
Personally believe that there is an opportunity for immunotherapy in this group of people. IMPOWER150, CT18, and ORIENT-31 studies are all used in cases where EGFR mutations are targeted to drug resistance without optional sensitive targets.
The genetic test of this patient suggests that there is still an EGFR L858R mutation. If the patient does not have high-risk factors such as immune drug resistance genes, individuals consider immune combined with chemotherapy treatment.
▎Doctor Wu Yilong:
First point, drug resistance mode, in 2013, Dr. Yang Jinji summarized three drug resistance modes, NCCN Guidelines emphasizes symptomatic and asymptomatic drug resistance modes. Patients with symptoms should change the original treatment plan, and asymptomatic treatment plan can continue, so asymptomatic treatment effect can maximize the efficacy of targeted treatment and should not be easily changed. Clinicians can follow three drug resistance modes, or symptomatic or asymptomatic. Specifically for a patient, it is necessary to change the treatment plan. The third-generation drug needs to have a T790M mutation after the first-generation TKI treatment before it can be used. The experts just discussed that it is difficult to operate the puncture site of the new suspicious lesions, and the patient does not show obvious symptoms, so it is feasible to continue using the original plan; if the clinician has excellent operating skills and then decide on the next step of treatment after taking a biopsy, this is also feasible.
Second point, in response to the second question, some doctors choose only the progressive site for biopsy, and some doctors choose two sites for biopsy. How do we view this case? If a patient has a lesion progression and a lesion PR, I personally believe that the T790M mutation may be located in the PR lesion, and only the site of progress can be biopsy. However, this case is more special. The T790M mutation has been detected in the gene. The liver lesions progressed after osimertinib treatment and the lung lesions are stable, which is not consistent with what has been observed in clinical practice. Why do patients with T790M mutation have no response and are in a stable state after osimertinib use? For the absence of standard treatment for T790M mutation, I agree that biopsy was performed at both sites and their molecular characteristics were analyzed.
Third point, the status of immunotherapy in patients with EGFR mutations has not been clarified. The subgroup analysis of IMPOWER150 is not enough to change clinical practice, but it has been used clinically. The ORIENT-31 Phase III clinical trial led by Professor Lu Shun is mainly a patient after EGFR mutation-targeted drug resistance, and a positive result was obtained. The status of immunotherapy in patients with EGFR mutations exists. Since ORIENT-31 only announced the results of the first phase, it is possible that in the future, we need more biomarkers for patients with EGFR mutations. At present, we should not give up the possibility of immunotherapy in EGFR mutations, and more research is still needed to explore.
△The above content was compiled by the on-site recording of the discussion. The experts at the meeting confirmed that
NO.3 MDT summary
suggested that the patient continue to undergo pemetrexed + carboplatin chemotherapy. If subsequent disease progression occurs, liver progression lesions should be considered for biopsy, and immunotherapy can be considered in the treatment plan.
References:
[1].Yang JJ, Chen HJ, Yan HH, et al.Clinical modes of EGFR tyrosine kinase inhibitor failure and subsequent management in advanced non-small cell lung cancer.Lung Cancer 2013;79:33-9.
Source of this article: CTONG
Sorted by this article: Yang Mingyi
Editor in charge: Sweet
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