Hundred cases of excellent brain metastases from advanced lung cancer-macromolecular anti-angiogenic drugs combined with chemotherapy bring tumor regression

*Only for medical professionals to read for reference.
This case is a patient with stage IV lung adenocarcinoma with mediastinal lymph node and brain metastasis
.

He was clearly diagnosed with brain metastases from lung adenocarcinoma in 2015.
The disease progressed 5 years after oral administration of tyrosine kinase inhibitor (TKI) drugs, and brain metastases caused brain edema, and symptoms related to increased intracranial pressure were obvious
.

After the application of the anti-angiogenic drug bevacizumab combined with chemotherapy, the symptoms related to brain metastases disappeared, the intracranial tumor was significantly reduced, and the tumor control effect was significant
.

Case review ▌Basic situation: The patient was 52 years old and was admitted to the hospital for “lung adenocarcinoma with mediastinal lymph node and brain metastasis”
.

Lung adenocarcinoma with distant metastasis was diagnosed for more than 6 years.
He denied other underlying diseases, had no history of smoking or drinking, and no family history of tumors
.

 ▌Diagnosis and treatment process: In 2015, the patient was admitted to the hospital due to "headache and discomfort".
The imaging examination revealed: lung and intracranial space-occupying lesions
.

Pulmonary puncture biopsy, pathological diagnosis: lung adenocarcinoma
.

Genetic testing: mutation of EGFR 21 exon, intracranial space occupation, consider brain metastasis of lung adenocarcinoma
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Immediately given oral erlotinib (150mg/day) treatment, the headache symptoms disappeared after 1 month, and the imaging review showed that the lung tumor lesions and intracranial metastases were reduced.
The effect evaluation: partial remission (PR)
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 In September 2016, the patient reappeared with "headache" symptoms.
A re-examination of the head MRI showed that the intracranial metastasis was larger than before
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CT examination of the lungs showed that the primary tumor was stable
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Because the patient only had brain metastases and isolated lesions progressed, he was given stereotactic radiotherapy and continued oral erlotinib, and the patient's symptoms eased again
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 On August 8, 2021, the patient was admitted to the hospital again for "dizziness, headache and discomfort".
The imaging review showed that the lung and intracranial tumor lesions had progressed compared with the previous ones.
The genetic test EFGR-T790M was negative.
The efficacy evaluation: disease progression (PD)
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The patient began systemic therapy with pemetrexed + cisplatin combined with bevacizumab on August 10, 2021
.

 Figure 1 Patient's reexamination of lung CT and head MRI on August 8, 2021.
On September 1, 2021, after the first cycle of combined treatment, the patient's "headache, dizziness" and other uncomfortable symptoms disappeared
.

On September 22, 2021, he was admitted to the hospital 20 days after the second cycle of combined treatment.
The lung CT reexamination revealed that the lesions in the lower lobe of the right lung were significantly smaller than before, and the upper mediastinum and subcarinal lymph nodes were enlarged.
Lymph node tumor metastasis should be considered
.

Head MRI re-examination showed that the brain metastasis was reduced from 5.
6cm*5.
1cm before the treatment to 5.
3cm*3.
6cm, and the edema around the lesion was significantly relieved compared with before.
The effect evaluation: PR
.

At the same time, the patient only experienced grade II gastrointestinal reactions during the treatment of chemotherapy combined with bevacizumab, which was significantly improved after symptomatic treatment
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There were no treatment-related adverse reactions such as hemoptysis, hematochezia, proteinuria, and hypertension, and the patient was well tolerated by the treatment
.

 Figure 2 The patient's reexamination of lung CT and head MRI on September 22, 2021.
Case summary and reflections.
Lung cancer has become a malignant tumor that seriously threatens human health
.

Among patients suffering from lung cancer, about 20%-65% will have brain metastases during the progression of the disease, and lung cancer has become the most common type of brain metastatic tumors
.

At the same time, lung cancer patients with brain metastases often have a worse prognosis, with an average survival time of only 1-2 months, and treatment is more difficult [1]
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 The patient's first puncture pathology revealed lung adenocarcinoma in 2015.
Genetic testing: EGFR exon 21 mutation
.

The first-generation EFGR-TKI drug erlotinib was given to the patient for oral treatment.
The primary lung tumors and brain metastases were reduced compared with the previous ones, and the tumor control was in good condition
.

In September 2016, the patient was admitted to the hospital due to the progression of intracranial metastases and symptoms related to increased intracranial pressure
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For patients diagnosed with lung adenocarcinoma and brain metastases, the treatment should be based on systemic therapy for brain metastases
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Therefore, the patient's lung lesions were controlled stably, and the intracranial lesions progressed.
On the basis of oral erlotinib systemic therapy, stereotactic radiotherapy was given, and the patient's intracranial lesions were also well controlled
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 When the patient was re-admitted to the hospital on August 8, 2021, the lung and brain metastatic lesions had progressed, suggesting that the first-line treatment of the patient's first-line TKI drugs failed
.

At the same time, the tumor genetic test was performed again and it was negative for T790M
.

Studies have shown that biopsy after EGFR-TKI drug resistance shows that T790M mutation accounts for about 50%.
If T790M mutation does not exist after drug resistance, chemotherapy is still a classic treatment option, but the "CSCO Guidelines for Non-small Cell Lung Cancer Diagnosis and Treatment" [2 ] It is not recommended to continue using EGFR-TKI drugs
.

The guidelines recommend the first choice to use platinum-containing dual-agent chemotherapy + bevacizumab treatment
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Therefore, the patient was given pemetrexed + cisplatin combined with bevacizumab systemic therapy
.

Until 20 days after the end of the second cycle of combined treatment on September 22, 2021, a reexamination of chest CT showed that the tumor was significantly smaller than before
.

MRI examination of the head showed that the brain metastases were significantly smaller than before, and the peritumoral edema was significantly relieved, and the efficacy evaluation reached PR
.

And no serious adverse reactions occurred during the treatment period, and the patient tolerated well
.

 The good efficacy and safety of bevacizumab combined with chemotherapy in the treatment of patients with advanced lung cancer were once again confirmed in the treatment of this patient
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As a macromolecular anti-angiogenic drug, bevacizumab can selectively bind to vascular endothelial growth factor (VEGF) and block its biological activity, inhibit the binding of VEGF to the receptor, and reduce the biological activity of VEGF The blood vessels of the tumor are formed, thereby inhibiting the growth of the tumor
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At the same time, it promotes the normalization of tumor blood vessels and can also effectively regulate the immune microenvironment, which really plays a role of "doubling the effort with half the effort"
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 A meta-analysis of bevacizumab in the treatment of patients with brain metastases from non-small cell lung cancer published in 2020 [3] showed that bevacizumab compared with a control group that was not treated with bevacizumab for conventional treatment The therapeutic effect was better in the treatment group.
The objective response rate (ORR) and disease control rate (DCR) of intracranial lesions of patients treated with bevacizumab were better than those of extracranial lesions, and it did not increase the risk of bleeding in patients with brain metastases
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In addition, many studies have shown that bevacizumab can reduce cerebral edema to a certain extent [4]
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The treatment of patients with advanced lung cancer and brain metastases has long been an urgent problem in the treatment of lung cancer
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It is believed that with the clinical application of bevacizumab combined with chemotherapy and the development of more related studies, it will bring survival benefits to more patients with lung cancer and brain metastases
.

References: [1] Oncologist Branch of Chinese Medical Doctor Association.
Oncology Branch of China Medical Care International Exchange Promotion Association.
"Chinese Treatment Guidelines for Lung Cancer Brain Metastasis (2021 Edition)" Chinese Journal of Oncology, Vol.
43, No.
3, March 2021 Chin J Oncol, March 2021, Vol.
43, No.
3 [2] Chinese Society of Clinical Oncology Guidelines Working Committee "Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer" [3] Liang P, Wang YD, Wei ZM, et al.
Bevacizumab for non-small cell lung cancer patients with brain metastasis: a meta-analysis [J].
Open Med (Wars), 2020, 15(1): 589-597.
DOI: 10.
1515 / med-2020 ⁃0192.
[4] Chinese Medical Doctor Association Oncologist Branch.
Chinese Medical Care International Exchange Promotion Association Medical Oncology Branch.
"Chinese Treatment Guidelines for Lung Cancer Brain Metastasis (2021 Edition)" Chinese Journal of Oncology, Vol.
43, No.
3, March 2021 Chin J Oncol, March 2021, Vol.
43, No.
3*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform