The treatment of brain metastases of Round Table lung cancer has made excellent progress, and the survival benefit of patients is expected to be prolonged

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Lung cancer is one of the
most common malignancies.
According to the latest data from the National Cancer Center published by Academician Hejie's team, lung cancer had the highest incidence and mortality in the burden of cancer disease in 2016 [^1], and about 20%~50% of lung cancers will have brain metastases ^[2].

。 This time, "Doctor Daily" specially invited Professor Wen Zhenping of Inner Mongolia Autonomous Region Cancer Hospital, Professor Liu Yonggang of Baotou Cancer Hospital, Professor Li Quanfu of Ordos Central Hospital, Professor Wang Dong of the Affiliated Hospital of Inner Mongolia University for Nationalities, and Professor Zhang Minghui of Chifeng City Hospital to analyze
the existing treatment methods and future development trends based on the current situation of lung cancer brain metastasis.

01

Professor Wen Zhenping: Targeted drugs have obvious efficacy, and Iruak is highly anticipated

Brain metastases are divided into brain parenchymal metastases and meningeal metastases, and meningeal metastases are further divided into dural metastases and pia mater metastases
.
Evidence-based medical research in the treatment of brain metastases confirms that individualized treatment
needs to be implemented on the basis of clinical evidence-based research evidence, combined with the clinical experience of doctors and the individual wishes of patients 。 Previous evidence-based medical studies have shown that although the first-generation targeted drug (EGFR-TKI) and the second-generation EGFR-TKI monotherapy are not satisfactory for patients with brain metastasis and meningeal metastasis, the combination therapy effect is good, such as TKI combined with chemotherapy (T+C), TKI combined with bevacizumab (T+A) and TKI combined with radiotherapy, and the third-generation TKI monotherapy has a good effect on the treatment of brain parenchymal metastasis, and also has a certain effect
on meningeal metastasis.

Iruac is a new generation of ALK-TKI drug that is also well used in ALK-positive non-small cell lung cancer, and Iruac's phase I and II clinical trials have shown progression-free survival (PFS) of up to 19.
8 months [^3].

Phase III clinical trials of the drug are underway, and it is expected that the drug will be marketed as soon as possible to benefit patients
.

02

Professor Liu Yonggang: Targeted combination therapy can still benefit, and the selection of ALK inhibitors should be carefully considered

A Japanese NEJ009 study of EGFR TKI and chemotherapy in combination therapy for advanced NSCLC showed that combination therapy was better than monotherapy TKI for OS (Figure 1) ^[4].

However, the results of this study are only from clinical data in Japan, and there is no large difference between PFS2 with combination therapy and monotherapy, so there is still a lot of debate
internationally.
TKI combined with chemotherapy has certain benefits, for patients with heavy tumor burden or multiple brain metastases, if the patient can tolerate the toxic side effects of the two treatments, the use of combination therapy mode can relieve symptoms quickly, in addition, in addition to the anti-tumor effect of chemotherapy itself, it also has a delayed effect on TKI resistance, which can prolong PFS
.
If the patient is judged to be intolerable, caution is
required.

Because ALK gene-positive patients have been treated with ALK inhibitors for a long time, the efficacy and adverse effects
of the drug need to be considered when choosing a drug treatment.
Preference can be given to more potent second- and third-generation ALK inhibitors
.
Long-term severe adverse drug reactions seriously affect the quality of life of patients, so priority should be given to ALK inhibitors
with small toxic side effects.
The results of randomized controlled trials (RCTs) of selected drugs also need to be judged on the efficacy of drugs, and differences in the inclusion criteria of RCTs may also lead to differences
in the results of the studies.
In addition, factors such as resistance after first-line treatment and the choice of follow-up therapy should also be considered
.

Fig.
1 Results of targeted combination and monotherapy for PFS^[4].

03

Prof.
Li Quanfu: Iruak brings new options to patients

Clinicians not only need to pay close attention to the progress of clinical research, but also have a certain understanding of research, combine research with practice, and summarize to better improve the clinical benefits
of patients.

The emergence of Iruac is not only an ALK inhibitor, but also a ROS1 inhibitor, and the emergence of Iruac has brought new options for the clinical treatment of patients who are positive for ALK gene and ROS1 gene, and more research results
of this drug are expected.

04

Professor Wang Dong: Improve the intrathecal injection treatment plan and improve the quality of life of patients

The treatment of patients with meningeal metastasis of lung cancer and cerebrospinal fluid detection of tumor cells is very difficult
.
Previous evidence-based medical studies have shown that first-generation targeted drugs (TKIs), second-generation TKIs and third-generation TKIs have very good efficacy in the treatment of meningeal metastasis, but there are also certain limitations, due to individual differences, the efficacy of small molecule TKI cannot be representative of the efficacy of the overall patient, and more studies are needed to confirm it
.
In addition, intrathecal injection of small doses of the drug is effective in prolonging OS (Figure 2) ^[5-6], but its overall efficacy in the clinic remains uncertain
because it is intolerable by patients.
The principle of intrathecal injection is also still debatable, because multiple injections are required, and the direct administration site is the patient's cerebrospinal fluid, even if the dose is small, each time can cause certain damage to the patient, and the patient's quality of life is also affected
during long-term treatment.
The treatment effect and humanistic care for patients are very important, so it is recommended that after the clinical evaluation does require intrathecal injection, the time of each drug action should be extended as much as possible, the number of times should be reduced, and the dose should be as small as possible to maintain a stable dose to improve the quality of life of
patients.

Fig.
2 Overall survival rate of intrathecal injection therapy^[6].

05

Professor Zhang Minghui: Intrathecal injection is still an effective treatment for meningeal metastasis

Patients with meningeal metastases have a poor prognosis, especially if EGFR-TKI is resistant and more difficult to treat
.
Diffuse meningeal metastasis is generally treated with medical therapy, and whole-brain radiotherapy is not
effective.
Intrathecal injection in the treatment of meningeal metastasis has a certain efficacy, and it still needs to be continued
clinically until there is no better method.
Recently, there are 3 patients with brain metastases with obvious symptoms of cranial hypertension such as headache and vomiting, and even the MRI can not see abnormal signals, but lumbar puncture found that the cerebrospinal fluid tumor exfoliation cytology is positive, and methotrexate plus dexamethasone intrathecal injection is given, the treatment effect is very good, the patient's symptoms are relieved obviously, of course, the premise is to combine effective systemic therapy
.
As early as 2019, Professor Xintao of the Second Hospital of Harbin Medical University did the dose climbing experiment of pemetrexed intrathecal injection, accumulated certain experience, and was also used in clinical practice, but the drug route was limited in the instructions, so our hospital currently chooses traditional methotrexate injection
.
In addition, administration through the Ommaya capsule avoids repeated punctures, and injecting the drug more upstream allows for a more uniform distribution of the drug in the cerebrospinal fluid and is more effective ^[7].

Our experience is that the frequency of intrathecal injections is twice a week in the first month, once a week in the second month, and gradually lengthened to once a month, which can be adjusted
appropriately according to the patient's situation.

06

Professor Wen Zhenping concluded

Compared with previous treatments, the treatment of brain metastases has made remarkable progress in recent years, and the treatment effect
will be further improved with the continuous launch of new drugs.
With the continuous improvement and updating of various treatments and drugs, in the future, the intracranial progression-free survival (iPFS), PFS, and OS of patients with brain metastases will make breakthrough improvements, so that more patients can benefit
.

Expert profiles

Professor Wen Zhenping

Chief physician, master tutor

Director of the Department of Medical Oncology, Inner Mongolia Autonomous Region Cancer Hospital

Chairman of the Geriatric Oncology Professional Committee of Inner Mongolia Anti-Cancer Association

Vice Chairman of the Medical Oncology Professional Committee of Inner Mongolia Medical Association

Vice Chairman of the Chemotherapy Professional Committee of Inner Mongolia Anti-Cancer Association

Vice Chairman of the Tumor Biological Immunotherapy Professional Committee of Inner Mongolia Anti-Cancer Association

Vice Chairman of the Precision Medicine and Oncology MDT Professional Committee of Inner Mongolia Anti-Cancer Association

Member of the Standing Committee of the Precision Medicine and Oncology MDT Professional Committee of the Chinese Research Hospital Association

Member of the Standing Committee of the Lung Cancer Group of the Precision Medicine and Oncology MDT Professional Committee of the Chinese Research Hospital Association

Member of the Hepatobiliary and Pancreatic MDT Professional Committee of the China Branch of the International Hepatobiliary and Pancreatic Association

Member of Cancer Rehabilitation Branch of Chinese Society of Gerontology and Geriatrics

Member of the Cancer Nutrition Professional Committee of the Chinese Anti-Aging Promotion Association

Member of the Peritoneal Tumor Professional Committee of the Chinese Anti-Cancer Association

Member of the Standing Committee of the Lung Cancer Branch, the Immunology Branch and the Breast Cancer Branch of the Beijing Cancer Research Association

Member of the Adverse Drug Reaction Management Subcommittee of Beijing Cancer Research Association

Expert profiles

Professor Liu Yonggang

Chief Physician, Master of Medicine, Department of Thoracic Oncology, Baotou Cancer Hospital, Assistant to the Director

Member of Lung Cancer Group and Colorectal Cancer Group of Chinese Hospital Research Association (PMOC).

Member of the Lung Cancer Professional Committee of Beijing Medical Award Foundation

Member of the Cancer Nutrition Professional Committee of the Chinese Anti-Aging Promotion Association

Member of Beijing Cancer Prevention and Treatment Research Association/Green Shade Salon Cancer Research Collaborative Group

Standing member and secretary of the Lung Cancer Professional Committee of Inner Mongolia Anti-Cancer Association

Member of Lymphoma Professional Committee of Inner Mongolia Anti-Cancer Association

Member of the Colorectal Cancer Professional Committee of Inner Mongolia Anti-Cancer Association

Member of the Medical Oncology Professional Committee of Inner Mongolia Medical Doctor Association

Member of Thoracic Oncology Professional Committee of Inner Mongolia Medical Doctor Association

Member of Inner Mongolia Traditional Chinese and Western Medicine Cancer Treatment Committee

Member of GIST Collaboration Group in Inner Mongolia

Member of Medical Oncology Professional Committee of Inner Mongolia Medical Association

Expert profiles

Professor Li Quanfu

Leader of oncology discipline and branch secretary of Ordos Central Hospital

Chief physician, professor, director of the Department of Oncology

Master tutor of Ordos Central Hospital

Inner Mongolia Autonomous Region grassland talent

Inner Mongolia Autonomous Region "New Century 321 Talents"

Ordos steppe talent

Member of the Standing Committee of the Geriatric Oncology Professional Committee of the Chinese Anti-Cancer Society, etc

Committed to the construction of tumor palliative medicine, based on local conditions, the first or corresponding author has published 9 SCI papers in the past five years (2 in the second region of the Chinese Academy of Sciences)

Expert profiles

Professor Wang Dong

Director of the Oncology Department of Integrated Medicine of Mengxi Medicine, Affiliated Hospital of Inner Mongolia University for Nationalities, Director of Multidisciplinary Diagnosis and Treatment of Oncology (MDT) Center, Director of Haifu Dao Treatment Center

Ph.
D.
, Master's supervisor, Chief physician

Member of the Youth Committee of Cancer Chemotherapy of China Medical Education Association

Member of the Tumor Metastasis Special Committee of the Chinese Medical Education Association

Member of the Translational Medicine Branch of the Chinese Society of Gerontology and Geriatrics

Director of Inner Mongolia Anti-Cancer Association

Vice Chairman of Geriatric Oncology Committee of Inner Mongolia Anti-Cancer Association

Member of the Standing Committee of the Department of Medical Oncology of Inner Mongolia Medical Doctor Association

Vice Chairman of Inner Mongolia Autonomous Region Mengxi Medical Interventional Radiology Specialty Alliance

Member of the Standing Committee of the Oncology Precision Committee of the Inner Mongolia Anti-Cancer Association

Chairman of the Medical Oncology Branch of Tongliao Medical Doctor Association

Vice Chairman of Oncology Branch of Tongliao Medical Association

Expert profiles

Professor Zhang Minghui

Director of the three departments of medical oncology, chief physician, master tutor of Chifeng City Hospital

Vice Chairman of the Youth Committee of the Medical Oncology Branch of the Inner Mongolia Autonomous Region Medical Association

Vice President of the Second Committee of Medical Oncology Branch of Inner Mongolia Autonomous Region Medical Doctor Association

Vice Chairman of the Oncology Cardiology Professional Committee of Inner Mongolia Anti-Cancer Association

Member of the Multidisciplinary Diagnosis and Treatment (MDT) Committee of the Colorectal Cancer Committee of the Chinese Medical Doctor Association

Youth member of MDT Professional Committee of Precision Medicine and Oncology of China Research Hospital Association

Member of Colorectal Cancer Committee of Inner Mongolia Medical Doctor Association

Standing member of the 4th Council of Inner Mongolia Anti-Cancer Association

Vice Chairman of the Quality Control Center of Oncology of Chifeng Health Commission