OVERVIEW
肺癌中一种相对少见的混合组织亚型
早期缺乏特异性表现，可有咳嗽、痰中带血或咯血、喘鸣、胸痛等症状
病因不明，与重度吸烟可能相关
手术是肺腺鳞癌的首选治疗方法，多采取综合治疗与个性化治疗相结合的方法
Definition
Adenosquamous carcinoma of the lung is a histologic subtype of non-small cell lung cancer, so named because both adenocarcinoma and squamous carcinoma components can be observed under the microscope.
According to the WHO classification, adenosquamous carcinoma can only be diagnosed if it has both squamous and adenocarcinomatous components, with each component accounting for at least 10% of the tumor.
Adenosquamous carcinoma of the lung is an aggressive tumor and is generally considered to have a worse prognosis than adenocarcinoma and squamous carcinoma of the lung. Genetic testing is recommended because of the presence of some adenocarcinoma components and the improved prognosis.
Staging
Since adenocarcinoma is present in squamous lung cancer, it can be further typed according to the status of the driver genes, etc. This can help in treatment planning and prognosis evaluation.
Molecular typing
Important genes related to cancer development are called driver genes. Currently, the main driver genes studied in lung cancer include EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, KRAS, and HER-2.
Targeted therapy against driver gene variants has gradually become the main treatment for lung cancer and has achieved significant efficacy.
常见分子分型
EGFR-positive lung adenosquamous carcinoma: This type can generally be treated with molecularly targeted drugs such as EGFR-TKIs (tyrosinase inhibitors), including gefitinib, erlotinib, erlotinib, ectinib, afatinib, daclatinib, and ositinib, etc. The NCCN guideline especially emphasizes the importance of EGFR testing in adenosquamous carcinoma.
ALK-positive lung adenosquamous carcinoma: molecularly targeted drugs such as alectinib, crizotinib and ceritinib are generally available for this type.
ROS1-positive lung adenosquamous carcinoma: molecularly targeted drugs such as crizotinib are generally available for this type of lung adenosquamous carcinoma.
其他分子分型
With the major breakthroughs in clinical research on rare driver gene targets, in addition to the above common molecular phenotypes, some rare molecular phenotypes have been gradually proposed, such as BRAF, NTRK, MET, RET, KRAS, HER-2 and other genes.
Patients with advanced lung adenosquamous carcinoma with MET14 exon skipping mutation who cannot tolerate chemotherapy can use sevortinib.
Patients with BRAF V600E mutation-positive advanced squamous lung cancer can use Darafenib in combination with Trametinib.
Most of the targeted drugs for the other genes mentioned above are still under therapeutic exploration and have not been approved for marketing in China, or have not been approved for indications regarding squamous lung adenocarcinoma.
Staging by site of occurrence
Lung adenosquamous carcinoma can be categorized into the following two types according to the site of occurrence.
Central type adenosquamous carcinoma of lung: the tumor occurs in the bronchus above the opening of segmental bronchus, which is less common. It has more clinical symptoms and the accuracy of fiberoptic bronchoscopy and sputum cytology is higher, but the difficulty of surgery is often greater than that of peripheral type.
Peripheral type lung adenosquamous carcinoma: the tumor occurs in the bronchus below the segmental bronchial opening, i.e., from the subsegmental bronchus to the alveoli.
Incidence
Lung adenosquamous carcinoma is relatively rare, so there is a lack of authoritative epidemiological data, the current study is based on a small number of samples, and its results vary somewhat, the following data is only for scientific reference.
Lung adenosquamous carcinoma is relatively rare, occupying only 0.6% to 2.3% of all lung cancers.
Some studies show that patients with adenosquamous carcinoma of the lung preferably occur in adults, with an average age of 69 years, a slightly higher proportion of males (53.8%) than females (46.2%), and the preferred location is the upper lobe of the right lung and the upper lobe of the left lung, with a proportion of 34.1% and 28.7%, respectively.
Focus
About diagnosis
Lung adenosquamous carcinoma is mainly diagnosed by cytologic or histologic pathology. Preoperative diagnosis is extremely difficult; pathologic examination of surgically resected gross specimens is the most effective means of adenosquamous carcinoma diagnosis.
About treatment and prognosis
The treatment of adenosquamous carcinoma of the lung needs to be decided according to the patient’s physical condition, molecular typing, staging and other factors, and generally adopts a multidisciplinary integrated treatment model.
Ⅰ期和Ⅱ期
Radical surgical resection is the main treatment method, and some patients need postoperative adjuvant chemotherapy or targeted therapy. For patients who cannot undergo surgery, radical radiotherapy ± chemotherapy can be used as the treatment plan.
Stages I and II belong to the early stage, and after active standardized treatment, most of the patients may have a normal natural life span.
Ⅲ期和Ⅳ期
Stage III lung adenosquamous carcinoma belongs to the locally advanced stage, some patients still have the opportunity of surgical treatment, and after surgery, supplemented with chemotherapy, radiotherapy, targeted therapy and other comprehensive treatments, they can still get better treatment effect, further prolong the survival period of patients and improve the quality of life.
Stage III inoperable patients, as well as stage IV patients, through targeted therapy, radiotherapy and immunotherapy and other integrated treatment, may also be able to obtain a long survival and improve the quality of life, it is recommended to actively accept standardized treatment.
Causes
Causes
The etiology of adenosquamous carcinoma of the lung is not different from that of lung cancer, which is not completely clear so far. From the perspective of lung cancer, it may be related to the following factors.
Smoking and passive smoking
Long-term heavy smoking is the most important causative factor of lung cancer. The higher the amount of smoking, the longer the duration of smoking, and the younger the age of starting smoking, the higher the risk of lung cancer.
Passive smoking is also a risk factor for lung cancer and is mainly seen in women.
The prevalence of lung cancer can be reduced when smokers quit smoking.
Occupational exposure
Carcinogenic substances such as asbestos, chromium, nickel, copper, tin, arsenic and radioactive substances are present in the working environment.
Long-term exposure to the above carcinogenic substances can lead to an increased risk of lung cancer.
Air pollution
Outdoor pollution: industrial exhaust, automobile exhaust, haze, etc., containing carcinogens identified by the World Health Organization as Class A carcinogens.
Indoor microenvironmental pollution: soot from indoor coal burning, kitchen oil smoke, carcinogens released by indoor decoration materials, etc.
Diet and Physical Activity
Some studies show that low intake of fruits and vegetables in adulthood is associated with an elevated risk of lung cancer.
People with low serum level of beta carotene have high risk of lung cancer.
Some studies have shown that long-term moderate to vigorous physical activity reduces the risk of lung cancer by 13% to 30%.
Radioactive factors
Natural stone containing radioactive elements such as radon, such as granite, brick sand, cement and plaster. Radioactive particles decaying from radon can cause radiation damage in the human respiratory system, leading to lung cancer.
Large dose of ionizing radiation is also a causative factor of lung cancer.
Heredity and gene
Family aggregation: there is family aggregation among lung cancer patients, if there are lung cancer patients or other malignant tumors patients in the family, their relatives have increased risk of developing lung cancer.
Gene mutation: Abnormalities in gene structure and function, such as EGFR mutation gene and ALK fusion gene, are closely related to lung cancer.
Other factors
The American Cancer Society lists tuberculosis as one of the factors in the development of lung cancer. The risk of lung cancer in patients with tuberculosis is 10 times higher than that in the normal population, and the main histologic type is adenocarcinoma.
Certain chronic lung diseases, such as chronic obstructive pulmonary disease, tuberculosis, idiopathic pulmonary fibrosis, scleroderma, viral infections, and fungal toxins (aflatoxins), may also have a relationship with the development of lung cancer.
Pathogenesis
The etiology of lung adenosquamous carcinoma is still not completely clear.
At the transcripton level, lung adenosquamous carcinoma is not just a simple mixture of two tissue components, squamous carcinoma and adenocarcinoma, but has unique molecular features, such as neuroendocrine differentiation and preferential opening of extracellular signal-regulated kinase proliferative pathways.
This may be the molecular mechanism of adenosquamous carcinoma that is clinically aggressive and prone to early metastasis.
Symptoms
Symptoms of adenosquamous carcinoma of the lung are not significantly different from those of other types of lung cancer, and it is not possible to determine the specific type of lung cancer by symptoms.
Early stage usually has no obvious symptoms, and symptoms appear only after the disease has developed to a certain stage, and the symptoms are related to the location of the tumor, size, type, whether it invades or oppresses the neighboring organs, and whether it has metastasis or not.
Special reminder: Lung adenosquamous carcinoma is a type of lung cancer that can only be confirmed by pathological examination, and it is generally difficult to identify it by symptoms, so the following are the symptoms that often appear in lung cancer patients. For more detailed symptoms, please refer to reading Lung Cancer.
Primary Symptoms
The main symptoms are cough, sputum, hemoptysis, dyspnea, fever, and some patients may have weight loss, fatigue and wheezing.
Invasive Compression Symptoms
External invasion and compression symptoms refer to the symptoms caused by primary tumor invasion and compression of neighboring organs and structures. It mainly manifests as hoarseness, dysphagia and other symptoms, and some patients may cause clinical syndromes such as superior vena cava obstruction syndrome, Horner’s syndrome, Pancoast’s syndrome and so on.
Distant metastatic symptoms
Metastatic symptoms refer to the symptoms caused by distant metastasis of the tumor. The most common is brain metastasis, followed by bone metastasis, liver metastasis and so on.
Paraneoplastic syndrome
About 10% to 20% of lung cancer patients may have some rare symptoms and signs not caused by direct invasion or metastasis of the tumor, but a series of manifestations caused by ectopic endocrine, metabolic abnormality of bone and joint, and neuromuscular conduction disorders, etc., which are called paraneoplastic syndrome or paraneoplastic syndrome.
The occurrence of paraneoplastic syndrome does not necessarily correlate positively with the degree of tumor lesions, and sometimes it may precede the clinical diagnosis of lung cancer.
Consultation
Medical consultation for adenosquamous carcinoma of the lung is not significantly different from that for other types of lung cancer.
Department of Medicine
Thoracic Surgery
Please consult the Department of Thoracic Surgery if nodules or space-occupying lesions are found in the lungs on chest imaging (X-ray, chest CT, etc.) during a routine physical examination or other tests.
Medical Oncology
Patients diagnosed with adenosquamous carcinoma of the lung may choose to undergo drug treatment, such as chemotherapy, targeted therapy and immunotherapy, in the Department of Medical Oncology.
Preparation for medical treatment
Consultation: Registration, Preparation of documents, Frequently Asked Questions
Consultation Tips
Chest X-ray or CT examination may be required during the visit. Please avoid wearing metallic clothing such as shirts with buttons, blouses with sequins, and dresses with zipper fasteners.
Preparation Checklist for Medical Treatment
症状清单
Pay particular attention to the time of onset of symptoms, special behavior, etc.
Have you had a cough or phlegm for a long time?
Is there blood in the sputum?
Have you had chest tightness and shortness of breath for a long time?
Do you have fatigue with unexplained weight loss?
病史清单
Do you smoke, how long and how many cigarettes per day?
Is there a family history of lung cancer or other malignant tumors?
Are there any other diseases such as hypertension, diabetes, heart disease, tuberculosis, etc.?
Any allergy to drugs or food?
检查清单
Examination results in the last six months, which can be carried to the doctor
Specialized tests: lung biopsy pathology report, chest X-ray or CT report, tumor markers.
Laboratory tests: blood test, urine test, stool test, blood biochemistry test.
Other tests: magnetic resonance imaging (MRI), PET-CT.
Diagnosis
The diagnosis of lung adenosquamous carcinoma can be divided into qualitative diagnosis and staging diagnosis.
Qualitative diagnosis: generally, it is necessary to obtain cytology or histology specimens and then carry out pathological examination, which is the “gold standard” for confirming the diagnosis.
Staging diagnosis: with the help of CT, ultrasound, magnetic resonance, bone scanning, PET-CT and other imaging examinations, the clinical stage of the patient can be comprehensively assessed, so as to preliminarily judge the severity of the patient’s condition and provide the basis for the formulation of subsequent treatment plans.
Pathologic examination
Pathological examination is the “gold standard” for the diagnosis of squamous lung cancer, while immunohistochemical examination and molecular biology examination can help to determine the molecular staging of squamous lung cancer.
Cytologic examination
The sources of cytology specimens mainly include bronchoscopy, plasmapheresis, fine needle aspiration, sputum and bronchial lavage.
According to the morphological characteristics of cytology specimens and immunocytochemistry (ICC) staining results, cytology specimens can be accurately diagnosed, typed, and the source of cells can be determined.
Histologic examination
Morphology (routine HE staining) and histomorphology clarify small cell lung cancer and non-small cell lung cancer.
Non-small cell lung cancer requires further clarification of lung adenocarcinoma, squamous lung cancer and adenosquamous lung cancer, and immunohistochemistry is necessary to assist diagnosis.
免疫组化标记
Immunohistochemical markers are important adjunctive diagnostic methods for adenosquamous lung cancer.
P63 and TTF1 markers can be used to distinguish between squamous (P63-positive) and adenocarcinoma (TTF1-positive) components. In the case of TTF1-negative, NapsinA helps in the diagnosis of adenocarcinoma component.
Special reminder] In the pathology report, the expression (positive) of a certain immunohistochemical index is usually represented by “+”, the more “+”, the higher the degree of expression, which may be more helpful to assist in the diagnosis, and the maximum number of “+” is three. “.
特殊染色检查
When the pathologist suspects that the tumor involves the pleura, special staining of elastic fibers may be required to aid in the diagnosis.
Molecular Biology Tests
Gene mutation testing can determine the molecular typing of the driver genes of squamous lung adenocarcinoma and provide a basis for decision-making for subsequent treatment planning.
常规检测
For patients with squamous lung adenocarcinoma, regardless of the stage at diagnosis, molecular biology testing for EGFR, ALK, and ROS1 is recommended routinely.
For patients with advanced lung adenosquamous carcinoma, it is recommended to detect genes EGFR, ALK, ROS1, c-MET, BRAFV600E, KRAS, HER-2, RET, NTRK and so on.
耐药监测
For EGFR tyrosine kinase inhibitor (EGFR-TKI)-resistant patients, secondary biopsy for secondary resistance EGFR T790M testing is recommended.
For patients in whom tissue cannot be obtained, plasma circulating tumor DNA (ctDNA) can be used for EGFR T790M testing.
When blood tests are negative, patients should still be advised to undergo tissue testing to clarify EGFR T790M mutation status to guide the choice of third-generation EGFR-TKI therapy.
Imaging tests
Commonly used imaging methods for lung adenosquamous carcinoma include chest X-ray, computed tomography (CT), ultrasound, magnetic resonance imaging (MRI), bone imaging (also known as bone scanning), positron emission tomography (PET) and so on.
Imaging tests can accurately stage the tumor so that precise treatment can be given.
X-ray examination
Frontal and lateral chest radiographs, which cannot provide details such as the extent of tumor invasion and lymph node enlargement, are often used as a general physical examination.
CT examination
This is the most commonly used imaging method for diagnosis, clinical staging and follow-up observation of lung adenosquamous carcinoma.
CT of chest and abdomen can accurately determine the invasion range of primary tumor, mediastinal lymph node metastasis, and whether there is tumor metastasis in important abdominal organs (e.g., adrenal gland, liver, retroperitoneal lymph nodes, etc.).
In the absence of contraindications, doctors may recommend enhanced scanning for better diagnosis.
MRI
Enhanced MRI of the brain is used as an important staging test before preoperative or primary staging of lung tumors.
It is significant in identifying lymph node microinvasive adenocarcinoma, adenocarcinoma in situ and infiltrating adenocarcinoma; it is also commonly used to evaluate the efficacy of chemotherapy and targeted drugs.
Under special circumstances, it can be used to determine the invasion of chest wall or mediastinum and show the relationship between suprapulmonary sulcus tumor and brachial plexus nerve and blood vessels.
PET-CT examination
Whole-body PET-CT examination can further improve the accuracy of staging diagnosis of lung adenosquamous carcinoma. However, it is relatively expensive.
Bone scan
Whole-body bone imaging is a routine test to exclude bone metastasis with high sensitivity but low specificity.
When suspected bone metastases are found in whole-body bone imaging, it is generally recommended to add MRI examination for clear diagnosis.
Ultrasonography
Ultrasonography of bilateral cervical and supraclavicular lymph nodes can make up for the insufficiency of physical examination and CT examination in determining lymph node metastasis in this region.
Puncture biopsy of lymph nodes suspected of metastasis can be performed, and further pathologic diagnosis can be made.
Laboratory examination
Lung adenosquamous carcinoma generally has no specific laboratory tests, similar to other types of lung cancer, and is mainly used for preliminary auxiliary diagnosis and differential diagnosis.
Serological tests, especially tumor marker tests, are helpful for the auxiliary diagnosis of lung cancer, judgment of therapeutic efficacy and follow-up monitoring.
Serum carcinoembryonic antigen (CEA) is generally used as the main marker for lung cancer (mainly lung adenocarcinoma and squamous lung cancer), and the serum level is correlated with the degree of infiltration of lung cancer and the presence of pleural metastasis, and the higher the level of CEA is, the later the clinical staging is.
Staging
The staging of squamous lung cancer follows the staging standard of lung cancer, and the staging of squamous lung cancer is helpful in formulating treatment plan, evaluating curative effect and judging prognosis.
TNM staging
Currently, TNM staging of lung cancer is a staging system jointly developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC), which is mainly based on the three elements of T, N and M. The TNM staging system is based on the following three elements
T: represents the extent of the primary tumor, mainly referring to the size of the primary tumor foci and the degree of extravasation.
N: represents the situation of regional lymph node metastasis, including the number of metastases and regional extent.
M: represents the situation of distant metastasis, which mainly means that cancer cells are also present in other organs.
Special reminder: TNM will be followed by Arabic numerals, the larger the number, the more serious it is.
Overall Staging
According to different TNM staging, the total overall staging (prognostic grouping) of the patient is finally determined, which is indicated by the Roman letters I, II, III and IV.
Overall staging TNM staging
Stage 0 TisN0M0
Stage 0
TisN0M0
Stage IA TisN0M0
ⅠA stage
T1N0M0
ⅠB period T2aN0M0
ⅠB period
T2aN0M0
ⅡA stage T2bN0M0
ⅡA stage
T2bN0M0
IIB stage T1a~cN1M0T2aN1M0T2bN1M0T3N0M0
Phase IIB
T1a～cN1M0T2aN1M0T2bN1M0T3N0M0
Phase IIIA T1a～cN2M0T2a～bN2M0T3N1M0T4N0M0T4N1M0
Stage IIIA
T1a～cN2M0T2a～bN2M0T3N1M0T4N0M0T4N1M0
Phase IIIB T1a～cN3M0T2a～bN3M0T3N2M0T4N2M0
Stage IIIB
T1a～cN3M0T2a～bN3M0T3N2M0T4N2M0
Stage IIICT3N3M0T4N3M0
Stage IIIC
肺腺鳞癌的治疗一般采取多学科综合治疗（MDT）与个体化治疗相结合的原则。
根据患者的身体状况、肿瘤的病理组织学类型和分子分型、侵及范围和发展趋向，采取多学科综合治疗的模式。
T3N3M0T4N3M0
Phase IVAAny T, any N, M1a～b
Stage IVA
Any T, any N, M1a～b
手术治疗
Phase IVB Any T, any N, M1c
Stage IVB
Any T, any N, M1c
Differential Diagnosis
术后治疗
Lung adenosquamous carcinoma is the final diagnosis after pathologic confirmation, but it may sometimes be confused with other lung diseases before the diagnosis is confirmed, and a differential is needed.
Differentiation of other subtypes of lung cancer
Similarities: In pathological examination, when lung adenosquamous carcinoma is poorly differentiated, the histologic features are similar to those of lung low-differentiated squamous carcinoma or adenocarcinoma or sarcomatoid carcinoma.
Differences: Some poorly differentiated adenosquamous carcinomas need to be distinguished from poorly differentiated squamous carcinomas, adenocarcinomas and sarcomatoid carcinomas with the help of immunohistochemistry.
完全切除的ⅠB期肺腺鳞癌患者，不推荐常规应用术后辅助化疗、放射治疗。
但有高危险因素者［如低分化肿瘤（包括神经内分泌肿瘤但不包括分化良好的神经内分泌肿瘤）、脉管侵犯、脏层胸膜侵犯、气腔内播散、姑息性切除］推荐进行术后辅助化疗。
EGFR突变阳性的患者，可考虑应用奥希替尼辅助治疗。
Differentiation between primary and metastatic
Although the same adenocarcinoma or squamous carcinoma is present, metastatic adenosquamous carcinoma may be formed by esophageal cancer, thyroid cancer, prostate cancer and gastrointestinal adenocarcinoma that have metastasized to the lungs.
Similarities: Tumors in the lung all show adenosquamous carcinoma pattern.
Differences: primary lung cancer and metastatic cancer need to be identified by combining immunohistochemical indexes such as TTF1, NapsinA, TG, PSA, PAP and villin.
Treatment
Purpose of treatment
辅助化疗
Through the planned application of surgery, radiotherapy, chemotherapy, molecular targeted therapy and immunotherapy, with a view to maximizing the survival time, increasing the survival rate, controlling tumor progression and improving the quality of life of patients.
Treatment principles
辅助靶向治疗
Special reminder] Lung adenosquamous carcinoma is rare, there is no authoritative and unified treatment plan, generally refer to the overall treatment strategy of non-small cell lung cancer, but radiotherapy and chemotherapy are less effective, please consult your doctor in detail and follow the doctor’s instruction strictly.
辅助免疫治疗
Stage I
Stage I adenosquamous lung cancer, which can be categorized into stage IA and stage IB, is preferred to be resected by radical surgery, and if patients are not suitable for surgery, radiotherapy can be chosen.
Patients suitable for surgery
There are mainly the following surgical treatment options, which need to be determined according to the specific conditions of patients.
Anatomic lobectomy + hilar mediastinal lymph node dissection.
Anatomic lobectomy + hilar mediastinal lymph node dissection with minimally invasive techniques (thoracoscopic, robot-assisted).
Reoperation is recommended for stage I patients with positive margins, and postoperative combined radiotherapy is recommended for patients who cannot undergo reoperation for any reason.
For incomplete surgical resection, such as stage I patients with positive margins, reoperation is generally recommended, and for patients who cannot be reopened for any reason, postoperative combined radiotherapy is recommended.
If complete surgical resection is achieved, the following follow-up treatment options are available depending on the circumstances:
N0～1的情况
Stage IA: Patients with completely resected stage IA lung adenosquamous carcinoma are not recommended to routinely apply postoperative adjuvant chemotherapy, radiotherapy and targeted drug therapy, etc.
Stage ⅠB
Patients who are not suitable for surgery
N2的情况
For patients with severe medical comorbidities, advanced age, refusal of surgery and other patients with contraindications to surgery, stereotactic radiotherapy (SBRT/SABR) can be performed.
手术切除+辅助化疗±术后放疗。
新辅助化疗±放疗+手术±辅助化疗±术后放疗。
Stage II
新辅助化疗±放疗+手术±辅助化疗±术后放疗。
靶向治疗
For stage II lung adenosquamous carcinoma, radical surgical resection is preferred, and radical radiotherapy can be chosen if the patient is not suitable for surgery.
免疫治疗
Patients suitable for surgery
The choice of operation is the same as stage I. However, reoperation is recommended for stage II patients with positive margins, and postoperative radiotherapy is recommended for patients who cannot undergo reoperation for any reason.
定义
For patients with completely resected stage II adenosquamous carcinoma of the lung, 4 cycles of postoperative adjuvant chemotherapy with platinum-containing two-drug regimen is recommended.
The starting time of adjuvant chemotherapy is recommended to be when the patient’s physical condition is basically back to normal after surgery, usually 4 to 6 weeks after surgery, and the latest recommendation is not more than 3 months after surgery.
Patients with stage II lung adenosquamous carcinoma who are tested positive for EGFR after surgery can consider applying oxitinib or ectinib for adjuvant treatment after adjuvant chemotherapy.
Patients with stage II lung adenosquamous carcinoma testing negative for driver genes after surgery, such as positive PD-L1 expression (≥1%) may be treated with adjuvant atirizumab after platinum-based chemotherapy.
治疗方案
Patients who are not suitable for surgery
若患者身体素质较好，如PS 0～1分，则推荐首选治疗为根治性同步化放疗。
若同步放化疗后无疾病进展，可考虑加用度伐利尤单抗维持治疗。
同步化疗方案：依托泊苷+顺铂；长春瑞滨+顺铂；培美曲塞+顺铂或卡铂；紫杉醇类+顺铂或卡铂
For patients with severe medical comorbidities, advanced age, refusal of surgery and other contraindications to surgery, there are several main treatment options, which need to be tailored to the patient’s specific situation.
若患者无法耐受同步化放疗，序贯放化疗优于单纯放疗。
序贯化疗方案：长春瑞滨+顺铂；紫杉醇+顺铂或卡铂；培美曲塞+顺铂或卡铂。
建议行化疗2～4个周期评估后再行放疗。
Radiation therapy followed by chemotherapy with a platinum-containing two-drug regimen.
Synchronized radiotherapy: three-dimensional conformal radiotherapy or conformal intensity-modulated radiotherapy + chemotherapy.
Stage III
Stage III lung adenosquamous carcinoma, including stages IIIA, IIIB and IIIC, is divided into resectable and unresectable categories according to whether the tumor has the possibility of surgical resection.
Treatment of patients with resectable category
The stage III resectable category refers to some patients with stage IIIA and IIIC. According to the regional lymph nodes (N), they can be further divided into N0 to 1 and N2 cases.
免疫药物
For patients with T3 to 4N1 or T4N0 in stage III, the following treatment options are available:
PD-L1检测
Surgery + adjuvant chemotherapy.
Neoadjuvant therapy ± radiotherapy + surgery.
For N2 stage with a single group of enlarged mediastinal lymph nodes and <3 cm in diameter, or two groups of enlarged mediastinal lymph nodes without fusion and expected to be completely resected, the following treatment options are available:
For patients with N2 multisite lymph node metastasis who also anticipate possible complete resection, the following treatment options are available:
EGFR敏感基因突变
Patients with stage III lung adenosquamous carcinoma, after radical surgery, can be treated with adjuvant therapy with ositinib or ecliptinib after surgery if the pathologic test is positive for EGFR mutation.
Patients with stage III lung adenosquamous carcinoma, after radical surgery, if the driver gene is negative. If PD-L1 expression is positive (≥1%) adjuvant treatment with atirizumab may be administered after platinum-based chemotherapy.
Treatment of patients in the unresectable category
Unresectable stage IIIA, IIIB, and IIIC are mainly defined as having the following imaging or lymph node pathologic evidence.
Multiple ipsilateral mediastinal lymph node metastases into a large mass or multiple metastases (IIIA: T1-2N2 or IIIB: T3-4N2).
ALK 融合基因阳性
Contralateral hilar and mediastinal lymph nodes, or ipsilateral and contralateral diagonal or supraclavicular lymph node metastases (IIIB: T1-2N3; IIIC: T3-4N3).
The lesion invades the heart, aorta, and esophagus (IIIA: T4N0-1).
Radical synchronized radiotherapy
ROS1融合基因阳性
Sequential radiotherapy
If the patient’s physical condition is poor, such as PS 0-2 points, radiotherapy alone (3D conformal radiotherapy) or sequential radiotherapy + chemotherapy can be considered.
其他基因阳性
Stage IV
Before starting treatment for stage IV lung adenosquamous carcinoma patients, tumor tissue should be obtained for gene mutation testing, such as EGFR, ALK and ROS1, etc., and the corresponding treatment strategy should be decided according to the status of the above driver genes.
Driver gene negative
For patients with negative driver genes, platinum-containing two-drug regimens are the standard first-line chemotherapy regimen, and can be combined with anti-vascular therapy such as bevacizumab or vascular endothelial inhibitory protein on top of chemotherapy.
Platinum-containing two-drug chemotherapy based on immune checkpoint inhibitors in combination with pemetrexed is recommended for patients with suitable conditions.
Commonly used immune checkpoint inhibitors include pembrolizumab, karelizumab, sindilizumab, tirilizumab, atelizumab, and sugilizumab.
PD-L1 expression testing is generally required when using immune checkpoint inhibitors.
For patients with positive PD-L1 expression (≥1%), a single agent such as pembrolizumab may be used, but the benefit is more pronounced in patients with high PD-L1 expression (≥50%).
寡转移
For patients with high PD-L1 expression (≥ 50%), atelizumab can be used as a single agent.
Driver gene positive
[Hint] For more, see the term EGFR-positive lung cancer.
广泛转移
EGFR-TKIs are recommended, and ositinib, gefitinib, erlotinib, ectinib, afatinib, and amitinib are available.
For patients with brain metastases, ositinib is preferentially recommended.
For patients with non-classical mutations such as G719X, L861Q, S768I, afatinib is first recommended.
For patients with EGFR-sensitive gene mutations detected in the course of first-line chemotherapy already started, it is recommended to switch to EGFR-TKIs after completing conventional chemotherapy (including maintenance therapy), or to start targeted therapy after interrupting chemotherapy.
【Tips】For more, please refer to the term ALK-positive lung cancer.
Choose from alectinib, ceritinib, enzatinib, crizotinib, and buxtitinib.
Patients who are found to be positive for ALK fusion genes during the course of chemotherapy already started in the first line are recommended to be able to complete conventional chemotherapy, including switching to targeted therapy after maintenance therapy or starting targeted therapy after interruption of chemotherapy.
For more information, see the term ROS1 fusion lung cancer.
Crizotinib is recommended, and platinum-containing two-agent chemotherapy or platinum-containing two-agent chemotherapy + bevacizumab may also be received.
Gene-related drugs
MET14 Sevortinib
MET14
Sevortinib
BRAF V600 Darafenib in combination with Trametinib
BRAF V600
Darafenib in combination with trametinib
NTRK entrectinib (Entrectinib) larotrectinib (larotrectinib)
NTRK
Entrectinib (Entrectinib) larotrectinib (larotrectinib)
RET Selpercatinib (Selpercatinib)
RET
Selpercatinib (Selpercatinib)
Most of the targeted drugs targeting the above genes are not approved for marketing in China or are not approved for indications regarding lung adenosquamous carcinoma, and patients may choose to participate in clinical trials or adopt driver gene-negative treatment regimens.
Treatment of distant metastasis
Most patients with stage IV adenosquamous lung cancer have distant metastasis, which can be categorized into oligometastasis (only a few distant metastatic lesions) and extensive metastasis (multiple distant metastatic lesions at the same time).
For patients with oligometastases, after effective systemic treatment, the use of radiotherapy, surgery and other local treatments can further prolong the survival of patients.
For brain or adrenal metastases: aggressive local treatment, including surgical resection of brain or adrenal metastases, or conventional radiotherapy/SBRT for brain or adrenal metastases, combined with systemic therapy as appropriate.
Bone metastases: receive radiotherapy in combination with bisphosphonates. For patients with weight-bearing bone metastases, surgery to the metastases plus radiotherapy is recommended, combined with systemic therapy as indicated.
For patients with extensive metastases of lung adenosquamous carcinoma, the treatment of oligometastases is generally referred to and supplemented by palliative treatment, aiming at relieving symptoms, alleviating pain, and improving the quality of life.
Palliative treatment includes taking palliative surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, and other means that can relieve patients’ symptoms, such as pain relief therapy.
Prognosis
Cure
Lung adenosquamous carcinoma cannot be completely cured at this time, and statistics such as the 5-year survival rate are generally used to assess patient survival.
Survival rate
Due to the small number of incidence of Lung Adenosquamous Carcinoma, there is no specific authoritative data on survival, but in general, Lung Adenosquamous Carcinoma is more malignant and has a worse prognosis.
Some studies have shown that the 5-year survival rates of patients with squamous lung adenocarcinoma, adenocarcinoma and squamous carcinoma are 6%-22%, 38%-49% and 39%-46%, respectively, and the prognosis of patients with squamous lung adenocarcinoma is significantly worse than that of adenocarcinoma and squamous carcinoma.
A domestic data study[5] showed that the 1-, 3- and 5-year survival rates of patients with squamous lung adenocarcinoma were 72.9%, 23.3% and 9.0%, respectively.
Special reminder.
The overall survival time of cancer patients can be roughly predicted by the 5-year survival rate, which refers to the proportion of patients whose tumors survive for more than 5 years after various comprehensive treatments. the probability of recurrence after 5 years is low, and it can generally be regarded as a clinical cure.
The statistics of 1, 3 and 5 year survival rates are only for clinical research and do not represent the specific survival period of an individual. The individual survival period of a patient needs to be determined by a combination of factors, and it is recommended to consult with the consulting physician.
Prognostic factors
Prognostic factors are factors that have an impact on the overall survival and quality of life of the patient.
It has been shown that distant metastasis, neural infiltration, and late staging are factors that are associated with a poorer prognosis in patients with pulmonary adenosquamous disease [13]. Systematic lymph node dissection significantly improves the survival time of patients with squamous lung adenocarcinoma.
Daily routine
The daily routine of squamous lung adenocarcinoma is not significantly different from that of other types of lung cancer. After treatment such as surgery, radiotherapy or chemotherapy, it does not mean that one can let down one’s guard, and active and strict daily management can help patients better overcome cancer.
Daily Management
Mindset and emotional adjustment
A good mood and mindset cannot be replaced by drugs.
After diagnosis, patients may develop a sense of fear and may be afraid of pain, abandonment and death. With the encouragement and help from doctors, family and friends, patients need to get rid of their fear as soon as possible, face the disease squarely, actively follow the medical advice and have an optimistic attitude towards the prognosis.
Family members should pay attention to listening to the patient’s heart, improve the patient’s psychological tolerance, and relieve anxiety symptoms.
It is recommended that the patient’s family give support so that the patient can face the surgery and other treatments positively with a good mindset.
During the period between treatments and after treatment, family members are advised to encourage the patient to do work and household chores that are within his/her ability to reintegrate into his/her social role.
Healthy lifestyle
参考文献
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