I. Overview.
Lung cancer is the tumor with the highest incidence and mortality rate among human malignant tumors, and it is still increasing at the rate of 0.5% per year. 1998, the number of new cases of lung cancer reached 1,037,000 worldwide, and the number of lung cancer deaths was over 921,000 in the same period. It accounts for about 17.8% of all cancer mortality. The annual incidence of lung cancer in the United States is 80.6 per 100,000. In 1998, the number of deaths due to lung cancer in Shanghai was 2800, accounting for 25% of all cancer deaths. Thus, it can be seen that lung cancer is extremely harmful to human beings. In order to reduce the harm and threat, a large-scale anti-smoking campaign and effective primary prevention of lung cancer are important and effective measures.
Clinical manifestations.
(1) Local symptoms: coughing is 54.7%, coughing blood or sputum blood is 18.9%, chest pain is 26.7%, and the above three are called early symptoms of lung cancer. Chest tightness and shortness of breath were 12.8%, mostly caused by airway obstruction. Advanced lung cancer complicated by large amount of pleural fluid or pericardial effusion may also cause chest tightness and shortness of breath.
(2) Systemic symptoms: obstructive infectious fever, cancerous necrotizing fever. In addition, wasting, fatigue, weakness, anemia, and loss of appetite are the manifestations of wasting.
(3) The manifestations of mediastinal invasion: hoarseness due to the involvement of the recurrent laryngeal nerve, diaphragm paralysis due to the involvement of the phrenic nerve, superior vena cava syndrome due to the involvement of the superior vena cava, pericardial filling and arrhythmia due to the involvement of the pericardium and myocardium, malignant pleural fluid due to the involvement of the pleura and dysphagia due to the involvement of the esophagus.
(4) Manifestations of extra-pulmonary metastases: Most of the pleural metastases are adenocarcinoma, characterized by bloody pleural fluid, but non-bloody pleural fluid does not exclude cancer. The involvement of the superior vena cava can lead to enlargement and thickening of the head and neck, as well as anger and cyanosis of the veins in the upper chest. Brain metastases may show symptoms such as increased cranial pressure and headache; liver metastases may show loss of appetite, nausea, emaciation and discomfort in the liver area; bone metastases may show bone destruction and severe fixed pain. Bone metastases may show bone destruction and severe pain.
III. Various examinations.
(a) Cancer marker test: serum concentrations of CEA, NSE, CyFRA21-1, β2-M and other tumor markers are often measured in lung cancer for diagnosis, efficacy and prognosis determination. (CEA<10ng/ml, NSE<14.5ng/ml, CyFRA21-1<3.3ng/ml, Scc antigen<2.5ug/L, β2-M<3.1±0.96mg/L are normal values).
(B) Chest X-ray examination: frontal and lateral chest radiographs as well as lateral lying for horizontal projection radiographs.
(iii) Chest CT examination: divided into plain and enhanced. HCT allows small lesions not to be missed; SCT has a fast scanning speed and the role of CT simulating endotracheal microscopy; PET examination is more sensitive to the benign and malignant characterization of lung lesions and lymph nodes in the mediastinum; if the imaging of CT and PET are fused, it can make up for the lack of anatomical localization accuracy of PET. It is useful for understanding early lung lesions and the presence of bone metastases.
(iv) Fibrinoscopy: F0B examination can detect both direct and indirect signs of lung tumors in the bronchial lumen, and it can also perform brush examination and biopsy, which is very helpful for diagnosis.
(E) Mediastinoscopy: It is suitable for those who have difficulty in characterizing intrapulmonary lesions but have enlarged mediastinal lymph nodes.
(f) Thoracoscopy: suitable for biopsy of peripheral lung lesions and removal of small lesions.
(vii) CT-guided lung penetration biopsy is the most commonly used invasive examination, which is valuable for clarifying the pathological diagnosis of lung cancer.
(iv) Lung cancer staging.
(a) Pathological staging: usually divided into small cell lung cancer, squamous cell carcinoma, adenocarcinoma, fine bronchoalveolar cell carcinoma, large cell carcinoma, etc. Each pathological type of lung cancer has different biological behaviors such as malignancy, growth rate, response to treatment, rapidity of metastasis and recurrence, and multiplication time.
(b) Therapeutic classification: They are usually divided into two major categories: small cell lung cancer (including oat cell carcinoma, intermediate cell carcinoma, and compound oat cell carcinoma) and non-small cell lung cancer (including squamous carcinoma, adenocarcinoma, fine bronchoalveolar cell carcinoma, and large cell carcinoma). The biological behaviors and therapeutic measures of each category are quite different.
(c) Classification according to the site of lung cancer: Central type, peripheral type and special type. Central type lung cancer refers to cancer foci occurring in the main bronchus and lobar bronchus; tumors below the lobar bronchus are peripheral type lung cancer. Special type lung cancer is divided into mediastinal type, fine bronchial lung cell carcinoma, and supraglottic lung sulcus tumor.
(D) General classification: usually divided into intraductal type, ductal wall type, spherical type (3-5 cm), giant type (>5 cm), and diffuse type.
V. Treatment of non-small cell lung cancer.
(a) Principles of treatment for NSCLC.
Stage I (T1-2N0M0): small primary lesions and no lymph node metastasis, surgical resection is preferred, among which chemotherapy should be given after surgery in stage IB. If the patient has contraindications to surgery or refuses surgery, radical radiotherapy should be administered.
Stage II (T1-2N1M0, T3N0M0): first surgery, followed by radiotherapy and chemotherapy after surgery, in order to improve long-term survival. For those who are not suitable for surgery or refuse surgery, radical radiotherapy and chemotherapy can be administered.
Stage IIIA (T1-2N2M0, T3N1M0): surgery is still possible for patients in this stage, but the efficacy of surgery is poor because N2 patients account for the majority of patients; surgery for T3N1 patients is also very difficult and has a low success rate. Neoadjuvant therapy (radiotherapy and chemotherapy) can improve the resection rate, delay metastasis and increase survival rate. For those who are not suitable for surgery, a combination of chemotherapy and radiotherapy should be developed; such as synchronous radiotherapy and chemotherapy, sequential radiotherapy and chemotherapy, chemotherapy + radiotherapy + chemotherapy, single radiotherapy or single chemotherapy, etc.
Stage IIIB (T4N0M0, T1-4N3M0): Patients in this stage should not be operated, and integrated treatment based on radiotherapy and chemotherapy should be formulated; such as synchronous radiotherapy and chemotherapy, sequential radiotherapy or chemoradiotherapy, simple palliative radiotherapy and simple chemotherapy.
Stage IV (T1-4N1-3M1): chemotherapy, biotherapy and symptomatic treatment should be the main treatment. If NR or PD appears in the above treatment, and if patients in this stage have brain, bone, liver and kidney metastases, palliative radiotherapy is appropriate.
(B) Chemotherapy for surgically resectable NSCLC.
1, neoadjuvant chemotherapy: its purpose is to control and shrink the primary lesions, control or eliminate micro-metastases, and improve the surgical resection rate and postoperative survival rate. In the past, neoadjuvant chemotherapy described using platinum-containing two-drug or three-drug regimen chemotherapy, such as NP, MIP, MVP regimen, etc.
2, adjuvant therapy: compared with neoadjuvant, adjuvant chemotherapy does not increase the risk of surgery, does not delay the chance of surgery, and has the correct pathological staging, but is less well tolerated. In the past, adjuvant chemotherapy was often chosen as a second-generation drug containing platinum two-drug or three-drug regimen, but there were also patients treated with third-generation drug containing platinum two-drug regimen chemotherapy.
(iii) Treatment of non-surgically resectable locally advanced NSCLC: These patients generally refer to stage IIIA and IIIB patients with multiple groups of enlarged lymph nodes or huge N2. Simultaneous chemotherapy and radiotherapy are the best treatment modality for such patients. In the past, the chemotherapy regimens used were mainly MVP, VP, and EP, and recently, NP, TP, and GP have been used more and more. For those who cannot tolerate synchronous chemotherapy and radiotherapy, sequential chemotherapy and radiotherapy can be used.
(D) chemotherapy for advanced metastatic NSCLC: For such patients, palliative chemotherapy should be given, which can significantly reduce symptoms, can reduce the use of pain medication, can improve the quality of survival, and can prolong survival time. New platinum-containing third-generation two-drug regimens are the first-line regimens, such as TP, TC, NP, GP, GC, etc., which have obvious advantages over platinum-containing second-generation drug two-drug regimens. For example, compared with TC and EP regimens, the former has significantly higher response rate, quality of survival and survival time than the latter, but has decreased toxic reactions. In addition, the second-line regimen and gold standard for this group of patients is DTX monotherapy, administered at 30 mg/m2 per week x 6 weeks off for two weeks, with approximately the same efficacy as DTX for three weeks as a chemotherapy cycle. pemetrexed alone or in combination with platinum as a second-line regimen has similar response rates, TTP and MST as DTX monotherapy.
(V) Review of chemotherapeutic agents and regimens for NSCLC.
1, chemotherapy drugs: first generation: CTX, MTX, ADM class.
Second generation: DDP, CBP, IFO, MMC, VP-16, VM-26, VCR, VLB.
Third generation: NVB, GEM, PTX, DTX, CPT-11, TPT.
4th generation: molecular targeted drugs such as Ivessa, Tarceva, IMC-C225, Avastin, Endostar, Celecoxib, etc.
2. 1st and 2nd generation platinum-containing regimens.
VP (VDS+DDP), MVP (MMC+VLB+DDP), EP (VP-16+DDP), VM-26+DDP, MIP (MMC+IFO+DDP), VIP (VP-16+IFO+DDP), etc.
3. Third-generation regimens.
Platinum-containing two-drug regimens: NP (NVB+DDP), GP (GeN+DDP), GC (GeN+CBP), NC (NVB+CBP), TP (TPX+DDP), TC (TPX+CBP), DP (DTX+DDP), DC (DTX+CBP).
Platinum-containing three-drug regimen: GNP (GeM+NVB+DDP or CBP), GDP (GeM+DTX+DDP or CBP) Platinum-free two-drug regimen: GD (GeM+DTX), DN (DTX+NVB), GN (Gem+NVB) 4. Fourth-generation regimen: molecular targeted drugs alone and in combination or in combination with chemotherapy and radiation.
VI. Treatment of small cell lung cancer.
(A) Staging of SCLC: In addition to TNM staging, SCLC can also be staged with limited and extensive type. Limited type is defined as hemithorax that includes lung, hilar, mediastinal and/or supraclavicular lymph nodes, i.e. localized in the same radiological area. The extensive type is defined as patients with lesions involving more tissue than the limited type refers to. TNM staging is commonly used for patients with nodular or mass-like disease, while patients with infiltrative or diffuse SCLC can be staged with both limited and extensive staging. However, there is no strict boundary between the two staging methods.
(B) Clinical characteristics of SCLC: SCLC accounts for about 15-20% of the incidence of lung cancer. Its main features are high malignancy, rapid development, early metastasis, short natural course, sensitivity to chemotherapy, good recent efficacy, high remission rate, but short maintenance time and poor prognosis. Therefore, the treatment principle of SCLC is chemotherapy-based combination therapy.
(c) The treatment principles of SCLC: surgery + chemotherapy for stage I, chemotherapy + hand + chemotherapy or synchronized chemotherapy, radiotherapy or sequential chemotherapy and radiotherapy for stage II, chemotherapy + hand + radiotherapy or radiotherapy + chemotherapy for stage IIIa, chemotherapy + radiotherapy + chemotherapy for stage IIIb, and chemotherapy + BSC for stage IV.
(iv) Chemotherapy for SCLC: Chemotherapy is the basis of treatment for SCLC, and commonly used drugs include Vp-16, DDP, CBP, CTX, IFO, VDS, VCR and ADM. The standard regimen is EP, other commonly used regimens ECP (Vp-16+CBP+DDP), ICE (IFO+CBP+Vp-16), CAO (CTX+ADM+VCR), CAE (CTX+ADM+Vp-16).SCLC is sensitive to chemotherapy but has a short maintenance of efficacy and poor prognosis.The MST for limited patients with PS score of 0,1 is 14-20 months and 7-10 months for extensive patients, with a two-year survival rate of 20-30% and a five-year survival rate of 5-10%. There is no significant difference in the efficacy of four-drug compared with two- or three-drug combinations in combination chemotherapy, but the toxic effects of chemotherapy with more than two drugs are greater. Six cycles of chemotherapy are appropriate. Increasing the number of cycles of chemotherapy is not beneficial to the efficacy and improvement of survival, but also increases toxicity. Combination chemotherapy containing platinum is beneficial to the survival of SCLC patients. Statistics show that there is no significant difference in the efficacy of DDP and CBP, and that increasing the dose of the drug in combination chemotherapy is not beneficial for survival, but increases toxicity. In SCLC patients with tolerable physical conditions, shortening the interval of combination chemotherapy is beneficial to improve the efficacy. In synchronous chemotherapy, radiotherapy or sequential chemotherapy and radiotherapy, it is better not to use anthracyclines such as ADM, because such drugs can increase the sensitivity of normal tissues and esophagus to chemotherapy and cause more serious damage.
Those who relapse after first-line chemotherapy have a very poor prognosis, and the MST is usually about 4 months. In these patients, they are classified into sensitive relapses and resistant relapses according to TTP. Those with relapse time > 3 months are sensitive relapses and can still be treated with the original first-line regimen, while those with relapse time < 3 months are resistant relapses and need to be treated with a different chemotherapy regimen, such as those who relapse after CAO regimen, can be treated with EP regimen. In addition, some new third-generation drugs, such as PTX or TPT, form a combination regimen for second-line treatment of sclc, and the efficacy is better than some of the original regimens.
VII. Treatment of complications of lung cancer.
(i) Superior vena cava syndrome: SVCS is caused by lung cancer metastasizing to mediastinal lymph nodes and compressing the superior vena cava, which is seen as head and neck swelling, cyanosis, angry chest wall veins and dyspnea. Treatment often adopts dehydrating agent, chemotherapy, hormone, etc., and radiotherapy is added if the symptoms are severe.
(2) Brain metastasis: the incidence of brain metastasis of lung cancer is high, about 20-50%, and it is a common cause of lung cancer treatment failure, among which SCLC is more common. Symptoms include headache, impaired consciousness, mental abnormalities, vision changes, aphasia, limited limb movement and ataxia. The diagnostic value of CT and MRI of the brain is high, and the treatment is appropriate for radiotherapy, chemotherapy, dehydration and hormones.
(c) Malignant pleural fluid: it is caused by the invasion of lung cancer into the pleura, and is often bloody and dark red, more easily caused by adenocarcinoma. The treatment principle is drainage first, followed by intrathoracic injection of drugs. The injected drugs can be immune agents or anti-cancer drugs, or both of them at the same time. A few hospitals also add whole pleural cavity radiotherapy with a dose of 30GY/15 times for three weeks.
(iv) Bone metastasis: bone metastasis is the most common distant metastasis of lung cancer, which can produce severe pain and pathological fracture. Vertebral metastasis can cause paraplegia. Palliative radiotherapy is the commonly used treatment with a dose of 5GY/time×5 or 3GY/time×10. In addition, phosphate preparations and painkillers also have obvious symptom relief effects, and the use of painkillers should conform to the principle of three-step drug administration.