“”>2 points should not be treated with chemotherapy.
(2) Patients with leukocytes <3.0×10< span="">9/L , neutrophils <1.5×10< span="">9/L, platelets <6×10< span="">9/L, erythrocytes <2×10< span="">12/L, and hemoglobin <8.0 g/dl should not be treated with chemotherapy in principle.
(3) Patients with abnormal liver or kidney function, laboratory indexes exceeding two times the upper limit of normal value, or those with serious complications and tendency to infection, fever or bleeding should not be treated with chemotherapy.
(4) In the course of chemotherapy, if the following conditions occur, discontinuation or change of regimen should be considered: if the lesion progresses after 2 cycles of treatment, or if the disease deteriorates during the rest period of the chemotherapy cycle, the original regimen should be discontinued and other chemotherapy regimens or treatment modalities should be selected as appropriate; if there is an adverse reaction of grade ≥3 of the National Cancer Institute Common Adverse Events Evaluation Criteria (version 4.0), which poses a significant threat to the patient’s life, the drug should be discontinued and the next cycle of chemotherapy should be scheduled. (5) It is important to emphasize that the treatment regimen should be discontinued and switched to another regimen at the next treatment.
(5) The standardization and individualization of treatment protocols must be emphasized. The basic principles and requirements of chemotherapy must be followed.
(6) The evaluation of the efficacy of chemotherapy should be performed according to RECIST criteria.
(5) Staged treatment model for NSCLC
(1) Comprehensive treatment for patients with stage I NSCLC: (1) Preferred surgical treatment, including lobectomy plus systemic hilar and mediastinal lymph node dissection, can be done by VATS or open-heart surgery. (2) Anatomic lung segmental or wedge resection plus systematic hilar and mediastinal lymph node dissection or sampling can be considered for some patients with stage IA NSCLC in advanced age or low lung function. (3) Postoperative adjuvant chemotherapy, radiation therapy and targeted drug therapy are not recommended for patients with completely resected stage IA and IB NSCLC lung cancer. However, stage IB patients with high risk factors can be selectively considered for adjuvant chemotherapy. (4) Re-operation is recommended for stage I lung cancer with positive cut margins, and postoperative chemotherapy combined with radiotherapy is recommended for patients who cannot be operated again for any reason. (5) Patients with severe medical comorbidities, advanced age, and refusal of surgery may be treated with large split radical radiation therapy.
2. Comprehensive treatment for patients with stage II NSCLC: (1) Preferred surgical treatment is anatomic pneumonectomy plus systematic hilar and mediastinal lymph node dissection or sampling. (2) Anatomic lung segmental or wedge resection plus systematic hilar and mediastinal lymph node dissection or sampling may be considered in patients of advanced age or low lung function. (3) Postoperative adjuvant chemotherapy is recommended for patients with completely resected stage II NSCLC. (4) Whole chest wall resection should be performed when the tumor invades the mural pleura or chest wall. The extent of resection should be at least 2 cm from the upper and lower margins of the nearest rib, and the length of resection of the invaded rib should be at least 5 cm from the tumor.(5) Re-operation is recommended for stage II lung cancer with positive margins, and postoperative chemotherapy combined with radiotherapy is recommended for patients who cannot be re-operated for any reason.
3. Comprehensive treatment for patients with stage III NSCLC: Locally advanced NSCLC is defined as patients with TNM stage III. Multidisciplinary comprehensive treatment is the best choice for stage III NSCLC. Locally advanced NSCLC is divided into two categories: resectable and unresectable.
(1) Resectable locally advanced NSCLC includes.
(1) Patients with T3 N1 stage NSCLC, who prefer surgery and adjuvant chemotherapy after surgery.
(2) Patients with stage N2 NSCLC with single mediastinal lymph node enlargement <3 cm in diameter or two mediastinal lymph nodes that are enlarged but not fused and estimated to be completely resectable should receive comprehensive treatment mainly surgical treatment; preoperative mediastinoscopy, EBUS-TBNA or ultrasound endoscopy-guided fine-needle aspiration (EUS guided fineneedle aspiration, EUS-FNA) is recommended in hospitals where available. EUS-FNA is recommended for preoperative neoadjuvant chemotherapy followed by surgery after the N2 staging is confirmed. For patients with fusion and fixation of mediastinal lymph nodes, chemotherapy, radiotherapy or synchronized chemoradiotherapy should be administered; for patients with reduced N2 stage after treatment, especially to N0, and distant metastases are excluded after re-staging, surgery is recommended in combination with the patient's physical condition.
(iii) Some patients with NSCLC in T4N0-1 stage: (a) Patients with satellite nodules in the same lung lobes: the first choice of treatment is surgical resection, and preoperative neoadjuvant chemotherapy with postoperative adjuvant chemotherapy is also an option. (b) Patients with other resectable stage T4N0-1 NSCLC: neoadjuvant chemotherapy may be preferred, as appropriate, or surgical resection may be an option. In case of complete resection, consider postoperative adjuvant chemotherapy. If positive cut margins, postoperative radiotherapy and adjuvant chemotherapy.
(4) Treatment of supraglottic sulcus tumor: For some patients who can be operated, it is recommended to consider preoperative neoadjuvant simultaneous radiotherapy and chemotherapy first, and then give surgical treatment and postoperative adjuvant chemotherapy to patients who are re-evaluated to have indications for surgery; for inoperable supraglottic sulcus tumor, radical radiotherapy combined with chemotherapy is performed.
(2) Patients with unresectable locally advanced NSCLC include.
(i) NSCLC with imaging suggestive of fusion-like enlarged lymph nodes in the mediastinum, confirmed positive by mediastinoscopy, EBUS-TBNA or EUS-FNA.
②Patients with T4N2-3.
③Patients with metastatic pleural nodes, malignant pleural fluid and malignant pericardial effusion, patients whose new staging has been classified as M1 and are not suitable for surgical resection, and in some cases, thoracoscopic pleural biopsy or pleural fixation.
④ The preferred treatment for unresectable locally advanced NSCLC is synchronized chemoradiotherapy.
4. Treatment for patients with stage IV NSCLC: Before starting treatment for patients with stage IV NSCLC, tumor tissues should be obtained for EGFR and ALK gene testing, and the corresponding treatment strategy should be decided according to the EGFR and ALK gene status. The main treatment for stage IV NSCLC is systemic therapy, and the aim of treatment is to improve the quality of life and prolong the survival of patients.
(1) Treatment of stage IV NSCLC patients with isolated brain metastases.
(1) For NSCLC patients with isolated brain metastases and resectable lung lesions, the brain lesions can be surgically resected or treated with stereotactic radiation therapy, while the primary lesions in the chest are treated according to the principle of staging.
For NSCLC patients with isolated adrenal metastasis and resectable pulmonary lesions, surgical resection of the adrenal lesions may be considered, while the primary lesions in the chest are treated according to the staging principles.
(3) Isolated nodules in the contralateral lung or other lobes of the ipsilateral lung can be treated according to the respective staging of the 2 primary tumors.
(2) Systemic therapy for patients with stage IV NSCLC.
(1) First-line treatment with EGFR-TKI is recommended for patients with stage IV NSCLC with EGFR gene-sensitive mutations, and first-line treatment with crizotinib is recommended for patients with ALK fusion gene positivity.
②Patients with stage IV NSCLC with EGFR gene sensitive mutations and ALK fusion gene negative or unknown mutation status should start systemic chemotherapy with both platinum-containing agents as early as possible if the ECOG PS score is 0-1. For patients who are not suitable for platinum-based therapy, non-platinum-based two-drug combination chemotherapy may be considered.
③Patients with advanced NSCLC with an ECOG PS score of 2 should be given single-agent chemotherapy, but cytotoxic chemotherapy is not recommended for patients with an ECOG PS score >2.
④ Current evidence does not support the use of age factors as a basis for selecting chemotherapy regimens.
⑤ Second-line treatment options include doxorubicin, pemetrexed, and EGFR-TKI. patients with EGFR gene sensitivity mutations who are not treated with EGFR-TKI at first-line and maintenance therapy should be given priority for EGFR-TKI at second-line therapy; for patients with negative EGFR gene sensitivity mutations, chemotherapy should be given priority.
(6) Patients with stage IV NSCLC with an ECOG PS score >2 generally do not benefit from chemotherapy, and best supportive care is recommended.
Based on systemic treatment, appropriate local treatment can be chosen to improve symptoms and quality of life for specific local conditions.
(VI) Staging pattern of SCLC
1. Stage I SCLC patients: surgery + adjuvant chemotherapy (EP regimen or EC regimen, 4-6 cycles). Postoperative prophylactic cranial irradiation (PCI) is recommended.
2. Patients with stage II-III SCLC: combination of chemotherapy and radiotherapy. (1) Sequential or simultaneous chemoradiotherapy can be chosen. (2) Sequential treatment is recommended for 2 cycles of induction chemotherapy followed by synchronized chemoradiotherapy. (3) PCI is recommended for those who achieve disease control.
3. Stage IV SCLC patients: chemotherapy-based combination therapy. First-line EP or EC, IP or IC regimens are recommended; patients with relapsed disease progression within 3 months are recommended to enter clinical trials; those with relapsed disease within 3-6 months are recommended to be treated with topotecan, irinotecan, gemcitabine or paclitaxel; those with disease progression after 6 months can choose the initial treatment regimen. PCI is recommended for patients with effective chemotherapy.
V. Palliative care
The purpose of palliative treatment is to relieve symptoms, relieve pain and improve quality of life. All lung cancer patients should be screened, evaluated and treated by palliative medicine throughout the whole process. The symptoms to be screened include both common physical symptoms such as pain, dyspnea and fatigue, and also psychological problems such as sleep disturbance and anxiety and depression.
Quality of life evaluation should be included in the overall evaluation system of lung cancer patients and in the evaluation of the efficacy of palliative care. The Chinese version of the Quality of Life Measurement Scale EORTC QLQ-C30 (V3.0) is recommended for overall assessment, and the Quality of Life Measurement Scale EORTC QLQ-LC13 can also be used to screen and assess common symptoms of lung cancer patients. Pain and dyspnea are the most common symptoms that affect the quality of life of lung cancer patients.
(i) Pain
1. Assessment: The patient’s complaints are the gold standard for pain assessment, and the intensity of the patient’s pain must be assessed before analgesic treatment. The numerical pain grading method is preferred, and the face-marking method can be used for children or elderly people with cognitive impairment. Pain intensity is divided into 3 categories, i.e. mild, moderate and severe pain; it is important to record not only the pain intensity at the time of the patient’s assessment, but also the heaviest, lightest and average pain intensity over the past 24h, and to understand the change in pain intensity at rest and during activity.
A comprehensive assessment of pain should be performed. The assessment should include the etiology, characteristics and nature of the pain, aggravating or relieving factors, the impact of the pain on the patient’s daily life, and the efficacy and side effects of analgesic treatment. A brief pain scale is recommended for the assessment.
The assessment should also clarify whether the patient has pain due to oncologic emergencies so that relevant treatment can be given immediately. Common oncologic emergencies include: pathologic fractures or precursor fractures of weight-bearing bones; metastatic cancer of the brain parenchyma, dura mater or soft meninges; pain associated with infection; visceral obstruction or perforation, etc.
2. Treatment: The goal is to achieve an optimal balance between analgesic effects and side effects. Analgesic drugs can relieve cancer pain in more than 80% of patients, but a small number of patients may need non-pharmacological analgesic means, including surgery, radiotherapy for pain relief or nerve block, so the analgesic effect should be dynamically evaluated and interdisciplinary collaboration should be actively carried out.
(1) Basic principles: WHO three-step analgesic principles are still the most basic principles of cancer pain treatment, which include the following five main aspects.
(1) Preferred oral administration: Non-invasive, simple and safe routes of administration should be chosen as far as possible; oral administration is the preferred route of administration, and transdermal absorption, subcutaneous injection or intravenous infusion can be considered as appropriate.
②Dosing by step: choose pain medication according to the degree of pain by step. For mild pain, choose acetaminophen or non-steroidal anti-inflammatory analgesics; for moderate pain, choose weak opioids, such as codeine and tramadol; for severe pain, choose strong opioids, such as morphine, oxycodone, fentanyl, etc. Low-dose strong opioids can also be used to treat moderate pain.
(3) Timely administration of drugs: if chronic persistent cancer pain occurs, patients should be given analgesic treatment in time after timely administration of drugs, and it is recommended to choose fast-acting immediate release drugs.
④Individualized treatment: The general condition of the patient, such as underlying diseases, heart, liver and kidney functions, concomitant symptoms and combined medications, should be comprehensively evaluated before formulating the pain relief plan, and appropriate drugs and doses should be selected.
⑤ Attention to details: details during analgesic treatment refer to all factors that may affect the analgesic effect. It is important to pay attention to the information obtained from pain assessment, and to pay attention to factors such as the patient’s psychological, spiritual, economic status, family and social support.
(2) Opioids are the core drugs for cancer pain treatment: whether opioid tolerance exists in patients should be judged before opioid treatment. The judgment of opioid tolerance is based on the standard of the U.S. Food and Drug Administration, namely: patients are currently taking at least 60 mg of morphine, 8 mg of hydromorphone, 30 mg of oxycodone, 25 mg of hydromorphone, 25 μg/h of fentanyl transdermal patch or other equivalent opioid daily for at least 1 week; not meeting this standard is considered as opioid intolerant.
In the selection of opioids, attention should be paid to: not using pethidine to control cancer pain; choosing pure receptor agonists as much as possible; avoiding morphine analgesia in patients with renal insufficiency. Opioid analgesic treatment is divided into short-acting titration phase and long-acting maintenance phase. Short-acting titration is the initial phase of opioid therapy, aiming to determine the opioid dose required for satisfactory analgesia as soon as possible. It is recommended that short-acting opioids be given on time, with the initial dose depending on whether the patient tolerates it or not. This phase should also be followed by on-demand pain relief with a single dose of 10%-20% of the total daily opioid dose, or the starting dose for those who are opioid intolerant.
After pain relief is achieved by opioid titration, short-acting opioids can be converted to controlled-release dosage forms to extend the dosing interval and simplify treatment. It is important to actively prevent and treat opioid adverse reactions. All opioid users need to prevent constipation, and the laxative composition should include at least ingredients that stimulate gastrointestinal motility, such as senna and bisacodyl; side effects such as nausea and vomiting, vertigo, paranoia and respiratory depression should be dynamically observed throughout the analgesic treatment and actively intervened if they occur.
(3) Treatment of neuropathic pain: analgesic drugs can only relieve part of the neuropathic pain. Treatment with strong opioids in combination with adjuvant medications is recommended. Potentially effective adjuvant medications include.
(i) gabapentin: 100-300 mg orally once/d, gradually increasing to 300-600 mg three times/d, with a maximum dose of 3600 mg/d.
(ii) Pregabalin: 75 mg orally twice/d, with the possibility of increasing the dose to 150 mg twice/d, up to a maximum of 600 mg/d.
(iii) Tricyclic antidepressants: e.g., amitriptyline, 10-25 mg orally once a night, commonly used at 25 mg twice a day, with incremental doses up to the optimal therapeutic dose of 150 mg/d.
Methadone and ketamine are effective for some neuropathic pain.
3. Education for patients and their relatives: Patients and relatives should be told that analgesic treatment is an important part of the overall treatment of tumor, and pain tolerance is not beneficial to patients. Morphine and its similar drugs are commonly used in cancer pain treatment, and addiction is rare; analgesic treatment should be carried out under the guidance of medical personnel, and patients should not adjust the treatment plan and drug dose by themselves; the efficacy and side effects of drugs should be closely observed, and communication with medical personnel should be made at any time and regular follow-up should be made.
(2) Breathing difficulty
It is one of the most common symptoms of advanced tumor patients. Among advanced tumor patients, 70% of them may have dyspnea, and 90-100% of lung cancer patients have dyspnea before death. Dyspnea is a subjective discomfort of breathing, and the patient’s complaint is the gold standard for diagnosis. The clinical manifestation of dyspnea is the change of respiratory rate, rhythm and amplitude, and in severe cases, the feeling of near death, fear and anxiety can aggravate dyspnea.
The complexity of dyspnea in lung cancer patients should be fully recognized and the reversible causes should be eliminated as much as possible. Anti-tumor and anti-infection treatment can be given in a targeted manner; bronchodilators and glucocorticoids can be given for chronic obstructive lung disease; glucocorticoids, radiotherapy or stent placement can be applied for superior vena cava and bronchial obstruction; thoracentesis and drainage can be given for pleural effusion, etc.
Non-pharmacological treatment includes oxygen, respiratory exercises, posture and position training, psychotherapy, etc., which should be implemented at the early stage of symptoms.
Opioids are the most common drugs used to treat dyspnea in cancer patients. Early administration of opioids can reduce the physical and psychological burden of patients and prolong the survival period.
Morphine is the drug of choice and is used in the same way as analgesic treatment for dyspnea. It is recommended to start with a small dose, give the drug on time, slowly increase the dose, closely observe and prevent side effects. Caution should be exercised in increasing the dose in elderly patients.
Sedation is an effective drug other than opioids to help relieve acute or severe dyspnea.
VI. Treatment flow and follow-up
(A) Treatment process of lung cancer
The general flow of lung cancer diagnosis and treatment is shown in Figure 1.
Click to view the original diagram
(II) Follow-up
Patients with new lung cancer should establish a complete case file and relevant data files, and conduct regular follow-up visits and corresponding examinations after diagnosis and treatment. The specific examination methods include medical history, physical examination, blood biochemistry and blood tumor marker examination, imaging examination and endoscopy, etc. The purpose is to monitor disease recurrence or treatment-related adverse effects and assess the quality of life. The frequency of follow-up for postoperative patients is every 3-6 months for 2 years, every 6 months for 2-5 years, and every year after 5 years.
The formulation of this guideline has made reference to the international authoritative guidelines for the diagnosis and treatment of lung cancer and other tumors, while taking into account the actual situation in China. Some of the new drugs marketed abroad are not included because they have not been approved for clinical application in China. Since there are great individual differences in clinical practice, this specification is for reference only.