(i) Treatment principles. The principle of comprehensive treatment should be adopted, that is: according to the patient’s body condition, the cytology and pathological type of tumor, the invasion scope (clinical stage) and development trend, adopt multidisciplinary comprehensive treatment (MDT) mode, apply surgery, chemotherapy, radiotherapy and biological targeting and other treatment means in a planned and reasonable manner, with the aim of achieving radical or maximum tumor control, increasing the cure rate, improving the patient’s quality of life and prolonging the patient’s survival. The aim is to achieve radical or maximum tumor control, increase the cure rate, improve patients’ quality of life and prolong their survival. At present, the treatment of lung cancer is still mainly based on surgery, radiation therapy and drug therapy. Chen Zetao, Department of Health Care, Affiliated Hospital of Shandong University of Traditional Chinese Medicine
(II) Surgical treatment.
1. Principles of surgical treatment.
Surgical resection is the main treatment for lung cancer and the only way to cure it clinically. Lung cancer surgery is divided into radical surgery and palliative surgery, and radical resection should be strived for. In order to achieve the best and complete resection of tumor, reduce metastasis and recurrence, and perform the final pathological TNM staging to guide the postoperative comprehensive treatment. The following surgical principles should be observed for surgically resectable lung cancer.
(1) Comprehensive treatment planning and necessary imaging studies (clinical staging) should be completed prior to non-emergency surgical treatment. The possibility of surgical resection should be fully evaluated and a surgical plan developed.
(2) Complete resection of the tumor and regional lymph nodes should be achieved as much as possible, while preserving as much functional healthy lung tissue as possible.
(3) Television-assisted thoracoscopic surgery (VATS) is a minimally invasive surgical technique that has developed rapidly in recent years and is mainly suitable for patients with stage I lung cancer.
(4) If the patient’s physical condition allows, anatomical pneumonectomy (lobectomy, bronchial sleeve lobectomy or total pneumonectomy) should be performed. If physical condition does not allow, limited resection: segmental lung resection (preferred) or wedge resection, or VATS.
(5) Complete resection (R0 surgery) In addition to complete resection of the primary lesion, the hilar and mediastinal lymph nodes (N1 and N2 lymph nodes) should be routinely removed and marked for pathological examination. At least 3 lymph nodes in the mediastinal drainage area (station N2) should be sampled or lymph node removal should be performed to ensure whole lymph node removal as much as possible. It is recommended that the right chest should be cleared to 2R, 3a,3p, 4R, 7-9 groups of lymph nodes and surrounding soft tissues; the left chest should be cleared to 4L, 5-9 groups of lymph nodes and surrounding soft tissues.
(6) Intraoperatively, the pulmonary veins and pulmonary arteries were treated sequentially, and the bronchi were treated last.
(7) Sleeve lobectomy is performed to preserve as much pulmonary function (including bronchus or pulmonary vessels) as possible with intraoperative rapid pathological examination to ensure negative cut margins (including bronchus, pulmonary artery or venous dissection), and the postoperative quality of life of patients is better than that of patients with total pneumonectomy.
(8) In cases of recurrence or isolated lung metastases 6 months after complete lung cancer resection, resection of the recurrent lateral residual lung or lung metastases is feasible if extra-pulmonary distant metastases are excluded.
(9) Patients with stage I and stage II disease whose cardiopulmonary function is assessed to be inaccessible for surgery can be treated with radical radiotherapy, radiofrequency ablation therapy and drug therapy instead.
2. Indications for surgery.
(1) Stage I, II and part of stage IIIa (T3N1-2M0; T1-2N2M0; T4N0-1M0 can be completely resected) non-small cell lung cancer and part of small cell lung cancer (T1-2N0 to 1M0).
(2) Stage N2 non-small cell lung cancer that is effective after neoadjuvant therapy (chemotherapy or chemotherapy plus radiotherapy).
(3) Some stage IIIb non-small cell lung cancer (T4N0-1M0) if the tumor can be completely resected locally, including invasion of superior vena cava, other adjacent large vessels, atrium, and augmentation.
(4) Some stage IV non-small cell lung cancer with single contralateral lung metastasis, single brain or adrenal metastasis.
(5) Intrapulmonary nodules with high clinical suspicion of lung cancer, which cannot be diagnosed qualitatively by various examinations, may be considered for surgical exploration.
3. Contraindications to surgery
(1) Those whose general condition cannot tolerate surgery, and those whose function of important organs such as heart, lung, liver and kidney cannot tolerate surgery.
(2) Most stage IV, most stage IIIb and some stage IIIa non-small cell lung cancer with a clear diagnosis, and small cell lung cancer with a stage later than T1-2N0-1M0.
(iii) Radiotherapy. Radiotherapy for lung cancer includes radical radiotherapy, palliative radiotherapy, adjuvant radiotherapy and prophylactic radiotherapy, etc.
1. Principles of radiotherapy.
(1) Radical radiotherapy is indicated for patients with KPS score ≥ 70 (see Annex 2 for Karnofsky score), including early-stage non-small cell lung cancer that is inoperable due to medical or/and personal factors, unresectable locally advanced non-small cell lung cancer, and limited-stage small cell lung cancer.
(2) Palliative radiotherapy is indicated for symptom reduction of primary and metastatic foci of advanced lung cancer. For patients with single brain metastases from non-small cell lung cancer, whole brain radiotherapy can be administered.
(3) Adjuvant radiotherapy is indicated for patients with preoperative radiotherapy and positive postoperative cut margins, and for patients with positive postoperative pN2, participation in clinical studies is encouraged.
(4) The design of postoperative radiotherapy should refer to the patient’s surgical pathology report and surgical records.
(5) Prophylactic radiotherapy is indicated for whole brain radiotherapy in patients with small cell lung cancer for whom systemic therapy is effective.
(6) Radiotherapy is usually combined with chemotherapy to treat lung cancer. Depending on the stage, treatment purpose and general condition of the patient, the combined regimen can choose synchronous radiotherapy and sequential radiotherapy. The recommended concurrent radiotherapy regimens are EP and violet shirt-containing regimens.
(7) Patients receiving radiotherapy will have increased potential toxic side effects and should be informed before treatment; attention should be paid to the protection of lung, heart, esophagus and spinal cord when designing and implementing radiotherapy; unplanned interruption of radiotherapy due to improper management of toxic side effects should be avoided as much as possible during the treatment.
(8) Advanced radiotherapy techniques such as three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) are recommended.
(9) Patients receiving radiotherapy or radiochemotherapy should be given adequate monitoring and supportive treatment during treatment breaks.
2. Indications for radiotherapy for non-small cell lung cancer (NSCLC).
Radiotherapy can be used for radical treatment of patients with early-stage NSCLC who cannot be treated surgically for medical reasons, preoperative and postoperative adjuvant therapy for operable patients, local treatment for patients with locally advanced lesions that cannot be resected, and as an important palliative modality for patients with advanced incurable disease.
Radiation therapy is one of the effective means of local control of lesions in patients with stage I NSCLC who cannot receive surgical treatment. For patients with surgically treated NSCLC who have negative postoperative pathological surgical margins and positive mediastinal lymph nodes (pN2), the addition of postoperative radiotherapy is also recommended in addition to the usual postoperative adjuvant chemotherapy. For pN2 tumors with positive margins, simultaneous postoperative radiotherapy is recommended if the patient is physically able to do so. For patients with positive tangential margins, radiotherapy should be started as early as possible.
For patients with stage II-III NSCLC who cannot undergo surgery due to medical reasons, conformal radiotherapy combined with concurrent chemotherapy should be given if physically possible. In patients with promise of cure, minimize interruptions in treatment duration or reduction in treatment dose through more modest radiotherapy planning and more aggressive supportive therapy when receiving radiotherapy or concurrent radiotherapy.
For patients with stage IV NSCLC with extensive metastases, some patients may receive radiation therapy to the primary site and metastases for palliative reduction.
3. Indications for radiotherapy for small cell lung cancer (SCLC).
Some patients with limited stage SCLC can achieve complete remission after systemic chemotherapy, but the risk of intrathoracic recurrence is high without the addition of thoracic radiotherapy, which not only significantly reduces the rate of local recurrence, but also significantly reduces the risk of death.
In patients with extensive stage SCLC, the addition of chest radiotherapy after distant metastases are controlled by chemotherapy can also improve tumor control rate and prolong survival.
If the disease permits, radiation therapy for small cell lung cancer should be started as early as possible and can be considered in parallel with chemotherapy. If the lesion is so large that the risk of lung injury due to radiation therapy is too high, 2-3 cycles of chemotherapy can also be considered and then radiation therapy can be started as soon as possible.
4. Prophylactic brain irradiation.
For patients with limited-stage small cell lung cancer, prophylactic brain irradiation is recommended after the intrathoracic lesions have been treated to achieve complete remission. If chemotherapy is effective, the addition of prophylactic brain irradiation can also reduce the risk of brain metastasis in small cell lung cancer.
The decision to add whole brain prophylactic irradiation for non-small cell lung cancer should be made after thorough discussion between the physician and patient, weighing the pros and cons of each patient’s situation.
5. Palliative radiotherapy for patients with advanced lung cancer.
The main purpose of palliative radiotherapy for patients with advanced lung cancer is to address local compression symptoms due to primary foci or metastases, pain due to bone metastases, and neurological symptoms due to brain metastases. For such patients, hypofractionated irradiation technique can be considered to make it more convenient for patients to receive treatment and at the same time can provide more rapid symptom relief.
6. Treatment efficacy.
The evaluation of the efficacy of radiation therapy should be based on the WHO criteria for evaluating the efficacy of solid tumors (Annex 3) or RECIST (Annex 4).
7. Protection.
Using conventional radiotherapy techniques, attention should be paid to the protection of lung, heart, esophagus and spinal cord in order to avoid serious radiation damage to vital organs of the body. Acute radiation lung injury should refer to the RTOG grading standard (Annex 5).
(D) Drug treatment of lung cancer. Drug therapy for lung cancer includes chemotherapy and molecular targeted drug therapy (EGFR-TKI therapy). Chemotherapy is divided into palliative chemotherapy, adjuvant chemotherapy and neoadjuvant chemotherapy, which should be strictly mastered for clinical indications and administered under the guidance of medical oncologists. Chemotherapy should be administered under the guidance of medical oncologists. Chemotherapy should take into full consideration the patient’s disease stage, physical condition, adverse effects, quality of life and patient’s wishes to avoid over- or under-treatment. The efficacy of chemotherapy should be evaluated in a timely manner, and adverse reactions should be closely monitored and prevented, and the drugs and/or doses should be adjusted as appropriate.
The indications for chemotherapy are: PS score ≤ 2 (Annex 6, ZPS score, 5-point method), important organ function can tolerate chemotherapy, and for SCLC the PS score of chemotherapy can be relaxed to 3. Patients are encouraged to participate in clinical trials.
1. Drug therapy for advanced NSCLC.
(1) First-line drug therapy.
The platinum-containing two-drug regimen is the standard first-line treatment; for patients with EGFR mutation, the treatment of targeted drugs can be selected; for those who are eligible, anti-tumor vascular drugs can be combined on the basis of chemotherapy. For patients who have achieved disease control (CR+PR+SD) with first-line therapy, maintenance therapy can be chosen if available.
(2) Second-line drug therapy. Second-line treatment options include doxorubicin, pemetrexed, and targeted EGFR-TKI.
(3) Third-line drug therapy. EGFR-TKI can be selected or entered into clinical trials.
2. Drug therapy for NSCLC that cannot be surgically resected.
Combination of radiotherapy and chemotherapy is recommended, and synchronous or sequential radiotherapy and chemotherapy can be chosen according to the specific situation. The recommended chemotherapeutic agents for synchronous treatment are pegylated glycosides/cisplatin or carboplatin (EP/EC) with paclitaxel or doxorubicin/platinum. Sequential therapy chemotherapeutic agents are shown in first-line therapy.
3. Perioperative adjuvant therapy for NSCLC.
For completely resected stage II-III NSCLC, 3-4 cycles of postoperative adjuvant chemotherapy with a platinum-containing two-drug regimen are recommended. Adjuvant chemotherapy begins when the patient’s postoperative physical status has largely returned to normal and is usually started 3-4 weeks after surgery.
Neoadjuvant chemotherapy: Two cycles of preoperative neoadjuvant chemotherapy with platinum-containing two-drug regimen can be chosen for resectable stage III NSCLC. Efficacy should be evaluated promptly and attention should be paid to determine adverse effects and avoid additional surgical complications. Surgery is usually performed 2-4 weeks after the end of chemotherapy. Postoperative adjuvant therapy should be based on preoperative staging and the efficacy of neoadjuvant chemotherapy.
4. Drug therapy for small cell lung cancer (SCLC).
Radiotherapy and chemotherapy-based combination therapy is recommended for limited-stage small cell lung cancer (stage II-III). The chemotherapy regimen is recommended to be EP or EC.
Extensive stage small cell lung cancer (stage IV) is recommended to be treated with chemotherapy-based combination therapy. Chemotherapy regimens recommended are EP, EC or cisplatin plus topotecan (IP) or plus irinotecan (IC).
Second-line regimens are recommended for topotecan. Patients are encouraged to participate in clinical studies of new drugs.
5. Principles of chemotherapy for lung cancer.
(1) Patients with lung cancer with KPS < 60 or ECOG > 2 should not be treated with chemotherapy.
(2) Lung cancer patients with white blood cells less than 3.0×109/L, neutrophils less than 1.5×109/L, platelets less than 6×1010/L, red blood cells less than 2×1012/L and hemoglobin less than 8.0g/dl should not be treated with chemotherapy in principle.
(3) Lung cancer patients with abnormal liver and kidney functions, laboratory indexes exceeding twice the normal value, or those with serious complications and infections, fever and bleeding tendency should not be treated with chemotherapy.
(4) Discontinuation or change of regimen should be considered if the following conditions occur in chemotherapy.
If the lesion progresses after 2 cycles of treatment or deteriorates again during the rest period of the chemotherapy cycle, the original regimen should be discontinued and other regimens should be used as appropriate; if the adverse reaction of chemotherapy reaches grade 3-4 and poses a significant threat to the patient’s life, the drug should be discontinued and other regimens should be used for the next treatment; if serious complications occur, the drug should be discontinued and other regimens should be used for the next treatment.
(5) The standardization and individualization of treatment regimens must be emphasized. The basic requirements of chemotherapy must be mastered. In addition to the routine application of antiemetic drugs, platinum drugs other than carboplatin require hydration and diuresis. Routine blood tests are performed twice a week after chemotherapy.
(6) The efficacy evaluation of chemotherapy should refer to the WHO criteria for evaluating the efficacy of solid tumors or RECIST.
(5) Staging treatment pattern of non-small cell lung cancer.
1. Comprehensive treatment of stage I non-small cell lung cancer.
(1) Preferred surgical treatment includes lobectomy plus hilar and mediastinal lymph node dissection, which can be done in open-heart or VATS.
(2) For patients with poor lung function, anatomical lung segmental or wedge resection plus hilar and mediastinal lymph node dissection can be considered.
(3) Postoperative adjuvant chemotherapy is not suitable for patients with completely resected stage IA lung cancer.
(4) Postoperative adjuvant chemotherapy is not recommended for patients with stage IB completely resected lung cancer.
(5) Re-operation is recommended for stage I lung cancer with positive cut margins. For patients who cannot be operated again for any other reason, postoperative chemotherapy plus radiotherapy is recommended.
2. Comprehensive treatment of stage II non-small cell lung cancer.
(1) Preferred surgical treatment includes lobectomy, double lobectomy or total pneumonectomy plus hilar and mediastinal lymph node dissection.
(2) Anatomic lung segmental or wedge resection plus hilar and mediastinal lymph node dissection can be considered for patients with poor lung function.
(3) Postoperative adjuvant chemotherapy is recommended for completely resected stage II non-small cell lung cancer.
(4) When the tumor invades the wall pleura or chest wall, whole chest wall resection should be performed. The extent of resection should be at least 50 px from the upper and lower margins of the nearest rib, and the length of resection of the invaded rib should be at least 125 px from the tumor.
(5) Re-operation is recommended for stage II lung cancer with positive margins, and postoperative chemotherapy plus radiotherapy is recommended for patients who cannot be re-operated for any other reason.
3. Comprehensive treatment of stage III non-small cell lung cancer.
Locally advanced non-small cell lung cancer is defined as lung cancer with TNM stage III. Adopting an integrated treatment model is the best choice for the treatment of III non-small cell lung cancer. Locally advanced NSCLC is divided into two categories: resectable and unresectable. Among them.
(1) resectable locally advanced non-small cell lung cancer includes.
(1) T3N1 NSCLC patients, for whom surgery is preferred and postoperative adjuvant chemotherapy is administered.
(2) Surgical resection for patients with stage N2 lung cancer is controversial. In cases where imaging reveals a single group of enlarged mediastinal lymph nodes, or two groups of enlarged mediastinal lymph nodes without fusion estimated to be completely resectable, preoperative mediastinoscopy is recommended, and preoperative neoadjuvant chemotherapy is administered after clear diagnosis, followed by surgery.
(iii) Some patients with T4N0-1: a) Satellite nodules in the same lung lobes: In the new staging, this type of lung cancer is T3 stage, and the preferred treatment is surgical resection, and preoperative neoadjuvant chemotherapy with postoperative adjuvant chemotherapy is also an option. b) Other resectable T4N0-1 stage non-small cell lung cancer, neoadjuvant chemotherapy may be preferred as appropriate, and surgical resection is also an option. In case of complete resection, postoperative adjuvant chemotherapy is considered. If the margins are positive, postoperative radiotherapy and platinum-containing regimen chemotherapy are administered.
Treatment of supraglottic sulcus tumor: For some patients with operable sulcus tumor, simultaneous radiotherapy followed by surgery + adjuvant chemotherapy is recommended. For inoperable supraglottic sulcus tumors, radiotherapy plus chemotherapy will be administered.
(2) Unresectable locally advanced non-small cell lung cancer includes.
(i) Non-small cell lung cancer with imaging suggestive of mass-like shadows in the mediastinum and positive mediastinoscopy.
②Most non-small cell lung cancers of T4 and N3.
③Patients with T4N2-3.
④Patients with metastatic pleural nodules, malignant pleural fluid and malignant pericardial effusion, which have been newly staged as M1, are not suitable for surgical resection. Thoracoscopic pleural biopsy or pleural fixation can be used in some cases.
4. Treatment of stage IV non-small cell lung cancer.
Before starting treatment for stage IV lung cancer, it is recommended to obtain tumor tissues for testing whether the epidermal growth factor receptor (EGFR) is mutated or not, and to formulate the corresponding treatment strategy according to the EGFR mutation status.
Stage IV lung cancer is mainly treated with systemic therapy, and the treatment aims to improve patients’ quality of life and prolong their lives.
(1) Treatment of isolated metastatic stage IV lung cancer.
(1) For isolated brain metastasis and resectable non-small cell lung cancer, the brain lesion can be surgically removed or treated with stereotactic radiation therapy, while the primary lesion in the chest is treated according to the principle of staging.
(2) Isolated adrenal metastasis and lung lesion is resectable non-small cell lung cancer, the adrenal lesion can be considered for surgical resection, and the primary lesion in the chest is treated according to the principle of staging.
(3) Isolated nodules in the contralateral lung or other lung lobes of the same lung can be treated according to the respective stages of the two primary tumors, respectively.
(2) Systemic treatment of stage IV lung cancer.
①For stage IV non-small cell lung cancer with EGFR-sensitive mutations, first-line treatment with gefitinib or erlotinib is recommended.
(2) For stage IV non-small cell lung cancer with EGFR wild-type or unknown mutation status, systemic chemotherapy with two platinum-containing agents should be started as early as possible if the functional status score is PS=0 to 1. For patients who are not suitable for platinum-based therapy, non-platinum-based two-drug combination chemotherapy may be considered.
(iii) Patients with advanced non-small cell lung cancer with PS=2 should receive single agent chemotherapy, but there is no evidence to support the use of cytotoxic analog chemotherapy for patients with PS>2.
④Current evidence does not support the use of age factors as a basis for selecting chemotherapy regimens.
⑤ For non-small cell lung cancer that has failed first-line chemotherapy, second-line chemotherapy with doxorubicin and pemetrexed, and second- or third-line oral therapy with gefitinib or erlotinib are recommended.
(vi) Stage IV non-small cell lung cancer with a score of PS>2 may be treated with best supportive care only, as appropriate.
In addition to systemic therapy, appropriate local treatment can be chosen for specific local conditions in order to improve symptoms and quality of life.
(F) Staging of small cell lung cancer.
1. Stage I SCLC. surgery + adjuvant chemotherapy (EP/EC 4-6 cycles).
2. Stage II-III SCLC: combination of radiotherapy and chemotherapy.
(1) Sequential or synchronous can be chosen.
(2) Sequential treatment is recommended to synchronize chemotherapy and radiotherapy after 2 cycles of induction chemotherapy.
(3) Prophylactic brain irradiation (PCI) is recommended for those who achieve disease control after standard treatment.
3. Stage IV SCLC: chemotherapy-based combination therapy to improve the quality of life.
EP/EC, IP, IC are recommended in the first line, and patients with progressive disease relapse within 3 months of standard treatment are recommended to enter clinical trials. topotecan, irinotecan, gemcitabine or paclitaxel are recommended for relapse within 3-6 months, and initial treatment regimens are recommended for disease progression after 6 months. (Source: Primary lung cancer treatment protocol (2011 version) O(∩_∩)O~)