The NCCN Lung Cancer Committee updates its guidelines at least once a year, and the latest edition of the non-small cell lung cancer guidelines was released in September of this year.
Risk Factors
Smoking, history of lung disease, history of cancer, family history of lung cancer, history of carcinogen exposure (e.g., arsenic, chromium, nickel, diesel, asbestos, cadmium, beryllium, silicon).
Classification and prognosis
Non-small cell lung cancer is classified as non-squamous (adenocarcinoma, large cell carcinoma and other lung cancers) and squamous carcinoma. Good prognostic factors include: early stage at diagnosis, PS score of 0 to 2, weight loss of no more than 5%, and female.
Markers predictive of treatment effectiveness: ALK fusion genes, EGFR mutations, but also HER2 BRAFV600 mutations, ROS1 and RET gene rearrangements, MET gene amplification.
Prognostic marker: KRAS gene, poor prognosis in patients with mutations, also suggesting no benefit to combination chemotherapy with cisplatin + vincristine and EGFR TKI therapy.
1. EGFR mutations
Up to 50% in Asians, most commonly exon 19 deletion and exon 21 L858R mutation, sensitive to TKIs, such as erlotinib, gefitinib, afatinib, recommended for first-line treatment. EGFR mutation detection is recommended for non-squamous NSCLC and NOS.
2.ALK rearrangement
2-7% of NSCLC have ALK rearrangement, preferentially recommend ALK testing for small biopsy specimens, non-smokers, mixed histology or non-squamous changes. Crizotinib is used as first-line/subsequent treatment for ALK-rearranged lung cancer and should be discontinued in the event of life-threatening pneumonia. Cretinib is used after progression of crizotinib therapy or in those who are intolerant.
3. KRAS mutations
Up to 25% of patients in the North American population have KRAS mutations, and KRAS mutations are more common in smokers. people with KRAS mutations have shorter survival than those without mutations and are not effective against EGFR-TKI therapy.
Treatment
1. Surgery
Surgery is the best cure for stage I/II patients, and may also be appropriate for some lung cancers in the superior pulmonary sulcus and chest wall involvement. Surgical resection is better than radiation therapy, and sleeve lobectomy is better than pneumonectomy.
Sublobar resection may be an option for those who are not suitable for lobectomy, have peripheral nodes less than 2 cm and do not have high risk features for cancer, and should ensure that the resection margin is more than 2 cm.
Lymph nodes at stations 2R, 4R, 7 and 8 should be resected for right-sided lung cancer and stations 4L, 5, 6, 7, 8 and 9 for left-sided lung cancer.
Patients with IIIA N2 should be carefully evaluated preoperatively for surgical appropriateness, and patients who meet the criteria for surgical resection can be treated with thoracoscopic lobectomy (VATS).
2. Radiotherapy
The aim is to control the tumor locally and reduce toxic side effects, and there are 5 indications.
(1) Combined with chemotherapy for radical treatment of locally progressive NSCLC. stage III is feasible, but potentially resectable patients with IIIA are controversial.
(2) Curative treatment of early-stage NSCLC that is not suitable for surgery, with adjuvant chemotherapy considered after completion of radiotherapy for those larger than 4 cm.
(3) For preoperative clinical stage I/II and postoperative pathological stage N2+, radiotherapy should be combined with other forms of treatment according to the status of the cut margin; or preoperative unresectable T3N0-1 supraglottic sulcus lung cancer should be combined with radiotherapy and chemotherapy before surgical resection.
(4) Salvage treatment for local recurrence or metastasis.
(5) Palliative treatment of incurable NSCLC for symptom relief.
The doses of preoperative, postoperative, radical and palliative radiotherapy are different. Usually the dose of radiotherapy tolerated by the lung before surgery is higher than that of postoperative patients, and the total dose of radical radiotherapy is 60-70 Gy.
Stereotactic radiotherapy, which is indicated for patients with stage I and T1-3N0M0 who are not suitable for surgery, can also be used for fewer metastases, and can be combined with targeted therapy for advanced patients with ALK rearrangements and EGFR mutations.
For single brain metastases, whole brain radiotherapy/stereotactic radiosurgery after surgery or whole brain radiotherapy after stereotactic radiosurgery or stereotactic radiosurgery alone may be given. For multiple brain metastases, whole-brain radiotherapy is the standard treatment, and stereotactic radiosurgery can be considered for smaller metastases.
3.Systemic treatment
It includes chemotherapy and targeted therapy.
The first-line chemotherapy regimen is recommended for no more than 4-6 courses, and those who respond to treatment or have stable disease can be transferred to maintenance therapy, but the benefit of maintenance therapy is not obvious.
Currently, commonly used targeted agents include bevacizumab, erlotinib, afatinib, crizotinib, ceritinib, nabumab and ramolutumab.
Bevacizumab can be combined with chemotherapy, and cisplatin + pemetrexed or bevacizumab + chemotherapy can be chosen for non-squamous cancers; the options for squamous cancers include gemcitabine + cisplatin, carboplatin + paclitaxel, cisplatin + vincristine, etc. Usually pemetrexed and bevacizumab-containing regimens are not recommended for squamous cancers.
For EGFR-sensitive mutations and ALK rearrangements, targeted therapies such as erlotinib, afatinib and crizotinib are available as first-line treatment. Most patients should continue with targeted drugs when progression occurs and add local or other systemic therapies depending on their condition.
Crizotinib is indicated for ALK rearrangements, but also for ROS1 rearrangements and cMET amplifications; darafenib and verofenib for BRAFV600E mutations; trastuzumab and afatinib for Her2 mutations; cabozantinib for RET rearrangements; and crizotinib for follow-up after progression of crizotinib therapy.
Maintenance therapy refers to systemic therapy after first-line chemotherapy for progressive NSCLC and is indicated for patients who have responded to treatment or have stable disease and good PS status. The drugs available include bevacizumab (non-squamous NSCLC), pemetrexed (non-squamous NSCLC), bevacizumab combined with pemetrexed (non-squamous NSCLC) or gemcitabine, and maintenance therapy with cytotoxic drugs should not exceed 4 to 6 cycles. The drugs used for conversion maintenance therapy include pemetrexed (adenocarcinoma), erlotinib (squamous carcinoma), and docetaxel (squamous carcinoma).
4. Treatment selection
It is strongly recommended to first determine whether the patient is suitable for surgery.
Multiple lung cancers should be noted as multiple primary or metastatic. multiple primary lung cancers are considered to be multiple primary if the following criteria are met: different histologic types; same histologic type but no lymph node invasion and no extrapulmonary metastasis. t2N0 high risk features: poorly differentiated tumor, >4 cm, vascular invasion, wedge resection, dirty pleural invasion, incomplete lymph node dissection biopsy.