Lung cancer is one of the most common malignant tumors in China. Our surveillance information shows that the incidence rate of lung cancer is 35.23/100,000 and the mortality rate of lung cancer is 27.93/100,000. Lung cancer is mainly divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC is a highly aggressive tumor characterized by rapid growth, short multiplication time, prone to distant metastasis and poor prognosis.
SCLC is mostly in the extensive stage when diagnosed, sensitive to radiotherapy and has a high rate of objective remission in the near future, but the majority of patients develop recurrence and metastasis within a short period of time after treatment. In contrast to the numerous research findings in NSCLC each year, the research progress in SCLC in the past 20 years has been slow.
As the most authoritative international guideline in the field of SCLC treatment, NCCN publishes 2 editions of clinical practice guidelines on SCLC each year, and the 1st edition of 2016 guidelines has been published. Compared with the 2nd edition of 2015, the 1st edition of 2016 guidelines has not changed much, and the following are the main updates.
The main update points of the guidelines
1. Smoking cessation counseling and interventions were added to the initial assessment.
2. Changed the criteria for performing unilateral bone marrow aspiration or biopsy: when peripheral blood smear shows nucleated red blood cells, neutropenia or thrombocytopenia, bone marrow aspiration or biopsy is required considering the possible presence of bone infiltration.
3. For extensive SCLC in complete or partial remission, the recommended level of treatment with prophylactic brain irradiation (PCI) is reduced from level 1 to level 2A; in addition, chest radiotherapy is added as a treatment option for extensive SCLC.
4. In the follow-up treatment, the recommended dose of temozolomide was removed; bendamustine was recommended as an option for follow-up treatment (Class 2B recommendation).
5.The main recommended dose of PCI is 25 Gy divided into 10 fractions, once a day. Short-course radiotherapy (20 Gy divided into 5 fractions) is an appropriate option in extensive stage SCLC. This version of the guidelines removes the 30 Gy fractionation of 10-15 times and the 24 Gy fractionation of 8 times.
Other updates of less relevance to SCLC have also been made and are not listed here.
Key elements of staging principles and treatment strategies in the guidelines
The current major staging systems for small cell lung cancer are the American Legion Staging and the 7th edition TNM staging. The American Legion staging is the earliest staging method used in SCLC and includes mainly limited and extensive stages.
Limited stage is defined as a lesion that is confined to the ipsilateral hemithorax and can be safely included by a single irradiation field.
Extensive stage is defined as more than ipsilateral hemithorax, including malignant pleural or pericardial effusion or hematogenous metastasis.
The TNM staging system is primarily used to screen patients with stage T1-2N0 who are suitable for surgical and radiotherapy planning. The TNM staging system should be used first in clinical studies because it can more accurately assess prognosis and guide treatment.
1. T1-2N0M0 treatment strategy (the only staging suitable for surgery in the guidelines)
Clinical staging of T1-2N0M0, pathologic evaluation without mediastinal lymph node metastasis, lobectomy (recommended) lymph node dissection or sampling. Postoperative pathology remains (N0) for postoperative adjuvant chemotherapy, if postoperative pathology is (N+) simultaneous chemotherapy + mediastinal radiotherapy.
2.T1-2N0M 0 postoperative adjuvant chemotherapy regimen and dose
The recommended regimen is etoposide and cisplatin/carboplatin. The chemotherapy cycle is 4-6.
Cisplatin 60 mg/m2 d1 and etoposide 120 mg/m2 d1,2,3
Cisplatin 80 mg/m2 d1 and etoposide 100 mg/m2 d1,2,3
Carboplatin AUC 5-6 d1 and etoposide 100 mg/m2 d1,2,3
* Radiotherapy is required if lymph node metastases are found after surgery, and the principles of radiotherapy are described in the relevant section below.
3. Other staging strategies (all patients except T1-2N0M0 surgery)
For patients with inoperable SCLC, radiotherapy is mainly recommended. The main recommended chemotherapy regimen is etoposide and cisplatin/carboplatin or irinotecan and cisplatin/carboplatin. Chemotherapy is administered over a 4-6 week period.
Recommended initial chemotherapy regimen and dose.
Limited phase (up to 4-6 cycles).
Cisplatin 60 mg/m2 d1 and etoposide 120 mg/m2 d1,2,3
Cisplatin 80 mg/m2 d1 and etoposide 100 mg/m2 d1,2,3
Carboplatin AUC 5-6 d1 and etoposide 100 mg/m2 d1,2,3
During chemotherapy + radiotherapy, cisplatin / etoposide (level 1)* is recommended
* Radiotherapy should be applied no later than 30 days after chemotherapy.
Granulocyte growth factor is not recommended during concurrent radiotherapy.
Extensive phase (up to 4-6 cycles).
Cisplatin 75 mg/m2 d1 and etoposide 100 mg/m2 d1,2,3
Cisplatin 80 mg/m2 d1 and etoposide 80 mg/m2 d1,2,3
Cisplatin 25 mg/m2 d1,2,3 and etoposide 100 mg/m2 d1,2,3
Carboplatin AUC 5-6 d1 and etoposide 100 mg/m2 d1,2,3
Cisplatin 60 mg/m2 d1 and irinotecan 60 mg/m2 d1,8,15
Cisplatin 30 mg/m2 and irinotecan 65 mg/m2 d1,8
Carboplatin (AUC 5 d1) and irinotecan 50 mg/m2 d1,8,15
4. Second-line treatment after relapse
Preferred clinical trial
Relapse <2-3 months, PS0-2.
Paclitaxel, docetaxel, topotecan oral/intravenous, irinotecan, temozolomide, gemcitabine, isocyclophosphamide, bendamustine.
Relapse > 2-3 months to 6 months.
Topotecan oral/intravenous (level 1), paclitaxel, docetaxel, irinotecan, gemcitabine, vincristine, oral etoposide, temozolomide, cyclophosphamide / adriamycin / vincristine (CAV), bendamustine.
Relapse > 6 months: apply the original protocol
5. Principles of radiation dose
For limited stage small cell lung cancer, the optimal dose of radiotherapy has not been established uniformly. However, three weeks of 45 Gy (fractionated dose of 1.5 Gy BID) is better than five weeks of 45 Gy (fractionated dose of 1.8 Gy QD). In the case of BID hyper-segmentation, there should be at least 6 hours between treatments to ensure normal tissue repair. If radiotherapy is given once daily, a high dose of 60-70 Gy should be used. Chest radiotherapy for extensive small cell lung cancer can be used in patients who are sensitive to chemotherapy. Studies have shown that thoracic radiotherapy is well tolerated, reduces recurrence of chest symptoms, and can extend 2-year survival.
Overall, the overall changes in the NCCN small cell lung cancer guideline update are minor, but of note are the addition of bendamustine to chemotherapy agents and adjustments to the principles of chest radiotherapy and PCI.