| BackgroundsAs Chinese Cancer Statistics said, in 2015, China has an approximate 4.3 million incidences of cancer.Meanwhile deaths by cancer reach about 2.8 million,equally 7500 deaths per day. Lung cancers account for 30%of all cancer incidences, which equal to 1.29 million new cases a year, or an incidence rate of 3.85/100,000.Currently lung cancer is the leading cause of cancer death in men and,second cause of cancer death in women (only after breast cancer). The American Cancer Society’s estimates for lung cancer in the United States for 2016 are:about 224,390 new cases of lung cancer or an incidence rate of 69.55/100,000. This shows that China is a high incidence country of lung cancer, and shows a rising trend. In Western countries-small cell lung cancer accounts for about 13% of the total incidence of lung cancer, the male to female ratio of 1:1, in our small cell lung cancer incidence of lung cancer accounts for 15% to 20% male to female ratio is about 3:1.Lung cancer, also known as primary bronchial cancer, mostly originate from epithelial cells lining the bronchial endotheliums, and seldom originate from epithelial cells lining the alveolus. Lung cancer can be classified as small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) based on histologic manifestations. SCLC is thought to be originating from neuroendocrinal cells of lung tissue, which is most common type of neuroendocrinal cancer. It is not until 1969,that people realized NSCLC and SCLC should be treated differently.SCLC is poorly differentiated, highly malignant and rapidly growing.It has a doubling time of only 23 days, while squamous cell carcinoma has a doubling time of 88 days, adenocarcinoma has a doubling time of 161 days. Early in the course of SCLC,a distant spread tend to present, usually accompanied by a large central hilar and mediastinal lymph node lesions. The vast majority of SCLC patients have blood metastasis when diagnosed. Only about one-third of patients with the disease confined to the chest cavity. According to the American Cancer Society Cancer report patients with stage I small cell lung cancer at diagnosis accounts for only 2-5%,while stage II patients accounts for only 20-25%. Small cell lung cancer clinically manifests a strong propensity of erosion,high proliferation rate.even though small cell lung cancer is sensitive to chemotherapy and radiation therapy, the phenomenon of drug resistance in clinical practice is present fast.it is difficult to obtain a long-term maintenance therapy.It is reported that limited-disease small cell lung cancer(LD-SCLC)has a local recurrence rate of 75%-90%,while extensive-disease small cell lung cancer (ED-SCLC)has a local recurrence rate reaching 100% even post chemotherapy. Small cell lung cancer is a high degree of malignancy and poor prognosis of lung cancer. It has been reported that patients with limited and extensive dieses small cell lung cancer obtain a 5-year survival rate rarely exceeding 10% and 2% respectively. If not given active treatment to control the disease right after the diagnosis, the survival time rarely surpasses 2-4 months. The 5-year survival rate over the same period of non-small cell lung cancer is more than 30%.In recent years, after surgery combined with radiotherapy and chemotherapy to get widely used in clinical, combination therapy SCLC has made some progress. Surgery combined with radiotherapy comprehensive treatment of small cell lung cancer stage I have been generally recognized academics in 2011 and have been recommended by ACCP and NCCN’s Small Cell Lung Cancer Treatment Guidelines since.European Society of Medical Oncology(ESMO) guidelines also recommended surgery for patients with T2N1M0 (part of IIA and IIB) since that surgery can improve progression-free survival and overall survival time.In 2012, US Surveillance, Epidemiology and End Results (SEER) published an analysis showing that 5-year survival rate of surgical resection of small cell lung cancer patients with stage I-III could be significantly improved.2015, Combs and other scholars analyzed more than 2,500 from the American Cancer Center who underwent surgical resection of small cell lung cancer. That study have shown that for patients with stage I-IIIA who underwentlobectomy combined with radiotherapy and chemotherapy the 5-year survival rate had improved significantly. Although some research suggests that surgery combined with radiotherapy and chemotherapy for stage II-IIIa small cell lung cancer patients can benefit, but surgical treatmentnecessity for stage II-IIIa sclc remains controversial. This study was designed to further investigate the prognosis of II-IIIa small cell lung cancer with surgical resection,ObjectiveIn this research, we try to introduce surgical resection into the treatment regimen of stage II-IIIA SCLC patients.We compare PFS,OS, one-year survival rate and two-year survival rate between surgical patients and non-surgical patients.In this way we explore the impact of surgical resection in patients with II-III A stage small cell lung carcinoma (SCLC).MethodsWe analyze the database of in-patients who diagnosed a II-IIIA stage SCLC from Jan 1st 2009 to Feb 1st 2014. Patients who undergo surgical resections are enrolled as the treatment group while patients who did not undergo surgical resection are enrolled as the control group. Disease progression are confirmed by monthly examination. The grouping is balanced by propensity score match. The progression-free survival (PFS) time and overall survival (OS) are analyzed with Kaplan-Meier survival method and Cox regression is applied to analyze the covariates. Applying Fisher’s exact test to compare one-year survival rate and two-year survival rate.Experimental group’s rule-in standard:(1) Videography datas(CT/PET-CT) suggested a lung mass pre-hospitalization or during hospitalization, no pre-operational antioncologic treatment, assured a SCLC by post-operational pathology; (2) no metastasis is found by thorough examination (M=0), pTNM staging is within II-III A (3) no other primary tumor; (4) there is a complete information of chemotherapy.Control group’s rule-in standard:(1) Videography datas (CT/PET-CT) suggested a lung mass pre-hospitalization or during hospitalization, receiving chemotherapy after pathologic confirmation of SCLC (2) no metastasis is found by thorough examination (M=0), pTNM staging is within II-III A (3) no other primary tumor.Rule-out standard:(1) can not confirm the pathological type or pTNM staging of the mass;(2) suffering from a second disease that can not be stabilized; (3) minors, pregnant or breast-feeding women; (4) already progressed to any distant metastasis; (5) the cause of death has nothing to do with the cancer;(6) surgery underwent after replase by chemotherapy; (7) patients who did not show up after the first treatment; (8) non-radical surgery such as wedge resection or a fine needle biopsy; (9) who have serious complications, such as the condition beyond the control of diabetes, tuberculosis and other wasting diseases.Periodic inspection projectThe two groups of patients before each chemotherapy first chest radiographs or chest enhanced CT, ECG and three conventional laboratory tests, the fourth line of systemic chemotherapy prior to inspection, giving the body PET-CT or enhanced chest CT + head MRI + ECT + abdominal ultrasound to observe the patient’s condition changes. Regular observation after chemotherapy finished included chest radiographs or chest enhanced CT scans by every three months.With using STATA13.0 statistical software, match the cases using logit regression by propensity scores of confounding factors such as age, gender, T stage, smoking history, N stage, tumor grade and others. After balancing both baseline indicators,the new sample would be generated. Then use SPSS22.0 statistical software to analyze survivals via the kaplan-meier method. In Cox regression analysis of the impact of various factors on the PFS and OS.When follow up OS we use telephone follow-ups and outpatient follow-ups. The follow-up time is between 2 to 6 years, with a median follow-up time of 3.5 years.The last follow-up date is February 1,2016. Some patients-relatives can not offer precise information of death date, thus allowing±7 days of statistical error. When follow up PFS we use hospitalization follow-ups and outpatient follow-ups. The follow-up time is between 2 to 6 years, with a median follow-up time of 2.75 years. The last follow-up date is February 1,2016. Lost criteria:(1) can not contact to the patients or the family or they were unwilling to provide information;(2) For the evaluation of PFS, those who have doubts in examination information that was taken outside this hospital.ResultsA total of 23 pairs of patients were included. Ages ranged from 40 to 78 yrs-old;the median age was 58; the average age was57.8.58 patients had simple SCLCs,3 patients had combined small cell lung cancer,2 of which were mixed with squamous carcinoma,1 of which was mixed with adenocarcinoma.Experimental group (group A):23 patients were included.7 of which were stage IIa,3 of which were stage IIb.13 of which were stage IIIa. Surgery method:18 patients underwent thoracoscopic lobectomy and mediastinal lymph node dissection, 4 of which thoracotomy lung resection and mediastinal lymph node dissection, just one of the patients underwent sleeve resection.22 patients of the group successed in R0 complete resection, one patient with a T3N2M0 cancer underwent R1 resection. The chemotherapies are used in systemic modes.2-6 of chemotherapy cycle, average 3.75. Chemotherapy are the selection criteria or a platinum-containing anthracycline-containing solution. Eight cases in which the CE chemotherapy, EP regimen 12 cases, CAO chemotherapy two cases, CAP chemotherapy in 1 case. Received thoracic irradiation sequential chemoradiotherapy in 19 cases,4 cases of concurrent chemoradiotherapy. Postoperative radiotherapy total dose 50-60Gy, conventional fractionated dose 1.8-2.0Gy. Wherein a routine preventive whole brain irradiation, radiation dose 25 Gy.The control group (group B):there are 38 prematch cases, including six cases of IIa, IIb 9 cases, IIIa of 23 cases. Mode of chemotherapy are used systemic chemotherapy, chemotherapy cycles 1-6 cycles, the average cycle 4.35. Chemotherapy are the selection criteria or a platinum-containing anthracycline-containing solution.12 cases in which undertook the CE program,20 cases undertook the EP program, three cases undertook the CAO program, three cases undertook the CAP program. In this group 29 cases Received thoracic irradiation by sequential chemoradiation therapy, seven cases of concurrent chemoradiotherapy. The total dose of postoperative radiotherapy was 55-60Gy, conventional fractionated dose 1.8-2.0Gy.3 of them underwent whole brain irradiation prevention, the radiation dose was 25Gy.The prosensity score match generated 23 pairs of cases whose statistics are as follows:Median PFS are 331 days for experimental group and 194 days for control group. The experimental group has a median OS of 684 days, one-year and two-year survival rates of 81.8%,39.4%.The control group has a median OS of 440 days, one-year and two-year survival rates of 69.6%,30.4%.The PFS and OS of the treatment group is longer than that of the control group (P<0.05). Both one-year and two-year survival rates of the treatment group outnumber those of the control group (P＜0.05). Cox regression indicates that surgical resection is an independent prognostic factor (P＜0.05)ConclusionsSurgical resection on tolerable patients with stage II-III A small-cell lung carcinoma is effective on improving the progression-free survival time, one-year and two-year survival rates, and also shows a propensity of a higher overall survival time. These data may warrant prospective studies including surgery in the multimodality treatment of SCLC in specific circumstances. |
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