非小细胞肺癌功能分子成像及临床病理学特征的相关研究

发布时间：2017-12-28 20:35

本文关键词：非小细胞肺癌功能分子成像及临床病理学特征的相关研究　出处：《南方医科大学》2017年博士论文　论文类型：学位论文

【摘要】：第一部分18F-FDG PET/CT对亚厘米非小细胞肺癌的临床意义及其预后研究背景肺癌的发病率和死亡率居世界上恶性肿瘤的首位。18F-FDG PET/CT是广泛应用于确诊肺部恶性肿瘤的无创成像方法。通常由于PET低空间分辨率的限制造成高假阴性的结果,使其评价亚厘米NSCLC的作用至今仍不明确,尤其是对以鳞屑样生长方式为主的小腺癌。因此即使是对亚厘米病变,18F-FDGPET/CT可能是预测肿瘤潜在恶性的有前景的定量评估的方法。然而很少有关于18F-FDG PET/CT评估直径≤1 cm结节的临床意义及其预后的研究。为了进一步评估亚厘米NSCLC患者肿瘤的恶性潜能及预测其预后,有必要阐明其临床病理特点、预后及合适的手术治疗方法。因此本研究回顾性分析了术前行PET/CT检查,手术切除后临床分期为NO的亚厘米NSCLC患者18F-FDG PET/CT检查的临床意义。研究目的探讨18F-FDG PET/CT对亚厘米非小细胞肺癌的临床意义及其预后研究。材料与方法回顾性分析2010-2015年我院PET/CT中心189例临床分期为NO的亚厘米NSCLC患者,术前行PET/CT检查及测量SUVmax。淋巴管侵犯、血管侵犯、胸膜侵犯和淋巴结转移至少含有以上因素之一被认为是:病理性侵犯(PI)。通过Kaplan-Meier生存曲线及对数秩检查计算生存率。结果平均的SUVmax为 1.7±1.8(SUVmax范围从0.6-13.0),中位数为 1.0。28例(15%)亚厘米NSCLC患者有PI。多变量回归分析结果显示SUVmax是预测PI(P=0.0251)及总体生存率(OS)(P=0.0485)的独立的重要的临床指标。ROC曲线分析结果显示以SUVmax = 2.0作为预测PI的阈值。与低SUVmax值组相比,高SUVmax值组(SUVmax2.0;n=42)在影像学上更多的表现为纯实性病变(91%vs 14%;p0.0001)及术后淋巴结侵犯(12%vs 0%;p0.0001)。高SUVmax组和低SUVmax组5年肺癌特异性OS(LCS-OS)存在着显著差异(LCS-OS分别为:(92.3%vs 96.9%;p=0.0054),在薄层CT上癌症的复发仅在纯实性亚厘米NSCLC。在本研究中高SUVmax组,尽管是亚厘米的病变,肺叶切除比亚肺叶切除有更好的3年无复发存活期(RFS)(88.3%vs 50.0%;p=0.0453)。结论1、PET/CT检查的SUVmax可反映肿瘤的侵袭性;2、PET/CT对亚厘米NSCLC的预后有显著的影响,尤其是在薄层CT上表现为纯实性的肿瘤。第二部分18F-FDG PET/CT全身显像对非小细胞肺癌诱导治疗的疗效及生存期的预测价值背景肺癌是全球发病率和死亡率最高的恶性肿瘤。2015年,我国约有429.2万癌症新发病例,其中,肺癌以新发病例73.3万例(占整体17.1%)成为中国人罹癌或因癌致死的最大威胁。在原发性肺癌中大约有80%为非小细胞肺癌,临床实验表明肿瘤诱导治疗期间,18F-FDG PET/CT测得的肺癌原发部位葡萄糖代谢活性的变化与肿瘤治疗后的疗效有关。关于诱导化疗期间PET/CT图像在通过肿瘤原发部位或转移淋巴结葡萄糖代谢变化预测肿瘤疗效方面的作用的研究很少。研究目的通过18F-FDG PET/CT全身显像预测非小细胞肺癌诱导治疗的疗效及生存期材料与方法回顾性分析2010年-2015年在我院诱导治疗前或治疗后行PET/CT检查的手术为非小细胞肺癌患者。肉眼和显微镜下完全切除的手术被划分为R0,显微镜下不完全切除术为R1,肉眼不完全切除为R2。整体生存期(OS)为从手术时间到死亡时间或随访结束时间。收集诊断性活检或术后活检确诊为淋巴结转移N2期的患者。记录原发肿瘤和N2期转移淋巴结的SUVmax及计算诱导治疗后SUVmax百分比的变化。肺癌原发部位的SUVmax是从Xeleris工作站获取的。SUVmax分为诱导治疗前或诱导治疗后。计算诱导治疗前后PET的SUVmax绝对值和百分比的变化。术前和术后SUVmax中位截点,四分位数截点为SUVmax的百分比的变化,0为SUVmax绝对值变化(SUVmax的增加vs无变化或减少)的截点,评估以上生存期的预测因素。结果诱导治疗期间肺癌原发部位标准化摄取值(SUV)的增加与术后患者总体生存期下降有关。无论是治疗前肿瘤原发部位SUV绝对值还是其百分比的变化都与术后患者的总体生存期无关。N2期纵隔淋巴结转移的非小细胞肺癌SUV减少大于60%是总生存期最佳的预测因素,其比肿瘤原发部位SUV的变化能更好的预测总体生存期。结论1、诱导治疗后SUV增加的非小细胞肺癌与SUV稳定的或减少的的患者相比前者预后差。2、纵隔转移淋巴结葡萄糖摄取的变化与原发部位PET/CT葡萄糖摄取变化相比,可更好的预测生存期。
[Abstract]:The first part is the clinical significance and prognosis of 18F-FDG PET/CT for subcentimeter non-small cell lung cancer. The incidence and mortality of lung cancer ranks the first in the world. 18F-FDG PET/CT is a noninvasive imaging method widely used in the diagnosis of malignant tumor of the lungs. PET is usually due to low spatial resolution limits caused by high false negative results, the evaluation of sub centimeter the role of NSCLC is still not clear, especially for lepidic growth oriented small adenocarcinoma. Therefore, even for subcentimetre lesions, 18F-FDGPET/CT may be a promising and quantitative method for predicting the potential malignancy of the tumor. However, there are few studies on 18F-FDG PET/CT and its clinical significance in prognosis evaluation of CM nodules diameter is less than or equal to 1. In order to further evaluate the malignant potential of tumor and predict its prognosis in sub centimeter NSCLC patients, it is necessary to elucidate its clinicopathological characteristics, prognosis and appropriate surgical treatment. Therefore, the clinical significance of 18F-FDG PET/CT examination in subcentimetre NSCLC patients with NO after surgical resection was reviewed in this study. Objective to investigate the clinical significance and prognosis of 18F-FDG PET/CT for subcentimetre non-small cell lung cancer. Materials and methods a retrospective analysis was made of 189 subcentimetre NSCLC patients in the PET/CT center of our hospital in 2010-2015 years. The PET/CT examination and the measurement of SUVmax were performed before the operation. Lymphatic invasion, vascular invasion, pleural invasion, and lymph node metastasis are considered to be at least one of the above factors: pathological invasion (PI). The survival rate was calculated by the Kaplan-Meier survival curve and logarithmic rank examination. The results showed that the average SUVmax was 1.7 + 1.8 (SUVmax range from 0.6-13.0), and the median was 1. 28 (15%) patients with subcentimetre NSCLC had PI. The results of multivariate regression analysis showed that SUVmax was an independent and important clinical index for predicting PI (P=0.0251) and overall survival (OS) (P=0.0485). The results of ROC curve analysis showed that SUVmax = 2 was used as the threshold for predicting PI. Compared with the low SUVmax group, the high SUVmax value group (SUVmax2.0; n=42) showed more pure solid lesions in imaging (91%vs 14%, P0.0001) and postoperative lymph node involvement (12%vs 0%; P0.0001). There was a significant difference in lung cancer specific OS (LCS-OS) in the high SUVmax group and low SUVmax group in 5 years (LCS-OS = 92.3%vs 96.9%; p=0.0054); the recurrence of cancer on thin lamina CT was only in pure solid sub centimeter NSCLC. In this study, the high SUVmax group had a sub centimeter lesion even though the lobectomy had a better 3 year recurrence free survival (RFS) (88.3%vs 50%; p=0.0453). Conclusion 1. SUVmax detected by PET/CT can reflect the invasiveness of tumor. 2, PET/CT has a significant effect on the prognosis of sub centimeter NSCLC, especially in thin slice CT. The second part is the predictive value of 18F-FDG PET/CT whole body imaging in the induction therapy and survival time of non-small cell lung cancer. Background lung cancer is the highest incidence and mortality rate in the world. In 2015, China has about 4 million 292 thousand new cases of cancer, including lung cancer, with 733 thousand new cases (total 17.1%) to become the people with cancer China or because of the greatest threat to cancer death. About 80% of primary lung cancer is non-small cell lung cancer. Clinical trials show that the change of glucose metabolism activity at the primary site of lung cancer is related to the efficacy of tumor treatment after 18F-FDG PET/CT treatment. There are few studies on the role of PET/CT image in predicting tumor efficacy through primary tumor sites or metastatic lymph node glucose metabolism during induction chemotherapy. The purpose of this study is to predict the efficacy and survival time of induction therapy for non-small cell lung cancer through 18F-FDG PET/CT whole body imaging. Materials and methods of survival in patients with non-small cell lung cancer were retrospectively analyzed. The patients who underwent PET/CT examination before induction or after treatment in 2010 -2015 were diagnosed as non-small cell lung cancer. The total excision of the naked eye and microscope was divided into R0, the incomplete resection under microscope was R1, and the naked eye was not fully excised as R2. The overall survival time (OS) was from the time of operation to the time of death or the end of the follow-up. A patient with a phase N2 of lymph node metastasis was diagnosed by diagnostic biopsy or postoperative biopsy. The SUVmax of primary and N2 metastatic lymph nodes and the changes in the percentage of SUVmax after induction therapy were recorded. The SUVmax of the primary site of lung cancer was obtained from the Xeleris workstation. SUVmax is divided into pre induced or induced therapy. The changes of SUVmax absolute value and percentage of PET before and after induction therapy were calculated. Before and after operation, the median cut-off point of SUVmax and the percentage of four quantile cut-off were SUVmax, and 0 was the cut-off point of SUVmax absolute value change (SUVmax increase or no change or decrease of VS), and the predictors of above survival time were evaluated. Results the increase of the primary location of lung cancer (SUV) was associated with the decrease of the overall survival period of the patients. The changes in the SUV absolute value or the percentage of the primary site of the tumor before treatment were not related to the overall survival of the postoperative patients. The decrease of SUV in stage N2 mediastinal lymph node metastasis is greater than 60%, which is the best predictor of overall survival. It is better than the primary site SUV in predicting the overall survival. Conclusion 1. The prognosis of non small cell lung cancer with increased SUV after induction therapy is poor compared to those with stable or reduced SUV. 2. The change of glucose uptake in the mediastinal metastatic lymph nodes is better than the PET/CT glucose uptake in the primary site, which can better predict the survival time.
【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R734.2;R730.44

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