摘要
目的:
肺癌是我国发病率很高的一种恶性疾病,其中80%为非小细胞肺癌(non-small cell lung cancer, NSCLC),初诊时2/3已不能手术切除或不能耐受手术。因此,肺癌的早期诊断及准确分期对其治疗和预后具有极其重要的意义。18F-FDG PET/CT (18F-fluorodeoxyglucose positron emission tomography/computed tomography)能从分子水平通过观察体内代谢变化,在疾病发生解剖结构变化之前做出诊断,已用于肿瘤的诊断、分期、疗效观察、区分肿瘤坏死及复发。然而关于治疗前后FDG标准摄取值(standardized uptake value,SUV)及其变化能否早期预测非小细胞肺癌的复发尚未有定论。本研究通过对入组的47例非小细胞患者同步放化治疗前后18F-FDG标准摄取值与其预后的关系分析,探讨非小细胞肺癌患者治疗前后18F-FDG PET/CT的标准摄取值及其变化在预测复发和转移中的作用。另外,我们通过对这些患者SUV值的分析,希望能找出可以预测非小细胞肺癌预后的最佳临界值,以指导其治疗方案的制定。
方法:
2005年2月至2006年3月,在山东省肿瘤医院进行了同步放化疗的47例Ⅲ期非小细胞肺癌患者进入了本研究,要求每位患者在行放化疗前及放化疗后1-3个月内均行全身18F-FDG PET/CT检查,测量出肺部肿瘤原发病灶感兴趣区的最高标准摄取值(maximal standardized uptake value)即SUVmax并分别记为SUV治疗前和SUV治疗后,通过公式计算出每个患者治疗前后SUVmax的变化百分率,均用△SUV来衡量,具体公式如下:△S UV=(SUV治疗前-SUV治疗后)×100%/SUV治疗前。与此同时我们还记录了患者的年龄、性别、病理类型、分期等各项临床指标,在治疗结束后对患者进行密切的随访,直到病情进展。用SPSS11.0统计软件包进行统计学分析,通过对不同预后患者的原发病灶处SUV值进行比较,找出非小细胞肺癌患者治疗前后SUV变化及其与各项临床指标及预后的关系,探讨18F-FDG PET/CT在预测复发和远处转移中的作用,并通过受试者工作特征曲线(receive operating characteristic curve,ROC曲线)的绘制,找出能够判断预后的临界SUV值。
结果:
经过中位随访期为20.5个月的随访,最后入组并进行结果分析的共有47例患者。在这些患者中,至随访期末,共有26例患者出现局部或区域复发、转移,我们将其归入A组。仍有21例未出现复发、转移者,我们将其归入B组。通过统计学分析我们得出如下结果:治疗前A组和B组的SUVmax分别为11.60±2.55和8.49±4.12,治疗后A组和B组的SUVmax分别为5.60±2.25和2.79±0.86,治疗前后A组的SUVmax均明显高于B组(p1=0.005,p2=0.000);A组治疗前后SUVmax变化百分率即△S UV平均值为52.56%±22.07%, B组治疗前后SUVmax变化百分率平均值为60.95%±19.64%,两组之间的差异无统计学意义(p=0.155);根据ROC曲线的分析结果,当取治疗前SUVmax=8.5作为临界值时,对47例患者复发和转移预测的准确率为83%,敏感性、特异性、阳性预测值、阴性预测值分别为96%、67%、78%、93%;当取治疗后SUVmax=4.5作为临界值时,对复发和转移预测的准确度为79%,敏感性、特异性、阳性预测值、阴性预测值分别为73%、95%、86%、72%;通过对年龄、性别、病理类型、分期及治疗前SUV值、治疗后SUV值、治疗前后SUV变化百分率(△SUV )各项因素进行Logistic回归分析,我们发现,只有治疗前SUV和治疗后SUV对预后的判断有显著性意义。
结论:
18F-FDG PET/CT显像作为一种安全、无创、准确的肺癌诊断分期方法,已逐渐被大家所接受。它从分子水平上帮助判断肿瘤的良恶性,具有较高的准确性,可以根据SUV值的大小来指导肿瘤个体化和预见性治疗。本研究发现,治疗前后SUVmax高者近期出现复发和转移的可能性较大,预后也相对SUVmax低者差。因此非小细胞肺癌患者治疗前后的SUV可以作为与生存相关的重要预后因素。根据治疗前后18F-FDG PET/CT的SUV值可以较早的预测非小细胞肺癌复发的高危人群。对于非小细胞患者来说,给予高危患者更为积极的治疗和密切随访,建立有效的辅助治疗措施,对提高晚期患者的生存质量和生存率具有重要意义。
Objective:
Lung cancer is one of the leading causes of death worldwide. About 80% percents of them are non-small cell lung cancer(NSCLC). It was found that about two third of those patients was too late to be on operation or intolerant of operation for their first visit to a doctor. Therefore, to improve the final outcomes, a reliable prognostic test is required to predict treatment response before its onset, to allow a more aggressive treatment strategy. A dual modality18F-FDG PET/CT allows the fusion of all diagnostic information from CT and PET scans with utmost accurate alignment, which helps to detect primary tumors and metastases by morphologic and functional characteristics. It has been used to evaluate focal pulmonary nodules and the stages of the lung cancer, and to detect a recurrent tumor. However, the potential of serial 18F-FDG PET/CT for being a prognostic factor has yet to be determined. The purpose of the present study was to evaluate if SUV was a significant predictor for local or regional recurrence, either before or after treatment. We also want to determine if the changes of SUV was a reliable predictor for prognosis. At the same time, we attempted to retrospectively determine a cut-off SUV to increase the accuracy in predicting prognosis in our study.
Methods:
This is a prospective study of 47 consecutive patients with locally advanced non small cell lung cancer (stageШA/ШB) who were treated with chemoradiotherapy in the department of radiotherapy of the Shandong Cancer Hospital and Institute from February 2005 to March 2006. All patients had at least two serial 18F-FDG PET/CT scans: one was performed before start of treatment (SUVbefore), and the other approximately 1-3 months after finishing of treatment (SUVafter). The maximum standardized uptake value(SUVmax)of the primary lung lesion was calculated in both pretreatment and post-treatment PET/CT to obtain the SUVbefore and SUVafter.. We also want to determine if the changes of SUV was a reliable predictor for prognosis. The value changes of SUV before and after treatment were calculated according to the following equation:△SUV=(SUVbefore-SUVafter)×100% / SUVbefore. We recorded the following variables: age, gender, histology type and clinical stage of all the patients. Follow-up examinations were planned their completion of therapy. Recurrence or metastasis was considered when there an abnormal finding suggesting recurrence or metastasis on serial imaging studies or pathologically confirmed malignancy. Statistical software (SPSS, version 11.0; SPSS Ins.) was used for the analysis. Logistic regression analysis was applied to assess the effects of the following variables: age, gender, histology type, clinical stage, SUVmax, and△SUV. The receiver operating characteristic(ROC) curve was constructed to determine an optimal cut-off value to differentiate different prognosis with the best trade-off between sensitivity and specificity.
Results:
After a median follow-up of 20.5 months, patients were classified into two categories: group A included the patients who had local and regional recurrence or metastasis. The other patients who had no local and regional recurrence or metastasis were group B. Before treatment, the SUV for group A and group B were 11.60±2.55、8.49±4.12 respectively, There was significant difference between the two groups (p =0.005). After treatment, the SUV for group A was 5.60±2.25 and for group B 2.79±0.86. Thus, the SUV was significantly lower in group B than those in group A (p =0.000); Also, the SUVmax were present in squamous cell carcinoma and adenocarcinoma. There were no significant differences between different histologies, either before treatment or after treatment in both group A and group B. The decreases in SUVmax between baseline and 1-3 months after completion of therapy were 52.56%±22.07% for group A . For group B, the decreases in SUVmax between baseline and 1-3 months after completion of therapy were 60.95%±19.64%.There was no significant difference between these two groups (p =0.155); Using the SUVmax of 8.5 as the cut-off for differentiating between the two groups, pretreatment PET/CT showed an overall sensitivity of 96% ,a specificity of 67%,a positive predictive value of 78%, a negative predictive value of 93% and an overall accuracy of 83%. The sensitivity、specificity、positive predictive value、negative predictive value and overall accuracy for post-treatment PET/CT scans were 73%、95%、86%、72% and 79% respectively when we used 4.5 as the cut-off; Logistic regression analysis was applied to assess the effects of the following variables: age, gender, histology type, clinical stage, SUVmax, and△SUV. SUVbefore and SUVafter were significant factors correlated with recurrence and metastasis(p1=0.003, p2=0.000). In contrast, histology、age、gender、stage and△SUV were not significant.
Conclusions:
18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can measure and image the glucose metabolism quantitatively using 18F-FDG and may be more sensitive than CT because the alterations in tissue metabolism measured by PET generally precede anatomical changes .This study has shown that 18F-FDG PET/CT SUVmax was an important complementary prognostic factor for inoperable NSCLC patients and was useful in predicting the outcome of chemoradiotherapy in patients with locally advanced NSCLC. In this study, patients with high SUVs were observed to have a worse outcome. Quantitative evaluation of 18F-FDG PET/CT scans before and after treatment might help to determine the most appropriate treatment strategy, and consequently improve treatment efficiency. Due to the limited number of patients in this study, a clinical study with a larger group of patients is warranted.
引文
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