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中华肝脏外科手术学电子杂志 ›› 2024, Vol. 13 ›› Issue (05) : 657 -664. doi: 10.3877/cma.j.issn.2095-3232.2024.05.012

临床研究

基于DWI信号值构建局部进展期胰腺癌放化疗生存获益预测模型
张瑜1, 姜梦妮2,()   
  1. 1. 201203 上海中医药大学附属曙光医院放疗科
    2. 200433 上海,海军军医大学第一附属医院消化内科;海军军医大学免疫与炎症国家重点实验室
  • 收稿日期:2024-05-11 出版日期:2024-10-10
  • 通信作者: 姜梦妮
  • 基金资助:
    上海中医药大学附属曙光医院四明基金(SGZXY-202202)

Establishment of prediction model for survival benefits of locally advanced pancreatic cancer patients after radiochemotherapy based on DWI signal value

Yu Zhang1, Mengni Jiang2,()   

  1. 1. Department of Radiotherapy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Department of Gastroenterology, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai 200433, China
  • Received:2024-05-11 Published:2024-10-10
  • Corresponding author: Mengni Jiang
引用本文:

张瑜, 姜梦妮. 基于DWI信号值构建局部进展期胰腺癌放化疗生存获益预测模型[J]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 657-664.

Yu Zhang, Mengni Jiang. Establishment of prediction model for survival benefits of locally advanced pancreatic cancer patients after radiochemotherapy based on DWI signal value[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(05): 657-664.

目的

基于治疗前磁共振弥散加权成像(DWI)信号值构建局部进展期胰腺癌(LAPC)续贯放化疗生存获益预测模型。

方法

回顾性分析2015年1月至2017年12月在海军军医大学第一附属医院接受立体定向放疗(SBRT)的39例LAPC患者临床影像学资料。患者均签署知情同意书。其中男26例,女13例;年龄33~80岁,中位年龄64岁。胰头癌33例,胰体尾癌6例。30例患者SBRT放疗后续贯替吉奥(S-1)化疗。SBRT放疗前均行多b值下DWI序列成像检查,成像时采用11个b值(0、25、50、75、100、150、200、400、600、800、1 000 s/mm2),得到11帧不同b值下的重叠DWI图像。采用Cox回归分析不同b值下的感兴趣区域(ROI)平均信号值(SI)与总体生存期(OS)之间的相关性,筛选独立风险因素,建立列线图预测模型,预测拟行续贯放化疗LAPC患者的生存获益情况。预测误差曲线(PEC)分析通过计算Brier综合分数(IBS)来评估预测误差。

结果

随访时间87~1 095 d,中位随访时间353 d;随访期间38例死亡,1例存活。患者OS为84~1 095 d,中位OS为352 d,1年生存率46%。Cox回归分析显示,SI100HR=0.997,95%CI:0.996~0.998)、SI600HR=0.996,95%CI:0.993~0.998)、SI800HR=0.994,95%CI:0.991~0.997)和S1000HR=0.993,95%CI:0.989~0.996)是OS的独立预测因素(P<0.05)。PEC分析显示,预测模型1 (SI100 + S-1,C-index 0.712)、模型2 (SI600 +年龄+S-1,C-index 0.731)、模型3 (SI800 +年龄+ S-1,C-index 0.736)、模型4 (SI1000 +年龄+ S-1,C-index 0.732)均较模型内其他组合预测误差小,IBS分别为0.134、0.133、0.130和0.133,并构建相应的列线图预测模型。线性校准图显示预测效果及实际观察效应之间具有很高的一致性,进一步证实列线图预测模型的可靠性。

结论

基于放化疗前DWI序列信号值的列线图预测模型能够对拟进行放化疗LAPC患者的生存期获益进行预测,为临床医师制定个体化治疗决策提供依据,避免过度医疗。

Objective

To establish a prediction model for survival benefits of locally advanced pancreatic cancer (LAPC) patients after sequential radiochemotherapy based on the signal value of diffusion-weighted imaging (DWI) before treatment.

Methods

Clinical imaging data of 39 patients with LAPC who received stereotactic body radiotherapy (SBRT) in the First Affiliated Hospital of Naval Medical University from January 2015 to December 2017 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 26 patients were male and 13 female, aged from 33 to 80 years, with a median age of 64 years. 33 patients were diagnosed with pancreatic head cancer and 6 cases of pancreatic body and tail cancer. 30 patients were treated with SBRT followed by S-1 chemotherapy. DWI sequence imaging with multiple b values was performed before SBRT. 11 b values (0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1 000 s/mm2) were adopted to obtain 11 overlapping DWI images with different b values. Cox regression model was used to analyze the correlation between the average signal intensity (SI) of the region of interests (ROI) and overall survival (OS) under different b values, to screen the independent risk factors, and to establish a nomogram prediction model, thereby predicting the survival benefits of patients with LAPC scheduled to undergo sequential radiochemotherapy. Prediction error curve (PEC) analysis was utilized to assess the prediction error by calculating integrated Brier score (IBS).

Results

The follow-up time was ranged from 87 to 1 095 d, with a median of 353 d. During follow-up, 38 patients died and 1 survived. The OS of all patients was ranged from 84 to 1 095 d, with a median OS of 352 d, and the 1-year survival rate was 46%. Cox regression analysis showed that SI100 (HR=0.997, 95%CI: 0.996-0.998), SI600 (HR=0.996, 95%CI: 0.993-0.998), SI800 (HR=0.994, 95%CI: 0.991-0.997) and SI1000 (HR=0.993, 95%CI: 0.989-0.996) were the independent predictive factors of OS (P<0.05). PEC analysis revealed that prediction model 1 (SI100 + S-1, C-index 0.712), model 2 (SI600 + age + S-1, C-index 0.731), model 3 (SI800 + age + S-1, C-index 0.736) and model 4 (SI1000 + age + S-1, C-index 0.732) had smaller errors than other combinations within each model, and the IBS was 0.134, 0.133, 0.130 and 0.133, respectively. Corresponding nomogram prediction models were also established. Linear calibration chart indicated a high degree of consistency between the prediction effect and the actual effect, which further confirmed the reliability of the nomogram prediction model.

Conclusions

The nomogram prediction model based on the signal value of DWI sequence before radiochemotherapy can predict the survival benefits of LAPC patients scheduled to undergo radiochemtherapy, providing evidence for clinicians to make individualized treatment decisions and avoid overtreatment.

图1 一例LAPC患者11组b值下的相应DWI信号值测量注:a为LAPC患者DWI图像(b为600 s/mm2),绿色区域内为ROI区域;b为不同b值下ROI信号值的线图;c为ROI具体信号值;LAPC为局部进展期胰腺癌,DWI为弥散加权成像,ROI为感兴趣区域
图2 LAPC患者11组b值下DWI信号值(SI0-1000)的集中及离散趋势箱形图注:箱形图的须距是箱形图四分位间距的1.5倍;LAPC为局部进展期胰腺癌,DWI为弥散加权成像,SI为不同b值下的DWI信号值
表1 LAPC患者ROI区域在11组b值下的DWI信号值
图3 基于SI构建LAPC患者生存获益预测模型的PEC曲线分析注:4种组合模型的IBS分数较组内其他预测因素均为最低,分别为0.134、0.133、0.130和0.133;PEC为预测误差曲线,IBS为Brier综合分数,用于评估和比较选定模型的预测误差;LAPC为局部进展期胰腺癌,DWI为弥散加权成像,SI为DWI信号值
图4 基于SI构建LAPC患者生存获益的四个高效列线图预测模型注:LAPC为局部进展期胰腺癌,DWI为扩散加权成像,SI为DWI信号值
图5 四个列线图预测模型预测LAPC患者的线性校准图注:a、b、c、d分别为基于SI100、SI600、SI800、SI1000预测模型的线性校准图,示预测效果及实际观察效应之间有很高的一致性;SI为DWI信号值,DWI为扩散加权成像
[1]
Petrelli F, Comito T, Ghidini A, et al. Stereotactic body radiation therapy for locally advanced pancreatic cancer: a systematic review and pooled analysis of 19 trials[J]. Int J Radiat Oncol Biol Phys, 2017, 97(2):313-322.
[2]
Mahadevan A, Moningi S, Grimm J, et al. Maximizing tumor control and limiting complications with stereotactic body radiation therapy for pancreatic cancer[J]. Int J Radiat Oncol Biol Phys, 2021, 110(1):206-216.
[3]
Ueno H, Okusaka T, Ikeda M, et al. An early phase Ⅱ study of S-1 in patients with metastatic pancreatic cancer[J]. Oncology, 2005, 68(2/3):171-178.
[4]
Hammel P, Huguet F, van Laethem JL, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial[J]. JAMA, 2016, 315(17):1844-1853.
[5]
Morizane C, Okusaka T, Furuse J, et al. A phase Ⅱ study of S-1 in gemcitabine-refractory metastatic pancreatic cancer[J]. Cancer Chemother Pharmacol, 2009, 63(2):313-319.
[6]
Sudo K, Yamaguchi T, Nakamura K, et al. Phase Ⅱ study of S-1 in patients with gemcitabine-resistant advanced pancreatic cancer[J]. Cancer Chemother Pharmacol, 2011, 67(2):249-254.
[7]
Tempero MA, Malafa MP, Al-Hawary M, et al. Pancreatic adenocarcinoma, version 2.2021, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2021, 19(4):439-457.
[8]
Xu W, Zhang H, Feng G, et al. The value of MRI in identifying pancreatic neuroendocrine tumour G3 and carcinoma G3[J]. Clin Radiol, 2021, 76(7):551.e1-551.e9.
[9]
Tsvetkova S, Doykova K, Vasilska A, et al. Differentiation of benign and malignant breast lesions using ADC values and ADC ratio in breast MRI[J]. Diagnostics, 2022, 12(2):332.
[10]
He D, Wang X, Fu C, et al. MRI-based radiomics models to assess prostate cancer, extracapsular extension and positive surgical margins[J]. Cancer Imaging, 2021, 21(1):46.
[11]
Hottat NA, Badr DA, Lecomte S, et al. Value of diffusion-weighted MRI in predicting early response to neoadjuvant chemotherapy of breast cancer: comparison between ROI-ADC and whole-lesion-ADC measurements[J]. Eur Radiol, 2022, 32(6):4067-4078.
[12]
de Silva S, Lockhart KR, Aslan P, et al. The diagnostic utility of diffusion weighted MRI imaging and ADC ratio to distinguish benign from malignant renal masses: sorting the kittens from the tigers[J]. BMC Urol, 2021, 21(1):67.
[13]
Cai PQ, Wu YP, An X, et al. Simple measurements on diffusion-weighted MR imaging for assessment of complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer[J]. Eur Radiol, 2014, 24(11):2962-2970.
[14]
Zhang Y, Zhu X, Liu R, et al. Combination of pre-treatment DWI-signal intensity and S-1 treatment: a predictor of survival in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy and sequential S-1[J]. Transl Oncol, 2018, 11(2):399-405.
[15]
Benedict SH, Yenice KM, Followill D, et al. Stereotactic body radiation therapy: the report of AAPM Task Group 101[J]. Med Phys, 2010, 37(8):4078-4101.
[16]
Iima M, Le Bihan D. Clinical intravoxel incoherent motion and diffusion MR imaging: past, present, and future[J]. Radiology, 2016, 278(1):13-32.
[17]
Klauss M, Lemke A, Grünberg K, et al. Intravoxel incoherent motion MRI for the differentiation between mass forming chronic pancreatitis and pancreatic carcinoma[J]. Invest Radiol, 2011, 46(1):57-63.
[18]
Lemke A, Laun FB, Klauss M, et al. Differentiation of pancreas carcinoma from healthy pancreatic tissue using multiple b-values: comparison of apparent diffusion coefficient and intravoxel incoherent motion derived parameters[J]. Invest Radiol, 2009, 44(12):769-775.
[19]
Kang KM, Lee JM, Yoon JH, et al. Intravoxel incoherent motion diffusion-weighted MR imaging for characterization of focal pancreatic lesions[J]. Radiology, 2014, 270(2):444-453.
[20]
Klau M, Mayer P, Bergmann F, et al. Correlation of histological vessel characteristics and diffusion-weighted imaging intravoxel incoherent motion-derived parameters in pancreatic ductal adenocarcinomas and pancreatic neuroendocrine tumors[J]. Invest Radiol, 2015, 50(11):792-797.
[21]
Klauß M, Maier-Hein K, Tjaden C, et al. IVIM DW-MRI of autoimmune pancreatitis: therapy monitoring and differentiation from pancreatic cancer[J]. Eur Radiol, 2016, 26(7):2099-2106.
[22]
Ma C, Li Y, Wang L, et al. Intravoxel incoherent motion DWI of the pancreatic adenocarcinomas: monoexponential and biexponential apparent diffusion parameters and histopathological correlations[J]. Cancer Imaging, 2017, 17(1):12.
[23]
Le Bihan D, Breton E, Lallemand D, et al. MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders[J]. Radiology, 1986, 161(2):401-407.
[24]
Lemke A, Stieltjes B, Schad LR, et al. Toward an optimal distribution of b values for intravoxel incoherent motion imaging[J]. Magn Reson Imaging, 2011, 29(6):766-776.
[25]
Anderson S W, Barry B, Soto JA, et al. Quantifying hepatic fibrosis using a biexponential model of diffusion weighted imaging in ex vivo liver specimens[J]. Magn Reson Imaging, 2012, 30(10):1475-1482.
[26]
Ma C, Guo X, Liu L, et al. Effect of region of interest size on ADC measurements in pancreatic adenocarcinoma[J]. Cancer Imaging, 2017, 17(1):13.
[27]
Bilgili Y, Unal B. Effect of region of interest on interobserver variance in apparent diffusion coefficient measures[J]. AJNR Am J Neuroradiol, 2004, 25(1):108-111.
[28]
Curvo-Semedo L, Lambregts DM, Maas M, et al. Rectal cancer: assessment of complete response to preoperative combined radiation therapy with chemotherapy—conventional MR volumetry versus diffusion-weighted MR imaging[J]. Radiology, 2011, 260(3):734-743.
[29]
Ma C, Liu L, Li J, et al. Apparent diffusion coefficient (ADC) measurements in pancreatic adenocarcinoma: a preliminary study of the effect of region of interest on ADC values and interobserver variability[J]. J Magn Reson Imaging, 2016, 43(2):407-413.
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