第一部分基线增强 CT 参数联合 CA19-9 的列线图在 治疗前对局部进展期胰腺癌术中放疗疗效的预测 价值

目的:探讨基线对比增强CT参数联合糖链抗原19-9 (carbohydrate antigen 19-9, CA19-9)在预测接受术中放疗( intraoperative radiotherapy, IORT )的局部进展期胰 腺癌 ( locally advanced pancreatic cancer, LAPC )进展风险中的价值，并构建模型 识别 IORT 的潜在受益者。

方法:回顾性纳入 88 例以 IORT 为初始治疗方式的 LAPC 患者，分析其临床参 数、CT 定量参数和 CT 影像征象。通过 Cox 回归分析确定无进展生存期 (progression-free survival, PFS ) 的独立危险因素并构建预测模型。风险评分 (risk-score)通过回归模型的系数计算得出，并用于进展风险的分层。

结果:Cox 多因素分析显示，门静脉期的相对强化值 (relative enhanced value in portal-venous phase, REV-PVP)、胰周脂肪浸润、坏死和 CA19-9 的水平与 PFS 显著相关(所有 p < 0.05)。根据上述变量构建的列线图在预测进展风险方面具 有良好的性能，一致性指数(Harrell’s concordance index, C-index)为 0.779。 风 险评分= REV-PVP (>20 HU) × 1.199 + 胰周脂肪浸润(存在)× 0.539 + CA19-9 (>37 U/mL) × 0.853 + 坏死(存在) × 0.661，根据风险评分，将 LAPC 患者分为低 风险组和高风险组，两组在 IORT 后的进展存在显著差异(中位 PFS: 3.0 月 vs. 10.6 个月, p <0.001)。

结论:基线 CT 影像特征联合 CA19-9 构建的综合模型可以在治疗之前帮助临床 医生识别可能受益于 IORT 的 LAPC 患者，并实施个体化的诊疗策略。

第二部分 增强 CT 定量参数对术中放疗后疾病稳定 的局部进展期胰腺癌的风险分层的价值

目的:探讨 CT 定量参数在接受术中放疗(intraoperative radiotherapy, IORT)的局部 进展期胰腺癌预后预测中的价值，以及其对 IORT 后病情稳定(stable disease, SD) 的患者进行风险分层的能力。

方法:回顾性纳入在 IORT 前后均进行 CT 增强扫描的 LAPC 患者。评估 CT 定 量参数(治疗前，治疗后及其变化值)、影像征象和治疗反应。通过 Cox 回归分析 确定无进展生存期(progression-free survival, PFS)的独立危险因素。根据生存 结局确定的 CT 定量参数的最佳截断值，将患者分为进展高危组和低危组。应用 Kaplan-Meier 分析方法比较 PFS。

结果:在接受 IORT 的 76 例患者中(平均年龄 58.52±10.09 岁，47 名男性和 29 名女性)，56 例(73.7%)根据 RECIST v.1.1 反应评估标准确定为 SD。门静脉期 的 REV 在 IORT 后显著升高(p = 0.018)。PFS 的独立危险因素包括 REV 变化值 (风险比 [hazard ratio, HR], 0.974; p = 0.003)和胰周脂肪浸润(HR, 2.251; p = 0.001)。3 HU作为REV变化值的截断值，可将患者分为进展高危组和低危组。 在SD患者中，两组的进展速度存在显著差异，中位PFS分别为8.77个月和5.13 个月(p = 0.010)。

结论: REV 变化值可作为预测接受 IORT 的 LAPC 患者预后的影像学生物标志 物。REV 变化值可能会改善 RECIST v.1.1 反应评估标准的局限性，实现对 SD 患者进一步风险分层。

Part I Nomogram based on contrast-enhanced CT parameters combined with CA19-9 in preoperative prediction of locally advanced pancreatic cancer progression after intraoperative radiotherapy

Purpose: The aim of this study was to evaluate the significance of baseline computed tomography (CT) imaging features and carbohydrate antigen 19-9 (CA19-9) in predicting prognosis of LAPC receiving IORT and to establish a progression risk nomogram that could identify the potential beneficiary of IORT.

Methods: A total of 88 LAPC patients with IORT as their initial treatment were enrolled retrospectively. Clinical data and CT imaging features, including quantitative parameters and semantic features were analyzed. Cox regression analyses were performed to identify the independent risk factors for progression-free survival (PFS) and to establish a nomogram. A risk-score was calculated by the coefficients of the regression model to stratify the risk of progression.

Results: Multivariate analyses revealed that relative enhanced value in portal-venous phase (REV-PVP), peripancreatic fat infiltration, necrosis, and CA19-9 were significantly associated with PFS (all p<0.05). The nomogram was constructed according to the above variables and showed a good performance in predicting the risk of progression with a concordance index (C-index) of 0.779. Our nomogram stratified patients with LAPC into low- and high-risk groups with distinct differences for progression after IORT (p<0.001).

Conclusion: The integrated nomogram could help clinicians to identify appropriate patients who might benefit from IORT before treatment and to adapt an individualized treatment strategy in advanced.

Part II A preliminary study of quantitative CT parameters on risk stratification of progression in locally advanced pancreatic cancer patients with initial stable disease after intraoperative radiotherapy

Objectives: The aim of this study was to evaluate the role of CT quantitative parameters in predicting overall survival (OS) and progression-free survival (PFS) in locally advanced pancreatic cancer after intraoperative radiotherapy (IORT), and to establish a more effective treatment plan for LAPC patients after IORT, helping patients establish individualized clinical diagnosis and treatment plans.

Methods: LAPC patients who underwent contrast-enhanced CT before and after IORT and were predicted to be at low risk of progression after IORT were retrospectively enrolled. The quantitative CT parameters, semantic features, and treatment responses were evaluated. Cox regression analysis was used to determine independent risk factors for overall survival (OS). The outcome-based optimal cut-off value for quantitative CT parameters was determined and stratified patients into high-risk and low-risk groups. PFS was compared using Kaplan–Meier analysis.

Results: Among the 76 patients (mean age, 58.52 ± 10.09 years, 47 men and 29 women) receiving IORT, the relative enhanced value (REV) in the portal-venous phase increased significantly after IORT (p = 0.018). Change in REV (delta-REV) was an independent risk factor for OS and PFS (hazard ratio [HR], 0.974; p = 0.003) and PFS (HR,0.953; p = 0.012). A 3-HU threshold in delta-REV was used to stratify patients into high-(delta-REV ≤ 3 HU; 31/76, 40.8%) and low-risk groups (delta-REV > 3 HU; 45/76, 59.2%). The difference in progression between the two groups was significant, with a median PFS of 12.53 months and 10.76 months, respectively (p = 0.028). Median OS was longer in patients receiving chemoradiotherapy than those receiving chemotherapy in responders (14.3 months vs 10.4 months) (p = 0.034), while median PFS was longer in patients receiving chemotherapy than in those receiving radiotherapy in non-responders (13.0 months VS 9.2 months) (p= 0.046).

Conclusion: Delta-REV could be used as an imaging biomarker in terms of prognostic prediction in LAPC patients receiving IORT. It could also assist clinicians in identifying a more suitable adjuvant treatment after IORT, which mights to achieve individualized precision treatment to improve patient outcomes.

Keywords: locally advanced pancreatic cancer; computed tomography; intraoperative radiotherapy; prognosis; chemoradiotherapy; chemotherapy.