胰腺癌非手术患者治疗模式与预后 —— 单中心230例回顾性研究

曹必样; 张乐天; 吴陈陈; 杨微; 刘小亮; 王倩倩; 王竞

doi:10.3969/j.issn.2095-5227.2023.05.003

胰腺癌非手术患者治疗模式与预后 —— 单中心230例回顾性研究

doi: 10.3969/j.issn.2095-5227.2023.05.003

曹必样^{1, 2,},
张乐天^{1, 2},
吴陈陈^{1, 2},
杨微²,
刘小亮²,
王倩倩²,
王竞^2, ,

1.
解放军医学院，北京　100853
2.
解放军总医院第一医学中心放疗科，北京　100853

基金项目: 国家重点研发计划(2017YFC0112100)

详细信息

作者简介:
曹必样，男，在读硕士。研究方向：肿瘤学。Email: cao18383042336@outlook.com

通讯作者:
王竞，男，主任医师，硕士生导师。 Email: wangjingmd@hotmail.com

中图分类号: R735.9
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出版历程
- 收稿日期: 2022-11-08
- 网络出版日期: 2023-05-09
- 刊出日期: 2023-05-28

Treatment modality and prognosis of non-surgical pancreatic cancer: A single-center retrospective analysis of 230 cases

CAO Biyang^{1, 2
,},
ZHANG Letian^{1, 2},
WU Chenchen^{1, 2},
YANG Wei²,
LIU Xiaoliang²,
WANG Qianqian²,
WANG Jing^{2
, ,}

1.
Chinese PLA Medical School, Beijing 100853, China
2.
Department of Radiation Oncology, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China

More Information

Corresponding author: WANG Jing. Email: wangjingmd@hotmail.com

摘要

摘要: 背景胰腺癌非手术患者的主要治疗手段仍是以放化疗为主的综合治疗，但其最佳治疗模式及疗效尚不明确。目的分析接受基于放疗的综合治疗的胰腺癌非手术患者临床病理特征、治疗模式及预后。方法分析2016年1月 - 2020年12月解放军总医院第一医学中心放疗科收治的230例接受基于放疗的综合治疗的胰腺癌非手术患者(医学上不能手术切除或不适合手术)。Kaplan-Meier法计算中位总生存期(median overall survival，mOS)和中位无进展生存期(median progression-free survival，mPFS)。Cox风险比例模型分析影响患者生存的独立预后因素。结果 230例患者中，男140例，女90例，中位年龄64(33 ~ 88)岁。全组患者中位随访时间19.9个月(95% CI：18.2 ~ 27.7个月)，mOS和mPFS分别为17.1个月和10.3个月，1年、2年、3年、4年和5年OS分别为68.1%、30.0%、16.0%、4.9%和2.5%。局限期(Ⅰ/Ⅱ期)、局部晚期(Ⅲ期)和转移性(Ⅳ期)胰腺癌患者mOS分别为21.1个月、17.0个月和14.1个月，mPFS分别为14.0个月、12.7个月和6.9个月。在局限期患者中，单纯放疗(radiotherapy，RT)组与放化疗联合(combined-modality therapy，CMT)组mOS无统计学差异(21.1个月 vs 19.3个月，P=0.620)；在局部晚期和转移性患者中CMT组mOS显著优于RT组(局部晚期：19.2个月 vs 11.6个月，P=0.003；转移：15.7个月 vs 8.0个月，P=0.017)。CMT组患者亚组分析显示，诱导化疗后放疗再巩固化疗(CT-RT-CT)组、化疗序贯放疗(CT-RT)组和放疗序贯化疗(RT-CT)组mOS分别为23.1个月、16.4个月、18.0个月(P=0.007)，且在局部晚期患者中mOS有统计学差异(25.5个月 vs 16.4个月和18.0个月，P=0.034)。临床分期、基线CA19-9、治疗模式和放疗部位与患者生存独立相关(P均＜0.05)。结论现代放化疗综合治疗背景下胰腺癌非手术患者整体生存明显改善。对于局限期患者，单纯放疗与放化疗联合的疗效相似，提示现代放疗可作为根治性治疗的可选治疗手段。对于局部晚期和转移性患者，放化疗联合仍是最佳治疗选择。不同放化疗模式影响放化疗联合治疗患者的生存，CT-RT-CT的放化疗模式可能是局部晚期患者的一种更优选择。
- 胰腺癌 /
- 非手术 /
- 放化疗 /
- 治疗模式 /
- 生存结局
Abstract: Background Comprehensive treatment remains the primary treatment for patients with non-surgical pancreatic cancer, but the optimal treatment modality and outcome are unclear. Objective To analyze the clinicopathological characteristics, treatment modality and prognosis of non-surgical patients receiving radiotherapy-based comprehensive treatment for pancreatic cancer. Methods From January 2016 to December 2020, a total of 230 medically unfit or inoperable pancreatic cancer patients treated with radiotherapy-based comprehensive treatment were enrolled. The median overall survival (mOS) and progression-free survival (mPFS) rates were calculated using the Kaplan-Meier method. Independent prognostic factors were identified by Cox proportional harzard model. Results There were 140 males and 90 females, with a median age of 64 years (range, 33 to 88 years). With a follow-up time of 19.9 months. The mOS and mPFS were 17.1 months and 10.3 months, respectively. The 1-year, 2-year, 3-year, 4-year and 5-year OS were 68.1%, 30.0%, 16.0%, 4.9% and 2.5%, respectively. In patients with localized, locally advanced, and metastatic pancreatic cancer, the median OS were 21.1, 17.0 and 14.1 months, and the mPFS was 14.0, 12.7 and 6.9 months, respectively. There was no significant difference in mOS of patients with localized stage treated with radiotherapy alone (RT) and combined-modality therapy (CMT) (21.1 months vs 19.3 months, P=0.620). Compared with the RT group, the CMT group demonstrated better survival in patients with locally advanced (19.2 vs 11.6 months, P=0.003) and metastatic pancreatic cancer (15.7 months vs 8.0 months, P=0.017). Subgroup analysis of patients in the CMT group showed that the mOS in the induction chemotherapy followed by radiotherapy and consolidation chemotherapy (CT-RT-CT) group, chemotherapy followed by radiotherapy (CT-RT) group and radiotherapy followed by chemotherapy (RT-CT) group were 23.1 months, 16.4 months and 18.0 months, respectively (P=0.007). There was a significant difference in survival of patients with locally advanced stage in above three groups (25.5 months vs 16.4 months and 18.0 months, P=0.034). Clinical stage, baseline CA19-9, treatment modality and radiotherapy site were independent factors affecting patients’ survival (all P<0.05). Conclusion Patients with non-surgical pancreatic cancer have a significantly improved overall survival when treated with radiotherapy-based comprehensive treatment. In patients with localized-stage pancreatic cancer who are medically unfit or inoperable, radiotherapy alone is as effective as a combination of radiotherapy and chemotherapy, indicating that modern radiotherapy can serve as an alternative treatment option for these entities. The combination of radiotherapy and chemotherapy remains the preferred treatment option for patients with locally advanced and metastatic pancreatic cancer, while CT-RT-CT may be a better treatment option for selective patients with locally advanced disease.
- pancreatic cancer /
- non-surgical /
- chemoradiotherapy /
- treatment modality /
- survival outcome

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图 1 230例以放疗为基础的综合治疗胰腺癌非手术患者的生存曲线

A：总生存和无进展生存曲线；B：局限期(Ⅰ/Ⅱ期)、局部晚期(Ⅲ期)、转移性(Ⅳ期)胰腺癌非手术患者治疗后总生存曲线；C：局限期(Ⅰ/Ⅱ期)、局部晚期(Ⅲ期)、转移性(Ⅳ期)胰腺癌非手术患者治疗后无进展生存曲线

Figure 1. Survival curves of the 230 non-surgical pancreatic cancer patients treated with radiotherapy-based comprehensive treatment

A: OS and PFS of 230 non-surgical pancreatic cancer patients treated with radiotherapy-based comprehensive treatment; B: OS of non-surgical patients with localized (stage Ⅰ/Ⅱ), locally advanced (stage Ⅲ), and metastatic (stage Ⅳ) pancreatic cancer; C: PFS of non-surgical patients with localized (stage Ⅰ/Ⅱ), locally advanced (stage Ⅲ), and metastatic (stage Ⅳ) pancreatic cancer

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图 2 230例以放疗为基础的综合治疗胰腺癌非手术患者放化疗组(CMT)和单纯放疗组(RT)的生存曲线

A：总生存曲线；B：CMT组和RT组中局限期、局部晚期、转移性胰腺癌非手术患者中的总生存曲线

Figure 2. Survival curves of the 230 non-surgical pancreatic cancer patients treated with radiotherapy-based comprehensive treatment in combined-modality therapy (CMT) group and radiotherapy alone (RT) group

A: OS of 230 non-surgical pancreatic cancer patients with radiotherapy-based comprehensive treatment in CMT group and RT group; B: OS of non-surgical patients with localized, locally advanced, metastatic pancreatic cancer in CMT and RT groups

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图 3 不同放化疗模式下的放化疗联合(CMT)治疗患者的总生存曲线

A： 105例接受CMT治疗的胰腺癌非手术患者不同放化疗模式的总生存；B： 62例接受CMT治疗的局部晚期胰腺癌非手术患者不同放化疗模式的总生存

Figure 3. Survival curves of non-surgical pancreatic cancer patients treated with CMT by different modalities

A: OS of the 105 non-surgical pancreatic cancer patients treated with CMT with different modalities; B: OS of the 62 non-surgical patients with locally advanced pancreatic cancer treated with CMT with different modalities

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图 4 不同化疗指标下的放化疗联合(CMT)治疗患者的总生存曲线

A：105例接受CMT治疗的胰腺癌非手术患者不同化疗方案数的总生存(OS)； B：105例接受CMT治疗的胰腺癌非手术患者不同化疗总周期数的OS； C：105例接受CMT治疗的胰腺癌非手术患者不同放疗前化疗周期数的OS

Figure 4. Survival curves of patients treated with CMT by different chemo-related indexes

A: OS of the 105 non-surgical pancreatic cancer patients treated with CMT for different number of chemotherapy regimens; B: OS for different number of total chemotherapy cycles; C. OS for different number of chemotherapy cycles before radiotherapy

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表 1 230例以放疗为基础的综合治疗胰腺癌非手术患者的临床特征(例，%)

Table 1. Clinical characteristics of the 230 non-surgical patients with pancreatic cancer treated with radiotherapy-based comprehensive treatment (n, %)

临床特征	例数(百分比)
年龄
≤65岁	133(57.8)
＞65岁	97(42.2)
性别
男	140(60.9)
女	90(39.1)
诊断依据
临床诊断	160(69.6)
病理诊断	70(30.4)
肿瘤部位
胰头	142(61.7)
胰体尾	88(38.3)
基线CA19-9
≤2 000 U·mL^-1	207(90.0)
＞2 000 U·mL^-1	23(10.0)
临床分期
Ⅰ期	26(11.3)
Ⅱ期	26(11.3)
Ⅰ~Ⅱ期	52(22.6)
Ⅲ期	122(53.0)
Ⅳ期	56(24.3)
治疗模式
CT-RT-CT	45(19.6)
CT-RT	38(16.5)
RT-CT	22(9.6)
CMT	105(45.7)
RT	125(54.3)
化疗总周期
≤8	60(57.1)
＞8	45(42.9)
放疗前化疗周期
≤6	49(59.0)
＞6	34(41.0)
免疫治疗
无	190(82.6)
有	40(17.4)
靶向治疗
无	190(82.6)
有	40(17.4)
放疗技术
IMRT	55(23.9)
SBRT	175(76.1)
放疗部位
原发肿瘤	173(75.2)
原发肿瘤 + 转移病灶	41(17.8)
转移病灶	16(7.0)
放疗目的
根治性	192(83.5)
姑息性	38(16.5)
BED₁₀
≤78.6 Gy	89(47.8)
＞78.6 Gy	141(52.2)

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表 2 230例以放疗为基础的综合治疗胰腺癌患者总生存(OS)相关预后因素分析

Table 2. Univariate and multivariate analyses for OS in the 230 patients with pancreatic cancer treated with radiotherapy-based comprehensive treatment

临床特征	单因素分析		多因素分析
临床特征	HR (95% CI)	P值	HR (95% CI)	P值
年龄
≤65岁	1
＞65岁	1.14(0.81 ~ 1.62)	0.451
性别
男	1
女	0.94(0.66 ~ 1.35)	0.752
肿瘤部位
胰头	1
胰体尾	1.14(0.80 ~ 1.61)	0.475
基线CA19-9
≤2 000 U·mL^-1	1		1
＞2 000 U·mL^-1	2.61(1.43 ~ 4.79)	0.002	2.10(1.08 ~ 4.08)	0.029
临床分期
Ⅰ~Ⅱ	1		1
Ⅲ	1.64(1.04 ~ 2.61)	0.035	1.61(0.98 ~ 2.63)	0.058
Ⅳ	2.65(1.57 ~ 4.49)	＜0.001	2.74(1.50 ~ 4.98)	0.001
治疗模式
RT	1		1
CMT	0.73(0.52 ~ 1.03)	0.076	0.63(0.42 ~ 0.94)	0.023
免疫治疗
无	1		1
有	0.61(0.39 ~ 0.97)	0.039	0.63(0.38 ~ 1.04)	0.073
靶向治疗
无	1
有	0.78(0.50 ~ 1.21)	0.265
放疗技术
IMRT	1
SBRT	1.01(0.68 ~ 1.50)	0.942
放疗部位
原发肿瘤	1		1
原发肿瘤 + 　　转移病灶	0.61(0.38 ~ 0.98)	0.043	0.57(0.34 ~ 0.95)	0.030
转移病灶	1.26(0.58 ~ 2.71)	0.563	0.53(0.22 ~ 1.33)	0.178
放疗目的
根治性	1		1
姑息性	1.81(1.12 ~ 2.93)	0.016	1.69(0.90 ~ 3.16)	0.103
BED₁₀
≤78.6 Gy	1		1
＞78.6 Gy	0.65(0.46 ~ 0.94)	0.022	0.87(0.54 ~ 1.39)	0.564

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