Abstract：
Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients.
LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies, including anticytotoxic T-lymphocyte-associated antigen-4 treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analysed.
A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3-71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses and 42.7% (n = 32) partial responses. Four of five cases of LS CRCs displaying proficient MMR (pMMR) or microsatellite stable (MSS) were not responsive. Mucinous/signet-ring cell differentiation was associated with a lower ORR (P = 0.013). The 3-year overall survival and progression-free survival were 91.2% and 82.2%, respectively. A polyp was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment, and they were all larger than 7 mm.
PD-1 inhibitors are highly effective for dMMR and MSI-H LS CRCs, but not for pMMR or MSS LS CRCs or mucinous/signet-ring cell CRC. Large LS adenomas may also be eliminated by anti-PD-1 treatment.
Due to the privacy of patients, the related data cannot be available for public access but can be obtained from Pei-Rong Ding (dingpr@sysucc.org.cn) upon reasonable request. The key raw data have been uploaded to the Research Data Deposit public platform (www.researchdata.org.cn).
LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included. PD-1 inhibitors were given as a monotherapy or in combination with other therapies, including anticytotoxic T-lymphocyte-associated antigen-4 treatment, radiotherapy, chemotherapy, and targeted therapy. Correlations of treatment responses with clinicopathological characteristics and genomic profiles were analysed.
A total of 75 LS patients were included, with a median age of 39 years. The median duration of follow-up was 27 months (range, 3-71). The objective response rate (ORR) was 70.7%, including 28.0% (n = 21) complete responses and 42.7% (n = 32) partial responses. Four of five cases of LS CRCs displaying proficient MMR (pMMR) or microsatellite stable (MSS) were not responsive. Mucinous/signet-ring cell differentiation was associated with a lower ORR (P = 0.013). The 3-year overall survival and progression-free survival were 91.2% and 82.2%, respectively. A polyp was detected in 26 patients during surveillance. Seven adenomas disappeared after treatment, and they were all larger than 7 mm.
PD-1 inhibitors are highly effective for dMMR and MSI-H LS CRCs, but not for pMMR or MSS LS CRCs or mucinous/signet-ring cell CRC. Large LS adenomas may also be eliminated by anti-PD-1 treatment.
Due to the privacy of patients, the related data cannot be available for public access but can be obtained from Pei-Rong Ding (dingpr@sysucc.org.cn) upon reasonable request. The key raw data have been uploaded to the Research Data Deposit public platform (www.researchdata.org.cn).
摘要：
背景：程序性死亡-1（PD-1）抑制剂对错配修复缺陷（dMMR）或微卫星不稳定性高（MSI-H）的结直肠癌（CRC）有效。我们旨在探讨其对Lynch综合征（LS）患者CRC和结肠息肉的影响。
方法：回顾性纳入患有可评估肿瘤并接受至少2个周期PD-1抑制剂的CRC患者。PD-1抑制剂作为单一疗法或与其他疗法联合使用，包括抗毒性T淋巴细胞相关抗原-4治疗，放射治疗,化疗,和靶向治疗。分析了治疗反应与临床病理特征和基因组谱的相关性。
结果：共纳入75例LS患者，平均年龄为39岁。中位随访时间为27个月(范围,3-71).客观反应率（ORR）为70.7%，包括28.0%(n=21)的完全反应和42.7%(n=32)的部分反应。5例表现出熟练MMR（pMMR）或微卫星稳定（MSS）的LSCRC中有4例没有反应。黏液/印戒细胞分化与较低的ORR相关(P=0.013)。3年总生存率和无进展生存率分别为91.2%和82.2%,分别。26例患者在监测中检测到息肉。7个腺瘤治疗后消失,它们都大于7毫米。
结论：PD-1抑制剂对dMMR和MSI-HLSCRC非常有效，但不适用于pMMR或MSSLSCRC或粘液性/印戒细胞CRC。大的LS腺瘤也可以通过抗PD-1治疗来消除。
■由于患者的隐私，相关数据无法公开访问，但可以从丁培荣(dingpr@sycic.org。cn)应合理要求。关键原始数据已上传到研究数据存款公共平台(www.researchdata.org.cn)。
方法：回顾性纳入患有可评估肿瘤并接受至少2个周期PD-1抑制剂的CRC患者。PD-1抑制剂作为单一疗法或与其他疗法联合使用，包括抗毒性T淋巴细胞相关抗原-4治疗，放射治疗,化疗,和靶向治疗。分析了治疗反应与临床病理特征和基因组谱的相关性。
结果：共纳入75例LS患者，平均年龄为39岁。中位随访时间为27个月(范围,3-71).客观反应率（ORR）为70.7%，包括28.0%(n=21)的完全反应和42.7%(n=32)的部分反应。5例表现出熟练MMR（pMMR）或微卫星稳定（MSS）的LSCRC中有4例没有反应。黏液/印戒细胞分化与较低的ORR相关(P=0.013)。3年总生存率和无进展生存率分别为91.2%和82.2%,分别。26例患者在监测中检测到息肉。7个腺瘤治疗后消失,它们都大于7毫米。
结论：PD-1抑制剂对dMMR和MSI-HLSCRC非常有效，但不适用于pMMR或MSSLSCRC或粘液性/印戒细胞CRC。大的LS腺瘤也可以通过抗PD-1治疗来消除。
■由于患者的隐私，相关数据无法公开访问，但可以从丁培荣(dingpr@sycic.org。cn)应合理要求。关键原始数据已上传到研究数据存款公共平台(www.researchdata.org.cn)。
