Evaluation of Overall Survival Rate of Patients with Metastatic Colorectal Cancer Depending on Choice of Treatment, Location of Primary Focus and RAS Genes Mutation Status

Nikolay P. Shiryayev, S. Cheporov, Viktor N. Malashenkо, Yuliya A. Kesel'man, Anastasiya E. Akimova, Valeriya V. Milafetnova
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Abstract

INTRODUCTION: Morbidity with colorectal cancer (CRC) in the Yaroslavl region (YR) accounts for 13.4% of all cases identified in 2021, and ranks third after skin cancer and lung cancer. In the mortality structure, CRC makes 14.2% and is the second leading cause of death. Locally advanced and metastatic forms of the tumor process are identified in more than half the patients. AIM: To evaluate the overall survival rate of patients with metastatic CRC (mCRC) in the territory of the YR depending on the volume of surgical treatment, chemo- and targeted treatment regimens and the presence of RAS genes mutations. MATERIALS AND METHODS: On the base of the Yaroslavl Regional Clinical Oncology Hospital, the data of 291 patients with mCRC who underwent treatment in the period from 2015 to 2022, were analyzed. The mean age of patients was 63.0 8.6 years. There were 52% of men (n = 151), and 48% of women (n = 140). The patients were divided to two groups depending on the status of RAS genes mutations: group I (n = 145) patients with the identified mutation; group II (n = 146) patients with wild-type mutation. The patients were additionally divided to three subgroups depending on the type of treatment: subgroup A (58.1%; n = 169) removal of the primary focus (PF) in combination with antitumor chemotherapy (CT); subgroup B (31.6%; n = 92) CT without surgical treatment; subgroup C (10.3%; n = 30) removal of the PF and resection of liver metastases in combination with CT. RESULTS: The overall survival rate (OSR) depending on the type of treatment was in subgroup A 21.0 (95% confidence interval (CI) 18.6-23.3) months; in subgroup B 11.2 (95% CI 9.912.5) months; in subgroup C 21.0 (95% confidence interval (CI) 18.623.3) months. OSR with RAS mutation: in subgroup 1A 17.7 (95% CI 13.821.7) months; in subgroup IB 11.1 (95% CI 8.313.2) months; in subgroup IC 13.2 (95% CI 4.0722.7) months. OSR with wild-type mutation: subgroup IIA: Cetuximab 33.6 (95% CI 26.740.4) months, Panitumumab 23.8 (95% CI 19.727.9) months (p = 0.01); subgroup IIB: Cetuximab 22.3 (95% CI 17.027.5) months, Panitumumab 15.2 (95% CI 10.719.6) months (p = 0.012); subgroup IIC: Cetuximab 27.5 (95% CI 17.837.1) months, Panitumumab 38.8 (95% CI 13.963.6) months (p = 0.013). CONCLUSIONS: In patients with mutation in RAS genes, the best OSR values were noted in case of surgical removal of the PF in combination with palliative drug therapy. In patients with wild-type mutation of RAS genes the best OSR parameters were recorded in surgical removal of the PF and of metastases in the liver in combination with palliative polyCT and Panitumumab. The lowest OSR was found in the subgroup of patients with use of CT without surgical treatment in the presence of RAS mutation. High OSR parameters were found with mutation in G13codon, and with use of surgical treatment with mutation in A146 codon.
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根据治疗选择、原发病灶位置和RAS基因突变状态评估转移性结直肠癌患者的总生存率
雅罗斯拉夫尔地区(YR)结直肠癌(CRC)的发病率占2021年发现的所有病例的13.4%,仅次于皮肤癌和肺癌,排名第三。在死亡结构中,结直肠癌占14.2%,是第二大死亡原因。在超过一半的患者中发现了局部晚期和转移形式的肿瘤过程。目的:评估YR范围内转移性CRC (mCRC)患者的总生存率,这取决于手术治疗、化疗和靶向治疗方案的数量以及RAS基因突变的存在。材料与方法:以雅罗斯拉夫尔地区临床肿瘤医院为基础,对2015 - 2022年291例接受治疗的mCRC患者资料进行分析。患者平均年龄63.0 ~ 8.6岁。52%的男性(n = 151), 48%的女性(n = 140)。根据RAS基因突变的状态将患者分为两组:I组(n = 145)已确定突变的患者;II组(n = 146)患者为野生型突变。根据治疗类型将患者进一步分为三个亚组:A亚组(58.1%);n = 169)原发病灶切除(PF)联合抗肿瘤化疗(CT);B亚组占31.6%;n = 92) CT未手术治疗;C亚组(10.3%);n = 30) PF切除及肝转移灶切除联合CT。结果:A亚组总生存率(OSR)取决于治疗类型为21.0个月(95%置信区间(CI) 18.6-23.3);B亚组11.2个月(95% CI 9.912.5);C亚组为21.0个月(95%可信区间(CI) 18.623.3)。伴有RAS突变的OSR: 1A亚组17.7个月(95% CI 13.821.7);IB亚组11.1个月(95% CI 8.313.2);IC亚组为13.2个月(95% CI 4.0722.7)。伴有野生型突变的OSR: IIA亚组:西妥昔单抗33.6 (95% CI 26.740.4)个月,帕尼单抗23.8 (95% CI 19.727.9)个月(p = 0.01);IIB亚组:西妥昔单抗22.3个月(95% CI 17.027.5),帕尼单抗15.2个月(95% CI 10.719.6) (p = 0.012);IIC亚组:西妥昔单抗27.5个月(95% CI 17.837.1),帕尼单抗38.8个月(95% CI 13.963.6) (p = 0.013)。结论:在RAS基因突变的患者中,手术切除PF联合姑息性药物治疗的OSR值最好。在RAS基因野生型突变的患者中,手术切除PF和肝脏转移瘤联合姑息性polyCT和Panitumumab记录了最佳的OSR参数。在存在RAS突变的患者中,使用CT而不进行手术治疗的患者的OSR最低。g13密码子突变和A146密码子突变的手术治疗均发现OSR参数较高。
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