PO.PS01.03 · 人群科学
与祖先相关、分期特异的三级诊疗延迟与结直肠癌的生存差异相关
Ancestry-linked, stage-specific delay to tertiary care is associated with survival differences in colorectal cancer
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摘要 Abstract
中文摘要
背景：非洲血统（AFR）的结直肠癌（CRC）患者的总生存期（OS）比非AFR患者更差。虽然已知生物学和社会经济（SES）因素起一定作用，但获得专科诊疗的延迟仍是这一不平等中一个关键但尚未充分探讨的驱动因素。本研究调查了从诊断（Dx）到抵达三级癌症中心的时间如何与祖先、疾病分期、SES和基因组学相互作用而影响OS。
方法：我们分析了自2014年以来在纪念斯隆-凯特琳癌症中心（MSK）接受治疗的4,328名CRC患者（259名AFR，4,069名非AFR）的数据。肿瘤采用MSK-IMPACT进行测序，这是一种靶向DNA测序检测，可分析341-505个基因中的基因组变化。遗传祖先根据测序数据推断，将非洲祖先比例>80%者归为AFR组。OncoKB识别具有临床可操作性的基因组改变。协变量包括肿瘤位置、诊断时分期、从诊断到抵达MSK的时间（早期≤90天 vs 晚期>90天）、保险类型和转移负荷。使用Kaplan-Meier曲线和log-rank检验比较从诊断起的OS，并对基因组测序日期进行左截断处理。
结果：AFR患者从诊断起的OS比非AFR患者更差（中位数39.3 vs 62.7个月，p<0.001）。按诊断时分期分层后，这一差异依然存在（I-III期：65.3 vs 96个月，p<0.001；IV期：31.6 vs 36.7个月，p=0.03）。AFR患者从诊断到抵达的延迟也显著更长（中位数：22[IQR：10, 173] vs 14[IQR：6, 38]天；p<0.001），晚期抵达的比例也更高（28.7 vs 17.1%，p<0.001）。这一差异在I-III期（49.6 vs 25.9%，p<0.001）比在IV期（6.3 vs 5.6%，p=0.69）更为明显。在I-III期早期抵达（中位数：未达到（NR）vs NR，p=0.98）、I-III期晚期抵达（中位数：36 vs 43.5个月，p=0.24）和IV期晚期抵达（中位数：43.7 vs 33.9个月，p=0.48）中，AFR与非AFR之间的OS无显著差异，但在IV期早期抵达中差异显著（中位数：31.6 vs 36.9个月，p=0.034）。诊断为I-III期疾病但晚期抵达MSK的患者，在抵达时往往已是IV期（AFR：68.9%，非AFR：65.8%），而在早期抵达者中这种情况少得多（AFR：6.1%，非AFR：2.6%）；并且这与AFR（10.8% vs 1.5%；p=0.03）和非AFR（4.4% vs 2.4%；p=0.015）患者中较高的医疗补助（Medicaid）使用率相关。AFR在所有分期和抵达组中的KRAS突变频率均高于非AFR（I-III期早期：51.5 vs 38.8%，p=0.04；I-III期晚期：58.2 vs 47.2%，p=0.10；IV期早期：58.5 vs 44.5%，p=0.004；IV期晚期：75 vs 50.5%，p=0.28）。
结论：专科诊疗延迟似乎与AFR患者的CRC生存差距相关，尤其是在非转移性情况下，此时及时的多学科诊疗至关重要。加快将AFR患者转诊至三级诊疗中心可能有助于实现CRC结局的平等。
查看英文原文 English abstract
Background: African-ancestry (AFR) patients with colorectal cancer (CRC) have worse overall survival (OS) than non-AFR patients. While biological and socioeconomic (SES) factors are known to play a role, delayed access to specialized care remains a critical, underexplored driver of this inequity. This study investigates how the time from diagnosis (Dx) to arrival at a tertiary cancer center interacts with ancestry, disease stage, SES, and genomics to affect OS.
Methods: We analyzed data from 4,328 CRC patients (259 AFR, 4,069 non-AFR) treated at Memorial Sloan Kettering Cancer Center (MSK) since 2014. Tumors were sequenced with MSK-IMPACT, a targeted DNA sequencing assay that profiles genomic changes in 341-505 genes. Genetic ancestry was inferred from sequencing data with >80% African ancestry fraction grouped as AFR. OncoKB identified clinically actionable genomic alterations. Covariates included tumor location, stage at Dx, time from Dx to MSK arrival (Early ≤90 days vs Late >90 days), insurance type and metastatic burden. OS from Dx was compared using Kaplan-Meier curves and log-rank test, with left-truncation for genomic sequencing date.
Results: AFR patients had worse OS from Dx than Non-AFR patients (median 39.3 vs 62.7 months, p<0.001). This difference remained when stratified by stage at Dx (Stage I-III: 65.3 vs 96 months, p<0.001; Stage IV: 31.6 vs 36.7 months, p=0.03). AFR patients also had significantly longer delays from Dx to arrival (median: 22 [IQR: 10, 173] vs 14 [IQR: 6, 38] days; p<0.001) and a higher proportion of late arrivals (28.7 vs 17.1%, p<0.001). This difference was more evident in Stage I-III (49.6 vs 25.9%, p<0.001) than in Stage IV (6.3 vs 5.6%, p=0.69). There was no significant difference in OS between AFR and Non-AFR for Stage I-III early (median: Not Reached (NR) vs NR, p=0.98), Stage I-III late (median: 36 vs 43.5 months, p=0.24), and Stage IV late (median:43.7 vs 33.9 months, p=0.48) arrival, but was significant in Stage IV early arrival (median: 31.6 vs 36.9 months, p=0.034). Patients diagnosed with Stage I-III disease who arrived late at MSK were often Stage IV at their time of arrival (AFR: 68.9%, Non-AFR 65.8%) but this was much less frequent among early arrivals (AFR: 6.1%, Non-AFR: 2.6%); and was linked to higher Medicaid use in both AFR (10.8% vs 1.5%; p=0.03) and Non-AFR (4.4% vs 2.4%; p=0.015) patients. AFR had higher KRAS mutation frequency compared to Non-AFR across all stages and arrival groups (Stage I-III Early: 51.5 vs 38.8%, p=0.04; Stage I-III Late: 58.2 vs 47.2%, p=0.10; Stage IV Early: 58.5 vs 44.5%, p=0.004; Stage IV Late: 75 vs 50.5%, p=0.28).
Conclusion: Delayed specialized care appears to be linked to CRC survival gaps in AFR patients, especially in the non-metastatic setting where timely multidisciplinary care is crucial. Expediting referral of AFR patients to tertiary care centers could help to achieve CRC outcome equity.
利益披露 Disclosure
S. D. Abubakar, None..
C. Lee, None..
C. Chen, None..
F. Shah, None..
M. Waters, None.