PO.SHP01.01 · 科学与健康政策
全国范围内癌症治疗相关神经系统疾病的流行病学与经济负担分析
Nationwide epidemiologic and economic burden analysis of neurologic disorders associated with cancer treatment
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：癌症治疗相关神经系统疾病（CIND）是许多化疗药物常见的剂量限制性毒性。它们可在治疗结束后长期持续，损害功能和生活质量。尽管其影响重大，但有关发病率、剂量-反应关系、医疗资源利用和经济负担的大规模数据仍然有限。目的：量化CIND的流行病学特征，按癌症状态、药物和给药途径分层，评估临床及治疗相关的危险因素，测量医疗资源利用和经济成本负担，所有这些均在一个全国性队列中进行。
方法：利用IBM Marketscan纵向理赔数据，我们采用多层级药物匹配来识别新发化疗的成人，并使用ICD 9肿瘤和神经系统编码对癌症和神经系统状态进行分类。患者根据相对于癌症诊断或首次化疗配药日期，被分类为同日或新发神经病变。以3个月为间隔评估CIND累积发病率和首次事件发生时间。我们对CIND按癌症状态和化疗途径建模调整后的比值比和风险比，并在校正年龄、性别和合并症的多变量Cox模型中评估剂量-反应关系。
结果：在三个队列（共约310万患者）中，接受化疗的癌症患者CIND发病率最高（40.4%），相比之下仅患癌症的患者为34.1%，二者又均高于普通人群（12%）。较高的平均每日增量剂量与CIND风险升高显著相关，口服药物每增加1个标准差的HR为1.09-2.23（bexarotene、capecitabine、hydroxyurea、mercaptopurine、tretinoin；均p≤0.046），静脉注射methotrexate的HR为1.34（95% CI 1.00-1.79；p=0.048）。大多数CIND事件发生在末次给药后一年内，表明存在显著的治疗期间和延迟性CIND风险。与静脉给药相比，口服化疗与略低的CIND风险相关（HR 0.862）。较大年龄和合并症（高血压、消化性溃疡、抑郁症、慢性肺病、糖尿病和凝血功能障碍）提供了额外的独立风险。医疗负担分析显示，化疗接受者更频繁地使用阿片类药物配药、CIND导向的药物治疗和康复服务，同时每位患者的成本比普通人群高51倍（约53000美元）。
结论：在这一全国性队列中，CIND很常见，常常延迟出现，并受给药途径、适应证、剂量强度和患者合并症的影响。CIND诊疗在化疗暴露人群中集中了大量的资源利用和经济负担，凸显了对剂量优化方案、主动监测和更好的支持性诊疗策略的需求。
查看英文原文 English abstract
Background: Neurologic disorders associated with cancer treatment (CIND) are common dose-limiting toxicities of many chemotherapies. They can persist long after treatment, impair function, and quality of life. Despite their import, large scale data on incidence, dose-response, and health care utilization and economic burden is limited. Objective: Quantify the epidemiology of CIND, stratified by cancer status, agent, and route of administration, evaluate clinical and treatment-related risk factors, measure health care utilization and economic cost burden, all in a nationwide cohort.
Methods: Using longitudinal IBM Marketscan claims data, we applied multi-tier drug matching to identify adults with incident chemotherapy and classify cancer and neurologic status using ICD 9 neoplasm and neurologic codes. Patients were categorized as having same day or incident neuropathy relative to the cancer diagnosis or first chemotherapy dispensing date. CIND cumulative incidence and time to first event were assessed at 3-month intervals. We modeled adjusted odds and hazards of CIND by cancer status and chemotherapy route and evaluated dose-response in multivariable Cox model adjusted for age, sex, and comorbidities.
Results: Across three cohorts (totaling ~ 3.1M patients), CIND incidence was highest in cancer patients receiving chemotherapy (40.4%) compared to cancer patients alone (34.1%) which was higher still relative to the general population (12%). Higher mean incremental daily dose was significantly associated with increased CIND hazard, with oral agents showing HRs per 1-SD from 1.09-2.23 (bexarotene, capecitabine, hydroxyurea, mercaptopurine, tretinoin; all p≤0.046) and IV methotrexate showing HR 1.34 (95% CI 1.00-1.79; p=0.048). Most CIND events occurred within one year of the last dose, indicating substantial on treatment and delayed CIND risk. Compared with IV administration, oral chemotherapy was associated with a modestly lower hazard of CIND (HR 0.862). Older age and comorbidities (hypertension, peptic ulcer, depression, chronic pulmonary disease, diabetes, and coagulopathy) provide additional independent risk. Healthcare burden analyses revealed opioid dispensing, CIND-directed pharmacotherapy, and rehabilitative services were more frequently used in chemotherapy recipients, accompanied by 51-fold higher per-patient costs (~$53k) relative to general population.
Conclusion: In this nationwide cohort, CIND is common, often delayed, and shaped by route of administration, indication, dose intensity, and patient comorbidity. CIND care concentrates substantial utilization and financial burden in chemotherapy exposed populations, underscoring the need for dose optimized regimens, proactive surveillance, and better supportive care strategies.
利益披露 Disclosure
I. Huseynli, None..
Y. Xu, None..
R. C. Jeter, None..
S. N. Housley, None.