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临床Ⅰ期非小细胞肺癌延迟手术治疗与肿瘤学结局分析。

Analysis of Delayed Surgical Treatment and Oncologic Outcomes in Clinical Stage I Non-Small Cell Lung Cancer.

机构信息

Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine in St Louis, Missouri.

VA St Louis Health Care System, St Louis, Missouri.

出版信息

JAMA Netw Open. 2021 May 3;4(5):e2111613. doi: 10.1001/jamanetworkopen.2021.11613.

Abstract

IMPORTANCE

The association between delayed surgical treatment and oncologic outcomes in patients with non-small cell lung cancer (NSCLC) is poorly understood given that prior studies have used imprecise definitions for the date of cancer diagnosis.

OBJECTIVE

To use a uniform method to quantify surgical treatment delay and to examine its association with several oncologic outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using a novel data set from the Veterans Health Administration (VHA) system. Included patients had clinical stage I NSCLC and were undergoing resection from 2006 to 2016 within the VHA system. Time to surgical treatment (TTS) was defined as the time between preoperative diagnostic computed tomography imaging and surgical treatment. We evaluated the association between TTS and several delay-associated outcomes using restricted cubic spline functions. Data analyses were performed in November 2021.

EXPOSURE

Wait time between cancer diagnosis and surgical treatment (ie, TTS).

MAIN OUTCOMES AND MEASURES

Several delay-associated oncologic outcomes, including pathologic upstaging, resection with positive margins, and recurrence, were assessed. We also assessed overall survival.

RESULTS

Among 9904 patients who underwent surgical treatment for clinical stage I NSCLC, 9539 (96.3%) were men, 4972 individuals (50.5%) were currently smoking, and the mean (SD) age was 67.7 (7.9) years. The mean (SD) TTS was 70.1 (38.6) days. TTS was not associated with increased risk of pathologic upstaging or positive margins. Recurrence was detected in 4158 patients (42.0%) with median (interquartile range) follow-up of 6.15 (2.51-11.51) years. Factors associated with increased risk of recurrence included younger age (hazard ratio [HR] for every 1-year increase in age, 0.992; 95% CI, 0.987-0.997; P = .003), higher Charlson Comorbidity Index score (HR for every 1-unit increase in composite score, 1.055; 95% CI, 1.037-1.073; P < .001), segmentectomy (HR vs lobectomy, 1.352; 95% CI, 1.179-1.551; P < .001) or wedge resection (HR vs lobectomy, 1.282; 95% CI, 1.179-1.394; P < .001), larger tumor size (eg, 31-40 mm vs <10 mm; HR, 1.209; 95% CI, 1.051-1.390; P = .008), higher tumor grade (eg, II vs I; HR, 1.210; 95% CI, 1.085-1.349; P < .001), lower number of lymph nodes examined (eg, ≥10 vs <10; HR, 0.866; 95% CI, 0.803-0.933; P < .001), higher pathologic stage (III vs I; HR, 1.571; 95% CI, 1.351-1.837; P < .001), and longer TTS, with increasing risk after 12 weeks. For each week of surgical delay beyond 12 weeks, the hazard for recurrence increased by 0.4% (HR, 1.004; 95% CI, 1.001-1.006; P = .002). Factors associated with delayed surgical treatment included African American race (odds ratio [OR] vs White race, 1.267; 95% CI, 1.112-1.444; P < .001), higher area deprivation index [ADI] score (OR for every 1 unit increase in ADI score, 1.005; 95% CI, 1.002-1.007; P = .002), lower hospital case load (OR for every 1-unit increase in case load, 0.998; 95% CI, 0.998-0.999; P = .001), and year of diagnosis, with less recent procedures more likely to have delay (OR for each additional year, 0.900; 95% CI, 0.884-0.915; P < .001). Patients with surgical treatment within 12 weeks of diagnosis had significantly better overall survival than those with procedures delayed more than 12 weeks (HR, 1.132; 95% CI, 1.064-1.204; P < .001).

CONCLUSIONS AND RELEVANCE

Using a more precise definition for TTS, this study found that surgical procedures delayed more than 12 weeks were associated with increased risk of recurrence and worse survival. These findings suggest that patients with clinical stage I NSCLC should undergo expeditious treatment within that time frame.

摘要

重要性

由于先前的研究使用了不精确的癌症诊断日期定义,因此对于非小细胞肺癌(NSCLC)患者延迟手术治疗与肿瘤学结果之间的关联了解甚少。

目的

使用统一的方法来量化手术治疗延迟,并检查其与多种肿瘤学结果的关联。

设计、地点和参与者:这项回顾性队列研究使用退伍军人健康管理局(VHA)系统中的一种新数据进行。纳入的患者具有临床 I 期 NSCLC,并在 VHA 系统中进行了 2006 年至 2016 年的切除术。手术治疗时间(TTS)定义为术前诊断性计算机断层扫描成像与手术治疗之间的时间。我们使用受限立方样条函数评估 TTS 与几种与延迟相关的结果之间的关联。数据分析于 2021 年 11 月进行。

暴露

癌症诊断和手术治疗之间的等待时间(即 TTS)。

主要结果和测量

评估了几种与延迟相关的肿瘤学结果,包括病理性升级、有阳性切缘的切除和复发。我们还评估了总生存情况。

结果

在接受临床 I 期 NSCLC 手术治疗的 9904 名患者中,9539 名(96.3%)为男性,4972 名患者(50.5%)目前吸烟,平均(SD)年龄为 67.7(7.9)岁。TTS 的平均值(SD)为 70.1(38.6)天。TTS 与病理性升级或阳性切缘的风险增加无关。在中位(四分位间距)随访 6.15(2.51-11.51)年时,4158 名患者(42.0%)检测到复发。与复发风险增加相关的因素包括年龄较小(每增加 1 岁的风险比[HR],0.992;95%置信区间[CI],0.987-0.997;P = .003)、Charlson 合并症指数评分较高(复合评分每增加 1 单位的 HR,1.055;95%CI,1.037-1.073;P < .001)、节段切除术(与肺叶切除术相比,HR 为 1.352;95%CI,1.179-1.551;P < .001)或楔形切除术(与肺叶切除术相比,HR 为 1.282;95%CI,1.179-1.394;P < .001)、肿瘤较大(例如,31-40 mm 与<10 mm;HR,1.209;95%CI,1.051-1.390;P = .008)、肿瘤分级较高(例如,II 与 I;HR,1.210;95%CI,1.085-1.349;P < .001)、检查的淋巴结较少(例如,≥10 与<10;HR,0.866;95%CI,0.803-0.933;P < .001)、较高的病理分期(III 与 I;HR,1.571;95%CI,1.351-1.837;P < .001)和更长的 TTS,超过 12 周后,复发风险逐渐增加。TTS 每延迟一周,复发的风险增加 0.4%(HR,1.004;95%CI,1.001-1.006;P = .002)。与手术延迟相关的因素包括非裔美国人(与白人相比,OR 为 1.267;95%CI,1.112-1.444;P < .001)、较高的地区贫困指数(ADI)评分(ADI 评分每增加 1 单位的 OR,1.005;95%CI,1.002-1.007;P = .002)、较低的医院病例量(每增加 1 单位病例量的 OR,0.998;95%CI,0.998-0.999;P = .001)和诊断年份,最近的手术程序延迟可能性较小(每年增加的 OR,0.900;95%CI,0.884-0.915;P < .001)。在诊断后 12 周内接受手术治疗的患者的总生存情况明显优于手术延迟超过 12 周的患者(HR,1.132;95%CI,1.064-1.204;P < .001)。

结论和相关性

使用更精确的 TTS 定义,本研究发现,超过 12 周的手术延迟与复发风险增加和生存状况恶化相关。这些发现表明,临床 I 期 NSCLC 患者应在该时间框架内接受迅速治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9605/8160592/721205991e53/jamanetwopen-e2111613-g001.jpg

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