Ferrari Andrea, Lo Vullo Salvatore, Giardiello Daniele, Veneroni Laura, Magni Chiara, Clerici Carlo Alfredo, Chiaravalli Stefano, Casanova Michela, Luksch Roberto, Terenziani Monica, Spreafico Filippo, Meazza Cristina, Catania Serena, Schiavello Elisabetta, Biassoni Veronica, Podda Marta, Bergamaschi Luca, Puma Nadia, Massimino Maura, Mariani Luigi
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Unit of Clinical Epidemiology and Trial Organization, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Pediatr Blood Cancer. 2016 Mar;63(3):479-85. doi: 10.1002/pbc.25833. Epub 2015 Nov 24.
The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools.
To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS.
Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, non-rhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61).
Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients.
诊断延迟对患者预后的潜在影响是儿科肿瘤学中一个存在争议的问题,目前已发表的结果并不一致。我们试图通过使用创新的统计工具分析一系列连续的351例实体恶性肿瘤儿童和青少年患者来解决这一问题。
为了处理症状出现到确诊的时间间隔与总生存期(OS)之间关联的非线性复杂性,构建了一种具有顺序二元分裂规则的回归树算法,并用于根据诊断延迟与OS之间的函数关系识别同质患者组。
识别出三个不同的组:A组,疾病局限且预后良好(5年总生存率85.4%);B组,局部或区域进展期或转移性疾病且预后中等(5年总生存率72.9%),包括神经母细胞瘤、肾母细胞瘤、非横纹肌肉瘤软组织肉瘤和生殖细胞肿瘤;C组,局部或区域进展期或转移性疾病且预后较差(5年总生存率45%),包括脑肿瘤、横纹肌肉瘤和骨肉瘤。症状出现到确诊的时间间隔与死亡风险之间的函数关系在三个亚组中有所不同,A组无关联(风险比[HR]:0.96),B组呈正线性关联(HR:1.48),C组呈负线性关联(HR:0.61)。
我们的分析表明,至少一部分患者在生存方面可以从早期诊断中获益。对于其他患者,肿瘤的内在侵袭性可能掩盖诊断延迟的潜在影响。基于这些发现,早期诊断仍应是儿童癌症患者的目标。