Tirtei Elisa, Michelsen Sascha Wilk, Haveman Lianne M, Meazza Cristina, Oliveira Joana F, Rasool Ayesha, Palmerini Emanuela, Wilson Will, Gaspar Nathalie, Strauss Sandra J, Papakonstantinou Andri, Baecklund Fredrik
Department of Pediatric Oncology, Regina Margherita Children's Hospital, Turin, Italy.
Department of Pediatric and Adolescence Medicine, Clinic for Pediatric Oncology and Hematology, University Hospital Rigshospitalet, Copenhagen, Denmark.
Cancer Med. 2025 Jul;14(14):e71044. doi: 10.1002/cam4.71044.
Pretreatment prognostic factors in newly diagnosed osteosarcoma are important for clinical management and stratifying patients in clinical trials. Such factors include the presence of metastases, primary tumor size, and site. Factors surrounded by controversy include pathological fracture, histologic subtype, and P-glycoprotein expression. No prognostic tumor biomarker has been established. We performed a systematic review with the aim to compile available evidence for pretreatment prognostic factors and define optimal cut-off values for patient stratification or further validation in the upcoming European FOSTER-CabOS trial.
Predefined search terms were used to search PubMed, Web-of-science, and Embase for all studies investigating pretreatment prognostic factors in newly diagnosed osteosarcoma patients published 2000-2023. After applying strict inclusion and exclusion criteria, 49 papers were included.
We found 14 factors investigated in at least two separate studies or in a single study using one discovery and at least one validation cohort.
We confirmed the prognostic value of patient age, presence of metastasis, tumor size, and site (axial vs. appendicular). Future studies of these factors should focus on specific patient populations and defining optimal cut-off values. Although serum level of alkaline phosphatase and lactate dehydrogenase were associated with outcome, it remains unclear if they are independent of other prognostic factors. The prognostic value remains unclear for sex, pathological fracture, histologic subtype, and P-glycoprotein expression. We could not establish any new prognostic biomarker. However, circulating tumor DNA in plasma and the G1/G2 RNA signature in diagnostic tumor biopsies show promise and will be further validated in the upcoming FOSTER-CabOS trial.
新诊断骨肉瘤的预处理预后因素对于临床试验中的临床管理和患者分层很重要。这些因素包括转移灶的存在、原发肿瘤大小和部位。存在争议的因素包括病理性骨折、组织学亚型和P-糖蛋白表达。尚未建立预后肿瘤生物标志物。我们进行了一项系统评价，旨在汇总预处理预后因素的现有证据，并为即将开展的欧洲FOSTER-CabOS试验中的患者分层或进一步验证确定最佳临界值。
使用预定义的检索词在PubMed、Web of Science和Embase中检索2000年至2023年发表的所有研究新诊断骨肉瘤患者预处理预后因素的研究。在应用严格的纳入和排除标准后，纳入了49篇论文。
我们发现至少在两项独立研究中或在一项使用一个发现队列和至少一个验证队列的单一研究中研究了14个因素。
我们证实了患者年龄、转移灶的存在、肿瘤大小和部位（轴向与附肢）的预后价值。对这些因素的未来研究应侧重于特定患者群体并确定最佳临界值。尽管碱性磷酸酶和乳酸脱氢酶的血清水平与预后相关，但它们是否独立于其他预后因素仍不清楚。性别、病理性骨折、组织学亚型和P-糖蛋白表达的预后价值仍不清楚。我们未能建立任何新的预后生物标志物。然而，血浆中的循环肿瘤DNA和诊断性肿瘤活检中的G1/G2 RNA特征显示出前景，并将在即将开展的FOSTER-CabOS试验中进一步验证。
