Roy Prabhat Gautam, Ganguly Shuvadeep, Sasi Archana, Kumar Vivek, Barwad Adarsh, Mridha Asit Ranjan, Khan Shah Alam, Kumar Venkatesan Sampath, Kapoor Love, Pushpam Deepam, Bakhshi Sameer
Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Department of Medical Oncology, Jawaharlal Institute of Post-graduate Medical Education and Research (JIPMER), Pondicherry, India.
J Bone Oncol. 2024 Nov 24;49:100651. doi: 10.1016/j.jbo.2024.100651. eCollection 2024 Dec.
Response to neoadjuvant chemotherapy in form of tumor necrosis predicts outcome in osteosarcoma; although response-adapted treatment escalation failed to improve outcome among patients treated with high-dose methotrexate-based (HDMTx) chemotherapy. This study aimed to identify factors predicting tumor necrosis and its impact on survival among patients with non-metastatic osteosarcoma treated with a response-adapted non-HDMTx regimen.
A retrospective single-institutional study was conducted among non-metastatic osteosarcoma patients treated with neoadjuvant therapy between 2004-2019. Patients were treated uniformly with three cycles of neoadjuvant cisplatin/doxorubicin. Post-operatively, patients with favourable necrosis (≥90 %) received 3 cycles of cisplatin/doxorubicin, while patients with poor necrosis (<90 %) received escalated treatment with alternating six cycles of cisplatin/doxorubicin and ifosfamide/etoposide. Propensity score matching (PSM) analyses were conducted to ascertain independent impact of necrosis on event-free survival (EFS) and overall survival (OS).
Of 594 registered osteosarcoma patients, 280 patients (median age 17 years; male 67.1 %) were included for analysis. 73 patients (26.1 %) achieved favourable necrosis. Patients with smaller tumor size (≤10 cm) (aOR = 2.28; p = 0.030), lower serum alkaline phosphatase (≤450 IU/L) (aOR = 2.10; p = 0.035), and who had surgery earlier (<115 days) (aOR = 2.28; p = 0.016) were more likely to have favourable necrosis. On 1:2 PSM analysis, patients not achieving favourable necrosis demonstrated inferior EFS (HR = 2.68; p = 0.003) and OS (HR = 3.42; p = 0.003).
Patients of osteosarcoma with smaller tumor, lower serum alkaline phosphatase and earlier surgery are more likely to achieve favourable necrosis. Tumor necrosis independently predicts outcome in osteosarcoma, and response-adapted treatment escalation fails to overcome the adverse impact of poor necrosis in non-HDMTx based regimen.
肿瘤坏死形式的新辅助化疗反应可预测骨肉瘤的预后；尽管基于高剂量甲氨蝶呤（HDMTx）化疗的反应适应性治疗强化未能改善患者的预后。本研究旨在确定预测肿瘤坏死的因素及其对接受反应适应性非HDMTx方案治疗的非转移性骨肉瘤患者生存的影响。
对2004年至2019年间接受新辅助治疗的非转移性骨肉瘤患者进行回顾性单机构研究。患者均接受三个周期的新辅助顺铂/阿霉素治疗。术后，坏死情况良好（≥90%）的患者接受三个周期的顺铂/阿霉素治疗，而坏死情况较差（<90%）的患者接受强化治疗，交替进行六个周期的顺铂/阿霉素和异环磷酰胺/依托泊苷治疗。进行倾向评分匹配（PSM）分析，以确定坏死对无事件生存期（EFS）和总生存期（OS）的独立影响。
在594例登记的骨肉瘤患者中，280例患者（中位年龄17岁；男性占67.1%）纳入分析。73例患者（26.1%）坏死情况良好。肿瘤较小（≤10 cm）（调整后比值比[aOR]=2.28；p=0.030）、血清碱性磷酸酶较低（≤450 IU/L）（aOR=2.10；p=0.035）且手术较早（<115天）（aOR=2.28；p=0.016）的患者更有可能坏死情况良好。在1:2 PSM分析中，坏死情况不佳的患者EFS较差（风险比[HR]=2.68；p=0.003），OS也较差（HR=3.42；p=0.003）。
肿瘤较小、血清碱性磷酸酶较低且手术较早的骨肉瘤患者更有可能坏死情况良好。肿瘤坏死可独立预测骨肉瘤的预后，基于非HDMTx方案的反应适应性治疗强化未能克服坏死情况不佳的不利影响。
