Parambil Badira Cheriyalinkal, Khemani Poonam, Puri Ajay, Gulia Ashish, Prasad Maya, Gollamudi Venkata Ram Mohan, Ramadwar Mukta, Rekhi Bharat, Panjwani Poonam, Nayak Prakash, Pruthi Manish, Qureshi Sajid, Purandare Nilendu, Janu Amit, Pawar Akash, Adhav Komal, Chinnaswamy Girish
Division of Pediatric Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India.
Department of Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India.
Pediatr Blood Cancer. 2025 Mar;72(3):e31471. doi: 10.1002/pbc.31471. Epub 2024 Dec 15.
Histopathological response to neoadjuvant chemotherapy (NACT) measured as tumor necrosis (TN) has been reported to be prognostic post-high-dose methotrexate (HDMTX)-based chemotherapy. We studied this on a non-HDMTX chemotherapy backbone.
Children ≤15 years, with osteosarcoma treated on OGS-2012 protocol and surgery post NACT from January 2013 to December 2020 were retrospectively analyzed. TN was expressed as percentage. Outcomes based on different TN cutoffs (used in a dichotomized manner dividing the cohort into two groups of less than/greater than the particular cutoff) and clinical-laboratory parameters predictive of TN were studied.
Analysis was done in 258 patients. Amputation was performed in 20.1%. Median TN was 94%. At a median follow-up of 38 months (range: 34-45 months), 3-year event free survival (EFS) and overall survival (OS) of the whole cohort were 56.1% (SE: 3.3%) and 87.8% (SE: 2.4%). For entire cohort, TN-70% (29.3% vs. 60.7%), 90% (38.7% vs. 69.0%), 100% (50.8% vs. 84.1%), were prognostic for EFS (p = 0.0001), while TN-90% (80.3% vs. 92.9%, p = 0.006) and 100% (85.5% vs. 97.7%, p = 0.023) were prognostic for OS. For localized disease, TN-70% (35.4% vs. 66.4%), 90% (41.6% vs. 77.0%), 100% (54.8% vs. 96.2%) were prognostic for EFS (p = 0.0001) and OS (p = 0.0001). For metastatic disease, TN-70% was prognostic for EFS (16.6% vs. 50.1%, p = 0.0047). Receiver-operator curve derived cutoff of 85.5% TN for EFS, 83.5% TN for OS prognosticated whole and localized cohorts the best. For metastatic cohort, 84.5% TN best prognosticated EFS. Among clinical-laboratory parameters, male gender (OR: 1.9, p = 0.01) and amputation (OR: 2.1, p = 0.014) had a higher risk of less than 90% TN.
Tumor necrosis at 90% cutoff in localized disease is prognostic of survival even on a non-HDMTX-based backbone, but exploring other cutoffs for survival predictive and prognostic value could guide future treatment modification strategies and resource allocation in LMICs. Amputation, male gender predicts poor histological necrosis.
据报道，以肿瘤坏死（TN）衡量的对新辅助化疗（NACT）的组织病理学反应是基于大剂量甲氨蝶呤（HDMTX）化疗后的预后指标。我们在非HDMTX化疗方案基础上对此进行了研究。
回顾性分析2013年1月至2020年12月期间，按照OGS - 2012方案接受治疗且在NACT后进行手术的15岁及以下骨肉瘤患儿。TN以百分比表示。研究了基于不同TN临界值（以二分法将队列分为低于/高于特定临界值的两组）的预后情况以及预测TN的临床实验室参数。
对258例患者进行了分析。截肢率为20.1%。TN中位数为94%。在中位随访38个月（范围：34 - 45个月）时，整个队列的3年无事件生存率（EFS）和总生存率（OS）分别为56.1%（标准误：3.3%）和87.8%（标准误：2.4%）。对于整个队列，TN - 70%（29.3%对60.7%）、90%（38.7%对69.0%）、100%（50.8%对84.1%）对EFS具有预后意义（p = 0.0001），而TN - 90%（80.3%对92.9%，p = 0.006）和100%（85.5%对97.7%，p = 0.023）对OS具有预后意义。对于局限性疾病，TN - 70%（35.4%对66.4%）、90%（41.6%对77.0%）、100%（54.8%对96.2%）对EFS（p = 0.0001）和OS（p = 0.0001）具有预后意义。对于转移性疾病，TN - 70%对EFS具有预后意义（16.6%对50.1%，p = 0.0047）。受试者工作特征曲线得出的TN临界值为85.5%时对EFS预后最佳，83.5%时对整个队列和局限性队列的OS预后最佳。对于转移性队列，TN为84.5%时对EFS预后最佳。在临床实验室参数中，男性（比值比：1.9，p = 0.01）和截肢（比值比：2.1，p = 0.014）发生TN低于90%的风险较高。
即使在非HDMTX方案基础上，局限性疾病中TN达到90%临界值对生存具有预后意义，但探索其他用于生存预测和预后价值的临界值可为低收入和中等收入国家（LMICs）未来的治疗调整策略和资源分配提供指导。截肢、男性预示着组织学坏死较差。
