{"title":"基于组织学肿瘤坏死和坏死预测性临床与实验室参数的骨肉瘤患儿非高剂量甲氨蝶呤化疗骨干治疗结果","authors":"Badira Cheriyalinkal Parambil, Poonam Khemani, Ajay Puri, Ashish Gulia, Maya Prasad, Venkata Ram Mohan Gollamudi, Mukta Ramadwar, Bharat Rekhi, Poonam Panjwani, Prakash Nayak, Manish Pruthi, Sajid Qureshi, Nilendu Purandare, Amit Janu, Akash Pawar, Komal Adhav, Girish Chinnaswamy","doi":"10.1002/pbc.31471","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19822,"journal":{"name":"Pediatric Blood & Cancer","volume":" ","pages":"e31471"},"PeriodicalIF":2.4000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Outcomes Based on Histological Tumor Necrosis and Predictive Clinical and Laboratory Parameters for Necrosis in Children With Osteosarcoma Treated on a Non-High Dose Methotrexate-Based Chemotherapy Backbone.\",\"authors\":\"Badira Cheriyalinkal Parambil, Poonam Khemani, Ajay Puri, Ashish Gulia, Maya Prasad, Venkata Ram Mohan Gollamudi, Mukta Ramadwar, Bharat Rekhi, Poonam Panjwani, Prakash Nayak, Manish Pruthi, Sajid Qureshi, Nilendu Purandare, Amit Janu, Akash Pawar, Komal Adhav, Girish Chinnaswamy\",\"doi\":\"10.1002/pbc.31471\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Materials and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":19822,\"journal\":{\"name\":\"Pediatric Blood & Cancer\",\"volume\":\" \",\"pages\":\"e31471\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pediatric Blood & Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/pbc.31471\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Blood & Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/pbc.31471","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：据报道，以肿瘤坏死（TN）衡量的新辅助化疗（NACT）的组织病理学反应是高剂量甲氨蝶呤（HDMTX）化疗后的预后。我们在非hdmtx化疗骨干上进行了研究。材料与方法：回顾性分析2013年1月至2020年12月，≤15岁，采用OGS-2012方案治疗的骨肉瘤患儿和NACT术后手术患者。TN以百分比表示。基于不同TN截断值（以二分类方式将队列分为小于/大于特定截断值的两组）和预测TN的临床-实验室参数的结果进行了研究。结果：对258例患者进行了分析。截肢者占20.1%。中位TN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% （SE: 3.3%）和87.8% （SE: 2.4%）。在整个队列中，TN-70% （29.3% vs. 60.7%）、90% （38.7% vs. 69.0%）、100% （50.8% vs. 84.1%）是EFS的预后（p = 0.0001）， TN-90% （80.3% vs. 92.9%, p = 0.006）和100% （85.5% vs. 97.7%, p = 0.023）是OS的预后。对于局部疾病，TN-70%（35.4%对66.4%）、90%（41.6%对77.0%）、100%（54.8%对96.2%）是EFS （p = 0.0001）和OS （p = 0.0001）的预后指标。对于转移性疾病，TN-70%是EFS的预后指标（16.6%对50.1%,p = 0.0047）。患者-操作者曲线得出的截断值，EFS为85.5% TN， OS为83.5% TN，预测整体和局部队列最佳。对于转移性队列，84.5% TN最能预测EFS。在临床-实验室参数中，男性（OR: 1.9, p = 0.01）和截肢（OR: 2.1, p = 0.014）小于90% tn的风险较高。结论：即使在非hdmtx基础的骨干上，局部疾病90%截断点处的肿瘤坏死是生存的预后，但探索其他截断点的生存预测和预后价值可以指导中低收入国家未来的治疗修改策略和资源分配。截肢，男性预示着较差的组织学坏死。
Outcomes Based on Histological Tumor Necrosis and Predictive Clinical and Laboratory Parameters for Necrosis in Children With Osteosarcoma Treated on a Non-High Dose Methotrexate-Based Chemotherapy Backbone.
Background: 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.
Materials and methods: 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.
Results: 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.
Conclusions: 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.
期刊介绍：
Pediatric Blood & Cancer publishes the highest quality manuscripts describing basic and clinical investigations of blood disorders and malignant diseases of childhood including diagnosis, treatment, epidemiology, etiology, biology, and molecular and clinical genetics of these diseases as they affect children, adolescents, and young adults. Pediatric Blood & Cancer will also include studies on such treatment options as hematopoietic stem cell transplantation, immunology, and gene therapy.
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