loading page

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
  • +14
  • BADIRA CHERIYALINKAL PARAMBIL,
  • Poonam Khemani,
  • Ajay Puri,
  • Ashish Gulia,
  • Maya Prasad,
  • Venkata Gollamudi,
  • Mukta Ramadwar,
  • Bharat Rekhi,
  • Poonam Panjwani,
  • Prakash Nayak,
  • Manish Pruthi,
  • Nilendu Purandare,
  • Amit Janu,
  • Akash Pawar,
  • Komal Adhav,
  • Girish Chinnaswamy,
  • Sajid Qureshi
BADIRA CHERIYALINKAL PARAMBIL
Tata Memorial Centre
Author Profile
Poonam Khemani
Tata Memorial Centre
Author Profile
Ajay Puri
Tata Memorial Centre
Author Profile
Ashish Gulia
Tata Memorial Centre
Author Profile
Maya Prasad
Tata Memorial Centre
Author Profile
Venkata Gollamudi
Tata Memorial Centre
Author Profile
Mukta Ramadwar
Tata Memorial Centre
Author Profile
Bharat Rekhi
Tata Memorial Centre
Author Profile
Poonam Panjwani
Tata Memorial Centre
Author Profile
Prakash Nayak
Tata Memorial Centre
Author Profile
Manish Pruthi
Tata Memorial Centre
Author Profile
Nilendu Purandare
Tata Memorial Centre
Author Profile
Amit Janu
Tata Memorial Centre
Author Profile
Akash Pawar
Tata Memorial Centre
Author Profile
Komal Adhav
Tata Memorial Centre
Author Profile
Girish Chinnaswamy
Tata Memorial Centre

Corresponding Author:[email protected]

Author Profile
Sajid Qureshi
Tata Memorial Centre
Author Profile

Abstract

1 Background Histopathological response to neoadjuvant-chemotherapy(NACT) measured as tumor necrosis(TN) has been reported to be prognostic of outcomes post HDMTX- based chemotherapy. We studied outcomes based on different cut-offs of TN and delineated clinical-laboratory parameters predictive of TN on a non-HDMTX chemotherapy backbone. 2 Materials and Methods Children ≤15years, with osteosarcoma treated on OGS-2012 protocol and surgery post-NACT from January 2013-December 2020 were retrospectively analysed. TN was reported as percentage necrosis. Kaplan-Meier, log-rank, Pearson’s Chi-square tests were used. 3 Results Analysis was done in 258 patients. Median age-12years(range,3-15years), M:F-1.7:1. Amputation was performed in 20.1%. Median TN was 94%. At a median follow-up of 38months(range,34-45months), 3year 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%vs60.7%), 90% (38.7%vs69.0%), 100%(50.8%vs84.1%), were prognostic for EFS(p=0.0001), while TN-90%(80.3%vs92.9%,p=0.006) and 100%(85.5%vs97.7%,p=0.023) were prognostic for OS. For localized disease, TN-70%(35.4%vs 66.4%), 90%(41.6%vs77.0%), 100%(54.8%vs96.2%) were prognostic for EFS(p=0.0001), and OS(p=0.0001). For metastatic disease, TN-70% was prognostic for EFS(16.6%vs50.1%,p=0.0047). Receptor-Operator Curve derived cut-off 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), amputation (OR:2.1,p=0.014) had a higher risk of <90%TN. 4 Conclusions Tumor necrosis at 90% cut-off in localized disease is prognostic of survival on a non-HDMTX based backbone, though best outcomes are seen with 100%TN, but 70%TN and other cut-offs require further exploration. A lower cut-off of 70%(or other) in metastatic disease could be used for prognostication. Amputation, male gender predicts poor histological necrosis.
07 Feb 2024Submitted to Pediatric Blood & Cancer
07 Feb 2024Assigned to Editor
07 Feb 2024Submission Checks Completed
13 Feb 2024Reviewer(s) Assigned