Histopathological Response to Neoadjuvant Chemotherapy Assessed Using the Huvos Grading System and its Correlation with Pretreatment Clinicopathological Variables in Osteosarcoma: A Cohort Study from North East India

Abstract

Introduction: Osteosarcoma is the most common primary bone malignancy affecting children and young adults. Neoadjuvant Chemotherapy (NACT) followed by surgery is the current modality of treatment for osteosarcoma. Histological evaluation of extent of tumour necrosis on resection is a well-established prognostic indicator in osteosarcoma correlating with survival in most cases. Identification of pretreatment clinicopathological factors associated with histological response may facilitate early risk stratification and individualised treatment planning. Aim: To evaluate the histopathological response to NACT using the Huvos grading system and to determine its association with pretreatment clinicopathological variables in patients with osteosarcoma. Material and Methods: A cohort study was conducted in the Department of Oncopathology, Dr. B. Borooah Cancer Institute, Guwahati, Assam, India, including biopsy-proven osteosarcoma patients treated with NACT followed by definitive surgery between September 2022 and August 2025 (data were collected from this time period). Study period was September 2025 to April 2026. Clinical, biochemical, radiological and pathological data were retrieved from the Institutional electronic medical records. Histopathological response was assessed on resection specimens according to the Huvos grading system. Patients with Huvos grades III-IV were classified as good responders, whereas those with grades I-II were considered poor responders. Associations between clinicopathological variables and histological response were analysed using Fisher’s-exact test. Overall Survival (OS) was estimated using the Kaplan-Meier method. Statistical analysis was performed using IBM Statistical Package for Social Sciences (SPSS) Statistics for Windows, version 29.0 (IBM Corp., Armonk, NY, USA). Results: A total of 27 patients fulfilled the study inclusion criteria. The mean age was 23.2 years, with a male predominance (77.8%). The lower extremity was the most common site of involvement. A total of 4 patients (14.8%) were classified as good responders, while 23 patients (85.2%) were poor responders. No statistically significant association was observed between Huvos response and age, sex, tumour size, anatomical site, histological subtype, or serum alkaline phosphatase level (p>0.05). The median followup duration was 18 months (range: 8-45 months). Kaplan-Meier survival analysis demonstrated a trend towards improved OS among good responders; however, the difference between the survival curves was not statistically significant (log-rank p=0.321). Cox proportional hazards regression demonstrated a hazard ratio of 3.17 (95% CI: 0.29-34.99; p=0.347) for good responders compared with poor responders. Conclusion: Histopathological assessment using the Huvos grading system remains a practical and reliable method for evaluating response to NACT in osteosarcoma. In the present study, pretreatment clinicopathological variables were not significantly associated with histological response. Larger multicentric prospective studies incorporating molecular and radiological biomarkers are required to improve prediction of chemotherapy response before treatment initiation.