Abstract

BackgroundResponse evaluation of neoadjuvant chemotherapy (NACT) in patients with osteosarcoma is significant for the termination of ineffective treatment, the development of postoperative chemotherapy regimens, and the prediction of prognosis. However, histological response and tumour necrosis rate can currently be evaluated only in resected specimens after NACT. A preoperatively accurate, noninvasive, and reproducible method of response assessment to NACT is required. In this study, the value of multi-parametric magnetic resonance imaging (MRI) combined with machine learning for assessment of tumour necrosis after NACT for osteosarcoma was investigated.MethodsTwelve patients with primary osteosarcoma of limbs underwent NACT and received MRI examination before surgery. Postoperative tumour specimens were made corresponding to the transverse image of MRI. One hundred and two tissue samples were obtained and pathologically divided into tumour survival areas (non-cartilaginous and cartilaginous tumour viable areas) and tumour-nonviable areas (non-cartilaginous tumour necrosis areas, post-necrotic tumour collagen areas, and tumour necrotic cystic/haemorrhagic and secondary aneurismal bone cyst areas). The MRI parameters, including standardised apparent diffusion coefficient (ADC) values, signal intensity values of T2-weighted imaging (T2WI) and subtract-enhanced T1-weighted imaging (ST1WI) were used to train machine learning models based on the random forest algorithm. Three classification tasks of distinguishing tumour survival, non-cartilaginous tumour survival, and cartilaginous tumour survival from tumour nonviable were evaluated by five-fold cross-validation.ResultsFor distinguishing non-cartilaginous tumour survival from tumour nonviable, the classifier constructed with ADC achieved an AUC of 0.93, while the classifier with multi-parametric MRI improved to 0.97 (P = 0.0933). For distinguishing tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.83, while the classifier with multi-parametric MRI improved to 0.90 (P < 0.05). For distinguishing cartilaginous tumour survival from tumour nonviable, the classifier with ADC achieved an AUC of 0.61, while the classifier with multi-parametric MRI parameters improved to 0.81(P < 0.05).ConclusionsThe combination of multi-parametric MRI and machine learning significantly improved the discriminating ability of viable cartilaginous tumour components. Our study suggests that this method may provide an objective and accurate basis for NACT response evaluation in osteosarcoma.

Highlights

  • Response evaluation of neoadjuvant chemotherapy (NACT) in patients with osteosarcoma is significant for the termination of ineffective treatment, the development of postoperative chemotherapy regimens, and the prediction of prognosis

  • Our study suggests that this method may provide an objective and accurate basis for NACT response evaluation in osteosarcoma

  • We have previously demonstrated by statistical methods that there are no significant differences in apparent diffusion coefficient (ADC) values among the cartilaginous tumour survival areas, the post-necrotic collagenised areas, and the tumour necrosis cystic/haemorrhagic areas [17], suggesting that ADC could not be used to assess the necrosis of chondroblastic osteosarcoma

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Summary

Introduction

Response evaluation of neoadjuvant chemotherapy (NACT) in patients with osteosarcoma is significant for the termination of ineffective treatment, the development of postoperative chemotherapy regimens, and the prediction of prognosis. Histological response and tumour necrosis rate can currently be evaluated only in resected specimens after NACT. NACT response evaluation allows terminating ineffective treatments, developing surgical regimens, and adjusting postoperative chemotherapy regimens to achieve personalised treatment, thereby improving the overall treatment outcomes [3]. Postoperative pathological tumour necrosis rate is the main criterion to evaluate the efficacy of NACT [4], but is invasive and cannot be used for real-time monitoring during NACT, or for guiding the choice of surgical timing and surgical plan, as it can be performed only postoperatively [5, 6]. The method requires pathologists to conduct extensive information processing to interpret highly complex pathological images, making it cumbersome, costly, time-consuming, and subjective [7]

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