Evaluation of response to neoadjuvant chemotherapy in osteosarcoma using dynamic contrast-enhanced MRI: development and external validation of a model

Abstract

Objective To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma. Methods Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort). Results Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81–0.97 with the whole slab and 0.57–0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75–0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86–1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80. Conclusion In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort.

Relative Wash-In Rate in Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a New Prognostic Biomarker for Event-Free Survival in 82 Patients with Osteosarcoma: A Multicenter Study

“…Of these, 53 were treated at the LUMC and 29 at the GUH. The entire study population of 82 patients was previously studied [ 9 , 10 ]. The first study provided an overview of survival and prognostic factors in 402 patients with skeletal high-grade osteosarcoma, including 53 patients from the current cohort [ 10 ].…”

“…The first study provided an overview of survival and prognostic factors in 402 patients with skeletal high-grade osteosarcoma, including 53 patients from the current cohort [ 10 ]. The second study described the development of the model, predicting the histological response to NAC in 85 osteosarcoma patients, incorporating 82 patients from the current cohort [ 9 ]. In this study, we report the potential of the rWIR as a prognostic factor for clinical outcomes and determine its added value to known prognostic factors.…”

“…The rWIR was calculated by dividing the maximum slope of contrast enhancement on the time–intensity curves (wash-in rate) from baseline imaging by the wash-in rate post-NAC. Details can be found in a previous study by Kalisvaart and Van Den Berghe et al [ 9 ]. A prior study by Evenhuis et al [ 10 ] identified prognostic factors for survival in 402 patients treated for a skeletal high-grade osteosarcoma at the LUMC between 1978 and 2017.…”

“…For the current study, patient records were reviewed by the local investigator to obtain demographics, treatment details, and clinical outcomes. Baseline variables included sex, age group (children: 0–<16 years; adolescents and young adults [AYA]: 16–<40 years; older adults: ≥40 years), tumor location, tumor size (≤8 cm or >8 cm), metastases at presentation, histological response according to the Huvos classification (poor response: ≥10% viable tumor cells; good response: <10% viable tumor cells and >90% response) and rWIR [ 4 , 9 ]. The rWIR was analyzed both as a dichotomous variable (rWIR < 2.3 indicated a poor radiological response, and rWIR ≥ 2.3 indicated a good radiological response) and as a continuous variable to evaluate the potential of rWIR to overcome the limitation of the arbitrary threshold for poor response originating from the 10% viable cells threshold in the Huvos classification.…”

“…In a previous study, the relative wash-in rate (rWIR) was described to correlate with a histological response. The rWIR, derived from the baseline imaging’s maximum slope of contrast enhancement (wash-in rate) divided by the post-NAC wash-in rate observed on DCE-MRI time-intensity curves, reflects alterations in tumor perfusion before and after NAC [ 9 ]. Utilizing this technique, the response to NAC can be predicted before tumor resection.…”