Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi-institutional study

Abstract

Background: In this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi-institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis-free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma.

Methods: This study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513).

Results: A patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS.

Conclusions: The nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery.

Keywords: external validation; nomogram; osteosarcoma; prognosis; survival.

Figure 1

Kaplan‐Meier curves for (A) metastasis‐free survival and (B) overall survival for all patients.

Figure 2

Nomogram predicting the probability of (A) distant metastasis and (B) overall survival at 3 and 5 years. The patient's value for each variable is plotted on the appropriate scale, and vertical lines are drawn to the line of points to obtain the corresponding scores. All scores should be summed to obtain the total point score. The total point score on the total point line is plotted, and a vertical line is drawn down to the bottom line. The corresponding value shows the predicted probability of distant metastasis or death.

Figure 3

Calibration plot for 3‐year probabilities of (A) distant metastasis and (B) death for external validation.