Multiple Indeterminate pulmonary nodules (IPNs) as independent prognostic indicators in pediatric osteosarcoma: A ten-year retrospective study

Abstract

Background: Osteosarcoma is the most common primary malignant bone tumor in pediatric and adolescent patients. Although pulmonary metastasis is a key driver of prognosis, the role of IPNs in risk stratification remains inadequately defined.

Objective: This study aims to assess the incidence, progression, and prognostic significance of IPNs in pediatric and adolescent osteosarcoma patients, providing insights for clinical staging and treatment strategy development.

Methods: We retrospectively analyzed clinical data from 126 osteosarcoma patients aged 20 years or younger who were treated at Henan Cancer Hospital between January 2012 and January 2022. Pre-treatment thin-slice computed tomography (CT) scans of lung were used to categorize patients into three groups: no IPN (n = 100), solitary IPN (n = 16), and multiple IPNs (n = 10). Baseline characteristics, primary tumor parameters, treatment modalities, and follow-up data were collected. Univariate and multivariate analyses were conducted to assess risk factors and survival outcomes.

Results: The overall incidence of IPNs was 20.6 %, with multiple IPNs accounting for 38.5 % of the IPN-positive cases. A significantly higher proportion of patients in the IPN-positive group had bone involvement exceeding one-third of the total affected bone compared to the no-IPN group (57.7 % vs. 34.0 %, p = 0.016). While univariate analysis suggested a potential association between tumor diameter > 8 cm and IPN occurrence (odds ratio [OR] = 2.08, 95 % confidence interval [CI]: 0.83-5.21, p = 0.120), this was not statistically significant in multivariate analysis (OR = 3.61, p = 0.283). Kaplan-Meier survival analysis revealed that the 3-year metastasis-free survival (MFS) and overall survival (OS) rates in the IPN-positive group were significantly lower than those in the no-IPN group (MFS: 57.7 % vs. 64.0 %, p = 0.03; OS: 65.4 % vs. 76.0 %, p = 0.04). Further subgroup analysis indicated that while solitary IPN cases had survival outcomes comparable to those without IPNs, multiple IPN cases exhibited a markedly reduced 5-year OS (30.0 % vs. 69.0 %, p = 0.045). Cox regression analysis demonstrated that multiple IPNs increased the risk of death by 2.87-fold (hazard ratio [HR] = 2.87, p = 0.020).

Conclusion: Indeterminate Pulmonary Nodules are relatively common in pediatric osteosarcoma patients. In particular, multiple IPNs are strongly associated with a higher tumor burden and increased metastatic potential, serving as an independent indicator of poor prognosis. These findings emphasize the importance of preoperative IPN assessment and risk stratification in guiding individualized treatment strategies.

Keywords: Adolescents; Indeterminate Pulmonary Nodules (IPNs); Osteosarcoma; Prognosis.

Fig. 1

Kaplan–Meier Curve for Metastasis-Free Survival (MFS) of pediatric osteosarcoma patients in three groups: no IPNs (no）, with a solitary IPN （Mono）, and with multiple IPNs (Muti). The log-rank test indicates a significant difference among the groups (p = 0.04).

Fig. 2

Kaplan–Meier Curve for Overall Survival (OS) of pediatric osteosarcoma patients in three groups: no IPNs (no）, with a solitary IPN （Mono）, and with multiple IPNs (Muti). The log-rank test indicates a significant difference among the groups (p = 0.045).

Fig. 3

Case 1. A 14-year-old female patient with distal femoral osteosarcoma. At initial presentation, an Indeterminate Pulmonary Nodule (IPN) was detected in the left lower lung, which remained unchanged over a 3-year follow-up period.

Fig. 4

Case 2. A 20-year-old female patient with proximal humeral osteosarcoma. At initial presentation, an IPN was identified in the left upper lung; following 2 months of chemotherapy, the nodule markedly decreased in size, but after 6 months of treatment and a 1-month treatment pause, the IPN increased in size and continued to enlarge after a subsequent 2-month pause, with biopsy confirming osteosarcoma metastasis.

Fig. 5

Case 3. A 13-year-old male patient with distal tibial osteosarcoma. At initial presentation, multiple scattered IPNs were detected in the left lower lung; after treatment and a 5-month follow-up, these nodules significantly increased in size, and imaging studies confirmed pulmonary metastasis.