Indeterminate pulmonary nodules are not associated with worse overall survival in Ewing Sarcoma

Abstract

Aim: Lung metastases are a negative prognostic factor in Ewing sarcoma, however, the incidence and significance of sub-centimetre pulmonary nodules at diagnosis is unclear. The aims of this study were to (1): determine the incidence of indeterminate pulmonary nodules (IPNs) in patients diagnosed with Ewing sarcoma (2); establish the impact of IPNs on overall and metastasis-free survival and (3) identify patient, oncological and radiological factors that correlate with poorer prognosis in patients that present with IPNs on their staging chest CT.

Materials & methods: Between 2008 and 2016, 173 patients with a first presentation of Ewing sarcoma of bone were retrospectively identified from an institutional database. Staging and follow-up chest CTs for all patients with IPN were reviewed by a senior radiologist. Clinical and radiologic course were examined to determine overall- and metastasis-free survival for IPN patients and to identify demographic, oncological or nodule-specific features that predict which IPN represent true lung metastases.

Results: Following radiologic re-review, IPN were found in 8.7% of patients. Overall survival for IPN patients was comparable to those with a normal staging chest CT (2-year overall survival of 73.3% [95% CI 43.6-89] and 89.4% [95% CI 81.6-94], respectively; p = 0.34) and was significantly better than for patients with clear metastases (46.0% [95% CI 31.9-59]; p < 0.0001). Similarly, there was no difference in metastasis-free survival between 'No Metastases' and 'IPN' patients (p = 0.16). Lung metastases developed in 40% of IPN patients at a median 9.6 months. Reduction of nodule size on neoadjuvant chemotherapy was associated with worse overall survival in IPN patients (p = 0.0084).

Conclusion: IPN are not uncommon in patients diagnosed with Ewing sarcoma. In this study, we were unable to detect a difference in overall- or metastasis-free survival between patients with IPN at diagnosis and patients with normal staging chest CTs.

Keywords: Ewing sarcoma; Lung nodules; Survival.

Fig. 1

Flowchart that shows the cohort included in this study.

Fig. 2

This figure shows overall survival for patients with no metastases, IPN, or metastases at diagnosis. At 2 years, patients with IPNs had an overall survival of 73.3% while those with no metastases at diagnosis had an overall survival rate of 89.4% (p = 0.34). The worst outcomes were experienced by patients with metastases, whose 2-year overall survival was 46.0% (p < 0.001).

Fig. 3

This figure shows metastasis-free survival for patients with no metastases or IPNs at diagnosis. At 2 years, patients with IPNs had a metastasis-free survival of 60% while those with normal staging chest CTs had a metastasis-free survival of 84.3% (p = 0.16).

Fig. 4

(a) This figure shows an example of reduction in size of an IPN on neoadjuvant chemotherapy. Shown is a representative slice from a T2-weighted MRI of an 11-year-old male with Ewing sarcoma of the proximal phalanx of his great toe. Staging chest CT revealed greater than 5 IPN, the largest measuring 8 mm in diameter. The IPN decreased in size while on neoadjuvant chemotherapy and then progressed at 8.9 months post-diagnosis. The patient died of disease 16.0 months after diagnosis. (b) This figure shows an example of IPN stability. Shown is a representative slice from a T2-weight MRI of a 33-year-old male with Ewing sarcoma of the left hemipelvis. He had a single 2 mm IPN on staging chest CT that did not change in size on neoadjuvant chemotherapy. He did not develop metastases and was alive, free of disease 61.3 months post-diagnosis.

Fig. 5

This figure shows overall survival for IPN patients whose nodules reduced in size (IPN smaller) or remained the same size (IPN stable) following neoadjuvant chemotherapy. No patients had IPN that increased in size during this period.