The clinical significance of indeterminate pulmonary nodules in melanoma patients at baseline and during follow-up chest CT

Abstract

Objective: This study aims to determine an appropriate timeline to monitor indeterminate pulmonary nodules (IPN) in melanoma patients to confirm metastatic origin.

Materials and methods: 588 clinically non-metastatic melanoma patients underwent curative intent surgery during 3 years. Patients with baseline chest CT and at least one follow-up (FU) CT were retrospectively analyzed to assess for IPN. Patients with definitely benign nodules, metastases and non-melanoma malignancies were excluded. Change in volume from first to FU CT, initial diameter (D1) and volume (V1), distance from pleura, peripheral and perifissural location, density and clinical stage were evaluated. Nodules were volumetrically measured on CTs and were considered metastases if they increased in size between two CTs or if increase was accompanied by multiple new nodules or extrapulmonary metastases.

Results: 148 patients were included. Two out of 243 baseline IPN detected in 70 patients, increased significantly in volume in 3 and 5 months and were proven metastases. During FU, 86% of 40 interval IPN detected in 28 patients, were proven metastases. Interval nodule (p < 0.0001, HR:243,CI:[57.32,1033.74]), 3-month volume change (OR:1.023,CI:[1.014,1.033]), V1 (OR:1.006,CI:[1.003,1.009]), D1 (OR:1.424,CI:[1.23,1.648]), distance from pleura (OR:1.03,CI:[1.003,1.059]), and combined stage IIC + III (OR:11.29,CI:[1.514,84.174]), were associated with increased risk for metastasis. 43%, 72% and 94% of patients with IPN were confirmed with metastases in the first FU CT at 3, 6 and 12 months respectively.

Conclusion: Baseline IPN are most likely benign, while interval IPN are high risk for metastasis. Absence of volume increase of IPN within 6 months excluded metastasis in most patients.

Keywords: FU, follow-up; GGO, ground glass opacity; IPN, indeterminate pulmonary nodules; Melanoma; Metastasis; Multiple pulmonary nodules; X-ray computed tomography.

Fig. 1

Flowchart showing the detection of IPN nodules at baseline chest CT (baseline IPN*) and during follow-up (interval IPN). *IPN: indeterminate pulmonary nodule.

Fig. 2

ROC curves of the regression analysis for significant independent univariable parameters: a) % increase V2**-V1*/V1, b) initial V1, c) initial D1***. *V1: volume of nodule at initial CT, **V2: volume of nodule at first follow-up CT, ***D1: diameter of nodule at initial CT.

Fig. 3

Kaplan-Meier plot shows time to event analysis for patients with an IPN nodule found at baseline chest CT (blue graph), or with an IPN nodule found at baseline and or during follow up (red graph) to be confirmed having pulmonary metastatic disease (event). Y axis shows the probability of not being confirmed with pulmonary metastatic disease and x axis shows the time to event (in months). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).