High Resolution Chest Computed Tomography Responses for a Cohort of Erdheim–Chester Disease Patients with Pulmonary Involvement

Background and aims: Erdheim–Chester disease (ECD) is a heterogeneous histiocytosis with various pulmonary manifestations and imaging. We aim to evaluate the pulmonary response of ECD by high resolution chest computed tomography (HRCT) through continuous follow-up.

Methods: We conducted a retrospective analysis of ECD patients with pulmonary involvement diagnosed between January 2013 and January 2023. HRCT response was assessed by the change of HRCT global score (lung score plus pleura score) between the baseline and after therapy. All HRCT scans were collected and interpreted independently by two pulmonologists; mean values obtained from the two readers were used for analysis. For each HRCT scan, a semiquantitative analysis assessed the extent of radiology imaging abnormalities. First, they independently scored all the chest HRCT scans and then established a global score, summing the lung and pleura subtotals. The lung score included five radiology imaging features: ground-glass opacities, interlobular septal thickening, parenchyma consolidations, nodules and cyst. The pleura score included two imaging features: pleura thickening and pleura effusion. The chest was divided into six fields (upper, middle, and lower of the left and right lungs). Each kind of imaging feature was scored separately according to the numbers of field involved. The maximum score for the extent of lung and pleura was 30 and 12, respectively.

Results: A total of 33 evaluable patients with pre- and post-therapy HRCT were included, with a median age of 52 years (range, 9–66). All patients had multi-system ECD with pulmonary involvement. BRAF^V600E mutation was detected in 78.1% patients. The most common HRCT findings were ground-glass opacities (n=32, 97.0%), thickening of interlobar fissures (n=22, 66.7%), interlobular septal thickening (n=19, 57.6%), consolidation (n=12, 36.4%), micronodules (n=18, 54.5%) and thin-wall cyst (n=7, 21.2%). Pleural involvement was observed in 31 patients (93.9%). Patients with BRAF^V600E alternations had a higher lung score (12.3 vs. 8.0, p=0.093) and pleura score (5.3 vs. 2.7, p=0.0045) at baseline. Regarding treatment regimens, 17 patients (51.5%) received interferon-α (IFN-α), 14 (42.4%) underwent target therapy. The ORR was 69.7%, with 7 patients (21.2 %) achieving a CR, 16 patients (48.5 %) achieving a PR. After therapy, the mean global score decreased from 15.8 to 11.1 (p < 0.0001) and the mean lung score decreased significantly, from 11.2 to 8.2 (p = 0.0002), while the mean pleura score also decreased significantly, from 4.6 to 2.9 (p < 0.0001). Overall, the global score decreased (HRCT response) in 21 patients (63.6%) and increased (HRCT progression) in 6 patients (18.2%) after therapy. Among patients with CR or PR, 100% and 81.3%, respectively, experienced an HRCT response, whereas 1/10 patients with SD or PD had an HRCT response (p < 0.0001). The estimated 5-year overall survival was 94.5% and the estimated median progression-free survival (PFS) was 138.6 months. Univariate prognostic analyses for PFS showed that patients with HRCT response (59.8 vs 31.1 months, p=0.035) after therapy have significantly better PFS, patients with a baseline number of organ involvement below 5 (48.0 vs. 25.8 months, p=0.075) and treated with target therapy (median PFS not reached vs. 33.6 months, p=0.062) and patients who achieved CR (not reached vs 33.6 months, p=0.062) tended to have better PFS. Patients with pleura effusions tended to have a poorer prognosis (39.2 months vs not reached, p=0.085).

Conclusion: Patients with BRAF^V600E exhibits higher HRCT global score. The lung and pleura score of HRCT significantly decreases after therapy. More patients with CR and PR or treated with target therapy had HCRT response. Patients achieving HRCT response predicted better outcomes.