MethodsA detailed description of our study method is provided in the supporting information. An event-enriched cohort was created to increase the number of patients with relapsed disease and consequently the statistical power of this study. We collected 73 samples of children (23 relapses/50 complete remission) diagnosed with cHL at the Erasmus Medical Center - Sophia Children’s Hospital. We analyzed CD15, CD30, PAX5, TARC and PD-L1 expression levels on the HRS cells, and PD-1+, PD-L1+, CD68+ and CD163+ cell counts in the TME. Primary outcome was the event free survival (EFS). The secondary outcome was the achievement of complete remission at interim PET scan and/or computed tomography (CT).
Results Sixty-seven of 73 patients met the inclusion criteria (Supplemental Figure S1). Baseline characteristics are presented in Supplemental Table S1. The mean follow-up time was 5.4 years (range 1.6 – 7.2 years). Twenty-two patients experienced treatment failure (32.8%), five of these patients (7.5%) passed away. We found no association between the expression of any of the immunohistochemical markers and EFS (Supplemental Table S2). All markers besides CD163 had an area under the curve (AUC) of < 0.5 and CD163 had an AUC of 0.613, suggesting a poor discrimination ability (Figure 1). Additional stacked histograms showed that none of the markers had discriminative power for EFS (Figure 1). There was also no association between any of the markers and early versus late relapse (Supplemental Table S3)
Thirty patients (44.8%) did not achieve complete remission (CR) at interim PET scan. Significantly more females than males achieved CR (Odds Ratio (OR) 3.60, 95% CI 1.31 – 9.90, p = 0.012). Patients with lower stage were more likely to achieve CR at interim PET-scan (OR 2.97, 95% CI 1.08 – 8.18, p = 0.033). For the total group, there were no statistically significant differences in achievement of CR at the interim PET scan for expression of any of the markers (Supplemental Table S4). A sub-analysis, only including patients treated according to the EuroNet-PHL protocols (n=45), showed that low expression of PD-L1 in the TME was significantly associated with complete remission (p = 0.04) (Table 1).