Persistence of CD30 expression by embryonal carcinoma (EC) in the treatment time course: A retrospective series of multirelapsing germ cell tumors (GCT).

Abstract

329 Background: CD30 is invariably expressed by untreated EC thus lending support to a rationale for a targeted approach. However, preliminary reports claimed an effect of chemotherapy (CT)-induced downmodulation of CD30 that might affect the potential use in relapsing disease. We aimed at evaluating the persistence of CD30-positivity in post-CT residuals. Methods: We retrieved paraffin-embedded post-CT samples yielding non-teratoma viable cells after ≥ 1 CDDP-based CT from the institutional surgical series. EC component was required and assessed by morphology and Oct-3/4 staining. The entire set was re-stained for CD30 and assessed by 2 pathologists blinded to study purpose. CD30-positivity was defined as a >80% membranous staining with a diffuse moderate-to-strong intensity. Clinical data included site of tumor primary, histology, CT regimen, and type of surgery. Results: From 12/1990 to 09/2012, a total of 246 cases with pure EC or mixed GCT residuals were treated. 49 (EC: 16; mixed GCT: 33) had both complete data and suitable tissue for study purposes. 40 pts had retroperitoneal or mediastinal nodes, 12 pts had lung metastases, 4 had either liver, bone or brain mets. 35/49 cases (70%) preserved CD30 positivity. 20/35 (57%) pts had residual disease after 1stline CT, 15/35 (43%) after multiple CTs (median 3.5, range 2-5). 2 pts (6%) had undergone high-dose CT and 4/35 (11%) were late relapses. 32/35 pts (91%) had gonadal primary, 1 had a retroperitoneal and another a mediastinal primary. The median survival of 35 CD30-positive patients was 16 mos (IQR 3.3-22.9) while it was 48.5 mos (IQR 21.7-72.6) for the 14 CD30-negative patients (p=0.0297 at Gehan-Breslow-Wilcoxon test). 5-year overall survival of CD30-positive and negative patients was 35.7% (95% CI: 18.2-53.6) and 49.7% (95% CI: 19.7-74.0), respectively. Conclusions: Our results on selected relapsing pts suggest that EC retained CD30 even in the far salvage setting, thus confirming to be a reliable target for treatment. A trend towards a poorer prognosis and shorter survival characterized CD30+ cases. A phase 2 study with the antibody-drug conjugate Brentuximab vedotin is currently in plan for GCT.