Marina Mencinger

Background: Adrenocortical carcinoma (ACC) is a rare cancer that presents significant diagnostic and therapeutic challenges. We analyzed the management and estimated survival of ACC patients in Slovenia over a 17-year period. Patients and methods: Patients registered in the National Cancer Registry and treated from 2000 to 2017 were included. The survival and prognostic factors were assessed using the Kaplan-Meier method and Cox regression, respectively. Results: Forty-eight patients were included in our analysis. At the time of diagnosis, 6%, 42%, 25% and 27% had stage according European Network for the Study of Adrenal Tumors (ENSAT) I, II, III and IV, respectively. Adjuvant treatment with mitotane was assigned to 18 of 34 potentially eligible patients. High-risk patients treated with adjuvant mitotane showed a reduced probability of death, although the difference was not statistically significant. Relapses had numerically higher rate of R1 resection and higher Ki67. Eleven patients underwent first-line therapy with etoposide, doxorubicin, cisplatin and mitotane (EDP-M). Their median progression-free survival was 4.4 months. The median overall survival of entire cohort was 28.9 and the median disease-specific survival (DSS) was 36.2 months. The 5-year DSS rate of ENSAT I, II, III and IV were 100%, 56%, 50% and 0%, respectively. The prognostic value of ENSAT stage and Helsinki score regarding overall survival was confirmed with the multivariate analysis. Conclusions: The 5-year DSS of our ENSAT II patients was worse than reported in contemporary cohorts. Suboptimal surgery and inconsistent adjuvant therapy with mitotane might have contributed to this outcome. Better outcomes of this rare disease might be accomplished with dedicated teams including various specialties, working towards optimal staging, diagnostic and therapeutic measures.

Liquid biopsy is becoming an important source of new biomarkers during the treatment of metastatic cancer patients. Using size-based microfluid technology, we isolated circulating tumor cells (CTCs) from metastatic breast cancer patients to evaluate their presence and cluster formation, as well as the presence of megakaryocytes and immune-inflammatory blood cells, and to correlate their presence with clinicopathological data and overall survival (OS). In total, 59 patients (median age 60.4 years) were included in the study: 62.7% luminal A/B-like, 20.3% HER2-positive, and 17% triple-negative. Our results showed that at least one CTC was present in 79.7% and ≥5 CTCs in 35.2% of the patients. CTC clusters were present in patients with ≥5 CTCs only (in 19.2% of them), and megakaryocytes were present in 52% of all patients. The presence of CTC clusters and megakaryocytes was positively associated with the CTC count. Patients with low pan-inflammatory value (PIV), low systemic immune-inflammatory index (SII), and low relative change from baseline (ΔPIV%, ΔSII%) were associated with significantly higher OS than their counterparts. ΔPIV%, the presence of infection in the last month, and a long duration of metastatic disease were identified as independent prognostic factors for OS. The interplay of CTCs, CTC clusters, megakaryocytes, and PIV needs to be further explored.

Background: Atezolizumab, a programmed-death ligand-1 (PD-L1) inhibitor, is a novel treatment option for patients with metastatic urothelial cancer (mUC). Clinical prognostic factors, survival outcomes, and the safety of patients with mUC treated with atezolizumab, in a real-world setting, were investigated. Patients and methods: 62 patients with mUC, treated at the Institute of Oncology Ljubljana between May 8th 2018 and Dec 31st 2019, were included. Response rates and immune-related adverse events (irAE) were collected. Progression-free survival and overall survival times were assessed using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting survival. Results: Of 62 patients, five (8.1%) have not yet been evaluated and 20 (32%) died prior to the first radiographic evaluation. We observed clinical benefit in 19 (33%), objective response in 12 (21%), and complete response in five (9%) patients. Median overall survival for the whole population was 6.8 (95% CI, 2.6–11.0), for platinum-naïve 8.7 (95% CI: 0.8–16.5), and for the platinum-treated group 6.8 (95% CI, 3.7–10) months. At the 5.8 (0.3–23.1) month median follow-up, the median duration of the response was not reached. IrAE occurred in 20 (32%) patients and seven (11%) of them discontinued the treatment. Multivariate analysis in platinum-treated patients showed that a treatment-free interval of more than six months was prognostic for overall survival (OS). Conclusions: Responses to atezolizumab led to long disease remission in a subset of our patients. The median OS in our real-world population was compromised by a large percentage of patients with poor ECOG performance status (PS). A treatment-free interval from chemotherapy was associated with the longer survival of platinum-treated patients with mUC receiving further atezolizumab.