Secondary Malignancies after Ewing Sarcoma-Epidemiological and Clinical Analysis of an International Trial Registry.

Ewing sarcoma (EwS) represents highly aggressive bone and soft tissue tumors that require intensive treatment by multi-chemotherapy, surgery and/or radiotherapy. While therapeutic regimens have increased survival rates, EwS survivors face long-term sequelae that include secondary malignant neoplasms (SMNs). Consequently, more knowledge about EwS patients who develop SMNs is needed to identify high-risk patients and adjust follow-up strategies. We retrospectively analyzed data from 4518 EwS patients treated in five consecutive EwS trials from the Cooperative Ewing Sarcoma Study (CESS) group. Ninety-six patients developed SMNs after primary EwS, including 53 (55.2%) with solid tumors. The latency period between EwS and the first SMN was significantly longer for the development of solid SMNs (median: 8.4 years) than for hematologic SMNs (median: 2.4 years) (p < 0.001). The cumulative incidence (CI) of SMNs in general increased over time from 0.04 at 10 years to 0.14 at 30 years; notably, the specific CI for hematologic SMNs remained stable over the different decades, whereas for solid SMNs it gradually increased over time and was higher for metastatic patients than in localized EwS patients (20 years: 0.14 vs. 0.06; p < 0.01). The clinical characteristics of primary EwS did not differ between patients with or without SMNs. All EwS patients received multi-chemotherapy with adjuvant radiotherapy in 77 of 96 (80.2%) patients, and the use of radiation doses ≥ 60 Gy correlated with the occurrence of SMNs. The survival rate after SMNs was 0.49, with a significantly better outcome for solid SMNs compared with hematologic SMNs (3 years: 0.70 vs. 0.24, respectively; p < 0.001). The occurrence of SMNs after EwS remains a rare event but requires a structured follow-up system because it is associated with high morbidity and mortality.

Ewing Sarcoma as Secondary Malignant Neoplasm-Epidemiological and Clinical Analysis of an International Trial Registry.

Ewing sarcoma (EwS) is the second most common bone and soft tissue tumor, affecting primarily adolescents and young adults. Patients with secondary EwS are excluded from risk stratification in several studies and therefore do not benefit from new therapies. More knowledge about patients with EwS as secondary malignant neoplasms (SMN) is needed to identify at-risk patients and adapt follow-up strategies. Epidemiology, clinical characteristics, and survival analyses of EwS as SMN were analyzed in 3844 patients treated in the last three consecutive international EwS trials, EICESS 92, Euro-E.W.I.N.G. 99, and EWING 2008. Forty-two cases of EwS as SMN (approximately 1.1% of all patients) were reported, preceded by a heterogeneous group of malignancies, mainly acute lymphoblastic leukemias (n = 7) and lymphomas (n = 7). Three cases of EwS as SMN occurred in the presumed radiation field of the primary tumor. The median age at diagnosis of EwS as SMN was 19.4 years (range, 5.9-72) compared with 10.8 years (range, 0.9-51.2) for primary EwS. The median interval between first malignancy and EwS diagnosis was 7.4 years. The 3-year overall survival (OS)/event-free survival (EFS) was 0.69 (SE = 0.09)/0.53 (SE = 0.10) for localized patients and 0.36 (SE = 0.13)/0.29 (SE = 0.12) for metastatic patients (OS: p = 0.02; EFS: p = 0.03). Survival in patients with EwS as SMN did not differ between hematologic or solid primary malignancies. EwS as SMN is rare; however, survival is similar to that of primary EwS, and its risk-adjusted treatment should be curative, especially in localized patients.

CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma.

Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with increasing incidence but dismal prognosis. Surgical treatment has remained the only potentially curative treatment option, but it remains unclear which patients benefit most from liver surgery, highlighting the need for new preoperative stratification strategies. In clinical routine, CA19-9 represents the most widely used tumor marker in CCA patients. However, data on the prognostic value of CA19-9 in CCA patients are limited and often inconclusive, mostly due to small cohort sizes. Here, we investigated the prognostic value of CA19-9 in comparison with other standard laboratory markers in a large cohort of CCA patients that underwent tumor resection. Of note, while CA19-9 and CEA were able to discriminate between CCA and healthy controls, CEA showed a higher accuracy for the differentiation between CCA and patients with primary sclerosing cholangitis (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C-reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9 represented an independent predictor of survival in multivariate Cox-regression analysis. Our data suggest that CEA might help to identify CCA patients with an unfavourable prognosis after tumor resection.

Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) represents a primary hepatic malignancy with incidence and mortality rising globally. Surgical treatment has remained the only potentially curative treatment option, but it is still unclear which patients benefit most from extended liver surgery, highlighting the need for new pre-operative stratification strategies. Osteopontin is a secreted extracellular glyco-phosphoprotein that has been associated with inflammation, metabolic disorders and cancer. Here, we examined the potential of circulating osteopontin serum levels as a diagnostic or prognostic biomarker in patients with CCA undergoing extended liver surgery. METHODS: Osteopontin expression levels were analysed in human and murine CCA tumour samples, using semi-quantitative reverse transcriptase PCR and immunohistochemistry. Osteopontin serum concentrations were measured by enzyme-linked immunosorbent assay in 107 patients with CCA undergoing elective tumour resection as well as 55 healthy controls. Results were correlated with clinical data. RESULTS: Correlating with an upregulation in CCA tumour cells and the tumour stroma, serum levels of osteopontin were elevated in patients with cholangiocarcinoma compared to healthy controls and patients with primary sclerosing cholangitis. Importantly, pre- and postoperative elevations of osteopontin showed a striking association with poor postoperative survival. CONCLUSIONS: Serum osteopontin concentrations represent a promising prognostic biomarker in patients resectable CCA which could help to guide preoperative treatment decisions and to identify patients that will particularly benefit from extended liver surgery. Lay summary: Extended liver surgery is the only potentially curative treatment for patients with cholangiocarcinoma (CCA/biliary cancer), but it is currently unclear which patients benefit most from surgery. Detecting serum levels of osteopontin - a specific secreted glycoprotein involved in multiple human diseases - in CCA patients might help to identify those patients that particularly benefit from tumour resection.