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. 2022 Nov 30;14(23):5935.
doi: 10.3390/cancers14235935.

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

Stefan K Zöllner  1   2   3 , Katja L Kauertz  1   2   3 , Isabelle Kaiser  1   2   3 , Maximilian Kerkhoff  1   2   3 , Christiane Schaefer  1   2   3 , Madita Tassius  1   2   3 , Susanne Jabar  1   2   3 , Heribert Jürgens  4 , Ruth Ladenstein  5 , Thomas Kühne  6 , Lianne M Haveman  7 , Michael Paulussen  8 , Andreas Ranft  1   2   3 , Uta Dirksen  1   2   3
Affiliations

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

Stefan K Zöllner et al. Cancers (Basel). .

Abstract

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.

Keywords: Ewing sarcoma; cancer survivor; childhood cancer; secondary malignancy; secondary malignant neoplasms.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Localization and frequency of primary malignancies and Ewing sarcoma as secondary malignant neoplams (EwS as SMN), and occurrence of EwS as SMN in previously irradiated fields. Non-EwS malignancies are shown with gray circles, EwS cases with blue circles, and cases of EwS as SMN in previously irradiated fields with yellow circles. The numbers indicate the number of tumors per localization. The size of the circles is proportional to the number of cases. Missing circles mean no tumor case in this localization. Data for primary malignancies, EwS as SMN, and EwS as SMN in previously irradiated localizations (i.e., information on treatment modalities) were available in n = 36, n = 41, and n = 27, respectively. Nine patients were irradiated in the primary tumor setting.
Figure 2
Figure 2
Box-and-whisker plot of latency between primary tumor and Ewing sarcoma as secondary malignant neoplasms (EwS as SMN) compared between hematologic and solid primary tumors in the EICESS 92, Euro-E.W.I.N.G. 99, and EWING 2008 trials. Statistical analysis by unpaired t test, ns = non-significant (p = 0.55).
Figure 3
Figure 3
Survival of patients withEwing sarcoma (EwS) as secondary malignant neoplasms as a function of metastatic status at diagnosis in the EICESS 92, Euro-E.W.I.N.G. 99, and EWING 2008 trials. (a) Overall survival (OS) and (b) event-free survival (EFS) were calculated using the Kaplan–Meier method. * (a) p = 0.02, (b) p = 0.03. # at risk—numbers at risk.
Figure 4
Figure 4
Survival of patients with Ewing sarcoma (EwS) as secondary malignant neoplasms as a function of type of primary hematological or primary solid malignancy in the EICESS 92, Euro-E.W.I.N.G. 99, and EWING 2008 trials. (a) Overall survival (OS) and (b) event-free survival (EFS) were calculated using the Kaplan–Meier method. Statistical analysis by Log-rank test. (a,b) p > 0.05. # at risk—numbers at risk.
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