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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Ewing sarcoma is a bone and soft-tissue cancer of teenagers driven by a single fusion gene, EWSR1-FLI1. Intensive chemotherapy with surgery or radiation cures most localised cases; disease that has spread at diagnosis, and relapse, remain hard to treat, and no drug against the fusion protein itself has yet succeeded.
Ewing sarcoma is defined by FET-ETS fusions, EWSR1-FLI1 in ~85% and EWSR1-ERG in ~10%, which act as aberrant transcription factors at GGAA microsatellites; the genome is otherwise quiet (STAG2, CDKN2A, TP53 alterations carry shorter survival). It arises in bone (pelvis, femur, chest wall) or soft tissue in adolescents and young adults.
Treatment is multimodal: interval-compressed VDC/IE (vincristine, doxorubicin, cyclophosphamide alternating with ifosfamide, etoposide) every 2 weeks (AEWS0031), which Euro Ewing 2012 showed superior to VIDE; local control by surgery, radiotherapy or both; and metastatic disease treated with the same backbone plus whole-lung irradiation, with high-dose busulfan-melphalan benefiting selected high-risk patients (Euro-EWING 99 R2). Relapse is treated with irinotecan-temozolomide, high-dose ifosfamide or topotecan-cyclophosphamide, ranked by the rEECur adaptive trial (high-dose ifosfamide best). Targeted attempts (IGF-1R antibodies, TK216 against EWS-FLI1, PARP inhibitors) have not succeeded; lurbinectedin and combinations are in trials.
| Setting | Approach | Guideline |
|---|---|---|
| Localised | Interval-compressed VDC/IE ×14 cycles (AEWS0031 / Euro Ewing 2012) with surgery ± radiotherapy (or definitive RT 55.8 Gy) after 6 induction cycles. | NCCN Category 1 |
| Metastatic (lung only) | Same chemotherapy plus whole-lung irradiation; busulfan-melphalan high-dose therapy in selected patients (Euro-EWING 99 R2pulm equivocal). | NCCN Category 2A |
| Metastatic (bone/marrow) | Chemotherapy with palliative-intent local therapy; survival <20%; trials strongly preferred. | not mapped |
| Relapsed | High-dose ifosfamide (rEECur), irinotecan-temozolomide, topotecan-cyclophosphamide, gemcitabine-docetaxel; local therapy; trials. | NCCN Category 2A |