This protocol addresses Ewing's sarcoma in patients with pulmonary metastases whose disease is not progressing on induction chemotherapy, but in whom the prior treatment line did not achieve the required pathological response targets.
The defining context is the presence of pulmonary metastases. Disease is not progressing on induction chemotherapy — it is stable or partially responding — but the pathological benchmarks set by the prior treatment line were not reached. This combination of findings defines the patient population for this protocol.
Previous therapy: Compressed interval two-weekly VDC/IE chemotherapy for 14 cycles (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide), plus surgical resection and/or radiotherapy for the primary tumour, followed by whole lung irradiation.
Targets not achieved: Histological necrosis rate greater than 90% in the resected specimen; tumour volume reduction on MRI.
This protocol defines the treatment step taken when those response thresholds are not met — while the disease itself remains non-progressive.
Intensified systemic chemotherapy is the foundation of management in this setting. Specific combinations are selected based on comparative efficacy data, with the choice guided by clinical factors.
The full regimen options, decision algorithm, and clinical criteria are detailed in the complete protocol.
Target endpoint: Tumour response on imaging after four cycles of chemotherapy.
DOI: 10.1038/s41416-024-02868-4
For patients with pulmonary metastases, whole lung irradiation (WLI) following VDC/IE chemotherapy is indicated if the disease is not progressing on induction chemotherapy.
Multiple pairwise comparisons between arms have defined the following hierarchy based on EFS, OS and RECIST 1.1 imaging response after four cycles of chemotherapy, in order of decreasing efficacy: high dose ifosfamide, topotecan and cyclophosphamide, irinotecan and temozolomide, and gemcitabine and docetaxel.
However, this does not appear advantageous for those with pulmonary metastases treated with standard chemotherapy and whole lung irradiation (WLI) and its utility following VDC/IE is not defined.
View source ↗