Histological response to induction chemotherapy (osteosarcoma and Ewing sarcoma)

What is measured: the proportion of the tumour killed by neoadjuvant chemotherapy. How: the whole resected specimen is mapped section by section and the percentage of viable tumour recorded; osteosarcoma uses the Huvos grades (I under 50 percent necrosis, II 50 to 90, III 90 to 99, IV 100), with 90 percent or more the good response after methotrexate, doxorubicin and cisplatin (MAP), and Ewing sarcoma uses Salzer-Kuntschik grades or the same threshold after vincristine, doxorubicin, cyclophosphamide with ifosfamide and etoposide (VDC/IE) or VIDE. About half of osteosarcomas are good responders, with five-year event-free survival near 75 percent against about 50 percent for poor responders. What a result changes: it is the strongest prognostic factor after metastasis, but in osteosarcoma EURAMOS-1 (2016) found that adding ifosfamide and etoposide for poor responders did not improve event-free survival and increased toxicity, and that interferon maintenance for good responders did not help, so MAP continues unchanged and the response now guides surveillance and trial entry; in Ewing sarcoma a poor response or large tumour volume defines the high-risk arm, in which high-dose busulfan and melphalan improved event-free survival in the Euro-EWING 99 R2Loc analysis (69 against 57 percent), and response also informs local-control decisions. Alkaline phosphatase, LDH and MRI response are surrogates before surgery, and ctDNA copy-number burden is being tested as a replacement. Where it matters: osteosarcoma and Ewing sarcoma.