Delayed Treatment Associated With Unfavorable Outcomes in Ewing Sarcoma

Uta Dirksen, MD

Delays between biopsy and the start of induction chemotherapy, induction chemotherapy and surgery, and surgery and consolidation chemotherapy were associated with a poor prognosis in patients with localized Ewing sarcoma, according to findings from a retrospective review of the GPOH Euro-EWING 99 trial (NCT00020566) that were presented during the 2021 ASCO Annual Meeting.

The results also showed that patients who experienced an interval delay between biopsy and the start of induction chemotherapy of 22 days or less had significantly improved event-free survival (EFS; P =.005) but not overall survival (OS; P = .06) vs patients who experienced an interval delay between biopsy and the start of induction chemotherapy of more than 22 days.

Similarly, patients who experienced an interval delay between the start of induction chemotherapy and surgery of 150 days or less had significantly improved EFS (P = .001) but not OS (P = .018) vs patients who experienced an interval delay between the start of induction chemotherapy and surgery of more than 150 days.

Patients who experienced an interval delay between surgery and the start of adjuvant chemotherapy of 21 days or less had significantly improved EFS (P = .003) but not OS (P = .008) vs patients who experienced an interval delay between surgery and the start of adjuvant chemotherapy of more than 21 days.

“Delays between induction chemotherapy and surgery were significantly associated with a poor prognosis in patients with localized disease in univariate and multivariate analysis,” lead study author Uta Dirksen, MD, a professor at the University Hospital Essen, said in a virtual presentation of the data. “Additionally, a delay between surgery and consolidation chemotherapy was independently associated with a poor prognosis in univariate analysis.”

Outcomes in Ewing sarcoma have improved over the past decade, but there is still room for improvement. Additionally, prognostic and predictive biomarkers, such as p53, STAG2, SOX2, and CNA, have been identified in a minority of patients, and it is unclear whether to pursue an alternative treatment strategy in this population.

As such, investigators sought to evaluate additional prognostic factors, such as treatment delays.

Investigators compiled data on patients enrolled in the Euro-EWING 99 trial, which evaluated 6 cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), 1 cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment consisting of surgery and/or radiotherapy, and high-dose busulfan-melphalan followed by autologous stem cell transplantation.

A total of 692 patients were eligible for evaluation. Inclusion criteria stipulated that patients had to have localized disease and surgical treatment.

The median interval from biopsy to the start of chemotherapy was 14 days (interquartile range [IQR], 8-21). A total of 485 patients had surgery after 6 cycles of VIDE.

The interval from chemotherapy to surgery was 141 days (IQR, 133-153), and the interval from surgery to the start of adjuvant chemotherapy was 17 days (IQR, 14-23).

Additional findings indicated that treatment delays occurred more often in low-volume centers vs high-volume centers (P =.005).

Moreover, patients who had a longer interval delay between surgery and the start of adjuvant chemotherapy had a significantly higher likelihood of postoperative complications (P < .001).

Multivariate analysis indicated that patients with pelvic tumor localization (HR, 2.14, P <.001; HR, 1.95, P =.001), a poor histological response to induction chemotherapy (HR, 1.94, P <.001; HR, 1.97, P <.001), and a longer interval delay between induction chemotherapy and surgery (HR, 1.55, P =.011; HR, 1.57, P =.014) had a higher likelihood of experiencing an event or death, respectively.

“There is a need to optimize supportive care to reduce such delays. There’s possibly also a need to optimize referral pathways from low-volume centers to centers where surgery is done. General treatment in high-volume centers in Europe is recommended,” concluded Dirksen.

Reference

1. Dirksen U, Ranft A, Baumhoer D, et al. Association of treatment delays with an unfavorable outcome in patients with localized Ewing sarcoma: A retrospective analysis of data from the GPOH Euro-E.W.I.N.G.99 trial. J Clin Oncol. 2021;39(suppl 15):11502. doi:10.1200/JCO.2021.39.15_suppl.11502