The post-recurrence survival in patients with Ewing sarcoma is dismal. We demonstrated that certain clinical features identified at the time of diagnosis were significantly related to the risk for death after initial recurrence. We also confirmed the importance of time to recurrence as a prognostic factor for post-recurrence survival.
In agreement with previous reports, time to first recurrence was the most significant predictor for post-recurrence survival for patients treated with INT0091 5–7;10;11
. However, certain differences exist between our data and other reported series. Time to first recurrence for patients with initially localized disease was significantly associated with the initial treatment regimen (2.1 vs. 1.4 years), consistent with the improved efficacy of the experimental regimen B as compared with regimen A 2;12
. The patient population described here included 46% patients with disease metastatic at initial diagnosis. The groups described by Rodriguez-Galindo et al. 10
, Barker et al. 11
and McTiernan et al. 6
included patients with metastases at initial diagnosis (42%, 38% and 47% respectively) while other reports of survival in patients post-recurrence did not include patients with initially metastatic disease 5;7
.We report that only 21% of patients were 2 or more years from initial diagnosis, fewer than in prior reports (29% 11
and 44% 10
). The patients reported here were all treated on a single prospective multi-institutional randomized study over a 6 year period. Although Shankar et al. 5
also reported data from a single multi-institutional trial (ET-2 UKCCSG), other reports describe outcome from single institutions for patients with recurrent Ewing sarcoma initially diagnosed over an 18 year period or treated with at least 3 protocols. Interestingly, although ET-2 was open only to patients with initially localized disease, the overall median post-recurrence survival is similar in patients treated on INT0091 and ET-2 UKCCSG (9 months and 14 months respectively). The 5 year overall survival for patients treated on INT0091 was 12%, quite different from the predicted survival reported by Barker et al. (23%) 11
. No detailed data on post-recurrence therapy was collected on INT0091. Therefore, while previous reports suggest either a benefit for high-dose therapy 6;11
or pulmonary radiation 10
for patients at first recurrence, we cannot examine the components of post-recurrence therapy that could have impacted outcome and therefore can only provide information on prognostic factors but cannot comment on the role of post-recurrence therapy.
We have documented that several prognostic indicators at initial diagnosis continue to have prognostic significance in multivariate analysis with post-recurrence survival. In our study, patient gender and stage at initial diagnosis were prognostic for post-recurrence survival as previously reported in studies by Shankar et al. 5
and Rodriguez-Galindo et al. 10
. We have also demonstrated an inferior outcome for patients with elevated LDH at diagnosis.
We did not find a statistically significant post-recurrence survival advantage for patients with an isolated pulmonary recurrence. This is in contrast to the survival advantage reported by Bacci et al. 7
and McTiernan et al. 6
for patients who had lung only recurrence. However recurrence at both distant and local sites was associated with an inferior outcome, in agreement with prior reports. We conclude that all patients with recurrent Ewing sarcoma would benefit from collaborative trials to improve post-recurrence survival. A subset of patients with longer time to first recurrence, initially localized disease and a normal LDH at diagnosis, represent the patients most likely to survive.