Clinical impact of post‐induction resolution of pulmonary lesions in metastatic Ewing sarcoma

Abstract

Background Patients with metastatic Ewing sarcoma experience poor outcomes despite intensive systemic and local therapy. Early chemotherapy response of pulmonary metastases has been associated with prognosis in other pediatric malignancies. We reviewed the outcomes of patients with Ewing sarcoma and pulmonary metastases treated at our institution based on therapy received and early pulmonary response. Materials and methods We retrospectively reviewed patients with newly diagnosed Ewing sarcoma and pulmonary metastases at St. Jude Children's Research Hospital between 1979 and 2015. Data obtained included demographic and treatment characteristics including chemotherapy, local control measures, whole lung irradiation (WLI) administration, autologous stem cell transplantation, and outcomes. Patients were evaluated for radiographic post‐induction pulmonary complete response (CR). We estimated event‐free survival (EFS) and overall survival (OS) and used Cox proportional hazards regression to examine the effects of clinical and treatment factors on outcomes. Results Fifty‐four patients (median age, 12.9 years) were evaluated. Post‐induction pulmonary CR was observed in 33 (61%) patients. WLI was delivered to 16 patients (4/33 with pulmonary CR and 12/21 with non‐CR). At median 3.6 years follow‐up, five‐year EFS and OS were 30.8% ± 6.4% and 49.6% ± 7.1%, respectively. Post‐induction pulmonary CR was associated with prolonged EFS (P < 0.001) but not improved OS (P = 0.065). Post‐induction pulmonary CR was associated with a lower incidence of lung failure (P = 0.031). Conclusions Post‐induction pulmonary CR is associated with improved EFS in patients with Ewing sarcoma who present with pulmonary metastases.

Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases

“…While our study showed improved OS, studies by Raciborska et al., Spunt et al., and Halalsheh et al. found that patients with RCR had improved event‐free survival, but no improvement in OS in children with RCR 7,11,16 . Raciborska et al.…”

“…Finally, Halalsheh et al. showed that patients with complete response of pulmonary nodules after induction chemotherapy had better 5‐year event‐free survival than those without complete response (45% vs. 6%; p < .01) 7 . Our study is larger than these studies, which could explain why we detected a difference in OS.…”

“…16 Finally, Halalsheh et al showed that patients with complete response of pulmonary nodules after induction chemotherapy had better 5-year event-free survival than those without complete response (45% vs. 6%; p < .01). 7 Our study is larger than these studies, which could explain why we detected a difference in OS. Multiple studies have shown that patients' outcomes are strongly associated with the tumor's primary histologic response to induction chemotherapy, [17][18][19] which supports our findings that patients with RCR have improved 5-year OS.…”

“…[4][5][6] Emerging data suggest that patients who have resolution of pulmonary metastatic disease at the end of induction chemotherapy may have improved survival compared to those with residual disease. 7 Patients who achieve this rapid complete response (RCR) are known to have improved outcomes in other diseases, including Wilms tumor. [8][9][10] Multi-institutional data in real-world conditions with heterogenous extent of disease and variable systemic therapy regimens are needed to confirm that achievement of RCR is associated with improved survival.…”

“…Emerging data suggest that patients who have resolution of pulmonary metastatic disease at the end of induction chemotherapy may have improved survival compared to those with residual disease 7 . Patients who achieve this rapid complete response (RCR) are known to have improved outcomes in other diseases, including Wilms tumor 8–10 .…”