Impact of Extent of Resection on Local Control and Survival in Patients From the COG A3973 Study With High-Risk Neuroblastoma

Abstract

Purpose This analysis of patients in the Children's Oncology Group A3973 study evaluated the impact of extent of primary tumor resection on local progression and survival and assessed concordance between clinical and central imaging review-based assessments of resection extent. Patients and Methods The analytic cohort (n = 220) included patients who had both central surgery review and resection of the primary tumor site. For this analysis, resection categories of < 90% and ≥ 90% were used, with data on resection extent derived from operating surgeons' assessments (all patients), as well as blinded central imaging review of computed tomography scans for a subset of 84 patients; assessment results were compared for concordance. Treatment outcomes included event-free survival (EFS), overall survival (OS), and cumulative incidence of local progression (CILP). Results Surgeon-assessed extent of resection was ≥ 90% in 154 (70%) patients and < 90% in 66 (30%). Five-year EFS, OS, and CILP (± SE) were 43.5% ± 3.7%, 54.9% ± 3.7%, and 11.9% ± 2.2%, respectively. EFS was higher with ≥ 90% resection (45.9% ± 4.3%) than with < 90% resection (37.9% ± 7.2%; P = .04). Lower CILP ( P = .01) was associated with ≥ 90% resection (8.5% ± 2.3%) compared with < 90% resection (19.8% ± 5.0%). On multivariable analysis, ≥ 90% resection was associated with longer EFS after adjustment for MYCN amplification or diploidy but had no significant effect on OS. Concordance between surgeons' assessments of resection extent and central image-guided review was low, with agreement of 63% (< 90% v ≥ 90%; simple κ = -0.0301). Conclusion Despite discordance between clinical assessment of resection extent and assessment via central imaging review, a surgeon-assessed resection extent ≥ 90% was associated with significantly better EFS and lower CILP. Improving OS, however, remains a challenge in this disease. These findings support continued attempts at ≥ 90% resection of the primary tumor in high-risk neuroblastoma.

Fig 1.

(A) Event-free survival and overall survival, and (B) cumulative incidence of local progression in 220 patients from Children’s Oncology Group high-risk neuroblastoma study A3973 whose data underwent surgical central review.

Fig 2.

Survival curves for the 220 patients from the Children’s Oncology Group A3973 high-risk neuroblastoma study whose data underwent surgical central review of extent of primary tumor resection (< 90%: n = 66; ≥ 90%: n = 154). (A) Event-free survival (EFS), P = .04; (B) overall survival (OS), P = .3; and (C) cumulative incidence of local progression (CILP), P = .014. NA, not applicable.

Fig 3.

Survival curves for the subset of 84 patients from the Children’s Oncology Group A3973 high-risk neuroblastoma study whose data underwent central, cross-sectional image review of pre- and postoperative computed tomography scans to determine extent of resection, by extent of primary tumor resection (< 90%: n = 22; ≥ 90%: n = 62). (A) Event-free survival (EFS), P = .3; (B) overall survival (OS), P = .1; and (C) cumulative incidence of local progression (CILP), P = .008. NA, not applicable.