Purpose/Objective(s): Locoregional relapse continues to be a significant contributor to treatment failure for high-risk neuroblastoma patients even after radiation therapy (RT). We aimed to examine the effects of increasing local dose of radiation to the residual primary tumor for patients with less than a gross total resection on overall survival (OS), event-free survival (EFS), and cumulative incidence of local progression (CILP) in the Children’s Oncology Group (COG) ANBL0532 phase 3 study, a question that constituted a Primary Objective of the trial.
Materials/Methods: Newly diagnosed high-risk neuroblastoma patients were enrolled on COG ANBL0532 from November 2007 to February 2012. Patients were randomized or assigned to receive single vs. tandem autologous stem cell transplantation (SCT). Local control of the primary tumor consisted of surgical resection during induction chemotherapy and RT following last SCT. Patients were prescribed RT (21.6 Gy in 1.8 Gy fractions) to the preoperative primary tumor volume. For patients with incomplete surgical resections of the primary tumor (defined as >1 cm3 residual soft tissue density as assessed by central review of end-induction scans), an additional boost of 14.4 Gy was delivered to the gross residual tumor for a total dose of 36 Gy. OS, EFS, and CILP were compared to COG A3973 historical cohort, in which all patients received 21.6 Gy without a boost. Kaplan-Meier curves of OS and EFS were compared using a log-rank test. CILP curves, with adjustment for competing risks (previous progression outside the primary, or death), were compared using Grey’s test.
Results: 323 patients received RT on ANBL0532. Of these, 133 patients received boost RT. For all patients receiving RT, five-year CILP, EFS, and OS were 11.2±1.8%, 56.7±3.0%, and 69.2±2.7% for the COG ANBL0532 cohort (n=323) compared to 7.0±1.4% (p=0.0566), 47.2±3.0% (p=0.0072), and 59.7±3.0% (p=0.0078) for the COG A3973 cohort (n=330), respectively. Five-year CILP, EFS, and OS for COG A3973 patients who had incomplete resection and received RT (n=47) were 10.6±4.6%, 48.9±8.7%, and 57.0±8.4%, respectively. In comparison, five-year CILP, EFS, and OS for COG ANBL0532 patients receiving boost RT (n=133) were 15.1±3.1% (p=0.4701), 52.2±4.8% (p=0.4537), and 67.9±4.4% (p=0.2706), respectively; and five-year CILP, EFS, and OS for COG ANBL0532 patients randomized or assigned to single SCT and received boost RT (n=74) were 16.3±4.3% (p=0.4083), 49.5±6.5% (p=0.6529), and 69.7±5.9%, (p=0.2864), respectively.
Conclusion: Five-year CILP was not improved on COG ANBL0532 despite the implementation of boost RT to gross residual tumor present at end-induction. New strategies are needed to decrease the risk of locoregional failure.