Trends in conditional survival and predictors of late death in neuroblastoma

Abstract

Purpose Significant advances in the treatment of neuroblastoma have been made in the past several decades. There are scant data examining how these improvements have changed over time and differentially affected conditional survival among high‐risk and non‐high‐risk patient groups. Methods We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results database. We analyzed clinical characteristics and survival outcomes for 4717 neuroblastoma patients. Kaplan‐Meier methods were used to estimate overall survival (OS) and conditional overall survival (COS) with estimates compared between groups using log‐rank tests. Results Five‐year OS was 41.46% (95% CI 38.77‐44.13) for the high‐risk group and 91.13% (95% CI 89.49‐92.53) for the non‐high‐risk group. Both groups saw significant improvements in OS by decade (P < .001). Five‐year COS among 1‐year survivors was 52.69% (CI 49.54‐55.73) for the high‐risk group and 96.75% (95% CI 95.57‐97.62) for the non‐high‐risk group. One‐year survivors in the high‐risk group showed a statistically significant improvement in COS over time. No difference in COS was observed among 5‐year high‐risk survivors. In the high‐risk and non‐high‐risk groups, 82% and 32% of late deaths were attributable to cancer, respectively. Statistically significant adverse prognostic factors for late death were age ≥ 1 year at diagnosis, metastatic disease, and nonthoracic primary site (P = .001). Conclusions Improvements in COS over time have largely benefited high‐risk patients, though they are still at higher risk for late death due to cancer when compared to non‐high‐risk patients. Age, stage, and primary site, but not treatment decade, influence outcomes among 5‐year survivors.

Systematic review of clinical drug development activities for neuroblastoma from 2011 to 2020

“…17 less than 10% for relapsed populations, expeditious and efficient trials are of the utmost importance. 18,19 We observed that only GD2 antibodies, B7-H3-targeted radiopharmaceutical, MIBG, isotretinoin and ALK inhibitors were advanced to evaluation in the phase 3 setting, and only GD2 antibodies and isotretinoin have thus far become front-line standard of care. Over our study period, only five phase 3 trials were identified, reflecting both the rarity of this disease and the complexities of initiating these trials.…”

“…Four of these trials were academically sponsored and were not trans-Atlantic, reflecting the general picture in pediatric oncology of a lack of academically sponsored trans-Atlantic trials. 18,20 Efforts to facilitate trans-Atlantic trials are needed.…”

“…A recent analysis of clinical trials submitted to the FDA for pediatric drug approvals found that the median of the maximum durations for biologic drug trials was 2.7 years 17 . Given a 5‐year estimated overall survival of only approximately 50% for high‐risk patients and less than 10% for relapsed populations, expeditious and efficient trials are of the utmost importance 18,19 …”

“…Over our study period, only five phase 3 trials were identified, reflecting both the rarity of this disease and the complexities of initiating these trials. Four of these trials were academically sponsored and were not trans‐Atlantic, reflecting the general picture in pediatric oncology of a lack of academically sponsored trans‐Atlantic trials 18,20 . Efforts to facilitate trans‐Atlantic trials are needed.…”

To transplant, or not to transplant? That is the question. A patient advocate evaluation of autologous stem cell transplant in neuroblastoma

“…22 Improving survival over time as demonstrated by epidemiological and other studies can also be partly attributed to major changes in standard of care-including transplant. [23][24][25][26]…”