Survival of Patients With Neuroblastoma After Assignment to Reduced Therapy Because of the 12- to 18-Month Change in Age Cutoff in Children's Oncology Group Risk Stratification

Abstract

PURPOSE In 2006, Children's Oncology Group (COG) reclassified subgroups of toddlers diagnosed with neuroblastoma from high-risk to intermediate-risk, when the age cutoff for high-risk assignment was raised from 365 days (12 months) to 547 days (18 months). The primary aim of this retrospective study was to determine if excellent outcome was maintained after assigned reduction of therapy. PATIENTS AND METHODS Children <3 years old at diagnosis, enrolled on a COG biology study from 1990 to 2018, were eligible (n = 9,189). Assigned therapy was reduced for two cohorts of interest on the basis of the age cutoff change: 365-546 days old with International Neuroblastoma Staging System (INSS) stage 4, MYCN not amplified ( MYCN-NA), favorable International Neuroblastoma Pathology Classification (INPC), hyperdiploid tumors (12-18mo/Stage4/FavBiology), and 365-546 days old with INSS stage 3, MYCN-NA, and unfavorable INPC tumors (12-18mo/Stage3/ MYCN-NA/Unfav). Log-rank tests compared event-free survival (EFS) and overall survival (OS) curves. RESULTS For 12-18mo/Stage4/FavBiology, 5-year EFS/OS (± SE) before (≤2006; n = 40) versus after (>2006; n = 55) assigned reduction in therapy was similar: 89% ± 5.1%/89% ± 5.1% versus 87% ± 4.6%/94% ± 3.2% ( P = .7; P = .4, respectively). For 12-18mo/Stage3/ MYCN-NA/Unfav, the 5-year EFS and OS were both 100%, before (n = 6) and after (n = 4) 2006. The 12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/ MYCN-NA/Unfav classified as high-risk ≤2006 had an EFS/OS of 91% ± 4.4%/91% ± 4.5% versus 38% ± 1.3%/43% ± 1.3% for all other high-risk patients <3 years old ( P < .0001; P < .0001, respectively). The 12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/ MYCN-NA/Unfav classified as intermediate-risk >2006 had an EFS/OS of 88% ± 4.3%/95% ± 2.9% versus 88% ± 0.9%/95% ± 0.6% for all other intermediate-risk patients <3 years old ( P = .87; P = .85, respectively). CONCLUSION Excellent outcome was maintained among subsets of toddlers with neuroblastoma assigned to reduced treatment after reclassification of risk group from high to intermediate on the basis of new age cutoffs. Importantly, as documented in prior trials, intermediate-risk therapy is not associated with the degree of acute toxicity and late effects commonly observed with high-risk regimens.

Functionalized GD2 Electrochemical Immunosensor to Diagnose Minimum Residual Disease of Bone Marrow in Neuroblastoma Effectively

“…Studies have shown that children with NB in the high-risk group are most likely to develop bone marrow metastasis, and children with NB in the high-risk group are highly susceptible to recurrence because of minimal residual disease (MRD) in the bone marrow [12][13][14][15][16][17][18][19]. Bone marrow-associated neuroblastoma detection is crucial in diagnosing metastasis and recurrence in children with high-risk NB [2,3,8,13,[20][21][22][23][24][25]. However, there is a lack of consensus on the standard determination of NB bone marrow recurrence and metastasis globally [14][15][16]26], and the existing diagnostic techniques cannot solve the critical clinical challenges in children with high-risk NB.…”

Maintaining excellent outcomes: the impact of age cutoff reclassification on reduced therapy for neuroblastoma patients

“…In 2005, several studies pointed out that certain high-risk neuroblastoma patients aged 12–18 months had favorable outcomes ( 18 ). Then, in 2006, with the aim to optimize treatment outcomes while minimizing exposure to treatment-related toxicities, the COG changed the age cut-off, from 12 to 18 months, which reclassified some patients from high to intermediate risk ( Figure 1 ) ( 19 ).…”

“…While this re-classification saved children to be exposed to unnecessary treatments, their outcome should remain unaltered. Thus, Bender et al analyzed the outcome after the reclassification of the toddler’s groups diagnosed with neuroblastoma from the high-risk category to intermediate risk ( 19 ).…”