Clinical and biological features prognostic of survival after relapse or progression of INRGSS stage MS pattern neuroblastoma: A report from the International Neuroblastoma Risk Group (INRG) project

Abstract

Background: Outcomes for patients with INRGSS metastatic special (MS) metastatic pattern neuroblastoma at initial diagnosis are well described. Prognosis after an initial event (relapse, progression, secondary malignancy) is unclear.

Methods: We investigated characteristics of MS pattern neuroblastoma patients in the International Neuroblastoma Risk Group database who subsequently experienced an event. Post-event overall survival (OS) ± standard error was calculated overall and by diagnosis era: before 2000 versus 2001 or after. Cox models were used to identify factors prognostic of post-event OS.

Results: Among 209 patients with an event, 88% were less than 365 days old at diagnosis; tumors were MYCN amplified in 24% and diploid in 33%. The median (range) time from diagnosis to first event was 8.16 months (7 days to 11.24 years). Of 96 patients with known relapse/progression pattern, 75% were metastatic or primary plus metastatic. Five-year post-event OS was 53% ± 3.6% and was higher for 2001 and afterwards (62% ± 5.0%) compared to before 2001 (44% ± 4.9%; p = .0046). In patients diagnosed in 2001 and after, older age, Hispanic ethnicity, MYCN amplification, 1p LOH, diploidy, high Mitotic Karyorrhexis Index, high lactate dehydrogenase (LDH), unfavorable histology, and longer time to first event were prognostic of worse post-event OS. Independent adverse prognostic factors on multivariable testing were non-White race, MYCN amplification, and diploidy.

Summary: Patients diagnosed in and after 2001 have substantially better post-event OS compared to before 2001. In those diagnosed in and after 2001, most well-accepted prognostic factors for OS at diagnosis are also prognostic of post-event OS. Future studies may evaluate strategies to improve outcomes in this rare population.

Keywords: INRGSS stage MS; neuroblastoma; prognosis; relapse.

Figure 1A.

Kaplan-Meier curve of OS from time of first event for all patients diagnosed with MS pattern neuroblastoma (n=209).

Figure 1B.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease <2001 (n=103) versus ≥2001 (n=106).

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)

Figure 2.

Kaplan-Meier curves of OS from time of first event for patients diagnosed with MS-pattern disease ≥2001 according to the following variables significantly associated with post-event OS on univariate analyses: A. age at diagnosis: 365–547 days (n=12) vs <365 days (n=94) B. ethnicity: Hispanic (n=7) vs non-Hispanic (n=72) C. MYCN: amplified (n=21) vs not amplified (n=81) D. 1p deletion: LOH, deletion, or imbalance (n=12) vs no loss or aberration (n=23) E. ploidy: diploid (n=20) vs hyperdiploid (n=44) F. MKI: high (n=14) vs low and intermediate (n=66) G. LDH (U/L): ≥1400 (n=13) vs <1400 (n=29) H. histologic classification: unfavorable (n=12) vs favorable (n=67) I. first event: ≥12 months (n=38) vs <12 months (n=68)