Metastatic Burden Defines Clinically and Biologically Distinct Subgroups of Stage 4 High-Risk Neuroblastoma
Abstract
:1. Introduction
2. Methods
2.1. Patient Cohort and Data Collection
2.2. Treatment
2.3. Assessment of Metastasis
2.4. Response Criteria
2.5. RNA Isolation
2.6. RNA Sequencing (RNA-Seq) and Data Analysis
2.7. Gene Set Variation Analysis (GSVA)
2.8. Statistical Methods
3. Results
3.1. Characteristics and Outcomes of the Study Population
3.2. Prognostic Significance of Metastatic Burden
3.3. Distinct Clinical Characteristics Based on the Metastatic Burden
3.4. Identification of DEGs and Gene Sets Based on the Metastatic Burden
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics | Number (%) a |
---|---|
Sex | |
Male | 77 (59) |
Female | 53 (41) |
Age at diagnosis, mean ± Std | 4.5 ± 2.9 |
Primary tumor site | |
Abdomen/Pelvis | 117 (90) |
Thorax/Cervix | 12 (9) |
Unknown | 1 (1) |
Primary tumor volume b (cm3) | 345 (67–510) |
MYCN status | |
Nonamplified | 95 (73) |
Amplified | 29 (22) |
Unknown | 6 (5) |
Cytogenetics | |
1p deletion (n = 74) | 16 (22) |
11q deletion (n = 79) | 23 (29) |
17q gain (n = 74) | 22 (29) |
Pathology | |
Undifferentiated | 15 (12) |
Poorly differentiated | 65 (50) |
Differentiating | 22 (17) |
Ganglioneuroblastoma | 19 (15) |
Unknown | 9 (7) |
INPC | |
Favorable | 28 (22) |
Unfavorable | 93 (72) |
Unknown | 9 (7) |
Curie score at diagnosis b | 12.5 (3–25) |
Metastatic site | |
Bone | 116 (89) |
Bone marrow | 92 (71) |
Distant lymph node | 66 (49) |
Lung | 14 (11) |
CNS | 3 (2) |
Liver | 17 (13) |
Skin | 5 (4) |
Other c | 47 (36) |
Variables | Low (n = 104) | High (n = 26) | p-Value |
---|---|---|---|
Sex, No. (%) | 0.964 | ||
Male | 61 (59) | 16 (62) | |
Female | 43 (41) | 10 (38) | |
Age at diagnosis, mean ± Std, years | 4.6 ± 3.1 | 3.9 ± 2.0 | 0.134 |
Primary tumor volume (cm3) b | 245 (1–2305) | 109 (9–1421) | 0.030 |
Residual tumor volume (%) a, b | 28 (2–98) | 31 (10–98) | 0.833 |
Reduction in Curie score, mean ± Std (%) c | 44 ± 37 | 48 ± 36 | 0.620 |
Response to induction treatment, No. (%) | |||
Complete response | 42 (40) | 9 (35) | |
Very good partial response | 23 (22) | 6 (23) | |
Partial response | 33 (32) | 8 (31) | |
Mixed response | 1 (1) | 1 (4) | |
Stable disease | 3 (3) | 1 (4) | |
Progressive disease | 2 (2) | 1 (4) | |
MYCN status, No. (%) | 0.762 | ||
Nonamplified | 74 (71) | 21 (81) | |
Amplified | 24 (23) | 5 (19) | |
Unknown | 6 (6) | 0 | |
Cytogenetics, No. (%) | |||
1p deletion (n = 74) | 14 (18) | 2 (15) | 0.920 |
11q deletion (n = 79) | 18 (27) | 5 (38) | 0.633 |
17q gain (n = 79) | 18 (27) | 4 (33) | 0.912 |
INPC (n = 121) | 1.000 | ||
Favorable | 22 (23) | 6 (25) | |
Unfavorable | 75 (77) | 18 (75) | |
Serum LDH (IU/L) b | 1302 (261–10000) | 1479 (597–14435) | 0.221 |
Serum ferritin (ng/mL) b | 224 (20–3771) | 400 (74–1245) | 0.025 |
Serum NSE (ng/mL) b | 97 (11–1081) | 99 (25–1815) | 0.426 |
24 h urine VMA (mg/day) b | 14.8 (0.4–588.4) | 40.0 (1.7–100) | 0.001 |
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Seo, E.S.; Lee, E.-j.; Lee, B.; Shin, M.; Cho, Y.-S.; Hyun, J.K.; Cho, H.W.; Ju, H.Y.; Yoo, K.H.; Koo, H.H.; et al. Metastatic Burden Defines Clinically and Biologically Distinct Subgroups of Stage 4 High-Risk Neuroblastoma. J. Clin. Med. 2020, 9, 2730. https://doi.org/10.3390/jcm9092730
Seo ES, Lee E-j, Lee B, Shin M, Cho Y-S, Hyun JK, Cho HW, Ju HY, Yoo KH, Koo HH, et al. Metastatic Burden Defines Clinically and Biologically Distinct Subgroups of Stage 4 High-Risk Neuroblastoma. Journal of Clinical Medicine. 2020; 9(9):2730. https://doi.org/10.3390/jcm9092730
Chicago/Turabian StyleSeo, Eun Seop, Eun-jin Lee, Boram Lee, Muheon Shin, Young-Seok Cho, Ju Kyung Hyun, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Hong Hoe Koo, and et al. 2020. "Metastatic Burden Defines Clinically and Biologically Distinct Subgroups of Stage 4 High-Risk Neuroblastoma" Journal of Clinical Medicine 9, no. 9: 2730. https://doi.org/10.3390/jcm9092730