Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | WNT | SHH | Group 3 | Group 4 |
---|---|---|---|---|
Proportion of patients | 10% (Rarest) | 30% (2nd common) | 25% (Common) | 35% (Most common) |
Age at initial presentation | Older children and adolescents (rarely in infants) | All age groups (2 peaks—infants and adults) | Infants and young children (rarely in adults) | All age groups (commonly in children) |
Male–Female ratio | Equal (1:1) | Equal (1:1) | Favors males (2:1) | Male preponderance (3–4:1) |
Histo-morphology | Classic, rarely LC/A | ND/MBEN or Classic | LC/A, Classic | Classic, LC/A |
Leptomeningeal metastases | Very rare (<5%) | Uncommon (15–20%) | Very common (40–50%) | Common (35–40%) |
Anatomic location of the tumour | Midline extending into cerebellopontine angle | Lateralized (cerebellar hemispheric) and superior | Midline and inferior (IVth ventricle) | Midline and inferior (IVth ventricle) |
Proposed cell of origin | Lower rhombic lip progenitors | Granule neuron precursor cells in the external granular layer | Prominin+/CD133+ lineage neural stem cell | Premature glutamatergic neuronal networks |
Candidate driver genes | CTNNB1, DDX3X | PTCH1, TP53, GLI2, KMT2D, MYC amplification | MYC amplification, SMARCA4, OTX2, | KDM6A, SNCAIP gain, MYCN amplification |
Five-year overall survival | Excellent: >90–95% | Intermediate: 70% (50–85%) | Poor: 45% (30–60%) | Good: 75% (50–85%) |
Characteristics | Number of Patients (%) |
---|---|
Median age (interquartile range) at diagnosis | 12 years (9–18 years) |
Gender | |
Male | 44 (65.7%) |
Female | 23 (34.3%) |
Postoperative residual tumour (n = 57) | |
<1.5 cm2 | 47 (82.4%) |
≥1.5 cm2 | 10 (17.6%) |
Metastatic status at diagnosis (n = 62) | |
Nonmetastatic (M0) | 57 (91.9%) |
Metastatic disease (M+) | 5 (8.1%) |
Conventional risk stratification (n = 55) | |
Average risk | 39 (70.9%) |
High risk | 16 (29.1%) |
Histological subtype | |
Medulloblastoma (not otherwise specified) | 22 (32.8%) |
Classic | 41 (61.2%) |
Desmoplastic | 3 (4.5%) |
Large cell/Anaplastic | 1 (1.5%) |
Time interval from surgery to adjuvant radiotherapy (n = 40) | |
≤6 weeks | 17 (42.5%) |
>6 weeks | 23 (57.5%) |
Craniospinal irradiation dose (n = 54) | |
23.4–26 Gy $ | 23 (42.6%) |
35–36 Gy | 31 (57.4%) |
Craniospinal irradiation technique (n = 39) | |
Conventional radiotherapy | 1 (2.6%) |
Three-dimensional conformal radiotherapy | 16 (41.0%) |
Intensity-modulated radiation therapy | 22 (56.4%) |
Adjuvant systemic chemotherapy (n = 54) | |
Yes | 39 (72.2%) |
No | 15 (27.8%) |
Cumulative cyclophosphamide dose (n = 39) | |
≤12 mg/m2 | 11 (28.2%) |
>12 mg/m2 | 28 (71.8%) |
Sr No. | Age (Years) /Gender | Stage | CSI Dose at Initial Diagnosis | Pattern of First Failure | PFS | Salvage Therapy at Relapse | Final Outcome | OS |
---|---|---|---|---|---|---|---|---|
W1 | 9/Male | Nonmetastatic | 36 Gy/18 fx | Tumour-bed recurrence | 25 months | Re-RT and chemotherapy | Died of disease | 80 months |
W2 | 11/Male | Nonmetastatic | 26 Gy/13 fx | Tumour-bed relapse plus metastases in brainstem, temporal lobe, and spine | 37 months | Re-CSI (36 Gy/36fx) and chemotherapy | Died of disease | 66 months |
W3 | 13/Female | Nonmetastatic | 35 Gy/21 fx | Leptomeningeal dissemination | 25 months | Best supportive care | Died of disease | 25 months |
W4 | 10/Male | Nonmetastatic | 14.4 Gy/8 fx (Incomplete RT) | Leptomeningeal dissemination | 61 months | Best supportive care | Died of disease | 62 months |
W5 | 27/Male | Nonmetastatic | 35 Gy/21 fx | Leptomeningeal dissemination | 58 months | Best supportive care | Died of disease | 60 months |
W6 | 14/Male | Metastatic (frontal horn lesion) | 35 Gy/21 fx | No evidence of disease progression/failure | 15 months | Not applicable | Died of toxicity | 15 months |
W7 | 9/Male | Nonmetastatic | 36 Gy/18 fx | Tumour-bed recurrence | 56 months | Resurgery | Died of disease | 60 months |
W8 | 22/Male | Nonmetastatic | 35 Gy/21 fx | Extra-neural metastases | 83 months | Chemotherapy | Alive with disease | Not applicable |
W9 | 15/Male | Nonmetastatic | Not known | Tumour-bed relapse plus metastases in frontal horn and multiple spinal metastases | 59 months | Resurgery | Died of disease | 67 months |
Variables | Category | 5-Year PFS (95%CI) | p-Value | 5 Years OS (95%CI) | p-Value |
---|---|---|---|---|---|
Gender | Male | 86.0% (73.8–100%) | 0.480 | 92.6% (83.1–100%) | 0.440 |
Female | 93.3% (81.5–100%) | 93.7% (82.6–100%) | |||
Age at diagnosis | Child (≤16-years) | 83.5% (83.0–100%) | 0.722 | 89.5% (87.5–100%) | 0.323 |
Adult (>16-years) | 90.0% (68.0–100%) | 90.9% (72.0–100%) | |||
Residual disease | <1.5 cm2 | 84.5% (72.6–98.4%) | 0.250 | 90.7% (80.9–100%) | 0.260 |
≥1.5 cm2 | 100% (NE) | 100% (NE) | |||
Metastatic status | Nonmetastatic (M0) | 89.1% (79.1–100%) | 0.320 | 94.2% (86.4–100%) | 0.270 |
Metastatic (M+) | 80.0% (51.6–100%) | 80.0% (51.6–100%) | |||
Risk stratification | Average risk | 93.3% (81.5–100%) | 0.560 | 100% (NE) | 0.640 |
High risk | 81.2% (63.9–100%) | 87.9% (73.5–100%) | |||
Time interval (Surgery to RT) | ≤42 days | 87.3% (72.4–100%) | 0.500 | 94.1% (83.6–100%) | 0.440 |
>42 days | 89.4% (76.7–100%) | 94.7% (85.2–100%) | |||
Dose of CSI | Low dose (14.4–26 Gy) | 94.1% (83.0–100%) | 0.441 | 100% (NE) | 0.698 |
High dose (35–40 Gy) | 81.0% (68.1–97.0%) | 84.6% (72.0–100%) | |||
Adjuvant chemotherapy | No | 91.6% (77.2–100%) | 0.990 | 100% (NE) | 0.940 |
Yes | 84.3% (70.6–100%) | 87.8% (75.2–100%) | |||
Cyclophosphamide dose | <12 gm/m2 | 92.8% (80.3–100%) | 0.970 | 100% (NE) | 0.970 |
≥12 gm/m2 | 88.7% (77.4–100%) | 92.6% (83.2–100%) |
Trial Identity [Ref] and Registration | Risk Category | WNT-MB Patients | WNT-MB Failures | Patterns of Relapse | 5-Year EFS/PFS | 5-Year OS | ||
---|---|---|---|---|---|---|---|---|
Local | Metastatic | Combined | ||||||
HIT 2000 [45] NCT00303810 | Nonmetastatic (average risk) | 15 | 0 | 0 | 0 | 0 | 100% | 100% |
SIOP PNET-4 [42] NCT01351870 | Average risk | 58 | 8 | 2 | 4 | 2 | 91% | 95% |
HIT 2000 [46] NCT00303810 | Metastatic (high risk) | 4 | 0 | 0 | 0 | 0 | 100% | 100% |
COG ACNS 0331 [11] NCT00085735 | Average risk | 64 | 4 | 4 | 0 | 0 | 93.3% | 95.5% |
SJMB-03 [12] NCT00085202 | Average risk and high risk | 46 | 0 | 0 | 0 | 0 | 100% | 100% |
COG ACNS 0332 [47] NCT00392327 | High risk | 14 | 1 | 0 | 0 | 1 | 92.9% | 100% |
SIOP PNET 5 HR+ [48] NCT00936156 | High risk | 3 | 0 | 0 | 0 | 0 | 100% | 100% |
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Mani, S.; Chatterjee, A.; Dasgupta, A.; Shirsat, N.; Pawar, A.; Epari, S.; Sahay, A.; Sahu, A.; Moiyadi, A.; Prasad, M.; et al. Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma. Diagnostics 2024, 14, 358. https://doi.org/10.3390/diagnostics14040358
Mani S, Chatterjee A, Dasgupta A, Shirsat N, Pawar A, Epari S, Sahay A, Sahu A, Moiyadi A, Prasad M, et al. Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma. Diagnostics. 2024; 14(4):358. https://doi.org/10.3390/diagnostics14040358
Chicago/Turabian StyleMani, Shakthivel, Abhishek Chatterjee, Archya Dasgupta, Neelam Shirsat, Akash Pawar, Sridhar Epari, Ayushi Sahay, Arpita Sahu, Aliasgar Moiyadi, Maya Prasad, and et al. 2024. "Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma" Diagnostics 14, no. 4: 358. https://doi.org/10.3390/diagnostics14040358
APA StyleMani, S., Chatterjee, A., Dasgupta, A., Shirsat, N., Pawar, A., Epari, S., Sahay, A., Sahu, A., Moiyadi, A., Prasad, M., Chinnaswamy, G., & Gupta, T. (2024). Clinico-Radiological Outcomes in WNT-Subgroup Medulloblastoma. Diagnostics, 14(4), 358. https://doi.org/10.3390/diagnostics14040358