Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach
Abstract
:Simple Summary
Abstract
1. Introduction
2. Patients and Methods
2.1. Prior Treatment
2.2. Histopathology
2.3. Tumor Molecular Profiling
2.4. Patient Evaluation
2.5. “MEMMAT-like” Antiangiogenic Treatment
2.6. Intraventricular Therapy
2.7. Treatment Response and Toxicity Evaluation
2.8. Statistical Methods
3. Results
3.1. Diagnosis of Recurrence
3.2. Patients with a Ventriculoperitoneal (VP) Shunt in Place
3.3. Histopathology
3.4. Response and Clinical Outcome after Relapse That Prompted “MEMMAT-like” Treatment
3.5. Molecular Profiling and Outcome Depending on Group Allocation
3.6. Treatment after “MEMMAT-like”
3.7. Feasibility and Tolerability of “MEMMAT-like” Treatment
3.8. Toxicity
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Case | Age at Primary Diagnosis (Years)/ Gender | Morphology | MB Group | Subgroup | Prior Therapy (RT/CT/ HDCT) | Stage at Primary Diagnosis | No. of Recurrences | Time to Relapse from Primary Diagnosis or Prior Relapse (Months) | Type of Recurrence | Age at MEMMAT Start (Years) | Duration of MEMMAT (Months) | i.th Therapy/ VP-Shunt | Best Response | RT during MEMMAT | Status/ Follow-Up in Months after First MEMMAT Start | Duration of Follow-Up after Discontinuation of Last MEMMAT |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1° | 12/M | classic | 4 | G34_VIII | +/+/− | M2/M3 | 1 | 132 | M2/M3 | 24 | 14 + 2 * | Yes/no | CR | focal | CCR, 164+ | 149+ |
2° | 4/F | classic | 3 | G34_IV | +/+/− | M1 | 1 | 34 | M3 | 7 | 12 + 16 * | Yes/yes | CR | focal | CCR, 160+ | 132+ |
3° | 10/M | classic | 4 | G34_VIII | + */+/− | M1 | 2 | 8 | M1 | 14 | 12 + 24 * | Yes/no | CR | no | CCR, 160+ | 124+ |
4° | 9/M | classic | NA | + */+/− | M0 | 3 | 9 | M2/M3 | 15 | 21 + 17 ** | Yes/no | PR | no | DOD, 63 | ||
5 | 7/M | classic | Non WNT/non SHH | +/+/− | M0 | 1 | 69 | Local/M3 | 13 | 19 + 12 | Yes/yes | CR | Focal # | AWD,131+ | 65+ | |
6° | 9/F | classic | WNT | WNT | +/+/− | M0 | 1 | 58 | Local | 14 | 25 | No/yes | NE | no | DOD, 27 | |
7° | 12/M | LCA | 3 | G34_II | +/+/− | M0 | 1 | 32 | Local | 15 | 10 + 13 * | Yes/IIIrd | CR | no | DOC, 23 | |
8 | 1/F | classic | 3 | G34_IV | −/+/+ | M2/M3 | 1 | 24 | M2 | 4 | 9 | Yes/no | CR | 18Gy CSI+focal | CCR, 96+ | 87+ |
9 | 12/M | classic | 3–4 *** | G34_V *** | +/+/− | M2 | 1 | 36 | M2 | 14 | 22 + 24 * | Yes/no | CR | focal | CR, 134+ | 57+ |
10 | 5/M | classic | 4 | G34_VIII | +/+/− | M0-1 | 2 | 3 | M2/M3 | 8 | 20 + 12 * | Yes/no | CR | focal | DOC, 54 | |
11 | 4/M | classic | 4 | G34_V | +/+/− | M0-1 | 1 | 26 | M2/M3 | 7 | 29 | Yes/no | PR | focal | DOD, 44 | |
12 | 7.5/M | classic | 4 | G34_VIII | +/+/− | NA | 1 | 22 | M2/M3 | 10 | 24 | Yes/yes | PR | no | DOD, 32 | |
13 | 7/M | classic | 4 | G34_VIII | +/+/− | M2/M3 | 1 | 25 | M1,M2 | 9 | 34 | Yes/IIIrd | PR | focal | CR, 86+ | 31+ |
14° | 6/M | LCA | NA | + §/+/− | M1 | 2 | 21 | Local | 10 | 6 | No/yes | PR | no | DOD, 10 | ||
15 | 8/M | desmoplastic | NA | +/+/− | NA | 2 | 21 | Local/M3 | 10 | 5 | Yes/yes | SD | no | DOD, 6 | ||
16 | 7/M | classic | 4 | G34_VIII | +/−/− | NA | 1 | 10 | M1–M3 | 8 | 10 | Yes/yes | PR | focal | DOC, 46 | |
17 | 9/F | classic | 4 | G34_VIII | +/+/− | M0 | 1 | 14 | M1–M3 | 11 | 12 | Yes/yes | SD | focal | DOD, 26 | |
18 | 0.4/F | desmoplastic | 2, SHH inf | SHH_Inf_1 | −/+/− | M0 | 1 | 7 | M2 | 1 | 3 | Yes/no | PD | no | DOD, 5 | |
19 | 1/M | LCA | 3, high MYC ampl | G34_II | −/+/− | M2/M3 | 1 | 4 | M2/M3 | 1 | 2 | Yes/yes SD | PD | no | DOD, 3 | |
20 | 10/M | classic | 4 | G34_VIII | + §/+/− | M0 | 3 | 12 | M2/M3 | 11 | 3 | Yes/no | SD | no | DOC, 3 | |
21 | 5/M | classic | Non WNT/non SHH | +/+/− | M0 | 2 | 16 | M2/M3 | Yes/IIIrd | SD | focal | DOD,30 | ||||
22 | 4.5/F | classic | 4 | + §/+/+ | M3 | 2 | 18 | M2/M3 | 10 | 36 | Yes/no | PR | focal& | DOD,42 | ||
23 | 5/M | classic | 4 | G34_V | +/+/− | M0 | 1 | 26 | Local/M2 | 7 | 14 + 14 * | Yes | CR | focal& | CCR, 111+ | 83+ |
24 | 7.5/M | classic | 4 | G34_V | +/+/− | M0 | 1 | 32 | M1–M3 | 10 | 15 | Yes | CR | focal& | DOD,26 | |
25 | 6.5/F | classic | 4 | G34_VI | +/+/− | M0 | 1 | 12 | M1–M3 | 7 | 3 | Yes | PD | no | DOD,3 | |
26 | 8/M | classic | NA | +/+/− | M0 | 1 | 109 | local | 17 | 10 | Yes | PD | focal | DOD,13 | ||
27 | 12/M | classic | 4 | G34_VIII | + §/+/− | NA | 3 | 31 | M2 | 17 | 19 | Yes | PR | no | DOC,20 | |
28 | 8/F | classic | 4 | +/+/− | M0 | 1 | 15 | M1-M3 | 9 | 8 | Yes | SD | no | DOD,13 | ||
29 | 12/F | classic | 3 | +/+/− | M0 | 1 | 18 | M3 | 14 | 11 | Yes | CR | no | AWD, 97+ | 88+ |
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Slavc, I.; Mayr, L.; Stepien, N.; Gojo, J.; Aliotti Lippolis, M.; Azizi, A.A.; Chocholous, M.; Baumgartner, A.; Hedrich, C.S.; Holm, S.; et al. Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach. Cancers 2022, 14, 5128. https://doi.org/10.3390/cancers14205128
Slavc I, Mayr L, Stepien N, Gojo J, Aliotti Lippolis M, Azizi AA, Chocholous M, Baumgartner A, Hedrich CS, Holm S, et al. Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach. Cancers. 2022; 14(20):5128. https://doi.org/10.3390/cancers14205128
Chicago/Turabian StyleSlavc, Irene, Lisa Mayr, Natalia Stepien, Johannes Gojo, Maria Aliotti Lippolis, Amedeo A. Azizi, Monika Chocholous, Alicia Baumgartner, Cora S. Hedrich, Stefan Holm, and et al. 2022. "Improved Long-Term Survival of Patients with Recurrent Medulloblastoma Treated with a “MEMMAT-like” Metronomic Antiangiogenic Approach" Cancers 14, no. 20: 5128. https://doi.org/10.3390/cancers14205128