Table 1.
Clinical parameters, molecular alterations, line of treatment, treatment modalities, and backbone treatment of patients treated with personalized approaches.
| # | Center | Age | Gender | Localization | Molecular alteration | Line of treatment | Personalized treatment | Mode of action /rationale | Literature | Backbone treatment | OS (months) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Brno | 4.9 | m | Pons | PIK3CA(E545K) | First | Miltefosin (2 mg/kg/day once daily) | AKT inhibitor | (31, 32) | RTX, nimotuzumab 150 mg/m2 + vinorelbine 20 mg/m2 every 7 days for 12 weeks, followed by nimotuzumab 150 mg/m2 + vinorelbine 25 mg/m2 every 14 days, valproate (plasma level 80–100 μg/ml) | 44.5 |
| 2 | Brno | 4.9 | f | Pons | ACVR1(R206H) | First | Palovarotene (0.4 mg/kg/day once daily) | Active in germline ACVR1 mutation | (33) | RTX, nimotuzumab 150 mg/m2 + vinorelbine 20 mg/m2 every 7 days for 12 weeks, followed by nimotuzumab 150 mg/m2 + vinorelbine 25 mg/m2 every 14 days, valproate (plasma level 80–100 μg/ml) | 16.5 |
| 3 | Brno | 18.2 | m | Pons | TMB 20 mut/MB | First | Nivolumab (1 mg/kg every 2 weeks first 4 months followed by 3 mg/kg every 2 weeks) | Immune checkpoint inhibitor | (34) | RTX, nimotuzumab 150 mg/m2 + vinorelbine 20 mg/m2 every 7 days for 12 weeks, followed by nimotuzumab 150 mg/m2 + vinorelbine 25 mg/m2 every 14 days, valproate (plasma level 80–100 μg/ml) | 17.5* |
| 4 | Brno | 6.4 | f | Pons | PIK3CA(E545K) | First | Miltefosin (2.5 mg/kg/day once daily) | AKT inhibitor | (31, 32) | RTX, nimotuzumab/vinorelbine, valproate | 15.0 |
| 7 | Brno | 6.6 | f | Pons | FGFR3/CSF1R mRNA overexpression | Second | Pazopanib (5 mg/kg once daily, dose reduction due to side effects to 200 mg every other day) | Receptor tyrosine kinase inhibitor | Drugbank Canada (35) | RTX, nimotuzumab/vinorelbine, valproate | 8.0 |
| 8 | Brno | 19.0 | m | Spinal (lower thoracic region) | KRAS(G12A) | First | Trametinib (2 mg once daily) | MEK inhibitor | NCT03704688 (36) | RTX, nimotuzumab 150 mg/m2 + vinorelbine 20 mg/m2 every 7 days for 12 weeks, followed by nimotuzumab 150 mg/m2 + vinorelbine 25 mg/m2 every 14 days, valproate (plasma level 80–100 μg/ml), metoclopramide (0.4 mg/kg/day three times daily) | 12.9 |
| 9 | Vienna | 8.2 | m | Thalamic | BRAF(V600E) | Second | Dabrafenib (5 mg/kg/day divided twice daily), trametinib (0.04 mg/kg/day once daily), bevacizumab (10 mg/kg every 2 weeks) | BRAF/MEK inhibitors | (37–39) | Re-RTX, temozolomide (concomitant to RTX 75 mg/m2/day once daily) | 28.8 |
| 10 | Vienna | 12.9 | m | Pons | PIK3CA(G118D) | Second | Everolimus (4.5 mg/m2/day once daily, increased until trough level 5–15 ng/ml) | mTOR inhibitor | (40) | Temozolomide (200 mg/m2/day for 5 days at 28-day cycles), mebendazole 1500 mg/day three times daily | 21.4 |
| 12 | Vienna | 4.9 | m | Pons | PDGFRA(R841_I843delinsL) XPC(P334H) | First | Pazopanib (260 mg/m2/day once daily) pembrolizumab (2 mg/kg every 3 weeks) | PDGFRA inhibitor Immune checkpoint inhibitor | (34, 35, 41) | RTX, temozolomide (40 mg/m2/day once daily) | 6.1 |
*
Alive with disease; OS, overall survival; TMB, tumor mutational burden.