Table 1.
Patient Characteristics
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | |
|---|---|---|---|---|
| Treatment center | University children’s hospital Essen | University children’s hospital Essen | University children’s hospital Tübingen | University children’s hospital Freiburg |
| Age at diagnosis | 15 months | 4 months | 10 months | 51 months |
| Sex | Male | Male | Male | Male |
| Initial extend | Bilateral | Bilateral | Bilateral | Unilateral left eye |
| Constitutional RB1 alteration |
del RB1 Exon 20–CHCL1 (3´ gene) Heterozygote |
IVS6 + 1G > C Heterozygote |
del(13)(q14.2)(RB1-) Heterozygote |
No |
| Therapy |
Enucleation RE Cryotherapy LE Systemic CT* Brachytherapy LE IVC LE IAC LE Systemic CT* Radiotherapy (proton) LE 50 Gy Resection metastasis paravertebral Systemic CT** HD + ASCT Radiotherapy (proton) 50 Gy mandibula, 46 Gy paravertebral |
Systemic CT Enucleation RE Radiotherapy (photon) Systemic CT* Cryotherapy LE IAC LE Enucleation LE Systemic CT CWS**** § Radiotherapy midface & lymph nodes (proton) 50,4 Gy § Systemic maintenance CT § Systemic CT **/*** HD + ASCT Radiotherapy (proton) 44,2 Gy craniospinal |
systemic CT* IAC RE IAC & IVC LE cryotherapy RE IAC RE IAC LE enucleation RE radiotherapy (proton) LE 50 Gy systemic CT*** enucleation LE systemic CT** HD + ASCT |
Enucleation LE Systemic CT* Radiotherapy (proton) left orbital, N. opticus, chiasm 39 Gy exenteratio orbitae systemic CT** HD + ASCT radiotherapy (proton) 45 Gy N. opticus |
| Pathology enucleated eyes | Right: IRSS I |
Right: not known Left: IRSS I |
Right: IRSS I; N0, C2, S1. Left: IRSS I; N1, C2, S2 | Left: IRSS III, N3, C2, S1 |
| Location of metastasis (before ASCT) | IRSS Stage IVa: para-vertebral with intraspinal epidural and neuro-foraminal infiltration Th7/8, left mandibula and bone marrow infiltration | IRSS Stage IVb: right temporo-basal dura mater and soft tissue |
IRSS Stage IVa paraspinal |
IRSS Stage IVb: relapse infiltrating N. opticus, expanding prechiasmal |
| Time to metastasized disease | 90 months | 117 months | 33 months | 15 months |
| Confirmation of RB metastasis |
Yes resection paravertebral |
Yes biopsy Temporo-basal |
No, biopsy not conclusive |
Yes |
| GD2-expression | Bone marrow infiltration | Metastasis temporo-basal | Primary tumor, LE | Metastasis, chiasma opticus |
| Remission status prior anti-GD2 mAb | Residual tumor left mandibula | Complete remission | Residual tumor left orbital | Complete remission |
| Time to anti-GD2 mAb treatment after ASCT | 5 months | 4 months | 54 days | 5 months |
| Number and dose of anti-GD2 mAb |
5 cycles á 10d 100 mg/m2 |
3 cycles á 10d 100 mg/m2 ¥ |
5 cycles á 5d 100 mg/m2 |
5 cycles á 10d 100 mg/m2 |
| Response to anti-GD2 mAb | Yes | Not assessable | Yes | Not assessable |
| Relapse from start anti-GD2 mAb | No | No |
Yes CNS left frontal GD2 negative, B7H3 positive 12 months |
Yes leptomeningeal 10 months |
| Last follow-up from start anti-GD2 mAb | 45 months | 26 months |
Death 18 months |
11 months |
| Accompanying disease | No | Alveolar rhabdomyosarcoma | No |
Seizure Stenosis left A. carotis int. and occlusion left A. cerebri media, ant, post CNS abscess encephalocele left frontal Intraventricular bleeding |
LE left eye, RE right eye, CT chemotherapy, IVC intravitreal chemotherapy, IAC intraarterial chemotherapy, HD + ASCT high dose chemotherapy and autologous stem cell transplantation
*systemic chemotherapy according RB Registry
**systemic chemotherapy according NB 2004-HR
***systemic chemotherapy, TECC–scheme according CWS Guidance
****systemic chemotherapy according CWS Guidance, subgroup H for very high-risk aRMS
§therapy for aRMS, ¥ first cycle 8d, therapy stopped at 3rd cycle