title: Treatment results in children and adolescents with loco-regional recurrences of abdominal germ cell tumors (GCTs): a pilot-study with PEI chemotherapy and regional deep hyperthermia (RHT) in comparison to a matched cohort.
abstract: In this study treatment results in children and adolescents (n = 32) suffering from loco-regional abdominal relapses of germ cell tumors (GCT) (7 embryonal carcinoma, 17 Yolk sac tumors, 8 immature teratomas) aged from 1;0 to 23;3 years (mean = 10;11 years) were evaluated. In this pilot study 9 patients were treated with cisplatinum (40 mg/m2 on days 1 and 4), etoposide (100 mg/m2 on days 1 to 4), and ifosfamide (2000 mg/m2 on days 1 to 4) (PEI) +/- radiation in combination with regional deep hyperthermia (RHI). In sedation RHT was induced by non-invasive heat applicators (Sigma-40 and Sigma 60, BSD Medical Corporation, Utah, USA). In 7 out of these 9 patients with recurrent GCT a tumor response (5 CR, 2 PR, 1 SD, 1 PD) was found. In addition, in 2 patients a complete tumor resection could be achieved inspite of 2 previous incomplete tumor resections each. Five out of 9 patients are living event-free after an observation period ranging from 8 to 40 months (median = 15 months). Treatment results of this RHT study population were compared with treatment results in patients with recurrent GCT, who received conventional relapse therapy (chemotherapy/ surgery +/- radiation) alone. In this matched cohort 5 out of 23 patients are living event-free after an observation time ranging from 1 to 120 months (median = 8 months). According to Kaplan-Maier life table analysis, patients with relapse therapy combined with RHT have an event-free survival (EFS) of 0.41 +/- 0.33 whereas the matched cohort without RHT have an EFS of 0.16 +/- 0.25. The difference in treatment results of both groups is significant (Wilcoxon/p = 0.03). From the data presented in this study we conclude that children with loco-regional recurrences of extracranial non-testicular GCT have an unfavorable prognosis, unless local tumor control can be achieved. The additional application of RHT in combination with conventional therapy (PEI chemotherapy +/- radiation) can improve local tumor control and EFS in GCT patients with loco-regional recurrences. Therefore, based upon these results in the future MAKEI trial RHT will be applied to GCT patients with poor response to neoadjuvant chemotherapy alone as first line treatment.
authors.affiliation: Department of Pediatric Hematology and Oncology, Heinrich-Heine University, Düsseldorf.
authors.forename: R
authors.initials: R
authors.lastname: Wessalowski
authors.forename: M
authors.initials: M
authors.lastname: Blohm
authors.forename: G
authors.initials: G
authors.lastname: Calaminus
authors.forename: J
authors.initials: J
authors.lastname: Engert
authors.forename: D
authors.initials: D
authors.lastname: Harms
authors.forename: I
authors.initials: I
authors.lastname: Krause
authors.forename: H
authors.initials: H
authors.lastname: Kruck
authors.forename: H P
authors.initials: HP
authors.lastname: Grüttner
authors.forename: H
authors.initials: H
authors.lastname: Pape
authors.forename: U
authors.initials: U
authors.lastname: Göbel
mesh_terms: D000008:Abdominal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D010865:Pilot Projects; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide