Salvage treatment for children with relapsed/refractory germ cell tumors: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience

Abstract

Background: Malignant germ cell tumors (GCTs) are a heterogeneous group of rare neoplasms in children. Optimal outcome is achieved with multimodal therapies for patients with both localized and advanced disease, especially after the introduction of platinum-based chemotherapy regimens. In this respect, data on salvage treatment for children with relapsed or platinum-refractory disease are still limited.Methods: Retrospective analysis of data regarding patients affected by malignant GCTs with platinum-refractory or relapsed disease after first-line treatment according to AIEOP TCGM 2004 protocol was conducted.Results: Twenty-one patients, 15 females and 6 males, were considered for the analysis. All 21 patients received second-line conventional chemotherapy (SLCT), two of these immediately after surgery for local relapse removal. Two patients showed a progression of disease during SLCT and died of disease shortly thereafter, whereas 19 patients were in partial remission (PR) or complete remission (CR) after SLCT. Treatment after SLCT consisted in surgery on residual tumor mass (9/19) followed by high dose of chemotherapy (HDCT) with autologous hematopoietic stem cell support (16/19). The overall survival (OS) and event-free survival of the whole populations are 71% and 66.6%, respectively. Platinum-refractory patients OS is 54.5% compared with 91.5% of the relapsed group. There were no treatment-related deaths. Conclusion:SLCT followed or not by HDCT is an effective salvage treatment for children with relapsed/refractory GCTs. However, the role of HDCT following SLCT needs to be further investigated, especially regarding the identification of specific patient subgroups, which can benefit from this more intensive treatment.

Outcomes of relapsed/refractory extracranial germ cell tumors treated on conventional salvage chemotherapy without stem cell rescue: Experience from a tertiary cancer center

“…17 to achieve better local control was associated with a favorable outcome in few studies, 2,11 age more than 10 years was found to be significant in some. 1 Interestingly in our cohort, children 11 years and older at the time of relapse had better survival (5-year EFS: 46.20 vs. 24.60; 5-year OS: 46.20 vs. 29.50), but this association was not statistically significant. This could be because of a higher proportion of gonadal rel/ref-GCTs in this cohort, which is known to be associated with a better outcome.…”

Malignant sacrococcygeal germ cell tumors in childhood: The Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) experience

“…Globally, thirty‐seven patients entered CR (two of them with surgery only), four obtained PR (and achieved CR through deferred surgery), and four were nonresponders. Of these four nonresponders, the first one aged 2 years, YST, stage III for lymph nodes and peritoneal involvement, showed local progression, an increase in AFP levels, and multiple central nervous system metastases; a second‐line treatment according to the ICE regimen 11 proved ineffective and she died of PD 6 months after the diagnosis. The second one, aged 2.7 years at diagnosis, YST, stage IV for bilateral lung metastases, which showed local and marker‐related progression after three courses of pPEB, received a second‐line therapy and obtained a second continuous CR; unfortunately she died due to a fatal ventricular arrhythmia, following a heart transplant, performed because of heart failure, more than 10 years after the discontinuation of antiblastic treatment.…”

“…Three children also underwent local radiotherapy (see Table 3). 11 Only one of the relapsed patients (aged 1.7 years at diagnosis, YST, stage IV for bilateral lung metastases, AFP > 150 000 ng/mL at diagnosis) died due to progression of the disease after several more lines of treatment. Of the remaining nine patients, eight are in second continuous CR and one is in fourth continuous CR after two further relapses and related systemic and local treatments.…”

Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors—A Retrospective Analysis

“…Among the six patients (UPN 2, 4, 7, 8, 12, and 13) without metastatic disease at HDCT, three were not eligible for complete resection (UPN 2, 12, and 13), and the two who underwent ASCT after complete resection eventually relapsed. Among the seven post-pubertal patients, only three are alive ( UPN 5,11,and 18), and the best achievable resection prior to HDCT was not complete. The post-pubertal patients who died of disease (UPN 3, 6, 9, and 15) had inoperable, metastatic disease that progressed after HDCT.…”

“…In this study, ACST was performed in five patients; however, only one of five patients was cured, and no details on the HDCT regimen were provided. In 2020, De Pasquale et al published results from Italy, showing that in children with platinum-refractory GCT, OS is 54.5% (compared with 91.5% for the relapsed group), and a conditioning regimen based on thiotepa and cyclophosphamide was used in 15 of 16 patients [18]. In this study, 19 of 21 patients received a median of three cycles of the second line chemotherapy ICE (ifosfamide 1.8 g/m 2 days 1 to 5, carboplatin 400 mg/m 2 days 1 and 2, etoposide 100 mg/m 2 days 1 to 5) and in nine patients, surgery was performed on the residual tumor mass.…”