A Case of Heavily Pretreated Metastatic Germ Cell Tumor With Ongoing Long-term Complete Response After Gemcitabine Treatment

559 Background: The oncofetal protein GPC3 has been tested as a therapy target. Early phase clinical trials established the safety and efficacy of anti-GPC3 chimeric antigen receptor modified T cells in patients with refractory or relapsed GPC3+ hepatocellular carcinoma. In TGCT, GPC3 is preferentially expressed at presentation in certain germ cell histological phenotypes (yolk sac tumor [YST], choriocarcinoma), but not in others (embryonal carcinoma, teratoma, seminoma). The aim of this study is to evaluate GPC3 expression in a lethal subgroup of refractory cisplatin-resistant TGCT. Methods: We retrospectively evaluated 615 patients diagnosed with TGCT from January 2000 to December 2010. We identified patients who died from their TGCT. The histologic makeup of primary tumors, next-generation sequencing data and the clinical course of disease were determined for each patient. We prospectively evaluated GPC3 expression by immunohistochemistry (IHC) using a mouse monoclonal antibody (YP7), on tumor tissue from these patients with lethal, heavily pretreated, cisplatin-resistant TGCT. Results: We identified seven patients with fatal and cisplatin-resistant TGCT, with a median age of 30 (28-50) years and a median number of prior therapies of 5 (2-8), including 3 patients who received high-dose chemotherapy with autologous stem-cell transplant. The prospectively collected samples were from different sites of metastasis: lymph nodes (n = 4), peritoneal carcinomatosis (n = 2), and lung (n = 1). The tissue histology comprised YST (n = 2), YST + choriocarcinoma (n = 1), YST + teratoma (n = 1), teratoma (n = 1), and somatic transformation (n = 2). No consistent genetic aberration was detected. The viable germ cell tumor components comprising YST and choriocarcinoma (n = 4) stained strongly positive in a membranous distribution for GPC3. While samples with teratoma and somatic transformation histology (n = 3) did not stain for GPC3. Conclusions: Potentially lethal, heavily pretreated, cisplatin-resistant viable germ cell tumors have enhanced expression of GPC3. Targeted therapy directed against GPC3 could benefit patients harboring such tumors and further investigation is of value.

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Long-term quality of life and neuropsychologic functioning for patients with CNS germ-cell tumors: From the First International CNS Germ-Cell Tumor Study

Neuro-Oncology ◽

10.1215/15228517-3-3-174 ◽

2001 ◽

Vol 3 (3) ◽

pp. 174-183 ◽

Cited By ~ 1

Author(s):

S. A. Sands

Keyword(s):

Quality Of Life ◽

Germ Cell ◽

Germ Cell Tumor ◽

Germ Cell Tumors ◽

Cell Tumor ◽

Tumor Study ◽

Cns Germ Cell Tumor

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Incidence of Late-Relapse Germ Cell Tumor and Outcome to Salvage Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.2005.21.956 ◽

2005 ◽

Vol 23 (28) ◽

pp. 6999-7004 ◽

Cited By ~ 59

Author(s):

Ellen A. Ronnen ◽

G. Varuni Kondagunta ◽

Jennifer Bacik ◽

Stephanie Marion ◽

Dean F. Bajorin ◽

...

Keyword(s):

Clinical Trial ◽

Germ Cell ◽

Retrospective Analysis ◽

Germ Cell Tumor ◽

Complete Response ◽

Salvage Chemotherapy ◽

Cell Tumor ◽

Late Relapse ◽

First Line ◽

Line Chemotherapy

Purpose To define the incidence, clinical features, and outcome to salvage chemotherapy in patients with late-relapse germ cell tumor (GCT) after a complete response to first-line chemotherapy. Patients and Methods Two patient populations were examined. First, retrospective analysis of 246 patients treated on a clinical trial with salvage chemotherapy was performed; 29 patients with late-relapse GCT were identified and evaluated for treatment outcome and survival. Salvage regimens included paclitaxel, ifosfamide, and cisplatin, single agents, or a high-dose chemotherapy program. Second, the incidence of late relapse was assessed by retrospective analysis of 551 patients after a complete response (CR) to first-line chemotherapy. Results Twenty-nine patients received salvage chemotherapy on a clinical trial for late relapse GCT. The median survival was 23.9 months. At a median follow-up of 50.6 months, there were nine survivors. The chemotherapy regimens varied, but the only CRs were observed in patients treated with paclitaxel, ifosfamide, and cisplatin. Seven (50%) of 14 patients treated with paclitaxel, ifosfamide, and cisplatin achieved a continuous CR. Among the second population of 551 patients who had previously achieved a CR to a first-line chemotherapy trial, 17 were identified as having a late relapse (3%). The median time to relapse for these 17 patients was 7.8 years. Conclusion Late-relapse GCT is uncommon and is associated with a poor prognosis resulting from a high degree of resistance to chemotherapy. Chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by surgery may be effective in patients with late-relapse GCT who are not considered candidates for primary surgery.

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