Glypican 3 (GPC3) expression in a lethal subgroup of refractory cisplatin-resistant testicular germ cell tumor (TGCT).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 559-559
Author(s):  
Jad Chahoud ◽  
Miao Zhang ◽  
Song-Chang Lin ◽  
Sue-Hwa Lin ◽  
Shi-Ming Tu
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Cell Tumor ◽  
Next Generation Sequencing Data ◽  
High Dose ◽  
Cell Transplant ◽  
Primary Tumors ◽  
Heavily Pretreated ◽  
Somatic Transformation ◽  
Gpc3 Expression

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.

Mesenteric lymphadenopathy in patients with germ cell tumor.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 347-347
Author(s):  
Hooman Djaladat ◽  
Craig R. Nichols ◽  
Siamak Daneshmand
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Mesenteric Lymph Node ◽  
Frozen Section ◽  
Cell Tumor ◽  
High Dose ◽  
Cell Transplant ◽  
Mesenteric Lymph

347 Background: Mesenteric lymphadenopathy may be secondary to inflammatory, infectious or tumoral pathologies. The most common malignancies causing mesenteric adenopathy are gastrointestinal and lymphoma. To the best of our knowledge, there are no reports of germ cell tumor (GCT) presenting with mesenteric adenopathy. Methods: Four patients with GCTs presenting with mesenteric adenopathies were treated in two academic centers (OHSU and USC) by a single surgeon since 2004. All pathologies were non-seminomatous GCT. Their presentation, clinico-pathologic findings and outcome are reviewed. Results: Two cases (19 and 51 yo) were IGCCC poor risk, stage II, testicular GCTs presenting with bulky retroperitoneal, periportal and mesenteric adenopathy. They both underwent post-chemo RPLND with mesenteric lymph node biopsy/resection. The intraoperative mesenteric lymph node frozen section study in one case revealed embryonal cell carcinoma and teratoma; he had early postoperative recurrence and is awaiting high dose chemotherapy and autologous stem cell transplant (HDC/ASCT). The other was teratoma and underwent resection, however he developed lung metastases with elevated AFP 6 months later and was treated with HDC/ASCT, being disease free for 2.5 years. The third case was a 29 yo IGCCC good risk testicular GCT who presented with retroperitoneal (II B) and mesenteric lymphadenopathy. He underwent post-chemo exploration and intraoperative frozen section of the mesenteric lymph nodes showed fibrosis and histiocytic infiltration; therefore classic RPLND was completed. The fourth case was a 24 yo HIV (-) patient with extragonadal GCT originating from the rectosigmoid. At presentation, he had a widespread mesenteric adenopathy, partially responded to primary (BEP) and salvage chemotherapy (VIP); he underwent recto/sigmoid resection, RPLND and PLND and had 52/104 lymph nodes positive for yolk sac tumor. He was referred for HDC/ASCT. Three cases were done recently with limited follow-up. Conclusions: The most common etiologies for mesenteric adenopathy are inflammatory, infection and neoplastic diseases. In the presence of germ cell tumor however, mesenteric adenopathy is most likely secondary to metastasis rather than secondary pathology.

scholarly journals Induction chemotherapy, surgical resection, and high-dose chemotherapy for mediastinal nonseminomatous germ-cell tumor

2005 ◽  
Vol 130 (4) ◽  
pp. 1205-1206 ◽  
Author(s):  
Hiroshi Date ◽  
Kiura Katsuyuki ◽  
Hiroshi Ueoka ◽  
Masahiro Tabata ◽  
Katsuyuki Hotta ◽  
...  
Keyword(s):  
Germ Cell ◽  
Surgical Resection ◽  
Induction Chemotherapy ◽  
Germ Cell Tumor ◽  
High Dose Chemotherapy ◽  
Cell Tumor ◽  
High Dose ◽  
Nonseminomatous Germ Cell Tumor

Decision Making in a Data-Poor Environment: Management of Brain Metastases From Testicular and Extragonadal Germ Cell Tumors

2016 ◽  
Vol 34 (4) ◽  
pp. 303-306 ◽  
Author(s):  
Timothy Gilligan
Keyword(s):  
Lymph Node ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Brain Magnetic Resonance Imaging ◽  
Acute Onset ◽  
Yolk Sac ◽  
Cell Tumor ◽  
High Dose ◽  
Hematopoietic Stem ◽  
History Of

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 32-year-old man with a history of a mixed germ cell tumor of the testis presented with acute-onset, right-sided weakness and numbness. His previous treatment included orchiectomy, which revealed a 5-cm tumor that was 95% yolk sac tumor and 5% embryonal carcinoma, and retroperitoneal lymph node dissection for clinical stage I disease in January 2010, which revealed no nodal metastases. Starting in June 2010, he was treated with four cycles of etoposide and cisplatin for pulmonary and thoracic lymph node metastases and a rising serum alpha-fetoprotein (AFP) level. He subsequently received four cycles of paclitaxel, ifosfamide, and cisplatin for relapse in the lungs and mediastinal nodes with a rising AFP level starting in January 2011. He reported having a 2-week history of intermittent headaches in December 2011, when he presented with acute-onset, right-sided weakness and numbness. Computed tomographs of the head was obtained and demonstrated a left parietal intracranial hemorrhage without midline shift or hydrocephalus. Brain magnetic resonance imaging (MRI) showed a complex, 4.5-cm mass consistent with a hemorrhagic metastasis. His serum AFP level was elevated at 47 ng/mL. The patient became progressively obtunded and underwent emergency surgical decompression and resection of the tumor. Histopathologic evaluation of the resected tissue showed metastatic germ cell tumor predominantly consisting of a yolk sac element ( Fig 1 ). His AFP level declined rapidly after resection, and computed tomography of the chest, abdomen, and pelvis showed no evidence of metastatic disease. However, 2 weeks later, his AFP level rose again, and repeat MRI of the brain showed a 3-cm mass in the left mesial parietal lobe adjacent to the resection site. He started treatment with filgrastim to facilitate collection of circulating hematopoietic stem cells. Several days later, after apheresis, he received his first of two cycles of high-dose carboplatin 700 mg/m2 on days −5, −4, and −3 and etoposide 750 mg/m2 on days −5, −4, and −3. The patient had a complete response to high-dose chemotherapy and no major acute complications. His cancer remains in complete remission 3 years later without additional treatment. His three lines of chemotherapy left him with chronic peripheral neuropathy.

Long-term outcome of salvage high-dose chemotherapy in patients with germ cell tumor with poor prognostic features

2011 ◽  
Vol 29 (3) ◽  
pp. 284-290 ◽  
Author(s):  
Ugo De Giorgi ◽  
Giovanni Rosti ◽  
Roberto Salvioni ◽  
Giorgio Papiani ◽  
Michela Ballardini ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
High Dose Chemotherapy ◽  
Cell Tumor ◽  
High Dose ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Prognostic Features

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

2019 ◽  
Vol 17 (3) ◽  
pp. e485-e487
Author(s):  
Cécile Vicier ◽  
Giulia Baciarello ◽  
Julia Arfi-Rouche ◽  
Christophe Massard ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumor ◽  
Complete Response ◽  
Cell Tumor ◽  
Heavily Pretreated ◽  
Gemcitabine Treatment

Site of metastases does not influence the clinical outcome of children with metastatic Germ Cell Tumors (GCT). A report from the Childrens Oncology Group (COG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9002-9002
Author(s):  
M. H. Malogolowkin ◽  
W. B. London ◽  
B. Cushing ◽  
R. Giller ◽  
M. Davis ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Germ Cell ◽  
Germ Cell Tumor ◽  
Germ Cell Tumors ◽  
Stage Iv ◽  
Yolk Sac ◽  
Cell Tumor ◽  
High Dose ◽  
Metastatic Site ◽  
Yolk Sac Tumors

9002 Background: To describe the clinical outcome of children with metastatic GCT (stage IV) at diagnosis according to the primary metastatic site(s). Methods: From March 1990 to February 1996, 299 children and adolescents with stage III/IV gonadal and stage I-IV extragonadal GCT were eligible for a Pediatric Intergroup high-risk (HR) GCT trial. Patients were randomized to receive 4–6 courses of cisplatin (P) standard dose [ 20 mg/m2/day (d) × 5] or high-dose (HDP) [40 mg/m2/d × 5] with etoposide (E) 100 mg/m2/d × 5 and bleomycin (B) 15 mg/m2 on d1. We retrospectively investigated the outcome of patients with stage IV and compared their outcome according to metastatic site(s). Results: There were 133 patients with stage IV disease. The median age was 2.6 years (y) [range, 3 d-19.3 y], 70 were female. Primary sites included: 43 testicular, 14 ovarian, 76 extragonadal (45 sacroccocygeal, 28 mediastinal, 3 other). Histologies included: 66 pure yolk sac tumors, 21 immature teratomas and yolk sac tumors, 26 mixed germ cell tumors, 7 pure germinoma/seminoma/dysgerminomas, 1 immature teratoma with a non-classic germ cell tumor, 2 mixed germ cell tumor admixed with a nonclassic germ cell tumor, 5 pure choriocarcinomas, and 5 patients with unknown histology. There were no statistically significant differences in the 5-year EFS or OS rates by site of metastases. Of the 19 patients with either bone or brain involvement, 17 patients had bone and 3 had brain metastases. Conclusion: The outcome for patients with metastatic GCT is excellent with contemporary cisplatin-based regimes and is independent of the site of metastatic disease. [Table: see text] No significant financial relationships to disclose.

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