Impact of Teratoma on the Cumulative Incidence of Disease-Related Death in Patients With Advanced Germ Cell Tumors

PURPOSE In men with metastatic germ cell tumors (GCTs), risk-directed treatment is determined, in part, by a distinction between seminoma and nonseminomatous GCT (NSGCT). The importance of NSGCT cell type is uncertain. We evaluated the long-term impact of teratoma on survival in patients with NSGCT. METHODS Prechemotherapy, primary tumors from patients who received platinum-based chemotherapy were studied, and the histology was confirmed by a genitourinary pathologist. The cumulative incidence of disease-related death (CIDD) was the primary end point, and a competing-risk analysis was performed. RESULTS Tumors were available from 232 patients, including 193 with NSGCT. An element of teratoma was present in 82 NSGCT primary tumors (42%). With a median follow-up of 17 years (range, 0.3 to 35 years), 58 patients with NSGCT died, 47 as a result of GCT and 11 as a result of other causes. Most GCT deaths occurred within the first 5 years and were associated with pretreatment risk status ( P < .001). Death as a result of other causes rose steadily after 15 years and was not associated with risk status ( P = .66). A higher CIDD was observed in patients who had NSGCT with teratoma than those with NSGCT without teratoma and seminoma (5-year CIDD rate, 27.4%, 17.4%, and 10.3%, respectively; P = .03). A higher CIDD was observed in patients who had NSGCT with mature teratoma compared with those with either NSGCT with immature teratoma or NSGCT without teratoma (5-year CIDD rate, 38.1%, 19.9%, and 17.4%, respectively; P = .01). CONCLUSION The presence of teratoma, particularly mature teratoma, in an NSGCT primary tumor is associated with a higher CIDD, consistent with the hypothesis that differentiation is associated with adverse outcomes. Death as a result of non-GCT causes is not associated with risk status and must be separated from GCT death when evaluating long-term survival.

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Results of Treatment After Relapse From High-Dose Chemotherapy in Germ Cell Tumors

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.6.1181 ◽

2000 ◽

Vol 18 (6) ◽

pp. 1181-1186 ◽

Cited By ~ 65

Author(s):

Pierluigi Porcu ◽

Sumeet Bhatia ◽

Matt Sharma ◽

Lawrence H. Einhorn

Keyword(s):

Germ Cell ◽

Response Rate ◽

Objective Response ◽

Germ Cell Tumors ◽

High Dose Chemotherapy ◽

Salvage Treatment ◽

High Dose ◽

Term Survival ◽

Platinum Based Chemotherapy

PURPOSE: To identify therapy-related or patient-related characteristics that predict response and long-term survival after failure of high-dose chemotherapy (HDCT) for germ cell tumors (GCT). PATIENTS AND METHODS: Between 1986 and 1997, 101 GCT patients relapsed after high-dose carboplatin and etoposide (VP-16) at Indiana University (Indianapolis, IN). Median time to relapse was 10 months (range, 1 to 17 months). HDCT was the first salvage treatment in 29 patients and second or later salvage treatment in 72 patients. RESULTS: Fifty-four of 101 patients received post-HDCT treatment. Of these, 47 received chemotherapy, alone (n = 35) or in combination with surgery (n = 12). Seven patients underwent surgery alone. There were only 12 objective responses (three complete and nine partial responses) for 66 chemotherapy regimens given to 47 patients, for an overall response rate of 18.2%. Fifteen patients received platinum-based chemotherapy, with only one objective response. Chemotherapy was discontinued in 17% of cases because of toxicity. A longer interval between HDCT and post-HDCT treatment was the only variable that was associated with response. Five patients (4.9%) are disease-free at 30, 53, 57, 85, and 93 months after relapse. Of these, three responded to oral VP-16 and underwent resection of residual mediastinal, retroperitoneal, and inguinal cancer, respectively. One had resection of residual mediastinal yolk sac tumor, followed by oral VP-16. One relapsed with teratoma and received thoracoabdominal resection without chemotherapy. CONCLUSION: Patients who experience disease progression after HDCT often receive further chemotherapy and/or surgery. Chemotherapy resulted in a response rate of less than 20%, with only three complete responses. All of the long-term survivors (4.9%) had surgery as a component of their post-HDCT regimen.

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Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study

Journal of Neurosurgery ◽

10.3171/2020.6.jns20638 ◽

2020 ◽

pp. 1-9

Author(s):

Hiroyuki Shimizu ◽

Kazuya Motomura ◽

Fumiharu Ohka ◽

Kosuke Aoki ◽

Kuniaki Tanahashi ◽

...

Keyword(s):

Germ Cell ◽

Poor Prognosis ◽

Mature Teratoma ◽

Germ Cell Tumors ◽

Progression Free Survival ◽

Survival Models ◽

Term Survival ◽

Platinum Based Chemotherapy ◽

Intracranial Germ Cell Tumors ◽

Prognosis Group

OBJECTIVEThe current study aimed to evaluate the treatment outcomes and toxicities of patients with intracranial germ cell tumors (GCTs).METHODSThis study retrospectively included 110 consecutive patients (70 patients in the germinomatous group and 40 patients in the nongerminomatous GCT [NGGCT] groups) receiving surgery, platinum-based chemotherapy, and radiotherapy for newly diagnosed primary intracranial GCTs. In the authors’ protocol, patients with GCTs were further divided into the following four groups: the germinomatous group and the NGGCT groups (mature teratoma, intermediate prognosis, or poor prognosis).RESULTSThe median overall survival (OS) and progression-free survival (PFS) rates of the patients in the germinomatous group were significantly higher than those in the NGGCT group (p < 0.001). The 5-, 10-, and 20-year OS rates in the germinomatous group were 97.1%, 95.7%, and 93.2%, respectively, with a median follow-up of 11.0 years. On the contrary, the 5-, 10-, and 20-year OS rates in the NGGCT group were 67.3%, 63.4%, and 55.4%, respectively. The 5-, 10-, and 20-year PFS rates were 91.4%, 86.6%, and 86.6%, respectively, in the germinomatous group, whereas those of the NGGCT group were approximately 67.4%, 60.2%, and 53.5%, respectively. Based on the four types of classification in our study, the 5-, 10-, and 20-year OS rates in the NGGCT intermediate prognosis group were 78.9%, 71.8%, and 53.8%, respectively. On the contrary, the 3- and 5-year OS rates in the NGGCT poor prognosis group were 42.9% and 34.3%, respectively. Moreover, toxicities with the treatment of intracranial GCTs were found to be tolerable in the present study population. The multivariate survival models for OS in the NGGCT intermediate prognosis and poor prognosis groups demonstrated that only the alpha-fetoprotein status was significantly associated with worsened OS (HR 3.88, 95% CI 1.29–11.66; p = 0.02).CONCLUSIONSThe authors found that platinum-based chemotherapy and radiotherapy result in favorable survival outcomes in patients with germinomatous GCTs. Clinical outcomes were still unfavorable in the NGGCT intermediate prognosis and poor prognosis groups; therefore, a new protocol that increases the survival rate of patients belonging in both groups should be considered.

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Multimodality treatment for intracranial germ cell tumors: Experience from an Asian tertiary hospital.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e13027 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e13027-e13027

Author(s):

Dawn QQ Chong ◽

Iain BeeHuat Tan ◽

Daniel HY Tan ◽

Eu Tiong Chua ◽

Chee Kian Tham

Keyword(s):

Germ Cell ◽

Survival Data ◽

Germ Cell Tumors ◽

Multimodality Treatment ◽

Tertiary Hospital ◽

Therapeutic Modality ◽

Platinum Based Chemotherapy ◽

Intracranial Germ Cell Tumors ◽

Multifocal Disease

e13027 Background: Intracranial germ cell tumors (GCTs) represent up to 11 percent of pediatric central nervous system (CNS) tumors in Asia. We compared the efficacy of radiotherapy alone (RT) with platinum-based chemotherapy (CT) in combination with dose-attenuated RT. Methods: We identified 61 patients treated at National Cancer Centre Singapore from 1995 to 2011. Patient’s demographics, histopathologic characteristics and survival data were collected. Median follow up was 39 months. Results: Forty-eight (79%) patients were male; mean age at diagnosis was 17 years. Most (87%) patients had pineal or suprasellar tumors. The distribution of pure germinomas, non-germinomatous tumors and mixed tumors was 54 (89%), 5 (8%) and 2 (3%) patients, respectively. Twenty patients had RT alone, 2 had CT alone, and 31 received a combination of CT and attenuated RT. There was no difference in overall survival (OS) between unifocal or multifocal disease (p = 0.81). Amongst the germinomas, there was no difference in OS between patients given RT alone and CT combined with attenuated RT (median OS not reached vs 145 months, respectively, p = 0.668). Conclusions: Treatment with CT followed by dose attenuated RT is an alternative to conventional craniospinal RT and did not compromise survival in patients with germinomas. This may represent a therapeutic modality with a more favorable long term toxicity profile in these patients who have excellent long term outcomes.

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Outcome of Patients With Residual Germ Cell or Non-Germ Cell Malignancy After Resection of Primary Mediastinal Nonseminomatous Germ Cell Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2004.07.102 ◽

2004 ◽

Vol 22 (7) ◽

pp. 1195-1200 ◽

Cited By ~ 28

Author(s):

Bryan P. Schneider ◽

Kenneth A. Kesler ◽

Jo Ann Brooks ◽

Constantin Yiannoutsos ◽

Lawrence H. Einhorn

Keyword(s):

Germ Cell ◽

Residual Disease ◽

Cell Cancer ◽

Elevated Serum ◽

Germ Cell Tumors ◽

Term Survival ◽

Poor Risk Patient ◽

Nonseminomatous Germ Cell Tumor ◽

Alive With Disease

PurposeTo identify prognostic variables and outcomes in patients with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) with postchemotherapy resection of persistent cancer.Patients and MethodsForty-seven consecutive patients with residual cancer after resection of PMNSGCT were retrospectively reviewed. Univariate comparisons were performed.ResultsAt diagnosis, 43 patients had elevated serum tumor markers (STMs), and 20 had extramediastinal disease. At resection, 21 patients had elevated STMs. After resection, 26 patients had germ cell tumors (GCT), 12 had malignant transformation of teratoma with elements of non-GCT, and nine had both GCT and non-GCT. Sixteen of 47 patients continuously have no evidence of disease (NED). This includes eight of 26 patients with GCT histology and two of 12 patients with non-GCT histology. Of 27 patients with mediastinal-only disease at presentation, 14 have continuously NED. Of 20 patients with extramediastinal disease at presentation, two have continuously NED. Seven of 21 patients with elevated STMs at time of resection have continuously NED. Sixteen patients received adjuvant chemotherapy, and seven have continuously NED. Overall, 16 of 47 patients have continuously NED, an additional four patients have NED with further therapy (currently NED), two patients are alive with disease, 23 patients died of disease, and two patients died postoperatively.ConclusionThe presence of elevated STMs at resection does not appear to alter outcome if residual disease is completely resected. In this poor-risk patient population, surgical resection of persistent cancer, even in the presence of elevated STMs, can still achieve long-term survival.

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Long-term survival with paclitaxel and gemcitabine for germ cell tumors after progression following high-dose chemotherapy with tandem transplants.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.4562 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 4562-4562

Author(s):

B. P. Mulherin ◽

M. J. Brames ◽

L. H. Einhorn

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

High Dose Chemotherapy ◽

High Dose ◽

Term Survival ◽

Long Term Survival

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Long-Term Survival After Treatment with Gemcitabine and Oxaliplatin With and Without Paclitaxel Plus Secondary Surgery in Patients with Cisplatin-Refractory and/or Multiply Relapsed Germ Cell Tumors

European Urology ◽

10.1016/j.eururo.2011.06.019 ◽

2011 ◽

Vol 60 (4) ◽

pp. 850-855 ◽

Cited By ~ 55

Author(s):

Karin Oechsle ◽

Christian Kollmannsberger ◽

Friedemann Honecker ◽

Frank Mayer ◽

Cornelius F. Waller ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Secondary Surgery ◽

Term Survival ◽

Long Term Survival

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Extragonadal Germ Cell Tumors of the Mediastinum and Retroperitoneum: Results From an International Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2002.07.062 ◽

2002 ◽

Vol 20 (7) ◽

pp. 1864-1873 ◽

Cited By ~ 258

Author(s):

Carsten Bokemeyer ◽

Craig R. Nichols ◽

Jean-P. Droz ◽

Hans-J. Schmoll ◽

Alan Horwich ◽

...

Keyword(s):

Survival Rate ◽

Germ Cell ◽

Germ Cell Tumor ◽

Germ Cell Tumors ◽

Treatment Strategies ◽

Cell Tumor ◽

Primary Tumor Site ◽

Primary Tumors ◽

Platinum Based Chemotherapy

PURPOSE: To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies.PATIENTS AND METHODS: Of an unselected population of 635 consecutive patients treated from 1975 through 1996 at 11 cancer centers, 341 patients (54%) had primary mediastinal EGCT, and 283 patients (45%) had retroperitoneal EGCT. Five hundred twenty-four patients (83%) had a nonseminomatous germ cell tumor (GCT), and 104 patients (16%) had a seminomatous histology.RESULTS: After platinum-based induction chemotherapy with or without secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow-up, 19 months; range, 1 to 178 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow-up, 29 months; range, 1 to 203 months) are alive (P = .0006). In contrast, the overall survival rate for patients with a seminomatous EGCT is 88%, with no difference between patients with mediastinal or retroperitoneal tumor location (median follow-up, 49 months; range, 4 to 193 months; respective 70 months; range, 1 to 211 months). A significantly lower progression-free survival rate was found in seminoma patients treated with initial radiotherapy alone compared with chemotherapy. Nonseminomatous histology, presence of nonpulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-human chorionic gonadotropin were independent prognostic factors for shorter survival. Hematologic malignancies (n = 17) occurred without exception in patients with primary mediastinal nonseminoma. Sixteen patients developed a metachronous testicular cancer despite the use of platinum-based chemotherapy.CONCLUSION: Whereas patients with pure seminomatous EGCT histology have a long-term chance of cure of almost 90% irrespective of the primary tumor site, 45% of patients with mediastinal nonseminomas are alive at 5 years. This outcome is clearly inferior compared with patients with nonseminomatous retroperitoneal primary tumors.

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Leukemia following treatment of germ cell tumors in men.

Journal of Clinical Oncology ◽

10.1200/jco.1984.2.10.1080 ◽

1984 ◽

Vol 2 (10) ◽

pp. 1080-1087 ◽

Cited By ~ 56

Author(s):

J R Redman ◽

D Vugrin ◽

Z A Arlin ◽

T S Gee ◽

S J Kempin ◽

...

Keyword(s):

Germ Cell ◽

Total Population ◽

Germ Cell Tumors ◽

Chronic Myelomonocytic Leukemia ◽

Cytotoxic Agents ◽

Review Of The Literature ◽

Secondary Leukemia ◽

Term Survival ◽

Myelomonocytic Leukemia

We investigated the incidence of leukemia occurring subsequent to the treatment of germ cell tumors in men at our institution over a 30-year interval and found four patients with acute nonlymphocytic leukemia (ANLL) and one patient with chronic myelomonocytic leukemia. The relative risk (observed/expected cases) estimates for the development of leukemia ranged from 13.7 (P = .0005) in the total population to 50.1 (P = .0001) in the group treated with cytotoxic agents alone. All three patients with ANLL treated with contemporary antileukemic therapy had complete responses, with survivals of 7, 29, and 133 + months. In a review of the literature, 14 additional cases of germ cell tumors were found in which the men subsequently developed leukemia. It is concluded that leukemia following germ cell tumors is increased in incidence and is likely to be treatment induced. Complete responses and long-term survival are possible in secondary leukemia and aggressive antileukemic therapy should be given.

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