Extragonadal germ cell tumors in Taiwan

An analysis of treatment results of 59 patients

Authors

  • Yu-Juei Hsu M.D.,

    1. Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
    Search for more papers by this author
  • Lu Pai Ph.D.,

    1. School of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China
    Search for more papers by this author
  • Yeu-Chin Chen M.D.,

    1. Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
    Search for more papers by this author
  • Ching-Liang Ho M.D.,

    1. Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
    Search for more papers by this author
  • Woei-Yau Kao M.D.,

    1. Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
    Search for more papers by this author
  • Tsu-Yi Chao M.D., D.M.S.

    Corresponding author
    1. Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
    • Division of Hematology/Oncology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Cheng Kung Road, Section 2, Neihu 114, Taipei, Taiwan, Republic of China
    Search for more papers by this author
    • Fax: 886-2-87927209


Abstract

BACKGROUND

Extragonadal germ cell tumors (EGCT) are rare. They are biologically distinct from their testicular counterparts. Information regarding these tumors from the Far East is limited. More investigations are warranted to define the optimal treatment.

METHODS

Retrospective review of the medical records of 59 patients with EGCT treated between 1983 and 2001 at a large, tertiary care institute in Taipei.

RESULTS

The study population comprised 54 males and 5 females, ranging in age from 1 to 68 years old (median age, 21 years). Primary tumors occurred in the mediastinum (n = 27), retroperitoneum (n = 6), central nervous system (CNS; n = 24), and other sites (n = 2). Patients received surgery, chemotherapy, radiotherapy, or a combination of treatment modalities as the primary treatment. Three patients with mediastinal seminoma achieved complete remission (CR) and are alive with no evidence of disease (NED), with a median follow-up of 118 months. Of 24 patients with mediastinal nonseminomas, 8 (33%) are alive with a median disease-free survival (DFS) period of 33 months. Two of six patients with retroperitoneal nonseminomas obtained CR and are alive with NED at 41 and 110 months, respectively. Of 24 patients with intracranial germ cell tumors, 16 had germinoma and 13 (81%) achieved CR with NED at 8–228 months (median duration, 104 months). Four of eight patients with CNS nongerminomas remain in CR and are alive with a median DFS period of 48 months. Four patients with mediastinal nonsemonimas treated with salvage chemotherapy died.

CONCLUSIONS

The treatment results of our patients with seminomatous EGCT are comparable to those of Western countries. However, the treatment results of patients with nonseminomatous EGCT are not as good. The reason for this discrepancy needs to be explored for a better treatment outcome of for patients in Taiwan with EGCT. Cancer 2002;95:766–74. © 2002 American Cancer Society.

DOI 10.1002/cncr.10738

Extragonadal germ cell tumors (EGCT) are rare and have distinct clinicopathologic features. They account for 2–5% of all germ cell malignancies,1 but their clinical behaviors are somewhat different from those of testicular germ cell tumors (GCT). Most studies of EGCT were reported from Western countries. The treatment results in these studies are good.2, 3 However, there are very few studies reported from the Far East.4 In this study, we retrospectively analyzed our cases of EGCT and compared our results with those in the literature.

PATIENTS AND METHODS

The Tri-Service General Hospital (TSGH) is a 1200-bed general hospital serving both military personnel from all Taiwan and civilians mainly from northern Taiwan. Most patients are young males. This unique character is rare in other hospitals. We searched the TSGH database of cancer registries for cases with the diagnosis of “germ cell neoplasm” and excluded cases with primary sites in the testis or ovary. For the period January 1983 to June 2001, there were 28,637 cancer patients registered; 228 patients had GCT and 59 of these had EGCT (Tables 1–3. The charts of the 59 patients with EGCT were reviewed retrospectively. Of the 59 patients, 54 were males and 5 were females. Of the 59 patients, 19 (32%) had seminomas (SEGCT) and 40 (68%) had nonseminomas (NSEGCT). Of the NSEGCT patients, 11 (27.5%) had yolk sac tumors (YST), 2 (5%) had embryonal carcinomas (EC), 3 (7.5%) had choriocarcinomas, 20 (50%) had malignant teratomas (MT), and 4 (10%) had mixed GCT. There were 27 patients with primary tumors in the mediastinum, 24 with primary tumors in the central nervous system (CNS), and 6 with primary tumors in the retroperitoneum. Two patients had primary tumors in the pancreas and neck, respectively. The clinical and radiologic features of 15 of the 27 patients with mediastinal EGCT had been reported previously.5

Table 1. Patient Characteristics
 SEGCTNSEGCT
  1. SEGCT: seminomatous extragonadal germ cell tumor; NSEGCT: nonseminomatous extragonadal germ cell tumor; CNS: central nervous system; AFP: α-fetoprotein; β-hcg: β-human chorionic gonadotropin.

No. of patients1940
Age (yrs)  
 Median (range)22 (3–31)20.5 (1–68)
Gender (males:females)18:136:4
Primary site  
 Mediastinum324
 Retroperitoneum06
 CNS168
 Other02
Tumor marker status  
 Elevated AFP (patients)029
 Mean level (ng/mL)012,688
 Range63–835,000
 Elevated β-hcg (patients)011
 Mean level (ng/mL)01855
 Range10–17,659
Table 2. Histology of EGCT in 59 Patients
 Mediastinum (n = 27)CNS (n = 24)Retroperitoneum (n = 6)Other (n = 2)a
  • EGCT: extragonadal germ cell tumor; CNS: central nervous system.

  • a

    Other sites include one mixed germ cell tumor in the pancreas and one embryonal carcinoma in the neck.

Seminoma31600
Nonseminoma    
 Yolk sac tumor8120
 Malignant teratoma13340
 Choriocarcinoma1200
 Embryonal carcinoma1001
 Mixed germ cell tumor1201
Table 3. Most Frequent Presenting Symptoms by Site of Disease
Site of diseaseNo.
Mediastinum (n = 27) 
 Chest pain12
 Shortness of breath15
 Cough12
 Superior vena cava obstruction8
 Systemic symptoms4
 Physical check-up1
Retroperitoneum (n = 6) 
 Abdominal mass or swelling6
 Abdominal pain2
Central nervous system (n = 24) 
 Headache14
 Blurred vision9
 Nausea and vomiting3
 Conscious disturbance5
 Polyuria and polydipsia2
 Limb weakness4
Other sites (n = 2) 
 Abdominal pain1
 Neck mass1

Pathologic diagnoses of EGCT in these patients were established by histologic studies of tumor biopsies, as well as by cytologic examination of fine-needle aspirates of primary and/or metastatic tumors.6 These tumors were classified according to the criteria of World Health Organization.7 Initial evaluation of all patients included history and physical examination, determination of serum levels of α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hcg), and imaging by roentgenograph and computed tomography (CT) scan. An EGCT was defined as a GCT arising in the mediastinum, retroperitoneum, or other site without demonstrable ovarian or testicular abnormalities by physical examination, ultrasonography, or CT scan.

Multimodality treatment, including surgery, cisplatin-based chemotherapy, and radiation therapy, is the principal therapy for EGCT patients (Table 4). The commonly used chemotherapeutic schedules were PVB (cisplatin 20 mg/m2 on Days 1–5, vinblastine 0.15 mg/m2 on Days 1–2, bleomycin 30 U on Days 2, 9, and 16 every 3 weeks), PEB (cisplatin 20 mg/m2 on Days 1–5, etoposide 100 mg/m2 on Days 1–5, bleomycin 30 U on Days 2, 9, and 16 every 3 weeks), EP (etoposide 100 mg/m2 on Days 1–5, cisplatin 20 mg/m2 on Days 1–5 every 3 weeks), and VIP (vinblastine 0.11 mg/m2 on Days 1–2, ifosfamide 1.2 g/m2 on Days 1–5 with sodium 2-mercaptoethane sulfonate, cisplatin 20 mg/m2 on Days 1–5 every 3 weeks). Twenty-two patients received PEB, five patients received PVB, three patients received EP, and four patients received salvage chemotherapy with VIP. A complete response (CR) was defined as disappearance of all measurable disease for at least 4 weeks, with normalization of all markers (AFP, β-hcG). A partial response (PR) was defined as a greater than 50% reduction in the sum of the areas of all measured lesions, including tumor markers, for a minimum of 4 weeks. Progressive disease (PD) was defined as a 25% increase in the sum of the areas of all measured lesions and/or appearance of new lesions. Response and survival rates were calculated from the beginning of initial diagnosis to the date of last follow-up or death. Survival distributions were estimated by the Kaplan–Meier method. Univariate comparisons were made using the log rank test. In a multivariate analysis of survival, the Cox regression model was used to study the effects of different variables. Data from patients who died of causes other than EGCT were not included.

Table 4. Histology, Treatment Modality, and Outcome of Nonseminomatous Mediastinal GCT
Treatment modalityHistologyNo.CRPRPDOutcome
  1. GCT: germ cell tumor; S: surgery; C: chemotherapy; RT: radiotherapy; MT: malignant teratoma; YST: yolk sac tumor; EC: embryonal carcinoma; CR: complete response; PR: partial response; PD: progressive disease; NED: no evidence of disease.

SMT43 1Three alive with NED at 55, 15, 36 mos; one died at 13 mos
CChoriocarcinoma1  1Died at 5 mos
 Mixed GCT1  1Died at 2 mos
C→RTYST31 2One alive with NED at 13 mos; two died at 8 and 17 mos
 MT2  2Two died at 15 and 5 mos
C→SYST2 2 Two died at 17 and 12 mos
 MT11  Alive with NED at 33 mos
S→CMT11  Alive with NED at 11 mos
S→RTMT1  1Died at 10 mos
C→S→RTYST211 One alive with NED at 29 mos; one died at 9 mos
 MT31 2One alive with NED at 160 mos; the other two died at 11 mos
S→RT→CYST1  1Died at 7 mos
 MT1  1Died at 11 mos
 EC1  1Died at 2 mos

RESULTS

Clinical Features

Most of our patients are young adult males (Table 1), probably because many of our patients are active duty, military personnel. The presenting signs and symptoms of these patients are usually due to mass effects related to the site of the primary tumor (Tables 2, 3).

Treatment and Patient Outcome

The treatment modalities and their sequence of institution are summarized in Table 5. The survival data are analyzed by primary site and histologic type of tumor (Figs. 1 and 2). The univariate analysis of survival and prognostic factors is shown in Table 6.

Table 5. Treatment and Outcome
SiteNo.Complete responsePartial responseProgressive diseaseRecurrenceAlive/NED
  1. C: chemotherapy; S: surgery; RT: radiotherapy; NED: no evidence of disease.

Mediastinum      
 Seminoma (n = 3)      
  C22   2/2
  C→S11   1/1
 Nonseminoma (n = 24)      
  S43 1 3/3
  C2  2 0/0
  C→RT51 4 1/1
  C→S312  1/1
  S→C11   1/1
  S→RT1  1 0/0
  C→S→RT5212 2/2
  S→RT→C3  3 0/0
Retroperitoneum      
 Nonseminoma (n = 6)      
  S3111 1/1
  S→C3111 1/1
CNS      
 Germinoma (n = 16)      
  RT1010  28/8
  S21 1 1/1
  S→RT44   4/4
 Nongerminoma (n = 8)      
  S1  1 0/0
  RT→S21 1 1/1
  S→RT22  11/1
  S→RT→C33  12/2
Other sites (n = 2)      
 C1  1 0/0
 S→C11   1/1
Figure 1.

Overall survival of patients comparing seminomatous and nonseminomatous histology.

Figure 2.

Overall survival of patients comparing primary sites (central nervous system, mediastinum, and retroperitoneum).

Table 6. Univariate Analysis of Survival in Patients with EGCT
VariablesNo.Hazard ratio95% Confidence intervalP value
  • EGCT: extragonadal germ cell tumor; CNS: central nervous system; AFP: α-fetoprotein; β-hcG: β-human chorionic gonadotropin; SVC: superior vena cava.

  • a

    Tumor limited to the primary site.

  • b

    Tumor spread to distant site.

  • c

    Only included patients with primary site in the mediastinum.

Gender    
 Female51.000  
 Male52.613.184–2.0400.425
Age (yrs)    
 < 20 or > 29201.000  
 20–2937.483.226–1.0330.061
Location    
 CNS241.000  
 Mediastinum273.0171.221–7.4570.017
 Retroperitoneum63.120.908–10.7280.071
Histology    
 Seminoma191.000  
 Nonseminoma387.6702.248–26.1690.001
Extent of disease    
 Locala471.000  
 Extensiveb103.0291.303–7.0370.010
AFP    
 Normal291.000  
 Elevated286.3132.524–15.792< 0.001
β-hcG    
 Normal471.000  
 Elevated101.914.756–4.8410.171
SVC syndrome presentc    
 No191.000  
 Yes82.592.960–6.9960.060

Mediastinal Tumors

SEGCT

Of the three patients with mediastinal SEGCT, one received chemotherapy with PEB for four courses, one was treated with EP for six courses, and one with EP for six courses followed by resection of residual tumor. All three patients achieved CR and are alive with no evidence of disease (NED) at 66, 119, and 118 months, respectively.

NSEGCT

The 24 patients with mediastinal NSEGCT were treated with debulking surgery alone (n = 4), chemotherapy alone (n = 2), chemotherapy followed by radiotherapy (n = 5), chemotherapy followed by resection of residual tumor (n = 3), debulking surgery followed by radiotherapy (n = 1), debulking surgery followed by chemotherapy (n = 1), chemotherapy followed by surgery in combination with radiotherapy (n = 5), or debulking surgery followed by chemotherapy in combination with radiotherapy (n = 3). The histology, treatment modality, and outcome are summarized in Table 4. Four patients received VIP for salvage chemotherapy and none showed any response. Overall, 4 of 24 patients with mediastinal NSEGCT obtained a PR (17%), 12 (52%) had PD, and 8 patients (30%) obtained a CR and were alive with NED at 11–160 months (median, 33 months). Of these 24 patients, 2 (8.8%) had Klinefelter syndrome and 8(33.3%) presented with superior vena cava (SVC) syndrome.

Retroperitoneal Tumors

Six patients had NSEGCT (two YST, four MT) and they received debulking surgery initially. Three of them underwent chemotherapy after surgery. Two obtained CR, two PR, and two had PD. Two of the four patients with MT who obtained CR are still alive with NED after 41 and 110 months, respectively. Of the remaining two patients with MT, one experienced PR initially but died of PD 48 months after diagnosis and the other died of PD 5 months after diagnosis. Of the two patients with YST, one obtained PR but died of pneumonia 5 months after diagnosis and the other died of PD 2 months after diagnosis.

CNS Tumors

Germinomas

Of the 16 patients with CNS germinomas, 10 received radiotherapy, 4 were treated initially with debulking surgery followed by radiotherapy, and 2 had debulking surgery alone. Of the 16 patients, 15 achieved CR initially. Of the 10 patients who underwent radiotherapy, 2 experienced recurrence without further treatment because of poor performance and died at 28 and 78 months, respectively, after diagnosis. Of the 16 patients, 13 (81%) are still alive with NED at 8–228 months (median, 104 months).

Nongerminomas

The eight patients with CNS nongerminomas were treated with debulking surgery alone (n = 1), debulking surgery followed by radiotherapy (n = 2), radiotherapy followed by resection of residual tumor (n = 2), and debulking surgery followed by radiotherapy in combination with chemotherapy (n = 3). CR occurred initially in six of eight patients (75%). Of these six patients, four remain in CR and were alive with NED at 12–121 months (median, 48 months).

Other Sites

Two patients were subgrouped to “other sites.” The first patient, a 23-year-old male with EC of the lymph nodes over the left neck, underwent debulking surgery and consolidation chemotherapy with PEB. He obtained a CR with NED at 95 months. The second patient, a 62-year-old male, had a mixed GCT in the pancreas with multiple liver metastasis. He was treated with PEB chemotherapy, but died of PD at 4 months.

Survival and Prognostic Factor

There were few patients with tumors in other sites and they are excluded from analysis. The overall survival rates for the 57 patients are illustrated in Figures 1 and 2. Survival analysis by histologic type shows that SEGCT patients have a better outcome than NSEGCT patients (Fig. 1), which is statistically significant (P = 0.001). The 2-year survival rate by primary site (Fig. 2) is 29.6% for the mediastinum, 79.1% for the CNS, and 33.3% for the retroperitoneum. Patients with mediastinal GCT had worse outcomes than those with CNS GCT or retroperitoneal GCT, but there is no statistically significant difference in survival rates between patients with mediastinal and retroperitoneal GCT (P = 0.952). The small number of retroperitoneal GCT patients may be the main reason. The univariate analysis of prognostic factors on survival is shown in Table 6. Location of tumor in the mediastinum, NSEGCT, extensive disease, and elevated tumor marker levels were predictive of adverse prognosis. In multivariate analysis, location of tumor no longer had prognostic value (P = 0.840) when these data were adjusted for histology and extent of disease. Rare cases with SEGCT in the mediastinum and retroperitoneum may explain this result.

Toxicity

Myelosuppression and nephrotoxicity were tolerable in most patients and only one patient had acute renal failure after cisplatin infusion. Of 59 patients, 5 (8%) experienced infectious complications. Hepatic toxicity was transient in two patients and five patients (8%) had acute hepatitis. Among these five patients, one with an MT in the mediastinum (treated with VIP) and one with a mixed GCT in the CNS (treated with PEB) experienced fulminant hepatitis during chemotherapy. Both patients were hepatitis B virus (HBV) carriers and were negative for HBV envelope antigen (HBeAg) and positive for the antibody to HBeAg. These two patients also received corticosteroids for antiemetic premedication. Three other patients with germinoma in the pineal gland suffered from acute hepatitis during cranial irradiation. Two of these three patients were hepatitis B carriers.

DISCUSSION

EGCT are distinct from testicular GCT because they are less responsive to cisplatin-based chemotherapy. The proportion of EGCT in all GCT registered in this series is as high as 26%, which is probably because TSGH is a tertiary hospital. Because this is a military hospital, most patients were young males. Many patients had EGCT of CNS origin, which is much higher than other reports. Among patients with mediastinal GCT, 30% had SVC syndrome, indicating that patients may have been diagnosed late. To our knowledge, this is the only report of EGCT from Taiwan.

The comparison of EGCT reported from local (current study), regional (India and Japan), and two large representative series from Western countries (United States and Toronto) is shown in Table 7. Several investigators have described the treatment results of patients with SEGCT. The reported CR rates were 92% in India, 67–95% in Japan, 64–96% in the United States, and 95% in Toronto.3, 4, 8–16 In the current study, all three patients with mediastinal SEGCT obtained a CR and long-term survival. Of the 16 patients with CNS germinoma, a CR was achieved in 15 patients (94%) and 13 patients (81%) are alive with a median DFS of 104 months. Our results indicated that treatment results for our patients with SEGCT were not different from the results of other countries, whereas results for patients with NSEGCT are not as good.

Table 7. Histology, Primary Site, and Results of EGCT in Different Countries
Authors/countryLocationHistologyNo.CRAlive (%)
  • EGCT: extragonadal germ cell tumor; M: mediastinum; R: retroperitoneum; C: central nervous system; S: seminoma; NS: nonseminoma; G: germinoma; NG: nongerminoma; CR: complete remission.

  • a

    Seven patients who had seminoma with syncytiotrophoblastic giant cells. (3-year survival rate = 100%) are not included.

  • b

    Only include 5 embryonal carcinomas, 3 yolk sac tumors, and 3 choriocarcinoma; 11 malignant teratomus (3-year survival rate = 70.7%), 16 mature teratomas (3-year survival rate = 92.9%), and 39 mixed tumors (3-year survival rate = 61%) are not included.

  • c

    Three-year survival rate.

  • d

    Two-year survival rate.

  • e

    Five-year survival rate.

Current series/TaiwanM+RS333 (100)
  NS301010 (33.3)
 CG161513 (81.3)
  NG864 (50)
Jacob et al.4/ IndiaM+RS999 (100)
  NS1556 (40)
 CG430
  NG100
Asamura et al.8/JapanMS3 2 (66.7)
  NS22 6 (27.2)
Matsutani et al.9/JapanCGa50 95.4%c
  NGb11 27.3%c
Bukowski et al.3/USAM+RS10673%d
  NS292273%d
Wolden et al.15/USACG2491%100%e
  NG1060%80%e
Goss et al.16/ TorontoM+RS121111 (91.7)
  NS19109 (47.4)
 CG776 (85.7)

It is important to establish an effective treatment for NSEGCT patients to improve the survival rate of patients with EGCT. In a literature review before 1975, Cox17 found no reported long-term survivors among 120 cases of NSEGCT. However, cispatin-based chemotherapy has improved the outlook for patients with NSEGCT. In a U.S. study, Hainsworth et al.2 analyzed prospectively 31 patients with EGCT using cisplatin-based combination chemotherapy. They reported a CR rate of 68% and a 2-year survival rate of 58% for NSEGCT patients. In another prospective study from the United States, Bukowski et al.3 analyzed 41 patients receiving cisplatin-based combination chemotherapy. Their 2-year survival rate for NSEGCT patients was 73% and their CR rate was 77%. Goss et al.16 from Toronto analyzed 40 patients with EGCT. In their study, 10 of 19 patients (53%) with NSEGCT obtained a CR and the 2-year survival rate was 47%. Jacob et al.4 reported results for 37 patients with EGCT from India. In their study, the CR rate was 33% and the 5-year survival rate for NSEGCT patients was 24%. In a study from Japan, Asamura et al.8 investigated 25 patients with mediastinal EGCT (3 SEGCT and 22 NSEGCT). Of the 25 patients, 5 (20%) obtained a CR and the 5-year survival rate was 33.5%. Overall, the cure rate in most Western series is much better than that reported from the Orient.2–3, 8, 10, 11, 13, 14, 18–24 In our retrospective series, we analyzed 30 patients with NSEGCT (24 with primary tumors in the mediastinum and 6 with primary tumors in the retroperitoneum). The CR rate was 33% and the 2-year survival rate was 26.7%. The possible reasons for our inferior results were that most of the patients had heavy tumor burden, a higher proportion of YST and MT, a higher percentage of mediastinal tumor, and a higher level of AFP. Toner et al.25 analyzed retrospectively 50 patients with NSEGCT. They found that patients with mediastinal EGCT had the worst outcome. Pretreatment values of serum AFP and β-hcG and the presence of YST were important prognostic indicators in the same study. Mediastinal NSEGCT and high AFP level (>10,000 ng/mL) were classified in the poor risk category of the new International Germ Cell Consensus Classification.26 Our results are in agreement with these investigations.

Although the retroperitoneum is the second most common site of EGCT, there were only six patients with primary retroperitoneal GCT in the current study and all patients had NSEGCT. Primary chemotherapy is recommended for patients with SEGCT and NSEGCT of this site, with resection of residual tumor in patients with NSEGCT.16, 27 McAleer et al.28 reported a similar outcome for patients with primary retroperitoneal GCT and primary testicular GCT with retroperitoneal involvement.

Radiotherapy is the standard treatment for intracranial GCT. Wolden et al.15 reported 5-year DFS rates of 91% for patients with germinoma and 60% for patients with nongerminoma. In a Japanese study of intracranial GCT, comprising the largest group of patients reported to date, Matsutani et al.9 treated 153 patients with intracranial GCT by surgically removing the tumor and administering radiotherapy with or without cisplatin-based chemotherapy. The 5-year survival rate was 95.4% for germinoma patients, 92.9% for patients with mature teratoma, 70.7% for patients with MT, 27.3% for patients with pure malignant GCT (choriocarcinoma, YST, and EC), and 57.1% for mixed GCT. There are reports of response to cisplatin-based chemotherapy as frontline treatment for refractory disease or PD in patients with germinomas and nongerminomas.9, 29, 30 The long-term results of chemotherapy in patients with intracranial GCT are still being studied and optimal treatment modalities have not been established. In the current study, 13 of 15 patients (81%) with germinomas achieved CR with a median DFS of 104 months. For nongerminomas, four of eight patients (50%) remained in CR with a median DFS of 48 months.

The total failure rate in our study was 47% (24 patients did not achieve complete remission and four had recurrence of disease). Saxman et al.31 reported the Indian experience with salvage chemotherapy in patients with recurrent NSEGCT. Only 5 of 73 patients (7%) were long-term disease-free survivors after salvage chemotherapy. In the current study, four patients with mediastinal NSEGCT received salvage chemotherapy and none achieved CR with long-term DFS. Because standard salvage treatments rarely provide a definite cure, the role of high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell rescue in patients with recurrent GCT is being studied.32

Taiwan is an endemic area of HBV infection. Cytotoxic chemotherapy could result in fatal hepatitis flare-up among HBV carriers, especially in patients with overt chronic hepatitis clinically or with serologies negative for HBeAg and positive for anti-HBe.33–35 Previous studies33–35 have shown that nucleotide mutation of the precore region at position 1896 (G to A) is associated with reactivation of HBV with fulminant course. In contrast, the relationship between cranial irradiation and HBV infection has never been reported. More cases are necessary to define the correlation between cranial radiotherapy and hepatitis infection. Routine screening of HBV carrier status is recommended before therapy and the prophylactic use of Lamivudine in these patients may be necessary.

In summary, EGCT are a distinct clinical entity predominantly occurring in young patients. Unfortunately, treatment results are still unsatisfactory. More investigations are warranted to define the optimal treatment. The necessity of high-dose chemotherapy and autologous bone marrow transplantation as the initial treatment for patients with EGCT with a poor prognosis needs to be studied in the future.

Ancillary