High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.     

Clinical study of high-dose chemotherapy with peripheral blood stem cell transplantation for poor-risk germ cell tumor

Between January 1997 and December 1998, six patients with germ cell tumor were treated with high-dose CEC: carboplatin (1,500 mg/m2), etoposide (1,200 mg/m2) and cyclophosphamide (100 mg/kg), followed by peripheral blood stem cell transplantation (PBSCT) at Nagoya University Hospital. Four patients received one cycle of high-dose CEC and two received two cycles. The reasons why the high-dose CEC was administered included: 1) refractory to the induction chemotherapy (AFP/beta-HCG elevated during the induction chemotherapy or prolonged half-life of each marker) in three patients, 2) relapse in two patients, and 3) consolidation in one with unresectable mediastinal residual tumor. There were no treatment-related deaths and grade 1 hepatotoxicity occurred in one (17%) patient. The median duration (range) from PBSCT until a granulocyte count of 500/microL and a platelet count of 50,000/microL was 8.5 (8-11) and 11 (9-16) days, respectively. Of the six patients studied, 5 responded to the treatment; two achieved a complete response (CR) and three achieved a partial response (PR). One patient achieving a CR and two achieving a PR remained in complete remission after 23 to 24 months of follow-up, while the remaining patients with a CR, a PR and an incomplete response died of the disease. High-dose CEC could be administered without serious toxicity but the effectiveness of high-dose CEC for the poor-risk patients with germ cell tumor needs to be further investigated.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Secondary leukemia following ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors in a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of secondary leukemia occurring in a 31-year-old man who received ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) for a refractory testicular cancer (pathology; Seminoma, Embryonal carcinoma, Yolk sac tumor, Choriocarcinoma) with IIIB2 under Japanese classification, poor-risk group under Indiana classification. The initial levels of serum LDH, AFP and beta-HCG were high at 959 IU/l, 1,452 ng/ml and 800 ng/ml. He received total 11 cycles of systemic chemotherapy (2 cycles of PVB regimen, 4 cycles of PEB regimen, 3 cycles of VIP regimen and 2 cycles of ultra high-dose chemotherapy with PBSCT for pulmonary and para-aortic lymph node metastasis following his initial orchiectomy. The total amount of etoposide (VP-16), cisplatin (CDDP), carboplatin (CBDCA) and ifosfamide (IFM), this patient received was 7,225 mg/m2, 1,510 mg/m2 1,750 mg/m2, and 50.5 g. He has survived with CR of disease. Severe and persistent pancytopenia developed 25 months after his initial orchiectomy. Bone marrow examination showed AML (M2 with eosinophilia) under French-America-British (FAB) classification. Therefore, he was diagnosed as secondary leukemia following high-dose chemotherapy. He received total 6 cycles of systematic chemotherapy for the secondary leukemia in the internal department. He is planing to have bone marrow transplantation. To our knowledge, this is the first reported case in the literature relevant to secondary leukemia following ultra high-dose chemotherapy with PBSCT in testicular tumor in Japan.     

High-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced extragonadal germ cell tumor--a case report]

We reported the experience of high-dose chemotherapy (HDC) combined with peripheral stem cell transplantation (PBSCT) in 29 years-old man with advanced retroperitoneal germ cell tumor accompanied with left supraclavicular lymph node metastases, who obtained complete remission after comprehensive treatment. The initial levels of serum AFP, hCG and beta-hCG were high at 30.2 ng/ml, 14,000 mIU/ml and 66 ng/ml, respectively. After 3 courses of chemotherapy (BEP regimen), while left supraclavicular lymph node swelling was disappeared, the retroperitoneal mass lesion persisted on CT scan. Not all of 3 markers fell to the normal range. After myelosuppressive chemotherapy (etoposide 500 mg/m2 Day 1-3), PBSCs were collected by two consecutive apheresises on Day 17 and 18. In total, 19.5 x 10(6)/kg CD 34 positive cells were obtained. The patient underwent PBSCT (all CD 34 positive cells were infused) on Day 0 following HDC (CBDCA 250 mg/m2/day, etoposide 300 mg/m2/day, IFM 1.5 g/m2/day, Day-7(-)-3, respectively). He became severely leukopenic and thrombopenic with nadir of 200/microliter on Day 6 and 2 x 10(4)/microliter on Day 2, respectively. By administration of platelet transfusion and G-CSF, the white blood cell counts and thrombocyte counts recovered to 6,400/microliter and 4.1 x 10(4)/microliter on Day 10, respectively. Microbiologically enterocolic and respiratory tract infections occurred with elevated body temperature (> 40 degrees C). Antibiotic and antimycotic treatments were continued until disappearance of all clinical and microbiological evidence. He was kept for 10 days in clean room. After HDC, all markers fell to the normal range, but the retroperitoneal residual mass still persisted. Resection of the residual mass and retroperitoneal lymph node dissection were performed with pathological examination revealing tissue necrosis without viable cell. The patient has survived with no sign of the disease for 9 months.     

Two-step ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer: a case report]

A 35-year-old male had advanced nonseminomatous germ cell tumor (stage IIIC, embryonal cell carcinoma) which proved refractory to conventional PVB combined chemotherapy. He was then treated with an ultra high-dose chemotherapy consisting of carboplatin (1.5 g/m2) and etoposide (1.3 g/m2), followed by the transplantation of peripheral blood stem cells (PBSCT) with a total of 1.9 x 10(5)/kg granulocyte colony-forming cells (CFU-GM). Because he developed lung metastasis, escalated doses of carboplatin (2.0 g/m2), and etoposide (1.8 g/m2) combined with cyclophosphamide (7.0 g/m2) were given with peripheral blood stem cell transplant of 3.2 x 10(5)/kg CFU-GM. He has remained free of any recurrence without maintenance therapy.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation for male germ cell tumor. Preliminary report

AIM: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7-15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

BACKGROUND: The present study was performed in order to investigate the efficacy and safety of high-dose chemotherapy for the treatment of patients with advanced testicular cancer. METHODS: Seven patients were treated with high-dose carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem cell transplantation. Five patients received one cycle and two patients received two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one achieved a complete response and four achieved partial responses with markers negative. As a result of subsequent surgery for residual tumors, three of the four partial responders showed no residual cancer cells. One patient who did not undergo surgery received radiotherapy after the high-dose chemotherapy and the residual tumors disappeared. All five patients who had either a complete or partial response are still alive and without evidence of disease at 12, 27, 30, 37 and 40 months. One patient is alive with disease at 7 months and one died of progressive disease at 6 months. The hematologic recovery after high-dose chemotherapy was rapid and non-hematologic toxicities were usually mild and manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem cell transplantation is safe and effective for use in patients with far-advanced testicular cancer, particularly when the high-dose chemotherapy is conducted as the initial treatment. Further larger and long-term follow-up studies are needed to define the role of high-dose chemotherapy on testicular cancer.     

Kinetics of peripheral blood CD34-positive cells and the optimum timing for harvesting peripheral blood stem cells during BEP chemotherapy in patients with testicular germ cell tumor

PURPOSE: Recently, high-dose chemotherapy with peripheral blood stem cell (PBSC) rescue has been developed for poor risk testicular germ cell cancer. In this study, we investigated the optimum timing for harvesting PBSCs with the use of bleomycin + etoposide + cisplatin (BEP) chemotherapy, which is a well known first-line regimen for the testicular cancer. MATERIAL AND METHOD: Peripheral blood CD34-positive cell ratios were measured during a total of 10 courses of BEP chemotherapy in 6 patients with metastatic germ cell cancer between 1996 and 1998. We performed 4 apheresis in 3 patients during this period. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) was administrated from the day on which the neutrophil count decreased less than 1,000/microliter. RESULTS: The peripheral blood CD34-positive cell ratios became maximum (3.0-24.6%; average 10.0%) on the day 18 to 21 (median day 19) of BEP chemotherapy with rhG-CSF administration. The maximum ratios of peripheral blood CD34 positive cells were achieved when the number of leukocyte were 6,880-23,600/microliter and exceeded 6,000/microliter after the 18th day of BEP chemotherapy. The average number of collected CD34 positive cells was 9.5 x 10(6)/kg at a single apheresis, and 12.6 x 10(6)/kg per patient. CONCLUSION: Efficient hematopoietic progenitor cells were mobilized by BEP chemotherapy with rhG-CSF administration of first-line setting. Our results suggest that the optimum timing of PBSCs harvest is the day when the numbers of leukocyte exceed 6,000/microliter after the 18th day of BEP chemotherapy and the following day.     

Clinical study for management of supportive treatment for high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) for intractable testicular tumor

The side effects of high-dose anti-cancer drug chemotherapy with peripheral blood stem cell transplantation (PBCST) for the treatment of intractable testicular tumor are very serious. In particular, agranulocytosis in bone marrow suppression may be life threatening. In this study, we examined opportunistic infectious diseases and preventive counter measures in the compromised conditions of anti-cancer drug chemotherapy. The patients underwent anti-cancer drug chemotherapy with PBCST for the treatment of intractable testicular tumors at Kobe University Hospital from September 1996 to September 2002. The high-dose chemotherapy regimen consisted of total doses per course of 1,250 mg/m2 carboplatin, 1,500 mg/m2 etoposide, and 7,500 mg/m2 ifosfamide. Twenty-four men (median age, 30 years; range, 18-70 years) received 50 courses of chemotherapy in total. The nadir of peripheral leukocyte counts was less than 1,000/mm3 in all courses, and the mean period was for 7.1 days. None of these patients developed critical sepsis leading to disseminated intravascular coagulation or treatment-related death. Our detailed data show that we can perform high-dose anti-cancer drug chemotherapy with PBSCT for intractable testicular tumors without serious infectious complications if we take sufficient preventive countermeasures for infectious diseases.     

Evaluation of relative anti-myeloma activity of high-dose melphalan followed by the first peripheral blood stem cell transplantation, as compared with the second transplantation, and to VAD chemotherapy

Current treatment in multiple myeloma consists of three courses of chemotherapy in low doses with subsequent hematopoietic stem cell mobilization to the peripheral blood using high-dose cyclophosphamide, collection and conditioning with high-dose chemotherapy (melphalan) followed by retransplantation of autologous peripheral blood stem cells (PBSCT). Only a few studies compare the effects of different phases of therapy on parameters, such as monoclonal immunoglobulin level and the presence of malignant CD38(+) and CD56(+) cells in blood and marrow. The aim of this study was to compare the effects of these two major phases of treatment (conventional and high dose) in the same patients, and furthermore, to compare the effects of the second course of high-dose therapy followed by PBSCT with the effects of the first one. Fifteen patients were included in the study. On average, conventional chemotherapy only slightly reduced the values of all disease markers. In contrast, high-dose therapy resulted in a dramatic effect, rapidly normalizing the values of all parameters. The effects of second PBSCT were only modest compared to the first. These data suggest that high-dose therapy is an efficient method to reduce tumor load in multiple myeloma. Conventional-dose chemotherapy may be simply a waste of time for some patients and may be either omitted or administered after high-dose therapy to consolidate remission.     

A multidisciplinary approach to primary nonseminomatous germ cell tumors of the mediastinum

The introduction of cis-platinum-based chemotherapy has dramatically improved the prognosis for patients with primary nonseminomatous germ cell tumors of the mediastinum. Since 1978, 12 male patients (mean age, 29 years) have been seen with a large mediastinal mass, normal testes, and abnormal testicular tumor markers. Eleven patients had raised alpha-fetoprotein levels (median, 1,300 micrograms/L; normal, less than 10 micrograms/L), and 3 had elevated levels of the beta fraction of human chorionic gonadotropin (median, 8,000 IU/L; normal, less than 5 IU/L). Two patients were treated by primary surgical intervention followed by chemotherapy. Ten patients were treated with primary chemotherapy (cis-platinum, vinblastine sulfate or etoposide, and bleomycin sulfate), and this was followed by timed surgical excision of the tumor mass in 7. Six (60%) patients responded to primary chemotherapy with normalization of tumor markers. In this group there was 1 postoperative death and 1 recurrence. The 4 remaining patients are alive and free from disease at a mean of five years. Of the 4 patients with persistently elevated tumor markers, 2 died within six months, 1 is alive with recurrence, and 1 is lost to follow-up at three months. Patients whose tumor markers return to normal after cis-platinum-based chemotherapy have a good long-term prognosis following radical surgery. If the tumor markers remain elevated, the prognosis is poor.     

Peripheral blood stem cell harvest for patients with germ cell tumors

From January 1996 to December 1999, fifteen patients with germ cell tumors underwent peripheral blood stem cell harvest during 15 courses of bleomycin, etoposide, cisplatin (BEP), 4 courses of etoposide, ifosfamide, cisplatin (VIP) and 3 courses of high-dose etoposide mobilization at Nagoya University Hospital. We performed 29 aphereses during BEP, eight during VIP, and six during high-dose etoposide. Although we were able to harvest 4.4 x 10(6)/kg of median CD34 positive cells per apheresis during BEP, the number of stem cells (more than 4 x 10(6)/kg of CD34 positive cells), which are needed for tandem high-dose chemotherapy, could not be obtained during four courses of BEP. For three patients in whom white blood cell counts at nadir were 2,000/microL or more, however, the required number of CD34 positive cells were harvested. VIP provided only 1.7 x 10(6)/kg of median CD34 positive cells per apheresis, while, 7.3 x 10(6)/kg of CD34 positive cells were harvested during high-dose etoposide mobilization. The dose of G-CSF was a significant factor for the number of CD34 positive cells harvested during BEP (p = 0.02); however, there might be some relationship between the harvest and the number of the peripheral white blood cells on the day of apheresis (p = 0.08), the day to start G-CSF (p = 0.13), or the day to initiate apheresis (p = 0.27). Based on our experience, it is recommended that 5 micrograms/kg of G-CSF should be started from the 14th or 15th day of BEP until the last apheresis and that aphereses should be performed between the 19th and 21st day, especially at the days when the peripheral white blood cell count increases beyond 10,000/microL.     

Chemotherapy immediately after surgery for patients with germ cell tumors

Six patients underwent surgery while receiving active chemotherapy for metastatic germ cell tumors. Surgical procedures included cholecystectomy, thoracotomy with tumor resection, and orchiectomy. Aggressive chemotherapy was reinitiated immediately after the surgery (average, 4.3 days; range, 3-6 days). Myelosuppression with nadir of granulocytes 80/dL (median) developed at day 13 (average). There were no immediate adverse effects of chemotherapy on wound healing, and all treatment courses were uneventful. We conclude that aggressive chemotherapy can safely be delivered to patients with germ cell tumors immediately after surgery.     

Successful treatment of intracranial nongerminomatous malignant germ cell tumors by administering neoadjuvant chemotherapy and radiotherapy before excision of residual tumors

OBJECT: The goal of this study was to confirm the effectiveness of our novel treatment strategy, neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy, which are performed before complete excision of residual tumor in patients with intracranial nongerminomatous malignant germ cell tumors (NGMGCTs). METHODS: The authors treated 11 consecutive patients with NGMGCTs by applying NAT consisting of combined platinum-based chemotherapy and radiotherapy, followed by complete excision of residual tumors. The pretreatment diagnosis, based on tumor markers with or without biopsy, was yolk sac tumor in five patients, embryonal carcinoma in one patient, immature teratoma in one patient, and mixed germ cell tumor containing malignant tumor components in four patients. Among the 11 patients, NAT achieved a complete response in two and a partial response in six patients; two patients manifested no change and one suffered disease progression. Residual tumors that occurred post-NAT were surgically removed in nine patients. Of the 11 patients, 10 are currently alive without recurrence of their disease, 30 to 177 months (mean 96 months) after diagnosis. In one patient a leptomeningeal tumor recurred and he died of the disease 21 months after diagnosis. CONCLUSIONS: Neoadjuvant therapy, consisting of combined chemo- and radiotherapy, followed by complete excision of residual tumors is highly effective in patients with intracranial NGMGCTs.     

Management of patients with malignant thymoma

This report documents the results of therapy in 23 patients treated for malignant thymoma between 1944 and 1979. Of the group, 22 patients had neoplasms which invaded mediastinal structures; six had distant metastases. Four patients had myasthenia gravis and one had erythroid hypoplasia associated with collagen vascular disease. No deaths were associated with primary therapy, which included an operative procedure in all cases. Follow-up ranged from 4 months to 18 years (mean 5.63 +/- 1.03 years, SEM). Fifteen patients died, with postoperative survival times ranging from 4 months to 18 years (mean 3.8 +/- 1.27 years). Five patients were alive without recurrence from 3 to 11 years postoperatively (mean 6.8 +/- 1.36 years), and three patients were alive with recurrence or distant metastases from 4 to 17 years postoperatively (mean 10.75 +/- 2.66 years). Differences in survival on the basis of tumor cell type were not statistically significant. Therapeutic groups were analyzed for 5 year survivors, tumor deaths within 5 years of therapy, deaths due to other causes, deaths due to tumor after 5 years, those presently alive, and longest known survivor. The data suggest that complete surgical excision offers the best chance of long-term survival when compared to partial resection plus irradiation (p less than 0.05). No statistical significance could be demonstrated between the groups who had complete resection with versus without postoperative irradiation. There also was no statistically significant difference between the group of patients receiving irradiation following partial excision of most of their tumor and the group receiving irradiation following only biopsy of the lesion. This observation suggests there is no value in so-called "debulking procedures" and suggests that irradiation may be of value in local control of thymoma. Perpetual surveillance is necessary since late recurrence is common.     

The pathology of late recurrence of testicular germ cell tumors

A total of 91 men had histologically documented late recurrences of testicular germ cell tumors characterized by a complete response to treatment with a subsequent disease-free interval of at least 2 years and no evidence of a second primary lesion. Ninety percent of the patients for whom information was available received chemotherapy shortly after their initial diagnosis of testicular germ cell tumors; most of the other patients were known to have stage I disease initially. Overall, 60% of patients had teratoma in their late recurrences, including 20 patients (22%) in whom teratoma was the only element. Thus, teratoma was the most common type of neoplasm in late recurrences. Excluding teratoma coexisting with other types of neoplasms, yolk sac tumor was the most frequent type of tumor in patients with late recurrence. It occurred in 47% of patients, either alone or with teratoma, another nonteratomatous germ cell tumor type, or a "nongerm cell malignant tumor." Unusual types of yolk sac tumor, including glandular, parietal, clear cell, and pleomorphic patterns, were seen frequently in late recurrences and often raised differential diagnostic problems with "nongerm cell" carcinomas. A smaller number of late recurrences consisted of other types of neoplasms. Twenty percent of patients with late recurrence had a nonteratomatous germ cell tumor other than yolk sac tumor, either alone, with yolk sac tumor, or with a "nongerm cell malignant tumor." Most of these nonteratomatous germ cell tumors other than yolk sac tumor were embryonal carcinoma, although rarely seminoma and choriocarcinoma were encountered. "Nongerm cell malignant tumors," including both sarcomas and carcinomas of various types, occurred in 23% of late-recurrence patients, either alone or with a nonteratomatous germ cell tumor. Late recurrences were seen in many different sites in these patients, including the retroperitoneum, abdomen, pelvis, liver, mediastinum, lung, bone (femur, vertebra, and rib), lymph nodes outside the retroperitoneum and mediastinum (supraclavicular, neck, and axillary regions), scrotum and inguinal regions, adrenal gland, chest wall, and buttocks. Follow-up data were available for 79 of the 91 patients studied. Duration of follow-up ranged from 2 months to 13 years after the patient's first late recurrences; the mean length of follow-up was 4.8 years. Patients whose late recurrences consisted of teratoma only had the most favorable outcomes, with 79% having no evidence of disease at last follow-up. Patients whose late recurrences consisted of pure "nongerm cell malignant tumor" or pure germ cell tumor (yolk sac tumor or other types) had a much worse prognosis: Only 36% to 37% were alive with no evidence of disease. Patients with two different types of nonteratomatous malignancies in their late recurrences had a dismal clinical course: Only 17% with both yolk sac tumor and other nonteratomatous germ cell tumor had no evidence of disease, whereas no patient with both nonteratomatous germ cell tumor and "nongerm cell malignant tumor" was disease free. Late recurrences consisting of teratoma alone often have a favorable outcome, but the prognosis in all other patients is poor. Furthermore, late recurrence is not likely to respond to chemotherapy and is best treated by surgical excision when possible.     

Clinical study of retroperitoneal lymph node dissection for patients with advanced germ cell tumors

We performed retroperitoneal lymph node dissection (RPLND) on 14 patients (IIA: 1, IIB: 4, IIIA: 3, IIIB2: 2, IIIC: 4) with testicular and one with retroperitoneal germ cell tumor at the Nagoya University Hospital between 1986 and 1997. According to the international germ cell consensus classification, 4 patients were classified as "good-prognosis", three as "intermediate-prognosis" and eight as "poor-prognosis". RPLND was performed on 12 patients with the tumor marker levels normalized preoperatively and on three without the marker normalization. The mean surgical time was 510 (195-1, 125) minutes and the mean bleeding volume was 3,806 (100-12,598) g. The surgical time and bleeding volume were correlated with the size of the tumor in the body axis. Intraoperative complications occurred in 5 (33%) out of 15 patients: injury of renal artery (2), renal vein (1), ureter (1) and common iliac artery (2). Postoperative complications occurred in 2 patients: ileus (2) and lower extremity edema resulting from resection of the inferior vena cava (1) and would dehiscence (1). Of the 8 patients whose completely resected retroperitoneal tumors were necrosis/fibrosis or teratoma (psCR), 6 achieved survival with no evidence of disease (NED). Among 4 patients, whose tumor was not completely resected but pathologically diagnosed as necrosis/fibrosis or teratoma (pCR), NED without recurrence was achieved in 2 and also in one with resection of relapsed teratoma 2.5 years after RPLND. All three patients with cancer tissues pathologically retained in the resected tumors (sCR or psIR), consequently died of the disease. In six patients with relapse, the initial sign was elevation of the tumor marker levels, which was noted more than 30 days postoperatively in 2 patients with psCR and 7 to 15 days in 4 patients without psCR. We believe that RPLND is needed to examine the pathology and to predict the prognosis of the poor-risk patients with NSGCT. Careful dissection of vessels is needed to reduce vascular complications.     

Health-related quality of life after chemotherapy for advanced germ cell tumors: A comparison of standard-dose and high-dose chemotherapy

BACKGROUND: The objective of this study was to evaluate the health-related quality of life (HRQoL) in patients with germ cell tumors who received standard-dose chemotherapy or high-dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT), and to compare the HRQoL of these patients with patients who had undergone surveillance therapy only. METHODS: Among the 102 patients included in this study, 38 underwent standard-dose cisplatin-based combination chemotherapy alone, 24 received high-dose chemotherapy with PBSCT following standard-dose chemotherapy, and 40 underwent surveillance monitoring. HRQoL was evaluated using the SF-36 survey, which contains 36 questions that assess eight quality-of-life aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. RESULTS: The follow-up period of the surveillance group was significantly longer than that of the remaining two groups receiving chemotherapy; however, scale scores were not affected by the duration of follow up in either group. No significant difference was observed in any scale scores between the patients undergoing chemotherapy and those in the surveillance group. In comparison with the general population in the USA, social functioning in both the chemotherapy and surveillance groups was significantly lower, whereas vitality in these two groups was significantly higher. Patients undergoing standard-dose chemotherapy alone had a significantly higher score for mental health than those undergoing high-dose chemotherapy. However, there were no significant differences in the remaining seven scores, irrespective of the type of chemotherapy. CONCLUSIONS: Seven of the eight scale scores of HRQoL were favorable in patients who received chemotherapy or surveillance, and no significant difference was observed between these two groups. Moreover, with the exception of the mental health score, HRQoL was not significantly affected by the type of chemotherapy. Therefore, patients who received chemotherapy, including high-dose chemotherapy with PBSCT, seem to be generally satisfied with their overall HRQoL.