Contemporary trends in management of stage 1 seminoma.

PURPOSE: Surveillance is now the preferred treatment strategy for patients with stage 1A/1B seminoma as reflected by the National Comprehensive Cancer Network guidelines. In this study, we aimed to describe trends in adjuvant management strategy for stage 1A/B seminoma from 2004 to 2016 using the National Cancer Database. MATERIALS AND METHODS: The database was queried for patients diagnosed with stage 1A/1B seminoma between 2004 and 2016. Staging was determined using the American Joint Committee on Cancer guidelines. Surveillance was defined as no treatment with chemotherapy or radiation within 60 days of diagnosis. Proportions of cancer patients utilizing surveillance, radiation, and single-agent chemotherapy were summarized annually. Kaplan-Meier survival analysis was used to compare overall survival between groups. RESULTS: 8,686 patients with stage 1A/1B seminoma met inclusion criteria over the course of the study period. Overall, 3,004 (34.6%) patients began adjuvant chemotherapy or radiation within 60 days. Utilization of surveillance increased from 39.8% in 2004 to 86.8% in 2016 while utilization of radiation decreased from 59.7% to 4.6%. High-volume centers adopted surveillance earlier than low-volume centers. CONCLUSION: This study describes trends in utilization of surveillance, chemotherapy, and radiotherapy for stage 1A/1B seminoma over 12 years. A major shift from utilization of adjuvant treatment to surveillance in patients with stage 1A/B seminoma is observed in this large national cancer database; a minority of patients now receive adjuvant treatment and risk-related toxicities. Survival analysis reveals similar survival at a median 5-year follow-up. The results provide insight into the time needed for clinical practice to adopt the preferred approach of surveillance over the time period studied.

Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214).

PURPOSE: Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported. PATIENTS AND METHODS: Random assignment was between RT and one infusion of carboplatin dosed at 7 × (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202). The trial was powered to exclude a doubling in RFRs assuming a 96-97% 2-year RFR after radiotherapy (hazard ratio [HR], approximately 2.0). RESULTS: Overall, 1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n = 904). RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89). One death as a result of seminoma (in RT arm) occurred. Patients receiving at least 99% of the 7 × AUC dose had a 5-year RFR of 96.1% (95% CI, 93.4% to 97.7%) compared with 92.6% (95% CI, 88.0% to 95.5%) in those who received lower doses (HR, 0.51; 95% CI, 0.24 to 1.07; P = .08). There was a clear reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT, n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03), and elevated pretreatment follicle-stimulating hormone (FSH) levels (> 12 IU/L) was a strong predictor (HR, 8.57; 95% CI, 1.82 to 40.38). CONCLUSION: These updated results confirm the noninferiority of single dose carboplatin (at 7 × AUC dose) versus RT in terms of RFR and establish a statistically significant reduction in the medium term of risk of second GCT produced by this treatment.

Stage I seminoma: what should a practicing uro-oncologist do in 2009?

Testicular tumors are uncommon, but they continue to represent an important group of malignancies in young men. It is the most common solid malignancy in males between the ages of 20 and 35, and primary germ cell tumors are the most common histological type. In the United States in 2008, approximately 4800 cases of seminoma, approximately 4100 of which were stage I disease were projected after the completion of staging investigations. Remarkable progress has been made in the treatment of testicular seminoma over the past 25 years. Management options of stage I seminoma include radiotherapy, surveillance, or adjuvant chemotherapy. Standard management until recent years has been adjuvant retroperitoneal radiotherapy. Although providing excellent long term results, this approach has been associated with increased risk of gonadal toxicity, development of secondary malignancies and an increased risk of cardiovascular disease. The use of surveillance in management of patients with stage I seminoma is therefore becoming more frequent as it minimizes the burden of treatment and maintains the cure rate at virtually 100%. Adjuvant chemotherapy using Carboplatin has been investigated as an alternative management approach. However, the long term outcomes of patients managed with Carboplatin are not yet clear and this strategy should only be used in a study setting. It has been suggested that more patients with stage I seminoma will die of their treatment than of their cancer; therefore, the thrust of modern management should be to maintain 100% cure while minimizing the burden of treatment.

Malignancies in beta-thalassemia patients: a single-center experience and a concise review of the literature.

Thalassemia represents the world's most common monogenic disease, characterized by absence of or decreased globin chain production. The lifespan of thalassemia patients has been extended as a result of current supportive treatment. We report three cases of cancer (non-Hodgkin lymphoma, Hodgkin disease, and seminoma) in thalassemic patients. Factors that may contribute to the pathogenesis of cancer seem to be infections and iron overload through mechanisms of oxidative damage; immunomodulation or coexistence of the two diseases may only be coincidental.

Testicular germ cell tumor with rhabdomyosarcoma successfully treated by disease-adapted chemotherapy including high-dose chemotherapy: case report and review of the literature.

Treatment and prognosis have not been well characterized in germ cell tumors (GCT) with a malignant nongerm cell component. Patients with a mediastinal tumor, neural or rhabdomyosarcomatous differentiation and distant metastases have the poorest prognosis. We report a rare case of mixed GCT composed of seminoma, teratoma and rhabdomyosarcoma with the rhabdomyosarcomatous component metastasized into the liver and bone marrow (BM) causing hypercalcemia. The patient was treated with differentiation-tailored chemotherapy (CHT) including a disease-adapted high-dose (HD) CHT regimen with purified autologous PBSCT (APBSCT) and pamidronate. To date, remission has lasted for 4 years. Tumor-adapted CHT including HD-CHT with APBSCT can induce long term remissions in high-risk patients with transformed GCT. A review of the literature is given.

Synchronous appearance of germ cell tumor and papillary carcinoma of the thyroid.

Synchronous appearance of 2 different malignancies in one patient is a rare phenomenon. We describe our experience of 2 patients with synchronous malignancies of the testis and thyroid gland, and of a third patient who developed a thyroid neoplasm unrelated to recent treatment for a germ cell tumor. The medical records of 3 male patients treated for both a germ cell tumor and a thyroid cancer between 1989 and 1994 were reviewed. Two patients with nonseminomatous germ cell tumor received postoperative chemotherapy after orchiectomy and developed a papillary carcinoma of the thyroid during treatment. A third patient, who received radiation therapy for a clinical stage 1 seminoma, recurred with biopsy proven seminoma in the neck in association with a thyroid nodule 2 years later. All 3 patients had their thyroid cancer treated by surgical resection, and one received adjuvant radioactive iodine. Two of the patients are currently alive and disease-free. One patient died of pulmonary complications that stemmed from bleomycin toxicity. Synchronous appearance of germ cell tumor and papillary carcinoma of the thyroid has not been previously described. Genetic predisposition may play a role in the development of such simultaneous neoplasms.

[Successful collection of peripheral blood stem cells mobilized by high-dose etoposide for patients with chemotherapy-resistant and/or poor prognostic testicular cancer].

Clinical effects of peripheral blood stem cell autotransplantation (PBSCT) after ultra high-dose chemotherapy were evaluated in patients with chemotherapy-resistant and/or poor prognostic testicular cancer. Four patients with testicular cancer, who had high-risk malignancy, were treated with high-dose etoposide (500 mg/m2 x 4 days) in order to collect peripheral blood stem cells. After the administration of high-dose etoposide, rG-CSF (250 micrograms/body) was administered from nadir state. Blood mononuclear cells were collected using a Fenwall CS-3000 blood cell separator. Fractions enriched for stem cells were obtained by discontinuous Percoll gradient centrifugation and were stored in liquid nitrogen using patient's sera and DMSO. The mean number of peripheral blood granulocyte-macrophage-colony-forming units (CFU-GM) collected by one apheresis was 22.3 x 10(5)/kg body weight. In addition, CFU-GM more than 2.0 x 10(5)/kg body weight could be collected in each apheresis, which was though to be sufficient dosis to perform PBSCT in safe, based upon our previous studies. All the patients were treated by a combination of cisplatin (20 mg/m2 x 5 days), etoposide (100 mg/m2 x 5 days) and bleomycin (15 mg x 3 days). Three patients responded to BEP therapy and obtained a CR, however, remaining 1 patient failed to achieve CR, who was later treated by ultrahigh-dose chemotherapy including carboplatin (200 mg/m2 x 4 days), etoposide (250 mg/m2 x 4 days) and cyclophosphamide (50 mg/kg x 2 days) followed by PBSCT. He responded to this therapy and obtained a CR for 10 months. The results suggested the method was promising for patients with chemotherapy-resistant and/or poor prognostic testicular cancer.

[Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer].

This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total, 6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x 10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious side effects or complications were encountered. The patient achieved partial remission for more than two months. However, he died of respiratory dysfunction caused by metastatic lung cancer 5 months later. It was thought that ultra high-dose chemotherapy with PBSCT might be a new therapy for refractory testicular cancer.

Secondary myelodysplastic syndrome following bone marrow transplantation: report of two cases.

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.