Outcomes of adolescent males with extracranial metastatic germ cell tumors: A report from the Malignant Germ Cell Tumor International Consortium.

BACKGROUND: Adolescents with extracranial metastatic germ cell tumors (GCTs) are often treated with regimens developed for children, but their clinical characteristics more closely resemble those of young adult patients. This study was designed to determine event-free survival (EFS) for adolescents with GCTs and compared them with children and young adults. METHODS: An individual patient database of 11 GCT trials was assembled: 8 conducted by pediatric cooperative groups and 3 conducted by an adult group. Male patients aged 0 to 30 years with metastatic, nonseminomatous, malignant GCTs of the testis, retroperitoneum, or mediastinum who were treated with platinum-based chemotherapy were included. The age groups were categorized as children (0 to <11 years), adolescents (11 to <18 years), and young adults (18 to ≤30 years). The study compared EFS and adjusted for risk group by using Cox proportional hazards analysis. RESULTS: From a total of 2024 individual records, 593 patients met the inclusion criteria: 90 were children, 109 were adolescents, and 394 were young adults. The 5-year EFS rate was lower for adolescents (72%; 95% confidence interval [CI], 62%-79%) than children (90%; 95% CI, 81%-95%; P = .003) or young adults (88%; 95% CI, 84%-91%; P = .0002). The International Germ Cell Cancer Collaborative Group risk group was associated with EFS in the adolescent age group (P = .0020). After adjustments for risk group, the difference in EFS between adolescents and children remained significant (hazard ratio, 0.30; P = .001). CONCLUSIONS: EFS for adolescent patients with metastatic GCTs was similar to that for young adults but significantly worse than for that children. This finding highlights the importance of coordinating initiatives across clinical trial organizations to improve outcomes for adolescents and young adults. LAY SUMMARY: Adolescent males with metastatic germ cell tumors (GCTs) are frequently treated with regimens developed for children. In this study, a large data set of male patients with metastatic GCTs across different age groups has been built to understand the outcomes of adolescent patients in comparison with children and young adults. The results suggest that adolescent males with metastatic GCTs have worse results than children and are more similar to young adults with GCTs. Therefore, the treatment of adolescents with GCTs should resemble therapeutic approaches for young adults.

Adjuvant chemoradiation for high-grade cardiac leiomyosarcoma in a child: Case report and review of literature.

A 13-year-old healthy girl presented with dizziness and palpitations, found to have a left atrial mass. An 8-cm tumor was removed en bloc. Pathology confirmed grade 3 leiomyosarcoma with multifocal positive margins. She received adjuvant ifosfamide and doxorubicin, followed by concurrent proton radiotherapy and ifosfamide. Radiotherapy included 66 Gy (RBE) in 33 fractions to the operative bed. Prospectively graded toxicities included Grade 2 esophagitis and Grade 1 anorexia, dermatitis, and fatigue. She completed six cycles of ifosfamide. Two years post operation, she had no evidence of disease, intermittent palpitations with normal cardiac function, and no other cardiopulmonary or esophageal symptoms.

α-Fetoprotein as a predictor of outcome for children with germ cell tumors: A report from the Malignant Germ Cell International Consortium.

BACKGROUND: There are several studies describing the correlation between unsatisfactory tumor marker decline and a poor prognosis for adult patients treated for germ cell tumors. In pediatric patients, the data are limited. Therefore, this study retrospectively analyzed data from Children's Oncology Group (COG) protocol AGCT0132 to determine whether a relationship exists between α-fetoprotein (AFP) decline and outcome. METHODS: One hundred thirty-one patients with germ cell tumors who were enrolled in COG protocol AGCT0132 were eligible for this analysis of AFP decline. The serum AFP half-life was calculated from levels collected postoperatively as a baseline and after the start of chemotherapy. AFP decline was defined as automatically satisfactory (AFP normalized within the first 2 AFP measures after the start of chemotherapy), calculated satisfactory (AFP half-life ≤7 days after the start of chemotherapy), and unsatisfactory. RESULTS: The 3-year cumulative incidence of relapse was 11% (95% confidence interval [CI], 6.0%-18%) for patients with a satisfactory decline and 38% (95% CI, 13%-64%) for patients with an unsatisfactory decline (P = .006). In stratified analyses, this effect was limited to patients who were 11 years of age or older and had standard risk 2 (SR2) disease (P = .004 and P = .007, respectively). Three-year overall survival (OS) for patients with a satisfactory decline versus an unsatisfactory decline was not statistically significant. CONCLUSIONS: This study is the first to show an association between AFP decline and the cumulative incidence of relapse in pediatric patients treated for germ cell tumors. Recognition of patients at high risk for relapse may allow for early intensification of therapy, which could affect future clinical trial design.

Ovarian cancer in adolescents and young adults.

The diagnosis of ovarian cancer in adolescents and young adults is always challenging. Many issues exist, and most important of these may be access to care with an appropriate provider. A range of histologies occur in the ovaries, and their frequency changes markedly as patients progress from adolescence to young adulthood. The very curable germ cell tumors of adolescence slowly give way to aggressive carcinomas, which require a different treatment approach. Special consideration is needed for treatment of toxicity. In an ideal world, centers consisting of pediatric, medical, and gynecological oncologists may be the most appropriate to care for these complex and diverse patients.

Is carboplatin-based chemotherapy as effective as cisplatin-based chemotherapy in the treatment of advanced-stage dysgerminoma in children, adolescents and young adults?

OBJECTIVE: Dysgerminoma is the most common malignant ovarian germ cell tumor (GCT) with peak incidence during adolescence and young adulthood. Current standard of care for patients with disease that has spread outside of the ovary (advanced-stage) utilizes platin-based chemotherapy regimens. The study objective was to compare clinical outcomes between platin-based (carboplatin versus cisplatin) strategies across all age groups (children < 11 years (y), adolescents = 11-25 y and young adult women > 25 y) for advanced-stage dysgerminoma. METHODS: The Malignant Germ Cell Tumor International Consortium (MaGIC) pooled data from six GCT trials (3 = pediatric, 3 = adult) conducted internationally by pediatric and gynecologic oncology clinical trial organizations (CTOs) between 1983 and 2009. Newly diagnosed patients, with advanced-stage (FIGO IC-IV) dysgerminoma, who received either carboplatin- or cisplatin-based chemotherapy were eligible for analysis. RESULTS: 126 eligible patients were identified; 56 patients (38 = pediatric, 18 = adult) received carboplatin-based and 70 patients (50 = pediatric, 20 = adult) received cisplatin-based chemotherapy. Mean age was 20 y (range = 6-46 y). The median follow-up was 10.3 y (range = 0.17-21.7 y). The five-year event-free survival (EFS5) and overall survival (OS5) was 0.94 (95%CI, 0.88-0.97) and 0.96 (95%CI, 0.91-0.99) respectively. Survival outcomes were comparable between carboplatin-(EFS5 = 0.96 (95%CI, 0.85-0.99), OS5 = 0.96 (95%CI, 0.85-0.99)) and cisplatin-(EFS5 = 0.93 (95%CI, 0.83-0.97), OS5 = 0.96 (95%CI, 0.87-0.99)) based regimens. Across three age groups, comparison of the EFS5 (<11 y = 0.1, 11-25 y = 0.91 (95%CI, 0.82-0.96), >25 y = 0.97 (95%CI, 0.81-0.99)) and OS5 (<11 y = 0.1, 11-25 y = 0.95 (95%CI, 0.87-0.99), >25 y = 0.97 (95%CI, 0.81-0.99)) did not demonstrate any statistically significant differences in outcomes. CONCLUSIONS: Patients diagnosed with dysgerminoma have an excellent OS, across all ages, even in the context of metastatic disease. Data from three large CTOs supports the investigation of carboplatin-based regimens in the frontline treatment of all patients with advanced-stage dysgerminoma to minimize treatment-related toxicities.

Ovarian Sertoli-Leydig tumor after bone marrow transplant for sickle cell disease.

As bone marrow transplant for sickle cell disease becomes increasingly common, long-term outcomes including secondary malignancies are beginning to be described. Here, we report a case of ovarian Sertoli-Leydig tumor that occurred after allogeneic bone marrow transplant for sickle cell disease.

Treatment of refractory germ cell tumors in children with paclitaxel, ifosfamide, and carboplatin: A report from the Children's Oncology Group AGCT0521 study.

BACKGROUND: Paclitaxel, ifosfamide, cisplatin (TIP) is commonly used as salvage for malignant germ cell tumors (MGCT) in adults; however, additional administration of cisplatin at a young age could cause significant short- and long-term toxicities in a group of patients with high expected salvage. Because carboplatin has been shown to be effective in pediatric MGCT with less toxicity, the TIP regimen was modified by substituting carboplatin for cisplatin. METHODS: The Children's Oncology Group conducted a phase II trial between November 2007 and June 2011 evaluating "TIC" (paclitaxel 135 mg/m2 /day Day 1, ifosfamide 1,800 mg/m2 /dose Days 1-5 and carboplatin with AUC 6.5 Day 1) in children < 21 years with relapsed MGCT. The endpoint of the trial was response after two cycles, incorporating RECIST response and marker decline. RESULTS: Twenty patients (12 male, median age 13.5 years) were enrolled. Seventeen patients had tumor markers ≥10 times above normal. After two cycles, by RECIST criteria, 8 patients achieved a partial response (response rate 40%), 10 had stable disease, and 2 had progressive disease. A ≥ 1 log reduction was achieved in 10/17 patients (58.8%) with elevated markers. By study defined criteria, combining response by RECIST and marker decline, the response rate was 44%. CONCLUSION: TIC is active in relapsed pediatric MGCT and should be considered for salvage therapy in children. In adolescents and older adults with relapse MGCT, TIP or high-dose chemotherapy with stem cell remain the standard therapy.

Gemcitabine/nab-paclitaxel for pediatric relapsed/refractory sarcomas.

BACKGROUND: Pediatric patients with relapsed/refractory sarcomas have poor outcomes and need novel therapies that provide disease control while maintaining an acceptable quality of life. The activity and toxicity of gemcitabine and nab-paclitaxel in combination has not been reported in pediatrics. PROCEDURE: We reviewed the records of fifteen relapsed/refractory patients and one treatment-naïve patient who received gemcitabine/nab-paclitaxel at our institution. RESULTS: Sixteen patients (median age 13.5 years, range 3-19 years) received 53 cycles of gemcitabine/nab-paclitaxel. Twenty-nine cycles (55%) resulted in ≥Grade 3 toxicity, with nonhematologic Grade ≥3 toxicities occurring in only eight of 53 cycles (15%). Patients received red blood cell and platelet transfusions in 23% and 4% of cycles, respectively. Grade ≥3 infectious toxicities occurred in 4% of cycles. Of 14 patients with measurable disease, there were no complete responses (CR), one partial response (PR; 7%), and six patients (43%) with stable disease (SD; median SD: 4.5 months, range: 2-19 months). In total, 31% of the patients derived clinical benefit (CR + PR + SD ≥ 4 months). Median time to progression was 72 days with a 4-month progression-free survival of 31% ± 12% and 1-year overall survival of 19% ± 10%. With a median follow-up for all 16 patients of 21 months from the first treatment with gemcitabine/nab-paclitaxel, one (6%) remains alive with disease. CONCLUSIONS: Gemcitabine/nab-paclitaxel is a relatively safe regimen with mainly hematologic toxicities. It offers a well-tolerated, palliative option providing clinical benefit in a subset of patients. A phase I trial of this combination is underway.

Gonadal dysgenesis is associated with worse outcomes in patients with ovarian nondysgerminomatous tumors: A report of the Children's Oncology Group AGCT 0132 study.

PURPOSE: In this report, we characterize the timing and behavior of malignant ovarian germ cell tumors (GCTs) in pediatric patients with dysgenetic gonads compared to those with normal gonadal development. PATIENTS AND METHODS: Patients from the Children's Oncology Group AGCT0132 with malignant ovarian GCTs were included. Within this population, we sought to identify patients with gonadoblastoma, streak ovaries, or other evidence of gonadal dysgenesis (GD). Patients with malignant GCTs containing one or more of the following histologies-yolk sac tumor, embryonal carcinoma, or choriocarcinoma-were included. Patients were compared with respect to event-free survival (EFS) and overall survival (OS). RESULTS: Nine patients with GD, including seven with gonadoblastoma (mean age, 9.3 years), were compared to 100 non-GD patients (mean age, 12.1 years). The estimated 3-year EFS for patients with GD was 66.7% (95% CI 28.2-87.8%) and for non-GD patients was 88.8% (95% CI 80.2-93.8%). The estimated 3-year OS for patients with GD was 87.5% (95% CI 38.7-98.1%) and for non-GD patients was 97.6% (95% CI of 90.6-99.4%). CONCLUSION: Patients presenting with nongerminomatous malignant ovarian GCTs in the context of GD have a higher rate of events and death than counterparts with normal gonads. These findings emphasize the importance of noting a contralateral streak ovary or gonadoblastoma at histology for any ovarian GCT and support the recommendation for early bilateral gonadectomy in patients known to have GD with Y chromosome material. In contrast to those with pure dysgerminoma, these patients may represent a high-risk group that requires a more aggressive chemotherapy regimen.

Paediatric extracranial germ-cell tumours.

Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.

Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative.

BACKGROUND: There is a debate regarding the management of ovarian immature teratomas (ITs). In adult women, postoperative chemotherapy is standard except for stage I, grade 1 disease, whereas surgery alone is standard in pediatric patients. To determine the role of chemotherapy, a pooled analysis of pediatric and adult clinical trials was conducted. METHODS: Data from 7 pediatric trials and 2 adult trials were merged in the Malignant Germ Cell International Collaborative data set. Four trials included patients with newly diagnosed pure ovarian ITs and were selected (Pediatric Oncology Group/Children's Cancer Group Intergroup Study (INT 0106), Second UKCCSG Germ Cell Tumor Study (GC2), Gynecologic Oncology Group (GOG 0078 and GOG 0090). Adult and pediatric trials were analyzed separately. The primary outcome measures were event-free survival (EFS) and overall survival (OS). RESULTS: One hundred seventy-nine patients were included (98 pediatric patients and 81 adult patients). Ninety pediatric patients were treated with surgery alone, whereas all adult patients received chemotherapy. The 5-year EFS and OS were 91% and 99%, respectively, for the pediatric cohort and 87% and 93%, respectively, for the adults. There were no relapses in grade 1 patients, regardless of the stage or age. Only 1 adult patient with a grade 2 IT relapsed. Among grade 3 patients, the 5-year EFS was 0.92 (0.72-0.98) for stage I/II and 0.52 (0.22-0.75) for stage III in the pediatric cohort (P = .005) and 0.91 (0.69-0.98) for stage I/II and 0.65 (0.39-0.83) for stage III/IV in the adult cohort (P = .01). Postoperative chemotherapy did not decrease relapses in the pediatric cohort. CONCLUSIONS: The grade was the most important risk factor for relapse in ovarian ITs. Among grade 3 patients, the stage was significantly associated with relapse. Adjuvant chemotherapy did not decrease relapses in the pediatric cohort; its role in adults remains unresolved. Cancer 2016;122:230-237. © 2015 American Cancer Society.

Gemcitabine and docetaxel (GEMDOX) for the treatment of relapsed and refractory pediatric sarcomas.

BACKGROUND: Patients with relapsed pediatric sarcomas have a poor outcome and are in need of novel effective therapies. METHODS: We retrospectively reviewed the records of patients at Children's Healthcare of Atlanta who were treated with gemcitabine (675 mg/m(2)) intravenously (IV) on Day 1 and Day 8, and docetaxel (75 mg/m(2)) IV on Day 8, repeated every 3 weeks. RESULTS: Nineteen patients with a median age of 11 years were treated from 2006-2010 and received 123 total courses. Two patients (11%), both with rhabdomyosarcoma, demonstrated objectives responses [one complete response (CR) and one partial response (PR)]. Seven other patients (39%) had stable disease (SD). The 1-year progression-free survival (PFS) of the entire cohort was 24% ± 10% with a median time to progression of 2 months (range: 0.5-14 months). The 1-year overall survival (OS) was 43% ± 11%. Grade 3 or 4 toxicities occurred in 14 patients (74%) and 52 courses (42%), and were most commonly hematologic (neutropenia = 37, anemia = 17, and thrombocytopenia = 23 courses). CONCLUSIONS: The dismal outcomes for patients with relapsed and refractory sarcomas and the lack of effective sarcoma salvage regimens highlight the need for new approaches. This report of the therapeutic activity of gemcitabine and docetaxel (GEMDOX) in rhabdomyosarcoma and other pediatric reports describing activity in osteosarcoma and Ewing sarcoma suggest that this combination should be considered for formal evaluation in a pediatric specific clinical trial. At a minimum, it appears to offer a reasonable, tolerable, palliative option.

The use of zoledronic acid in pediatric cancer patients.

BACKGROUND: The third generation bisphosphonate zoledronic acid has demonstrated efficacy in reducing skeletal-related events in adult patients with multiple cancer types that have skeletal disease. The use of zoledronic acid in pediatric oncology patients with bone metastases for the purpose of reducing pain, improving bone strength and altering the progression of metastatic disease has not been thoroughly evaluated. PROCEDURE: From October 2005 to December 2008, 19 patients at the Aflac Cancer Center received one or more doses of zoledronic acid as part of their therapy. A retrospective review of these patients was performed and information was collected including indication for treatment, toxicities, and outcomes. RESULTS: Most patients (n = 15) received zoledronic acid following relapse of their malignancy with metastatic disease present in one or more bony sites. Hypocalcemia and hypophosphatemia were frequent, but did not result in clinical symptoms. More significant toxicities associated with zoledronic acid, including clinically apparent renal insufficiency and osteonecrosis of the jaw, were not seen. Overall, zoledronic acid was well tolerated in this population. CONCLUSIONS: The benefits of zoledronic acid seen in randomized trials of adults with bone metastases have sparked interest in its use for children with metastatic cancer. The administration of zoledronic acid in pediatric oncology appears safe, and may result in improved bone strength and pain control. Further evaluation is warranted to prospectively evaluate its efficacy and long-term safety in pediatric patients with cancer and skeletal metastases.

Fibrocartilaginous mesenchymoma, a unique osseous lesion: case report with review of the literature.

Fibrocartilaginous mesenchymoma is a rare osseous tumor that primarily arises in the long bones of children and adolescents. This lesion can grow quickly and reach a considerable size, despite its benign nature. It has proved challenging to diagnose and can be mistaken for a spectrum of benign and malignant bone tumors. The histological presentation of unique epiphyseal plate-like cartilage with destruction of the surrounding cortical bone and exhibition of dense fibrous stroma are important indicators for the diagnosis of fibrocartilaginous mesenchymoma. An 11-year-old boy presented with a left proximal humerus mass thought to be an aneurysmal bone cyst. The patient was lost to follow-up and came back 3 years later with massive growth of the lesion. Owing to the aggressive nature of the tumor, a left forequarter amputation was performed. Histological examination demonstrated numerous islands of cartilage with an exuberant spindle cell component characteristic of FCM. No distant metastases or local recurrences were identified at 2 years post-amputation. Because of the rapid growth of this lesion, it should be considered in the differential diagnosis of bone lesions in children and young adults.

Vaginal Yolk Sac Tumor: A Case Series and Review of the Literature.

OBJECTIVE: To report diagnosis, treatment, and outcomes of vaginal yolk sac tumor (YST) cases at a single institution and review literature on vaginal YST to outline advancements in diagnosis, treatment, and survival. DESIGN: Retrospective chart review of female patients less than 21 years of age with pathologic diagnosis of vaginal YST treated at a large children's hospital, and summary of a 100-year review of the literature on vaginal yolk sac tumor. SETTING: Children's Healthcare of Atlanta, a tertiary center in Atlanta, GA. PARTICIPANTS: Female patients less than 21 years of age diagnosed with vaginal YST. RESULTS: Two cases of vaginal YST at our institution are outlined. Both patients presented within the first 2 years of life with vaginal bleeding and were treated successfully with chemotherapy alone. After review of the literature, 137 cases of vaginal YST were found. The mean age at diagnosis was 11 months, and all patients presented with vaginal bleeding. Before 2000, more radical treatments were pursued, and 40% resulted in death. Since the year 2000, treatment has shifted toward chemotherapy and more conservative surgical management, with 51% of vaginal YST cases treated with chemotherapy alone with 92% of patients alive at time of publication. CONCLUSION: Our cases contribute to the limited literature demonstrating the efficacy of conservative management of rare cases of vaginal YST with chemotherapy alone. This case series and review of the literature provide mounting evidence that vaginal YST should be in the differential diagnosis in young girls with vaginal tumors, and conservative management of vaginal YST has excellent outcomes.

Intracavitary cisplatin therapy for pediatric malignancies.

BACKGROUND: Local control is essential for the successful treatment of pediatric solid tumors. Complete excision is often not possible and local control therapies are limited. Intracavitary cisplatin (IC-CDDP) may be utilized to supplement local control. The aim of the study was to determine the toxicity and efficacy of locally instilled intracavitary cisplatin in patients with recurrent tumors in closed body cavities. PROCEDURE: From 2001 to 2009, 12 patients (1-20 years) with recurrent or unresectable malignant tumors were treated with IC-CDDP. Nine had pulmonary lesions. Three patients had abdominal tumors. CDDP (200 mg/m(2)) was instilled by chest tube or Tenckhoff catheter. Patients were shifted every 15-30 min to allow distribution. After 4 hr, residual was drained by gravity. In 10/13 courses, sodium thiosulfate (STS) was administered to prevent nephrotoxicity. Three other patients received amifostine. RESULTS: Malignant pleural effusions resolved in 5/7 patients. This response was temporary in three patients. No patients had ascites prior to treatment. Three patients are alive and disease-free, 18 months, 4 years, and 6 years from treatment. They also had surgery and chemotherapy. Transient renal toxicity was noted in most patients. One patient, treated with amifostine, had persistent renal dysfunction. CONCLUSIONS: IC-CDDP was effective in treating malignant pleural effusions and may be a palliative option for refractory disease. Long-term survival was achieved in two patients, treated at first diagnosis. The benefit of IC-CDDP in these patients is difficult to assess. Renal dysfunction is usually mild, and typically resolves, but warrants preventive measures with IC-CDDP therapy.

Metastatic primary angiosarcoma of the breast in a pediatric patient with a complete response to systemic chemotherapy and definitive radiation therapy: case report and review of the literature.

We present a case of a rare malignancy, primary breast angiosarcoma, in a 15-year-old girl. She presented with a locally advanced tumor and suspected metastatic disease to the mediastinum and bones on PET imaging. The patient was treated with systemic chemotherapy and definitive radiation therapy to her left breast and achieved a complete response. She has no evidence of disease recurrence 44 months from her initial diagnosis.

Routine Surveillance Imaging Is Associated with Improved Postrelapse Survival in Patients with Ewing Sarcoma.

Purpose: Children with Ewing sarcoma (ES) routinely undergo surveillance imaging after completion of therapy; however, the medical benefit of this imaging remains unclear. We aimed to determine whether there is a difference in survival between patients whose relapse was detected based on development of new symptoms or by routine imaging. Methods: We retrospectively reviewed all patients consecutively diagnosed with ES at Children's Healthcare of Atlanta from 2000 to 2011. Patient characteristics and outcomes were compared based on whether their relapse was diagnosed based on symptoms or by routine surveillance imaging alone. Results: Thirty-three percent (28/85) of patients relapsed. Median age at time of relapse was 15.5 years (interquartile range: 12.5-18.0). Among the relapsed patients, 57% (16/28) were symptomatic and 43% (12/28) were asymptomatic, having relapse detected on surveillance imaging alone. The most common presenting symptom was bone pain occurring in 69% (11/16) of patients. The 5-year postrelapse overall survival for patients with symptomatic relapse was 0% (95% confidence interval [CI]: not estimated) compared with 15% (95% CI: 1-48) for patients with an asymptomatic relapse (p < 0.01). After adjusting for extent of disease and time to relapse, having a symptomatic relapse was still strongly associated with a worse outcome (hazard ratio: 9.68; 95% CI: 3.09-30.34). Conclusion: Patients with ES whose relapse is detected on imaging before the development of symptoms have significantly better outcomes, suggesting a potentially beneficial role of routine surveillance imaging in this population of patients. Further prospective analyses are needed to confirm these findings, and determine the optimal evidence-based imaging modality and schedule.

Age-Dependent Presentation and Clinical Course of 1465 Patients Aged 0 to Less than 18 Years with Ovarian or Testicular Germ Cell Tumors; Data of the MAKEI 96 Protocol Revisited in the Light of Prenatal Germ Cell Biology.

OBJECTIVE: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). METHODS: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. RESULTS: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. CONCLUSIONS: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.

One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab.

BACKGROUND: We previously showed in a prospective study that rituximab appears to be effective in some children and adolescents with severe chronic immune thrombocytopenia. Eleven of 36 patients achieved and maintained platelet counts over 50,000/mm(3) within the first 12 weeks. These patients were followed for the next year. METHODS: Platelet counts were monitored monthly and all subsequent bleeding manifestations and need for further treatment was noted. RESULTS: Eight of the 11 initial responders maintained a platelet count over 150,000/mm(3) without further treatment intervention. Three patients had a late relapse. One initial non-responder achieved a remission after 16 weeks, and two additional patients maintained platelet counts around 50,000/mm(3) without the need for further intervention. CONCLUSIONS: Rituximab resulted in sustained efficacy with platelet counts of 50,000/mm(3) or higher in 11 of 36 patients (31%).