65 research outputs found

    Paediatric extracranial germ-cell tumours.

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    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.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/S1470-2045(15)00545-

    Surveillance after initial surgery for pediatric and adolescent girls with stage I ovarian germ cell tumors: report from the Children's Oncology Group

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    PURPOSE: To determine whether overall survival (OS) can be preserved for patients with stage I pediatric malignant ovarian germ cell tumor (MOGCT) with an initial strategy of surveillance after surgical resection. PATIENTS AND METHODS: Between November 2003 and July 2011, girls age 0 to 16 years with stage I MOGCT were enrolled onto Children's Oncology Group study AGCT0132. Required histology included yolk sac, embryonal carcinoma, or choriocarcinoma. Surveillance included measurement of serum tumor markers and radiologic imaging at defined intervals. In those with residual or recurrent disease, chemotherapy with compressed PEB (cisplatin, etoposide, and bleomycin) was initiated every 3 weeks for three cycles (cisplatin 33 mg/m(2) on days 1 to 3, etoposide 167 mg/m(2) on days 1 to 3, bleomycin 15 U/m(2) on day 1). Survivor functions for event-free survival (EFS) and OS were estimated using the Kaplan-Meier method. RESULTS: Twenty-five girls (median age, 12 years) with stage I MOGCT were enrolled onto AGCT0132. Twenty-three patients had elevated alpha-fetoprotein (AFP) at diagnosis. Predominant histology was yolk sac. After a median follow-up of 42 months, 12 patients had evidence of persistent or recurrent disease (4-year EFS, 52%; 95% CI, 31% to 69%). Median time to recurrence was 2 months. All patients had elevated AFP at recurrence; six had localized disease, two had metastatic disease, and four had tumor marker elevation only. Eleven of 12 patients experiencing relapse received successful salvage chemotherapy (4-year OS, 96%; 95% CI, 74% to 99%). CONCLUSION: Fifty percent of patients with stage I pediatric MOGCT can be spared chemotherapy; treatment for those who experience recurrence preserves OS. Further study is needed to identify the factors that predict recurrence and whether this strategy can be extended successfully to older adolescents and young adults

    Comparison of carboplatin versus cisplatin in the treatment of paediatric extracranial malignant germ cell tumours: A report of the Malignant Germ Cell International Consortium.

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    PURPOSE: To compare the outcomes of paediatric and adolescent extracranial malignant germ cell tumour (GCT) patients treated with either carboplatin or cisplatin on clinical trials conducted by the Children's Oncology Group (COG) and the Children's Cancer and Leukaemia Group (CCLG). METHODS: The Malignant Germ Cell International Consortium (MaGIC) has created a database of the GCT clinical trials conducted since 1983 by COG (United States, Canada and Australia), which used cisplatin-based regimens, and by CCLG (United Kingdom), which used carboplatin-based regimens. Using the parametric cure model, this study compared the overall 4-year event-free survival (EFS), stratified by age, stage, site and the a-priori defined MaGIC 'risk' groups: standard risk ((SR) 1 (EFS >80%; age 80%, age ≥ 11y) and poor risk (PR) (EFS ≤ 70%, age ≥ 11y). RESULTS: Cisplatin-based therapy was used in 620 patients; carboplatin was used in 163 patients. In the overall multivariate cure model, the two regimens did not differ significantly (cisplatin: 4-year EFS 86%; 95% confidence interval (CI) 83-89% versus carboplatin 4-year EFS 86%; 95% CI 79-90%; p = 0.87). No significant differences were noted in stratified analyses by site, stage, age and MaGIC risk groups: SR1 (p = 0.20), SR2 (p = 0.55) or PR (p = 0.72) patients. CONCLUSIONS: In these trials conducted contemporaneously, there is no significant difference in outcome observed overall, or any subset of patients, who were treated with regimens containing cisplatin versus carboplatin These results suggested sufficient equipoise to justify a randomised trial to evaluate the effectiveness of carboplatin versus cisplatin in the treatment of children, adolescents and young adults with standard risk GCT, which is currently underway

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

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    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.This is the author accepted manuscript. The final version is available from Wiley at http://dx.doi.org/10.1002/cncr.29732

    Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma

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    Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report

    Hemoglobin level and macular thinning in sickle cell disease

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    S Amal Hussnain,1–4 Patrick A Coady,1,5 Martin D Slade,6 Judith Carbonella,7 Farzana Pashankar,7 Ron A Adelman,1 Kathleen M Stoessel11Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA; 2Department of Ophthalmology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; 3Vitreous Retina Macula Consultants of New York, New York, NY, USA; 4Department of Ophthalmology, New York University School of Medicine, New York, NY, USA; 5New England Retina Associates, Hamden, CT, USA; 6Department of Internal Medicine, Yale University School of Medicine and Yale School of Public Health, New Haven, CT, USA; 7Department of Pediatric Hematology and Oncology, Yale University School of Medicine, New Haven, CT, USAPurpose: To study the relationship between complete blood count (CBC) indices over time, particularly serum hemoglobin (Hb) levels, and severity of macular thinning on spectral domain optical coherence tomography (SD-OCT) in patients with sickle cell disease (SCD).Methods: This is a single-center, retrospective analysis of 141 consecutive SCD patients over a 10-year period, of which 40 patients (79 eyes) had SD-OCT imaging of the macula and 29 (58 eyes, mean age 17.5 years) were eligible for the study. Investigators reviewed electronic medical records for documentation of retinopathy stage, disease genotype, CBC values, and SD-OCT imaging. SD-OCT parameters and CBC values were compared between different retinopathy stages and disease genotypes. Regression analyses were performed on SD-OCT parameters and CBC values.Results: Of the 58 eligible eyes (34HbSS, 18HbSC, 4HbSβ +thal, 2HbS βthal), 18 had PSR (proliferative sickle retinopathy), 14 had NPSR (nonproliferative sickle retinopathy), and 26 had NSR (no sickle retinopathy). Hb values were higher in SC group compared to SS group. Macular thickness in the temporal inner (Δ=26±33 um, p=0.01) and outer (Δ=21±30 um, p=0.02) subfields was higher in SC compared to SS group. Patients with SD-OCT thinning below the 5th percentile in the temporal outer subfields had lower recorded Hb nadirs (6.0±0.9) compared to those with thickness within the top 95th percentile (9.1±2.3). Regression analysis showed temporal macular thickness to be positively correlated with Hb values in the SS group.Conclusion: Macular thinning observed on SD-OCT in SCD patients with SS genotype may be related to the level of anemia in this population.Keywords: sickle cell retinopathy, macular thinning, spectraldomain optical coherence tomography, hemoglobi

    Utility of frozen section in pediatric and adolescent malignant ovarian nonseminomatous germ cell tumors: A report from the children's oncology group

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    Purpose: In adult women, most malignant ovarian tumors are epithelial in origin. The use of intra-operative frozen section to distinguish between benign and malignant histology is reliable in guiding operative decision-making to determine the extent of surgical staging required. Pediatric and adolescent patients with ovarian masses have a much different spectrum of pathology with most tumors arising from germ cell precursors. This review was undertaken to assess the concordance between the intra-operative frozen section and the final diagnosis as an aid to guide extent of surgical staging in a group of pediatric and adolescent patients with malignant ovarian germ cell tumors. Methods: Records of patients aged 0 to 20 years with malignant ovarian germ cell tumors enrolled on Children's Oncology Group study AGCT0132 were reviewed. Pathology reports from patients who had both intra-operative frozen section diagnosis and final paraffin section diagnosis were compared using descriptive statistics. By inclusion criteria for the study, all patients had a final diagnosis of malignancy with required yolk sac tumor, choriocarcinoma or embryonal carcinoma histology. Available central review of pathology final paraffin section slides were compared with final institution pathology reports. Results: Of 131 eligible patients with ovarian germ cell tumors, 60 (45.8%) had both intra-operative frozen section and final paraffin section diagnoses available. Intra-operative frozen section diagnoses were classified as: incorrect diagnosis of benign tumor (13.3%), confirmation of malignancy (61.7%), immature teratoma (16.7%), germ cell tumor not otherwise specified (5%) and no diagnosis provided (3.3%). Intra-operative frozen section was incorrect in 23 of 60 (38.3%) patients evaluated. Central pathology review was concordant with the final institution pathology diagnosis in 76.3% of patients. Central pathology review identified additional germ cell tumor components in 23.7% of patients. Conclusions: In pediatric and adolescent patients with a confirmed final diagnosis of ovarian germ cell malignancy, intra-operative frozen section diagnosis is not reliable to inform the extent of surgical staging required. Central review by an expert germ cell tumor pathologist provides important additional information to guide therapy

    Weight Status of Children With Sickle Cell Disease

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