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1.
J Natl Compr Canc Netw ; 21(5): 487-495.e15, 2023 05.
Article in English | MEDLINE | ID: mdl-37156484

ABSTRACT

BACKGROUND: This study sought to evaluate the current services and delivery models of adolescent and young adult oncology (AYAO)-specific programs at NCI-designated Cancer Centers (NCI-CCs). PATIENTS AND METHODS: NCI, academic, and community cancer centers were electronically sent surveys from October to December 2020 and administered via REDCap. RESULTS: Survey responses were received from 50 of 64 (78%) NCI-CCs, primarily completed by pediatric oncologists (53%), adult oncologists (11%), and social workers (11%). Half (51%) reported an existing AYAO program, with most (66%) started within the past 5 years. Although most programs combined medical and pediatric oncology (59%), 24% were embedded within pediatrics alone. Most programs saw patients aged 15 (55%) to 39 years (66%) mainly via outpatient clinic consultation (93%). Most centers reported access to a range of medical oncology and supportive services, but dedicated services specifically for adolescent and young adults (AYAs) were available at a much lower extent, such as social work (98% vs 58%) and psychology (95% vs 54%). Although fertility preservation was offered by all programs (100%), only two-thirds of NCI centers (64%) reported providing sexual health services to AYAs. Most NCI-CCs (98%) were affiliated with a research consortium, and a lesser extent (73%) reported collaboration between adult and pediatric researchers. Nearly two-thirds (60%) reported that AYA oncology care was important/very important to their respective institution and reported providing good/excellent care to AYAs with cancer (59%), but to a lesser extent reported good/excellent research (36%), sexual health (23%), and education of staff (21%). CONCLUSIONS: Results of this first-ever national survey to assess AYAO programs showed that only half of NCI-CCs report having a dedicated AYAO program, and that areas of improvement include staff education, research, and sexual health services for patients.


Subject(s)
Neoplasms , Humans , Young Adult , Adolescent , Child , Neoplasms/epidemiology , Neoplasms/therapy , Neoplasms/psychology , Delivery of Health Care , Medical Oncology , Surveys and Questionnaires , Cancer Care Facilities
2.
J Surg Oncol ; 123(1): 342-351, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33051865

ABSTRACT

BACKGROUND AND OBJECTIVES: Success rates for initial image-guided biopsy of musculoskeletal (MSK) lesions have been well documented; evidence regarding success rates for repeat biopsy following initially nondiagnostic (ND) image-guided biopsy of MSK lesions is more limited. This study evaluates the outcomes of repeat computerized tomography-guided MSK biopsies following ND biopsies using a multidisciplinary approach. MATERIALS AND METHODS: Electronic medical record search covering a 10-year period identified patients that received two or more biopsies for an MSK tumor or tumor-like process. The decision for initial and repeat image-guided biopsy of each lesion was made following multidisciplinary MSK tumor board review. Lesion location, histopathology results, size of biopsy needle when available, and change in technique between biopsy attempts was documented. RESULTS: Repeat biopsy rate was 1.6%. 23 patients with repeat MSK biopsy were identified. A total of 17 of 23 (74%) repeat biopsy attempts were diagnostic. A total of 22 of 23 (96%) repeat biopsy attempts were clinically useful. Diagnostic repeat biopsies were described as employing one or more of five technical differences compared to the first biopsy attempt, the most common being improved targeting of the lesion itself. CONCLUSIONS: A multidisciplinary approach may yield improved repeat-biopsy rates and clinical utility of repeat MSK biopsies compared to prior reports.


Subject(s)
Image-Guided Biopsy/methods , Interdisciplinary Communication , Musculoskeletal Diseases/pathology , Tomography, X-Ray Computed/methods , Follow-Up Studies , Humans , Musculoskeletal Diseases/diagnostic imaging , Prognosis , Retrospective Studies
3.
Pediatr Dev Pathol ; 22(4): 329-333, 2019.
Article in English | MEDLINE | ID: mdl-30600764

ABSTRACT

Children with neuroblastoma rarely present with metastatic disease without identifiable primary tumors. We describe the clinical and histopathologic characteristics of 4 patients aged 1, 7, 7, and 11 years with neuroblastoma involving bone or bone marrow without an apparent primary site. One patient presented with a periorbital bone lesion, 1 presented with a distal femoral lesion, and 2 presented with diffuse bone marrow involvement. All tumors were negative for MYCN amplification. All patients were alive without evidence of disease 5 years after completion of multimodality therapy. Patients with neuroblastoma of the bone and bone marrow without an apparent primary site may constitute a unique group characterized by older age at diagnosis, nonamplified MYCN tumors, and good response to treatment.


Subject(s)
Bone Marrow Neoplasms/diagnostic imaging , Bone Neoplasms/diagnostic imaging , Neuroblastoma/diagnostic imaging , Biopsy , Bone Marrow/diagnostic imaging , Bone Marrow/pathology , Bone Marrow Neoplasms/pathology , Bone Marrow Neoplasms/radiotherapy , Bone Neoplasms/pathology , Bone Neoplasms/radiotherapy , Bone and Bones/diagnostic imaging , Bone and Bones/pathology , Child , Combined Modality Therapy , Follow-Up Studies , Humans , Infant , Neuroblastoma/pathology , Neuroblastoma/radiotherapy , Treatment Outcome
4.
Pediatr Blood Cancer ; 65(4)2018 04.
Article in English | MEDLINE | ID: mdl-29286555

ABSTRACT

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.


Subject(s)
Gonadal Dysgenesis/mortality , Neoplasms, Germ Cell and Embryonal/mortality , Ovarian Neoplasms/mortality , Adolescent , Adult , Child , Child, Preschool , Disease-Free Survival , Female , Gonadal Dysgenesis/diagnosis , Gonadal Dysgenesis/pathology , Gonadal Dysgenesis/therapy , Humans , Infant , Infant, Newborn , Neoplasms, Germ Cell and Embryonal/diagnosis , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/therapy , Survival Rate
5.
J Pediatr Hematol Oncol ; 40(5): e315-e318, 2018 07.
Article in English | MEDLINE | ID: mdl-29023302

ABSTRACT

Lymphoid interstitial pneumonia (LIP) is a rare disease characterized by benign reactive polyclonal proliferation of bronchus-associated lymphoid tissue after exposure to inhaled or circulating antigen(s), leading to a disease symptomatology similar to idiopathic interstitial pneumonia. Its association with diseases that are caused due to immune dysregulation (autoimmune diseases, congenital/acquired immunodeficiency, and allogeneic bone marrow transplant) and response to immunomodulatory/suppressive medications suggests an immunologic pathophysiology. Although LIP has been reported in association with lymphoproliferative diseases like Castleman disease, it has never been described in patients with leukemia. We report the first case of LIP in a patient with juvenile myelomonocytic leukemia (JMML) who was found to have a novel germline mutation of unknown significance in additional sex combs-like-1 (ASXL1) gene and a pathogenic somatic mutation of protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) gene at diagnosis. The patient underwent a matched unrelated bone marrow transplant for JMML with complete resolution of JMML and LIP with no recurrence to date. We also emphasize the importance of considering LIP in differential diagnosis of pulmonary lesions seen in conjunction with hematologic malignancies and distinguishing it from malignant infiltration of the lung.


Subject(s)
Bone Marrow Transplantation , Leukemia, Myelomonocytic, Juvenile/therapy , Lung Diseases, Interstitial/therapy , Allografts , Germ-Line Mutation , Humans , Infant , Leukemia, Myelomonocytic, Juvenile/diagnosis , Leukemia, Myelomonocytic, Juvenile/genetics , Leukemia, Myelomonocytic, Juvenile/pathology , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/genetics , Lung Diseases, Interstitial/pathology , Male , Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics , Repressor Proteins/genetics
6.
Hum Pathol ; 68: 147-153, 2017 10.
Article in English | MEDLINE | ID: mdl-28414089

ABSTRACT

Myeloid malignancies showing CD141+ myeloid dendritic cell (MDC) differentiation have not been documented. Here, we describe a patient with juvenile myelomonocytic leukemia in which a prominent CD141+ cell population was identified most consistent with CD141+ MDCs based on phenotypic similarity with normal CD141+ MDCs. Molecular studies demonstrated a KRAS mutation. The findings from the spleen and bone marrow are described. This is the first well-documented demonstration of CD141+ MDC differentiation of a hematopoietic neoplasm.


Subject(s)
Antigens, Surface/analysis , Biomarkers, Tumor/analysis , Cell Differentiation , Dendritic Cells/immunology , Leukemia, Myelomonocytic, Juvenile/immunology , Antigens, CD1/analysis , Biomarkers, Tumor/genetics , Biopsy , CD13 Antigens/analysis , Child , Dendritic Cells/pathology , Flow Cytometry , Genetic Predisposition to Disease , Glycoproteins/analysis , Humans , Immunohistochemistry , Leukemia, Myelomonocytic, Juvenile/genetics , Leukemia, Myelomonocytic, Juvenile/pathology , Leukemia, Myelomonocytic, Juvenile/therapy , Male , Mutation , Phenotype , Proto-Oncogene Proteins p21(ras)/genetics , Thrombomodulin
7.
J Clin Oncol ; 35(11): 1203-1210, 2017 Apr 10.
Article in English | MEDLINE | ID: mdl-28240974

ABSTRACT

Purpose To investigate whether event-free survival (EFS) can be maintained among children and adolescents with intermediate-risk (IR) malignant germ cell tumors (MGCT) if the administration of cisplatin, etoposide, and bleomycin (PEb) is reduced from four to three cycles and compressed from 5 to 3 days per cycle. Patients and Methods In a phase 3, single-arm trial, patients with IR MGCT (stage II-IV testicular, II-III ovarian, I-II extragonadal, or stage I gonadal tumors with subsequent recurrence) received three cycles of PEb. A parametric comparator model specified that the observed EFS rate should not be significantly < 92%. As recommended for trials that test a reduction of therapy, a one-sided P value ≤ .10 was used to indicate statistical significance. In a post hoc analysis, we also compared results to the EFS rate of comparable patients treated with four cycles of PEb in two prior studies. Results Among 210 eligible patients enrolled from 2003 to 2011, 4-year EFS (EFS4) rate was 89% (95% confidence interval, 83% to 92%), which was significantly lower than the 92% threshold of the comparison model ( P = .08). Among 181 newly diagnosed patients, the EFS4 rate was 87%, compared with 92% for 92 comparable children in the historical cohort ( P = .15). The EFS4 rate was significantly associated with stage (stage I, 100%; stage II, 92%; stage III, 85%; and stage IV, 54%; P < .001). Conclusion The EFS rate for children with IR MGCT observed after three cycles of PEb was less than that of a prespecified parametric model, particularly for patients with higher-stage tumors. These data do not support a reduction in the number of cycles of PEb from four to three. However, further investigation of a reduction in the number of cycles for patients with lower-stage tumors is warranted.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Neoplasms, Germ Cell and Embryonal/drug therapy , Ovarian Neoplasms/drug therapy , Testicular Neoplasms/drug therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Child , Cisplatin/administration & dosage , Cisplatin/adverse effects , Disease-Free Survival , Drug Administration Schedule , Etoposide/administration & dosage , Female , Humans , Male , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/secondary , Neoplasms, Germ Cell and Embryonal/surgery , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Prospective Studies , Risk Factors , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery
8.
J Pediatr Hematol Oncol ; 39(5): e293-e296, 2017 07.
Article in English | MEDLINE | ID: mdl-28230570

ABSTRACT

Primary progress has been made in the last 2 years, particularly in finding novel disease-causing genes for a number of autoinflammatory diseases and primary immunodeficiencies. Whole-exome sequencing has dramatically increased the pace at which causative genes are being discovered. CECR1 (Cat eye syndrome chromosome region, candidate 1) gene encodes adenosine deaminase 2 (ADA2) protein. Patients who carry CECR1 mutation(s) suffer from deficiency of ADA2 (DADA2). Here, we describe a patient with pure red cell aplasia discovered to have DADA2. We also review the literature on DADA2. This report will help raise awareness of physicians for this complex disease.


Subject(s)
Adenosine Deaminase/deficiency , Intercellular Signaling Peptides and Proteins/deficiency , Red-Cell Aplasia, Pure/diagnosis , Severe Combined Immunodeficiency/diagnosis , Bone Marrow Transplantation/methods , Child, Preschool , Diagnosis, Differential , Humans , Male , Red-Cell Aplasia, Pure/complications , Sequence Analysis, DNA
9.
Medicine (Baltimore) ; 96(2): e5858, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28079820

ABSTRACT

RATIONALE: Hepatoblastoma is a rare malignancy. Approximately 100 cases are diagnosed yearly in the United States. The highest incidence occurs in infants and in children younger than 5 years. Cases involving patients older than 5 years are very rare. We describe the case of a patient who was diagnosed with hepatoblastoma at an atypical age of presentation for this type of malignancy. We also performed Ovid MEDLINE search for hepatoblastoma and epidemiology reports occurring in children between the ages of 5 and 18 years. In this article we review the epidemiology and summarize case reports published between 1997 and 2012 of patients with hepatoblastoma, who were older than 5 years. PATIENT CONCERNS AND DIAGNOSIS: Our patient is an 11 year old boy with stage IV hepatoblastoma with lung and omental metastases at diagnosis. INTERVENTIONS: The patient received 7 cycles of chemotherapy following the treatment plan of COG protocol AHEP 0731, off study. He also had tumor resection and omentectomy and achieved complete remission. OUTCOMES: He later had disease recurrence and after undergoing treatment with different modalities, ultimately died of his disease. Review of SEER program data shows that the incidence of hepatoblastoma in children above the age of 5 years is too infrequent to be calculated. Literature review revealed 13 cases of patients diagnosed at age older than 5 years. Most cases were published due to unusual associations and/or complications. There are no obvious unifying characteristics for these cases, although there may be a slight male preponderance and many patients in this selected series presented with elevated Alpha-fetoprotein. LESSONS: The reported case is rare, given the very low incidence of hepatoblastoma outside of infancy. A systematic review of characteristics and outcomes for patients older than 5 years who are enrolled in cooperative group hepatoblastoma trials may reveal important information about the epidemiology and tumor biology in this rare patient population.


Subject(s)
Hepatoblastoma , Liver Neoplasms , Age of Onset , Child , Fatal Outcome , Hepatoblastoma/epidemiology , Hepatoblastoma/pathology , Hepatoblastoma/therapy , Humans , Incidence , Liver Neoplasms/epidemiology , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Lung Neoplasms/secondary , Male , Omentum , Peritoneal Neoplasms/secondary , Recurrence
10.
J Pediatr Hematol Oncol ; 39(6): e338-e341, 2017 08.
Article in English | MEDLINE | ID: mdl-27879545

ABSTRACT

Epstein-Barr virus-associated mucocutaneous ulcer (EBV-MCU) is a recently characterized entity that falls under the spectrum of EBV-lymphoproliferative disorders. First described in 2010 by Dojcinov et al, it is an EBV-driven localized proliferation of B cells, occurring in mucocutaneous tissues including the skin, the oropharynx, and the gastrointestinal tract of immunosuppressed patients in the absence of an intact T-cell repertoire. Typically, it has been described in elderly patients with age-related immunosenescence and patients who are on immunosuppressive therapy. However, only 2 cases have been reported in pediatric, adolescent, and young adult age groups, with all these patients manifesting after solid organ transplant. To the best of our knowledge there are no case reports of EBV-MCU occurring in association with hematologic malignancy. Here, we present a case of EBV-MCU in a young adult patient with T-cell acute lymphoblastic leukemia. Our report serves to promote awareness among clinicians regarding this newly described and extremely rare clinical entity in young immunosuppressed patients. In addition, we highlight the importance of accurate diagnosis to prevent overtreatment of this indolent, often self-resolving disease that has a significant clinicopathologic overlap with other aggressive forms of EBV-lymphoproliferative disorders that require more intensive therapy.


Subject(s)
Herpesvirus 4, Human , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/virology , Skin Ulcer/virology , Adult , Conservative Treatment , Epstein-Barr Virus Infections/complications , Humans , Immunocompromised Host , Lymphoproliferative Disorders/virology , Skin Ulcer/complications
11.
Pediatr Blood Cancer ; 64(5)2017 05.
Article in English | MEDLINE | ID: mdl-27786428

ABSTRACT

BACKGROUND: Sacrococcygeal teratoma (SCT) is the most common germ cell tumor (GCT) of infancy. Up to 35% of infants may have malignant elements. The standard of care for SCT with malignant elements (SCT-ME) has been surgery and chemotherapy. However, cases where low-stage SCT-ME have been successfully observed following resection have been reported. PROCEDURE: To better understand the outcomes of low-stage SCT-ME that do not receive chemotherapy, we reviewed SCT pathology reports from five children's hospitals from 1999 to 2009. Information regarding staging workup, tumor markers, treatment, and outcome was collected for patients with stage I or II SCT-ME. An English language literature review was also performed. RESULTS: Seventy-four SCT were identified: 51 stage I and 23 stage II; 13 (18%) were SCT-ME: 5 stage I and 8 stage II; four stage I and four stage II tumors were not treated with chemotherapy. No stage I tumors recurred; all of the stage II tumors recurred and were successfully salvaged, two had no ME at recurrence. We identified another 10 stage I SCT-ME in the literature managed with active surveillance-two recurred and were successfully treated with surgery and chemotherapy. CONCLUSIONS: Overall, of the 14 cases of stage I SCT-ME, 12 survived with no recurrence and the two who did recur were successfully treated with platinum-based chemotherapy (EFS = 86%, overall survival [OS] = 100%); this suggests that patients with stage I SCT-ME could be observed after surgery and treated only upon recurrence. Stage II SCT-ME require further study in a clinical trial setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/surgery , Sacrococcygeal Region/pathology , Biomarkers, Tumor , Combined Modality Therapy , Disease-Free Survival , Humans , Infant , Infant, Newborn , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/drug therapy , Retrospective Studies , Sacrococcygeal Region/surgery , Teratoma/pathology
12.
J Pharmacol Pharmacother ; 7(2): 62-71, 2016.
Article in English | MEDLINE | ID: mdl-27440950

ABSTRACT

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that predominantly occurs in children between 2 and 10 years of age. L-asparaginase is an integral component of treatment for patients with ALL and since its introduction into pediatric treatment protocols in the 1960s, survival rates in children have progressively risen to nearly 90%. Outcomes for adolescent and young adult (AYA) patients, aged 15-39 years and diagnosed with ALL, have historically been less favorable. However, recent reports suggest substantially increased survival in AYA patients treated on pediatric-inspired protocols that include a greater cumulative dose of asparaginase. All  currently available asparaginases share the same mechanism of action - the deamination and depletion of serum asparagine levels - yet each displays a markedly different pharmacokinetic profile. Pegylated asparaginase derived from the bacterium Escherichia coli is used as first-line therapy; however, up to 30% of patients develop a treatment-limiting hypersensitivity reaction. Patients who experience a hypersensitivity reaction to an E. coli-derived asparaginase can continue treatment with Erwinia chrysanthemi asparaginase. Erwinia asparaginase is immunologically distinct from E. coli-derived asparaginases and exhibits no cross-reactivity. Studies have shown that with adequate dosing, therapeutic levels of Erwinia asparaginase activity can be achieved, and patients switched to Erwinia asparaginase due to hypersensitivity can obtain outcomes similar to patients who do not experience a hypersensitivity reaction. Therapeutic drug monitoring may be required to ensure that therapeutic levels of asparaginase activity are maintained.

13.
Pediatr Blood Cancer ; 62(9): 1674-6, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25900577

ABSTRACT

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia.


Subject(s)
Agammaglobulinemia/therapy , Genetic Diseases, X-Linked/therapy , Leukemia, Myeloid, Acute/therapy , Peripheral Blood Stem Cell Transplantation , Agammaglobulinemia/complications , Allografts , Antibodies, Bacterial/biosynthesis , Antigens, CD19/analysis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B-Lymphocyte Subsets/chemistry , Child, Preschool , Combined Modality Therapy , Genetic Diseases, X-Linked/complications , Humans , Immunoglobulins, Intravenous/therapeutic use , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/drug therapy , Lymphocyte Count , Male , Pneumococcal Vaccines , Recurrence , Remission Induction , Streptococcus pneumoniae/immunology , Transplantation Conditioning
14.
J Pediatr Surg ; 50(6): 1000-3, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25812445

ABSTRACT

PURPOSE: The purpose of this study was to determine prognostic factors correlating with outcome in boys with Stage I malignant testicular germ cell tumors (MTGCT) initially managed with surveillance after surgical resection. METHODS: Between November 2003 and July 2011, 80 boys 0-15 years with Stage I MTGCT were enrolled in Children's Oncology Group Study AGCT0132. Those with residual or recurrent disease were treated with chemotherapy. RESULTS: Characteristics include: age (65, 0-5 years and 15, 11+years), pure YST (93.9%, 0-5 years and 0%, 11+years); and lymphovascular invasion (LVI) (50.6% present vs. 49.4% absent). At median follow-up of 4.94 years, 19 had persistent or recurrent disease, all detected by elevated AFP at a median of 87 days after study enrollment. The outcome from enrollment was 4-year EFS 74% (95% CI: 63%-83%) and 4-year OS 100%. 4-year EFS was improved with younger age (<11 years, 80% vs. 11+years, 48%, p<0.01); pure YST vs. mixed histology (81% vs. 45%, p<0.01), and lack of LVI (84% vs. 62%, p=0.03). CONCLUSIONS: Boys with Stage I MTGCT have excellent overall survival when treated with surgery alone. Age greater than 10 years, mixed histology and presence of LVI are each associated with relapse and may allow identification of high risk boys at time of enrollment.


Subject(s)
Neoplasm Recurrence, Local/diagnosis , Neoplasms, Germ Cell and Embryonal/surgery , Testicular Neoplasms/surgery , Adolescent , Child , Child, Preschool , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/pathology , Prognosis , Testicular Neoplasms/pathology , Treatment Outcome , Watchful Waiting
15.
J Clin Oncol ; 32(5): 465-70, 2014 Feb 10.
Article in English | MEDLINE | ID: mdl-24395845

ABSTRACT

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.


Subject(s)
Neoplasms, Germ Cell and Embryonal/surgery , Ovarian Neoplasms/surgery , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Child , Child, Preschool , Cisplatin/administration & dosage , Disease-Free Survival , Etoposide/administration & dosage , Female , Humans , Infant , Infant, Newborn , Kaplan-Meier Estimate , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Neoplasm, Residual , Neoplasms, Germ Cell and Embryonal/blood , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/secondary , Ovarian Neoplasms/blood , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Radiography , Risk Factors , Salvage Therapy , Time Factors , Treatment Outcome , alpha-Fetoproteins/metabolism
16.
Proteomics Clin Appl ; 5(9-10): 532-41, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21833997

ABSTRACT

PURPOSE: Despite intensive treatment regimens, overall survival for high-risk neuroblastoma (HRNB) is still poor. This is in part due to an inability to cure the disease once a patient has reached clinical relapse. Identifying plasma biomarkers of active disease may provide a way of relapse monitoring in HRNB. EXPERIMENTAL DESIGN: In this study, we developed an integrated proteomic approach to identify plasma biomarkers for HRNB. RESULTS: We identified seven candidate biomarkers (SAA, APOA1, IL-6, EGF, MDC, sCD40L and Eotaxin) for HRNB. These biomarkers were then used to create a multivariate classifier of HRNB, which showed a specificity of 90% (95% confidence interval (CI), 73%, 98%), and a sensitivity of 81% (95%CI, 54%, 96%) for classifying HRNB in a training set. When evaluated on independent test samples, the classifier exhibited 86% accuracy (95% CI, 42%, 100%) of identifying diagnostic samples, and 86% accuracy (95% CI, 70%, 100%) of detecting post-diagnosis longitudinal samples that having active disease. CONCLUSION AND CLINICAL RELEVANCE: Further validation of these biomarkers may improve patients' outcomes by developing a simple blood test for the detection of relapse prior to the development of clinically evident disease. Understanding the role of these biomarkers in immune surveillance of neuroblastoma may also provide a new direction of therapeutic strategies.


Subject(s)
Biomarkers/blood , Neuroblastoma/diagnosis , Proteomics/methods , Adolescent , Child , Child, Preschool , Cytokines/metabolism , Female , Humans , Infant , Longitudinal Studies , Male , Neoplasm Staging , Neuroblastoma/metabolism , Neuroblastoma/prevention & control , Recurrence , Risk Factors , Sensitivity and Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
17.
Mol Cancer Ther ; 8(8): 2461-9, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19671766

ABSTRACT

We studied expression of the Aurora A gene and its clinical significance in a cohort of neuroblastoma patients. In addition, we investigated the antitumor activity of MLN8054, a novel small-molecule inhibitor of Aurora A kinase, on cultured NB cell lines in vitro. Aurora A mRNA expression was assessed by quantitative real-time PCR in tumor tissue specimens from 67 patients at diagnosis and in 9 human neuroblastoma cell lines. Western blot assays for Aurora A protein were done on tumor tissue of 53 patients. The results were correlated with various prognostic factors of neuroblastoma. Aurora A mRNA and protein expression were identified in 9 of 9 neuroblastoma cell lines. Overexpression of Aurora A mRNA in neuroblastoma tumor tissue is associated with high risk (P = 0.019), high-stage (International Neuroblastoma Staging System III and IV) tumors (P = 0.007), unfavorable histology (P = 0.007), MYCN amplification (P = 0.017), disease relapse (P = 0.019), and decreased progression-free survival (P < 0.0001) but not correlated with the age at diagnosis (P = 0.877). Similarly, Aurora A protein expression also significantly correlated with high risk (P = 0.011), high stage (P = 0.0028), unfavorable histology (P = 0.0006), MYCN amplification (P = 0.0029), and disease relapse (P = 0.044). Small interfering RNA-mediated knockdown of the endogenous Aurora A gene causes a proliferation defect and enhances chemosensitivity in human neuroblastoma cell lines. In support of these observations, the Aurora A kinase inhibitor, MLN8054, markedly inhibited growth of cultured neuroblastoma cell lines through an apoptosis-dependent pathway. Overexpression of Aurora A is associated with disease progression in neuroblastoma. Inhibition of this kinase is a promising modality for neuroblastoma treatment.


Subject(s)
Neuroblastoma/enzymology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/genetics , Antineoplastic Agents/pharmacology , Apoptosis , Aurora Kinases , Benzazepines/pharmacology , Cell Line, Tumor , Cell Proliferation , Cohort Studies , Humans , Neuroblastoma/diagnosis , Neuroblastoma/drug therapy , Prognosis , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/metabolism
18.
J Pediatr Adolesc Gynecol ; 22(5): e114-7, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19576820

ABSTRACT

BACKGROUND: Juvenile granulosa cell tumors (JGCT) are rare ovarian tumors that frequently present with precocious puberty. Presentation in infants less than a year of age is also rare. CASE: We describe a 10-month-old infant who presented with both premature thelarche and adrenarche due to JGCT. Laboratory evaluation revealed classic elevation of estradiol and inhibin B, and less classic elevation of total and free testosterone. Oophorectomy and staging resulted in a diagnosis of Stage IA JGCT. SUMMARY AND CONCLUSION: Survival rates are >95% among patients diagnosed under 10 years of age. Tumor recurrence is rare but can occur as late as 48 months. Therefore, tumor surveillance is warranted for patients with even a Stage IA JGCT and involves monitoring serial inhibin B levels along with intermittent imaging.


Subject(s)
Granulosa Cell Tumor/diagnosis , Ovarian Neoplasms/diagnosis , Adrenarche , Age Determination by Skeleton , Female , Granulosa Cell Tumor/diagnostic imaging , Granulosa Cell Tumor/pathology , Granulosa Cell Tumor/surgery , Humans , Immunohistochemistry , Infant , Ovarian Neoplasms/diagnostic imaging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Ovariectomy , Puberty, Precocious/etiology , Ultrasonography
20.
Clin Cancer Res ; 14(21): 7028-34, 2008 Nov 01.
Article in English | MEDLINE | ID: mdl-18980999

ABSTRACT

PURPOSE: To explore the relationships between interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) levels and disease extent and clinical outcome in childhood neuroblastoma. EXPERIMENTAL DESIGN: Pretreatment peripheral blood (PB; n=53) and bone marrow (n=18) samples from patients with neuroblastoma were assayed by ELISA for IL-6 and sIL-6R. PB values were compared with healthy pediatric controls (n=28). RESULTS: PB IL-6 levels were significantly elevated in patients with high-risk disease compared with those with low and intermediate risk disease (23.9 versus 4.3 pg/mL; P<0.001) and the normal control group (23.9 versus 3.3 pg/mL; P<0.001). Similarly, bone marrow IL-6 levels were higher in high-risk patients when compared with low- and intermediate-risk patients (15 versus 0 pg/mL; P<0.02). Other factors correlated with higher IL-6 levels were age of >18 months, bony metastases, and unfavorable histology. sIL-6R levels were not significantly correlated with disease stage. Patients with detectable PB IL-6 at diagnosis had significantly lower event-free survival rates (P<0.008). sIL-6R levels <2.5 x 10(4) pg/mL were also associated with a significantly worse event-free survival (P=0.016). CONCLUSION: Elevated PB IL-6 levels correlated with features of high-risk neuroblastoma and poor prognosis in this population. Decreased PB sIL-6R levels correlated with the presence of metastatic disease. Further study of these markers in children with neuroblastoma seems warranted.


Subject(s)
Biomarkers, Tumor/analysis , Interleukin-6/analysis , Neuroblastoma/metabolism , Receptors, Interleukin-6/analysis , Bone Marrow/chemistry , Disease-Free Survival , Female , Humans , Infant , Interleukin-6/blood , Male , Neuroblastoma/diagnosis , Prognosis , Receptors, Interleukin-6/blood
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