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.
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.
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%).
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.
Germ cell tumors (GCTs) are neoplasms of the testis, ovary and extragonadal sites that occur in infants, children, adolescents and adults. Post-pubertal (type II) malignant GCTs may present as ...seminoma, non-seminoma or mixed histologies. In contrast, pre-pubertal (type I) GCTs are limited to (benign) teratoma and (malignant) yolk sac tumor (YST). Epidemiologic and molecular data have shown that pre- and post-pubertal GCTs arise by distinct mechanisms. Dedicated studies of the genomic landscape of type I and II GCT in children and adolescents are lacking. Here we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 years. Activation of the WNT pathway by somatic mutation, copy-number alteration, and differential promoter methylation is a prominent feature of GCTs in children, adolescents and young adults, and is associated with poor clinical outcomes. Significantly, we find that small molecule WNT inhibitors can suppress GCT cells both in vitro and in vivo. These results highlight the importance of WNT pathway signaling in GCTs across all ages and provide a foundation for future efforts to develop targeted therapies for these cancers.
Paediatric extracranial germ-cell tumours Shaikh, Furqan, Dr; Murray, Matthew J, PhD; Amatruda, James F, MD ...
The lancet oncology,
04/2016, Volume:
17, Issue:
4
Journal Article
Peer reviewed
Open access
Summary 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.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Presence of contrast agent in the urinary system in infants after small-bowel follow-through study with low-osmolar contrast media has been described as a sign of bowel perforation.
...Objective
To evaluate how often the presence of contrast agent in the bladder after small-bowel follow-through is a reliable sign of bowel perforation or necrosis.
Materials and methods
From the radiology information system, we retrieved imaging reports of infants evaluated with small-bowel follow-through and findings of contrast agent in the bladder. We retrieved demographic and clinical information from the medical records. Presence of bladder contrast medium was considered true-positive evidence of bowel perforation or necrosis if confirmed by pneumoperitoneum, extraluminal contrast agent, surgery or pathology within 3 days of the small-bowel follow-through. False-positives for bowel perforation or necrosis were based on surgical findings or clinical follow-up.
Results
Of the 207 infants who had small-bowel follow-through, 18 infants (12 boys; mean age 50 days, range 14 days to 8.5 months) had contrast medium in the bladder after the small-bowel follow-through. Fifteen of the 18 (83.3%) had a history of prematurity and 11 had prior abdominal surgery. Four of the 18 (22.2%) had bowel perforation or necrosis at surgery or pathology performed more than 3 days after the small-bowel follow-through and were considered indeterminate and excluded. Eight of the remaining 14 infants (57.1%) had bowel perforation or necrosis based on surgical evidence of perforation or pathology confirmation of necrosis (
n
=6), pneumoperitoneum (
n
=1) or contrast agent leakage from enterocutaneous fistula (
n
=1). Six of the 14 (42.9%) were false-positives, without evidence of bowel perforation or necrosis based on clinical follow-up (
n
=4) or surgery (
n
=2).
Conclusion
Demonstration of urinary contrast agent post small-bowel follow-through with low-osmolar contrast medium in newborns/infants with complex medical problems is not a definitive indication of bowel perforation or necrosis. More than one-third of our patients with contrast medium in the bladder did not have bowel perforation or necrosis.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
During the past 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have increased significantly. Success has been achieved primarily through the application of ...platinum-based chemotherapy regimens; however, clinical challenges in GCTs remain. Excellent outcomes are not distributed uniformly across the heterogeneous distribution of age, histologic features, and primary tumor site. Despite good outcomes overall, the likelihood of a cure for certain sites and histologic conditions is less than 50%. In addition, there are considerable long-term treatment-related effects for survivors. Even modest cisplatin dosing can cause significant long-term morbidities. A particular challenge in designing new therapies for GCT is that a variety of specialists use different risk stratifications, staging systems, and treatment approaches for three distinct age groups (childhood, adolescence, and young adulthood). Traditionally, pediatric cancer patients younger than 15 years have been treated by pediatric oncologists in collaboration with their surgical specialty colleagues. Adolescents and young adults with GCTs often are treated by medical oncologists, urologists, or gynecologic oncologists. The therapeutic dilemma for all is how to best define disease risk so that therapy and toxicity can be appropriately reduced for some patients and intensified for others. Further clinical and biologic insights can only be achieved through collaborations that do not set limitations by age, sex, and primary tumor site. Therefore, international collaborations, spanning different cooperative groups and disciplines, have been developed to address these challenges.
Abstract Purpose The incidence of button battery ingestions is increasing and injury due to esophageal impaction begins within minutes of exposure. We changed our management algorithm for suspected ...button battery ingestions with intent to reduce time to evaluation and operative removal. Methods A retrospective study was performed to identify and evaluate time to treatment and outcome for all esophageal button battery ingestions presenting to a major children’s hospital emergency room from February 1, 2010 through February 1, 2012. During the first year, standard emergency room triage (ST) was used. During the second year, the triage protocol was changed and Trauma I triage (TT) was used. Results 24 children had suspected button battery ingestions with 11 having esophageal impaction. One esophageal impaction was due to 2 stacked coins. Time from arrival in emergency room to battery removal was 183 minutes in ST group (n = 4) and 33 minutes in TT group (n = 7) (p = 0.04). One patient in ST developed a tracheoesophageal fistula. There were no complications in the TT group. Conclusions The use of Trauma 1 activations for suspected button battery ingestions has led to more expedient evaluation and shortened time to removal of impacted esophageal batteries.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lymphovascular invasion (LVI) has been identified as a poor prognostic factor for a variety of tumors; however, its significance in malignant ovarian germ cell tumors (MOGCT) in pediatric and ...adolescent patients is not well described. We aim to clarify the significance of LVI in the subset of patients with nongerminomatous MOGCT.
Records of patients 0-20 years of age with MOGCT enrolled on Children's Oncology Group study AGCT0132 were reviewed. Patients with documented presence or absence of LVI in either institutional or central review pathology reports were included.
Of 130 patients with MOGCTs, 83 patients had of the presence or absence of LVI documented in their pathology report. 42/83 patients (50.6%) were found to have LVI present. The estimated odds of having LVI was higher in patients with stage II and III disease, 11 years and older and with the presence of choriocarcinoma. Event-free survival (EFS) and overall survival (OS) remained high in patients with LVI. Approximately 50% of patients with a documented LVI status in either institutional pathology report or central review were found to have LVI.
The presence of LVI was higher in tumors with adverse risk factors including higher stage and age greater than 11 years. While LVI was not associated with EFS or OS in the intermediate risk group, further work is necessary to determine the effect of LVI on long-term disease-free survival. We, therefore, recommend routinely incorporating LVI status into institutional pathology reports for pediatric and adolescent patients with MOGCT.
III.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
