Children's Oncology Group Stage Research Articles

Half-life of serum alpha-fetoprotein in prepubertal testicular yolk sac tumors: an index significantly associated with prognosis.

To evaluate the association between serum alpha-fetoprotein (AFP) half-life (HL) and prognosis in prepubertal children with elevated AFP values 3 to 4 weeks after surgery for testicular yolk sac tumors (YST). Prepubertal patients with testicular YST treated with radical orchiectomy between January 2016 and December 2022 were retrospectively reviewed. Negative outcomes were defined as relapse, metastasis or death. Univariate and multivariate logistic regression analyses were conducted to select risk factors for negative outcomes. A total of 42 patients were eventually enrolled into the study. Patients were divided into non-negative and negative outcomes groups, consisting of 35 and 7 patients, respectively. Thirty-five patients were stage I, two cases were stage II, and five cases were stage IV, according to the Children's Oncology Group staging system. The overall survival (OS) rate was 100%. Average AFP values significantly decreased after resection (P < 0.001). A significant positive correlation was shown between pre- and postoperative AFP values (r = 0.60, P < 0.001). Long AFP HL was considered as an independent risk factor for negative outcomes in YST patients underwent radical orchiectomy (P = 0.04). The cut-off value for AFP HL was 5.78 days, regardless of age division. Testicular YST is a relatively rare disease in children with an OS of 100%, and salvage chemotherapy is effective even in grade IV patients. The postoperative AFP HL was significantly associated with prognosis in prepubertal patients with testicular YST. The cut-off value for AFP HL is 5.78 days regardless of the effect of physiological AFP elevation.

Outcomes based on histopathologic response to preoperative chemotherapy in children with bilateral Wilms tumor: A prospective study (COG AREN0534).

An objective of the Children's Oncology Group AREN0534 Study was to improve the survival of patients with bilateral Wilms tumors (BWT) by using preoperative chemotherapy of limited duration and tailoring postoperative therapy based on histopathologic response. The authors report outcomes based on postoperative histopathologic responses. Patients with BWT received treatment with vincristine, dactinomycin, and doxorubicin for 6 or 12 weeks followed by surgery. Postoperative therapy was prescribed based on the highest risk tumor according to the International Society of Pediatric Oncology classification and the Children's Oncology Group staging system. Analyses were performed on data from 180 evaluable children. The 4-year event-free survival (EFS) and overall survival (OS) rates were 81% (95% CI, 74%-87%) and 95% (95% CI, 91%-99%), respectively. Seven patients who had completely necrotic tumors had a 4-year EFS rate of 100%. Of 118 patients who had tumors with intermediate-risk histopathology, the 4-year EFS and OS rates were 82% (95% CI, 74%-90%) and 97% (95% CI, 94%-100%), respectively. Fourteen patients who had blastemal-type tumors had 4-year EFS and OS rates of 79% (95% CI, 56%-100%) and 93% (95% CI, 79%-100%), respectively. Eighteen patients who had diffuse anaplasia had 4-year EFS and OS rates of 61% (95% CI, 35%-88%) and 72% (95% CI, 47%-97%), respectively; and the 4-year EFS and OS rates of 7 patients who had focal anaplasia were 71% (95% CI, 38%-100%) and 100%, respectively. There was no difference in the outcomes of patients who had different histopathologic subtypes within the intermediate-risk group (P = .54). A risk-adapted treatment approach for BWT results in excellent outcomes. This approach was not successful in improving the outcome of patients who had diffuse anaplasia.

Fever and Abdominal Pain in a 10-year-old with Autism.

Fever and Abdominal Pain in a 10-year-old with Autism.

Imaging for Staging of Pediatric Abdominal Tumors: An Update, From the AJR Special Series on Cancer Staging.

The three most common pediatric solid tumors of the abdomen are neuroblastoma, Wilms tumor, and hepatoblastoma. These embryonal tumors most commonly present in the first decade of life. Each tumor has unique imaging findings, including locoregional presentation and patterns of distant spread. Neuroblastoma, Wilms tumor, and hepatoblastoma have unique staging systems that rely heavily on imaging and influence surgical and oncologic management. The staging systems include image-defined risk factors for neuroblastoma, the Children's Oncology Group staging system for Wilms tumor, and the pretreatment extent of tumor system (PRETEXT) for hepatoblastoma. It is important for radiologists to be aware of these staging systems to optimize image acquisition and interpretation. This article provides a practical and clinically oriented approach to the role of imaging in the staging of these common embryonal tumors of childhood. The selection among imaging modalities, key findings for determining tumor stage, and the role of imaging in posttreatment response evaluation and surveillance are discussed. Recent updates to the relevant staging systems are highlighted with attention to imaging findings of particular prognostic importance. The information presented will help radiologists tailor the imaging approach to the individual patient and guide optimal oncologic management.

Factors affecting lymph node sampling patterns and the impact on survival of lymph node density in patients with Wilms tumor: a Surveillance, Epidemiology, and End Result (SEER) database review

Lymph node (LN) involvement is an important prognostic indicator for patients with Wilms tumor (WT), and there have been previous reports of utilizing LN density (LND=positive LN/LNs examined) as an advanced metric to risk-stratify patients with WT. The purpose of this study was to describe patient characteristics that affect LN yield and assess the effect of LND on the overall survival (OS) in patients with WT, with the expectation that patients with LNDs above a critical cut-point would demonstrate lower OS. The Surveillance, Epidemiology, and End Result (SEER) database was queried for all patients diagnosed with unilateral WT from 2004 to 2015. Patient and disease characteristics were collected, and Poisson regression was used to identify characteristics correlated with LN yield. LND was calculated for LN-positive patients, and multivariable survival analysis was performed, including patient demographics and LND as variables. 1489 patients with unilateral WT were identified for analysis, 231 (15.51%) of whom were LN-positive. Median patient age at diagnosis was three years (IQR 1-5). On Poisson regression, the year of diagnosis, patient age, tumor size and laterality, and stage were found to impact LN yield. For patients with positive LNs, five-year OS of patients with LNDs above 0.4 was worse than those below 0.4 (76.1% vs 89.6%, p=0.041). On multivariable analysis, tumor size and LND remained significant predictors of OS. Administrative databases such as SEER provide an excellent resource for studying conditions where large patient numbers for analysis are difficult to obtain. Unfortunately, the SEER database is unable to account for every factor that could affect LN sampling patterns. Additionally, favorable vs unfavorable histology is not available in SEER, and SEER utilizes its own staging system, which makes comparison to Children's Oncology Group staging difficult. Despite these limitations, the findings of this study are similar to those previously published using administrative databases analyzing LN sampling patterns and the effect of LND on OS in WT. Analysis of the SEER database confirms that there are several patient- and disease-specific factors that affect the number of LNs sampled during nephrectomy for WT, and that LND may be a predictor of OS. These findings highlight the need for standardization of LN sampling patterns for pediatric renal tumors and support the investigation of LND in future studies to further risk-stratify WT patients to tailor therapy intensity.

Imaging of Wilms tumor: an update.

Wilms tumor is the most common pediatric renal tumor, accounting for approximately 7% of all childhood cancers. Imaging plays an important role in the detection, staging, post-therapy evaluation and surveillance of Wilms tumor. Wilms tumor can be detected during surveillance of a known cancer predisposition or after a child presents with symptoms. In this manuscript we describe an evidence-based approach to the initial evaluation of Wilms tumor using current guidelines from the Children's Oncology Group (COG). We illustrate the COG staging system for pediatric renal tumors and highlight key imaging findings that are critical for surgical management. We also discuss the controversies regarding detection and significance of <5-mm pulmonary nodules at initial staging. And finally, we present some thoughts regarding surveillance of Wilms tumor, where overall survival has now approached 90%.

Pediatric ovarian immature teratoma: Histological grading and clinical characteristics

BackgroundOvarian immature teratomas (ITs) are relatively rare among all pediatric ovarian tumors. The histological grading for ovarian ITs, which ranges from 1 to 3, is based on the proportion of immature neuroepithelial component. Higher-grade ITs in adults are treated as malignant neoplasms and require adjuvant chemotherapy. However, there is no consensus on the therapeutic management of pediatric ovarian ITs. The aim of our study was to analyze the histological grades and clinical characteristics of ovarian ITs in pediatric patients. MethodsThis retrospective chart review consisted of seven patients, including one, three, and three patients with histological grade 1, 2, and 3 pediatric ovarian ITs, respectively, who were treated at our institute between 2000 and 2016. Collected data comprised age, alpha-fetoprotein (AFP) level, clinical stage, tumor size, treatment, and prognosis. ResultsThe median age and AFP levels of patients with grade 1, 2, and 3 ovarian ITs were 8, 7, and 10 years and 37, 112, and 221 ng/ml, respectively. All cases were Children Oncology Group (COG) stage I and International Federation of Gynecology and Obstetrics (FIGO) stage IA. All patients had unilateral tumors in the right ovary. The median tumor sizes of the grade 1, 2, and 3 IT patients were 104, 160, and 100 cm2, respectively. All patients underwent primary open surgery alone. Two patients, including one patient each with grade 2 and 3 ITs, underwent tumor enucleation as ovary-sparing surgery, whereas the remaining five patients underwent unilateral salpingo-oophorectomy. The median follow-up was seven years, and all cases achieved event-free survival. ConclusionsClinical characteristics of patients with grade 3 ovarian ITs were relatively older and had higher AFP levels than those with lower-grade ITs. According to our patient’s clinical course and prognosis, COG stage I pediatric ITs should be treated by surgery alone and that postoperative chemotherapy is unnecessary even for those with grade 3 ITs as well as patients with rather low AFP levels. Level of evidenceIV

Poor adherence to staging guidelines for children with malignant ovarian tumors

PurposeHistorically, surgical staging practices for pediatric malignant ovarian tumors mirrored adult guidelines. In 2004, the Children's Oncology Group (COG) developed guidelines specific to pediatric patients with ovarian germ cell tumors. We sought to characterize the operative management of pediatric ovarian lesions and adherence to COG surgical staging guidelines. MethodsWe conducted a single institution, retrospective study of pediatric patients who underwent surgical intervention for ovarian lesions between 1995 and 2012. The primary outcome was adherence to COG staging guidelines. ResultsAmong 502 patients, 44 (8.8%) had malignant ovarian tumors. Two patients (2/44, 4.5%) underwent correct surgical staging. Therefore, 95.5% (42/44) underwent incorrect surgical staging by omitting recommended maneuvers (surgical understaging) or performing clinically unnecessary surgical staging steps (surgical overstaging). Of the 42 patients with incorrect surgical staging, 85.7% (36/42) were surgically overstaged and 76.2% (32/42) were surgically understaged. In the entire cohort, 12 (27.3%) patients had complete staging procedures, including 10 surgically overstaged patients (10/12, 83.3%). Staging practices were not significantly different before and after the release of the 2004 COG guidelines. ConclusionIncorrect surgical staging of pediatric ovarian malignancies is commonplace. These data stress the need for greater education among all surgeons caring for children with malignant ovarian tumors.

Analysis of national and single-center incidence and survival after liver transplantation for hepatoblastoma: New trends and future opportunities

Liver transplantation (LTx) for hepatoblastoma appears to be increasing. Favorable tumor histology is increasingly linked to survival after surgical resection and could also determine posttransplantation outcomes. To evaluate national trends in tumor and LTx incidence as the basis for observations at some LTx centers, and determinants of survival after LTx for hepatoblastoma, we queried the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry representing 9.451% of the U.S. population (1975-2007), the United Network for Organ Sharing (UNOS, 1988-2010, n = 332), and Children's Hospital of Pittsburgh database (CHP, 1987-2011, n = 35). In the United States, hepatoblastoma cases increased 4-fold, LTx for hepatoblastoma increased 20-fold, and hepatoblastoma surpassed other unresectable liver malignancies requiring LTx by nearly 3-fold. Actuarial 5-year patient survival exceeded 75%. Recurrences in 16% were greater after segmental LTx in the total U.S. experience (P = .049). At CHP, 5 children died from recurrences (n = 4) and sepsis (n = 1). Tumors were epithelial (57%) or mixed epithelial-stromal (42%), Children's Oncology Group stage III (77%) or IV (23%). Recurrences were related to previous pulmonary metastases (P = .016), and tumor necrosis <50% (P = .013), but not to small cell undifferentiated tumor histology (P = NS). Hepatic artery thrombosis was more common after LTx for hepatoblastoma compared with nonmalignant indications (P = .0089). Thirty-three children received pre-LTx chemotherapy, 88.6% with cisplatin, and 85.7% received post-LTx chemotherapy. Outcomes after LTx for hepatoblastoma may benefit from improved detection and treatment of pretransplantation metastases, adequate tumor lysis after chemotherapy, and perioperative antithrombotic agents but are unaffected by undifferentiated tumor histology.

Protocol for the Examination of Specimens From Pediatric and Adult Patients With Extragonadal Germ Cell Tumors

The College of American Pathologists offers these protocols to assist pathologists in providing clinically useful and relevant information when reporting results of surgical specimen examinations. The College regards the reporting elements in the ‘‘Surgical Pathology Cancer Case Summary (Checklist)’’ portion of the protocols as essential elements of the pathology report. However, the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice. The College developed these protocols as an educational tool to assist pathologists in the useful reporting of relevant information. It did not issue the protocols for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the protocols might be used by hospitals, attorneys, payers, and others. Indeed, effective January 1, 2004, the Commission on Cancer of the American College of Surgeons mandated the use of the checklist elements of the protocols as part of its Cancer Program Standards for Approved Cancer Programs. Therefore, it becomes even more important for pathologists to familiarize themselves with these documents. At the same time, the College cautions that use of the protocols other than for their intended educational purpose may involve additional considerations that are beyond the scope of these documents.

Pediatric ovarian malignancies: how efficacious are current staging practices?

Purpose Conventional staging is not routinely practiced because of a lack of preoperative indicators for pediatric ovarian malignancy. Children's Oncology Group (COG) developed guidelines for germ cell tumors to revise staging to correlate with primary pediatric ovarian pathology. Are COG guidelines being used, and are they applicable to all pediatric ovarian malignancies? Methods A 15½-year retrospective review of operative ovarian masses from a single academic center was performed. Results There were 424 patients identified, with 46 malignancies (11%). Most were stage I (73%). Complete COG staging was performed in 24%. Each staging component performed was as follows: oophorectomy (91%), examination with or without biopsy of omentum (72%), peritoneum (67%), retroperitoneum (63%), contralateral ovary (56%), and washings (46%). Advanced stages had visible findings at exploration to guide biopsies. Of site-directed biopsies, 40.5% were positive, whereas all random biopsies (n = 38) were negative. Two recurrences and all mortalities (n = 4) had complete initial COG operative staging. Mean duration of follow-up was 3.62 ± 0.365 years. Conclusion The COG staging is not consistently followed. All cases of advanced disease were visibly obvious and confirmed with site-directed biopsies. Random samplings were all negative and did not impact stage. Negative outcomes reflected inherent tumor biology not deviation from COG staging. The COG guidelines appear to be sufficient for all pediatric ovarian malignancies.

Predictive power of pretreatment prognostic factors in children with hepatoblastoma: A report from the Children's Oncology Group

PRETEXT is used to stratify risk in children with hepatoblastoma by the Liver Tumor Strategy Group (SIOPEL) of the International Society of Pediatric Oncology (SIOP). A recent analysis excluding patients that did not survive neoadjuvant chemotherapy, concluded that PRETEXT was superior to Children's Oncology Group (COG) stage for predicting survival. Puzzled by this result, we made a similar comparison of PRETEXT and COG stage. This time, however, we include all patients, and we compare predictive value at diagnosis, instead of after neoadjuvant chemotherapy. Hepatoblastoma patients in INT-0098 were retrospectively reviewed for PRETEXT and other potential prognostic factors including pathologic subtype, and alpha-fetoprotein (AFP). Five-year overall survival by PRETEXT was 88.9%, 84.5%, 71.6%, and 30.9%, for PRETEXT I, II, III, and IV, respectively. The 5-year overall survival rates by COG stage were 100%, 97.5%, 100%, 70.2%, and 39.3% for Stage I pure fetal histology (PFH), Stage I unfavorable histology (UH = not PFH), Stage II, Stage III, and Stage IV, respectively. PRETEXT added significant additional prognostic information within the COG Stage III, but not COG Stage IV. Additional prognostic factors statistically significant for an increased risk of death were small-cell-undifferentiated (SCU) histologic subtype and AFP < 100 at diagnosis. PRETEXT, COG stage, SCU histology, and AFP < 100, as assessed at diagnosis, are important determinants of survival that will allow us to better develop common international criteria for risk stratification. Common risk stratification is an essential prerequisite to establish effective cooperation across the ocean in this field of rare tumors.

Surgical resection of pulmonary metastatic lesions in children with hepatoblastoma

Although the most common site of metastasis for hepatoblastoma is the lung, the role of thoracotomy and surgical resection of pulmonary metastasis remains uncertain. In this study, we aimed to determine the long-term outcome of patients with hepatoblastoma who have a surgical resection of pulmonary metastatic lesions. Patients with hepatoblastoma in the Children's Oncology Group INT-0098 were reviewed. Detailed reports enabling comprehensive review were available for 175 of 181 eligible patients. Prognostic factors (histology, tumor margin, surgical complications, alpha-fetoprotein) were also reviewed. Thoracotomy for initial pulmonary metastasis: 38 patients presented with pulmonary metastasis, Children's Oncology Group stage IV. Nine of these 38 underwent thoracotomy and pulmonary metastectomy either before (2), simultaneous (5), or after (2) resection of their primary liver tumor. Eight of these 9 patients with metastectomy were long-term survivors. Thoracotomy for tumor relapse: 20 patients who had previously achieved complete tumor clearance experienced subsequent pulmonary relapse of their tumor (11 stage I or III, 9 stage IV). All 20 patients with pulmonary relapse had salvage chemotherapy; 13 also had thoracotomy and pulmonary metastectomy (8) or thoracotomy and biopsy (5). Only 4 of 13 were long-term survivors: 2 were stage I and 2 were stage IV. As pediatric surgeons, we varied tremendously in our timing and surgical approach to the management of pulmonary metastasis in hepatoblastoma. This large multicenter review suggests that thoracotomy should be used cautiously in the management of pulmonary relapse and perhaps more aggressively in the management of metastases present at diagnosis that persist after neoadjuvant chemotherapy.