The Effect of COVID-19 on Oncology Care for Adolescents and Young Adults in Latin America.

Children with cancer in low- and middle-income countries were disproportionately impacted by the COVID-19 pandemic, but little is known about how adolescents and young adults (AYAs) with cancer were affected. Sixty-seven physicians and nonphysician providers were interviewed about their experiences caring for AYAs with cancer in Latin America. Quotes related to the COVID-19 pandemic were identified and grouped into themes. Barriers from the COVID-19 pandemic included limited space, restrictions on travel, reduced funding, limited staff, limited services, and changes to treatment. However, improvements to care that arose from the COVID-19 pandemic included better access to distance learning and telemedicine.

Receipt of Guideline-Concordant Care Is Associated With Improved Survival in Patients With Osteosarcoma in California: A Population-Based Analysis.

PURPOSE: To examine the relationship between guideline-concordant care (GCC) on the basis of national clinical practice guidelines and survival in children (0-14 years), adolescents and young adults (AYAs, 15-39 years), and adults (40 years and older) with osteosarcoma, and to identify sociodemographic and clinical factors associated with receipt of GCC and survival. METHODS: We used data from the California Cancer Registry (CCR) on patients diagnosed with osteosarcoma during 2004-2019, with detailed treatment information extracted from the CCR text fields, including chemotherapy regimens. Multivariable logistic and Cox proportional hazard regression were used for statistical analyses. RESULTS: Of 1,716 patients, only 47% received GCC, with variation by age at diagnosis: 67% of children, 43% of AYAs, and 30% of adults. In multivariable models, patients who received part or all care (v none) at specialized cancer centers were more likely to receive GCC. AYAs and adults were less likely to receive GCC than children (odds ratio [OR], 0.38 [95% CI, 0.30 to 0.50] and OR, 0.40 [95% CI, 0.28 to 0.56], respectively). In a model excluding adults, patients treated by pediatric (v medical) oncologists were more likely to receive GCC (OR, 3.44 [95% CI, 2.40 to 4.94]). Patients with metastatic osteosarcoma at diagnosis who did not receive GCC had a greater hazard of death (hazard ratio [HR], 2.02 [95% CI, 1.55 to 2.63]) but no statistical differences were found in those diagnosed at earlier stages (HR, 1.15 [95% CI, 0.92 to 1.43]). CONCLUSION: GCC was associated with improved survival in patients with metastatic osteosarcoma in California. However, we found disparities in the delivery of GCC, highlighting the need for target interventions to improve delivery of GCC in this patient population.

Late venous thromboembolism in survivors of adolescent and young adult cancer: A population-based study in California.

INTRODUCTION: Venous thromboembolism (VTE), a common complication in cancer patients, occurs more often during the initial phase of treatment. However, information on VTE beyond the first two years after diagnosis ('late VTE') is scarce, particularly in young survivors. METHODS: We examined the risk of, and factors associated with, late VTE among adolescents and young adults (AYA, 15-39 years) diagnosed with cancer (2006-2018) who survived ≥2 years. Data were obtained from the California Cancer Registry linked to hospitalization, emergency department and ambulatory surgery data. We used non-parametric models and Cox proportional hazard regression for analyses. RESULTS: Among 59,343 survivors, the 10-year cumulative incidence of VTE was 1.93 % (CI 1.80-2.07). The hazard of VTE was higher among those who had active cancer, including progression from lower stages to metastatic disease (Hazard Ratio (HR) = 10.41, 95 % confidence interval (CI): 8.86-12.22), second primary cancer (HR = 2.58, CI:2.01-3.31), or metastatic disease at diagnosis (HR = 2.38, CI:1.84-3.09). The hazard of late VTE was increased among survivors who underwent hematopoietic cell transplantation, those who received radiotherapy, had a VTE history, public insurance (vs private) or non-Hispanic Black/African American race/ethnicity (vs non-Hispanic White). Patients with leukemias, lymphomas, sarcoma, melanoma, colorectal, breast, and cervical cancers had a higher VTE risk than those with thyroid cancer. CONCLUSIONS: VTE risk remained elevated ≥2 years following cancer diagnosis in AYA survivors. Active cancer is a significant risk factor for VTE. Future studies might determine if late VTE should prompt evaluation for recurrence or second malignancy, if not already known.

Documentation of Infertility Risk Discussion in Cancer Patients Receiving Cancer-Directed Therapy: The UC Davis Cancer Center Experience.

Purpose: A complication of cancer-directed therapy that often goes undiscussed is infertility. Although guidelines recommend addressing the possibility of infertility and fertility preservation approaches before initiating treatment, an internal review at our institution showed only 49% of female patients had infertility risk counseling documented. As a result, a fertility assessment communication was added into all oncology treatment plans to improve rates of fertility discussion and documentation. Methods: This retrospective observational study included newly diagnosed patients of childbearing potential who initiated cancer-directed therapy between January 1, 2020, and October 31, 2021. Patients who were no longer of childbearing potential due to age or surgery were excluded. Patients were divided into pre- and post-implementation groups to assess the impact of the fertility assessment communication implemented on November 1, 2020. Results: A total of 152 patients met inclusion criteria, with 80 patients in the pre-implementation group and 72 patients in the post-implementation group. The primary outcome of documentation of infertility risk discussion was 47.5% in the pre-implementation group and 86.1% in the post-implementation group (p < 0.0001). Discussion of fertility preservation options was documented in 28.7% of the pre-implementation group and 43.1% in the post-implementation group (p = 0.13). In the pre-implementation group, 5% underwent fertility preservation versus 27.8% in the post-implementation group (p = 0.0001). Of the 27 patients who received fertility preservation, 13 received hormonal therapy, 11 sperm banking, and 3 egg harvesting. Conclusion: This intervention significantly increased rates of infertility risk discussion and fertility preservation approaches received. There are opportunities to help patients receive fertility preservation, especially sperm banking and egg harvesting.

Treatment of children with favorable histology Wilms tumor with extrapulmonary metastases: A report from the COG studies AREN0533 and AREN03B2 and NWTSG study NWTS-5.

BACKGROUND: Patients with stage IV favorable histology Wilms tumor (FHWT) with extrapulmonary metastases (EPM) constitute a small subset of patients with FHWT. Because of their rarity and heterogeneity, optimal FHWT treatment is not well understood. Children's Oncology Group protocol AREN0533 assigned patients with FHWT and EPM to intensified chemotherapy, regimen M, after initial DD-4A chemotherapy. To improve understanding of prognostic factors and best therapies, experiences of patients with EPM on AREN0533, as well as on protocols AREN03B2 and NWTS-5, were reviewed. METHODS: Combined outcomes for patients with EPM from NWTS-5, AREN0533, and AREN03B2 were determined. Those treated on AREN0533 were compared with those treated on NWTS-5. Prognostic factors were explored in the pooled cohort. RESULTS: Forty-seven patients with FHWT with EPM enrolled on AREN0533, 37 enrolled on NWTS-5, and 64 were followed only on AREN03B2. The pooled cohort of all 148 patients demonstrated a 4-year event-free survival (EFS) of 77.3% (95% CI, 70.8-84.4) and 4-year overall survival of 88.9% (95% CI, 83.9-94.2). Four-year EFS of patients with EPM treated on AREN0533 was 76.0% (95% CI, 64.6-89.4) vs 64.9% (95% CI, 51.7-82.2) on NWTS-5; hazard ratio, 0.64, p = .26; no difference in overall survival was observed. Increasing linear age and slow incomplete lung response were associated with worse EFS in a pooled cohort. CONCLUSIONS: Outcomes for patients with EPM are among the lowest for children with FHWT. Further trials with standardized surgical and radiation treatment to metastatic sites, and prospectively collected biologic and treatment details are needed. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifiers: NCT00379340, NCT00898365, and NCT00002611.

How Do Adolescent and Young Adult Patients with Cancer Manage Their Chemotherapy-Related Symptoms at Home?

Chemotherapy can cause many distressing side effects, potentially impacting treatment completion and quality of life in adolescent and young adult (AYA) patients with cancer. To identify ways to help mitigate chemotherapy-related symptoms, we sought to elicit barriers and facilitators to managing symptoms experienced by AYAs with cancer through interviews. Qualitative thematic analysis identified three main domains: (1) managing chemotherapy symptoms (e.g., medication, home remedies), (2) anticipating and mitigating symptoms (e.g., management of symptoms at home, anticipatory guidance), and (3) knowing when to seek care (e.g., unexpected and unusual symptoms). This study elucidated that AYAs can successfully manage symptoms at home when given the proper guidance and this could be a focus of future efforts to improve outcomes in this population. The Clinical Trial Registration number is NCT04594096.

Challenges and Opportunities of Epidemiological Studies to Reduce the Burden of Cancers in Young Adults.

There are >1.9 million survivors of adolescent and young adult cancers (AYA, diagnosed at ages 15-39) living in the U.S. today. Epidemiologic studies to address the cancer burden in this group have been a relatively recent focus of the research community. In this article, we discuss approaches and data resources for cancer epidemiology and health services research in the AYA population. We consider research that uses data from cancer registries, vital records, healthcare utilization, and surveys, and the accompanying challenges and opportunities of each. To illustrate the strengths of each data source, we present example research questions or areas that are aligned with these data sources and salient to AYAs. Integrating the respective strengths of cancer registry, vital records, healthcare data, and survey-based studies sets the foundation for innovative and impactful research on AYA cancer treatment and survivorship to inform a comprehensive understanding of diverse AYA needs and experiences.

Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Children's Oncology Group's 2023 blueprint for research: Liver tumors.

Liver tumors account for approximately 1%-2% of all pediatric malignancies, with the two most common tumors being hepatoblastoma (HB) and hepatocellular carcinoma (HCC). Previous Children's Oncology Group studies have meaningfully contributed to the current understanding of disease pathophysiology and treatment, laying groundwork for the ongoing prospective international study of both HB and HCC. Future work is focused on elucidating the biologic underpinnings of disease to support an evolution in risk categorization, advancements in the multidimensional care required to treat these patients, and the discovery of novel therapies.

Consensus classification of pediatric hepatocellular tumors: A report from the Children's Hepatic tumors International Collaboration (CHIC).

BACKGROUND: Liver tumors are rare in children with histologic heterogeneity that makes diagnosis challenging. Systematic histopathological review, performed as part of collaborative therapeutic protocols, identified relevant histologic subtypes that are important to distinguish. The Children's Hepatic tumors International Collaboration (CHIC) was established to study pediatric liver tumors on a global scale and led to establishment of a provisional consensus classification for use in international clinical trials. The current study is the validation of this initial classification and first large-scale application by international expert reviewers. PROCEDURE: The CHIC initiative includes data from 1605 children treated on eight multicenter hepatoblastoma (HB) trials. Review of 605 available tumors was performed by seven expert pathologists from three consortia (US, EU, Japan). Cases with discordant diagnoses were collectively reviewed to reach a final consensus diagnosis. RESULTS: Of 599 cases with sufficient material for review, 570 (95.2%) were classified as HB by all consortia, and 29 (4.8%) as non-HB, which included "hepatocellular neoplasm, NOS" and malignant rhabdoid tumors. 453 of 570 HBs were classified as epithelial by final consensus. Some patterns (i.e., small cell undifferentiated, macrotrabecular, cholangioblastic) were selectively identified by reviewers from different consortia. All consortia identified a similar number of mixed epithelial-mesenchymal HB. CONCLUSIONS: This study represents the first large-scale application and validation of the pediatric malignant hepatocellular tumors consensus classification. It is a valuable resource to train future generations of investigators on accurate diagnosis of these rare tumors and provides a framework for further international collaborative studies and refinement of the current classification of pediatric liver tumors.

Vincristine/irinotecan/temsirolimus upfront window treatment of high-risk hepatoblastoma: A report from the Children's Oncology Group AHEP0731 Study Committee.

BACKGROUND: Survival for children with metastatic hepatoblastoma (HB) remains suboptimal. We report the response rate and outcome of two courses of vincristine/irinotecan/temsirolimus (VIT) in children with high-risk (HR)/metastatic HB. PROCEDURES: Patients with newly diagnosed HB received HR window chemotherapy if they had metastatic disease or a serum alpha-fetoprotein (AFP) level less than 100 ng/mL. Patients received vincristine (days 1 and 8), irinotecan (days 1-5), and temsirolimus (days 1 and 8). Cycles were repeated every 21 days. Responders had either a 30% decrease using RECIST (Response Evaluation Criteria in Solid Tumors) criteria OR a 90% (>1 log10 decline) AFP decline after two cycles. Responders received two additional cycles of VIT intermixed with six cycles of cisplatin/doxorubicin/5-fluorouracil/vincristine (C5VD). Nonresponders received six cycles of C5VD alone. RESULTS: Thirty-six eligible patients enrolled on study. The median age at enrollment was 27 months (range: 7-170). Seventeen of 36 patients were responders (RECIST and AFP = 3, RECIST only = 4, AFP only = 10). The median AFP at diagnosis was 222,648 ng/mL and the median AFP following two VIT cycles was 19,262 ng/mL. Three-year event-free survival was 47% (95% confidence interval [CI]: 30%-62%), while overall survival was 67% (95% CI: 49%-80%). CONCLUSION: VIT did not achieve the study efficacy endpoint. Temsirolimus does not improve the response rate seen in patients treated with vincristine and irinotecan (VI) alone as part of the initial treatment regimen explored in this study. Additionally, AFP response may be a more sensitive predictor of disease response than RECIST in HB.

Localized Synovial Sarcoma: A Population-Based Analysis of Treatment Patterns and Survival.

Purpose: Synovial sarcoma (SS) is a rare, high-grade soft tissue tumor that requires multidisciplinary and multimodal care with surgery, radiotherapy, and chemotherapy. We examined the impact of sociodemographic and clinical factors on treatment patterns and survival in localized SS patients. Methods: Adolescents and young adults (AYAs, 15-39 years) and older adults ("adults," ≥40 years) diagnosed with localized SS from 2000 to 2018 were identified in the California Cancer Registry. Multivariable logistic regression identified clinical and sociodemographic factors associated with receipt of chemotherapy and/or radiotherapy. Cox proportional hazards regression identified factors associated with overall survival (OS). Results are reported as odds ratios (ORs) and hazard ratios (HRs), respectively, with 95% confidence intervals (CIs). Results: More AYAs (n = 346) than adults (n = 272) received chemotherapy (47.7% vs. 36.4%) and radiotherapy (62.1% vs. 58.1%). Age at diagnosis, tumor size, treatment at National Cancer Institute-Children's Oncology Group (NCI-COG)-designated facilities, insurance status, and neighborhood socioeconomic status (SES) influenced treatment patterns. Among AYAs, treatment at NCI-COG-designated facilities was associated with receiving chemotherapy (OR 2.74, CI 1.48-5.07) and low SES was associated with worse OS (HR 2.28, 1.09-4.77). In adults, high SES was associated with receiving chemoradiotherapy (OR 3.20, CI 1.40-7.31), whereas public insurance was associated with decreased odds of chemoradiotherapy (OR 0.44, CI 0.20-0.95). With regard to treatment, absence of radiotherapy (HR 1.94, CI 1.18-3.20) was associated with worse OS in adults. Conclusion: In localized SS, both clinical and sociodemographic factors influenced treatment patterns. Further research should investigate how SES-related factors produce treatment disparities and identify interventions to improve treatment equity and outcomes.

Nephron sparing surgery and surgical management of intravascular extension of Wilms tumor.

Although general treatment approaches for Wilms tumor differ between Children's Oncology Group and Société Internationale d'Oncologie Pédiatrique-Renal Tumors Study Group protocols, complex tumors that may be candidates for nephron sparing surgery (NSS) and those with intravascular tumor extension represent a management challenge. In both of these scenarios, anatomic considerations are important in guiding management, making these areas of significant similarities in management between the international groups. This paper aims to explore the current approaches to NSS and intravascular tumor extension by both international groups, with attention to the evidence supporting these approaches and current knowledge gaps.

Outcomes of Patients Treated for Hepatoblastoma with Low Alpha-Fetoprotein and/or Small Cell Undifferentiated Histology: A Report from the Children's Hepatic Tumors International Collaboration (CHIC).

Small cell undifferentiated (SCU) histology and alpha-fetoprotein (AFP) levels below 100 ng/mL have been reported as poor prognostic factors in hepatoblastoma (HB); subsequent studies reported SMARCB1 mutations in some SCU HBs confirming the diagnosis of rhabdoid tumor. The Children's Hepatic tumors International Collaboration (CHIC) database was queried for patients with HB who had AFP levels less than 100 ng/mL at diagnosis or were historically diagnosed as SCU HBs. Seventy-three of 1605 patients in the CHIC database were originally identified as SCU HB, HB with SCU component, or HB with low AFP levels. Upon retrospective review, they were re-classified as rhabdoid tumors (n = 11), HB with SCU component (n = 41), and HB with low AFP (n = 14). Seven were excluded for erroneously low AFP levels. Overall survival was 0% for patients with rhabdoid tumors, 76% for patients with HB with SCU component, and 64% for patients with HB with AFP less than 100 ng/mL. Patients with HB with SCU component or low AFP should be assessed for SMARCB1 mutations and, if confirmed, treated as rhabdoid tumors. When rhabdoid tumors are excluded, the presence of SCU component and low AFP at diagnosis were not associated with poor prognosis in patients diagnosed with HB.

Treatment-related toxicities associated with hospitalization in children, adolescents, and young adults with acute lymphoblastic leukemia: population level analysis.

Treatment-related toxicities (TRTs) are a potential cause of survival disparities in patients with acute lymphoblastic leukemia (ALL). We aimed to identify the most frequent TRTs associated with hospitalizations at a population level in children, adolescents and young adults (AYAs). We used the California Cancer Registry linked to a statewide hospital discharge database to identify children and AYAs with TRTs within 3 years of diagnosis. We assessed the frequency of TRTs, length of stay (LOS), admission rates associated with TRTs and TRTs impact on survival. Febrile neutropenia, hypertension, and thrombocytopenia were the most common TRTs for both children and AYAs. AYAs had longer median LOS compared to children for most toxicities. AYAs at non-specialized cancer centers (SCCs) had higher frequency of admissions associated with TRTs compared to non-SCC. Cardiovascular, respiratory, gastrointestinal, renal, and infectious TRTs were associated with worse survival. This study demonstrates the burden of TRTs in patients with ALL.

Outcomes of children with well-differentiated fetal hepatoblastoma treated with surgery only: Report from Children's Oncology Group Trial, AHEP0731.

BACKGROUND: Hepatoblastoma (HB) requires surgical resection for cure, but only 20-30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4-6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone. PATIENTS AND METHODS: Patients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology. RESULTS: A total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8-84 months) and the median AFP at enrollment was 714 ng/ml (range: 18-77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6-9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%. CONCLUSION: This report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation. LEVEL OF EVIDENCE: Prognosis study, Level I evidence.

Impact of local treatment modality on overall- and disease-specific survival for nonmetastatic pelvic and sacral Ewing sarcoma.

PURPOSE: The ideal local treatment modality for pelvic and sacral Ewing sarcoma (EWS) is controversial. METHODS: We present the data from the American College of Surgeon's National Cancer Database (NCDB) and the National Cancer Institute's Surveillance, Epidemiology and End Result (SEER) database to investigate the impact of local treatment modalities on survival for nonmetastatic pelvic and sacral Ewing sarcoma. Local treatment includes "surgery," "radiation," and a combination of "surgery and radiation." RESULTS: A total of 235 cases from SEER and 285 cases from NCDB were analyzed. Patients with "localized" stage (intraosseous) in the SEER database did not show any statistically significant difference in the disease-specific survival (DSS) for any of the local treatment modalities. Similar findings were observed for overall survival among patients with American Joint Committee on Cancer (AJCC) stage II and III in the NCDB database. However, patients with nonmetastatic disease, particularly regional disease (extraosseous), showed improved DSS with surgery only, in the SEER. CONCLUSION: We found similar levels of efficacy for different treatment modalities for patients with intraosseous and AJCC II and III pelvic and sacral EWS. "Radiotherapy" is the most common local treatment modality employed in the United States. A prospective, randomized controlled trial with a direct head-to-head comparison is needed for a definitive conclusion.

Doxorubicin in combination with cisplatin, 5-flourouracil, and vincristine is feasible and effective in unresectable hepatoblastoma: A Children's Oncology Group study.

BACKGROUND: The Children's Oncology Group (COG) adopted cisplatin, 5-flourouracil, and vincristine (C5V) as standard therapy after the INT-0098 legacy study showed statistically equivalent survival but less toxicity in comparison with cisplatin and doxorubicin. Subsequent experience demonstrated doxorubicin to be effective in patients with recurrent disease after C5V, and this suggested that it could be incorporated to intensify therapy for patients with advanced disease. METHODS: In this nonrandomized, phase 3 COG trial, the primary aim was to explore the feasibility and toxicity of a novel therapeutic cisplatin, 5-flourouracil, vincristine, and doxorubicin (C5VD) regimen with the addition of doxorubicin to C5V for patients considered to be at intermediate risk. Patients were eligible if they had unresectable, nonmetastatic disease. Patients with a complete resection at diagnosis and local pathologic evidence of small cell undifferentiated histology were also eligible for an assessment of feasibility. RESULTS: One hundred two evaluable patients enrolled between September 14, 2009, and March 12, 2012. Delivery of C5VD was feasible and tolerable: the mean percentages of the target doses delivered were 96% (95% CI, 94%-97%) for cisplatin, 96% (95% CI, 94%-97%) for 5-fluorouracil, 95% (95% CI, 93%-97%) for doxorubicin, and 90% (95% CI, 87%-93%) for vincristine. Toxicity was within expectations, with death as a first event in 1 patient. The most common adverse events were febrile neutropenia (n = 55 [54%]), infection (n = 48 [47%]), mucositis (n = 31 [30%]), hypokalemia (n = 39 [38%]), and elevated aspartate aminotransferase (n = 28 [27%]). The 5-year event-free and overall survival rates for the 93 patients who did not have complete resection at diagnosis were 88% (95% CI, 79%-93%) and 95% (95% CI, 87%-98%), respectively. CONCLUSIONS: The addition of doxorubicin to the previous standard regimen of C5V is feasible, tolerable, and efficacious, and this suggests that C5VD is a good regimen for future clinical trials.

Small Cell Undifferentiated Histology Does Not Adversely Affect Outcome in Hepatoblastoma: A Report From the Children's Oncology Group (COG) AHEP0731 Study Committee.

PURPOSE: Small cell undifferentiated (SCU) histology in hepatoblastoma (HB) tumors has historically been associated with a poor prognosis. Tumors from patients enrolled on Children's Oncology Group (COG) study AHEP0731 underwent institutional and central pathologic review for identification of SCU histology. PATIENTS AND METHODS: Patients with SCU histology identified at the local treating institution who had otherwise low-risk tumors were upstaged to the intermediate-risk treatment stratum, whereas those only identified by retrospective central review were treated per the local institution as low-risk. Patients with otherwise intermediate- or high-risk tumors remained in that treatment stratum, respectively. Central review was to be performed for all tissue samples obtained at any time point. Treatment was per local review, whereas analysis of outcome was based on central review. RESULTS: Thirty-five patients had some elements (1%-25%) of SCU identified on central review of diagnostic specimens. All but two patient tissue sample retained nuclear INI1 expression. The presence of SCU histology did not correlate with age, alpha-fetoprotein level at diagnosis, or sex. The presence of SCU did not affect event-free survival (EFS). EFS at 5 years for patients with low-risk, intermediate-risk, and high-risk with SCU HB was 86% (95% CI, 33 to 98), 81% (95% CI, 57 to 92), and 29% (95% CI, 4 to 61), respectively, compared with EFS at 5 years for patients without SCU enrolled with low-risk, intermediate-risk, and high-risk of 87% (95% CI, 72 to 95), 88% (95% CI, 79 to 94), and 55% (95% CI, 32 to 74; P = .17), respectively. CONCLUSION: The presence of SCU histology in HB does not appear to adversely affect outcome. Future studies should be able to treat patients with SCU HB according to risk stratification without regard to the presence of SCU histology.