Excellent Outcomes in Children, Adolescents, and Young Adults with Ovarian Germ Cell Tumors Treated by Either Reduced- or Standard-Dose Bleomycin.

To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.

Characteristics and clinical course of thyroid abnormalities arisen in long term survivors of childhood cancer.

BACKGROUND: Thyroid abnormality is a common late effect seen in childhood cancer survivors (CCSs). We analyzed the prevalence and risk factors of thyroid abnormalities based on diagnoses and treatment modalities in CCSs. METHODS: The medical records of 257 CCSs who were diagnosed with cancer less than 20 year of age were retrospectively reviewed. The median age was 11.8 years (0.1-19.8). The median follow-up period after completion of therapy was 9.6 years (5.0-19.5). RESULTS: Of 257 subjects, thyroid abnormalities were identified in 107 (41.6%). Sixty-five out of 257 (25.3%) had subclinical hypothyroidism, and 16 (6.2%) developed central hypothyroidism. Five CCSs (1.9%) had primary overt hypothyroidism. Five (1.9%) and 6 (2.3%) CCSs were diagnosed with autoimmune thyroiditis and thyroid cancer, respectively. Among the different diagnostic groups, thyroid abnormalities were frequent in the brain tumor or Hodgkin disease or nasopharyngeal cancer groups. CCSs who received irradiation directly or near hypothalamus-pituitary-thyroid (HPT) axis had more thyroid abnormalities compared to the rest CCSs (P < 0.0001). CCSs who were treated with SCT had an increased prevalence of thyroid abnormalities (60.5%) compared to the other CCSs (37.9%) (P = 0.0069). Forty-five (42%) of 107 subjects with thyroid abnormalities had normalized thyroid hormone levels at the last follow-up. Irradiation directly or near HPT axis were thought to be a predicting factor of persistent subclinical hypothyroidism. CONCLUSIONS: Subclinical hypothyroidism was common in CCSs. CCSs with irradiation directly or near HPT axis were at risk for persistent thyroid dysfunction.

Gonadal Function in Female Adolescent and Young Adult Survivors of Childhood Cancer.

PURPOSE: Childhood cancer survivors (CCSs) are at risk for premature ovarian insufficiency (POI). The aim of this study is to evaluate ovarian function and associated health outcomes in female adolescent and young adult survivors of childhood cancer. Materials and Methods: Sixty-nine female CCSs were enrolled. Medical records of CCSs were retrospectively reviewed. The subjects were categorized into three groups according to follicular stimulating hormone (FSH) levels (cutoff, 12, 40 IU/L). Anti-müllerian hormone (AMH) level less than 1 ng/mL was considered low AMH level. RESULTS: Of 69 subjects, 14 (20.3%) had POI and 14 (20.3%) had FSH levels between 12 and 40 IU/L. Forty-one of 69 (59.4%) had normal FSH levels. Pelvic irradiation and stem cell transplantation (SCT) were more frequently performed in subjects with POI (p=0.001 and p < 0.001). AMH levels were remarkably low when FSH levels were over 12 IU/L (p < 0.001). In multivariate analysis, cyclophosphamide equivalent dose and SCT were significant treatment factors for developing low AMH levels (p=0.005 and p=0.002, respectively). Total, low-density lipoprotein cholesterol and triglyceride were significantly different in three groups according to FSH levels (p=0.047, p=0.030, and p=0.045). Z-score of femur neck bone mineral density was significantly reduced when FSH levels were increased (p=0.011). CONCLUSION: Gonadal dysfunction is common in CCSs. Gonadal function was associated with a few treatment factors known to increase the risk of POI. Regular monitoring of gonadal function is needed for better health outcomes.

Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data.

PURPOSE: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. MATERIALS AND METHODS: From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. RESULTS: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). CONCLUSION: The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Prevalence and Risk Factors of Metabolic Syndrome Components in Childhood Cancer Survivors.

Purpose: It is crucial for childhood cancer survivors (CCSs) to manage metabolic syndrome. The prevalence and predictive factors of metabolic syndrome components in CCSs were investigated. Methods: This study included CCSs who were diagnosed with cancer under the age of 20 and completed therapy more than 1 year ago. The anthropometric and laboratory data were obtained from the medical records retrospectively. The reference group was extracted from the Korea National Health and Nutrition Examination Survey (2016-2019). Results: Of the participants, 29.1% (75 of 258) of the CCSs and 26.4% (1339 of 5081) of the reference group were obese. Blood pressure and triglyceride levels were significantly different in the two groups. Metabolic syndrome was identified in 35 of 258 (13.6%) patients. The reference group showed a 9.4% of prevalence (480 of 5086) (p = 0.028). A total of 127 of 230 (59.6%) met at least one of the dyslipidemia criteria. In multivariate analysis, current age and growth hormone deficiency (GHD) (OR = 5.905) were significant prognostic factors for dyslipidemia, and GHD was a significant prognostic factor for hypertriglyceridemia (OR = 2.864, p = 0.0316) and hypercholesterolemia (OR = 3.053, p = 0.0467). Cranial radiotherapy (RT) was a prognostic variable for hyper low-density lipoprotein cholesterolemia (OR = 2.866, p = 0.0032). Conclusions: The frequency of metabolic syndrome was higher in CCSs compared with the reference group. Dyslipidemia was common in CCSs with clinical parameters such as GHD and cranial RT. Risk-based long-term follow-up is needed, and early intervention is required for CCSs.

Clinical characteristics and long-term outcomes of rhabdomyosarcoma in Korean children, adolescents and young adults: a single-center experience.

PURPOSE: This study aimed to analyze characteristics, treatment, long-term outcomes, and prognostic factors for children, adolescents and young adults with rhabdomysosarcoma (RMS). METHODS: This retrospective historical study included 75 patients with RMS treated between 2002 and 2019. Clinical data and follow-up results were collected including all diagnosis, treatment and prognosis information. RESULTS: Patients median-age-at-diagnosis was 6 years. Embryonal and alveolar histology occurred in 51 (68.0%) and 21 (28.0%) patients, respectively. The tumors most frequently originated from parameningeal site (28.0%). Of 74 evaluable patients for treatment outcome, 60 (81.1%) achieved complete response for first-line treatment, of whom, 34 (56.6%) maintained complete response, 26 (43.3%; 23/26, local relapse) showed relapse. Of 40 patients with treatment failure, 16 and 6 occurred in parameningeal area and retroperitoneum/perineum, respectively. The 5-year progression-free survival (PFS) and overall survival (OS) were 45.0% and 64.5%, respectively. In multivariate analyses, parameningeal site (p = 0.027), no gross total resection (p = 0.047), and no radiation therapy (RT) (p < 0.001) for PFS; and parameningeal site (p < 0.001) and no RT (p = 0.010) for worse OS, were significant. The median PFS and OS from treatment failure date in 40 patients with primary treatment failure were 1.3 and 4.1 years, respectively. Of 26 patients with relapse, interval to relapse < 7 months, retroperitoneum/perineum site, TNM stages III/IIV, and no salvage RT were independently associated with OS. CONCLUSION: The importance of adequate local therapy was highlighted in RMS treatment. Treatment failure was largely a local failure. Whether as a component of initial or salvage treatment, RT could improve patients' survival.

Therapeutic Potential of Ex Vivo Expanded γδ T Cells against Osteosarcoma Cells.

Immunotherapy is an attractive therapeutic strategy for the treatment of osteosarcoma (OS). The unique features of γδ T cells have made them popular for cancer immunotherapy. Here, we expanded γδ T cells using human peripheral blood mononuclear cells (PBMCs) and investigated their therapeutic potential against OS cells. PBMCs from healthy donors were cultured for 10 days with CON medium (unstimulated control); EX media, CON with recombinant human interleukin-2 (rhIL-2) and zoledronate; and EX28 media, CON with rhIL-2, zoledronate, and CD3/CD28 activator. The expanded γδ T cells were isolated by magnetic cell separation or fluorescence-activated cell sorting, cultured with two OS cell lines (KHOS/NP and MG-63) at various cell ratios with or without doxorubicin or ifosfamide, and analyzed for cytotoxicity and cytokine secretion. The number of CD3+γδTCR+Vγ9+ triple-positive γδ T cells and concentrations of IFN-γ and TNF-α were highest in the rhIL-2 (100 IU) and zoledronate (1 µM) supplemented culture conditions. The CD3/CD28 agonist did not show any additional effects on γδ T cell expansion. The expanded γδ T cells exhibited potent in vitro cytotoxicity against OS in a ratio- and time-dependent manner. The γδ T cells may enhance the effect of chemotherapeutic agents against OS and may be a new treatment strategy, including chemo-immunotherapy, for OS.

Identifying serum miRNA biomarkers for radiation exposure in hematopoietic humanized NSG-SGM3 mice.

BACKGROUND: Humans are commonly exposed to ionizing radiation. The conventional approach for estimating radiation exposure is to integrate physical and clinical measurements for optimizing the dose calculation. However, these methods have several limitations. The present study attempted to identify candidate microRNA (miRNA) biomarkers for radiation exposure in a hematopoietic humanized NSGS (hu-NSGS) mouse model. METHODS: We grafted human CD34+ hematopoietic stem cells into NSG-SGM3 (NSGS) mice. The hu-NSGS mice underwent total body irradiation at doses of 2, 3, and 4 Gy. Tissues from the spleen, thymus, and lymph nodes of hu-NSGS mice were prepared to analyze levels of CD45+ and CD3+ T cells and CD 20+ B cells using flow cytometry and immunohistochemistry. Serum miRNAs were profiled using a digital multiplexed NanoString n-Counter. RESULTS: The expression of 45 miRNAs was upregulated/downregulated hu-NSGS mice. The miRNAs hsa-mir-188-5p, hsa-let-7a-5p, hsa-mir-612, hsa-mir-671-5p, and hsa-mir-675-5p were highly radiation-responsive in irradiated hu-NSGS mice. When compared with control mice, radiation-exposed mice exhibited significant upregulated of hsa-let-7a-5p expression and significant downregulation of hsa-mir-188-5p expression. CONCLUSIONS: Single miRNAs or combinations of hsa-mir-188-5p, hsa-let-7a-5p, hsa-mir-675-5p, hsa-mir-612, and hsa-mir-671-5p can be used as biomarkers for predicting the impact of radiation exposure. The current findings suggest the usefulness of hu-NSGS models for investigating radiation biomarkers.

Incidence Patterns and Outcomes of Ewing Sarcoma in South Korea (1999-2017): A Retrospective Analysis Using Korea Central Cancer Registry Data.

PURPOSE: Due to low incidence, epidemiologic data of Ewing sarcoma in the Asian population are scarce. We aimed to examine the incidence pattern and outcome of patients with Ewing sarcoma in the Republic of Korea. MATERIALS AND METHODS: Data of patients with Ewing sarcoma diagnosed between 1999 and 2017 were obtained from the Korea Central Cancer Registry (KCCR). Incidence, clinical characteristics, and survival rates were analyzed and compared between different age groups. RESULTS: There were 788 cases (459 males, 329 females), with a median age at diagnosis of 20 years. The age-standardized rate of Ewing sarcoma was 1.01. The number of cases and incidence rates in each age group were as follows: children, 1.6; adolescents and young adults (AYA), 0.93; adults, 0.44; and elderly, 0.53. There were more male cases in children and the AYA group (p < 0.001). Extraskeletal tumors (p < 0.001), primary sites other than extremity (p=0.007), and presence of metastasis at diagnosis (p=0.031) were more frequent in the adults and elderly group. With a median survival time of 78 months, the 5-year overall survival (OS) rate of the entire cohort was 52%. Children fared best (5-year OS, 75%), and the 5-year OS of AYA patients (51%) approximated the OS of the entire cohort. A two-fold difference of 5-year OS was observed between adults and elderly patients (42% vs. 19%). On univariate and multivariate analyses, age ≥ 15 years and presence of metastasis were adverse prognostic factors. CONCLUSION: This was the first epidemiologic study of Ewing sarcoma using the KCCR data. With a similar incidence to other Asian countries, the survival rate was slightly lower than that of Euro-American cases. Collaborative clinical studies are necessary to improve the outcome of Ewing sarcoma in low-incidence populations.

Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults.

PURPOSE: No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults. MATERIALS AND METHODS: We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m2 intravenously on day 1, irinotecan, 50 mg/m2/day intravenously on days 1-5, and temozolomide, 100 mg/m2/day orally on days 1-5. RESULTS: A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality. CONCLUSION: The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

Osteosarcoma in Adolescents and Young Adults.

The epidemiology of osteosarcoma in adolescents and young adults (AYA) remains unclear. We aimed to assess and compare the clinical features of osteosarcoma between AYA and other age groups. We retrieved osteosarcoma cases diagnosed between 1999 and 2017 from the Korea Central Cancer Registry. We compared survival trends and clinical characteristics between AYA and other age groups. AYA comprised 43.3% (1309/3022) of the osteosarcoma cases. Compared to other age groups, the male-to-female ratio was highest in AYA (1.61:1). The proportion of tumors located in an extremity was 80.3% in AYA, which was lower than in young children (92.5%) or pubertal children (93.8%) but higher than in adults (55.7%) or the elderly (47.5%). As for treatments, 71.2% of AYA received local treatment and systemic chemotherapy, and 28.8% received only local treatment (surgery: 261, radiotherapy: 9, surgery and radiotherapy: 5). The 5-year overall survival (OS) was lower in AYA (68%) than in young children (78%) or pubertal children (73%) but higher than in adults (47%) or the elderly (25%). When AYA were divided into five subgroups by age, patients aged 15-19 years constituted the largest proportion (45.4%, n = 594). Additionally, the proportion of patients with a non-extremity tumor increased in an age-dependent manner, from 10.3% in AYA aged 15-19 years to 35.3% in AYA aged 35-39 years. OS did not significantly differ among the different age subgroups of AYA. The clinical characteristics and OS of the AYA were more similar to those of children than to those of adults. There is a need for cooperation between pediatric and adult oncologists for effective osteosarcoma treatment in AYA.

Incidence and outcomes of malignant ovarian germ cell tumors in Korea, 1999-2017.

OBJECTIVE: Malignant ovarian germ cell tumor (MOGCT) is a rare ovarian malignancy accounting for less than 5% of all ovarian cancers. We aimed to evaluate the incidence, survival, and subsequent malignancies after the diagnosis of MOGCT. METHODS: Data from the Korea Central Cancer Registry were used to identify MOGCTs between 1999 and 2017. The age-standardized rates (ASRs), 5-year relative survival rates (RSR) and standardized incidence ratio (SIR) for subsequent cancer after diagnosis of MOGCT were estimated. RESULTS: Of 2125 cases of newly diagnosed MOGCTs, 596 (28.0%) were diagnosed with dysgerminoma and 1529 (72.0%) with non-dysgerminoma. The ASR per 100,000 women-years was 0.539; ASR slightly increased over the study period (annual percent change [APC] = 1.01%; p = 0.02). There was an increase and decrease in the incidence of MOGCTs in the age groups 0-19 years (APC = 1.96%; p < 0.01) and ≥ 50 years (APC = -6.51%; p < 0.01), respectively. Patients with dysgerminoma showed significantly higher RSR than patients with non-dysgerminoma (98.0% vs. 94.9%, p < 0.01). Patients aged ≥50 years showed worst 5-year RSR (68.7%) than patients aged 0-19 years (97.8%) and 20-34 years (96.4%) (p < 0.01). The overall SIR for a subsequent cancer occurrence was 2.07, with the most frequent site of subsequent primary cancer being the thyroid (SIR = 2.78). CONCLUSIONS: Our data demonstrated an excellent prognosis of MOGCTs among Korean women. There was a slight increase in MOGCT prevalence, which was more pronounced among those aged <19 years. After MOGCT diagnosis, the risk of developing a subsequent malignancy was doubled compared with the general population.

Development of a Bioluminescent Human Osteosarcoma Model in Humanized NSG Mice: A Pilot Study.

BACKGROUND/AIM: Osteosarcoma is the most common type of bone cancer, but current therapeutic interventions remain largely insufficient. The development of new treatment strategies is needed, and moreover, optimal rodent models are necessary for testing the efficacy of new treatment modalities of osteosarcoma. Humanized mice carry human hematopoietic and immune systems, and are considered an ideal tool to study human diseases including cancer immunology. Herein, we performed a preliminary study toward developing an in vivo bioluminescent osteosarcoma model using humanized immunodeficient (NSG) mice. MATERIALS AND METHODS: To establish the xenograft and orthotopic mouse model, NSG mice engrafted with human CD34+ hematopoietic stem cells were injected with luciferase-expressing KHOS/NP cells at two different time points. Bioluminescence images were obtained to monitor in vivo tumor growth and metastasis. Influence of the degree of human cell engraftment on tumor growth and metastatic behavior was analyzed and compared between the two groups. RESULTS: KHOS/NP-luc cells injected in humanized NSG mice formed macroscopic tumors. The percentage of human CD45+ cells in these models was similar, but the percentage of human CD45+CD3+ and their subset was higher in the late-injection group compared to that of the early-injection group. The rate of KHOS/NP tumor growth was higher in the early-injection group than in the late-injection group. In the present study, human hematopoietic cell engraftment was not influenced by KHOS/NP cell injection, but KHOS/NP osteosarcoma showed more aggressive behavior in the early-injection group than that in the late-injection group, forming larger tumor volumes and earlier metastases. CONCLUSION: The results indicated that tumor growth and progression in humanized NSG mice may have been influenced by higher levels of human cell engraftment, especially T cells. Although there exist some limitations to our study, our preliminary results can provide the basis for the development of a humanized osteosarcoma mouse model.

Erratum: Correction of Affiliations in the Article "Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study".

This corrects the article on p. e393 in vol. 35, PMID: 33258329.

Cancer Incidence and Survival among Adolescents and Young Adults in Korea: An Update for 2016.

PURPOSE: This study investigated the incidence and relative survival rates (RSRs) for cancers among adolescents and young adults (AYAs) aged 15-39 years between 1993 and 2016 in Korea. MATERIALS AND METHODS: Data from the Korea Central Cancer Registry were used to calculate percent distributions, age-specific incidence rates, age-standardized incidence rates (ASRs) per million, annual percent changes (APCs), average APCs, and RSRs for cancers diagnosed in AYAs. RESULTS: ASR of all cancers among AYAs was 654.5 per million. The largest diagnosed group of cancers was carcinomas (almost 80%). Crude incidence increased with age, from 170.4 per million for those aged 15-19 years to 1,639.8 per million for those aged 35-39 years. ASR increased from 414.8 per million to 820.4 per million, with an APC of 9.0%. The incidence of thyroid carcinoma showed the most rapid increment (APC, 14.0%), followed by non-Hodgkin lymphoma (APC, 13.4%). The 5-year RSR among AYAs significantly improved from 62.1% to 90.8%. Survival improvement in AYAs was higher than that in children but lower than that in older adults (APC, 2.1% vs. 1.9% vs. 3.1%). The most marked survival improvement was found for leukemia and lymphoma. Astrocytoma, rhabdomyosarcoma, and carcinoma of the trachea, bronchus, and lung had a 5-year RSR of < 50%. CONCLUSION: There was an improvement in cancer survivals in AYAs, comparable to that achieved in children. However, survivals in several cancer types do not appear to be improving. Further research focusing on the epidemiology and therapeutic strategies for cancers in AYAs is needed.

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years.

PURPOSE: Atypical teratoid/rhabdoid tumor (ATRT) is a highly aggressive malignancy with peak incidence in children aged less than 3 years. Standard treatment for central nervous system ATRT in children under the age of 3 years have not been established yet. The objective of this study was to analyze characteristics and clinical outcomes of ATRT in children aged less than 3 years. MATERIALS AND METHODS: A search of medical records from seven centers was performed between January 2005 and December 2016. RESULTS: Forty-three patients were enrolled. With a median follow-up of 90 months, 27 patients (64.3%) showed at least one episode of disease progression (PD). The first date of PD was at 160 days after diagnosis. The 1- and 3-year progression-free survivals (PFS) were 51.2% and 28.5%, respectively. The 1- and 3-year overall survivals were 61.9% and 38.1%, respectively. The 3-year PFS was improved from 0% in pre-2011 to 47.4% in post-2011. Excluding one patient who did not receive any further therapy after surgery, 27 patients died due to PD (n=21), treatment-related toxicity (n=5), or unknown cause (n=1). In univariate analysis, factors associated with higher 3-year PFS were no metastases, diagnosis after 2011, early adjuvant radiotherapy, and high-dose chemotherapy (HDCT). In multivariate analysis, the use of HDCT and adjuvant radiotherapy remained significant prognostic factors for PFS (both p < 0.01). CONCLUSION: Aggressive therapy including early adjuvant radiotherapy and HDCT could be considered to improve outcomes of ATRT in children under the age of 3 years.

Hyperammonemic Encephalopathy Mimicking Ornithine Transcarbamylase Deficiency in Fibrolamellar Hepatocellular Carcinoma: Successful Treatment with Continuous Venovenous Hemofiltration and Ammonia Scavengers.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver cancer affecting adolescents and young adults without any pre existing liver disease. Hyperammonemic encephalopathy (HAE) is a serious paraneoplastic syndrome, and several cases of HAE have been reported in patients with FLHCC. This condition is rare; hence, there are currently no management guidelines for cancer-related HAE. Herein, we report a case of an 18-year-old man with advanced FLHCC who developed HAE during the first course of chemotherapy consisting of cisplatin, doxorubicin, 5-fluorouracil, and interferon-α. He was successfully treated with continuous venovenous hemofiltration, sodium benzoate, sodium phenylbutyrate, and amino acid supplementation for HAE. After the second course of chemotherapy, he underwent surgery, and thereafter, his ammonia levels were normal without any ammonia scavenger therapy. Treatments for HAE described here will be helpful for this rare, but serious metabolic complication of FLHCC and could partially applied to HAE related to any malignancies.

Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study.

BACKGROUND: Hodgkin's lymphoma (HL) constitutes 10%-20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. METHODS: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. RESULTS: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype. Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, high-risk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level. In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. CONCLUSION: This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

Low bone mineral density in children and adolescents with cancer.

Maximizing accumulation of bone mass during childhood and adolescence is essential to attaining optimal peak bone mass. Childhood cancer survivors (CCS) have lower bone mineral density (BMD) than the general population. Chemotherapeutic agents including steroids and radiotherapy can affect BMD. Cancer itself, hormonal insufficiency, a poor nutritional state, and a deficit of physical activities during or after treatment also influence BMD in CCS, resulting in failure to achieve appropriate peak bone mass. Low BMD in childhood and adolescence can lead to osteoporosis in adult life and complications such as bone pain, bone deformity, and fractures. Thus, BMD in CCS should be monitored with appropriate intervention. Adequate intake of calcium and vitamin D and an increase in physical activity are recommended. Timely supplements of hormones are needed in some cases. Some publications have reported that bisphosphonate therapies using pamidronate or alendronate were well tolerated in CCS and helped increase BMD.

Epidemiological Study of Hereditary Hemolytic Anemia in the Korean Pediatric Population during 1997-2016: a Nationwide Retrospective Cohort Study.

BACKGROUND: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA. METHODS: We collected the data of a newly diagnosed pediatric HHA cohort (2007-2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997-2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey. RESULTS: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased (P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia. CONCLUSION: In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA.