Cancer Research and Treatment

Original Articles

Pediatric cancer

The Effect of Hematopoietic Stem Cell Transplantation on Treatment Outcome in Children with Acute Lymphoblastic Leukemia: Hee Young Ju, Na Hee Lee, Eun Sang Yi, Young Bae Choi, So Jin Kim, Ju Kyung Hyun, Hee Won Cho, Jae Kyung Lee, Ji Won Lee, Ki Woong Sung, Hong Hoe Koo, Keon Hee Yoo; Cancer Res Treat. 2025;57(1):240-249. Published online July 5, 2024; DOI: https://doi.org/10.4143/crt.2024.155

Abstract PDF PubReader ePub: Purpose
Hematopoietic stem cell transplantation (HSCT) has been an important method of treatment in the advance of pediatric acute lymphoblastic leukemia (ALL). The indications for HSCT are evolving and require updated establishment. In this study, we aimed to investigate the efficacy of HSCT on the treatment outcome of pediatric ALL, considering the indications for HSCT and subgroups.
Materials and Methods
A retrospective analysis was conducted on ALL patients diagnosed and treated at a single center. Risk groups were categorized based on age at diagnosis, initial white blood cell count, disease lineage (B/T), and cytogenetic study results. Data on the patients’ disease status at HSCT and indications of HSCT were collected. Indications for HSCT were categorized as upfront HSCT at 1st complete remission, relapse, and refractory disease.
Results
Among the 549 screened patients, a total of 418 patients were included in the study; B-cell ALL (n=379) and T-cell ALL (T-ALL) (n=39). HSCT was conducted on a total of 106 patients (25.4%), with a higher frequency as upfront HSCT in higher-risk groups and specific cytogenetics. The overall survival (OS) was significantly better when done upfront than in relapsed or refractory state in T-ALL patients (p=0.002). The KMT2A-rearranged ALL patients showed superior event-free survival (p=0.002) and OS (p=0.022) when HSCT was done as upfront treatment.
Conclusion
HSCT had a substantial positive effect in a specific subset of pediatric ALL. In particular, frontline HSCT for T-ALL and KMT2A-rearranged ALL offered a better prognosis than when HSCT was conducted in a relapsed or refractory setting.

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Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors: Hana Lim, Minji Im, Eun Seop Seo, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Sung Yoon Cho, Jong-Won Kim, Do Hoon Lim, Ki Woong Sung, Ji Won Lee; Cancer Res Treat. 2024;56(2):642-651. Published online November 24, 2023; DOI: https://doi.org/10.4143/crt.2023.999

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Purpose
This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT).
Materials and Methods
Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk.
Results
A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively.
Conclusion
The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

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Rising Prevalence of Low-Frequency PPM1D Gene Mutations after Second HDCT in Multiple Myeloma
Katja Seipel, Nuria Z. Veglio, Henning Nilius, Barbara Jeker, Ulrike Bacher, Thomas Pabst
Current Issues in Molecular Biology.2024; 46(8): 8197. CrossRef

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Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data: Kyung-Nam Koh, Jung Woo Han, Hyoung Soo Choi, Hyoung Jin Kang, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Kyung Taek Hong, Jung Yoon Choi, Sung Han Kang, Hyery Kim, Ho Joon Im, Seung Min Hahn, Chuhl Joo Lyu, Hee-Jo Baek, Hoon Kook, Kyung Mi Park, Eu Jeen Yang, Young Tak Lim, Seongkoo Kim, Jae Wook Lee, Nack-Gyun Chung, Bin Cho, Meerim Park, Hyeon Jin Park, Byung-Kiu Park, Jun Ah Lee, Jun Eun Park, Soon Ki Kim, Ji Yoon Kim, Hyo Sun Kim, Youngeun Ma, Kyung Duk Park, Sang Kyu Park, Eun Sil Park, Ye Jee Shim, Eun Sun Yoo, Kyung Ha Ryu, Jae Won Yoo, Yeon Jung Lim, Hoi Soo Yoon, Mee Jeong Lee, Jae Min Lee, In-Sang Jeon, Hye Lim Jung, Hee Won Chueh, Seunghyun Won, the Korean Pediatric Hematology and Oncology Group (KPHOG); Cancer Res Treat. 2023;55(1):279-290. Published online August 11, 2022; DOI: https://doi.org/10.4143/crt.2022.073

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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.

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Congenital Mesoblastic Nephroma Mimic Wilms Tumor on 18F-FDG PET/CT and PET/MR
Wenzhu Hu, Chunxia Qin, Fuqiang Shao, Mengting Li, Xiaoli Lan
Clinical Nuclear Medicine.2024; 49(4): 353. CrossRef
Progress towards Therapies for Solid Renal Tumors in Children
洁林
Advances in Clinical Medicine.2024; 14(06): 245. CrossRef

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Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma: Ji Won Lee, Joon Seol Bae, Jin Ho Kim, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Hong Hoe Koo, Sook-young Woo, Seonwoo Kim, Ki Woong Sung; Cancer Res Treat. 2022;54(1):259-268. Published online April 12, 2021; DOI: https://doi.org/10.4143/crt.2021.010

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Purpose
We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma.
Materials and Methods
The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed.
Results
An ANC of 32.5/μL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/μL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC.
Conclusion
In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.

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Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy‐Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single‐Centre Experience
Suzanne Busser, Laura Blackwood, Constanza Pereira, Margo Chase‐Topping, Spela Bavcar, Quentin Fournier
Veterinary and Comparative Oncology.2024; 22(4): 542. CrossRef
Targeting the myeloid microenvironment in neuroblastoma
Marjolein C. Stip, Loes Teeuwen, Miranda P. Dierselhuis, Jeanette H. W. Leusen, Daniëlle Krijgsman
Journal of Experimental & Clinical Cancer Research.2023;[Epub] CrossRef

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Central nervous system

Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System in Children under the Age of 3 Years: Meerim Park, Jung Woo Han, Seung Min Hahn, Jun Ah Lee, Joo-Young Kim, Sang Hoon Shin, Dong-Seok Kim, Hong In Yoon, Kyung Taek Hong, Jung Yoon Choi, Hyoung Jin Kang, Hee Young Shin, Ji Hoon Phi, Seung-Ki Kim, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Do Hoon Lim, Hyung Jin Shin, Hyery Kim, Kyung-Nam Koh, Ho Joon Im, Seung Do Ahn, Young-Shin Ra, Hee-Jo Baek, Hoon Kook, Tae-Young Jung, Hyoung Soo Choi, Chae-Yong Kim, Hyeon Jin Park, Chuhl Joo Lyu; Cancer Res Treat. 2021;53(2):378-388. Published online October 28, 2020; DOI: https://doi.org/10.4143/crt.2020.756

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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.

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Metabolic profiling of patient-derived organoids reveals nucleotide synthesis as a metabolic vulnerability in malignant rhabdoid tumors
Marjolein M.G. Kes, Francisco Morales-Rodriguez, Esther A. Zaal, Terezinha de Souza, Natalie Proost, Marieke van de Ven, Marry M. van den Heuvel-Eibrink, Jeroen W.A. Jansen, Celia R. Berkers, Jarno Drost
Cell Reports Medicine.2025; 6(1): 101878. CrossRef
Supratentorial ATRT in a young Infant: Expanding the diagnostic spectrum beyond medulloblastoma
Ali Msheik, Mohamad Aoun, Youssef Fares
Interdisciplinary Neurosurgery.2024; 35: 101857. CrossRef
Radiation Therapy Plays an Important Role in the Treatment of Atypical Teratoid/Rhabdoid Tumors: Analysis of the EU-RHAB Cohorts and Their Precursors
Sabine Frisch, Hanna Libuschewski, Sarah Peters, Joachim Gerß, Katja von Hoff, Rolf-Dieter Kortmann, Karolina Nemes, Stefan Rutkowski, Martin Hasselblatt, Torsten Pietsch, Michael C. Frühwald, Beate Timmermann
International Journal of Radiation Oncology*Biology*Physics.2024; 119(4): 1147. CrossRef
An adult with recurrent atypical teratoid rhabdoid tumor of the spine
Antoinette J Charles, Vanessa L Smith, C Rory Goodwin, Margaret O Johnson
CNS Oncology.2024;[Epub] CrossRef
Dynamic Survival Risk Prognostic Model and Genomic Landscape for Atypical Teratoid/Rhabdoid Tumors: A Population-Based, Real-World Study
Sihao Chen, Yi He, Jiao Liu, Ruixin Wu, Menglei Wang, Aishun Jin
Cancers.2024; 16(5): 1059. CrossRef
ESTRO-SIOPE guideline: Clinical management of radiotherapy in atypical teratoid/rhabdoid tumors (AT/RTs)
Beate Timmermann, Claire Alapetite, Karin Dieckmann, Rolf-Dieter Kortmann, Yasmin Lassen-Ramshad, John H. Maduro, Monica Ramos Albiac, Umberto Ricardi, Damien C. Weber
Radiotherapy and Oncology.2024; 196: 110227. CrossRef
Development and epigenetic regulation of Atypical teratoid/rhabdoid tumors in the context of cell-of-origin and halted cell differentiation
Laura Huhtala, Goktug Karabiyik, Kirsi J Rautajoki
Neuro-Oncology Advances.2024;[Epub] CrossRef
Comparative treatment results of children with atypical teratoid/rhabdoid tumor of the central nervous system in the younger age group
L. V. Olkhova, O. G. Zheludkova, L. S. Zubarovskaya, A. S. Levashov, A. Yu. Smirnova, Yu. V. Dinikina, Yu. V. Kushel, A. G. Melikyan, S. K. Gorelyshev, M. V. Ryzhova, Yu. Yu. Trunin, A. G. Gevorgyan, O. B. Polushkina, V. E. Popov, L. P. Privalova, N. B. Y
Russian Journal of Pediatric Hematology and Oncology.2023; 10(1): 11. CrossRef
Current Challenges of Asian National Children's Cancer Study Groups on Behalf of Asian Pediatric Hematology and Oncology Group
Chi-kong Li, Purna Kurkure, Ramandeep Singh Arora, Bow Wen Chen, Kirill Kirgizov, Yasuhiro Okamoto, Panya Seksarn, Yongmin Tang, Keon Hee Yoo, Bharat Agarwal, Godfrey C.F. Chan, Rashmi Dalvi, Hiroki Hori, Muhammad Saghir Khan, Alice Yu, Akira Nakagawara
JCO Global Oncology.2023;[Epub] CrossRef
Survival and Malignant Transformation of Pineal Parenchymal Tumors: A 30-Year Retrospective Analysis in a Single-Institution
Tae-Hwan Park, Seung-Ki Kim, Ji Hoon Phi, Chul-Kee Park, Yong Hwy Kim, Sun Ha Paek, Chang-Hyun Lee, Sung-Hye Park, Eun Jung Koh
Brain Tumor Research and Treatment.2023; 11(4): 254. CrossRef
Atypical Teratoid/Rhabdoid Tumor in Taiwan: A Nationwide, Population-Based Study
Yen-Lin Liu, Min-Lan Tsai, Chang-I Chen, Noi Yar, Ching-Wen Tsai, Hsin-Lun Lee, Chia-Chun Kuo, Wan-Ling Ho, Kevin Li-Chun Hsieh, Sung-Hui Tseng, James S. Miser, Chia-Yau Chang, Hsi Chang, Wen-Chang Huang, Tai-Tong Wong, Alexander T. H. Wu, Yu-Chun Yen
Cancers.2022; 14(3): 668. CrossRef
Atypical Teratoid Rhabdoid Tumor: A Possible Oriented Female Pathology?
Cinzia Baiano, Rosa Della Monica, Raduan Ahmed Franca, Maria Laura Del Basso De Caro, Luigi Maria Cavallo, Lorenzo Chiariotti, Tamara Ius, Emmanuel Jouanneau, Teresa Somma
Frontiers in Oncology.2022;[Epub] CrossRef
Clinical predictors of survival for patients with atypical teratoid/rhabdoid tumors
Vismaya S. Bachu, Pavan Shah, Adrian E. Jimenez, Adham M. Khalafallah, Jignesh Tailor, Debraj Mukherjee, Alan R. Cohen
Child's Nervous System.2022; 38(7): 1297. CrossRef
Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumors
Yukitomo Ishi, Yongzhan Zhang, Ali Zhang, Takahiro Sasaki, Andrea Piunti, Amreena Suri, Jun Watanabe, Kouki Abe, Xingyao He, Hiroaki Katagi, Pankaj Bhalla, Manabu Natsumeda, Lihua Zou, Ali Shilatifard, Rintaro Hashizume
Molecular Cancer Therapeutics.2022; 21(5): 715. CrossRef
Molecular targeted therapies for pediatric atypical teratoid/rhabdoid tumors
Chang Zhang, Hao Li
Pediatric Investigation.2022; 6(2): 111. CrossRef
The results of multicenter treatment of atypical teratoid/rhabdoid tumors of the central nervous system in children under 3 years
L. V. Olkhova, O. G. Zheludkova, L. S. Zubarovskaya, A. Yu. Smirnova, Yu. V. Dinikina, Yu. V. Kushel, A. G. Melikyan, S. K. Gorelyshev, M. V. Ryzhova, Yu. Yu. Trunin, E. I. Shults, A. G. Gevorgyan, S. V. Gorbatykh, A. N. Kislyakov, V. E. Popov, L. P. Priv
Pediatric Hematology/Oncology and Immunopathology.2021; 20(2): 121. CrossRef

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Pediatric malignancy

Genome-Wide Association Study for the Identification of Novel Genetic Variants Associated with the Risk of Neuroblastoma in Korean Children: Joon Seol Bae, Ji Won Lee, Jung Eun Yoo, Je-Gun Joung, Keon Hee Yoo, Hong Hoe Koo, Yun-Mi Song, Ki Woong Sung; Cancer Res Treat. 2020;52(4):1251-1261. Published online June 30, 2020; DOI: https://doi.org/10.4143/crt.2020.140

Abstract PDF Supplementary Material PubReader ePub

Purpose
Neuroblastoma (NB) is the most common extracranial solid tumor found in children. To identify significant genetic factors for the risk of NB, several genetic studies was conducted mainly for Caucasians and Europeans. However, considering racial differences, there is a possibility that genetic predispositions that contribute to the development of NB are different, and GWAS study has not yet been conducted on Korean NB patients.
Materials and Methods
To identify the genetic variations associated with the risk of pediatric NB in Korean children, we performed a genome-wide association analysis with 296 NB patients and 1000 unaffected controls (total n = 1,296) after data cleaning and filtering as well as imputation of non-genotyped SNPs using IMPUTE v2.3.2.
Results
After adjusting for multiple comparisons, we found 21 statistically significant SNPs associated with the risk of NB (P^corr < 0.05) within 12 genes (RPTN, MRPS18B, LRRC45, KANSL1L, ARHGEF40, IL15RA, L1TD1, ANO7, LAMA5, OR7G2, SALL4, and NEUROG2). Interestingly, out of these, 12 markers were nonsynonymous SNPs. The SNP rs76015112 was most significantly associated with the risk of NB (p = 8.1E-23, P^corr = 2.3E-17) and was located in the RPTN gene. In addition, significant nonsynonymous SNPs in ADGRE1 were found in patients with MYCN amplification (rs7256147, p = 2.6E-05). In high-risk group, rs7256147 was observed as a significant SNP (p = 5.9E-06).
Conclusion
Our findings might facilitate improved understanding of the mechanism of pediatric NB pathogenesis. However, functional evaluation and replication of these results in other populations are still needed.

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Expression of anoctamin 7 (ANO7) is associated with poor prognosis and mucin 2 (MUC2) in colon adenocarcinoma: a study based on TCGA data
Chen Chen, Siripat Aluksanasuwan, Keerakarn Somsuan
Genomics & Informatics.2023; 21(4): e46. CrossRef
An Overview of Long Non-Coding (lnc)RNAs in Neuroblastoma
Francesca Baldini, Matilde Calderoni, Laura Vergani, Paola Modesto, Tullio Florio, Aldo Pagano
International Journal of Molecular Sciences.2021; 22(8): 4234. CrossRef

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Loss of Heterozygosity at Chromosome 16q Is a Negative Prognostic Factor in Korean Pediatric Patients with Favorable Histology Wilms Tumor: A Report of the Korean Pediatric Hematology Oncology Group (K-PHOG): Jun Eun Park, O Kyu Noh, Yonghee Lee, Hyoung Soo Choi, Jung Woo Han, Seung Min Hahn, Chuhl Joo Lyu, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Seon-Yong Jeong, Ki Woong Sung; Cancer Res Treat. 2020;52(2):438-445. Published online September 10, 2019; DOI: https://doi.org/10.4143/crt.2019.313

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Purpose
Loss of heterozygosity (LOH) at chromosomes 1p and 16q is a poor prognostic factor in favorable histology Wilms tumor (FHWT). This study investigated the prevalence of LOH at 1p and 16q and evaluated its prognostic value in Korean children with FHWT. Materials and Methods We analyzed 101 FHWT patients who were diagnosed between 1996 and 2016 in Korean Society of Pediatric Hematology Oncology Group hospitals. Using paraffin-embedded kidney tissue samples sent from each center, we reviewed LOH at 1p and 16q in each patient and assessed the prognostic value of LOH status for clinical parameters affecting event-free survival (EFS).
Results
Of the 101 patients, 12 (11.9%) experienced recurrence; the 3-year EFS was 87.6%. LOH at 1p or 16q was detected in 19 patients (18.8%), with five having LOH at both 1q and 16q. The frequency of LOH at 1p was higher among younger patients (p=0.049), but there was no difference in LOH prevalence according to tumor stage. In the multivariate analysis, LOH at 16q was a significant negative prognostic factor affecting EFS (3-year EFS, 73.7% vs. 91.1%; hazard ratio, 3.95; p=0.037), whereas LOH at 1p was not (p=0.786). Conclusion LOH at 16q was a significant negative prognostic factor affecting outcome in Korean pediatric FHWT patients. Due to the small sample size of this study, large-scale multicenter trials are warranted to investigate the prognostic value of LOH at 1p and 16q in Korean children with FHWT.

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Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes: A meta-analysis
Yuan-Hua Song, Wen-Ling Li, Zhen Yang, Yan Gao, Zhi-Ping Feng
World Journal of Gastrointestinal Oncology.2024; 16(5): 2159. CrossRef
Inter-Ethnic Variations in the Clinical, Pathological, and Molecular Characteristics of Wilms Tumor
Kia Teng Lim, Amos H. P. Loh
Cancers.2024; 16(17): 3051. CrossRef
Characterization of malignant kidney tumors in childhood by 18F-FDG PET/CT
Jinyu Gou, Xueli Ji, Shuqi Wu, Hui Wang, Suyun Chen
World Journal of Urology.2024;[Epub] CrossRef
Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data
Kyung-Nam Koh, Jung Woo Han, Hyoung Soo Choi, Hyoung Jin Kang, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Kyung Taek Hong, Jung Yoon Choi, Sung Han Kang, Hyery Kim, Ho Joon Im, Seung Min Hahn, Chuhl Joo Lyu, Hee-Jo Baek, Hoon Kook, Kyung Mi Pa
Cancer Research and Treatment.2023; 55(1): 279. CrossRef
Research Advances of Prognostic Risk Factors of Wilms Tumor
建宇汪
World Journal of Cancer Research.2023; 13(02): 51. CrossRef
Current Challenges of Asian National Children's Cancer Study Groups on Behalf of Asian Pediatric Hematology and Oncology Group
Chi-kong Li, Purna Kurkure, Ramandeep Singh Arora, Bow Wen Chen, Kirill Kirgizov, Yasuhiro Okamoto, Panya Seksarn, Yongmin Tang, Keon Hee Yoo, Bharat Agarwal, Godfrey C.F. Chan, Rashmi Dalvi, Hiroki Hori, Muhammad Saghir Khan, Alice Yu, Akira Nakagawara
JCO Global Oncology.2023;[Epub] CrossRef

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Pediatric Adenocarcinoma in Korea: A Multicenter Study: Hee-Beom Yang, Jung-Man Namgoong, Ki Hoon Kim, Dae Yeon Kim, Jinyoung Park, Hyun Beak Shin, Joong Kee Youn, Sanghoon Lee, Ji Won Lee, Sung Eun Jung, Jae Hee Chung, Yun-Mee Choe, Tae Gil Heo, In Geol Ho, Hyun-Young Kim; Cancer Res Treat. 2020;52(1):117-127. Published online June 3, 2019; DOI: https://doi.org/10.4143/crt.2019.092

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Purpose
Adenocarcinoma is an extremely rare malignancy in the pediatric population. Research regarding pediatric adenocarcinoma is very rare in Korea. This study aimed to investigate the clinical features of pediatric adenocarcinomas of various primary organ sites in Korea.
Materials and Methods
Pediatric patients under 18 years, diagnosed with adenocarcinoma of various sites between January 1995 and December 2016, were included. We retrospectively reviewed patient and tumor characteristics and calculated survival estimates, reported as 5-year survival rate and 95% confidence interval.
Results
Of 80 patients (median age, 15 years; range, 10 to 17 years), 37 (46.3%) were men, and 24 (30%) had a family history of cancer or underlying disease relevant to malignancy. The cancer locations were the colon and rectum (n=32), ovaries (n=18), stomach (n=15), lung (n=4), small bowel (n=1), and other sites (n=10). Totally, 54.8% patients (42/77) had stage 3 or 4 disease. The median follow-up period was 2.0 years (range, 0 to 20.4). The 5-year overall survival estimate for all patients, and for those with stomach, colorectal, ovarian, and other cancer sites were 57.9%±11.5%, 58.2%±25.7%, 41.5%±18.2%, 87.5%±16.2%, and 64.0%±34.4%, respectively. The 5-year survival rate differed significantly between categories of adenocarcinomas into gastrointestinal (GI) (44.7%) and non-GI adenocarcinomas (78.8%) (p=0.007). The 5-year survival rate also differed significantly according to carcinoembryonic antigen level (69.3% in < 3 ng/mL, 23.8% in > 3 ng/mL; p < 0.001).
Conclusion
In pediatric patients, adenocarcinomas arise from various organs and are often diagnosed at advanced stages. Large, prospective studies for their accurate clinical characteristics and prognostic factors are needed.

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Pretreatment level of circulating tumor cells is associated with lymph node metastasis in papillary thyroid carcinoma patients with ≤ 55 years old
Ming Yu, Jiaqin Deng, Yihua Gu, Yeqian Lai, Yuedong Wang
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Nomogram to predict central lymph node metastasis in papillary thyroid carcinoma
Dehui Qiao, Xian Deng, Ruichen Liang, Xu Li, Rongjia Zhang, Zhi Lei, Hui Yang, Xiangyu Zhou
Clinical & Experimental Metastasis.2024; 41(5): 613. CrossRef
Artificial intelligence–based prediction of cervical lymph node metastasis in papillary thyroid cancer with CT
Cai Wang, Pengyi Yu, Haicheng Zhang, Xiao Han, Zheying Song, Guibin Zheng, Guangkuo Wang, Haitao Zheng, Ning Mao, Xicheng Song
European Radiology.2023; 33(10): 6828. CrossRef
Primary lung adenocarcinoma in three adolescent patients affected by bone sarcomas
Luisella Righi, Alberto Righi, Simona Vatrano, Ida Rapa, Angela Listì, Jasna Metovic, Michele Rocca, Mariacristina Salone, Paolo Giovenali, Angelo Sidoni, Fabrizio Tabbò, Angelo Paolo Dei Tos, Marco Volante, Mauro Papotti
Virchows Archiv.2021; 478(6): 1125. CrossRef
Case Report: Primary Bilateral Minimally Invasive Adenocarcinoma of the Lungs in an 11-Year-Old Child: A Rare Case
Xing Lei, Yongfei Zheng, Guohua Zhang, Hailan Zheng
Frontiers in Surgery.2021;[Epub] CrossRef

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NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia: Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo; Cancer Res Treat. 2018;50(3):872-882. Published online September 13, 2017; DOI: https://doi.org/10.4143/crt.2017.283

Abstract PDF PubReader ePub

Purpose
We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL).
Materials and Methods
Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated.
Results
A total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p < 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p < 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p < 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group.
Conclusion
NUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.

Citations

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Editorial Response to the Letter Relating to our Article “Predicting Adverse Events to Thiopurines in IBD: Are We a Step Closer?”
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The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia
Muhammad Muhammad, Maher Saifo, Majd Aljamali, Mousa Alali, Khaled M. Ghanem
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Mercaptopurine induced myelosuppression in a child with a NUDT15 rs116855232 homozygous variant
Navya Gupta, Latha Sneha Magatha, Dhaarani Jayaraman, Julius Xavier Scott, Sharon Benita Antony, Teena Koshy
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Density functional study of transition metal (Fe,Co,Ni)‐doped C60 fullerenes as 6‐thioguanine delivery system
ShiQuan Wu, Li Li, QiQi Liang, HuaXu Gao, DeYuan Hu, TianYu Tang, Yanlin Tang
Applied Organometallic Chemistry.2023;[Epub] CrossRef
The influence of NUDT15 variants on 6-mercaptopurine-induced neutropenia in Vietnamese pediatric acute lymphoblastic leukemia
Mai-Lan Nguyen, Anh Vu Hoang, Bich Tram Duong, Nguyen The Nguyen Phung
Human Genetics and Genomics Advances.2023; 4(2): 100183. CrossRef
NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China
XiaoXia Wei, Jing Zhuang, Na Li, Bin Zheng, Hong Sun, JiaQin Cai, Xuhui Huang, Guifeng Zhang, Jie Zhuang
International Journal of Hematology.2022; 115(2): 278. CrossRef
NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine
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Drug Metabolism and Pharmacokinetics.2022; 43: 100436. CrossRef
NUDT15 Genetic Variants in Chinese Han, Uighur, Kirghiz, and Dai Nationalities
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Kok-Siong Poon, Izz Irfan B. Imran, Silvester Kheng-Han Chew, Patrice Tan, Karen Mei-Ling Tan
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NUDT15Genotyping in Thiopurine Drug Therapy
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Laboratory Medicine Online.2022; 12(4): 217. CrossRef
The Effect of NUDT15, TPMT, APEX1, and ITPA Genetic Variations on Mercaptopurine Treatment of Pediatric Acute Lymphoblastic Leukemia
Jae Min Lee, Ye Jee Shim, Do-Hoon Kim, Nani Jung, Jung-Sook Ha
Children.2021; 8(3): 224. CrossRef
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Abdelbaset A. Elzagallaai, Bruce C. Carleton, Michael J. Rieder
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DNA-thioguanine nucleotide as a treatment marker in acute lymphoblastic leukemia patients with NUDT15 variant genotypes
Hee Young Ju, Ji Won Lee, Hee Won Cho, Ju Kyung Hyun, Youngeun Ma, Eun Sang Yi, Keon Hee Yoo, Ki Woong Sung, Rihwa Choi, Hong Hoe Koo, Soo-Youn Lee, A. M. Abd El-Aty
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Ann M. Moyer
Clinical Biochemistry.2021; 92: 1. CrossRef
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Zhao-Yang Chen, Yang-Hui Zhu, Ling-Yan Zhou, Wei-Qiao Shi, Zhou Qin, Bin Wu, Yu Yan, Yu-Wen Pei, Ning-Ning Chao, Rui Zhang, Mi-Ye Wang, Ze-Hao Su, Xiao-Jun Lu, Zhi-Yao He, Ting Xu
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Gangling Pu, Yali Wang, Shaoqin Duan, Jingpei Chen, Chunhui Yang, Tingting Cui, Chunlian Fang, Yan Zhou, Han Zhang, Xin Tian
Pediatrics International.2021; 63(7): 790. CrossRef
Significance of TPMT and NUDT15 variants in 6-mercaptopurine metabolism in acute lymphoblastic leukaemia/lymphoma patients
E. S. Kotova, O. A. Gavrilina, A. B. Sudarikov
Russian journal of hematology and transfusiology.2021; 66(2): 253. CrossRef
NUDT15 c.415C>T Polymorphism Predicts 6-MP Induced Early Myelotoxicity in Patients with Acute Lymphoblastic Leukemia Undergoing Maintenance Therapy
Aswin Anand Pai, Ajith Mohan, Esther Sathya Bama Benjamin, Raveen Stephen Stallon Illangeswaran, Infencia Xavier Raj, Nancy Beryl Janet, Arun Kumar Arunachalam, ML Kavitha, Uday Kulkarni, Anup J Devasia, NA Fouzia, Aby Abraham, Alok Srivastava, Biju Georg
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Yue Zhou, Li Wang, Xiao‐Ying Zhai, Li Wen, Fang Tang, Fan Yang, Xi‐Ting Liu, Lei Dong, Li‐Juan Zhi, Hai‐Yan Shi, Guo‐Xiang Hao, Yi Zheng, Evelyne Jacqz‐Aigrain, Tian‐You Wang, Wei Zhao
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NUDT15 Genetic Variants are Related to Thiopurine-Induced Neutropenia in Thai Children with Acute Lymphoblastic Leukemia
Apichaya Puangpetch, Rawiporn Tiyasirichokchai, Samart Pakakasama, Supaporn Wiwattanakul, Usanarat Anurathapan, Suradej Hongeng, Chonlaphat Sukasem
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Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia
Rihwa Choi, Insuk Sohn, Min‐Ji Kim, Hye In Woo, Ji Won Lee, Youngeun Ma, Eun Sang Yi, Hong Hoe Koo, Soo‐Youn Lee
British Journal of Clinical Pharmacology.2019; 85(7): 1585. CrossRef
Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients
Xia Zhu, Kang Chao, Miao Li, Wen Xie, Hong Zheng, Jin-Xin Zhang, Pin-Jin Hu, Min Huang, Xiang Gao, Xue-Ding Wang
World Journal of Gastroenterology.2019; 25(38): 5850. CrossRef
Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report
Juan Cheng, Hao Zhang, Hai‑Zhen Ma, Juan Li
Experimental and Therapeutic Medicine.2019;[Epub] CrossRef
Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping
Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa
Journal of Gastroenterology.2018; 53(2): 172. CrossRef

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ALK Protein Expression Is Related to Neuroblastoma Aggressiveness But Is Not Independent Prognostic Factor: Ji Won Lee, Sung Hye Park, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyo Seop Ahn; Cancer Res Treat. 2018;50(2):495-505. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.577

Abstract PDF PubReader ePub

Purpose
In this study, anaplastic lymphoma kinase (ALK) mutation and amplification, ALK protein expression, loss of the nuclear alpha thalassemia/mental retardation syndrome X-linked (ATRX) protein, and telomerase reverse transcriptase (TERT) protein expressionwere studied to investigate potential correlations between these molecular characteristics and clinical features or outcomes in neuroblastoma.
Materials and Methods
Seventy-two patients were enrolled in this study. Polymerase chain reaction amplification and direct sequencing were used for mutation analysis. ALK and MYCN amplifications were detected by fluorescence in situ hybridization. Protein expressionwas evaluated by immunohistochemical (IHC) staining.
Results
ALK mutation was found in only two patients (4.1%); ALK amplification was not detected. ALK positivity, loss of nuclear ATRX protein, TERT positivity by IHC were detected in 40 (55.6%), nine (13.0%), and 42 (59.2%) patients, respectively. The incidence of ALK expression increased in accordance with increasing tumor stage (p=0.001) and risk group (p < 0.001). The relapse rate was significantly higher in ALK⁺ patients compared to that of other patients (47.5% vs. 11.3%, p=0.007). However, there was no significant difference in relapse rate when the survival analysis was confined to the high-risk patients.
Conclusion
Although ALK mutation was rare and no amplification was observed, ALK protein expression was found in a significant number of patients and was correlated with advanced stage and high-risk neuroblastoma. ALK protein expression could be considered as a marker related to the aggressive neuroblastoma, but it was not the independent prognostic factor for the outcome.

Citations

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Immunohistochemical expression of anaplastic lymphoma kinase in neuroblastoma and its relations with some clinical and histopathological features
Thu Dang Anh Phan, Thao Quyen Nguyen, Nhi Thuy To, Thien Ly Thanh, Dat Quoc Ngo
Journal of Pathology and Translational Medicine.2024; 58(1): 29. CrossRef
Multi-omics revealed that ELAVL3 regulates MYCN in neuroblastoma via immunogenic cell death: Risk stratification and experimental research
Peng Hong, Zaihong Hu, Jie Lin, Kongkong Cui, Zhiqiang Gao, Xiaomao Tian, Qinlin Shi, Tao Lin, Guanghui Wei
International Journal of Biological Macromolecules.2024; 282: 137045. CrossRef
Prominent Staining of MYCN Immunohistochemistry Predicts a Poor Prognosis in MYCN Non-Amplified Neuroblastoma
Manli Zhao, Weizhong Gu, Fei Liu, Lihua Yu, Yan Shu, Lei Liu, Jiahui Hu, Yang Liu, Hongfeng Tang, Jianhua Mao
Pediatric and Developmental Pathology.2023; 26(2): 124. CrossRef
ALKGene Mutation and ALK Protein Expression in Advanced Neuroblastoma and the Potential Value in Risk Stratification in Fine-Needle Aspiration Biopsy Samples
Neha Bhardwaj, Manish Rohilla, Upasana Gautam, Amita Trehan, Deepak Bansal, Nandita Kakkar, Radhika Srinivasan
American Journal of Clinical Pathology.2023;[Epub] CrossRef
Rapid detection of telomerase expression of neuroblastoma in paraffin-embedded tissue: combination of in situ hybridisation and quantitative PCR
Manli Zhao, Zhonghai Guan, Liang Gong, Fei Liu, Weizhong Gu, Lei Liu, Kewen Jiang, Jiabin Cai, Chunyue Feng, Chik Hong Kuick, Kenneth Tou En Chang, Jinhu Wang, Hongfeng Tang, Minzhi Yin, Jianhua Mao
Pathology.2023; 55(7): 958. CrossRef
Interactions of Butyrylcholinesterase with Neuroblastoma-associated Oncoproteins
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
Current Enzyme Inhibition.2023; 19(2): 109. CrossRef
Combined Detection of Copy Number Variations of MYCN and ALK using Droplet Digital Polymerase Chain Reaction to Identify High-Risk Patients with Neuroblastoma
Trupti Trivedi, Kinjal Panchal, Neha Bhalala, Priti Trivedi, Harsha Panchal
World Neurosurgery.2022; 159: e48. CrossRef
ALK expression, prognostic significance, and its association with MYCN expression in MYCN non-amplified neuroblastoma
Dinesh Babu Somasundaram, Sheeja Aravindan, Nandita Gupta, Zhongxin Yu, Ashley Baker, Natarajan Aravindan
World Journal of Pediatrics.2022; 18(4): 285. CrossRef
Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo
Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Erin M. McIntyre, John G. Sharp, Don W. Coulter
Journal of Pediatric Hematology/Oncology.2022; 44(6): 293. CrossRef
Differential Impact of ALK Mutations in Neuroblastoma
Tara O'Donohue, Nitya Gulati, Audrey Mauguen, Brian H. Kushner, Neerav Shukla, M. I. Rodriguez-Sanchez, Nancy Bouvier, Stephen Roberts, Ellen Basu, Nai-Kong Cheung, Shakeel Modak
JCO Precision Oncology.2021; (5): 492. CrossRef
The challenge of defining “ultra‐high‐risk” neuroblastoma
Daniel A. Morgenstern, Rochelle Bagatell, Susan L. Cohn, Michael D. Hogarty, John M. Maris, Lucas Moreno, Julie R. Park, Andrew D. Pearson, Gudrun Schleiermacher, Dominique Valteau‐Couanet, Wendy B. London, Meredith S. Irwin
Pediatric Blood & Cancer.2019;[Epub] CrossRef
ALK in Neuroblastoma: Biological and Therapeutic Implications
Ricky Trigg, Suzanne Turner
Cancers.2018; 10(4): 113. CrossRef

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Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Atypical Teratoid/Rhabdoid Tumor: Ki Woong Sung, Do Hoon Lim, Eun Sang Yi, Young Bae Choi, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Ji Hye Kim, Yeon-Lim Suh, Yoo Sook Joung, Hyung Jin Shin; Cancer Res Treat. 2016;48(4):1408-1419. Published online April 1, 2016; DOI: https://doi.org/10.4143/crt.2015.347

Abstract PDF PubReader ePub

Purpose
We prospectively evaluated the effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in improving the survival of patients with atypical teratoid/rhabdoid tumors while reducing the risks of late adverse effects from radiotherapy (RT).
Materials and Methods
For young children (< 3 years old), tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy. RT was deferred until after 3 years of age unless the tumor showed relapse or progression. For older patients (> 3 years old), RT including reduced-dose craniospinal RT (23.4 or 30.6 Gy) was administered either after two cycles of induction chemotherapy or after surgery, and tandem HDCT/auto-SCT was administered after six cycles of induction chemotherapy.
Results
A total of 13 patients (five young and eight older) were enrolled from November 2004 to June 2012. Eight patients, including all five young patients, had metastatic disease at diagnosis. Six patients (four young and two older) experienced progression before initiation of RT, and seven were able to proceed to HDCT/auto-SCT without progression during induction treatment. Three of six patients who experienced progression during induction treatment underwent HDCT/auto-SCT as salvage treatment. All five young patients died from disease progression. However, four of the eight older patients remain progression-freewith a median follow-up period of 64 months (range, 39 to 108 months). Treatment-related late toxicities were acceptable.
Conclusion
The required dose of craniospinal RT might be reduced in older patients if the intensity of chemotherapy is increased. However, early administration of RT should be considered to prevent early progression in young patients.

Citations

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Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors
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Pediatric Blood & Cancer.2023;[Epub] CrossRef
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Clinical Significance of Tyrosine Hydroxylase mRNA Transcripts in Peripheral Blood at Diagnosis in Patients with Neuroblastoma: Na Hee Lee, Meong Hi Son, Young Bae Choi, Eunsang Yi, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo; Cancer Res Treat. 2016;48(4):1399-1407. Published online March 24, 2016; DOI: https://doi.org/10.4143/crt.2015.481

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to investigate the clinical significance of tyrosine hydroxylase (TH) expression in peripheral blood (PB) at diagnosis in patients with neuroblastoma.
Materials and Methods
TH mRNA expression in PB was measured by reverse transcription quantitative real-time polymerase chain reaction in 210 patients who were newly diagnosed with neuroblastoma from July 2005 to June 2015 and the clinical significance of TH expression in PB at diagnosis was evaluated.
Results
TH expression was positive in 60 patients (28.6%). Fifty of 60 TH-positive patients had metastatic tumors and the remaining 10 had localized tumors. TH expression was associated with high-risk features (i.e., advanced stage, older age, unfavorable pathology, and MYCN amplification) at diagnosis. Among TH-positive patients, higher TH expression level was observed in high-risk patients than in low- or intermediate-risk patients (p=0.035). The probability of 5-year progression-free survival (PFS) was lower in TH-positive patients than in TH-negative patients (63.8±6.9% vs. 94.7±2.1%, p < 0.001). In analysis confined to high-risk patients, the 5-year probability of PFS remained lower in TH-positive patients (55.7±8.2% vs. 89.6±5.8%, p < 0.001). Among TH-positive patients, a higher expression level of TH was associated with a worse outcome. In multivariate analyses, positive TH expression in PB at diagnosis was an independent poor prognostic factor for PFS.
Conclusion
The treatment intensity should be tailored according to TH expression in PB at diagnosis.

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Extra-cranial Malignant Rhabdoid Tumor in Children: A Single Institute Experience: Che Ry Hong, Hyoung Jin Kang, Hee Young Ju, Ji Won Lee, Hyery Kim, Sung-Hye Park, Il Han Kim, Kyung Duk Park, Hee Young Shin; Cancer Res Treat. 2015;47(4):889-896. Published online January 2, 2015; DOI: https://doi.org/10.4143/crt.2013.176

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Purpose
Malignant rhabdoid tumor (MRT) is a rare and highly aggressive tumor that affects young children. Due to its extreme rarity, most of the available data are based on retrospective case series. To add to the current knowledge of this disease, we reviewed the patients treated for extra-cranial MRT in our institute. Materials and Methods A retrospective medical record review was conducted on children treated for pathologically confirmed extra-cranial MRT at Seoul National University Children’s Hospital between January 2003 and May 2013. Results Eleven patients (7 boys, 4 girls) were diagnosed with extra-cranial MRT at a median age of 9 months old. INI1 staining was important in the pathological confirmation. Six patients (55%) had renal MRT and five (45%) had soft tissue MRT. Five patients (45%) had metastases at diagnosis. All patients underwent chemotherapy, eight patients (73%) underwent surgery, six patients (55%) received therapeutic radiotherapy, and four patients (36%) underwent high dose chemotherapy with autologous stem cell rescue (HDCT/ASCR) with melphalan, etoposide, and carboplatin. Five patients (45%) died of disease following progression (n=3) or relapse (n=2), however, there was no treatment related mortality. The overall survival of the cohort was 53.0% and the event-free survival was 54.5% with a median follow-up duration of 17.8 months (range, 2.3 to 112.3 months). Conclusion Extra-cranial MRT is still a highly aggressive tumor in young children. However, the improved survival of our cohort is promising and HDCT/ASCR with melphalan, etoposide, and carboplatin may be a promising treatment option.

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Clinical Outcome of Relapsed or Refractory Burkitt Lymphoma and Mature B-Cell Lymphoblastic Leukemia in Children and Adolescents: Hyery Kim, Eun Sil Park, Soo Hyun Lee, Hong Hoe Koo, Hyo Sun Kim, Chuhl Joo Lyu, So Eun Jun, Young Tak Lim, Hee Jo Baek, Hoon Kook, Ji Won Lee, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, Hyeo Seop Ahn; Cancer Res Treat. 2014;46(4):358-365. Published online July 21, 2014; DOI: https://doi.org/10.4143/crt.2013.047

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Purpose
Despite the rapid improvement in survival rate from Burkitt lymphoma and mature B-cell lymphoblastic leukemia (B-ALL) in children, a small subset of patients do not respond to first-line chemotherapy or experience relapse (RL). Herein, we report the clinical characteristics and outcomes of these patients.
Materials and Methods
RL or refractory Burkitt lymphoma and mature B-ALL in 125 patients diagnosed from 1990 to 2009 were retrospectively analyzed.
Results
Nineteen patients experienced RL or progressive disease (PD). Among them, 12 patients had PD or RL less than six months after initial treatment and seven had late RL. Seven patients achieved complete response (CR), 11 had PD, and one had no more therapy. Six patients who achieved CR survived without evidence of disease and four of them underwent high-dose chemotherapy (HDC) followed by stem cell transplantation (SCT). However, 11 patients who failed to obtain CR eventually died of their disease. Five-year overall survival (OS) was 31.6±10.7%. OS of patients with late RL was superior to that of patients with early RL (57.1±18.7%, vs. 16.7±10.8%, p=0.014). Achievement of CR after reinduction had significant OS (p < 0.001). OS for patients who were transplanted was superior (p < 0.01). In multivariate analysis, achievement of CR after reinduction chemotherapy showed an association with improved OS (p=0.05).
Conclusion
Late RL and chemotherapy-sensitive patients have the chance to achieve continuous CR using HDC/SCT, whereas patients who are refractory to retrieval therapy have poor prognosis. Therefore, novel salvage strategy is required for improvement of survival for this small set of patients.

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Clinical Characteristics and Treatment Results of Pediatric Osteosarcoma: The Role of High Dose Chemotherapy with Autologous Stem Cell Transplantation: Ji Won Lee, Hyery Kim, Hyoung Jin Kang, Han-Soo Kim, Sung-Hye Park, In-One Kim, Hyo Seop Ahn, Hee Young Shin; Cancer Res Treat. 2008;40(4):172-177. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.172

Abstract PDF PubReader ePub

Purpose

In this study, we investigated the clinical characteristics and treatment results of osteosarcoma during the past 7 years, and evaluated the role of high dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT).

Materials and Methods

We retrospectively analyzed the clinical data of patients who were diagnosed as osteosarcoma at our center from January, 2000 to December, 2007.

Results

The 5-year overall survival and event-free survival of the patients were 72.6% and 55.9%, respectively. Seventeen (41.5%) patients showed disease progression during treatment or relapse after the end of treatment. The patients who had metastasis at diagnosis or who had a lower grade of necrosis after neoadjuvant chemotherapy showed decreased overall and event-free survival. Four patients received ASCT after HDCT, and 3 of them are alive without disease.

Conclusions

The patients who relapsed or had refractory osteosarcoma or who had metastasis at diagnosis or a lower grade of necrosis after neoadjuvant chemotherapy showed poor prognosis. HDCT with ASCT could be an alternative treatment option for these patients.

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Clinical Results of Chemotherapy based Treatment in Retinoblastoma Patients: A Single Center Experience: Hyery Kim, Ji Won Lee, Hyoung Jin Kang, Hyeon Jin Park, Yoon Yi Kim, Hee Young Shin, Young Suk Yu, Il Han Kim, Hyo Seop Ahn; Cancer Res Treat. 2008;40(4):164-171. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.164

Abstract PDF PubReader ePub

Purpose

Retinoblastoma is the most common intraocular malignancy in children. Since the 1990s, chemotherapy was indicated for intraocluar disease to reduce the frequency of enucleation and spare the complications associated with external beam radiation. In this study, we analyzed treatment results of retinoblastoma in our institute.

Materials and Methods

Datas from children diagnosed with retinoblastoma and treated at Seoul National University Children's Hospital between 1986 and 2008 were analyzed retrospectively. We utilized cyclophosphamide, vincristine, adriamycin, and methotrexate (CVAM) for OPD-based adjuvant chemotherapy. From 1990, primary chemotherapy was administered to patients with intraocular disease for eyeball-saving and patients received a combination of etoposide, vincristine, cisplatin (or ifosfamide) as a moderately intensive regimen, or a combination of cisplatin, doxorubicin, etoposide, and cycophosphamide (CDEC) as a highly intensive regimen.

Results

One hundred eighteen children were analyzed. There were 68 unilateral and 50 bilateral diseases. The median age at diagnosis was 1 year and Reese-Ellsworth stage V was the most common stage at the time of diagnosis. All patients were treated by chemotherapy-based multimodality methods, and primary chemotherapy was administered to 80 patients. The 10-year overall and event-free survival rate of all patients were 93.9% and 91.6%, respectively. Two patients who died were in the CDEC regimen group, but there was no significant statistical difference in survival rates by chemotherapy regimens. Fifty-six of 114 eyeballs were saved after primary chemotherapy-based treatment, and the eyeball-saving rate was 49.1%. Six patients relapsed after enucleation and 2 patients were treated successfully after autologous PBSCT. Osteosarcoma occurred in 2 patients as a secondary malignancy, and facial asymmetry after radiotherapy was the most common long-term sequelae.

Conclusions

In this study, the overall and event-free survival rates of retinoblastoma were satisfactory and eye-saving was possible with primary chemotherapy. Development of new chemotherapeutic regimens and a team approach are necessary to improve the eyeball-saving rate.

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