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Original Articles
Sarcoma
Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin Song, Guangqi Li, Zhenqi Zhang, Yinbo Liu, Huiqing Jia, Chao Zhang, Jigang Wang, Yanjiao Hu, Fengyun Hao, Xianglan Liu, Yunxia Xie, Ding Ma, Ganghua Li, Zaixian Tai, Xiaoming Xing
Cancer Res Treat. 2025;57(1):250-266.   Published online July 10, 2024
DOI: https://doi.org/10.4143/crt.2024.343
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs).
Materials and Methods
Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients.
Results
A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804.
Conclusion
USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Citations

Citations to this article as recorded by  
  • Mitochondrial Ribosomal Proteins and Cancer
    Huiyi Wu, Xiaowei Zhu, Huilin Zhou, Min Sha, Jun Ye, Hong Yu
    Medicina.2025; 61(1): 96.     CrossRef
  • Molecular Insights in Endometrial Stromal Sarcomas: Exploring New Targets for Novel Therapeutic Approaches
    Alice Costa, Annalisa Astolfi, Livia Gozzellino, Margherita Nannini, Gianandrea Pasquinelli, Maria Abbondanza Pantaleo
    Biomolecules.2025; 15(2): 265.     CrossRef
  • 2,252 View
  • 135 Download
  • 2 Web of Science
  • 2 Crossref
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Lung and Thoracic cancer
Genomic Landscape of Pulmonary Sarcomatoid Carcinoma
Hyun Jung Kwon, Sejoon Lee, Yeon Bi Han, Jeonghyo Lee, Soohyeon Kwon, Hyojin Kim, Jin-Haeng Chung
Cancer Res Treat. 2024;56(2):442-454.   Published online November 14, 2023
DOI: https://doi.org/10.4143/crt.2023.764
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples.
Materials and Methods
A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed.
Results
TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs.
Conclusion
Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

Citations

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  • PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma
    Shipra Agarwal, Chan Kwon Jung, Pranitha Gaddam, Mitsuyoshi Hirokawa, Takuya Higashiyama, Jen-Fan Hang, Wei-An Lai, Somboon Keelawat, Zhiyan Liu, Hee Young Na, So Yeon Park, Junya Fukuoka, Shinya Satoh, Zhanna Mussazhanova, Masahiro Nakashima, Kennichi Ka
    American Journal of Surgical Pathology.2024; 48(10): 1233.     CrossRef
  • 3,759 View
  • 199 Download
  • 1 Web of Science
  • 1 Crossref
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Sarcoma
Case Series of Soft Tissue Sarcoma Patients with Brain Metastasis with Implications from Genomic and Transcriptomic Analysis
Changhee Park, Rokhyun Kim, Jaeyong Choi, Miso Kim, Tae Min Kim, Ilkyu Han, Jong-Il Kim, Han-Soo Kim
Cancer Res Treat. 2024;56(2):665-674.   Published online September 27, 2023
DOI: https://doi.org/10.4143/crt.2023.864
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles.
Materials and Methods
We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas.
Results
The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus.
Conclusion
The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.
  • 4,360 View
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Gynecologic cancer
Genomic and Transcriptomic Characterization Revealed the High Sensitivity of Targeted Therapy and Immunotherapy in a Subset of Endometrial Stromal Sarcoma
Nan Kang, Yinli Zhang, Shichao Guo, Ran Chen, Fangzhou Kong, Shuchun Wang, Mingming Yuan, Rongrong Chen, Danhua Shen, Jianliu Wang
Cancer Res Treat. 2023;55(3):978-991.   Published online February 2, 2023
DOI: https://doi.org/10.4143/crt.2022.1647
AbstractAbstract PDFPubReaderePub
Purpose
The unique chromosomal rearrangements of endometrial stromal sarcoma (ESS) make it possible to distinguish high-grade ESS (HGESS) and low-grade ESS (LGESS) from the molecular perspective. Analysis of ESS at the genomic and transcriptomic levels can help us achieve accurate diagnosis of ESS and provide potential therapy options for ESS patients.
Materials and Methods
A total of 36 ESS patients who conducted DNA- and/or RNA-based next-generation sequencing were retrospectively enrolled in this study. The molecular characteristics of ESS at genomic and transcriptomic levels, including mutational spectrum, fusion profiles, gene expression and pathway enrichment analysis and features about immune microenvironment were comprehensively explored.
Results
TP53 and DNMT3A mutations were the most frequent mutations. The classical fusions frequently found in HGESS (ZC3H7B-BCOR and NUTM2B-YWHAE) and LGESS (JAZF1-SUZ12) were detected in our cohort. CCND1 was significantly up-regulated in HGESS, while the expression of GPER1 and PGR encoding estrogen receptor (ER) and progesterone receptor (PR) did not differ significantly between HGESS and LGESS. Actionable mutations enriched in homologous recombination repair, cell cycle, and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathways were detected in 60% of HGESS patients. Genes with up-regulated expression in HGESS were significantly enriched in five immune-related pathways. Most HGESS patients (85.7%) had positive predictors of immunotherapy efficacy. Moreover, immune microenvironment analysis showed that HGESS had relatively high immune infiltration. The degree of immune infiltration in HGESS patients with ZC3H7B-BCOR fusion was relatively higher than that of those with NUTM2B-YWHAE fusion.
Conclusion
This study investigated the molecular characteristics of ESS patients at the genomic and transcriptomic levels and revealed the potentially high sensitivity of targeted therapy and immunotherapy in a subset of HGESS with specific molecular features, providing a basis for guiding decision-making of treatment and the design of future clinical trials on precision therapy.

Citations

Citations to this article as recorded by  
  • Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
    Yaolin Song, Guangqi Li, Zhenqi Zhang, Yinbo Liu, Huiqing Jia, Chao Zhang, Jigang Wang, Yanjiao Hu, Fengyun Hao, Xianglan Liu, Yunxia Xie, Ding Ma, Ganghua Li, Zaixian Tai, Xiaoming Xing
    Cancer Research and Treatment.2025; 57(1): 250.     CrossRef
  • Molecular Insights in Endometrial Stromal Sarcomas: Exploring New Targets for Novel Therapeutic Approaches
    Alice Costa, Annalisa Astolfi, Livia Gozzellino, Margherita Nannini, Gianandrea Pasquinelli, Maria Abbondanza Pantaleo
    Biomolecules.2025; 15(2): 265.     CrossRef
  • Risk factors, survival analysis, and nomograms for high-grade endometrial stromal sarcoma patients with distant metastasis: a population-based study (2010–2019)
    Cheng Wang, Dongni Liang, Wei Kuang, Huanxin Sun, Yuling Kou, Wei Wang, Jing Zeng
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival
    Muwen Nie, Zhao Sun, Ningning Li, Liangrui Zhou, Shuchun Wang, Mingming Yuan, Rongrong Chen, Lin Zhao, Ji Li, Chunmei Bai
    Thoracic Cancer.2024; 15(19): 1502.     CrossRef
  • Single-cell RNA-seq reveals FGF12 as a prognostic biomarker in low-grade endometrial stromal sarcoma
    Yu Miao, Meng Dong, Qiyin Zhou, Julia Thiel, Na Li, Ying Cai, Dan Yuan, Haitao Wang, Su-Han Jin, Hua Yang, Jinjing Wang, Benjamin Frey, Udo S. Gaipl, Hu Ma, Jian-Guo Zhou
    Frontiers in Immunology.2024;[Epub]     CrossRef
  • High-Grade Endometrial Mesenchymal Sarcoma: Current Status and Future Trends
    Zhang Lushuang, Zhao Liubiqi
    Clinical Journal of Obstetrics and Gynecology.2023; 6(3): 132.     CrossRef
  • 4,584 View
  • 192 Download
  • 4 Web of Science
  • 6 Crossref
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Sarcoma
Comprehensive Molecular Characterization of Soft Tissue Sarcoma for Prediction of Pazopanib-Based Treatment Response
Jung Yong Hong, Hee Jin Cho, Kum-Hee Yun, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Sang Kyum Kim, Yurimi Lee, Yoon-La Choi, Minsuk Kwon, Hyo Song Kim, Jeeyun Lee
Cancer Res Treat. 2023;55(2):671-683.   Published online September 27, 2022
DOI: https://doi.org/10.4143/crt.2022.251
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Even though pazopanib, a multitargeted tyrosine kinase inhibitor, has been approved for refractory soft tissue sarcoma (STS), little is known about the molecular determinants of the response to pazopanib. We performed integrative molecular characterization to identify potential predictors of pazopanib efficacy.
Materials and Methods
We obtained fresh pre-treatment tumor tissue from 35 patients with advanced STS receiving pazopanib-based treatment. Among those, 18 (51.4%) received pazopanib monotherapy, and the remaining 17 (48.6%) received pazopanib in combination with durvalumab, programmed death-ligand 1 blockade. Whole-exome and transcriptome sequencing were performed for each tumor and patient germline DNA.
Results
Of the 35 patients receiving pazopanib-based treatment, nine achieved a partial response (PR), resulting in an objective response rate (ORR) of 27.3%, and the median progression-free survival (PFS) was 6.0 months. Patients with CDK4 amplification (copy ratio tumor to normal > 2) exhibited shorter PFS (3.7 vs. 7.9 months, p=2.09×10–4) and a poorer response (ORR; 0% vs. 33.3%) compared to those without a gene amplification (copy ratio ≤ 2). Moreover, non-responders demonstrated transcriptional activation of CDK4 via DNA amplification, resulting in cell cycle activation. In the durvalumab combination cohort, seven of the 17 patients (41.2%) achieved a PR, and gene expression analysis revealed that durvalumab responders exhibited high immune/stromal cell infiltration, mainly comprising natural killer cells, compared to non-responders as well as increased expression of CD19, a B-cell marker.
Conclusion
Despite the limitation of heterogeneity in the study population and treatment, we identified possible molecular predictors of pazopanib efficacy that can be employed in future clinical trials aimed at evaluating therapeutic strategies.

Citations

Citations to this article as recorded by  
  • Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial
    Hee Jin Cho, Kum-Hee Yun, Su-Jin Shin, Young Han Lee, Seung Hyun Kim, Wooyeol Baek, Yoon Dae Han, Sang Kyum Kim, Hyang Joo Ryu, Joohee Lee, Iksung Cho, Heounjeong Go, Jiwon Ko, Inkyung Jung, Min Kyung Jeon, Sun Young Rha, Hyo Song Kim
    Nature Communications.2024;[Epub]     CrossRef
  • The high-density lipoprotein binding protein HDLBP is an unusual RNA-binding protein with multiple roles in cancer and disease
    Jonathan Feicht, Ralf-Peter Jansen
    RNA Biology.2024; 21(1): 312.     CrossRef
  • Intracranial Relapse in Pediatric Sarcoma
    Danielle E. Smith, Tyler Hamby, Kenneth Heym, Ashraf Mohamed, Kelly L. Vallance, Anish Ray
    Journal of Pediatric Hematology/Oncology.2023; 45(7): e810.     CrossRef
  • 5,800 View
  • 209 Download
  • 3 Web of Science
  • 3 Crossref
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Incidence Patterns and Outcomes of Ewing Sarcoma in South Korea (1999-2017): A Retrospective Analysis Using Korea Central Cancer Registry Data
Jun Ah Lee, Jiwon Lim, Dayeon Park, Hye Young Jin, Meerim Park, Hyeon Jin Park, Jong Woong Park, June Hyuk Kim, Hyun Guy Kang, Young-Joo Won
Cancer Res Treat. 2022;54(2):590-596.   Published online July 20, 2021
DOI: https://doi.org/10.4143/crt.2021.311
AbstractAbstract PDFPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • Twenty‐year outcome of prevalence, incidence, mortality and survival rate in patients with malignant bone tumors
    Yao Xu, Fanqi Shi, Yanting Zhang, Mengfan Yin, Xiuxin Han, Jinyan Feng, Guowen Wang
    International Journal of Cancer.2024; 154(2): 226.     CrossRef
  • A Machine Learning-Based Predictive Model for Predicting Lymph Node Metastasis in Patients With Ewing’s Sarcoma
    Wenle Li, Qian Zhou, Wencai Liu, Chan Xu, Zhi-Ri Tang, Shengtao Dong, Haosheng Wang, Wanying Li, Kai Zhang, Rong Li, Wenshi Zhang, Zhaohui Hu, Su Shibin, Qiang Liu, Sirui Kuang, Chengliang Yin
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • TrkC, a novel prognostic marker, induces and maintains cell survival and metastatic dissemination of Ewing sarcoma by inhibiting EWSR1-FLI1 degradation
    Min Soo Kim, Won Sung Lee, Hanki Lee, Wook Jin
    Cell Death & Disease.2022;[Epub]     CrossRef
  • 6,362 View
  • 128 Download
  • 2 Web of Science
  • 3 Crossref
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Clinicopathologic Characteristics and Clinical Outcome of Localized Liposarcoma: A Single-Center Experience over 25 Years and Evaluation of PD-L1 Expression
Heejung Chae, Jeong Eun Kim, Wanlim Kim, Jong-Seok Lee, Si Yeol Song, Min Hee Lee, Hye Won Chung, Kyung-Ja Cho, Joon Seon Song, Jin-Hee Ahn
Cancer Res Treat. 2022;54(2):579-589.   Published online July 6, 2021
DOI: https://doi.org/10.4143/crt.2021.496
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
For liposarcoma (LPS), clinical course and proper treatment strategies have not been well-established. Recently, immune-checkpoint inhibitors have shown potential efficacy in LPS. We aimed to describe the clinical course of LPS and evaluate the clinical impact of programmed death-ligand 1 (PD-L1).
Materials and Methods
We reviewed all consecutive patients (n=332) who underwent curative-intent surgery for localized LPS at Asan Medical Center between 1989 and 2017. PD-L1 testing was performed in well-differentiated and dedifferentiated LPS.
Results
The median age was 56 years with males comprising 60.8%. Abdomen-pelvis (47.6%) and well-differentiated (37.7%) were the most frequent primary site and histologic subtype, respectively. During a median follow-up of 81.2 months, recurrence was observed in 135 (40.7%), and 86.7% (117/135) were loco-regional. Well-differentiated subtype (hazard ratio [HR], 0.38), abdomen-pelvis origin (HR, 2.43), tumor size larger than 5 cm (HR, 1.83), positive resection margin (HR, 2.58), and postoperative radiotherapy (HR, 0.36) were significantly related with recurrence-free survival as well as visceral involvement (HR, 1.84) and multifocality (HR, 3.79) in abdomen-pelvis LPS. PD-L1 was positive in 31.5% (23/73) and 51.3% (39/76) of well-differentiated and dedifferentiated LPS, respectively, but had no impact on survival outcomes.
Conclusion
Clinical course of LPS was heterogeneous according to histology and anatomic location. Clear resection margin was important to lower recurrence and postoperative radiotherapy might have additional benefit. A decent portion of well-differentiated and dedifferentiated LPS were positive for PD-L1, but its prognostic role was unclear. Further research is needed to determine clinical implications of PD-L1, especially for advanced-stage LPS with unmet needs for effective systemic treatment.

Citations

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  • Recurrent Intrathoracic Liposarcoma: A Case Report and a Comprehensive Literature Review of a Rare Clinical Entity
    Vasileios Leivaditis , Manfred Dahm , Athanasios Papatriantafyllou, Hans-Georg Keul, Lydia Kohl, Hans-Joachim Schäfers
    Cureus.2024;[Epub]     CrossRef
  • Clinicopathological Features of Intrathoracic Liposarcoma—A Systematic Review with an Illustrative Case
    Kajetan Kiełbowski, Nikola Ruszel, Seweryn Adam Skrzyniarz, Małgorzata Edyta Wojtyś, Rafał Becht, Konrad Ptaszyński, Darko Gajić, Janusz Wójcik
    Journal of Clinical Medicine.2022; 11(24): 7353.     CrossRef
  • 6,465 View
  • 116 Download
  • 1 Web of Science
  • 2 Crossref
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Pediatric cancer
Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults
Hee Young Ju, Meerim Park, Jun Ah Lee, Hyeon Jin Park, Seog Yun Park, June Hyuk Kim, Hyun Guy Kang, Hee Chul Yang, Byung-Kiu Park
Cancer Res Treat. 2022;54(2):563-571.   Published online June 14, 2021
DOI: https://doi.org/10.4143/crt.2021.178
AbstractAbstract PDFPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • MGMT protein expression is a reliable predictive biomarker for temozolomide‐containing chemotherapy in osteosarcoma
    Yoshinori Uchihara, Katsutsugu Umeda, Yosuke Yamada, Hiroaki Ito, Keiji Tasaka, Kiyotaka Isobe, Ryo Akazawa, Naoko Kawabata, Satoshi Saida, Itaru Kato, Hidefumi Hiramatsu, Takashi Noguchi, Akio Sakamoto, Yoshiki Arakawa, Ayumu Arakawa, Nobuyuki Yamamoto,
    Cancer Science.2024; 115(10): 3394.     CrossRef
  • Anlotinib combined with radiotherapy and chemotherapy for recurrent pelvic osteosarcoma treatment: a case report and literature review
    Qian Chen, Kai Zheng, Ming Xu, Ning Yan, Gong Hai, Xiuchun Yu
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Irinotecan/temozolomide/vincristine

    Reactions Weekly.2022; 1910(1): 267.     CrossRef
  • Acetylenic Synthetic Betulin Derivatives Inhibit Akt and Erk Kinases Activity, Trigger Apoptosis and Suppress Proliferation of Neuroblastoma and Rhabdomyosarcoma Cell Lines
    Sylwia K. Król, Ewa Bębenek, Magdalena Dmoszyńska-Graniczka, Adrianna Sławińska-Brych, Stanisław Boryczka, Andrzej Stepulak
    International Journal of Molecular Sciences.2021; 22(22): 12299.     CrossRef
  • 6,803 View
  • 382 Download
  • 5 Web of Science
  • 4 Crossref
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Sarcoma
Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma
Zhengbo Hu, Lugen Li, Wenxing Lan, Xiao Wei, Xiangyuan Wen, Penghuan Wu, Xianliao Zhang, Xinhua Xi, Yufa Li, Liqi Wu, Wenhu Li, Xiaohong Liao
Cancer Res Treat. 2022;54(1):277-293.   Published online May 11, 2021
DOI: https://doi.org/10.4143/crt.2021.320
AbstractAbstract PDFPubReaderePub
Purpose
Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells.
Materials and Methods
Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP.
Results
A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice.
Conclusion
Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.

Citations

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  • Wee1 inhibitor PD0166285 sensitized TP53 mutant lung squamous cell carcinoma to cisplatin via STAT1
    Qi Li, Wenjie Yang, Qingyi Zhang, Daoming Zhang, Jun Deng, Binxin Chen, Ping Li, Huanqi Zhang, Yiming Jiang, Yangling Li, Bo Zhang, Nengming Lin
    Cancer Cell International.2024;[Epub]     CrossRef
  • BRK confers tamoxifen-resistance in breast cancer via regulation of tyrosine phosphorylation of CDK1
    Aditya Mandapati, Zhibin Ning, Akanksha Baharani, Kiven Erique Lukong
    Cellular Signalling.2023; 108: 110723.     CrossRef
  • Inhibiting WEE1 Augments the Antitumor Efficacy of Cisplatin in Urothelial Carcinoma by Enhancing the DNA Damage Process
    Yu-Li Su, Ling-Yi Xiao, Shih-Yu Huang, Chia-Che Wu, Li-Chung Chang, Yi-Hua Chen, Hao-Lun Luo, Chun-Chieh Huang, Ting-Ting Liu, Jei-Ming Peng
    Cells.2023; 12(11): 1471.     CrossRef
  • Network pharmacology-based research on the effect of angelicin on osteosarcoma and the underlying mechanism
    Yafang Zhang, Junqiang Wei, Lingwei Kong, Mingze Song, Yange Zhang, Xiangyu Xiao, Haiying Cao, Zhehong Li, Ning Yang, Yu Jin
    Aging.2023;[Epub]     CrossRef
  • Identification of Cell Subpopulations and Interactive Signaling Pathways From a Single-Cell RNA Sequencing Dataset in Osteosarcoma: A Comprehensive Bioinformatics Analysis
    Rong Wu, Xiaojie Dou, Haidong Li, Zhenguo Sun, Heng Li, Yuxin Shen, Wei Weng, Jikang Min
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • MicroRNAs and osteosarcoma: Potential targets for inhibiting metastasis and increasing chemosensitivity
    Negin Soghli, Gordon A. Ferns, Fatemeh Sadeghsoltani, Durdi Qujeq, Tooba Yousefi, Mostafa Vaghari-Tabari
    Biochemical Pharmacology.2022; 201: 115094.     CrossRef
  • Inhibiting WEE1 and IKK-RELA Crosstalk Overcomes TNFα Resistance in Head and Neck Cancers
    Zhengbo Hu, Ramya Viswanathan, Hui Cheng, Jianghong Chen, Xinping Yang, Angel Huynh, Paul Clavijo, Yi An, Yvette Robbins, Christopher Silvin, Clint Allen, Pinar Ormanoglu, Scott Martin, Shaleeka Cornelius, Anthony Saleh, Zhong Chen, Carter Van Waes, Ethan
    Molecular Cancer Research.2022; 20(6): 867.     CrossRef
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Real-World Clinical Outcomes and Prognostic Factors for Patients with Advanced Angiosarcoma who Received Systemic Treatment
Changhee Park, Miso Kim, Yoonjin Kwak, Kyung Chul Moon, Se Hyun Kim, Bhumsuk Keam, Yu Jung Kim, Tae Min Kim, Dong-Wan Kim
Cancer Res Treat. 2021;53(4):1195-1203.   Published online February 1, 2021
DOI: https://doi.org/10.4143/crt.2020.1337
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated.
Materials and Methods
We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions.
Results
Among the patients evaluated, 51 patients were male (68%) and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression free survival (mPFS) of 4.0 months (95% confidence interval [CI] 3.0–6.1), and a median overall survival (mOS) of 10.2 months (95% CI 7.0–14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 vs. 3.2 months, respectively, p=0.014) with a tendency for prolonged mOS (13.8 vs. 11.6 months, respectively, p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI 1.8–4.3) and a mOS of 5.4 months (95% CI 3.5–NA).
Conclusion
Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.

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Characteristics and Treatment Patterns of Patients with Advanced Soft Tissue Sarcoma in Korea
Hyo Song Kim, Chung Mo Nam, Suk-Yong Jang, Sun Kyu Choi, Minkyung Han, Seonmin Kim, Maria Victoria Moneta, Sae Young Lee, Jae Min Cho, Diego Novick, Sun Young Rha
Cancer Res Treat. 2019;51(4):1380-1391.   Published online February 18, 2019
DOI: https://doi.org/10.4143/crt.2018.476
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status.
Materials and Methods
The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases.
Results
A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis.
Conclusion
This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.

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Case Reports
PTEN Mutation Identified in Patient Diagnosed with Simultaneous Multiple Cancers
Hye Sung Won, Eun Deok Chang, Sae Jung Na, In Yong Whang, Dong Soo Lee, Sun Hyong You, Yong Seok Kim, Jeong Soo Kim
Cancer Res Treat. 2019;51(1):402-407.   Published online February 27, 2018
DOI: https://doi.org/10.4143/crt.2017.579
AbstractAbstract PDFPubReaderePub
PTEN hamartoma tumor syndrome is a spectrum of disorders characterized by unique phenotypic features including multiple hamartomas caused by mutations of the tumor suppressor gene PTEN. Cowden syndrome and Bannayan–Riley–Ruvalcaba syndrome are representative diseases, and both have several common clinical features and differences. Because PTEN mutations are associated with an increased risk of malignancy including breast, thyroid, endometrial, and renal cancers, cancer surveillance is an important element of disease management. We report a germline mutation of the PTEN (c.723dupT, exon 7) identified in a young woman with a simultaneous occurrence of breast cancer, dermatofibrosarcoma protuberans, and follicular neoplasm. This case suggests that it is critical for clinicians to recognize the phenotypic features associated with these syndromes to accurately diagnose them and provide preventive care.

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    Belinda Asare, Babita Panigrahi
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    Manjula Vinayak
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Pembrolizumab for Refractory Metastatic Myxofibrosarcoma: A Case Report
Haa-Na Song, Min Gyu Kang, Jeong Rang Park, Jin-Yong Hwang, Jung Hun Kang, Won Seop Lee, Gyeong-Won Lee
Cancer Res Treat. 2018;50(4):1458-1461.   Published online January 22, 2018
DOI: https://doi.org/10.4143/crt.2017.529
AbstractAbstract PDFPubReaderePub
Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of programmed death receptor ligand 1 antibody proven to be useful for numerous types of cancer cells. A patient had been diagnosed with metastatic myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic chemotherapy. The patient achieved a partial response during palliative chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this is the first case report demonstrating the efficacy of pembrolizumab for refractory myxofibrosarcoma.

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Original Articles
Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study
Yunjung Choi, Mi Sun Yun, Sang Hee Lim, Jeeyun Lee, Jin-Hee Ahn, Yu Jung Kim, Kyong Hwa Park, Young Suk Park, Ho Yeong Lim, Hyonggin An, Dong-Churl Suh, Yeul Hong Kim
Cancer Res Treat. 2018;50(1):175-182.   Published online March 30, 2017
DOI: https://doi.org/10.4143/crt.2016.535
AbstractAbstract PDFPubReaderePub
Purpose
This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for advanced soft tissue sarcoma, which has limited treatment options owing to its rare occurrence.
Materials and Methods
A total of 228 patients received GD therapy for advanced soft tissue sarcoma from 2009 to 2014 in Korea. We retrospectively reviewed the clinical medical records and claims data of these patients.
Results
A total of 218 patients in 20 medical centers were included in the final analysis (median age, 50.0 years). The objective response rate was 15.1% (34/218, in the leiomyosarcoma subgroup; 26.3%). The median overall survival and progression-free survival were 10.3 months (95% confidence interval [CI], 8.4 to 12.2) and 3.3 months (95% CI, 2.8 to 4.7), respectively. The treatment was discontinued in 7.8% of patients owing to adverse events; however, there was no adverse event-related death. Neutropenia (35.7%) and anemia (15.1%) were the most frequent grade 3/4 toxicities. Univariate analysis for identifying the predictors of the progression-free survival period revealed that patients aged ≤ 50 years had a hazard ratio of 1.388 (95% CI, 1.027 to 1.875; p < 0.05) relative to those aged > 50 years, and the group with leiomyosarcoma had a hazard ratio of 0.693 (95% CI, 0.493 to 0.975; p < 0.05) relative to the group with other histopathological subtypes.
Conclusion
GD therapy was tolerable and effective for Korean patients with soft tissue sarcoma. In conclusion, for patients with advanced soft tissue sarcoma, especially leiomyosarcoma, GD therapy could be an important therapeutic option.

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Outcomes of Treatment for Malignant Peripheral Nerve Sheath Tumors: Different Clinical Features Associated with Neurofibromatosis Type 1
In Kyung Hwang, Seung Min Hahn, Hyo Sun Kim, Sang Kyum Kim, Hyo Song Kim, Kyoo‑Ho Shin, Chang Ok Suh, Chuhl Joo Lyu, Jung Woo Han
Cancer Res Treat. 2017;49(3):717-726.   Published online December 1, 2016
DOI: https://doi.org/10.4143/crt.2016.271
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of sarcoma that occur spontaneously or in association with neurofibromatosis type 1 (NF-1). This study aimed to clinically differentiate these types of MPNSTs.
Materials and Methods
The study reviewed 95 patients diagnosed with and treated for MPNST at Yonsei University Health System, Seoul, Korea over a 27-year period. The clinical characteristics, prognostic factors, and treatment outcomes of sporadic MPNST (sMPNST) and NF-1 associated MPNST (NF-MPNST) cases were compared.
Results
Patients with NF-MPNST had a significantly lower median age (32 years vs. 45 years for sMPNST, p=0.012), significantly larger median tumor size (8.2 cm vs. 5.0 cm for sMPNST, p < 0.001), and significantly larger numbers of imaging studies and surgeries (p=0.004 and p < 0.001, respectively). The 10-year overall survival (OS) rate of the patients with MPNST was 52±6%. Among the patients with localized MPNST, patients with NF-MPNST had a significantly lower 10-year OS rate (45±11% vs. 60±8% for sMPNST, p=0.046). Univariate analysis revealed the resection margin, pathology grade, and metastasis to be significant factors affecting the OS (p=0.001, p=0.020, and p < 0.001, respectively). Multivariate analysis of the patients with localized MPNST identified R2 resection and G1 as significant prognostic factors for OS.
Conclusion
NF-MPNST has different clinical features from sMPNST and requires more careful management. Further study will be needed to develop specific management plans for NF-MPNST.

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Case Reports
Severe Hepatic Sinusoidal Obstruction Syndrome in a Child Receiving Vincristine, Actinomycin-D, and Cyclophosphamide for Rhabdomyosarcoma: Successful Treatment with Defibrotide
Aery Choi, Young Kyung Kang, Sewon Lim, Dong Ho Kim, Jung Sub Lim, Jun Ah Lee
Cancer Res Treat. 2016;48(4):1443-1447.   Published online March 30, 2016
DOI: https://doi.org/10.4143/crt.2016.096
AbstractAbstract PDFPubReaderePub
Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening syndrome that generally occurs as a complication after hematopoietic stem cell transplantation or, less commonly, after conventional chemotherapy. Regarding SOS in rhabdomyosarcoma patients who received conventional chemotherapy, the doses of chemotherapeutic agents are associated with the development of SOS. Several cases of SOS in rhabdomyosarcoma patients after receiving chemotherapy with escalated doses of cyclophosphamide have been reported. Here, we report on a 9-year-old female with rhabdomyosarcoma who developed severe SOS after receiving chemotherapy consisting of vincristine, actinomycin-D, and a moderate dose of cyclophosphamide. She was treated successfully with defibrotide without sequelae to the liver.

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    Marc R. Lawrence, Mylène Bassal, Raveena Ramphal, Donna L. Johnston
    Journal of Pediatric Hematology/Oncology.2022; 44(3): e788.     CrossRef
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  • Adjuvant recombinant thrombomodulin therapy for hepatopathy induced by vincristine, actinomycin D, and cyclophosphamide in pediatric rhabdomyosarcoma: A case report
    Tetsuko Kobayashi, Maiko Noguchi, Hideki Nakayama, Reiji Fukano, Shouichi Ohga
    Molecular and Clinical Oncology.2019;[Epub]     CrossRef
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    Revathi Rajagopal, Marianne B. Phillips, Nicholas G. Gottardo
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  • Cyclophosphamide/dactinomycin/vincristine

    Reactions Weekly.2017; 1637(1): 75.     CrossRef
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A Case of Metastatic Low-Grade Endometrial Stromal Sarcoma Treated with Letrozole after Ovarian Ablation by Radiotherapy
Kyung Ho Yang, Jung A Shin, Joo Hyuk Jung, Hae Won Jung, Hye Ran Lee, Sunhee Chang, Ji Yeon Park, Seong Yoon Yi
Cancer Res Treat. 2015;47(4):958-962.   Published online February 17, 2015
DOI: https://doi.org/10.4143/crt.2014.154
AbstractAbstract PDFPubReaderePub
A 50-year-old woman was admitted to our hospital due to multiple lung nodules detected incidentally on a chest X-ray. A video-assisted thoracoscopic lung biopsy revealed low-grade endometrial stromal sarcoma (LG-ESS). She had undergone a simple hysterectomy 1 year earlier owing to a diagnosis of adenomyosis. A review of her previous hysterectomy specimen showed not endometriosis but LG-ESS. According to the patient’s levels of serum follicle stimulating hormone and estradiol, she was in the premenopausal state with retained and normally functioning ovaries. She then underwent ovarian ablation by radiotherapy, after which she was administered 2.5 mg of letrozole once per day. Three months later, the size of the metastatic nodules in both lungs had decreased. The patient was followed up for 24 months while continuing on letrozole, and maintained a partial remission. We report herein on a case of metastatic LG-ESS treated with letrozole after ovarian ablation by radiotherapy.

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    Jingjing Bi, Guoyun Li, Juan Chen, Ying Yang, Cimei Li
    Journal of Biomedical Nanotechnology.2023; 19(1): 117.     CrossRef
  • Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma
    Munekage Yamaguchi, Chimeddulam Erdenebaatar, Fumitaka Saito, Takeshi Motohara, Yo Miyahara, Hironori Tashiro, Hidetaka Katabuchi
    International Journal of Gynecological Cancer.2015; 25(9): 1645.     CrossRef
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Original Articles
Role of Radiotherapy in the Multimodal Treatment of Ewing Sarcoma Family Tumors
Yunseon Choi, Do Hoon Lim, Soo Hyun Lee, Chuhl Joo Lyu, Jung Ho Im, Yun-Han Lee, Chang-Ok Suh
Cancer Res Treat. 2015;47(4):904-912.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.158
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to evaluate the role of radiotherapy (RT) in the management of Ewing sarcoma family tumors (ESFT). Materials and Methods Retrospective analysiswas performed on 91 patientswith localized ESFT treated from 1988 to 2012. Primary tumor size was ≥ 8 cm in 33 patients. Surgery, RT, and combined surgery with RT were applied in 37, 15, and 33 patients, respectively.
Results
Median follow-up was 43.8 months. Forty-three patients (47.3%) showed recurrence or progressive disease. Twelve patients (13.2%) showed local failure after initial treatment. Thirty-nine patients (42.9%) experienced distant metastases. The 5-year overall survival (OS), progression-free survival, and local control (LC) were 60.5%, 58.2%, and 85.1%, respectively. According to treatment, 5-year LCwas 64.8% with RT and 90.2% with combined surgery and RT (p=0.052). Prognostic factors for OS were tumor size (≥ 8 cm, p < 0.001) and surgical resection (p < 0.001). In large tumors (≥ 8 cm), combined surgery and RT produced better LC compared to RT (p=0.033). However, in smaller tumors (< 8 cm), RT without surgery resulted in a similar LC rate as RT with surgery (p=0.374). Conclusion RT used for patients with unfavorable risk factors resulted in worse outcome than for patientswho received surgery. Smallertumors could be controlled locallywith chemotherapy and RT. For large tumors, combined surgery and RT is needed. Proper selection of local treatment modality, RT, surgery, or both is crucial in the management of ESFT.

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Long-term Outcome of Chondrosarcoma: A Single Institutional Experience
Srimanth Bindiganavile, Ilkyu Han, Ji Yeon Yun, Han-Soo Kim
Cancer Res Treat. 2015;47(4):897-903.   Published online February 12, 2015
DOI: https://doi.org/10.4143/crt.2014.135
AbstractAbstract PDFPubReaderePub
Purpose
The prognostic factors of chondrosarcoma remain uncertain as only a few large studies with long-term follow-up have been reported. The aim of this study was to analyze oncological outcomes and prognostic factors.
Materials and Methods
A retrospective review of oncological outcomes and prognostic factors was performed on 125 consecutive chondrosarcoma patients who underwent surgery at our institution.
Results
Overall survival was 91.6%±2.5%, 84.1%±3.8%, and 84.1%±3.8% at 5, 10, and 15 years respectively. Among the histological types, dedifferentiated type showed the worst survival (p < 0.001). As for conventional type chondrosarcoma, histologic grade and anatomical location predicted outcome, with high-grade with axial location having the worst outcome (p < 0.001). In contrast, low-grade chondrosarcoma of appendicular skeleton could be treated safely by intralesional curettage.
Conclusion
Histological type was significantly associated with the outcome of chondrosarcoma. For the conventional type, histologic grade and anatomical location predicted outcome, with highgrade with axial location having the worst outcome.

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Incidence and Treatment Pattern of Extremity Soft Tissue Sarcoma in Korea, 2009-2011: A Nationwide Study Based on the Health Insurance Review and Assessment Service Database
Seungcheol Kang, Han-Soo Kim, Eun-Seok Choi, Ilkyu Han
Cancer Res Treat. 2015;47(4):575-582.   Published online January 2, 2015
DOI: https://doi.org/10.4143/crt.2014.047
AbstractAbstract PDFPubReaderePub
Purpose
We conducted a nationwide study to assess the incidence and treatment patterns of extremity soft tissue sarcoma (STS) in South Korea.
Materials and Methods
The nationwide incidence and treatment patterns of extremity STS were assessed using two nationwide databases, the Korea National Cancer Incidence (KNCI) database and the Health Insurance Review and Assessment Service (HIRA) database.
Results
A total of 1,236 patients were newly diagnosed with extremity STS during the 3-year study period, from 2009 to 2011. The annual incidence of extremity STS in the Korean population was approximately 0.9 per 100,000 people with a male bias that increased with age and was especially pronounced amongst individuals aged > 80 years. Approximately 7% of patients did not receive any treatment, and surgical excision was performed for 85% of those who were treated.
Conclusion
This is the first nationwide study of the incidence and treatment patterns of extremity STS in Korea using two national databases (KNCI and HIRA), which include the entire Korean population. The results of this study may be useful for future planning and management of STS, at the national level.

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Case Report
Usefulness of Digital Tomosynthesis for the Detection of Airway Obstruction: A Case Report of Bronchial Carcinosarcoma
Sung-Joon Park, Ji Yung Choo, Ki Yeol Lee, Je-Hyeong Kim, Jung-Woo Choi, Suk Keu Yeom, Baek Hyun Kim
Cancer Res Treat. 2015;47(3):544-548.   Published online September 11, 2014
DOI: https://doi.org/10.4143/crt.2013.220
AbstractAbstract PDFPubReaderePub
Bronchial carcinosarcoma is a very rare malignant tumor that is composed of carcinomatous and sarcomatous elements. We describe the first case in which digital tomosynthesis was useful for the evaluation of airway obstruction by bronchial carcinosarcoma that was overlooked on initial chest radiography.

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Original Article
Adjuvant Treatment Modalities, Prognostic Predictors and Outcomes of Uterine Carcinosarcomas
Kemal Gungorduk, Aykut Ozdemir, Ibrahim E. Ertas, Mehmet Gokcu, Elcin Telli, Tufan Oge, Ahmet Sahbaz, Sevil Sayhan, Muzaffer Sanci, Mehmet Harma, Sinan Ozalp
Cancer Res Treat. 2015;47(2):282-289.   Published online September 4, 2014
DOI: https://doi.org/10.4143/crt.2014.009
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to evaluate the clinicopathological characteristics, treatment, and prognosis of uterine carcinosarcoma (UC). Materials and Methods A retrospective review of three cancer registry databases in Turkey was conducted for identification of patients diagnosed with UC between January 1, 1996, and December 31, 2012. We collected clinicopathological data in order to evaluate factors important in disease- free survival (DFS) and overall survival (OS). Results A total of 66 patients with UC with a median age of 65.0 years were included in the analysis. The median survival time of all patients was 37.5 months and the 5-year OS rate was 59.1%. In early stage patients (I-II) who received adjuvant chemotherapy (CT) with radiation therapy (RT), the median DFS and OS was 44 months and 55 months, respectively, compared to 34.5 months and 36 months, respectively, in patients who received adjuvant RT or CT alone (hazard ratio [HR], 1.4; 95% confidence interval [CI], 0.7 to 3.1 for DFS; p=0.23 and HR, 2.2; 95% CI, 0.9 to 5.3 for OS; p=0.03). In advanced stage patients (III-IV), the median DFS and OS of patients receiving adjuvant RT with CT was 25 months and 38 months, respectively, compared to 23.5 months and 24.5 months, respectively, in patients receiving adjuvant RT or CT alone (HR, 3.1; 95% CI, 0.6 to 16.0 for DFS; p=0.03); (HR, 3.3; 95% CI, 0.7 to 15.0 for OS; p=0.01). In multivariate analysis, advanced International Federation of Gynecology and Obstetrics (FIGO) stage and suboptimal surgery showed significant association with poor OS. Conclusion In patients with early or advanced stage UC, adjuvant CT with RT is associated with improved DFS and OS, as compared to CT or RT alone.

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Case Report
Primary Histiocytic Sarcoma of the Central Nervous System
Hoonsub So, Sun A Kim, Dok Hyun Yoon, Shin Kwang Khang, Jihye Hwang, Chong Hyun Suh, Cheolwon Suh
Cancer Res Treat. 2015;47(2):322-328.   Published online August 29, 2014
DOI: https://doi.org/10.4143/crt.2013.163
AbstractAbstract PDFPubReaderePub
Histiocytic sarcoma is a type of lymphoma that rarely involves the central nervous system (CNS). Its rarity can easily lead to a misdiagnosis. We describe a patient with primary CNS histocytic sarcoma involving the cerebral hemisphere and spinal cord, who had been initially misdiagnosed as demyelinating disease. Two biopsies were necessary before a correct diagnosis was made. A histologic examination showed bizarre shaped histiocytes with larger nuclei and nuclear atypia. The cells were positive for CD68, CD163, and S-100 protein. As a resection was not feasible due to multifocality, he was treated with highdose methotrexate, but showed no response. As a result, he was switched to high dose cytarabine; but again, showed no response. The patient died 2 months from the start of chemotherapy and 8 months from the onset of symptoms. Since few patients with this condition have been described and histopathology is difficult to diagnose, suspicion of the disease is essential.

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Original Article
Incidence and Survival of Pediatric Soft Tissue Sarcomas: Comparison between Adults and Children
Sun Min Lim, Cheol Joo Yoo, Jung Woo Han, Yong Jin Cho, Soo Hee Kim, Joong Bae Ahn, Sun Young Rha, Sang Joon Shin, Hyun Cheol Chung, Woo Ick Yang, Kyoo-Ho Shin, Jae Kyung Rho, Hyo Song Kim
Cancer Res Treat. 2015;47(1):9-17.   Published online August 21, 2014
DOI: https://doi.org/10.4143/crt.2013.157
AbstractAbstract PDFPubReaderePub
Purpose
Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. Materials and Methods We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. Results A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. Conclusion Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.

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  • 141 Download
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Case Report
A Case of Paratesticular Leiomyosarcoma Successfully Treated with Orchiectomy and Chemotherapy
Bong Suk Ko, Nae Yu Kim, Ah Jung Ryu, Dong Soon Kim, Soo Jung Gong, Dae Kyung Kim, Hyun Jin Son, Jung-Ae Lee
Cancer Res Treat. 2012;44(3):210-214.   Published online September 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.3.210
AbstractAbstract PDFPubReaderePub
A 50-year-old male patient presented with a right scrotal mass that had been growing rapidly for more than one year. A heterogeneous enhancing right scrotal mass (12x9 cm) with para-aortic and peri-caval lymphadenopathies was found on abdominal computed tomography (CT). Right orchiectomy was performed and the gross finding had shown intact testis with a well-defined, huge, whitish solid mass adjacent to the testis. According to pathology, the mass was characterized as a leiomyosarcoma, grade 3 (by National Cancer Instituted [NCI] system). Therefore, the diagnosis was stage III, grade 3 paratesticular leiomyosarcoma. The patient underwent additional systemic chemotherapy using ifosfamide and adriamycin. After nine cycles of chemotherapy, positron emission tomography-CT was performed and no FDP uptake was observed. The patient has been followed up for 12 months after systemic chemotherapy, and he has maintained a complete response. We report here on a rare case of paratesticular leiomyosarcoma treated successfully with orichiectomy and additional systemic chemotherapy.

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    Anurag Mishra, Tridibes Mandal
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Original Articles
Epidermal Growth Factor Receptor: Is It a Feasible Target for the Treatment of Osteosarcoma?
Jun Ah Lee, Yunmi Ko, Dong Ho Kim, Jung Sub Lim, Chang-Bae Kong, Wan Hyeong Cho, Dae-Geun Jeon, Soo-Yong Lee, Jae-Soo Koh
Cancer Res Treat. 2012;44(3):202-209.   Published online September 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.3.202
AbstractAbstract PDFPubReaderePub
PURPOSE
Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated.
MATERIALS AND METHODS
Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTEN were performed in four osteosarcoma cell lines.
RESULTS
EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume<150 mL (p<0.001) and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation.
CONCLUSION
In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR.

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Weekly Gemcitabine and Docetaxel in Refractory Soft Tissue Sarcoma: A Retrospective Analysis
Ha-young Lee, Sang Joon Shin, Hyo Song Kim, Soo Jung Hong, Jung Woo Han, Seung Taek Lim, Jae Kyung Roh, Sun Young Rha
Cancer Res Treat. 2012;44(1):43-49.   Published online March 31, 2012
DOI: https://doi.org/10.4143/crt.2012.44.1.43
AbstractAbstract PDFPubReaderePub
PURPOSE
The combination of gemcitabine and docetaxel (GD) is used to effectively treat patients with soft tissue sarcoma (STS). It is widely considered that the conventional doses used are too high for long term use and many patients must discontinue GD treatment due to its toxicity. Therefore, to determine the appropriate dose meeting acceptable efficacy results, while minimizing toxic side effects, we treated patients with a weekly infusion of GD (weekly GD).
MATERIALS AND METHODS
A total of 22 patients presenting a variety of STSs were treated at Yonsei Cancer Center. All patients had metastatic or recurrent cancer and had previously received doxorubicin and ifosfamide combination chemotherapy. In all cases, gemcitabine (1,000 mg/m2) and docetaxel (35 mg/m2) were administered intravenously on days 1 and 8 of a 21-day cycle. We retrospectively reviewed the medical records of these patients.
RESULTS
The response rate was 4.5%, with one patient diagnosed with leiomyosarcoma having a partial response, and the disease control rate was 40.9%. The median progression-free survival (PFS) duration was 2.7 months and the PFS was correlated with the treatment response to a weekly GD. The median overall survival (OS) duration was 7.8 months and the OS was correlated with histology. There was no significant difference in OS between patients who received weekly GD as a 2nd line chemotherapy and those who received 3rd line or more. Treatment was generally well tolerated.
CONCLUSION
Weekly GD was well tolerated and showed moderate efficacy, indicating that this could be a reasonable option as a salvage treatment for metastatic STS.

Citations

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Up-regulation of the DR5 Expression by Proteasome Inhibitor MG132 Augments TRAIL-Induced Apoptosis in Soft Tissue Sarcoma Cell Lines
Hee-Jeong Cheong, Kyu Sang Lee, In Sook Woo, Jong-Ho Won, Jae Ho Byun
Cancer Res Treat. 2011;43(2):124-130.   Published online June 30, 2011
DOI: https://doi.org/10.4143/crt.2011.43.2.124
AbstractAbstract PDFPubReaderePub
PURPOSE
Current chemotherapeutics for treating locally advanced or metastatic soft tissue sarcomas (STS) are limited. Accordingly, the present in vitro study was conducted to evaluate the effects of treatment of STS cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) applied as a single agent or in combination with a proteasome inhibitor, MG132.
MATERIALS AND METHODS
Sensitivity to TRAIL and activity of TRAIL-induced apoptotic pathways were analyzed in four STS cell lines: HTB-82 (rhabdomyosarcoma), HT-1080 (fibrosarcoma), HTB-93 (synovial sarcoma), and HTB-94 (chondrosarcoma). Reduction of the dye dimethylthiazolyl 2,5 diphenyltetrazolium bromide (MTT) was used to evaluate cytotoxic activity; western blots were used to evaluate TRAIL-induced apoptosis.
RESULTS
TRAIL induced apoptosis in HTB-93 cells, but had little effect in HTB-82, HT-1080, or HTB-94 cells. Expression of TRAIL receptor-1 and -2 did not correlate with sensitivity to TRAIL. Co-incubation of cells with TRAIL and a proteasome inhibitor, MG132, augmented the apoptotic effect of TRAIL in both TRAIL-sensitive and TRAIL-resistant cells. This effect was due to up-regulation of TRAIL receptors and members of the pro-apoptotic BCL-2 family by MG132.
CONCLUSION
These data show that combining TRAIL with MG132 enhances apoptosis and overcomes TRAIL resistance. This restoration of TRAIL sensitivity occurs through an increase in the expression of death receptor 5 and of pro-apoptotic BCL-2 family members such as BAX.

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Case Report
Two Pediatric Osteosarcoma Cases with Delayed Methotrexate Excretion: Its Clinical Course and Management
Kang Min Lee, Hee Woo Lee, Seung Yeon Kim, Hyeon Jeong Lee, Dong Hwan Kim, Joongbum Cho, Dong Ho Kim, Jung Sub Lim, Jin Kyung Lee, Jun Ah Lee
Cancer Res Treat. 2011;43(1):67-70.   Published online March 31, 2011
DOI: https://doi.org/10.4143/crt.2011.43.1.67
AbstractAbstract PDFPubReaderePub
High-dose methotrexate (MTX) chemotherapy extends the duration of hospitalization and introduces the risks of serious complications related to delayed MTX excretion. The treatment of delayed MTX excretion is largely dependent on invasive measures such as hemodialysis because the clinical data regarding the efficacy or safety of carboxypetidase G2 is limited. We report here on the cases of two pediatric osteosarcoma patients with delayed MTX excretion and who were successfully managed using supportive measures. Potential life-threatening complications were prevented by administering high doses of leucovorin.

Citations

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  • The Role of Single Nucleotide Polymorphisms in Transporter Proteins and the Folate Metabolism Pathway in Delayed Methotrexate Excretion: A Case Report and Literature Review
    Jun Wang, Yue-Tao Zhao, Meng-Jiao Sun, Feng Chen, Hong-Li Guo
    Pharmacogenomics and Personalized Medicine.2022; Volume 15: 919.     CrossRef
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    Blandine Aloy, Nicolas Janus, Corine Isnard-Bagnis, Gilbert Deray, Vincent Launay-Vacher
    Néphrologie & Thérapeutique.2021; 17(7): 553.     CrossRef
  • Delayed High-dose Methotrexate Excretion and Influencing Factors in Osteosarcoma Patients
    Wei Zhang, Qing Zhang, Ting-Ting Zheng, Jian-Cun Zhen, Xiao-Hui Niu
    Chinese Medical Journal.2016; 129(21): 2530.     CrossRef
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Original Article
Prognostic Role of Rb, p16, Cyclin D1 Proteins in Soft Tissue Sarcomas
Byoung Yong Shim, Jinyoung Yoo, Yeon-Soo Lee, Young Sun Hong, Hoon-Kyo Kim, Jin-Hyoung Kang
Cancer Res Treat. 2010;42(3):144-150.   Published online September 30, 2010
DOI: https://doi.org/10.4143/crt.2010.42.3.144
AbstractAbstract PDFPubReaderePub
Purpose

The aim of this study was to determine the expressions of Rb, p16, and cyclin D1 in soft tissue sarcomas, and we also wanted to identify the prognostic factors according to the clinicalpathologic features.

Materials and Methods

We reviewed the charts and radiographic films of 66 sarcoma patients. Tissue samples were collected from these patients. Immunochemistry was performed using formalin-fixed, paraffin-embedded tissue samples to examine the expressions of p16, Rb, and cyclin D1 proteins.

Results

The median duration of overall survival was 47.8 months (range, 20.0 to 70.7 months) and the 5 years survival rate was 39%. As for the correlation between the degree of immunohistochemical staining for Rb protein and the histological tumor grades, there was a significant difference with a p-value of 0.019. However, no significant correlation was shown for p16 and cyclin D1. The overall survival duration of the Rb negative group (staining cell <20%) and the heterogeneous group (cell staining 20 to 80%) was 53.5±6.6 months and the overall survival duration of the Rb homogeneous group was 18.3±6.4 months, and there was a significant difference with a p-value of 0.016. However, no significant difference was shown between the survival rate according to the p16 and cyclin D1 expressions. On the multivariate analysis that was done with Rb, p16, the tumor size, grade and site, and patient age, the Rb gene expression was the most significant independent prognostic factor with a risk ratio of 3.01 (p=0.04).

Conclusion

The expression of Rb protein was correlated with the histologic grade and overall survival of patients with soft tissue sarcomas.

Citations

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    Mala Sagar, Rita Yadav, Pankaj Deval, Madhu Kumar, Malti K Maurya, Sumaira Qayoom
    Cureus.2023;[Epub]     CrossRef
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    Jaffar Khan, Liang Cheng, Michael G. House, Shunhua Guo
    Current Oncology.2021; 28(6): 5295.     CrossRef
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    Yu Jin Kim, Mingi Kim, Hyung Kyu Park, Dan Bi Yu, Kyungsoo Jung, Kyoung Song, Yoon-La Choi
    Laboratory Investigation.2019; 99(9): 1309.     CrossRef
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    Gang Lin, Yue Lou
    Indian Journal of Cancer.2017; 54(3): 580.     CrossRef
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    Toshiaki Haraguchi, Hiroaki Miyoshi, Koji Hiraoka, Shintaro Yokoyama, Yukinao Ishibashi, Toshihiro Hashiguchi, Koutaro Matsuda, Tetsuya Hamada, Takahiro Okawa, Naoto Shiba, Koichi Ohshima, Ichiro Aoki
    PLOS ONE.2016; 11(6): e0156524.     CrossRef
  • Sarcoma spreads primarily through the vascular system: are there biomarkers associated with vascular spread?
    Elisabetta Pennacchioli, Giulio Tosti, Massimo Barberis, Tommaso M. De Pas, Francesco Verrecchia, Claudia Menicanti, Alessandro Testori, Giovanni Mazzarol
    Clinical & Experimental Metastasis.2012; 29(7): 757.     CrossRef
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