Cancer Research and Treatment

Original Articles

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

Abstract PDF Supplementary Material PubReader ePub

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

5,976 View
212 Download
3 Web of Science
3 Crossref

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

Abstract PDF Supplementary Material PubReader ePub

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.

Citations

Citations to this article as recorded by

Punch Biopsy as a Diagnostic Keystone for Metastatic Cardiac Angiosarcoma Treated With Anthracycline-Based Chemotherapy: A Case Report
Aonghus Joyce, Gráinne Murphy, Cynthia C Heffron, David Aherne, Richard M Bambury
Cureus.2025;[Epub] CrossRef
Chest Wall Angiosarcoma with an Initial Presentation of Multiple Lung Metastases: a Case Report
Hitoshi Suzuki, Mari Shinoda, Daisuke Ito, Shin Shomura, Kentaro Inoue, Kazuo Fukutome, Akira Shimamoto, Hisamichi Yuda
Haigan.2024; 64(7): 917. CrossRef
Hepatic Angiosarcoma with Peliosis Hepatis
Kensuke Kitsugi, Kazuhito Kawata, Moe Matsumoto, Masahiro Umemura, Tomohiko Hanaoka, Maho Yamashita, Shingo Takatori, Jun Ito, Kazuyoshi Ohta, Takeshi Chida, Hidenao Noritake, Takafumi Suda
Internal Medicine.2023; 62(8): 1157. CrossRef
Conversion surgery for recurrent hepatic angiosarcoma after systemic chemotherapy with paclitaxel
Yuta Ushida, Takafumi Sato, Tomotaka Kato, Yasuyuki Shigematsu, Hiromichi Ito, Takeshi Suzuki, Yosuke Inoue, Yoshihiro Ono, Atsushi Oba, Yu Takahashi
Clinical Journal of Gastroenterology.2022; 15(2): 427. CrossRef
Management of Cutaneous Angiosarcoma: an Update Review
Siwei Bi, Ai Zhong, Xiya Yin, Jingyi Li, Ying Cen, Junjie Chen
Current Treatment Options in Oncology.2022; 23(2): 137. CrossRef
Results of NC-6300 (Nanoparticle Epirubicin) in an Expansion Cohort of Patients with Angiosarcoma
Richard F Riedel, Victoria Chua, Ania Moradkhani, Natalie Krkyan, Amir Ahari, Atsushi Osada, Sant P Chawla
The Oncologist.2022; 27(10): 809. CrossRef

9,064 View
183 Download
4 Web of Science
6 Crossref

Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study: Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim; Cancer Res Treat. 2018;50(2):488-494. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.584

Abstract PDF Supplementary Material PubReader ePub

Purpose
The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.
Materials and Methods
Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).
Results
A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.
Conclusion
In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.

Citations

Citations to this article as recorded by

Systemic therapy for non–clear cell renal cell carcinomas: A systematic review
Balqees Ara, Anum Babar, Durkho Atif, Bushra Ghafoor, Mustafa Shah, Syed Maaz Abdullah, Danish Safi, Amir Kamran
Journal of Oncology Pharmacy Practice.2025; 31(1): 128. CrossRef
Liver metastasis from a chromophobe renal cell carcinoma 18 years after initial diagnosis: a case report
Alexandra Ökrösi, Lothar Ponhold, Simon Turba, Melitta Kitzwögerer, Gertraud Heinz
Journal of Medical Case Reports.2025;[Epub] CrossRef
Chromophobe Renal Cell Carcinoma With Sarcomatoid Differentiation: A Case Report and Review of the Literature
Mouhsine Omari, Mohammed Bendimya, Fadoua Jebrouni, Nassira Karich, Ouissam Al Jarroudi, Sami Aziz Brahmi, Amal Bennani, Said Afqir
Cureus.2025;[Epub] CrossRef
Integrated Bioinformatics and Experimental Validation to Identify a Disulfidptosis-Related lncRNA Model for Prognostic Prediction in Papillary Renal Cell Carcinoma
Yidong Zhu, Xiaoyi Jin, Jun Liu
Combinatorial Chemistry & High Throughput Screening.2025; 28(5): 883. CrossRef
Advances in non‐clear cell renal cell carcinoma management: From heterogeneous biology to treatment options
Nathaniel R. Wilson, Yusuf Acikgoz, Elshad Hasanov
International Journal of Cancer.2024; 154(6): 947. CrossRef
Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update
Andrey Soares, Fernando Sabino Marques Monteiro, Karine Martins da Trindade, Adriano Gonçalves e Silva, Ana Paula Garcia Cardoso, André Deeke Sasse, André P. Fay, André Paternò Castello Dias Carneiro, Antonio Machado Alencar Junior, Augusto César de Andra
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Papillary Renal Cell Carcinoma: Current Evidence and Future Directions
Albert Jang, Charbel S. Hobeika, Shilpa Gupta
Kidney Cancer.2024; 8(1): 61. CrossRef
Comparison of the efficacy of sunitinib and pazopanib in patients with advanced non-clear renal cell carcinoma
Hasan Cagri Yildirim, Ertuğrul Bayram, Elvin Chalabiyev, Nargız Majidova, Tugay Avci, Halil Göksel Güzel, Caner Kapar, Mehmet Uzun, Perihan Perkin, Fahri Akgül, Saadet Sim Yildirim, Seda Sali, Anil Yildiz, Seher Nazli Kazaz, Engin Hendem, Murat Arcagok, G
Journal of Chemotherapy.2024; : 1. CrossRef
Genomic profiling and molecular characterization of non-clear cell renal cell carcinoma: a narrative review from a clinical perspective
Gaetano Pezzicoli, Vittoria Musci, Federica Ciciriello, Francesco Salonne, Paola Cafforio, Nicoletta Lionetti, Anna Ragno, Mimma Rizzo
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Effectiveness of systemic treatments for advanced non-clear cell renal cell carcinoma: a systematic review and meta-analysis
Yaping Zhang, Jian Chen, Xiaoyan Wang, Hui Wang, Xiaoli Chen, Jianfeng Hong, Hongming Fang
Frontiers in Oncology.2024;[Epub] CrossRef
Real World Data of Diagnosis, Survival, and Treatment Outcomes in Patients With Metastatic Non Clear Cell Renal Cell Carcinoma
Floriane Izarn, Benoît Allignet, Romane Gille, Helen Boyle, Eve-Marie Neidhardt, Sylvie Négrier, Aude Fléchon
Clinical Genitourinary Cancer.2023; 21(2): e35. CrossRef
SEOM SOGUG clinical guideline for treatment of kidney cancer (2022)
María José Méndez-Vidal, Martin Lázaro Quintela, Nuria Lainez-Milagro, Begoña Perez-Valderrama, Cristina Suárez Rodriguez, José Ángel Arranz Arija, Ignacio Peláez Fernández, Enrique Gallardo Díaz, Julio Lambea Sorrosal, Aránzazu González-del-Alba
Clinical and Translational Oncology.2023; 25(9): 2732. CrossRef
Clinical Features and Prognostic Factors of Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multicenter Study from the Turkish Oncology Group Kidney Cancer Consortium
Cihan Erol, Emre Yekedüz, Deniz Tural, Serdar Karakaya, Nihan Şentürk Öztaş, Gökhan Uçar, Saadettin Kılıçkap, İsmail Ertürk, Özlem Nuray Sever, Çağatay Arslan, Ahmet Küçükarda, Orçun Can, Özlem Balvan, Satı Coşkun Yazgan, Mustafa Özgüroğlu, Berna Öksüzoğl
Urologia Internationalis.2023; 107(6): 595. CrossRef
The efficacy of molecular targeted therapy and nivolumab therapy for metastatic non‐clear cell renal cell carcinoma: A retrospective analysis using the Michinoku Japan urological cancer study group database
Tomoyuki Koguchi, Sei Naito, Shingo Hatakeyama, Kazuyuki Numakura, Yumina Muto, Renpei Kato, Takahiro Kojima, Yoshihide Kawasaki, Kento Morozumi, Shuya Kandori, Sadafumi Kawamura, Hiroyuki Nishiyama, Akihiro Ito, Tomonori Habuchi, Wataru Obara, Chikara Oh
Cancer Medicine.2023; 12(22): 20677. CrossRef
Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology
Robert J. Motzer, Eric Jonasch, Neeraj Agarwal, Ajjai Alva, Michael Baine, Kathryn Beckermann, Maria I. Carlo, Toni K. Choueiri, Brian A. Costello, Ithaar H. Derweesh, Arpita Desai, Yasser Ged, Saby George, John L. Gore, Naomi Haas, Steven L. Hancock, Pay
Journal of the National Comprehensive Cancer Network.2022; 20(1): 71. CrossRef
Systematic Review of Treatment of Metastatic Non-Clear Cell Renal Cell Carcinoma
Jason R. Brown, Adam Calaway, Erik Castle, Jorge Garcia, Pedro C. Barata
Kidney Cancer.2022; 6(1): 53. CrossRef
Non-Clear Cell Renal Cell Carcinoma: Molecular Pathogenesis, Innovative Modeling, and Targeted Therapeutic Approaches
Niloofar Khoshdel Rad, Maryam Vahidyeganeh, Mahsa Mohammadi, Anastasia Shpichka, Peter Timashev, Nikoo Hossein-Khannazer, Massoud Vosough
International Journal of Translational Medicine.2022; 2(4): 555. CrossRef
Systemic Therapies for the Management of Non–Clear Cell Renal Cell Carcinoma: What Works, What Doesn’t, and What the Future Holds
Panagiotis Zoumpourlis, Giannicola Genovese, Nizar M. Tannir, Pavlos Msaouel
Clinical Genitourinary Cancer.2021; 19(2): 103. CrossRef
Comprehensive review of chromophobe renal cell carcinoma
Rohan Garje, Dean Elhag, Hesham A Yasin, Luna Acharya, Daniel Vaena, Laila Dahmoush
Critical Reviews in Oncology/Hematology.2021; 160: 103287. CrossRef
A Systematic Review of Systemic Treatment Options for Advanced Non-Clear Cell Renal Cell Carcinoma
Chelsea K. Osterman, Tracy L. Rose
Kidney Cancer.2020; 4(1): 15. CrossRef
Occurrence of abscesses during treatment with pazopanib in metastatic renal cancer: a case report
Ivana Puliafito, Alessio Russo, Dorotea Sciacca, Caterina Puglisi, Dario Giuffrida
Journal of Medical Case Reports.2020;[Epub] CrossRef
On the Shoulders of Giants: The Evolution of Renal Cell Carcinoma Treatment—Cytokines, Targeted Therapy, and Immunotherapy
Janice P. Dutcher, Ronan Flippot, Jaleh Fallah, Bernard Escudier
American Society of Clinical Oncology Educational Book.2020; (40): 418. CrossRef
Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review
Melissa Bersanelli, Matteo Brunelli, Letizia Gnetti, Umberto Maestroni, Sebastiano Buti
Therapeutic Advances in Medical Oncology.2020;[Epub] CrossRef
Management of Metastatic Renal Cell Carcinoma with Variant Histologies
Ronan Flippot, Vijay Damarla, Bradley A. McGregor
Urologic Clinics of North America.2020; 47(3): 319. CrossRef
Discovery of Pyrido[3′,2′:5,6]thiopyrano[4,3-d]pyrimidine-Based Antiproliferative Multikinase Inhibitors
Silvia Salerno, Elisabetta Barresi, Aída Nelly García-Argáez, Sabrina Taliani, Francesca Simorini, Giorgio Amendola, Stefano Tomassi, Sandro Cosconati, Ettore Novellino, Federico Da Settimo, Anna Maria Marini, Lisa Dalla Via
ACS Medicinal Chemistry Letters.2019; 10(4): 457. CrossRef
Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study
Nieves Martínez Chanzá, Wanling Xie, Mehmet Asim Bilen, Hannah Dzimitrowicz, Jarred Burkart, Daniel M Geynisman, Archana Balakrishnan, I Alex Bowman, Rohit Jain, Walter Stadler, Yousef Zakharia, Vivek Narayan, Benoit Beuselinck, Rana R McKay, Abhishek Tri
The Lancet Oncology.2019; 20(4): 581. CrossRef
Recent advances in the systemic treatment of metastatic non‐clear cell renal cell carcinomas
Keiichi Ito
International Journal of Urology.2019; 26(9): 868. CrossRef
Long-term response of metastatic hereditary leiomyomatosis and renal cell carcinoma syndrome associated renal cell carcinoma to bevacizumab plus erlotinib after temsirolimus and axitinib treatment failures
Inkeun Park, Young Sup Shim, Heounjeong Go, Bum Sik Hong, Jae Lyun Lee
BMC Urology.2019;[Epub] CrossRef
Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma
Jii Bum Lee, Hyung Soon Park, Sejung Park, Hyo Jin Lee, Kyung A Kwon, Young Jin Choi, Yu Jung Kim, Chung Mo Nam, Nam Hoon Cho, Beodeul Kang, Hyun Cheol Chung, Sun Young Rha
Cancer Research and Treatment.2019; 51(4): 1578. CrossRef
The Role of Pazopanib in Non-Clear Cell Renal Cell Carcinoma: A Systematic Review
Gregory T. Sneed, Sukdong Lee, Jamie N. Brown, Julia M. Hammond
Clinical Genitourinary Cancer.2019; 17(6): 419. CrossRef
A Multicenter Phase II Trial of Axitinib in Patients With Recurrent or Metastatic Non–clear-cell Renal Cell Carcinoma Who Had Failed Prior Treatment With Temsirolimus
Inkeun Park, Se Hoon Lee, Jae Lyun Lee
Clinical Genitourinary Cancer.2018; 16(5): e997. CrossRef
Clinical Outcomes in Patients With Metastatic Papillary Renal-Cell Carcinoma: A Multi-Institutional Study in Japan
Keiichi Ito, Shuji Mikami, Katsunori Tatsugami, Naoya Masumori, Nobuo Shinohara, Tsunenori Kondo, Shotaro Nakanishi, Yoji Nagashima, Masatoshi Eto, Tomomi Kamba, Naoto Kuroda, Yoshihiko Tomita, Hideyasu Matsuyama, Tetsuro Onishi, Tomoyasu Tsushima, Hayaka
Clinical Genitourinary Cancer.2018; 16(6): e1201. CrossRef

11,223 View
494 Download
38 Web of Science
32 Crossref

Case Report

Pazopanib for Non-small Cell Lung Cancer: The First Case Report in Korea: Jaemin Jo, Jung Ho Kim, Ji Young Kim, Changlim Hyun, Jiyoung Rhee, Jungmi Kwon, Sanghoon Han, Wookun Kim; Cancer Res Treat. 2016;48(1):393-397. Published online February 17, 2015; DOI: https://doi.org/10.4143/crt.2014.209

Abstract PDF PubReader ePub: Pazopanib is a potent multitargeted tyrosine kinase inhibitor that has been shown to have good efficacy in patients with renal cell carcinoma. A previous phase II trial demonstrated that short-term pazopanib administration was generally well tolerated and showed antitumor activity in patients with early-stage non-small cell lung cancer. Herein, we report on the case of a 66-year-old man with simultaneous metastatic squamous cell carcinoma of the lung and renal cell carcinoma who was treated with pazopanib. The patient showed an unexpected partial response and experienced a 10-month progression-free survival without significant toxicity. To the best of the authors’ knowledge, this is the first report of pazopanib treatment in a non-small cell lung cancer patient in Korea. The results in this patient suggest that pazopanib may be a valid treatment option for advanced non-small cell lung cancer.

11,699 View
104 Download

First
Prev
Page of 1
Next
Last

Search