Cancer Research and Treatment

Original Articles

Hematologic malignancy

A New Prognostic Index for Extranodal Natural Killer/T-Cell Lymphoma:Incorporation of Serum β-2 Microglobulin to PINK: Sora Kang, Hyungwoo Cho, Shin Kim, Kyoungmin Lee, Eun Hee Kang, Jung Sun Park, Yoon Sei Lee, Chan-Sik Park, Heounjeong Go, Jooryung Huh, Jin Sook Ryu, Sang-Wook Lee, Seok Jin Kim, Won Seog Kim, Sang Eun Yoon, Young Hyeh Ko, Cheolwon Suh; Cancer Res Treat. 2023;55(1):314-324. Published online March 31, 2022; DOI: https://doi.org/10.4143/crt.2022.015

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Purpose
Prognostic Index for Natural Killer Lymphoma (PINK) is the most widely accepted prognostic model for patients withextranodal natural killer/T-cell lymphoma (ENKTL) treated with non-anthracycline–based therapy. We aimed to evaluate the prognostic implications of serum β-2 microglobulin (β2M) in the context of PINK and proposed a new prognostic model.
Materials and Methods
A total of 138 patients who were newly diagnosed with ENKTL and treated with non-anthracycline-based chemotherapy were identified. The cut-off value of high serum β2M was calculated by maximal-chi square methods (4.1 mg/L). A new prognostic model incorporating serum β2M into PINK was proposed and validated in an independent validation cohort (n=88).
Results
The patients’ median age was 53.5 years (range, 19 to 80 years). Patients with high serum β2M levels had significantly worse overall survival (OS) and progression-free survival (PFS). In multivariate analysis, high serum β2M was an independent adverse prognostic factor for OS. A new PINK-B (Prognostic Index for Natural Killer Lymphoma-serum β-2 microglobulin) model stratifiedpatients into three groups with distinct OS and PFS in the training cohort (3-year OS, 84.1% [95% confidence interval, 75.1 to 94.2], 46.8% [36.1 to 60.8] and 17.6% [6.3 to 49.2] for the low-, intermediate, and high-risk groups, respectively; 3-year PFS, 70.6% [59.4 to 83.8], 35.9% [25.9 to 49.8], and 7.35% [1.1 to 46.7] for the low-, intermediate-, and high-risk groups, respectively). The PINK-B model was further validated in an independent cohort.
Conclusion
Serum β2M is an independent prognostic factor for ENKTL patients. The new serum β2M-based prognostic model may be useful for identifying ultra-high-risk patients, and it can easily be adopted into daily clinical practice.

Citations

Citations to this article as recorded by

Elevated serum IL-6 and total IgEAb are associated with poor survival in natural killer/T-cell lymphoma
Yun Hui, Yingjun Gao, Jiawei Li, Qingtao Kong, Yuanyuan Duan, Haibo Liu, Fang Liu, Hong Sang
Annals of Hematology.2024; 103(4): 1285. CrossRef
Prognostic Impact of Serum β2-Microglobulin Levels in Hodgkin Lymphoma Treated with ABVD or Equivalent Regimens: A Comprehensive Analysis of 915 Patients
Theodoros P. Vassilakopoulos, Maria Arapaki, Panagiotis T. Diamantopoulos, Athanasios Liaskas, Fotios Panitsas, Marina P. Siakantaris, Maria Dimou, Styliani I. Kokoris, Sotirios Sachanas, Marina Belia, Chrysovalantou Chatzidimitriou, Elianna A. Konstantin
Cancers.2024; 16(2): 238. CrossRef
Prognostic Value of18F-FDG PET/CT Radiomics in Extranodal Nasal-Type NK/T Cell Lymphoma
Yu Luo, Zhun Huang, Zihan Gao, Bingbing Wang, Yanwei Zhang, Yan Bai, Qingxia Wu, Meiyun Wang
Korean Journal of Radiology.2024; 25(2): 189. CrossRef
A novel prognostic index for extranodal natural killer/T-cell lymphoma in the era of pegaspargase/L-asparaginase
Ziyuan Shen, Xudong Zhang, Yujie Li, Xicheng Chen, Xing Xing, Hao Zhang, Jingjing Ye, Ling Wang, Tao Jia, Taigang Zhu, Yuqing Miao, Chunling Wang, Hui Liu, Liang Wang, Wei Sang
Future Oncology.2024; 20(28): 2071. CrossRef

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Genitourinary cancer

PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI–Resistant Metastatic Clear Cell Renal Cell Carcinoma: Se Un Jeong, Hee Sang Hwang, Ja-Min Park, Sun Young Yoon, Su-Jin Shin, Heounjeong Go, Jae-Lyun Lee, Gowun Jeong, Yong Mee Cho; Cancer Res Treat. 2023;55(1):231-244. Published online March 2, 2022; DOI: https://doi.org/10.4143/crt.2021.1526

Abstract PDF Supplementary Material PubReader ePub

Purpose
Tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism.
Materials and Methods
To determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib.
Results
Among differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway.
Conclusion
These results showed that PD-L1 expression may be increased in a subset of VEGFR-TKI–resistant mCCRCC patients via the mTOR pathway.

Citations

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IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma
Se Un Jeong, Ja-Min Park, Sun Young Yoon, Hee Sang Hwang, Heounjeong Go, Dong-Myung Shin, Hyein Ju, Chang Ohk Sung, Jae-Lyun Lee, Gowun Jeong, Yong Mee Cho
Investigative and Clinical Urology.2024; 65(1): 84. CrossRef
Targeting apoptosis in clear cell renal cell carcinoma
Adam Kowalewski, Jędrzej Borowczak, Mateusz Maniewski, Karol Gostomczyk, Dariusz Grzanka, Łukasz Szylberg
Biomedicine & Pharmacotherapy.2024; 175: 116805. CrossRef
Therapeutic advances of targeting receptor tyrosine kinases in cancer
Ciprian Tomuleasa, Adrian-Bogdan Tigu, Raluca Munteanu, Cristian-Silviu Moldovan, David Kegyes, Anca Onaciu, Diana Gulei, Gabriel Ghiaur, Hermann Einsele, Carlo M. Croce
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
Mechanisms of sunitinib resistance in renal cell carcinoma and associated opportunities for therapeutics
Yunxia Wang, Xiaolin Liu, Luyao Gong, Weihong Ding, Wenjing Hao, Yeheng Peng, Jun Zhang, Weimin Cai, Yuan Gao
British Journal of Pharmacology.2023; 180(23): 2937. CrossRef
Prior Anti-Angiogenic TKI-Based Treatment as Potential Predisposing Factor to Nivolumab-Mediated Recurrent Thyroid Disorder Adverse Events in mRCC Patients: A Case Series
Luigi Liguori, Angelo Luciano, Giovanna Polcaro, Alessandro Ottaiano, Marco Cascella, Francesco Perri, Stefano Pepe, Francesco Sabbatino
Biomedicines.2023; 11(11): 2974. CrossRef

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Lymphoma

Prognostic Impact of Age at the Time of Diagnosis in Korean Patients with Diffuse Large B-cell Lymphoma in the Rituximab Era: A Single Institution Study: Hee Sang Hwang, Meejeong Kim, Chan-Sik Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh, Heounjeong Go; Cancer Res Treat. 2021;53(1):270-278. Published online September 15, 2020; DOI: https://doi.org/10.4143/crt.2020.626

Abstract PDF Supplementary Material PubReader ePub

Purpose
In contrast to the Western diffuse large B-cell lymphoma (DLBCL), prognostic impact of age in a Korean population with DLBCL has not been fully evaluated.
Materials and Methods
Six hundred and eight DLBCL patients treated with rituximab-containing chemotherapeutic regimens from January 2002 to March 2012 in Asan Medical Center were enrolled. Survival models using the restricted cubic spine−transformed age variable were constructed to evaluate non-linear relationships between age and survival outcome. Finally, age was categorized according to the conventional international prognostic index (IPI), National Comprehensive Cancer Network (NCCN)-IPI, and Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI schemes and the prognostic implications were evaluated.
Results
The relative hazard did not change significantly during the first to fifth decades, but began to increase exponentially in patients aged over 62 years. This pattern or relationship was also retained in a multivariate model fitted to the age-adjusted IPI and relative dose intensity. Multivariate survival analysis revealed that age > 75 years, but not age > 60 years, was associated independently with poor overall and progression-free survival when the relative dose intensity and age-adjusted IPI were taken into account.
Conclusion
The outcome of DLBCL in Korean populations may deteriorate rapidly as age exceeds 62 years. Therefore, a consensus cutoff value for age in Korean DLBCL patients should be determined to better predict prognosis.

Citations

Citations to this article as recorded by

Two distinct age-prognosis patterns in patients with esophageal cancer undergoing surgical and radiotherapy treatments: a combined analysis of 3JECROG and SEER databases
Chen Li, Xiao Chang, Qifeng Wang, Qingsong Pang, Zefen Xiao, Wencheng Zhang, Zhiyong Yuan
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
SOHO State of the Art Updates and Next Questions | Diffuse Large B-Cell Lymphoma in Older Adults: A Comprehensive Review
Varun Iyengar, Paul Hamlin, Pallawi Torka
Clinical Lymphoma Myeloma and Leukemia.2024;[Epub] CrossRef
Impact of R-CHOP dose intensity on survival outcomes in diffuse large B-cell lymphoma: a systematic review
Edward J. Bataillard, Chan Yoon Cheah, Matthew J. Maurer, Arushi Khurana, Toby A. Eyre, Tarec Christoffer El-Galaly
Blood Advances.2021; 5(9): 2426. CrossRef

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