Prognostic Nomogram for Overall Survival in Early Stage Extranodal Natural Killer/T Cell Lymphoma Treated With High-Dose Radiotherapy

Hy, Luo; Wu, Yongzhong; Wang, Ying; Xie, Yue; Wu, Fuqiang; Li, Shujie; Liang, Zhong‐Guo; Zhu, Xiao‐Dong

doi:10.1016/j.clml.2019.10.010

Cited by 4 publications

(6 citation statements)

References 32 publications

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“…The infection of Epstein-Barrvirus (EBV) may be closely related to its pathogenesis [ 2 ]. At an early stage of ENKTL, the combination of chemotherapy and radiotherapy prolongs patients’ survival and improves the quality of life [ 3 , 4 ]. However, for advanced refractory ENKTL patients, the efficacy of current treatment is not satisfactory [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The identification of gene signatures in patients with extranodal NK/T-cell lymphoma from a pair of twins

et al. 2021

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Background There is no unified treatment standard for patients with extranodal NK/T-cell lymphoma (ENKTL). Cancer neoantigens are the result of somatic mutations and cancer-specific. Increased number of somatic mutations are associated with anti-cancer effects. Screening out ENKTL-specific neoantigens on the surface of cancer cells relies on the understanding of ENKTL mutation patterns. Hence, it is imperative to identify ENKTL-specific genes for ENKTL diagnosis, the discovery of tumor-specific neoantigens and the development of novel therapeutic strategies. We investigated the gene signatures of ENKTL patients. Methods We collected the peripheral blood of a pair of twins for sequencing to identify unique variant genes. One of the twins is diagnosed with ENKTL. Seventy samples were analyzed by Robust Multi-array Analysis (RMA). Two methods (elastic net and Support Vector Machine-Recursive Feature Elimination) were used to select unique genes. Next, we performed functional enrichment analysis and pathway enrichment analysis. Then, we conducted single-sample gene set enrichment analysis of immune infiltration and validated the expression of the screened markers with limma packages. Results We screened out 126 unique variant genes. Among them, 11 unique genes were selected by the combination of elastic net and Support Vector Machine-Recursive Feature Elimination. Subsequently, GO and KEGG analysis indicated the biological function of identified unique genes. GSEA indicated five immunity-related pathways with high signature scores. In patients with ENKTL and the group with high signature scores, a proportion of functional immune cells are all of great infiltration. We finally found that CDC27, ZNF141, FCGR2C and NES were four significantly differential genes in ENKTL patients. ZNF141, FCGR2C and NES were upregulated in patients with ENKTL, while CDC27 was significantly downregulated. Conclusion We identified four ENKTL markers (ZNF141, FCGR2C, NES and CDC27) in patients with extranodal NK/T-cell lymphoma.

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Section: Introductionmentioning

confidence: 99%

The identification of gene signatures in patients with extranodal NK/T-cell lymphoma from a pair of twins

et al. 2021

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“… 4 , 32 To date, neither an optimal treatment strategy nor a valuable prognostic index has been identified. 5 , 33 Several prognostic models have been used for ENKTL, including IPI, 34 KPI, 13 PINK, and PINK-E. 15 However, these prognostic models for ENKTL are still controversial. Although the IPI systematically predicted the prognosis for aggressive NHL, it failed to properly predict survival outcomes in a few studies of early-stage ENKTL.…”

Section: Discussionmentioning

confidence: 99%

“…ENKTL is a rare subtype of non‐Hodgkin lymphoma with poor outcome, the 5‐year OS rates in large cohort studies range from 30% to 86%, and most studies showed that the rates were less than 50% 4,32 . To date, neither an optimal treatment strategy nor a valuable prognostic index has been identified 5,33 . Several prognostic models have been used for ENKTL, including IPI, 34 KPI, 13 PINK, and PINK‐E 15 .…”

Section: Discussionmentioning

confidence: 99%

“…Extranodal NK/T‐cell lymphoma (ENKTL) is a highly aggressive and heterogeneous disease predominant in Asian and South American populations 1–4 . Substantial heterogeneity in survival exists for newly diagnosed ENKTL, and the reported 5‐year overall survival (OS) rates vary from 40% to 90% 5 . For patients with low‐risk early‐stage disease, radiotherapy alone could achieve a favorable OS, and incorporation of chemotherapy may not provide additional benefit.…”

Section: Introductionmentioning

confidence: 99%

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The Novel Prognostic Index Model of Combining Circulating Tumor DNA and PINK-E Predicts the Clinical Outcomes for Newly Diagnosed Extranodal NK/T-cell Lymphoma

Huang

et al. 2022

HemaSphere

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Extranodal NK/T-cell lymphoma (ENKTL) is a highly aggressive and heterogeneous disease with poor clinical outcome. Our previous work had demonstrated that circulating tumor DNA (ctDNA) analyses were feasible in ENKTL, and dynamic tracing of ctDNA could be used to monitor the disease status. However, the prognostic value of ctDNA in ENKTL has not been fully investigated. Patients with newly diagnosed ENKTL from February 2017 to December 2021 (n = 70) were enrolled. The pretreatment ctDNA concentration (hGE/ mL) was measured. The prognostic value of ctDNA, international prognostic index (IPI), Korean prognostic index (KPI), PINK-E, and the combination of PINK-E and ctDNA (PINK-EC) were investigated in our cohort. The IPI and PINK-E risk categories had a significant difference in progression-free survival (PFS) and overall survival (OS) between the low-risk and intermediate-risk groups. The KPI risk category had a difference in PFS and OS between the intermediate-risk and high-risk groups. Furthermore, integrating ctDNA into the PINK-E model could overcome the shortcomings of other prognostic models, which could significantly distinguish the different-risk groups. Overall, our results demonstrated that PINK-EC showed a superior prognostic prediction value and stability compared with IPI, KPI, and PINK-E. The integration of molecular features of the tumor into classic risk categories might better characterize a high-risk group where novel treatment approaches are most needed.

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“…13,30,32 These experimental findings corroborate the clinical correlations of an elevated serum LDH with a poor prognosis and suboptimal tumour response. 13,15,33,34 However, it is unknown if this observed correlation between LDH activity and cancer outcomes is isoenzyme-specific (LDH 1–5). Given that LDH isoenzymes are highly tissue-specific, it is plausible to consider that different isoenzymes could be predictive of tumour response to CT at specific anatomical organs, which could be investigated going forward.…”

Section: Discussionmentioning

confidence: 99%

Lactate dehydrogenase kinetics predict chemotherapy response in recurrent metastatic nasopharyngeal carcinoma

Sim

et al. 2020

Ther Adv Med Oncol

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Background: Lactate dehydrogenase (LDH) is a known prognostic biomarker for the endemic variant of nasopharyngeal carcinoma (NPC). Here, we investigate whether serial changes in LDH level between chemotherapy (CT) cycles are associated with tumour response to CT. Methods: Patients with biopsy-proven, recurrent or treatment-naïve metastatic NPC (mNPC) were recruited. All patients had received at least two cycles of platinum-based doublet or triplet CT, with serial assessment of LDH prior to every cycle of chemotherapy (CT1–6). Patients harbouring conditions that affect LDH levels (IU/L) were excluded. Tumour response was assessed after every two cycles of CT by RECIST v1.1. Results: A total of 158 patients were analysed, including 77 with recurrent and 81 with treatment-naïve mNPC. High pre-CT LDH was associated with an inferior overall survival [hazard ratio 1.93 for ⩾240 versus <240 (1.34–2.77), p < 0.001], which is consistent with published literature. We found that both absolute LDH levels and LDH ratios (LDHCTn: LDHCTn–1) were associated with tumour response [partial response versus progressive disease: median value across CT1–6 = 168–190 versus 222–398 (absolute); 0.738–0.988 versus 1.039–1.406 (ratio)], albeit LDH ratio had a tighter variance between patients. Finally, we showed that an LDH ratio cut-off of 1.0 at CT1, CT3 and CT5 was predictive of progressive disease at CT2, CT4, CT6 [area under the curve of 0.73 (0.65–0.80)]. Conclusion: Herein, we characterised the longitudinal variation of LDH in response to CT in mNPC. Our findings suggest the potential utility of interval LDH ratio to predict subsequent tumour response to CT.

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Prognostic Nomogram for Overall Survival in Early Stage Extranodal Natural Killer/T Cell Lymphoma Treated With High-Dose Radiotherapy

Cited by 4 publications

References 32 publications

The identification of gene signatures in patients with extranodal NK/T-cell lymphoma from a pair of twins

The identification of gene signatures in patients with extranodal NK/T-cell lymphoma from a pair of twins

The Novel Prognostic Index Model of Combining Circulating Tumor DNA and PINK-E Predicts the Clinical Outcomes for Newly Diagnosed Extranodal NK/T-cell Lymphoma

Lactate dehydrogenase kinetics predict chemotherapy response in recurrent metastatic nasopharyngeal carcinoma

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