Update on Molecular Diagnosis in Extranodal NK/T-Cell Lymphoma and Its Role in the Era of Personalized Medicine

Sun, Ka-Hei; Wong, Y.; Cheung, Ka Man; Yuen, Carmen; Chan, Y.K.; Lai, W.‐Y.; Chao, Chun; Fan, Wing-Sum; Chow, Yuen-Kiu; Law, Man Fai; Tam, Ho-Chi

doi:10.3390/diagnostics12020409

Cited by 7 publications

(20 citation statements)

References 115 publications

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“…First, currently available prognostic indices for ENKTL, for example, IPI, KPI, and PINK-E, do not incorporate molecular mutations as one of the prognostic markers. 45 To the best of our knowledge, PINK-EC was the first prognostic model incorporating ctDNA concentration for ENKTL. Second, the PINK-EC score integrated molecular pathology results, providing superior predictive accuracy and stability.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…The positive rate of PD-L1 in ENKTCL cells is 39-100% ( 8 ). Overexpression of PD-L1 induced by EBV infection, on the one hand, is a potential mechanism by which ENKTCL avoids immune surveillance ( 182 , 183 ), on the other hand, is a predictor of favorable response to PD-1 blockade treatment ( 159 , 160 ).…”

Section: Treatment Of Advanced-stage and R/r Enktclmentioning

confidence: 99%

“…In particular, we mainly focused on several neglected or unanswered issues in the treatment of ENKTCL, including the optimal staging method, the best partner of Asp, the individualized administration of Asp, the preferred sequence of CT and RT and so on. The pathologic and genetic features of this disease have recently been well reviewed by others (8)(9)(10). When analyzing the outcomes of patients treated with different approaches or modalities, we visualized the data using figures, as most data are from retrospective studies with small cohorts and heterogenous treatments, which are difficult to compare directly.…”

Section: Introductionmentioning

confidence: 99%

Treatment of extranodal NK/T-cell lymphoma: From past to future

et al. 2023

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Extranodal NK/T-cell lymphoma (ENKTCL) is the most common subtype of T/NK-cell lymphoma in Asia and Latin America, but very rare in North American and Europe. Patient survival has improved significantly over the past two decades. However, standard treatment has not yet been established, although dozens of prospective trials have been conducted. To help understand how the treatment of ENKTCL has evolved in the past and what trends lie ahead, we have comprehensively reviewed the treatment of this aggressive malignancy, with a particular focus on neglected or unanswered issues, such as the optimal staging method, the best partner of asparaginase (Asp), the individualized administration of Asp, the preferred sequence of CT and RT and so on. Overall, the 5-year overall survival (OS) of patients with Ann Arbor stage I/II disease increased from < 50% in the early 20th century to > 80% in recent years, and the median OS of patients with Ann Arbor stage III/IV disease increased from < 1 year to more than 3 years. The improvement in patient survival is largely attributable to advances in radiation technology and the introduction of Asp and anti-PD-1/PD-L1 immunotherapy into practice. Radiotherapy is essential for patients with early-stage disease, while Asp-based chemotherapy (CT) and PD-1/PD-L1 inhibitors significantly improved the prognosis of patients with advanced-stage disease. ENKTCL management is trending toward simpler regimens, less toxicity, and higher efficacy. Novel drugs, such as manufactured T cells, monoclonal antibodies, and small molecule inhibitors, are being intensively investigated. Based on the fact that ENKTCL is highly resistant to cytotoxic drugs except Asp, and aggressive CT leads to higher toxicity rather than better outcomes, we recommend it is unnecessary to expend additional resources to compare different combinations of Asp with cytotoxic agents. Instead, more efforts should be made to optimize the use of Asp and immunotherapy to maximize efficacy and minimize toxicity, explore ways to overcome resistance to Asp and immunotherapy, identify novel treatment targets, and define subpopulations who may benefit more from specific treatments.

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“…ENKTL is notoriously resistant to anthracycline-based chemotherapy, whereas the use of L-asparaginase-based chemotherapy combined with radiotherapy has improved the outcome for this aggressive lymphoma [ 78 ]. However, as chemotherapy is often unable to achieve long-term remissions in advanced stages of the disease, it is extremely important that novel therapies targeting different molecular pathways are currently available [ 79 , 80 ].…”

Section: Differential Diagnoses Of Ivnktlmentioning

confidence: 99%

“…Despite still lacking a standardized expression cutoff for predicting the response to PD-1/PD-L1 inhibitors, several clinical trials are ongoing, and immune checkpoint inhibitor therapy is used in relapsed or refractory disease [ 81 ]. Due to the relevant role played by the activation of both JAK/STAT and NF-kB pathways in ENKTL pathogenesis, these pathways are potentially targetable for therapy [ 74 , 75 , 76 , 79 , 80 ]. Further studies are needed to evaluate the efficacy of the anti-CD30 antibody brentuximab vedotin, particularly in combination with chemotherapy, for the treatment of ENKTL [ 82 ].…”

Section: Differential Diagnoses Of Ivnktlmentioning

confidence: 99%

Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease

Zanelli

Parente

Sanguedolce

et al. 2022

Cancers

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Intravascular lymphoma is a form of lymphoid malignancy characterized by neoplastic cells growing almost exclusively within the lumina of small- to medium-sized blood vessels. Most cases are of B-cell origin with rare cases of natural killer or T-cell lineage. Extranodal sites are affected, mainly the skin and central nervous system, although any organ may be involved. Intravascular NK/T-cell lymphoma deserves special attention because of its clinicopathologic features and the need for adequate immunophenotyping combined with clonality test for a proper diagnosis. Moreover, intravascular NK/T-cell lymphoma is strongly linked to Epstein–Barr virus (EBV), which is considered to play a role in tumorigenesis and to be responsible for the aggressive behavior of the disease. In this paper, we review the current knowledge on this rare lymphoma and, in particular, the most recent advances about its molecular landscape. The main distinguishing features with other EBV-related entities, such as extranodal NK/T-cell lymphoma, EBV-positive primary nodal T/NK-cell lymphoma, and aggressive NK-cell leukemia, are discussed to help pathologists obtain the correct diagnosis and consequently develop an adequate and prompt therapy response.

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Update on Molecular Diagnosis in Extranodal NK/T-Cell Lymphoma and Its Role in the Era of Personalized Medicine

Cited by 7 publications

References 115 publications

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

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

Treatment of extranodal NK/T-cell lymphoma: From past to future

Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease

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