Dataset Information

Phase II study of sequential chemoradiotherapy with L-asparaginase, dexamethasone, ifosfamide, cisplatin, and etoposide (DICE-L) in the early stage of extranodal natural killer (NK)/T-cell lymphoma.

ABSTRACT:

Background

To explore a more effective treatment strategy for newly diagnosed stage I and II extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, we conducted a prospective phase II study of sequential chemoradiotherapy with the L-asparaginase, dexamethasone, ifosfamide, cisplatin, and etoposide (DICE-L) regimen.

Methods

Patients with newly diagnosed stage I and II ENKTL in the upper-aerodigestive tract were enrolled. Treatment was comprised of up to 4 cycles of DICE-L followed by 50 Gy of intensity modulated radiation therapy (IMRT) to the involved field. The primary endpoint was the complete response (CR) rate. The secondary endpoints were the objective response rate (ORR), the 5-year overall survival (OS) rate, the 5-year progression-free survival (PFS) rate, and safety.

Results

A total of 81 patients were enrolled from June 2009 to May 2012 in Shanghai Cancer Hospital. Among these patients, 68 patients achieved CR and 1 patient achieved partial response (PR). The CR rate was 84%, and the ORR was 85.2%. With a median follow up of 88.1 months, the 5-year OS and 5-year PFS rates were 82.4% and 63.4%, respectively. The most common adverse events were grade 3 to 4 neutropenia (73.5%) and febrile neutropenia (21%).

Conclusions

Sequential chemoradiotherapy using DICE-L followed by radiotherapy is an effective treatment modality for stage I to IIE ENKTL and is safe with acceptable toxicity.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC8350702 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Asparaginase (ASP) is the cornerstone drug in the treatment of extranodal NK/T-cell lymphoma (ENKTCL), and the mechanisms of resistance to ASP remain largely unknown. Long non-coding RNAs play important roles in chemotherapy resistance in various cancers. However, the expression of BCYRN1 and its role in ENKTCL still remain unidentified. Methods: Lentivirus-mediated BCYRN1 overexpression and knockdown were performed in SNK-6 cells. Cell autophagy was analyzed by adenovirus expressing GFP-LC3B fusion protein. RNA pull-down and RNA Binding Protein Immunoprecipitation Assay were performed to investigate the relationship between BCYRN1 and p53. Western blot analysis was performed to assess the effect of BCYRN1 on different autophagy pathways. Finally, in vivo xenograft tumor model was constructed to analyze the effect of BCYRN1 on tumor growth and ASP resistance. Results: BCYRN1 was overexpressed in ENKTCL than normal NK cells, and patients with higher expression had significantly inferior progression-free survival (PFS). The IC50 value of ASP was significantly increased in BCYRN1-overexpressed SNK-6 cells and BCYRN1 overexpression could resist the inhibitory effect of ASP on proliferation. ASP could induce concurrent apoptosis and autophagy in ENKTCL, and the latter process was enhanced by overexpression of BCYRN1, mainly through affecting both PI3K/AKT/mTOR and p53/mTOR pathways. BCYRN1 could induce the degradation of p53 via ubiquitination, thus resulting in enhancement of autophagy and ASP resistance, which could be reversed by drug-induced autophagy inhibition. The effect of BCYRN1 on tumor growth and autophagy were confirmed in vivo xenograft model. Conclusions: It was found that BCYRN1 was a valuable prognostic biomarker in ENKTCL. BCYRN1 could promote resistance to ASP by inducing autophagy, which could be reversed by inhibition of autophagy. Our findings highlight the feasibility of combining autophagy inhibition and ASP in the treatment of ENKTCL.