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Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

ABSTRACT: Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a distinct subtype of non-Hodgkin lymphoma and most of the patients presented localized disease. Combined modality therapy (CMT), namely chemotherapy combined with radiotherapy, has been recommended for patients with early-stage ENKTL. However, the optimal CMT has not been fully clarified. This study reports the efficacy and toxicity of sequential P-GEMOX (pegaspargase, gemcitabine and oxaliplatin) and radiotherapy in a large Chinese cohort comprising of 202 patients diagnosed with early-stage ENKTL from six medical centers. The observed best overall response rate was 96.0% and 168 (83.2%) patients achieved complete remission. With a median follow-up of 44.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 74.6% and 85.2%, respectively. Multivariate analysis suggested that extensive primary tumor (PFS, hazard ratio [HR] 3.660, 95% CI 1.820-7.359, p < 0.001; OS, HR 3.825, 95% CI 1.442-10.148, p = 0.007) and Eastern Cooperative Oncology Group performance status ≥ 2 (PFS, 3.042, 95% CI 1.468-6.306, p = 0.003; OS, HR 3.983, 95% CI 1.678-9.457, p = 0.02) were independent prognostic factors for survival outcomes. Among the established prognostic models for ENKTL, the nomogram-revised risk index model had optimal prognostic risk stratification ability (PFS, p < 0.001; OS, p < 0.001) and relatively balanced population distribution. The adverse events of this CMT were well-tolerated and manageable. In conclusion, sequential P-GEMOX and radiotherapy showed favorable efficacy with acceptable toxicity, and could be an effective treatment option for early-stage ENKTL patients.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9291061 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Prognosis of early-stage extranodal natural killer/T-cell lymphoma (NKTCL) is usually estimated and stratified at diagnosis, but how the prognosis actually evolves over time for patients who survived after curative treatment is unknown. Objective:To assess conditional survival and failure hazard over time based on risk categories, previous survival, and treatment. Design, Setting, and Participants:This retrospective cohort study reviewed the clinical data of 2015 patients with early-stage NKTCL treated with radiotherapy identified from the China Lymphoma Collaborative Group multicenter database between January 1, 2000, and December 31, 2015. Patients were stratified into low-, intermediate- and high-risk groups according to a previously established prognostic model. Median follow-up was 61 months for surviving patients. Data analysis was performed from December 1, 2017, to January 30, 2018. Exposures:All patients received radiotherapy with or without chemotherapy. Main Outcomes and Measures:Conditional survival defined as the survival probability, given patients have survived for a defined time, and annual hazard rates defined as yearly event rate. Results:A total of 2015 patients were included in the study (mean [SD] age, 43.3 [14.6] years; 1414 [70.2%] male); 1628 patients (80.8%) received radiotherapy with chemotherapy, and 387 (19.2%) received radiotherapy without chemotherapy. The 5-year survival rates increased from 69.1% (95% CI, 66.6%-71.4%) at treatment to 85.3% (95% CI, 81.7%-88.2%) at year 3 for conditional overall survival and from 60.9% (95% CI, 58.3%-63.3%) at treatment to 84.4% (95% CI, 80.6%-87.6%) at year 3 for conditional failure-free survival. The annual hazards decreased from 13.7% (95% CI, 13.0%-14.3%) for death and 22.1% (95% CI, 21.0%-23.1%) for failure at treatment to less than 5% after 3 years (death: range, 0%-3.9% [95% CI, 3.7%-4.2%]; failure: 1.2% [95% CI, 1.0%-1.4%] to 4.2% [95% CI 3.9%-4.6%]). Intermediate-risk (11.4% [95% CI, 10.5%-12.3%]) and high-risk (21.6% [95% CI, 20.0%-23.2%]) patients had initially higher but significantly decreased death hazards after 3 years (<6%, range: 0%-5.9% [95% CI, 5.2%-6.7%]), whereas low-risk patients maintained a constantly lower death hazard of less than 5% (range, 0%-4.8%; 95% CI, 4.4%-5.3%). In high-risk patients, radiotherapy combined with non-anthracycline-based regimens were associated with higher conditional overall survival before year 3 compared with anthracycline-based regimens (hazard ratio [HR] for death, 1.49; 95% CI, 1.13-1.95; P = .004 at treatment; HR, 1.60; 95% CI, 1.07-2.39; P = .02 at 1 year; and HR, 1.77; 95% CI, 0.94-3.33; P = .07 at 2 years) or radiotherapy alone (HR, 2.42; 95% CI, 1.73-3.39; P < .001 at treatment; HR, 1.82; 95% CI, 1.05-3.17; P = .03 at 1 year; and HR, 2.69; 95% CI, 1.23-5.90; P = .01 at 2 years). Conclusions and Relevance:The survival probability increased and the hazards of failure decreased in a risk-dependent manner among patients with early NKTCL after radiotherapy. These dynamic data appear to provide accurate information on disease processes and continual survival expectations and may help researchers design additional prospective clinical trials and formulate risk-adapted therapies and surveillance strategies.

Project description:Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NNKTL) has very unique epidemiological, etiologic, histologic, and clinical characteristics. It is commonly observed in Eastern Asia, but quite rare in the United States and Europe. The progressive necrotic lesions mainly in the nasal cavity, poor prognosis caused by rapid local progression with distant metastases, and angiocentric and polymorphous lymphoreticular infiltrates are the main clinical and histologic features. Phenotypic and genotypic studies revealed that the lymphoma is originated from either NK- or ?? T-cell, both of which express CD56. In 1990, the authors first reported the presence of Epstein-Barr virus (EBV)-DNA and EBV-oncogenic proteins, and EBV has now been recognized to play an etiological role in NNKTL. in vitro studies revealed that a wide variety of cytokines, chemokines, and micro RNAs, which may be produced by EBV-oncogenic proteins in the lymphoma cells, play important roles for tumor progression in NNKTL, and could be therapeutic targets. In addition, it was revealed that the interaction between NNKTL cells and immune cells such as monocytes and macrophages in NNKTL tissues contribute to lymphoma progression. For diagnosis, monitoring the clinical course and predicting prognosis, the measurements of EBV-DNAs and EBV-micro RNAs in sera are very useful. For treatment with early stage, novel concomitant chemoradiotherapy such as DeVIC regimen with local radiotherapy and MPVIC-P regimen using intra-arterial infusion developed with concomitant radiotherapy and the prognosis became noticeably better. However, the prognosis of patients with advanced stage was still poor. Establishment of novel treatments such as the usage of immune checkpoint inhibitor or peptide vaccine with molecular targeting therapy will be necessary. This review addresses recent advances in the molecular understanding of NNKTL to establish novel treatments, in addition to the epidemiologic, clinical, pathological, and EBV features.

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Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: A multicenter study.

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