Nasal Type Research Articles

Early-Stage Extranodal NK/T-Cell Lymphoma, Nasal Type: A Role for Elective Nodal Irradiation?

Early-Stage Extranodal NK/T-Cell Lymphoma, Nasal Type: A Role for Elective Nodal Irradiation?

Fifteen Years of Non-Hodgkin Lymphoma in an Indonesian National Referral Hospital: Epidemiologic Trends and Diagnostic Challenges

PURPOSE The global burden of lymphoma is substantial because of the increase in its incidence in recent decades. However, disease characteristics vary across different geographical locations. Numerous immunohistochemistry markers and molecular studies are essential to determine lymphoma diagnosis and prognosis. This poses significant challenges in developing countries with limited health care resources. This large-scale study assesses the frequency of non-Hodgkin lymphoma (NHL) in Indonesia over the past 15 years, analyses its clinicopathologic features, and predicts future trends. METHODS This retrospective study collected lymphoma patients diagnosed at the Department of Anatomical Pathology Dr. Cipto Mangunkusumo National Central General Hospital, Indonesia, from 2009 until 2023. All lymphoma diagnoses were confirmed by using ancillary tools classified as an enhanced lymphoma panel according to a resource-stratified guideline. We analyzed the clinicopathologic features of each NHL type and further applied the Autoregressive Integrated Moving Average model to predict future incidence trends. RESULTS The study consisted of 7,368 NHL patients. Among these, B-cell lymphomas accounted for 90.6%, with diffuse large B-cell lymphoma being the most prevalent subtype (68.8%), followed by follicular lymphoma (8.8%) and marginal zone lymphoma (5.8%). Extranodal natural killer/T-cell lymphoma, nasal type, is the most common T-cell lymphoma found (26.3%). All types of lymphoma were found to be more common in males (57.7%). Extranodal involvement, particularly in the tonsil and upper respiratory tract, was frequently observed. Projection analysis indicates a steady increase in lymphoma patients in the future. CONCLUSION This study highlights the distribution and burden of NHL in Indonesia over 15 years. The overall epidemiologic pattern of NHL in this study aligns with the results observed in other Asian countries. The rising incidence of lymphoma requires improved health care infrastructure and prevention strategies.

Effects of different masks on diaphragm motion in OSAS patients undergoing CPAP: results from an ultrasound-based proof of concept study.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway narrowing or collapse during sleep. Continuous positive airway pressure (CPAP) remains the preferred treatment in selected patients and masks' choice plays an important role for subsequent respiratory events' reduction. It is known that oronasal masks are not as effective at opening the upper airway compared to nasal ones. Thus, the objective of this study was to investigate differences in US-assessed diaphragmatic excursion (DE) using oronasal vs. nasal CPAP masks. This observational study included 50 OSA patients presenting a moderate to severe apnea-hypopneaindex and requiring CPAP treatment. All participants received US evaluations on diaphragm motion during their oronasal and nasal CPAP trial at equal positive end-expiratory pressure level. The difference of DE switching mask during CPAP was assessed by using the non-parametric Wilcoxon signed-rank test. A statistically significant increase in US- assessed DE was found when shifting from oronasal to nasal mask (p-value < 0.01). Linear regression models revealed that increased neck circumference and more severe AHI were associated with decreased DE when shifting to an oronasal mask. This study evaluated the acute impact on US-assessed DE after changing CPAP route from oronasal to nasal mask. Our results suggest that the nasal type should be the more suitable option for most patients with OSA, especially those with higher nasal circumference. Diaphragmatic motion throughout US may become a practical tool to help in the choice of the fittest mask in patients undergoing CPAP.

Deviation parameters of intraoral scanning with and without artificial markers versus conventional impression of total, partial and congenital nasal defects: A pilot non-randomized clinical trial

PurposeThis pilot clinical trial aimed to investigate accuracy of intra-oral scanning (IOS) with and without artificial reference markers in capturing total, subtotal and congenital nasal defects. Basic proceduresThirteen patients with 3 types of nasal defects were selected and digitally scanned using an IOS with (ScM) and without artificial markers (Sc). Patients were grouped as follows; Group T (total nasal defect), Group P (partial/subtotal nasal defect), Group C (congenital defect). Silicone impressions of the defects were made and poured to get a model that was scanned using a Desktop scanner (Imp). The standard tessellation language (STL) files obtained from IOS were registered and compared to each other using a processing software. RMS, positive and negative average values were used to report deviations between the scans. Kruskal Wallis test was used to study the effect of defect type, while Friedmann was used to study the effect of impression technique. Results were considered significant at P≤.05. Main findingsAll deviation values showed statistically significant differences among the 3 studied nasal defects and among the 3 investigated impression techniques. The smallest deviation values were recorded in Sc-ScM of congenital defects (RMS= 0.13±0.04, +average=0.08±0.01, -average=-0.09±0.02), while the largest deviation values were recorded in IMP-Sc in the total defects (RMS= 0.38±0.05, +average=0.29±0.04, -average=-0.29±0.04). ConclusionsWithin the limitations of this study, it was concluded that the nasal defect type and the use of artificial markers during scanning affect the deviation parameters of the obtained scan. The combined effect of the studied parameters calls for the use of markers in when scanning total nasal defects.

The Effect of Two Different Nasal Interfaces Used in Post-Extubation Non-Invasive Respiratory Support on Extubation Success in Newborns

Background: Non-invasive ventilation support is frequently used in newborns after extubation. The efficiency of non-invasive ventilation support is associated to type of nasal interface used. We aimed to investigate the effect of nasal interface type in our study on extubation success. Materials and Methods: We retrospectively evaluated a total of 105 term and preterm patients who were extubated to non-invasive ventilation. We divided the patients into two groups according to nasal interface type: RAM cannula or short binasal prongs (SBPs). We examined extubation failure between the two groups. Results: While 63 of the patients were in RAM cannula group, 42 of them were in SBPs group, and the demographic characteristics of the patients were similar. There was no statistically significant differen-ce in the extubation failure rates between the groups (RAM; %44.4 vs SBPs; %38.1, p=0.518). The Ram cannula group had a higher beginning median positive end-expiratory pressure value (7.0 vs 6.5 cmH2O, p=0.038; respectively) and a lower median respiratory rate (60 vs 62/minute, p=0.032; res-pectively) than the SBPs group. Conclusions: We believe that the easy-to-use RAM cannula can be used in selected patients, especially by setting the PEEP value approximately 1 cmH2O higher.

Primary intestinal T-cell and natural killer-cell lymphomas: Clinicopathologic and prognostic features of 79 cases in South China.

Primary intestinal T-cell and natural killer-cell lymphomas (PITNKLs) are aggressive and make pathologic diagnoses in biopsy specimens challenging. We analyzed different subtypes' clinicopathologic features and treatment outcomes. Seventy-nine PITNKL cases were characterized by clinical, morphologic, and immunohistochemical features. Among 79 cases of PITNKLs from 2008 to 2017 in our institution, 40 (50.63%) were extranodal NK/T-cell lymphoma, nasal type (ENKTL); 32 (40.51%) monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL); 6 (7.59%) intestinal T-cell lymphoma, not otherwise specified; and 1 (1.27%) indolent T-cell lymphoma of the gastrointestinal tract. Small intestine (n = 47) was the most common site. Monomorphic epitheliotropic intestinal T-cell lymphoma showed distinctive clinicopathologic features from other subtypes with high expression (96.88%) of spleen tyrosine kinase (SYK) and PD-L1 (87.5%) and the poorest prognosis (P < .001). CD30 was highly expressed in ENKTL (9/17, 57.94%) and irrelevant to prognosis (P > .05). Cases of PITNKL are biologically heterogeneous; most have a dismal prognosis. SYK and PD-L1 expression might be a significant marker for MEITL and helps differential diagnosis.

Diagnosis and Treatment of Skin Lesions in Renal Transplant Recipients: A Retrospective Review.

Immunosuppressive therapy is essential for to prevent graft rejection in renal transplant patients; however, it is associated with elevating the risk of several pathologies in these patients particularly infectious and neoplastic conditions. In this study, we explore the diagnosis and treatment of skin lesions in renal transplant patients. A retrospective chart review of 12 renal transplant recipients referred to plastic and reconstructive surgery with skin lesions from 2000 to 2020 was performed. The mean age of the 12 patients was 49.6 years. Time to plastic surgery after renal transplantation ranged between 1 and 16 years. Nine cases of basal cell carcinoma, 2 cases of squamous cell carcinoma, and 1 case of skin and soft tissue infection of the lower extremity and cutaneous extranodal NK/T-cell lymphoma, nasal type was observed. Flaps, skin grafts, and artificial dermis grafts constitute the main reconstructive methods. There were no postoperative infections or wound dehiscence. Cutaneous infections and skin malignancy account for most of the skin lesions developing after renal transplantation. Posttransplant lymphoproliferative disorder warrants equal attention and should not be disregarded. Early diagnosis and treatment significantly improve prognosis as patients with longer duration of transplant were found to have more aggressive tumors. Plastic and reconstructive surgery offers a safe therapeutic method of treatment in these cases.

Clinical and Paraclinical Features, Outcome, and Prognosis of ExtranodalNatural Killer/T-CellLymphoma,NasalType: A Retrospective Study of 31 Vietnamese Patients.

Background: Extranodal natural killer (NK)/T-cell lymphoma, nasal type is a rare, aggressive, and poor prognostic subtype. The concurrent chemoradiotherapy followed by chemotherapy showed a relatively high response rate and the toxicity due to the treatment is acceptable. The study attempted to report the clinicopathological features, the survival outcome, and response rates of stages I-II, nasal type ENKTL patients treated with CCRT followed by adjuvant VIPD chemotherapy in Vietnam. Materials and Methods: The current study was conducted on 31 stage I or II NK/T cell lymphoma, nasal-type patients received by CCRT, followed by adjuvant VIPD chemotherapy. Information on patient demographics, disease stage, clinical symptoms, tumor, and paraclinical characteristics were collected. The primary endpoints of this study were OS and response rates. Results: After CCRT, 26 out of 31 (83.9%) patients had stable disease or response. Overall response rate (ORR) was observed in 80.6% of patients with a complete response rate of 67.7%. Low-risk PINK patients had a higher response rate than the intermediate- risk group (p=0.038). Mean disease-free survival was 44.3±4.5 months (95% CI, 35.4-53.1 months). Mean overall survival was 46.8±4.5 months (95% CI, 37.99-55.8 months). The intermediate-risk PINK patients had a significantly lower OS rate than low-risk patients. Conclusion: Concurrent chemoradiotherapy followed by adjuvant VIPD chemotherapy showed a high response rate and survival benefit in stages I-II, nasal type, and extranodal natural killer (NK)/T-cell lymphoma Vietnamese patients.

Clinical epidemiology of Epstein-Barr virus-associated Lymphoproliferative Disorders (EBV-LPDs) in hospitalized children: A six-year multi-institutional study in China

BackgroundEpstein-Barr virus-associated lymphoproliferative disorders (EBV-LPDs) are a group of disorders involving lymphoid tissues or lymphocytes. The epidemiology and economic burden of hospitalized children with EBV-LPDs in China have not been well studied. This study aimed to reveal the epidemic characteristics and disease burden of EBV-LPDs among the Chinese hospitalized children, providing strategies for the prevention and management.MethodsThis study was based on the FUTang Updating medical REcords (FUTURE) database of China and collected the medical records from 27 tertiary children’s hospitals between January 2016 and December 2021 in China, counting five types of EBV-LPDs, namely EBV-positive T-cell lymphoproliferative disease, NK/T cell lymphoma, extranodal NK/T-cell lymphoma (nasal type), systemic EBV-positive T-cell lymphoproliferative disease of childhood and posttransplant lymphoproliferative disorders. We conducted a retrospective syhthesis and analysis of the epidemiological characteristics, expenses, length of stay (LOS), as well as complications among hospitalized children diagnosed with five types of EBV-LPDs and compared parameters using appropriate statistical tests.ResultsThe study described 153 children aged 0–18 years hospitalized with EBV-LPDs from 2016 to 2021 in the FUTURE database. The male-to-female ratio was 1.10:1, and more than half of the age distribution was in the 6–12 y group. Among EBV-LPDs cases, EBV+ T-LPD accounted for the largest proportion (65.36%). Complications were presented in 93 children with EBV-LPDs, mainly hemophagocytic lymphohistiocytosis (HLH). The median LOS of NKTL was 26.5 days [interquartile range (IQR) = 3–42], which was the longest among EBV-LPDs. The median hospitalization cost of PTLD was 10 785.74 United States dollars (IQR = 7 329.38–16 531.18), which was the heaviest among EBV-LPDs.ConclusionsCompared with the total number of hospitalized children in China during the same period and in the same age group, the proportion of EBV-LPD is very low. EBV-LPD can develop in all age groups, but it is more common in school-age children. Among 5 EBV-LPDs, the disease with the highest proportion is EBV+ T-LPD. The overall disease burden of EBV-LPD was heavy, especially the economic burden. HLH was one of the most common complications, which could directly affect the burden of patients because of prolonged hospitalization. These data are taken from a very large database, illustrating the epidemiological and economic burden of EBV-LPDs hospitalized children in China, which enriched the existing epidemiological and disease burden content of EBV-LPDs.

Genomic Sequencing and Analysis of Enzootic Nasal Tumor Virus Type 2 Provides Evidence for Recombination within the Prevalent Chinese Strains.

In recent years, the clinical cases of ENTV-2 infection have increased and become prevalent in several provinces of China. In this study, we reported the occurrence of ENTV-2 in one goat farm in Chongqing, southwest China. The complete genome of an emerged ENTV-2 isolate (designated as CQ2) was sequenced with 7468 bp in length. Phylogenetic analysis revealed that ENTV-2 consisted of two main lineages. Lineage 1 was composed of Chinese strains and could be subdivided into five sublineages. CQ2 and the other six recent isolates from China were clustered in sublineage 1.5; however, CQ2 was significantly different from the other six isolates. Furthermore, recombination analysis suggested that CQ2 might be a recombinant variant derived from sublineage 1.5 and sublineage 1.2 strains, with the recombination region in areas of pro and pol genes. In conclusion, we sequenced and analyzed the complete genome of a potential ENTV-2 recombinant, which may contribute to our understanding of the genetic variation and evolution of ENTV-2 in China.

EXTRANODAL NK/T-LYMPHOMA, NASAL TYPE: CASE REPORT

Extranodal NK/T-lymphoma, nasal type (ENKTCL-NT), is a highly aggressive malignancy linked to Epstein-Barr virus infection. This type of lymphoma primarily affects nasal or upper aerodigestive structures, resulting in a necrotic process. Despite its clinical stage or treatment, ENKTCL-NT is known for itsunfavorableprognosis,Wepresentis a case of a 57-year-old patient who presented with an ulcerated nasal swelling accompanied by nasal obstruction. Imaging revealed a tumorous process within the nasal cavity. Histological and immunohistochemical studies favored a diagnosis of NK/T lymphomanasal-type.The patient underwent primary chemotherapy followed by radiotherapy, achieving complete clinical and radiological response. This response has been maintained for three years after completing the treatment.

Succinylation of 14–3–3 theta by CPT1A promotes survival and paclitaxel resistance in nasal type extranodal natural killer/T-cell lymphoma

BackgroundThe aggressive and refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL-NT) is a subtype of non-Hodgkin's lymphoma. Succinylation promotes progression in a variety of tumors, but its mechanism in ENKTL-NT is unclear. MethodsBioinformatic analysis was performed to screen differentially expressed genes in the ENKTL dataset. Cell transfection techniques were used for knockdown and overexpression of genes. The mRNA and protein expression were detected using RT-qPCR and western blot, respectively. Immunohistochemical staining was used to assess protein expression in situ. For the detection of cell proliferation activity, CCK-8, clonal formation, and EDU staining assays were used. Flow cytometry was employed to detect apoptosis. Co-immunoprecipitation was utilized for the identification of protein interactions and succinylation modifications. ResultsSuccinyltransferase CPT1A was highly elevated in ENKTL-NT and was associated with a dismal prognosis. CPT1A knockdown suppressed SNK-6 cells’ proliferation and induced apoptosis, while these effects were reversed by the overexpression of 14–3–3theta. Co-immunoprecipitation results showed that CPT1A caused succinylation of 14–3–3theta at site of K85, thereby enhancing the protein stability. Suppression of CPT1A-induced succinylation of 14–3–3theta by ST1326 resulted in the inhibition of SNK-6 cell proliferation and increased apoptosis. Paclitaxel combined with knockdown of CPT1A significantly inhibited the proliferation of ENKTL-NT compared to paclitaxel alone. ConclusionCPT1A induces succinylation of 14–3–3theta at the K85 site, promoting ENKTL-NT proliferation. The anti-ENKTL activity of paclitaxel was improved when combined with CPT1A knockdown.

Characteristics of upper respiratory tract rhinovirus in children with allergic rhinitis and its role in disease severity.

Our study revealed high human rhinovirus (HRV) detection rate in children with allergic rhinitis (AR), and HRV infection (A, B, or C species) is positively associated with the symptom severity in AR children. Elevated nasal IgE, interleukin-25 (IL-25), IL-4, and CXCL13 levels suggest a potential pathogenic mechanism by which HRV infection induces nasal type 2 immune/inflammation responses and local IgE production in AR patients. In addition, etiological analysis found that the main prevalent HRV species in AR children are A and B (~80%), which is different from acute respiratory infection and asthma exacerbation, where species A and C are dominant. The data reveal the distinct species prevalence characteristics of HRV infection in AR. Finally, we isolated all three species of HRV strains from nasal cavity of AR children with varying degrees of antigenic epitope mutations and in vitro infectivity, highlighting the importance of strengthening monitoring and intervention for respiratory HRV infection in AR children.

Epstein-Barr virus-related lymphoproliferative disorders of the skin.

Epstein Barr Virus (EBV) is associated both solid (nasopharyngeal carcinoma, non-nasopharyngeal lymphoepithelioma-like carcinoma, gastric carcinoma, leiomyosarcoma) and hematolymphoid malignancies, some of the latter, however, spanning over a spectrum ranging from reactive and self-limiting to severe and life-threatening conditions. This review will focus on the disorder most commonly involving the skin, namely: EBV-positive mucocutaneous ulcer; lymphomatoid granulomatosis; EBV-positive diffuse large B cell lymphoma; plasmablastic lymphoma; post-transplant lymphoproliferative disorder; extranodal NK/T cell lymphoma, nasal type; angoimmunoblastic T cell lymphoma; severe mosquito bite allergy; hydroa vacciniformelike lymphoproliferative disorder. Given the uncommon occurrence of all these infiltrates in the skin, multidisciplinary approach, as well as referral to tertiary care centers are always advisable.

Baseline characterization of a cohort of colombian patients with chronic rhinosinusitis with nasal polyps

To present the baseline clinical and demographic characteristics of CRSwNP patients over the age of 18 enrolled in a Patient Support Program (PSP) prior to biologic treatment. Descriptive, cross-sectional study performed in a Colombian CRSwNP asthma PSP sponsored by Sanofi from Aug-2021 to Jul-2022. Data was collected from CRSwNP patients, prior to the start of Dupilumab treatment, who consented to the use of their data. The following information was reported: Age, reporting city, treating medical specialty, comorbidities, and persistence of treatment. 339 patients were included, 171 (50,4%) were women and 168 (49,6%) were men. The mean age at Dupilumab treatment initiation was 52,4 years. 62,8% began treatment during adulthood (26-59y), while 34.1% started at elderly (+60y) and 3.1% were young adults (18-25y). Most cases (29,7%) were included in Bogotá, followed by Antioquia (19%), Valle del Cauca (7,3%) and the remaining 44% nationwide. Comorbidities were present in 67,1% of the patients, with diagnosis of allergic rhinitis, atopic dermatitis, asthma, and other non-type 2 inflammatory diseases. Nasal surgical history was present in 89,6% of the patients, most of them with one to three previous surgeries. Continuous treatment was observed in 70,3% of patients for 6 to 12 months, in 21,3% for more than 12 months and in 8,4% for less than six months. The most frequently treating medical specialty was otorhinolaryngology (79,6%), followed by allergology (16%) and other medical professionals (4,4%). There is concordance with the literature on a higher presentation of the disease in women than in men. There is a large proportion of patients with nasal surgical history and type 2 inflammatory comorbidities by the moment of biologic treatment initiation. The care and identification of CRSwNP colombian patients is mainly provided by otorhinolaryngologists, followed by allergologists.

Serum aspartate aminotransferase, a novel potential biomarker of prognosis in extranodal natural killer/T cell lymphoma, nasal type.

Aspartate aminotransferase (AST), an indicator of liver cell damage, was related to the prognosis of certain malignant tumors. This study examined the predictive value of AST in patients with extranodal natural killer/T cell lymphoma (ENKTL). We reviewed 183 cases diagnosed with ENKTL and selected 26 U/L as the optimum cut-off value of AST. We used the univariate and multivariate Cox regression to compare the different AST groups' overall survival (OS) and progression-free survival (PFS). Prior to propensity score matching (PSM), Kaplan-Meier analysis showed that patients in the low AST subgroup had better OS and PFS than the high AST subgroup. Multivariate analysis revealed that AST was an independent indicator for prognosis. After PSM, the low AST subgroup maintained a significantly better OS and PFS than the high AST subgroup. AST might represent a significant prognostic marker for ENKTL patients.

Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.

Clinical characteristics and prognostic analysis of primary extranodal non-Hodgkin lymphoma of the head and neck.

Primary extranodal non-Hodgkin's lymphoma (PE-NHL) of the head and neck is the second common site of extranodal lymphoma, accounting for approximately one-third of all extranodal non-Hodgkin's lymphoma (E-NHL). However, in recent years, large-scale PE-NHL case studies in China and worldwide are rare and not comprehensive enough. This work analyzed the clinical manifestations, pathological features, immunophenotypes and diagnosis of PE-NHL, as well as the factors affecting the treatment and prognosis. A retrospective study was performed on 74 patients who were diagnosed with head and neck PE-NHL and treated for the first time. The clinical manifestations, pathological features, and immunophenotypes were summarized, and the factors related to the treatment and prognosis were analyzed. The most common site of this disease was the Waldeyer's ring, followed by the nasal cavity. Diffuse large B-cell lymphoma was the most common type, followed by extranodal NK T-cell lymphoma nasal type. The 1-year, 2-year, and 5-year progression-free survival (PFS) rates were 76.4%, 67.9%, and 59.3%. The 1-year, 2-year, and 5-year overall survival (OS) rates were 89.4%, 85.6%, and 63.2%. ECOG score ≥ 2, Ann Arbor stage III or IV and IPI risk stratification identifying patients as the high-risk group were independent risk factors affecting the OS of patients with PE-NHL of the head and neck. The most common site of PE-NHL in these Chinese patients was the Waldeyer's ring, but the incidence in the nasal cavity was higher than that reported in Western countries. Radiotherapy combined with chemotherapy had better efficacy than chemotherapy alone, and the prognosis depended on the ECOG score and clinical stage. IPI had a better prognostic value in patients in the high-risk group of head and neck PE-NHL.

Analysis of the treatment and prognosis of 266 cases of extranodal natural killer/T-cell lymphoma, nasal type in a single medical center.

To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05. Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis. Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.

First-line sintilimab with pegaspargase, gemcitabine, and oxaliplatin in advanced extranodal natural killer/T cell lymphoma (SPIRIT): a multicentre, single-arm, phase 2 trial

Programmed cell death protein 1 (PD-1) inhibitor sintilimab is effective in relapsed and refractory extranodal natural killer/T cell lymphoma (ENKTL), nasal type. We aimed to assess the safety and activity of sintilimab plus P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) in the first-line setting for advanced ENKTL. The multicentre, single-arm, phase 2 trial was done at three medical centres in China. Patients aged 18-75 years with treatment-naive pathologically confirmed advanced ENKTL and an with Eastern Cooperative Oncology Group performance status score of 0-2 were eligible. Patients received intravenous sintilimab (200 mg on day 1), intramuscular pegaspargase (2000 U/m2 on day 1), intravenous gemcitabine (1 g/m2 on days 1 and 8), and intravenous oxaliplatin (130 mg/m2 on day 1) every 3 weeks for six cycles, followed by intravenous sintilimab (200 mg) every 3 weeks for up to 2 years or until disease progression or unacceptable toxicities. The primary endpoint was the complete response rate in the intention-to-treat population. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease-free survival (DFS), and overall survival. This trial is registered with ClinicalTrials.gov, NCT04127227. Enrolment has been completed, and follow-up is ongoing. Between Nov 29, 2019, and Sept 7, 2022, 34 eligible patients were enrolled (median age 39 years [IQR 32-55]; 25 [74%] of 34 patients were male; nine [26%] were female; and all were of Asian ethnicity). At the data cutoff (July 20, 2023), the median follow-up was 21 months (IQR 13-32). The complete response rate was 85% (29 of 34 patients, 95% CI 70-94). Five patients (15%; 95% CI 7-30) attained partial response and the ORR was 100% (34 of 34 patients). 24-month PFS was 64% (95% CI 48-86), 24-month DFS was 72% (54-95), and 36-month overall survival was 76% (52-100). The most common grade 3 or 4 treatment-related adverse events were neutropenia (17 [50%] of 34 patients), anaemia (10 [29%] patients), and hypertriglyceridemia (10 [29%] patients). Hypothyroidism was the most frequent immune-related adverse event (18 [53%]), including grade 3 hypothyroidism in one (3%) patient that caused treatment termination. No severe adverse events occurred. There were three deaths: one due to haemophagocytic syndrome, one due to disease progression, and one due to unknown cause, which were not considered to be treatment related. Combination of sintilimab with P-GEMOX seems to be an active and safe first-line regimen for patients with advanced ENKTL. National Key Research and Development Program and National Natural Science Foundation of China, Guangzhou Science and Technology Program and the Clinical Oncology Foundation of Chinese Society of Clinical Oncology.