Benefit of consolidative radiation in patients with extranodal limited-stage diffuse large B-cell lymphoma: a multicenter retrospective study in China.

Approximately 40% of limited-stage (stage I and II) diffuse large B-cell lymphoma (LS-DLBCL) presents with extranodal disease. Extranodal LS-DLBCL may have significant biological differences and associated with worse outcomes than nodal disease. Although rituximab based chemoimmunotherapy is standard of first-line treatment, the role of consolidative radiotherapy (RT) in this particular subgroup is controversial. In this multicenter retrospective study, we evaluated the survival benefit of consolidative RT in patients diagnosed with extranodal LS-DLBCL and received rituximab-based chemoimmunotherapy with or without consolidative RT. A total of 328 patients were included, 129 patients (39.3%) received chemoimmunotherapy and consolidative RT, and 199 patients (60.7%) received chemoimmunotherapy alone. With a median follow-up of 5.1 years (range, 0.3-14.8 years), 5-year progression-free survival (PFS) and overall survival (OS) for all patients were 75.4% and 83.9%, respectively. In multivariate analyses, the addition of consolidative RT was associated with superior OS (P = 0.004) and PFS (P = 0.005). High stage-modified International Prognosis Index (SM-IPI) risk predicted worse OS (P = 0.001) and PFS (P = 0.005). Also, propensity score-matched analyses showed RT improved both OS (hazard ratio [HR] 0.228, 95% confidence index [CI] 0.111-0.467, P < 0.001) and PFS (HR 0.308, 95% CI 0.167-0.566, P < 0.001). Among patients who achieved CR, 49 patients (16.6%) developed disease relapse, of which 30.6% relapsed at local sites. Consolidative RT significantly reduced relapse risk (P = 0.002). Our results demonstrated that consolidative RT significantly improved outcomes in patients with extranodal LS-DLBCL in the rituximab era.

Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression.

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. METHODS: Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. RESULTS: Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0-C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. CONCLUSIONS: The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.

Novel agents and regimens in relapsed or refractory peripheral T-cell lymphoma: latest updates from 2023 ASH annual meeting.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological malignancies with poor survival, while treatment options for relapsed or refractory (R/R) disease remain quite limited, with a median progression-free survival of only 3-4 months. Notably, the emergence of innovative therapeutic agents and regimens holds promise for durable responses and improved survival for patients with R/R PTCL. We summarize recent advances in the treatment of R/R PTCL from the 2023 ASH Annual Meeting, highlighting novel agents targeting EZH1/2, JAK1, PI3K, KIR3DL2, CD38/CD3xCD28, or CDK9, as well as therapeutic regimens in combination with stem cell transplantation, immunomodulators, epigenetic modifying agents, or CD30/CD16A bispecific antibodies.

Development and validation of a novel prognostic nomogram for advanced diffuse large B cell lymphoma.

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and ß2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.

Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.

Tetrahedral DNA loaded siCCR2 restrains M1 macrophage polarization to ameliorate pulmonary fibrosis in chemoradiation-induced murine model.

Idiopathic pulmonary fibrosis (IPF) is a chronic lethal disease in the absence of demonstrated efficacy for preventing progression. Although macrophage-mediated alveolitis is determined to participate in myofibrotic transition during disease development, the paradigm of continuous macrophage polarization is still under-explored due to lack of proper animal models. Here, by integrating 2.5 U/kg intratracheal Bleomycin administration and 10 Gy thorax irradiation at day 7, we generated a murine model with continuous alveolitis-mediated fibrosis, which mimics most of the clinical features of our involved IPF patients. In combination with data from scRNA-seq of patients and a murine IPF model, a decisive role of CCL2/CCR2 axis in driving M1 macrophage polarization was revealed, and M1 macrophage was further confirmed to boost alveolitis in leading myofibroblast activation. Multiple sticky-end tetrahedral framework nucleic acids conjunct with quadruple ccr2-siRNA (FNA-siCCR2) was synthesized in targeting M1 macrophages. FNA-siCCR2 successfully blocked macrophage accumulation in pulmonary parenchyma of the IPF murine model, thus preventing myofibroblast activation and leading to the disease remitting. Overall, our studies lay the groundwork to develop a novel IPF murine model, reveal M1 macrophages as potential therapeutic targets, and establish new treatment strategy by using FNA-siCCR2, which are highly relevant to clinical scenarios and translational research in the field of IPF.

Discontinuation and nonpublication of nasopharyngeal carcinoma clinical trials.

OBJECTIVES: To determine the extent of research waste in the field of nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: In this cross-sectional study, we explored the rates, causes and predictors of discontinuation and nonpublication of NPC clinical trials. The sample was derived using the ClinicalTrials.gov advanced search function. Adjusted logistic regression was used to ascertain the effect of trial characteristics on completion and publication status. If a trial discontinuation explanation or publication status could not be determined through the systematic search, the corresponding author was emailed. RESULTS: Ultimately, 311 NPC clinical trials were included (255 [82.0 %] completed and 56 [18.0 %] discontinued trials). The most common reason for trial discontinuation was poor accrual (50 %, 23/46). Industry funding (adjusted OR, 3.12; P = 0.003) and recurrent/metastatic setting (adjusted OR, 11.95; P = 0.003) were significantly associated with increased likelihood of trial discontinuation. Of the 207 completed trials included in the publication query, 141 (68.1 %) were published in peer-reviewed journals, 10 (4.8 %) had results only available on ClinicalTrials.gov, and 56 (27.1 %) remained unpublished 3 or more years after trial completion. Radiation with or without pharmacologic interventions significantly increased the potential of publication (adjusted OR, 3.20; P = 0.048). Among published trials, the median time to publication was 28.47 months (interquartile range, 15.27-44.98 months). CONCLUSION: We identified the difficulties inherent in NPC clinical trials from completion to publication. This represents considerable research waste in NPC, thus raising ethical concerns about the concealment of clinical data and futile patient participation and attendant risks.

Primary breast diffuse large B-cell lymphoma in the rituximab era: A retrospective study of the Chinese Southwest Oncology Group.

BACKGROUND: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of extranodal DLBCL, and the standard treatment remains controversial. In this study, we aimed to define the optimal treatment management in the rituximab era. METHODS: A total of 5089 newly diagnosed DLBCL patients treated with rituximab-containing immunochemotherapy between 2008 and 2019 from the Chinese Southwest Oncology Group-affiliated institutes were identified, of whom 135 diagnosed with PB-DLBCL were eligible for this analysis. RESULTS: PB-DLBCL accounted for 2.7% of all DLBCLs. With a median follow-up of 4.2 years, the 5-year overall survival and progression-free survival rates were 84.8% and 71.6%, respectively. Breast and central nervous system (CNS) relapses were the main cause of treatment failure. We observed that consolidative breast radiotherapy (RT) significantly decreased breast relapse risk (5-year risk, 2.9% vs. 20.1%, p = 0.007). The CNS relapse risk was lower for patients who received high-dose methotrexate (HD-MTX) than for patients who did not (5-year risk, 0% vs. 15.2%, p = 0.015). We further screened the genetic mutation profile of 20 patients from two institutes, and found that MYD88 (25%) and CD79B mutations (25%) frequently occur in PB-DLBCL. In addition, four patients with MYD88 and/or CD79B mutations experienced CNS relapse, while three patients with MYD88 and/or CD79B mutations who received HD-MTX did not experience CNS relapse. CONCLUSION: Collectively, our results indicate combined modality therapy including rituximab-containing immunochemotherapy and consolidative breast RT is a promising approach for PB-DLBCL, while HD-MTX is useful for preventing CNS relapse.

Characteristics of immunotherapy trials for nasopharyngeal carcinoma over a 15-year period.

Background: Immunotherapy has been a hotspot in nasopharyngeal carcinoma (NPC) in recent years. This study aimed to provide a comprehensive landscape of the characteristics of immunotherapy clinical trials in NPC and to determine whether contemporary studies are of sufficient quality to demonstrate therapeutic value. Methods: This is a cross-sectional analysis of NPC trials registered on ClinicalTrials.gov in the last 15 years (Jan 1, 2008-Nov 20, 2022). Only interventional trials with a primary purpose of treatment were included in the final analysis. Characteristics of immunotherapy trials were compared with those of other NPC trials. Chronological shifts in NPC immunotherapy trials were also analyzed. Results: Of the 440 NPC studies selected, 161 (36.6%) were immunotherapy trials and 279 (63.4%) were other NPC trials. NPC immunotherapy trials were more likely than other NPC trials to be phase 1-2 (82.6% vs. 66.7%, P < 0.001), single-arm (51.3% vs. 39.6%, P = 0.020), non-randomized (64.8% vs. 44.4%, P < 0.001), and enroll fewer than 50 participants (46.3% vs. 34.4%, P = 0.015). Blinding was used in 8.8% of NPC immunotherapy trials. Also, 90.7% of NPC immunotherapy trials were recruited nationally and 82.6% were Asia-centric. Although academic institutions and governments (72.7%) were the major sponsors of NPC trials, immunotherapy trials were more likely to be industry-funded than other NPC trials (34.2% vs. 11.5%, P < 0.001). The number of NPC immunotherapy trials increased exponentially after 2017, attributed to the exploration of immune checkpoint inhibitors. Immunotherapy combined with chemotherapy was the most commonly investigated regimen. Conclusion: NPC immunotherapy trials over a 15-year period were predominantly exploratory. To generate high-quality evidence and advance the clinical application of immunotherapy in NPC, more attention and concerted efforts are needed.

Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL: Final Results From the GALLIUM Study.

The phase III GALLIUM trial assessed the safety and efficacy of obinutuzumab-based versus rituximab-based immunochemotherapy in patients with previously untreated follicular lymphoma (FL) or marginal zone lymphoma (MZL). At the primary analysis, the trial met its primary end point, demonstrating improvement in investigator-assessed progression-free survival (PFS) with obinutuzumab-based versus rituximab-based immunochemotherapy in patients with FL. We report the results of the final analysis in the FL population, with an additional exploratory analysis in the MZL subgroup. Overall, 1202 patients with FL were randomized 1:1 to obinutuzumab- or rituximab-based immunochemotherapy followed by maintenance with the same antibody for up to 2 years. After a median 7.9 (range, 0.0-9.8) years of follow-up, PFS remained improved with obinutuzumab- versus rituximab-based immunochemotherapy, with 7-year PFS rates of 63.4% versus 55.7% (P = 0.006). Time-to-next antilymphoma treatment was also improved (74.1% versus 65.4% of patients had not started their next antilymphoma treatment at 7 y; P = 0.001). Overall survival was similar between the arms (88.5% versus 87.2%; P = 0.36). Irrespective of the treatment received, PFS and OS were higher in patients with a complete molecular response (CMR) versus those with no CMR (P < 0.001). Serious adverse events were reported in 48.9% and 43.4% of patients in the obinutuzumab and rituximab arms, respectively; there was no difference in the rate of fatal adverse events (4.4% and 4.5%, respectively). No new safety signals were reported. These data demonstrate the long-term benefit of obinutuzumab-based immunochemotherapy and confirm its role as a standard-of-care for the first-line treatment of advanced-stage FL, taking into account patient characteristics and safety considerations.

Immunotherapy for nasopharyngeal carcinoma: Current status and prospects (Review).

Nasopharyngeal carcinoma (NPC) is an epithelial tumor located in the nasopharynx and is highly associated with Epstein­Barr virus (EBV) infection. Although radiotherapy alone can cure ~90% of patients with early­stage disease, >70% of patients with NPC have locoregionally advanced or metastatic disease at the first diagnosis due to the insidious and aggressive nature of NPC. After comprehensive radiochemotherapy, 20­30% of patients with advanced NPC still fail treatment, mainly due to recurrence and/or metastasis (R/M). Conventional salvage treatments, such as radiotherapy, chemotherapy and surgery, are suboptimal and frequently accompanied by severe adverse effects and limited efficacy. In recent years, immunotherapy has emerged as a promising treatment modality for R/M NPC. An increasing number of clinical studies have investigated the safety and efficacy of immunotherapy for advanced NPC and have shown considerable progress. In the present review, the rationale for the use of immunotherapy to treat NPC was summarized and the current status, progress and challenges of NPC clinical research on different immunotherapeutic approaches were highlighted, including immune checkpoint inhibitors, vaccines, immunomodulators, adoptive cell transfer and EBV­specific monoclonal antibodies. The comprehensive overview of immunotherapy in NPC may provide insight for clinical practice and future investigation.

A new prognostic nomogram in patients with mucosa-associated lymphoid tissue lymphoma: a multicenter retrospective study.

Background: The present study sought to understand how clinical factors and inflammatory biomarkers affected the prognosis of mucosa-associated lymphoid tissue (MALT) lymphoma and develop a predictive nomogram to assist in clinical practice. Methods: We conducted a retrospective study on 183 cases of newly diagnosed MALT lymphoma from January 2011 to October 2021, randomly divided into two groups: a training cohort (75%); and a validation cohort (25%). The least absolute shrinkage and selection operator (LASSO) regression analysis was combined with multivariate Cox regression analysis to construct a nomogram for predicting the progression-free survival (PFS) in patients with MALT lymphoma. To evaluate the accuracy of the nomogram model, the area under the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used. Results: The PFS was significantly associated with the Ann Arbor Stage, targeted therapy, radiotherapy, and platelet-to-lymphocyte ratio (PLR) in MALT lymphoma. These four variables were combined to establish a nomogram to predict the PFS rates at three and five years. Importantly, our nomogram yielded good predictive value with area under the ROC curve (AUC) values of 0.841 and 0.763 in the training cohort and 0.860 and 0.879 in the validation cohort for the 3-year and 5-year PFS, respectively. Furthermore, the 3-year and 5-year PFS calibration curves revealed a high degree of consistency between the prediction and the actual probability of relapse. Additionally, DCA demonstrated the net clinical benefit of this nomogram and its ability to identify high-risk patients accurately. Conclusion: The new nomogram model could accurately predict the prognosis of MALT lymphoma patients and assist clinicians in designing individualized treatments.

Diagnostic and prognostic value of pretreatment PET/CT in extranodal natural killer/T-cell lymphoma: a retrospective multicenter study.

PURPOSE: The objective of this research was to assess the utility of positron emission tomography combined with computed tomography (PET/CT) to detect bone marrow invasion (BMI) and the predictive value of PET/CT in extranodal natural killer/T-cell lymphoma (ENKTL) patients. PATIENTS AND METHODS: This multicentre study enrolled ENKTL patients who underwent pretherapy PET/CT and bone marrow biopsy (BMB). The specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT and BMB for BMI were evaluated. Multivariate analysis was used to identify predictive parameters for constructing a nomogram. RESULTS: Seven hundred and forty-eight patients were identified from four hospitals, with eighty (10.7%) having focal skeletal lesions on PET/CT and fifty (6.7%) having positive BMB. When BMB is considered as the gold standard, the specificity, sensitivity, PPV, and NPV of PET/CT for diagnosing BMI were found to be 93.8%, 74.0%, 46.3%, and 98.1%, respectively. PET/CT-positive individuals showed significantly worse OS than PET/CT-negative patients in the subgroup of BMB-negative cases. The nomogram model created according to the significant risk factors from multivariate analysis performed well in predicting survival probability. CONCLUSION: PET/CT offers a superior degree of precision for determining BMI in ENKTL. A nomogram model including the parameters of PET/CT can predict survival probability and may help in applying appropriate personalized therapy.

Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

A study on the prevention of hemorrhage and perforation in patients with primary gastric diffuse large-B cell lymphoma during treatment with immunochemotherapy.

BACKGROUND: Stomach hemorrhage and perforation are very severe and common complications in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL) during treatment with immunochemotherapy. However, no relevant clinical studies have been performed on the prevention of these serious complications. METHODS: Patients diagnosed with PG-DLBCL were enrolled in this retrospective study. The prevention group received standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) treatment without prednisone combined with antacids and anti-Helicobacter pylori (Hp) therapy. These patients received R-CHOP-based treatment until the complete recovery of gastric ulcers, as proven by gastroscopy. The control group received a standard R-CHOP regimen. Toxicity and survival were the main endpoints. RESULTS: A total of 52 patients received preventative treatment, while 146 patients did not. Among patients with stage I, II-1, and II-2 disease, the prevention group had a lower rate of hemorrhage and perforation (0/40) than the control group (10/78, p = 0.044). At a median follow-up time of 25 months, the 5-year event-free survival (EFS) rates were 97.1% in the prevention group and 66.1% in the control group (p = 0.025), and the 5-year overall survival (OS) rates were 100% and 72.0%, respectively (p = 0.021). However, the differences in the 5-year EFS and OS of patients with disseminated disease were not statistically significant. CONCLUSIONS: Preventative treatment can decrease the risk of hemorrhage and perforation in patients with localized PG-DLBCL during immunochemotherapy, leading to better EFS and OS in these patients. However, preventative treatment failed to reduce the risk of gastric hemorrhage and perforation and did not improve survival (EFS and OS) in advanced-stage patients.

The clinical and genomic distinctions of Class1/2/3 BRAF-mutant colorectal cancer and differential prognoses.

BRAF mutations are the oncogenic drivers in colorectal cancer and V600 mutations (Class1), which lead to RAS-independent active monomers, are the most common mutation types. BRAF non-V600 mutants can be further classified as RAS-independent active dimers (Class2) and RAS-dependent impaired kinase (Class3). We retrospectively reviewed the mutational profiles of 328 treatment-naïve colorectal tumors with BRAF mutations detected using capture-based hybrid next-generation sequencing targeting 400 + cancer-related genes. The clinical and genetic distinctions of patients harboring Class1/2/3 BRAF mutations were investigated, which revealed that tumors with Class1 BRAF mutations showed more unique genomic profiles than those with Class2/3 mutations. Also, by using an external dataset from cBioPortal, we demonstrated that patients with Class3 BRAF mutations had the best survival outcomes compared to the other two subgroups. These findings promoted the development of anti-BRAF strategies by distinguishing BRAF mutant subgroups.

Proposed prognostic subgroups and facilitated clinical decision-making for additional locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma: a retrospective study based on recursive partitioning analysis.

BACKGROUND: The high heterogeneity of de novo metastatic nasopharyngeal carcinoma (dmNPC) makes its prognosis and treatment challenging. We aimed to accurately stage dmNPC and assess the patterns of treatment strategies for different risk groups. METHODS: The study enrolled a total of 562 patients, 264 from 2007 to 2013 in the training cohort and 298 from 2014 to 2017 in the validation cohort. Univariate and multivariate Cox regression analyses were conducted to determine the independent variables for overall survival (OS). Recursive partitioning analysis (RPA) was applied to establish a novel risk-stratifying model based on these variables. RESULTS: After pairwise comparisons of OS, three risk groups were generated: low-risk (involved lesions ≤ 4 without liver involvement), intermediate-risk (involved lesions ≤ 4 with liver involvement or involved lesions > 4 with Epstein-Barr virus (EBV)-DNA < 62,000 copies/ml), and high-risk (involved lesions > 4 with EBV-DNA > 62,000 copies/ml). The 3-year OS rate differed significantly between groups (80.4%, 42.0%, and 20.4%, respectively, all P < 0.05). Adding locoregional intensity-modulated radiotherapy (LRRT) followed by palliative chemotherapy (PCT) resulted in a significant OS benefit over PCT alone for the low- and intermediate-risk groups (P = 0.0032 and P = 0.0014, respectively). However, it provided no survival benefits for the high-risk group (P = 0.6). Patients did not benefit from concurrent chemotherapy during LRRT among the three subgroups (P = 0.12, P = 0.13, and P = 0.3, respectively). These results were confirmed with the validation cohort. CONCLUSIONS: The novel RPA model revealed superior survival performance in subgroup stratification and could facilitate more effective treatment strategies for dmNPC.

Clinical features and treatment outcome of lymphoepithelioma-like carcinoma from multiple primary sites: a population-based, multicentre, real-world study.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a rare and unique subtype of cancer that histologically resembles undifferentiated nasopharyngeal carcinoma (NPC). The population-based analysis of LELC and the optimal treatment remains unclear. MATERIALS AND METHODS: This real-world, retrospective study investigated 770 patients with LELC for primary site, treatment, and survival outcomes from 2005 to 2019 from five cancer centres in China. The overall survival (OS) of different subgroups was appraised by log-rank tests and Kaplan-Meier analysis. RESULTS: Primary sites LELC included the lung (597 cases, 77.5%), salivary gland (115 cases, 14.9%), and others. The median progression-free survival (PFS) of LELC patients was 47.4 months. The median overall survival (OS) was not reached. The 5-year survival rate for LELC patients was 77.8%. Most patients in stages I and II received surgery. The majority of patients in stage III received surgery and radiotherapy. More than half of the patients in stage IV received chemotherapy. Among relapsed or metastatic cases receiving chemotherapy, patients who received immunotherapy at any time presented with a superior OS than those without immunotherapy (P < 0.0001, HR = 0.39, 95% CI 0.25-0.63). Compared with the SEER database, patients with LELC had a better prognosis than NPC, with a 5-year overall survival of 77.3% vs. 56.8% (P < 0.001). CONCLUSION: Our data provide treatment patterns and outcomes for LELC from various primary sites. Randomized controlled studies are necessary to further define the standard of care for patients with LELC. Trial registration This clinical trial was registered at ClinicalTrials.gov (No. NCT04614818).

A novel prognostic nomogram for patients with extragastric mucosa-associated lymphoid tissue lymphoma: A multicenter study.

BACKGROUND: The aim of this study was to explore predictors and construct a nomogram for risk stratification in primary extragastric mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: Extragastric MALT lymphoma cases newly diagnosed between November 2010 and April 2020 were assessed to construct a progression-free survival (PFS)-related nomogram. We also performed external validation of the nomogram in an independent cohort. RESULTS: We performed multivariate analyses of 174 patients from 3 hospitals who were included in the training cohort. Stage, hepatitis B virus surface antigen (HBsAg) status, and Ki67 expression were significantly associated with PFS. These three factors were used to construct a nomogram, which was shown to have a C-index of 0.89. Two risk groups (low risk and high risk) were identified by the prognostic model. The 5-year PFS was 98.9% for the low-risk group and 69.3% for the high-risk group (p < 0.001). The overall survival (OS) could also be effectively distinguished by the nomogram, resulting in an OS of 100% for the low-risk group and 94.6% for the high-risk group (p = 0.01). These results were validated and confirmed in an independent cohort with 165 patients from another three hospitals. The 5-year PFS rates were 94.8% and 66.7% for the low-risk and high-risk groups, respectively (p < 0.001). The 5-year OS rates were 97.9% and 88.4%, respectively (p = 0.016). CONCLUSION: The nomogram could well distinguish the prognosis of low- and high-risk patients with extragastric MALT lymphoma and is thus recommended for clinical use.