Diffuse large B-cell lymphoma (DLBCL) remains a therapeutic challenge, with a substantial proportion of patients failing to respond to standard regimens. Natural biflavonoids have demonstrated antitumor potential, but their effects on the metabolic vulnerabilities of DLBCL are poorly understood. This study aimed to elucidate the antitumor efficacy and of pulvinatabiflavone (PUF), a novel biflavonoid monomer isolated from Selaginella cuspidata, against DLBCL and the related mechanism. The antiproliferative effects of PUF were evaluated in multiple DLBCL cell lines (OCI-LY8, SU-DHL-2, SU-DHL-8, and RIVA) and a xenograft mouse model using CCK-8, flow cytometry (apoptosis/cell cycle), and Western blotting. Metabolomics, transcriptomics, functional rescue experiments (with IMP and dGTP), and SLC25A15 knockdown models were used to investigate the mechanism of PUF. PUF potently inhibited DLBCL cell proliferation (IC₅₀ < 2 μg/ml at 48 h), induced apoptosis, and caused G2/M cell cycle arrest. Multiomics analyses revealed that PUF disrupted purine nucleotide metabolism, leading to critical dGTP depletion and subsequent DNA damage, as evidenced by increased γ-H2AX expression. This DNA damage was ameliorated by supplementation with the purine metabolites IMP or dGTP. PUF was found to downregulate the mitochondrial transporter SLC25A15, which is highly expressed in DLBCL. Molecular docking and cellular thermal shift assay (CETSA) confirmed that PUF directly binds to the mitochondrial transporter SLC25A15. Knockdown of SLC25A15 ameliorated the DNA damage phenotype, which was similarly rescued by dGTP. Importantly, in the xenograft model, PUF treatment not only suppressed tumor growth but also downregulated SLC25A15 and upregulated γ-H2AX in tumor tissues, confirming the mechanism in vivo. The biflavonoid PUF exerts profound anti-DLBCL effects by directly targeting SLC25A15, disrupting purine nucleotide metabolism, thereby inducing dGTP shortage-mediated DNA damage. Our integrated findings from in silico, cellular, and animal models suggest that PUF is a promising therapeutic candidate and reveal that SLC25A15 is a novel metabolic target in DLBCL.

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of malignant plasma cells. While proteasome inhibitors and novel immunotherapies have markedly shifted the clinical trajectory of multiple myeloma, the persistence of therapeutic resistance and disease recurrence remains a formidable challenge. Metabolic reprogramming has emerged as a critical functional layer driving MM progression and drug resistance. It extends beyond mere energetic anomalies, integrating genetic context, bone marrow microenvironmental stress, and therapeutic selection pressure into a dynamic, systemic adaptive network. This review aims to systematically elucidate the molecular mechanisms underlying the rewiring of major metabolic pathways in MM, including the aberrant activation and interaction of glucose, lipid, amino acid, nucleotide, and trace element (iron/copper) metabolism. It also explores the role of the gut microbiota as a distal regulator influencing disease progression through its metabolites. Collectively, these pathways constitute an interconnected metabolic network that sustains tumor proliferation, stress adaptation, immune evasion, and drug resistance. Furthermore, it discusses how metabolic states encode functional information largely invisible to conventional staging systems, thereby positioning metabolic vulnerabilities as conditional therapeutic targets and a complementary layer for biomarker development, risk stratification, and treatment selection in MM. In conclusion, this framework establishes a conceptual and translational reference, defining stress-adaptive metabolic states as actionable biological insight guiding metabolism-informed therapeutic and biomarker strategies in multiple myeloma.

The Warburg effect states that cancer cells preferentially undergo aerobic glycolysis, producing lactate as a key metabolic byproduct. Lactate acidifies the tumor microenvironment (TME) and serves as a signaling molecule and substrate for lysine lactylation (Kla), a novel posttranslational modification (PTM) discovered in 2019 that links glycolytic metabolism to epigenetic and proteomic reprogramming. The reversible modification of histones and nonhistone proteins orchestrates oncogenic adaptation and drives tumor progression. However, gaps persist in our understanding of the multifactorial regulation of lactylation and its translational potential in overcoming tumor heterogeneity and resistance. This review highlights the emerging roles of lactylation in cancer therapies, including the enhancement of DNA repair mechanisms during chemotherapy, stabilization of key signaling effectors upon targeted therapy, and promotion of an immunosuppressive TME in immunotherapy. We further examined regulatory factors associated with lactylation, from competitive PTMs and genetic mutations to microbial influences and environmental signals. Additionally, we discuss the therapeutic potential of targeting lactylation via indirect modulators currently under investigation and the visualization of lactate and lactylation modifications. By synthesizing these insights, this review highlights lactylation as a reversible metabolic-epigenetic axis for precision oncology, enabling predictive biomarkers, combination strategies, and novel interventions to address the dynamic challenges of cancer.

Background/Objectives: While a preference for an equal distribution of health gains is common, there are situations where individuals may opt to concentrate health gains for a select few. This study investigates how distributive preferences, defined as societal valuations of alternative allocations of fixed total health benefits, vary with the magnitude of individual health gains. Methods: Using the person trade-off (PTO) method, we conducted an online survey with a nationally representative sample of Chinese adults (N = 500). The respondents evaluated five allocation programs differing in both individual health gain magnitude and number of beneficiaries. Distributive preferences are classified into five distinct types: diffusion, concentration, maximization, extreme egalitarianism and extreme inequality seeking. Threshold regression analysis identified critical transition points in preference patterns. Results: Non-maximizing tendencies were dominant (79% of the respondents). The health gain threshold was estimated to be 4.6 years (95% CI: [4.28, 4.85]): below this threshold, respondents tend to allocate smaller benefits to more patients (diffusion preference); above the threshold, people are inclined to allocate larger benefits to fewer patients (concentration preference). The income level and self-reported health status of the participants were identified as potential factors influencing distributive preferences. Conclusions: This study provides the first quantitative evidence from China that distributive preferences exhibit a non-linear shift based on the magnitude of health benefits. The identified 4.6-year threshold provides policymakers with an empirically based instrument to strike a balance between efficiency and the reduction in inequality in resource allocation. These findings advocate for incorporating social value weights into health technology assessments, especially for interventions that offer substantial individual benefits.

Fibrosis is the ultimate, common pathological ending of most chronic inflammatory diseases and increases the chances of developing life-threatening illnesses. Pyroptosis, a newfound form of lytic programmed cell death initiated by the inflammasome, has received more and more attention because of its association with fibrotic diseases. Therefore, this study visualizes the connection between pyroptosis and fibrosis research through bibliometric methods, aimed at providing global research hits and tendencies in the field. We collected and analyzed the articles on pyroptosis and fibrosis from 2010 to 2024 via Web of Science. Visual data analysis was performed for countries, institutions, authors, references, and keywords in the field using VOSviewer, CiteSpace software, the “Bibliometrix” R package, the bibliometric website ( https://bibliometric.com/ ), and Excel software. We analyzed the data by utilizing the bibliometric review method. A total of 566 articles and reviews relating to pyroptosis and fibrosis were identified in the Web of Science. The number of publications in the domain has continued to grow since 2010. These scientific outputs were mainly from 129 countries/regions and 1919 institutions, particularly China (n = 423) and the USA (n = 83). More importantly, although China publishes a vast majority of articles, its centrality is lower than that of the USA (0.59 vs 0.61). Among the 3833 authors involved in this field, Feldstein, A. E. is the most prolific author. Shi, J. J. is the world’s most-cited author among the 12,143 authors in these academic journals. Frontiers in Immunology was a prolific contributor, and Nature was the most frequently cited journal. After analysis, Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death were the top-cited articles. The analysis of keywords displayed that pyroptosis, fibrosis, and pathways were the main research hotspots and frontier directions in recent years. We analyzed the characteristics of published articles and drew a fundamental knowledge structure on pyroptosis and fibrosis research via bibliometric analysis. The potential mechanism between fibrosis and pyroptosis is deeply tied to the current moment. Our findings can help researchers make clear the research status and value of fibrosis and pyroptosis and provide new directions for future research as soon as possible.

Background: Classical Hodgkin lymphoma (cHL) is highly curable by frontline therapy. However, the search for an effective standard second-line therapy for patients with refractory or relapsed (R/R) cHL continues. Sintilimab, a fully human IgG4 monoclonal antibody targeting the PD-1 receptor, has demonstrated significant efficacy in R/R cHL. This study evaluates the efficacy of sintilimab combined with gemcitabine, cisplatin, and dexamethasone (S-GDP), an economical regimen cost only 600 dollars per cycle, as second-line therapy for R/R cHL. Methods: We conducted a retrospective study including 24 patients with R/R cHL who received S-GDP (gemcitabine, 800 mg/m2, d1,8; cisplatin, 25 mg/m2, d1-3; dexamethasone, 20mg bid, d1-4; sintilimab, 200mg, d8; 21 days/cycle) as second-line therapy from March 2020 to January 2024. After the combination treatment, patients could receive ASCT or RT as consolidation therapy, followed by sintilimab maintenance. The primary endpoint was the best overall response rate (ORR) during the second-line therapy according to the 2014 version of Lugano efficacy evaluation criteria, and the secondary endpoints included complete response (CR), partial response (PR), progression-free survival (PFS), and adverse events (AEs). Results: Twenty-four patients (15 males; median age 34 years, range, 17-55) from 4 institutions with histologically confirmed cHL were included in this retrospective study, of whom 18 patients were Ⅲ-Ⅳ stage, 13 patients were refractory. Fourteen advanced-stage patients (77.8%) had International Prognostic Score (IPS) scores≥3. Six early-stage patients (100%) had unfavorable factors. The median number of treatment cycles was 6 (range 1-8). The ORR and CRR were 83.3% and 62.5%, respectively. In refractory patients, the ORR and CRR were 76.9% and 61.5%, respectively, while in relapsed patients, the ORR and CRR were 90.9% and 63.6%, respectively. With a median follow-up of 45.2 months, the median PFS was 42.5 months for all patients, 45.2 months for refractory patients, 34.2 months for relapsed patients. Among the 24 patients, 11 patients received ASCT with subsequent sintilimab maintenance, 3 patients rejected ASCT as consolidation therapy with only sintilimab maintenance, 1 patient received only RT as consolidation therapy. The most common AEs were leukopenia (91.6%) and anemia (83.3%), with grade 3-4 AEs including leukopenia (20.8%), thrombocytopenia (8.3%), and pneumonia (8.3%). No treatment-related severe AEs or mortality occurred. Conclusion: The S-GDP regimen is an effective, economical, and well-tolerated second-line therapy for R/R cHL, efficiently bridging patients to ASCT and offering a promising alternative for this patient population.

Background Bedside procedures are a necessary skill for many residents. Practice changes, including the discontinuation of a minimum number of procedures required by the American Board of Internal Medicine, may have resulted in decreased incentive for residents to seek procedural opportunities. Objective To improve residents’ procedural output and confidence in abdominal paracentesis, arterial and central venous line placement, nasogastric intubation, and ultrasound-guided peripheral intravenous catheter insertions (USPIV). Methods A novel Resident Procedure Team (RPT) model was created using crowdsourced proficient (having completed ≥5 procedures) near-peers in combination with peer-led USPIV simulation workshops to increase the number of supervising residents available. Procedure logs and the number of residents who became qualified to perform and supervise procedures were tracked from July 2018 to June 2022 and compared before and after the implementation of the RPT in July 2020. Results Implementing the novel RPT model significantly increased the number of procedures performed (1875 procedures post-RPT vs 1292 pre-RPT; P=.02). Abdominal paracentesis increased from 411 to 482 (17.3%), central venous line placement increased from 344 to 401 (16.6%), USPIV increased from 318 to 389 (22.3%), arterial line placement increased from 189 to 360 (90.5%), and nasogastric intubation increased from 30 to 243 (710.0%). Resident confidence levels increased significantly after RPT-led USPIV workshops (P<.05 for all). Conclusions Implementation of a novel, crowdsourced, resident-led procedure team and peer-led USPIV workshops helped increase the number of procedures performed by residents.

Purpose: Central nervous system lymphoma (CNSL) is an aggressive non-Hodgkin's lymphoma (NHL) confined to the central nervous system (CNS). Orelabrutinib is an oral second-generation Bruton tyrosine kinase (BTK) inhibitor and a novel therapeutic strategy for CNSL. The purpose of this study was to evaluate the effectiveness and safety of high-dose methotrexate (HD-MTX), thiotepa, and orelabrutinib combined with or without rituximab (MTO±R)regimen in the treatment of patients with CNSL. Methods: A total of 14 patients with CNS diffuse large B-cell lymphoma (DLBCL) were included in this retrospective study. All patients received the regimen MTO±R. Overall response rate (ORR), complete response rate(CR), partial response (PR), stable disease (SD), progressive disease (PD), progression-free survival (PFS), overall survival (OS), and the safety of MTO±R were assessed by the investigator. Results: Fourteen patients were evaluable for safety, and 13 patients were evaluable for efficacy. The overall CR rate was 69.2%, and the ORR was 92.3% for total patients. For PCNSL, the CR rate and ORR were 55.6% and 88.9%, respectively. For relapsed/refractory CNSL, the CR rate and ORR were 66.7% and 91.7%, respectively. The median follow-up time was 12.8 months. The median PFS was 11.3 months, and the median OS was not achieved. The 12-month PFS and OS rates were 60% and 70%, respectively. Adverse events occurred in 17 cycles, and Grade 3 AEs occurred in 5 patients (35.7%). Conclusion: MTO±R was an efficacious and well-tolerated regimen in patients with CNSL. A novel BTK inhibitor in combination with chemotherapy offers a new potential therapeutic strategy for patients with CNSL.

CAR-T cell therapy, a novel therapeutic approach that has attracted much attention in the field of cancer treatment at present, has become the subject of many studies and has shown great potential in the treatment of hematological malignancies, such as leukemia and lymphoma. This study aims to analyze the characteristics of articles published on CAR-T cell therapy in the lymphoma field and explore the existing hotspots and frontiers. The relevant articles published from 2013 to 2022 were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, Bibliometric online analysis platform, Microsoft Excel, and R software were used for bibliometric analysis and visualization. The number of publications related to the research has been increasing year by year, including 1023 articles and 760 reviews from 62 countries and regions, 2092 institutions, 1040 journals, and 8727 authors. The United States, China, and Germany are the main publishing countries in this research field. The top 10 institutions are all from the United States, the journal with the highest impact factor is BLOOD, the author with the most publications is Frederick L Locke, and the most influential author is Carl H June. The top three keywords are "Lymphoma," "Immunotherapy," and "Therapy." "Maude (2014)" is the most cited and strongest burstiness reference over the past decade. This study provides a comprehensive bibliometric analysis of CAR-T cell therapy in lymphoma, which can help researchers understand the current research hotspots in this field, explore potential research directions, and identify future development trends.

Background. Longitudinal measurement of glioma burden with MRI is the basis for treatment response assessment. In this study, we developed a deep learning algorithm that automatically segments abnormal fluid attenuated inversion recovery (FLAIR) hyperintensity and contrast-enhancing tumor, quantitating tumor volumes as well as the product of maximum bidimensional diameters according to the Response Assessment in Neuro-Oncology (RANO) criteria (AutoRANO). Methods. Two cohorts of patients were used for this study. One consisted of 843 preoperative MRIs from 843 patients with low- or high-grade gliomas from 4 institutions and the second consisted of 713 longitudinal post-operative MRI visits from 54 patients with newly diagnosed glioblastomas (each with 2 pretreatment "baseline" MRIs) from 1 institution. Results. The automatically generated FLAIR hyperintensity volume, contrast-enhancing tumor volume, and AutoRANO were highly repeatable for the double-baseline visits, with an intraclass correlation coefficient (ICC) of 0.986, 0.991, and 0.977, respectively, on the cohort of postoperative GBM patients. Furthermore, there was high agreement between manually and automatically measured tumor volumes, with ICC values of 0.915, 0.924, and 0.965 for preoperative FLAIR hyperintensity, postoperative FLAIR hyperintensity, and postoperative contrast-enhancing tumor volumes, respectively. Lastly, the ICCs for comparing manually and automatically derived longitudinal changes in tumor burden were 0.917, 0.966, and 0.850 for FLAIR hyperintensity volume, contrast-enhancing tumor volume, and RANO measures, respectively. Conclusions. Our automated algorithm demonstrates potential utility for evaluating tumor burden in complex posttreatment settings, although further validation in multicenter clinical trials will be needed prior to widespread implementation.

Objectives: To compare the overall survival (OS) outcomes of sublobar resection (SLR) with stereotactic body radiation therapy (SBRT) or ablation for patients with early stage non-small cell lung cancer (NSCLC). Methods: Patients with clinical stage I (T1-T2aNoMo) NSCLC from 2004 to 2014 who were treated with SLR, SBRT, or ablation as the sole treatment were identified from the National Cancer Database. OS was estimated using the Kaplan-Meier method and evaluated by log-rank test, univariate and multivariate Cox proportional hazard regression, and propensity score-matched analysis. Relative survival analyses compared with age- and sex-matched US population were performed. Results: A total of 53,973 patients were identified. The 1-, 2-, 3-, and 5-year relative survival rates were 96%, 90%, 84%, and 71% for SLR (n = 30,451); 93%, 78%, 65%, and 46% for SBRT (n = 22,134); and 90%, 73%, 58%, and 37% for ablation (n = 1388). Propensity score matching resulted in 9967 patients in the SBRT group versus 9967 in the SLR group and 1062 patients in the ablation group versus 1984 in the SLR group. After matching, both SBRT (hazard ratio, 1.559; 95% confidence interval, 1.497-1.623; P < .001) and ablation (hazard ratio, 1.906; 95% confidence interval, 1.730-2.101; P < .001) were associated with shorter OS when compared with SLR. These results persisted in patients with tumor size <= 2 cm. Conclusions: Preliminary results suggest SLR may be associated with longer OS in patients with early-stage NSCLC compared with SBRT or ablation. Future prospective, randomized, controlled clinical trials comparing these treatments are needed to confirm these results.

The effect of insurance status on overall survival (OS) of patients with cutaneous T-cell lymphoma (CTCL) is unclear. We identified 11,861 patients from the US National Cancer Data Base diagnosed with CTCL from 2004-2014, of which 6088 had private insurance, 756 had Medicaid, 4536 had Medicare, and 481 are uninsured. Privately insured patients were more likely to present at an early stage (p < .001). On multivariate Cox regression analysis, privately insured patients had significantly longer OS than patients with Medicaid (HR: 1.936, 95% CI: 1.680-2.230, p < .001), Medicare (HR: 1.342, 95% CI: 1.222-1.474, p < .001), or no insurance (HR 1.849, 95% CI: 1.539-2.222, p < .001). The survival advantage of privately insured patients persisted on relative survival and propensity score-matched analyses. In conclusion, privately insured patients were more likely to present at an early stage, and had longer OS than patients who were Medicaid-, Medicare-, or not insured.

Systemic anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma with extranodal involvement (ALCL-E) is a rare form of non-Hodgkin lymphoma. No large study in the literature has compared the survival outcomes among different primary extranodal sites of involvement in ALK+ ALCL-E. We identified 1306 patients with ALK+ ALCL-E diagnosed between 2004 and 2014 in the US National Cancer Database, among whom 387 had primary extranodal site in the chest/abdomen/pelvis, 103 in the bone, 62 in the central nervous system, 134 in the head and neck and 620 in the cutaneous/soft tissue. Younger age, lower Charlson-Deyo score, lower clinical stage, receipt of chemotherapy and receipt of radiotherapy were predictors of longer overall survival. Patients with extranodal involvement of central nervous system and chest/abdomen/pelvis had shorter overall survival than those with involvement of head and neck, bone, and cutaneous/subcutaneous tissue after adjusting for confounding variables. We recommend treating these patients upfront with more aggressive therapy.

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Studies on various types of CTCL have shown the prognostic significance of primary disease site (Su et al, 2017; Nguyen et al, 2018), while few studies have investigated the prognostic potential of primary disease site for MF. The primary aim of our study is to compare the survival outcomes of patients with MF among different primary disease sites, while controlling for confounders. The National Cancer Database (NCDB) was used to ascertain de-identified patients with MF using the International Classification of Disease – Oncology, third edition (ICD-O3) morphological code 9700 diagnosed between 2004 and 2014. Information extracted from the user participant file included demographics, clinical information, the first course of treatment received that contribute to the long-term control of the cancer, length of follow-up and overall survival (OS). Patients with no known primary disease site, follow-up, treatment or income data were excluded. A Kaplan–Meier estimate was used to evaluate OS, and differences in survival were examined by the log-rank test. Univariate and multivariate Cox proportional hazards regression was used to evaluate independent predictors associated with survival. Pairwise comparisons of different primary sites in OS were performed using propensity score matching to account for confounders (MatchIt package [https://gking.harvard.edu/matchit], R version 2.15.1 [https://www.r-project.org/]). Statistical significance was defined as P ≤ 0·05. Analysis was performed using IBM SPSS Statistics 22 (IBM Corporation, North Castle, NY, USA), and the figure was generated with GraphPad Prism 6 (GraphPad Software, La Jolla, CA, USA). Survival of the MF patient cohort relative to the expected survival in the age- and gender-matched general US population was analysed with the ‘strs' command in STATA/SE 13 (Stata Corporation, College Station, TX, USA) as detailed previously by Dickman et al (2015). US Census Bureau and the Centers for Disease Control and Prevention databases (www.census.gov; www.cdc.gov) were used to obtain information on the yearly age- and sex-matched segments of the US population. A total of 2428 patients with MF identified using the NCDB met the inclusion criteria. Trunk, upper limbs, lower limbs, head and neck and overlapping lesion of skin constituted 36·0% (n = 873), 12·2% (n = 297), 22·0% (n = 535), 10·1% (n = 244) and 19·7% (n = 479) of the entire cohort, with the mean age at diagnosis being 58·2, 57·3, 57·1, 60·5 and 58·5 years, respectively. The 5-year OS rate of the entire MF cohort was 84·8%. Significant differences in survival outcomes were present among different primary sites, with 5-year survival rates of 85·5%, 82·5%, 88·2%, 79·5%, and 78·3% for patients with disease localized to trunk, upper limbs, lower limbs, head and neck and overlapping lesion of skin (Fig 1). The 5- and 10-year survival relative to the expected survival of an age- and gender-matched US standard population was 90·9% (95% confidence interval [CI] 88·5–93·0%) and 87·8% (95% CI 82·4–92·9%), respectively. Stratified by primary disease sites, 5-year relative survivals to an age- and gender- matched US standard population were 93·0% (95% CI 89·2–96·3%), 87·0% (95% CI 79·6–93·0%), 97·0% (95% CI 92·0–101·0%), 88·5% (95% CI 80·0–95·4%) and 84·1% (95% CI 78·4–89·1%) for patients with disease localized to trunk, upper limbs, lower limbs, head and neck and overlapping lesion of skin. On multivariate Cox regression analysis, older age (P < 0·001), male gender (P < 0·001), African American race (P = 0·044), Charlson-Deyo score of 1 (P = 0·018) or >2 (P = 0·019), higher clinical stage (P < 0·001), the receipt of chemotherapy (P < 0·001) and immunotherapy (P = 0·048) were associated with shorter OS (Table 1). Academic facility type (P = 0·006) and private insurance status (P < 0·001) were associated with longer OS. Patients with disease localized to the trunk (Hazard ratio [HR] 1·378, 95% CI: 1·045–1·817, P = 0·023), upper limbs (HR 1·727, 95% CI: 1·234–1·417, P = 0·001) or overlapping lesion of skin (HR 1·545, 95% CI: 1·515–2·230074, P = 0·004) had shorter OS than those with disease localized to the lower limbs. After pair-wise propensity score matching based on age at diagnosis, gender, facility type, race, insurance status, Charlson-Deyo score, clinical stage and treatments received, patients with lesions localized to the lower limbs had significantly longer OS than those with lesions localized to the overlapping lesion of skin (P = 0·028). Furthermore, patients with lesion localized to the lower limbs demonstrated a trend of longer OS than patients with lesion localized to the upper limb (P = 0·175), head and neck (P = 0·124) and trunk (P = 0·122). Our results demonstrated that patients with disease located in the lower limbs had the longer OS than patients with disease located in head and neck, and upper limbs, trunk, while patients with disease located in the overlapping lesion of the skin had the worst survival, after adjusting for disease characteristics, socioeconomic factors and treatments received. In addition, age- and gender-matched relative survival data demonstrated that a component of mortality can be attributed to MF in the affected US population, and that the survival difference among different primary disease sites persisted relative to the expected survival of the general US population. The poorer OS for patients with lesions located in the overlapping lesion of the skin was possibly attributed to the diffuse nature of the disease, which has been shown to be an unfavourable prognostic factor of MF, resulting in difficult categorization of the primary site (Wilson et al, 2012; Nath et al, 2014; Desai et al, 2015). A recent study by Su et al (2017) of 4057 patients from the NCDB showed that primary cutaneous peripheral T-cell lymphoma patients with lesions localized to the lower extremity had significantly shorter OS when compared to those with disease localized to the head and neck, trunk, and upper extremity after adjusting for confounding factors. A prior study by Grange et al (1999) on non-MF/Sézary syndrome/lymphomatoid papulosis CTCL suggested that anatomical site was not a significant prognostic factor. The contradictory results between our study and other studies on CTCL are probably because the disease process of subtypes of CTCL, patient cohorts and factors included in the analysis are inherently different. Further studies are needed to investigate the underlying pathophysiology of different survival outcome by location in MF. None. The authors have no conflict of interest to declare. CS and HXB: designed research, performed research, interpreted data, wrote the paper, contributed to critical revisions/edits. RT: performed research, analysed data, wrote the paper. MG, GK, PJZ, RX and GZ: designed research, interpreted data, contributed to critical revisions/edits.

To compensate for the lack of disease-specific survival data in the study by Rae et al., the US National Cancer Data Base was used to identify patients with histologically confirmed central neurocytoma from 2004 to 2013 based on the same inclusion criteria and relative survival analysis was performed. A total of 781 patients were identified. The 5-year overall survival (OS) for the overall cohort was 87.2%, and the 5-year survival relative to the expected survival of an age-, and gender-matched US standard population was 89.5% (95% CI 86.6%-91.9%). In summary, the relative survival analysis presented here indicates that central neurocytoma was a component of the cause of mortality in the affected US population.

BACKGROUND:Cytoreductive surgery is considered controversial for primary central nervous system lymphoma (PCNSL).OBJECTIVE:To investigate survival following craniotomy or biopsy for PCNSL.METHODS:The National Cancer Database-Participant User File (NCDB, n = 8936), Surveillance, Epidemiology, and End Results Program (SEER, n = 4636), and an institutional series (IS, n = 132) were used. We retrospectively investigated the relationship between craniotomy, prognostic factors, and survival for PCNSL using case-control design.RESULTS:In NCDB, craniotomy was associated with increased median survival over biopsy (19.5 vs 11.0 mo), independent of subsequent radiation and chemotherapy (hazard ratio [HR] 0.80, P < .001). We found a similar trend with survival for craniotomy vs biopsy in the IS (HR 0.68, P = .15). In SEER, gross total resection was associated with increased median survival over biopsy (29 vs 10 mo, HR 0.68, P < .001). The survival benefit associated with craniotomy was greater within recursive partitioning analysis (RPA) class 1 group in NCDB (95.1 vs 29.1 mo, HR 0.66, P < .001), but was smaller for RPA 2-3 (14.9 vs 10.0 mo, HR 0.86, P < .001). A surgical risk category (RC) considering lesion location and number, age, and frailty was developed. Craniotomy was associated with increased survival vs biopsy for patients with low RC (133.4 vs 41.0 mo, HR 0.33, P = .01), but not high RC in the IS.CONCLUSION:Craniotomy is associated with increased survival over biopsy for PCNSL in 3 retrospective datasets. Prospective studies are necessary to adequately evaluate this relationship. Such studies should evaluate patients most likely to benefit from cytoreductive surgery, ie, those with favorable RPA and RC.

To the Editor: We read with great interest a retrospective study by Singh et al comparing the demographics and outcomes of stage I-II Merkel cell carcinoma (MCC) treated with Mohs micrographic surgery (MMS) compared with wide local excision (WLE) in the National Cancer Database.1Singh B. Qureshi M.M. Truong M.T. Sahni D. Demographics and outcomes of stage I-II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Data Base.J Am Acad Dermatol. 2018; 79: 126-134.e3Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar However, as the authors indicated, a major limitation of the study is the lack of data on cause-specific death. Therefore, it is unclear if the presence of stage I-II MCC is relevant to the death observed. We identified 1185 patients with stage I-II MCC diagnoses during 2004-2014 from the National Cancer Database treated with WLE (n = 1095) or MMS (n = 90) following the same inclusion criteria as that in Singh et al.1Singh B. Qureshi M.M. Truong M.T. Sahni D. Demographics and outcomes of stage I-II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Data Base.J Am Acad Dermatol. 2018; 79: 126-134.e3Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar To account for the lack of cause-specific survival, we performed survival analysis of the stage I-II MCC patient cohort relative to expected survival in the age- and sex-matched US general population stratified by treatment. The analysis was performed with the strs command in STATA/SE 13 (Stata Corporation, College Station, TX, USA) as detailed in an article in The Stata Journal by Dickman and Coviello.2Dickman P.W.C. Coviello E. Estimating and modeling relative survival.Stata J. 2015; 15: 186-215Crossref Google Scholar Information on the yearly age- and sex-matched segments of the US population was abstracted from the US Census Bureau (www.census.gov). Information on mortality among the same population subgroups was obtained from the Centers for Disease Control and Prevention (www.cdc.gov). The 5-year survival relative to the expected survival of an age- and sex-matched US standard population was 86.3% (95% confidence interval [CI] 81.6%-90.9%) (Fig 1), suggesting a significant contribution of stage I-II MCC to overall mortality. We also analyzed overall and relative survival stratified by treatment type. The 5-year overall survival was 59.7% and 65.1% for patients who received WLE and MMS, respectively (Fig 2). Similar to the study by Singh et al, the overall survival between the treatment groups did not differ significantly (log-rank test, P = .448), with longer 3-year survival rates than those reported by Singh et al: 69.9% versus 65.1% for WLE and 76.3% versus 68.1% for MMS for our study and the Singh et al, respectively.1Singh B. Qureshi M.M. Truong M.T. Sahni D. Demographics and outcomes of stage I-II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Data Base.J Am Acad Dermatol. 2018; 79: 126-134.e3Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar Five-year relative survival rates were 85.4% (95% CI 80.5%-90.1%) for patients who received WLE and 97.8% (95% CI 78.6%-113.1%) for patients who received MMS. Patients who received MMS trended toward increased survival both in overall survival and relative survival compared with patients who received WLE. However, the relative survival rates of MMS and WLE were within the 95% CI of each other, and the overall survival did not differ significantly based on treatments. The potential survival advantage of MMS might be due to selection bias, treatment bias, or other unmeasured variables. In conclusion, the relative survival analysis presented here indicates that stage I-II MCC was a component of the cause of mortality in the affected US population. Our study also confirmed that WLE and MMS have similar survival outcomes. Additional study will be required to determine whether there is a significant survival benefit of MMS over WLE. We believe that our analysis provides new information on relative survival of early stage MCC and addresses a significant limitation of the study by Singh et al. Demographics and outcomes of stage I and II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer DatabaseJournal of the American Academy of DermatologyVol. 79Issue 1PreviewThe optimal surgical approach (wide local excision [WLE] vs Mohs micrographic surgery [MMS]) for treating Merkel cell carcinoma (MCC) is yet to be determined. Full-Text PDF Optimal surgical modality for early Merkel cell carcinoma: Results from the National Cancer DatabaseJournal of the American Academy of DermatologyVol. 88Issue 3PreviewTo the Editor: We read with great interest the Letter to the Editor written by Su et al, in response to our original article.1,2 We are delighted to see other authors share the same interest in investigating optimal treatment in early stage Merkel cell carcinoma (MCC). In their Letter to the Editor, Su et al attempted to address a particular limitation of our study that is inherent to the National Cancer Database.2 Essentially the National Cancer Database does not report on disease-specific survival. Full-Text PDF

Primary cutaneous peripheral T-cell lymphoma, unspecified (PCPTL) accounts for <6% of cutaneous T-cell lymphoma cases. Due to its rarity, no large study exists in the literature on PCPTL. Among 4057 patients with PCPTL diagnosed from 2004 to 2014 in the National Cancer Database, 428, 913, 517, 754, and 1435 had lesions localized primarily to the upper extremity, head and neck, lower extremity, trunk, and overlapping lesion or unspecified site, respectively. PCPTL that primarily involved the head and neck had the longest overall survival (OS), followed by PCPTL that primarily involved the trunk, upper extremity, and lower extremity. Patients with lesions localized to the lower extremity had significantly shorter OS when compared to those with disease localized to other primary sites after adjusting for confounding factors. The difference in OS among disease sites was only significant in stage I disease, but not higher stages, and persisted in younger patients.