Search

Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Objective: Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP. Methods: Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry. Results: The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes. Conclusions: This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.

Background: Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma. Methods: In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored. Results: Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy (P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 109/L (range 18–219) among patients who received rhTPO and 73 × 109/L (range 42–197) among those who received GCSF alone (P=0.982). After the use of rhTPO, the incidence of platelet count

Background This study aimed to recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy. Method RNA sequencing data of dataset GSE65135 (n = 24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n = 137) and independent patient cohort from Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n = 32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. The Gene Set Enrichment Analysis (GSEA), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis were performed. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan–Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95% CI [0.25–0.86], p = 0.014). Higher serum CCL19 concentration was associated with longer progression-free survival (PFS, p = 0.014) and OS (p = 0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line chemoimmunotherapy.

Highlights • Juvenile COVID-19 patients have faster time to RP result than any other aged groups. • Sampling from digestive tract may be better in identifying RP. • No marked difference on imaging change between RP and NRP patients was observed. • Nearly three-quarters of patients had protective antibodies 6 months post-discharge. • The disappearance rate of antibody is more rapid in juveniles than adults., Background Almost a year after the outbreak of coronavirus disease 2019 (COVID-19), numerous hospitalized COVID-19 patients have recovered. However, little is known about the long-term follow-up (>2 months) of discharged patients. Methods We enrolled 527 discharged COVID-19 patients in a study from February 5 to March 11, 2020. These patients’ basic characteristics, imaging features, nucleic acid detection results, and antibody levels were retrospectively reviewed. Results of the 527 discharged patients, 32 (6.1%) had re-detectable positive (RP) nucleic acid results for SARS-CoV-2 during follow-up examinations with 11 and four detections entailing stool samples and anal swabs, respectively, rather than respiratory samples. Juveniles were more accessible to “infection recurrence” than other age groups, with shorter time spans for RP RNA tests (an average of 8.8 days [6.0–9.0 days]), while the reverse was true for the middle-aged group (17.5 days on average [14.0-17.5 days]). Similar improvements in the imaging features of both RP and none RP (NRP) groups were observed. Negative antibody detections in patients 3 and 6 months after discharge were 14.2% and 25.0%, respectively. Cases evidencing negative antibodies were more common among juvenile patients (40% vs. 15.6%, p = 0.03) 6 months post-discharge. Conclusions 6.1% of 527 discharged patients showed RP status, which may be easier to be identified from stool samples than from other samples. Given the dropping rate of SARS-CoV-2 antibody, reinfection may happen especially in juvenile patients (age less than 18 years). Our findings have implications for the long-term management of recovered COVID-19 patients.

Background Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. Conclusions In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. Trial registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

Renal cell carcinoma (RCC) with anaplastic lymphoma kinase (ALK) rearrangement is rare, and the genetic profiles of the tumor have not been elucidated. Here, we report a case with recurrent papillary RCC and lung metastasis after nephrectomy for nearly 7 years. The patient first received sunitinib, whereas the drug toxicity was intolerable. Combined Immunohistology (IHC) and fluorescence in situ hybridization (FISH) revealed the patient has an ALK rearrangement, and the patient then was treated with crizotinib. The patient had good tolerance, and a partial response in the target lesions was achieved. In order to further understand the benefit of crizotinib in ALK-rearranged RCC, the patient was detected with whole exome sequencing (WES) to study her genetic profiles. Compared those of RCC cases without ALK rearrangement (nALK-RCC), the patient and nine RCC cases with ALK rearrangement (ALK-RCC) revealed unique genetic characteristics: 1) The common mutations that occurred in RCC were not found in ALK-RCC.; 2) A total of 11 co-existing mutations in ALK-RCC were found, and they occurred in nALK-RCC at a relatively low frequency. DNMT3A mutations were concurrent with ALK fusions in our case. These findings indicated a different genetic alteration pattern of ALK-RCC from nALK-RCC. Our case demonstrated the efficacy of crizotinib in an RCC patient with ALK rearrangement.

Background/aim TP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53 mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53 mut DLBCL patients. Methods A total of 44 DLBCL patients with TP53 mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease. Results Among 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP-like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53 mut DLBCL patients compared to R-CHOP-only treatment. Conclusion This study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.

Highlights • Middle-aged adults with no underlying diseases could be a severe COVID-19 patient. • Lung biopsies were rarely reported in patients with serious COVID-19. • Pathological and inflammatory features are investigated in a severe COVID-19 patient., We reported a patient diagnosed with severe pneumonia from coronavirus disease 2019(COVID-19), and did the percutaneous lung biopsy with the guidance of ultrasound. Then we presented the patient's lung morphological, ultrastructure, and some important inflammatory biological markers changes, to help better understand the disease and make a clue for all the multidisciplinary team to save more people.

AIM The prognosis and treatment options for follicular lymphoma (FL) remain heterogenous. This study aimed to analyze the prognostic impact of rituximab maintenance and evaluate the prognostic models in Chinese FL patients. METHODS We retrospectively evaluated patients with treatment-naive advanced stage FL who were treated in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between January 2008 and December 2018. We compared the baseline characteristics, long-term survival outcomes, prognostic factors and the performance of four common prognostic models (i.e., FLIPI, FLIPI2, PRIMA-PI and LDH+β2M) between them. RESULTS A total of 158 patients were included (rituximab maintenance group, 77 patients; observation group, 81 patients). The median follow-up time was 61.0 months. The rituximab maintenance group showed significantly higher 5-year progression-free survival (PFS; 83.3% vs 52.7%, P

Aim The aim of the study was to compare the therapeutic strategies and prognostic factors of patients with primary intestinal diffuse large B-cell lymphoma (PI-DLBCL). Methods A total of 50 PI-DLBCL patients who accepted standard first-line treatment at National Cancer Center in China were included in this retrospective study. Survival analysis was performed to evaluate the prognostic risk factors. Results The 3-year overall survival (OS) and 3-year progression-free survival (PFS) for the entire group were 76.0% and 65.9%, respectively. Univariate analysis showed that B symptom, advanced Lugano stage, elevated LDH status, poor ECOG PS and immunochemotherapy alone were significantly correlated with a poor PFS. Elevated LDH status, poor ECOG PS, advanced Lugano stage, high IPI score and immunochemotherapy alone were significantly correlated with a poor OS. Multivariate analysis revealed that ECOG PS (P= 0.035; HR = 0.233; 95% CI, 0.060-0.905), LDH level (P = 0.010; HR = 0.223; 95% CI, 0.072-0.693) and surgery (P = 0.002; HR = 5.584; 95% CI, 1.883-16.563) were independent prognostic factors for OS. LDH level (P = 0.035; HR = 0.210; 95% CI, 0.049-0.894) and surgery (P = 0.003; HR = 6.410; 95% CI, 1.903-21.593) were independent risk factors for PFS in PI-DLBCL. R-CHOP immunochemotherapy combined surgery treatment was also associated with a lower rate of refractory/relapsed (R/R) disease (P = 0.004). Furthermore, stratified analysis revealed that partial resection or radical resection combined with immunochemotherapy had no significantly difference which affect OS (P = 0.338) and PFS (P = 0.207). Conclusion R-CHOP immunochemotherapy plus surgery was associated with a superior prognosis compared with R-CHOP alone in Chinese PI-DLBCL population.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous malignancy. Following front-line immunochemotherapy, 30–40% of DLBCL patients develop relapsed or refractory (r/r) disease, which can be treated with ibrutinib. It has been previously reported that MYD88MUT affects the response to ibrutinib in patients with r/r DLBCL. Here, we aimed to gather understanding of MYD88MUT in r/r DLBCL patients and to evaluate its influence on response to ibrutinib. In this study, tissue samples from DLBCL patients (n = 212) were retrospectively collected and sequenced by target-capturing panels of either 413 or 112 genes that are frequently mutated in non-Hodgkin’s lymphoma. Sixty patients with MYD88 mutations and available clinical information were included for further analysis. Seven MYD88MUT variants were identified, L265P (65.0%, n = 39), S219C (13.3%, n = 8), S243N (8.3%, n = 5), P258L (6.7%, n = 4), F283V (1.7%, n = 1), P141R (1.7%, n = 1), and V217F (1.7%, n = 1). One patient had MYD88 amplification. In addition, mutations in PIM1 (67%, n = 40), IGH fusion (48%, n = 29), CD79B (43%, n = 26), KMT2D (30%, n = 18), and TP53 (27%, n = 17) were identified. For patients with L265P, IRF4 (p = 0.011) was frequently mutated. Otherwise, TET2 (p = 0.016), NOTCH2 (p = 0.044), MET (p = 0.037), SOCS1 (p = 0.011), TNFRSF14 (p = 0.011), EZH2 (p = 0.037), and BCL6 (p

Background: The clinical course of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) is variable, with limited efficacy data of second-line treatment in a post-rituximab real-world context. Hence, we explored the predictors and constructed a nomogram for risk stratification in this population. Patients and methods: Among 296 r/r DLBCL patients pretreated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) at the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between 2006 and 2017, 231 were included for nomogram construction. After randomization, we constructed the prognostic nomogram in the primary cohort (n=161) based on a multivariate analysis and confirmed it in the validation cohort (n=70). Additionally, we explored predictive factors for second-line therapy using a ordinal regression analysis. Results: Four independent prognostic factors including rituximab in the second-line setting, initial Eastern Cooperative Oncology Group (ECOG) performance status (PS), response to front-line treatment, and invasion on progression/recurrence were used to construct the nomogram. The nomogram had a C index of 0.70 with AUC values of 0.73 and 0.71 for the primary and validation cohorts, respectively. Subsequently, three risk groups (low, intermediate, and high) were determined with median overall survival (OS) of 38.0, 25.0, and 7.0 months, respectively. Additionally, we conducted a multivariate ordinal regression analysis and identified prior response to front-line treatment (odds ratio=4.50, 95% CI: 1.84-11.27, p=0.001) and bulky disease at diagnosis (odds ratio=0.36, 95% CI: 0.182-0.702, p=0.003) were two independent factors for second-line treatment efficacy. Conclusions: The established predictors for treatment efficacy and the novel nomogram for survival in r/r DLBCL patients could potentially be applied for risk stratification and treatment guidance in the post-rituximab era.

Background: This study aimed to explore the interactions and relationships of genes and recognize the hub genes associated with prognosis in follicular lymphoma (FL) treated with first-line rituximab combined with chemotherapy.Method: RNA sequencing data of dataset GSE65135 (n=24) were included in differentially expressed genes (DEGs) analysis. Weighted gene co-expression network analysis (WGCNA) was applied for exploring the coexpression network and identifying hub genes. Validation of hub genes expression and prognosis were applied in dataset GSE119214 (n=137) and patient cohort of Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (n=32), respectively, by analyzing RNAseq expression data and serum protein concentration quantified by ELISA. CIBERSORT was applied for tumor-infiltrating immune cells (TIICs) subset analysis. Results: A total of 3260 DEGs were obtained, with 1861 genes upregulated and 1399 genes downregulated. Using WGCNA and Cytoscape analysis, eight hub genes, PLA2G2D, MMP9, PTGDS, CCL19, NFIB, YAP1, RGL1, and TIMP3 were identified. Kaplan-Meier analysis and multivariate COX regression analysis indicated that CCL19 independently associated with overall survival (OS) for FL patients treated with rituximab and chemotherapy (HR = 0.47, 95%CI [0.25-0.86], p = 0.014). Higher Serum CCL19 concentration was associated with longer progression-free survival (PFS, p=0.014) and OS (p=0.039). TIICs subset analysis showed that CCL19 expression had a positive correlation with monocytes and macrophages M1, and a negative correlation with naïve B cells and plasma cells. Conclusion: CCL19 expression was associated with survival outcomes and might be a potential prognostic biomarker for FL treated with first-line immunochemotherapy.

We conducted a retrospective study in 274 previously untreated advanced Hodgkin lymphoma (HL) patients to investigate the prognostic value of baseline platelet (PLT) count, platelet distribution width (PDW), mean platelet volume (MPV), and platelet/lymphocyte ratio (PLR). The median follow-up time was 89 (range 0.3-240) months. By univariate analysis, PLT/PDW

Purpose This study aimed to develop a prognostic nomogram in diffuse large B-cell lymphoma (DLBCL) and compare it with traditional prognostic systems. Materials and methods We included 1,070 consecutive and nonselected patients with DLBCL in the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, between 2006 and 2012. A nomogram based on the Cox proportional hazards model was developed. Results The entire group were divided into the primary (n = 748) and validation (n = 322) cohorts. The 5-year overall survival (OS) rate was 64.1% for the entire group. Based on a multivariate analysis of the primary cohort, seven independent prognostic factors including age, Ann Arbor stage, Eastern Cooperative Oncology Group performance status score, lactate dehydrogenase, β2-microglobulin, CD5 expression, and Ki-67 index were identified and entered the nomogram. The calibration curve showed the optimal agreement between nomogram prediction and actual observation. In addition, the concordance index (C-index) of the nomogram for OS prediction was 0.77 (95% confidence interval [CI], 0.73–0.81) in the primary cohort and 0.76 (95% CI, 0.70–0.81) in the validation, superior to that of the international prognostic index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI (range, 0.69–0.74, p Conclusions The proposed nomogram provided an accurate estimate of survival of patients with DLBCL, especially for those receiving R-CHOP or R-CHOP-like regimens, allowing clinicians to optimized treatment plan based on individualized risk prediction. Implications for Practice A diffuse large B-cell lymphoma (DLBCL)-specific prognostic nomogram was developed based on Chinese patients with DLBCL. As a tertiary hospital, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences is the number 1 ranked cancer center in China, with more than 800,000 outpatients in 2018. Patients included in this study were nonselected and came from 29 different provinces, municipalities, and autonomous regions in China. Thus, the data is believed to be representative to an extent.

Background Primary lymphoma of the skull base (PLSB) is an extremely rare neoplasm and not much is known regarding the clinical features of, treatment strategies for, and prognoses of these lesions. We investigated the manifestations and clinical outcomes of Chinese patients with PLSB. Methods We retrospectively reviewed the data from 8 consecutive patients with PLSB who had been treated at our center from October 2008 to December 2016 and analyzed their clinical features, treatment strategies, and prognoses. Results Of the 8 patients, 3 were men and 5 were women, with a male/female ratio of 0.6. The median age was 53.5 years. In most instances, the onset was characterized by headache, followed by dysfunction of the cranial nerves. The most frequently affected region was the cavernous sinus. On magnetic resonance imaging, the main characteristic was that the internal carotid artery was encased by the tumor without an obvious tendency to be deformed, dislocated, or narrowed. All patients underwent surgical biopsy via a transsphenoidal or sublabial–transmaxillary approach. The pathological diagnosis was non-Hodgkin lymphoma for all 8 patients, with diffuse large B-cell lymphoma in 7 patients. The patients underwent chemotherapy and involved-field radiotherapy. The median overall survival was 52 months, and the 1-year progression-free survival rate was 87.5%. Conclusions PLSB is a rare disease and a diagnostic challenge, with most cases in the Chinese due to diffuse large B-cell lymphoma. We found that the incidence peaked in middle and old age, and the cavernous sinus was usually affected. Multidisciplinary treatment involving surgical biopsy, chemotherapy, and radiotherapy was an effective therapeutic strategy.

Background Extensive‐stage small cell lung cancer (ES‐SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES‐SCLC since 2018, ES‐SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES‐SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES‐SCLC population. Methods We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from January 1, 2011 to December 31, 2018 in a Chinese top‐level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. Results The median overall survival (OS) of ES‐SCLC patients (N = 358) was 14.0 months, the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR, This study provides real‐world evidence of survival and prognosis of untreated extensive stage small cell lung cancer (ES‐SCLC). We retrospectively collected the detailed medical records of 358 patients with ES‐SCLC from 2011 to 2018 in a Chinese top‐level cancer hospital. The median overall survival (OS) of all patients was 14.0 months, and the one‐ and two‐year OS rates were 56.2% and 21.7%, respectively. The median progression‐free survival (PFS) of 238 patients was 6.2 months, and the six‐month and one‐year PFS rates were 51.7% and 14.3%, respectively. Moreover, several independent prognostic factors for OS and PFS of ES‐SCLC were identified.

Aim Little is known about the outcome and prognostic factors of relapsed or refractory T-cell lymphoblastic lymphoma (T-LBL), especially in adult patients. The aim of this study was to analyze the characteristics, outcome and prognostic factors for this patient population. Methods Between January 2006 and December 2017, we retrospectively analyzed 84 adult patients with T-LBL, and 44 relapsed or primary refractory patients were included in this analysis. Clinical features, treatment and follow-up information were collected. Results For all 44 patients, the median time to disease progression or relapse was 9.5 months after diagnosis. At a median follow-up of 19.6 months, 40 (90.9%) patients died. The 3- and 5-year overall survival (OS) rates after disease progression or relapse were 7.8% and 5.2%, respectively. Among 30 patients who had detailed information of second-line treatment, only eight achieved a second complete remission (CR). Two of these eight patients subsequently underwent autologous or allogeneic stem cell transplantation (SCT), of whom one died from disease progression after autologous SCT, and one was free of event at 84 months after allogeneic SCT. Three of the rest six patients in second CR were still alive after chemotherapy alone. All the remaining patients who failed to gain second CR eventually died. In univariate analysis, only the achievement of second CR was positively predictive of OS (hazard ratio (HR) = 0.307; 95% confidence interval (CI), 0.104-0.905; P = 0.032). Conclusion The outcome of adult patients with relapsed or refractory T-LBL is extremely dismal. Patients with relapsed or refractory T-LBL should be encouraged to participate in clinical trials where novel therapeutic approaches are available.

Shengyu Zhou,1,2,* Jiawei Xu,1,* Wenqing Sun,3 Jintao Zhang,1 Fayan Zhang,4 Xuesong Zhao,5 Ximing Wang,6 Wei Zhang,7 Yu Li,1 Kang Ning,8 Yun Pan,1 Tian Liu,1 Jiping Zhao,1 Jiguang Yu,9 Yunbo Sun,10 Feng Gao,11 Rumin Zhang,12 Chunsheng Fu,13 Yu Sun,14 Xiuhe Ouyang,15 Fusen Zhang,16 Qing Hu,17 Haifeng Teng,18 Yun Li,19 Chunke Zhang,20 Wei Tan,21 Jinlai Li,22 Lixia Yin,23 Liang Dong,1 Chunting Wang5 1Department of Respiratory and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Clinical Nursing Department, School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Intensive Care Unit, Shandong Provincial Chest Hospital, Jinan, People’s Republic of China; 4College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 5Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 6Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong University, Jinan, People’s Republic of China; 7Department of Lung Disease, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 8The First Affiliated Hospital of Shandong First Medical University Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China; 9Department of Infectious Diseases, Qishan Hospital, Yantai, People’s Republic of China; 10Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 11Department of Infectious Disease, Linyi People’s Hospital, Linyi, People’s Republic of China; 12Department of Critical Care Medicine, Zibo Central Hospital, Zibo, People’s Republic of China; 13Liaocheng Contagion Hospital, Liaocheng, People’s Republic of China; 14Jining Hospital of Infectious Diseases, Jining, People’s Republic of China; 15Department of Respiratory and Critical Medicine, Binzhou People’s Hospital, Binzhou, People’s Republic of China; 16Intensive Care Unit, Taian City Central Hospital, Taian, People’s Republic of China; 17Department of Respiratory Medicine, Heze Municipal Hospital, Heze, People’s Republic of China; 18Weihai Municipal Hospital, Weihai, People’s Republic of China; 19Jinan Central Hospital, Jinan, People’s Republic of China; 20Weihai Central Hospital, Weihai, People’s Republic of China; 21Department of Respiratory Medicine, Weifang People’s Hospital, Weifang, People’s Republic of China; 22Intensive Care Unit, Zaozhuang Municipal Hospital, Zaozhuang, People’s Republic of China; 23Department of Respiratory Medicine, Dezhou People’s Hospital, Dezhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Dong; Chunting Wang Email dl5506@126.com; wcteicu@126.comBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel pathogen, has caused an outbreak of coronavirus disease 2019 (COVID-19) that has spread rapidly around the world. Determining the risk factors for death and the differences in clinical features between severely ill and critically ill patients with SARS-CoV-2 pneumonia has become increasingly important.Aim: This study was intended to provide insight into the difference between severely ill and critically ill patients with SARS-CoV-2 pneumonia.Methods: In this retrospective, multicenter cohort study, we enrolled 62 seriously ill patients with SARS-CoV-2 pneumonia who had been diagnosed by March 12, 2020. Clinical data, laboratory indexes, chest images, and treatment strategies collected from routine medical records were compared between severely ill and critically ill patients. Univariate and multivariate logistic regression analyses were also conducted to identify the risk factors associated with the progression of patients with severe COVID-19.Results: Of the 62 patients with severe or critical illness, including 7 who died, 30 (48%) patients had underlying diseases, of which the most common was cardiovascular disease (hypertension, 34%, and coronary heart disease, 5%). Compared to patients with severe disease, those with critical disease had distinctly higher white blood cell counts, procalcitonin levels, and D-dimer levels, and lower hemoglobin levels and lymphocyte counts. Multivariate regression showed that a lymphocyte count less than 109/L (odds ratio 20.92, 95% CI 1.76– 248.18; p=0.02) at admission increased the risk of developing a critical illness.Conclusion: Based on multivariate regression analysis, a lower lymphocyte count (< 109/L) on admission is the most critical independent factor that is closely associated with an increased risk of progression to critical illness. Age, underlying diseases, especially hypertension and coronary heart disease, elevated D-dimer, decreased hemoglobin, and SOFA score, and APACH score also need to be taken into account for predicting disease progression. Blood cell counts and procalcitonin levels for the later secondary bacterial infection have a certain reference values.Keywords: SARS-CoV-2, COVID-19, clinical features, severely ill patients, critically ill patients

Background: Palliative chemotherapy has been the mainstay treatment for patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). However, little is known about the efficacy and toxicity of nimotuzumab (NTZ) – a monoclonal antibody drug targeting epidermal growth factor receptor – plus chemotherapy (CT) versus CT alone for these patients. Methods: The database at Cancer Hospital of Chinese Academy of Medical Sciences was queried for patients diagnosed with NPC who received CT with or without NTZ between 2004 and 2018. Treatment compliance, survival outcomes, and adverse effects were compared among these groups. Results: Records of 70 patients with R/M-NPC were reviewed: 21 (30%) received NTZ plus CT (NTZ+CT) and 49 (70%) received CT. CT regimens included gemcitabine plus platinum, taxane plus platinum (TP), and fluorouracil plus platinum. Comparing the CT group with NTZ+CT group, the median follow up was 62 months (range = 3–133) versus 59 months (range = 9–117); median progression free survival was 7.5 [95% confidence interval (CI) 6.552–8.381] months versus 8.5 (95% CI 6.091–10.976) months, p = 0.424; median overall survival (OS) was 25.6 (95% CI 18.888–32.379) months versus 48.6 (95% CI 35.619–61.581) months, p = 0.017, respectively. Multivariable analysis established treatment group (CT versus NTZ+CT) as an independent prognostic factor for OS (hazard ratio, 0.5; 95% CI 0.255–0.979; p = 0.043). No significant difference with regard to toxicities was observed between the two groups. Among them, a subgroup analysis was performed in 53 (75.7%) patients who received TP with or without NTZ, which showed similar results. Conclusion: Our findings suggested that NTZ+CT provides a novel treatment option and prolongs survival significantly for R/M-NPC.

Bevacizumab is the first antiangiogenetic monoclonal antibody, combined with platinum‐based double agent chemotherapy, which has been reported to improve the objective response rate (ORR) and progression‐free survival (PFS) in patients with advanced nonsquamous non‐small cell lung cancer (NSCLC), and to improve overall survival (OS) in patients when combined with carboplatin and paclitaxel. However, serious adverse effects have been reported to be associated with bevacizumab therapy. In this multicenter prospective cohort study of advanced lung adenocarcinoma patients with stable disease after two cycles of platinum‐based double agent chemotherapy, we will compare the ORR between the group who continued with their original chemotherapy regimen and the group in which bevacizumab was added to the original regimen. It is expected that there will be an ORR improvement of 20% in patients in the bevacizumab group plus chemotherapy, compared with those in the original chemotherapy group. This study has been registered as Clinical Trial NCT03240549., Bevacizumab combined with platinum‐based double agent chemotherapy has been reported to improve the objective response rate (ORR) and progression‐free survival (PFS) in patients with advanced nonsquamous non‐small cell lung cancer (NSCLC), but also cause more adverse effects. We hypothesize that the improvement in the response rate in the bevacizumab group comes from the patients with stable disease in the chemotherapy group. A multicenter prospective cohort study will be conducted in advanced lung adenocarcinoma patients with stable disease after two cycles of platinum‐based double agent chemotherapy, in which we will compare the ORR between the group who continued with their original chemotherapy regimen and those where bevacizumab was added to the original regimen.

T cell lymphoblastic lymphoma (T-LBL) has an aggressive clinical behavior. To date, powerful and consistent prognostic factors have not been established for T-LBL. In this study, we first evaluated the association of event-free survival (EFS) at 24 months (EFS24) with overall survival (OS) in T-LBL patients. Besides, we sought to identify clinical factors of prognostic importance in this rare entity. Between January 2006 and December 2017, ninety-one patients with newly diagnosed T-LBL were retrospectively analyzed. EFS was defined as the time from diagnosis to relapse or progression, unplanned retreatment, death from any cause, or to the last follow-up. In total, 91 patients with a median age of 24 years were enrolled. At a median follow-up of 40.4 months (range, 1.4 to 163.3 months), the 5-year OS and EFS was 47.9% and 43.2%, respectively. Of all patients, 45 (49.5%) achieved EFS24 and 46 (50.5%) did not. Patients who achieved EFS24 showed a markedly superior outcome, compared with those who failed to achieve EFS24 (5-year OS, 90.5% vs 3%, P

Background: Programmed cell death protein 1 (PD1) inhibitors have revolutionized cancer therapy, yet many patients fail to respond. Thus, the identification of accurate predictive biomarkers of therapy response will improve the clinical benefit of anti-PD1 therapy. Method: We assessed the baseline serological autoantibody (AAb) profile against ~2300 proteins in 10 samples and ~4600 proteins in 35 samples with alveolar soft part sarcoma (ASPS), non-small-cell lung cancer (NSCLC) and lymphoma using Nucleic Acid Programmable Protein Arrays (NAPPA). 23 selected potential AAb biomarkers were verified using simple, affordable and rapid enzyme linked immune sorbent assay (ELISA) technology with baseline plasma samples from 12 ASPS, 16 NSCLC and 46 lymphoma patients. SIX2 and EIF4E2 AAbs were further validated in independent cohorts of 17 NSCLC and 43 lymphoma patients, respectively, using ELISA. The IgG subtypes in response to therapy were also investigated. Results: Distinct AAb profiles between ASPS, NSCLC and lymphoma were observed. In ASPS, the production of P53 and PD1 AAbs were significantly increased in non-responders (p=0.037). In NSCLC, the SIX2 AAb was predictive of response with area under the curve (AUC) of 0.87, 0.85 and 0.90 at 3 months, 4.5 months, 6 months evaluation time points, respectively. In the validation cohort, the SIX2 AAb was consistently up-regulated in non-responders (p=0.024). For lymphoma, the EIF4E2 AAb correlated with a favorable response with AUCs of 0.68, 0.70, and 0.70 at 3 months, 4.5 months, and 6 months, respectively. In the validation cohort, the AUCs were 0.74, 0.75 and 0.66 at 3 months, 4.5 months, and 6 months, respectively. The PD1 and PD-L1 IgG2 AAbs were highly produced in ~20% of lymphoma responders. Furthermore, bioinformatics analysis revealed antigen functions of these AAb biomarkers. Conclusion: This study provides the first evidence that AAb biomarkers selected using high-throughput protein microarrays can predict anti-PD1 therapeutic response and guide anti-PD1 therapy.

Background: Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods: We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Findings: Between July 8, 2018 and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At data cutoff (Feb 15, 2020), the median follow-up was 4.06 months (range: 0.30-16.7). For 84 patients in FAS, 33 achieved objective response (39.3%, 95% CI 28.80-50.55), of which 10 (11.9%) were complete response and 23 (27.4%) had partial response assessed by IRRC. The 6-month duration of response (DOR) rate was 61.8% (95% CI 41.4, 76.9). Patients with PD-L1 expression ≥50% derived more benefit from geptanolimab treatment compared to

Objective This study aimed to develop a novel prognostic nomogram and a web-based survival rate calculator to improve discriminative and predictive accuracy for diffuse large B cell lymphoma (DLBCL) in rituximab era. Methods We retrospectively collected data about 906 DLBCL patients who received R-CHOP or R-CHOP-like chemotherapy from January 2005 to December 2018 in National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences. COX proportional hazard regression analysis was performed to assess the independent prognostic significance of clinical and histopathological variables on overall survival, which were used to develop the nomogram. We performed internal and external validation of the nomogram, and compared it's discriminative and predictive accuracy with the traditional IPI, R-IPI, and NCCN-IPI. ResultsThe patients were divided into the training (n = 636) and validation (n = 270) cohorts at a ratio of 7:3. We identified six independent predictors for survival including age, ECOG, number of extranodal sites, bulky, and β2-MG, which were used to construct the nomogram and the web-based survival rate calculator. The C-index of the nomogram was 0.767 (95% CI, 0.735-0.799) in the training cohort and 0.732 (95% CI, 0.678-0.786) in the validation cohort. The AUC values of the nomogram for predicting the 1-, 5-, and 10-year OS rates for DLBCL were 0.794, 0.799, 0.805 in the training cohort and 0.828, 0.773, 0.771 in the validation cohort. All calibration curves revealed optimal consistency between predicted and actual survival both in the training and validation cohort. The nomogram divided DLBCL patients into three risk groups, the score of low risk, moderate risk, and high risk were 0-45，46-228，and higher than 228, respectively. The risk stratification model generated based on the nomogram showed a favorable level of predictive accuracy compared with the IPI, R-IPI, and NCCN-IPI in both cohorts according to the K-M survival curves. The AUC values of the nomogram model compared with the IPI, R-IPI, and NCCN-IPI for predicting the 10-year OS rates for DLBCL patients were 0.756 vs 0.748, 0.732, 0.713 in the training cohort and 0.742 vs 0.712, 0.713, 0.757 in the validation cohort. ConclusionsIn conclusion, we have established and validated a novel prognostic nomogram model and a web-based survival rate calculator, which revealed more discriminative and predictive accuracy than IPI, R-IPI, and NCCN-IPI in the rituximab era. Disclosures No relevant conflicts of interest to declare.

Background The prognostic value of platelet count in diffuse large B-cell lymphoma (DLBCL) has not been extensively investigated. We aimed to examine the association of pretreatment platelet count with disease features, and further examine the prognostic significance of platelet count in DLBCL treated with the R−CHOP regimen. Methods Patients with DLBCL diagnosed between Jan 1 st, 2005 and Dec 31 st, 2018 at Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Propensity score matching (PSM) was used to balance confounding factors. Results A total of 1007 eligible patients who received frontline R−CHOP or R−CHOP-like regimens were included in this study. The optimal cutoff value of platelet count was 157 × 109/L, as determined by the Maximally Selected Rank Statistics method. Patients with the platelet count ≤157 × 109/L had significantly inferior overall survival (OS) (5-year OS, 44.4 % vs. 74.9 %, P 157×109/L. Multivariate analyses showed that pretreatment platelet count ≤ 157 × 109/L was an adversely independent prognostic factor for OS (hazard ratio [HR] 1.960, 95 % confidence interval [CI] 1.418−2.709, P Conclusion The pretreatment platelet count may be a simple, cost-effective and useful prognostic factor in DLBCL patients treated with frontline R−CHOP regimens. Further investigation is warranted to elucidate the biologic mechanism underlying the prognostic significance of platelet count in DLBCL.

Reactive oxygen species (ROS) with strong oxidability have been considered as effective agents for antitumor therapy through oxidative damage to lipids, proteins, DNA and RNA. In this work, a multifunctional hollow cobaltosic sulfide (Co3S4)/photosensitizer indocyanine green (ICG) nanocomplex (Co3S4-ICG) has been synthesized by efficiently loading ICG into the hollow Co3S4 to realize synergistic antitumor therapy via chemodynamic therapy (CDT), photodynamic therapy (PDT) and photothermal therapy (PTT) under near-infrared (808 nm) laser irradiation. Co3S4 nanoparticles would be degraded in tumor acidic microenvironment into Co2+, which locally triggers a Fenton-like reaction to produce cytotoxic hydroxyl radicals ( OH) for CDT. Co3S4-ICG could also produce singlet oxygen (1O2) through a multi-step photochemical process for PDT under 808 nm laser irradiation. The slow release of ICG in the tumor region was achieved due to hollow-structured Co3S4 working as nanocarriers, and which has been proved an effective approach for combined CDT/PDT. In addition, Co3S4-ICG showed high photothermal conversion efficiency (40.5%) for PTT, and excellent OH generation capability via photothermal-improved Fenton reaction, leading to the synergistically improved antitumor efficacy. In vitro and in vivo experimental results confirm that the combined PTT/PDT/photothermal-enhanced CDT therapy can effectively ablate tumors with a negligible systemic toxicity. This work provides a valuable strategy for designing and constructing of a multifunctional nanoplatform for synergistic antitumor therapy of solid tumors.

Extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKTL) is an aggressive non-Hodgkin lymphoma and the majority of ENKTL cases are diagnosed at the localized stage. Radiotherapy in combination with chemotherapy has been used for localized ENKTL, but the optimal combination treatment modality and the best first-line chemotherapy regimen have not been defined. In this retrospective study, 44 patients with newly diagnosed, stages I/II ENKTL were enrolled and received intensity-modulated radiation therapy (IMRT, 50-56 Gy) followed by GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy. The median number of chemotherapy cycles per patient was 4 (range, 2-6 cycles). At the end of treatment, the overall response rate was 95% (42/44), including 39 patients (89%) who attained complete response. Two patients developed systemic progression after IMRT. With a median follow-up of 37.5 months, the 3-year overall survival (OS) rate and progression-free survival (PFS) rate were 85% (95% CI, 74 to 96%) and 77% (95% CI, 64 to 91%), respectively. Locoregional and systemic failure rates for this treatment were 9% (4/44) and 14% (6/44), respectively. The most common grades 3 to 4 adverse events included leukopenia (37%), neutropenia (34%), and mucositis (25%). No treatment-related deaths were observed. This study suggested high efficacy and low toxicity of IMRT followed by GDP regimen chemotherapy for newly diagnosed stage I/II ENKTL patients. These results require further investigation in prospective trials.

// Wumin Dai 1 , Bo Jia 1 , Jianliang Yang 1 , Shengyu Zhou 1 , Peng Liu 1 , Xiaohui He 1 , Yan Qin 1 , Lin Gui 1 , Changgong Zhang 1 , Xiaohong Han 1 , Yan Sun 1 , Yuankai Shi 1 1 Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100021, China Correspondence to: Yuankai Shi, email: syuankai@cicams.ac.cn , syuankaipumc@126.com Keywords: beta2-microglobin to lymphocytes ratio index, lactate dehydrogenase to lymphocytes ratio index, systemic immune-inflammation, prognosis, extranodal natural killer/T cell lymphoma Received: January 13, 2017 Accepted: March 15, 2017 Published: March 30, 2017 ABSTRACT To identify simple non-invasive prognostic factors for extranodal natural killer/T cell lymphoma (ENKTL), we have investigated the prognostic value of pretreatment β2-microglobin to lymphocytes ratio index (βLRI) or lactate dehydrogenase to lymphocytes ratio index (LLRI), by analyzing the retrospective data from 211 ENKTL patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off value of pretreatment βLRI and LLRI. The univariate analysis indicated that Ann Arbor Stage ( p = 0.008), Eastern Cooperative Oncology Group score (ECOG) ( p = 0.009), International Prognostic Index (IPI) ( p = 0.023), βLRI ( p = 0.003), LLRI ( p = 0.04), neutrophil-lymphocyte ratio index ( p = 0.025) and monocyte/granulocyte to lymphocyte ratio ( p = 0.030) were significantly associated with overall survival (OS) in ENKTL patients. However, multivariate analysis demonstrated that only Ann Arbor Stage ( p = 0.028), βLRI ( p < 0.001) and LLRI ( p = 0.006) were only correlated independently with OS. Furthermore, βLRI and LLRI based new prognostic model showed improved discrimination for stage IE/IIE upper aerodigestive tract in ENKTL patients than IPI and Korean Prognostic Index. Overall, our study concluded that new βLRI-based prognosis model is useful to stratify ENKTL patients and higher βLRI and LLRI can act as independent prognostic predictor candidates in early stage ENKTL.

The difference in clinical features and treatment outcomes between localized sinonasal diffuse large B cell lymphoma (SN-DLBCL) and sinonasal extranodal NK/T cell lymphoma (SN-ENKTL) is unclear. Therefore, we analyzed a total of 47 patients with localized SN-DLBCL and 211 patients with localized SN-ENKTL. The age distribution for these two subtypes is very distinct and the B symptoms were more common in SN-ENKTL. However, both SN-DLBCL and SN-ENKTL patients could achieve high overall response rate (ORR) and favorable prognoses. The 3-year overall survival (OS) rates for patients with SN-DLBCL and SN-ENKTL were 79.7 and 83.6% (p = 0.707), and the 3-year progression-free survival (PFS) rates were 61.4 and 70.1% (p = 0.294), respectively. For SN-DLBCL patients, chemotherapy followed by involved-field radiotherapy (IFRT) resulted in higher OS (83.7 vs 62.5%) and PFS (63.9 vs 50.0%) compared with chemotherapy alone, but the difference was not significant. No significant difference was found in the OS or PFS between radiotherapy alone and radiotherapy combined with chemotherapy for all patients with SN-ENKTL. But in extensive stage I and stage II SN-ENKTL patients, radiotherapy combined with chemotherapy could significantly improve the PFS (73.8 vs 50.0%) compared with radiotherapy alone. These results indicate that remarkable clinical disparities exist between localized SN-DLBCL and SN-ENKTL. However, different treatment strategies for them can result in similarly favorable prognoses. Electronic supplementary material The online version of this article (doi:10.1186/s13045-016-0368-9) contains supplementary material, which is available to authorized users.

Background Cigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring. We have previously shown that maternal L-Carnitine treatment can reduce the adverse impacts of maternal SE on renal and brain disorders in offspring. Here, we investigated the effect of maternal L-Carnitine supplementation on lung inflammatory pathways, autophagy, and mitophagy markers in the offspring in response to maternal SE. Methods Female BALB/c mice (8 weeks) were exposed to cigarette smoke for 6 weeks prior to mating, during gestation and lactation. Some of the SE dams were given L-Carnitine supplementation (1.5 mM in drinking water, SE + LC) during gestation and lactation. Lungs from the offspring were studied at birth and adulthood (13 weeks). Results At birth, in male offspring, there were increased levels of inflammatory markers (phosphorylated(p)-ERK1,2, p-P38 MAPK, p- NF-κB), and inflammasome marker (NLRP3), as well as mitophagy fission marker Drp-1 and autophagosome marker (LC3A/B-II) in the lung. Maternal L-Carnitine supplementation significantly reduced NLRP3 level. In contrast, maternal SE only increased IL1-β in female offspring, which was reversed by maternal L-Carnitine supplementation. At 13 weeks, there was an increase in LC3A/B-II and p- NF-κB in the male SE offspring with reduced p-JNK1,2, which were partially normalised by maternal L-Carnitine treatment. Female offspring were not affected by maternal SE at this age. Conclusion Maternal SE had adverse impacts on the male offspring’s lung, which were partially alleviated by maternal L-Carnitine supplementation. Females seem to be less affected by the adverse effects of maternal SE.

Diffuse large B-cell lymphoma (DLBCL) is a clinically aggressive and heterogenous disease. Although most patients can be cured by immunochemotherapy, 30% to 40% patient will ultimately develop relapsed or refractory disease. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. We performed capture-based targeted sequencing on baseline samples of 105 DLBCL patients using a panel consisting of 112 lymphoma-related genes. Subsequently, 81 treatment-naive patients with measurable disease and followed for over 1 year were included for survival analysis. Collectively, the most commonly seen mutations included IGH fusion (69%), PIM1(33%), MYD88 (29%), BCL2 (29%), TP53 (29%), CD79B (25%) and KMT2D (24%). Patients with TP53 mutations were more likely to have primary refractory disease (87.0% vs 50.0%, P = .009). For those with TP53 disruptive mutations, 91.7% patients were in the primary refractory group. Interestingly, BCL-2 somatic hypermutation was only seen in patients without primary refractory disease (P = .014). In multivariate analysis, BCL-2 amplification (hazard ratio [HR] = 2.94, P = .022), B2M mutation (HR = 2.99, P = .017) and TP53 mutation (HR = 3.19, P < .001) were independently associated with shorter time to progression (TTP). Furthermore, TP53 mutations was correlated with worse overall survival (P = .049). Next, we investigated mutation landscape in patients with wild-type (WT) TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior TTP than those with WT or non-265P (P = .046). Our study reveals the mutation spectrum of treatment-naive Chinese DLBCL patients. It also confirms the clinical significance of TP53 mutations and indicates the prognostic value of MYD88 L265P in TP53 WT patients.

Cigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of asthma. We have previously shown that maternal L-Carnitine treatment reduces renal and brain adverse impacts in SE offspring, but its effect on the lung is unknown. Here, in order to investigate the effect of maternal L-Carnitine supplementation on lungproinflammatory signalling pathwayswe measured inflammasome NLRP3 activation, signalling pathway activation (ERK1,2, JNK1,2, MAPK, and NF-KB), and markers of autophagy (LC3A/B-I, II) and mitophagy (Drp-1 and Opa-1). Female Balb/c mice (8 weeks) were exposed to cigarette smoke before mating for 6 weeks, during gestation and lactation. Half SE mothers were given L-Carnitine supplementation through drinking water during gestation and lactation. Lung samples were collected at postnatal day 1 and 13 weeks from both male and female offspring. At P1, there was an increase in phospho-ERK1,2, total ERK1,2, total JNK1,2, phospho-P38 MAPK and P38 MAPK, phospho-NFKB, NFKB and NLPR3 protein levels in male offspring. The mitochondrial fission marker Drp-1 and autophagosome markers (LCA3A/B-I,II) were increased in SE offspring, L-Carnitine significantly reduced protein levels of phospho-ERK1 and Drp-1. At 13 weeks, there was an increase in autophagosome markers (LCA3A/B-I,II) and MAPK signaling pathway markers (phospho-ERK2, total ERK2, total P38 MAPK and phospho-NFKB), which were partially normalized by L-Carnitine treatment. Maternal SE did not affect the female offspring with no changes found after L-Carnitine treatment. L-Carnitine supplementation during pregnancy may alleviate the adverse impact of maternal smoking in the male offspring’s lung.

Early/upfront radiation was associated with improved survivals compared with late radiation for early-stage NK/T-cell lymphoma (NKTCL) in the old era when anthracycline-base chemotherapy (CT) prevailed. However, in the modern era of effective l-asparaginase/gemcitabine-based CT, the optimal timing of radiation is unclear. In this study, 75 patients with newly diagnosed NKTCL, who were treated with combined involved-field intensity-modulated radiotherapy and GDP (gemcitabine, dexamethasone, and cisplatin) were retrospectively reviewed, including 45 from the RT + CT group and 30 from the CT + RT ± CT group. Compared with CT + RT ± CT, RT + CT sequence achieved superior progression-free survival (5-year PFS: 81.6% vs. 56.0%

Introduction Pemetrexed combined with platinum complexes can be used as first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC), however, the efficacy and safety is varying from individuals. There is a need to better understand the genetic variations associated with platinum response. Materials and Methods We performed next-generation sequencing (NGS) based on BGI Oseq-ctDNA panel to analyze 98 longitudinal plasma samples from 32 lung adenocarcinoma patients during platinum-based chemotherapy, and a bioinformatic pipeline was developed to detect point mutations. Results We found that mutation burden was decreased after chemotherapy, which reflected chemotherapy sensitivity, especially the frequency of C>G and C>A substitutions. Moreover, neoplastic cells carrying a specific set of somatic mutations, such as EGFR(L858R), KRAS (p.G12C) were obviously correlated with platinum treatment. In addition, the MAPK pathway was found to have a pivotal role in NSCLC and platinum based response. Finally, we found that smokers benefit less from platinum-based chemotherapy. Conclusions Collectively, this work described the dynamic changes of ctDNA mutation status during platinum-based treatment, which may contribute to advanced lung adenocarcinoma patients stratification and precision treatment.

Aim The clinical course of diffuse large B-cell lymphoma (DLBCL) is variable and there is a lack of prognostic markers and models for relapsed or refractory (r/r) DLBCL. Hence, we conducted this study to identify independent factors that can predict the survival rate of r/r DLBCL patients. Methods A total of 416 r/r DLBCL patients who were pretreated with first-line anthracycline-based chemotherapy at the National Cancer Center in China between 2006 and 2016 were divided into the primary (n = 291) and validation (n = 125) cohorts. The effect of preclinical and clinical indicators on DLBCL survival rates of the two cohorts were evaluated by univariate and multivariate analyses. Factors showing good correlation with patient survival rates were used to construct a prognostic nomogram. Results Multivariate analysis of the primary cohort revealed five independent prognostic factors: lactate dehydrogenase level at diagnosis, response to front line treatment, progression/recurrence pattern, location, and invasion on progression/recurrence, which were then used to construct a nomogram. The nomogram was shown to have a C-index of 0.76 and AUC values of 0.81 and 0.80 for the primary and validation cohorts, respectively, suggesting good prognostic power. We further stratified the r/r DLBCL patients into four risk groups according to the newly developed nomogram. Conclusion The prognostic nomogram constructed using the five identified clinical indicators can potentially be applied in the clinical setting to guide treatment decision.

ObjectivesPatients’ stress and satisfaction concerning cancer clinical trials (CCT) may affect study accrual and quality. Our study aimed to evaluate stress and satisfaction in CCT and the influencing factors.DesignCross-sectional analysis done by a questionnaire after informed consent.SettingCancer Hospital, Chinese Academy of Medical Sciences.Participants199 CCT participants. Primary and secondary outcome measures self-assessed stress and satisfaction in CCT.ResultsAmong 199 participants, 83.9% would join CCT again; 72.9% had enough time to decide on trial participation; 73.9% claimed complete awareness of CCT; 3.5% doubted CCT’s significance and scientific quality; 33.2% deemed CCT time-consuming; 73.9% scored satisfaction ≥9/10; and 25.6% claimed moderate to severe stress. Positive factors for satisfaction were enough decision time (OR=0.36, p=0.0003), better impressions of doctors (OR=0.41, p=0.047) and less time-consuming trials (OR=0.43, pConclusionsOur study addressed factors influencing CCT participants’ stress and satisfaction. We suggested measures to improve patients’ experiences in CCT.Trial registration numberNCT03412344; Pre-results.

Background Because of rapid disease progression and lack of optimal treatment strategies beyond the second‐line, the prognosis of patients with extensive‐stage (ES) small cell lung cancer (SCLC) still remains depressing. Alternative treatment strategies are required to improve their prognosis. In this prospective clinical study, we aimed to evaluate the feasibility of single‐agent apatinib, a vascular endothelial growth factor receptor‐2 tyrosine kinase inhibitor, as a treatment option for patients with ES‐SCLC after failure of at least two prior chemotherapy regimens. Materials and Methods Twenty‐two patients with ES‐SCLC treated with 500 mg single‐agent apatinib as subsequent‐line regimen in our institution from November 2016 to August 2018 were enrolled in the study. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results Clinical outcomes included partial response in 3 patients (13.6%), stable disease in 18 patients (81.8%), and disease progression in 1 patient (4.5%), with an ORR of 13.6% and DCR of 95.5%. The median PFS and OS were 5.4 and 10.0 months, respectively. Apatinib demonstrated a manageable toxicity profile, with grade I–III secondary hypertension and proteinuria as the most common AEs. No grade IV and V AEs were observed among the patients. Multivariate analysis revealed secondary hypertension as an independent predictor of OS (p = .047); however, the association became insignificant after Q correction (p = .455). Conclusions Apatinib was safe and effective in the management of patients with ES‐SCLC and can be considered as a treatment option after failure of at least two prior chemotherapy regimens. http://ClinicalTrials.gov identifier. NCT02995187 Implications for Practice This study indicated the acceptable toxicity profile and promising efficacy of apatinib in the management of patients with extensive‐stage small cell lung cancer after failure from at least two prior chemotherapy regimens. Secondary hypertension can be a potential prognostic factor for apatinib treatment., Alternative treatment strategies are needed to improve prognosis for patients with small‐cell lung cancer. This article evaluates the feasibility of single‐agent apatinib as a treatment option for patients with extensive‐stage small‐cell lung cancer.

Objective To explore the clinicobiologic features and outcomes of diffuse large B-cell lymphoma (DLBCL) patients in China according to the primary site. Methods A total of 1,085 patients diagnosed with DLBCL in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College during a 6-year period were enrolled. Their clinical characteristics and outcomes were analyzed according to the primary site. Results In the 1,085 patients, 679 (62.6%) cases were nodal DLBCL (N-DLBCL) and 406 cases (37.4%) were extranodal DLBCL (EN-DLBCL). The most common sites of N-DLBCL were lymphonodus (64.8%), Waldeyer's ring (19.7%), mediastinum (12.8%) and spleen (2.7%), while in EN-DLBCL, stomach (22.4%), intestine (16.0%), nose and sinuses (8.9%), testis (8.4%), skin (7.9%), thyroid (6.9%), central nervous system (CNS) (6.4%), breast (5.7%), bone (3.4%), and salivary gland (2.7%) were most common. N-DLBCL patients tend to present B symptoms, bulky disease, and elevated LDH more often, while age >60 years, extranodal sites >1, Ann Arbor stage I or II, bone marrow involvement, and Ki-67 index >90% were usually seen in EN-DLBCL. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate for all patients were 62.5% and 54.2%. The 5-year OS rate for patients with N-DLBCL and EN-DLBCL were 65.5% and 56.9% (P=0.008), and the 5-year PFS were 57.0% and 49.0% (P=0.020). Waldeyer's ring originated DLBCL possessed the highest 5-year OS rate (83.6%) and PFS rate (76.9%) in N-DLBCL. The top five EN-DLBCL subtypes with favorable prognosis were stomach, breast, nose and sinuses, lung, salivary gland, with 5-year OS rate: 70.3%, 69.6%, 69.4%, 66.7% and 63.6%, respectively. While CNS, testis, oral cavity and kidney originated EN-DLBCL faced miserable prognosis, with 5-year OS rate of 26.9%, 38.2%, and 42.9%. Conclusions In our study, primary sites were associated with clinical characteristics and outcomes. Compared with EN-DLBCL, N-DLBCL had better prognosis.

Purpose: TP53 mutation was recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Exploratory therapy for this group of patients is in great need for potential clinical benefit. Here, we investigated the effect of adding surgical procedure to standard immunochemotherapy on survival of TP53 MUT DLBCL patients. Methods: Capture-based targeted sequencing was performed on 214 DLBCL patients, of which 47 was detected TP53MUT and included for further analysis. Refractory patients were defined as individuals did not achieve complete remission (CR) or develop relapse after 6 months in response to initial treatment. Findings: For 47 patients confirmed with TP53 mutation, 44 (93·6%) received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regime were included for survival analysis with a median follow-up of 13 months. The median progression-free survival (PFS) and overall survival (OS) were 10.0 months (95%CI, 6·7-13·3) and 46.0 months (95%CI, 11·8-80·2). Among them, 26 patients developed refractory and received second-line chemotherapy. Seven limited-stage patients after early complete resection and one patient with residue resection remained event free with a median follow-up of 37 months. A multivariate analysis showed adding surgery to R-CHOP regime significantly improved PFS of TP53 MUT DLBCL patients compared to R-CHOP only treatment (p=0·039, HR=0·109, 95%CI=0·013-0·894). Conclusions: TP53 mutation is associated with unfavorable prognosis in DLBCL patients. Our study showed surgical resection may provide additional clinical benefit, which offered new treatment consideration for this group of patients. Funding Statement: This study was supported by National Key Technology Support Program (2014BAI09B12), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001), and National New Drug Innovation Program (2017ZX09304015). Declaration of Interests: JL is an employee of Burning Rock Biotech. All other authors declare no conflicts of interest. Ethics Approval Statement: The study was approved by the local ethic committee and was conducted in accordance with the Declaration of Helsinki.

Two-dimensional MoS2 (2D-MoS2) and its nanocomposites have been extensively studied in cancer therapy research since their prominent surface area and NIR absorption ability. In this work, Eu3+-incorporated MoS2 (MoS2:Eu3+) nanoflowers with enhanced photothermal conversion efficiency (PCE) were successfully developed by a one-step bottom-up hydrothermal method. Under 808 nm near-infrared (NIR) laser irradiation, the photothermal agents MoS2:5%Eu3+ nanoflowers have a PCE at ~ 49.05%, which is 1.75 times higher than the pristine MoS2. MoS2:5%Eu3+ as efficient photosensitizers also promote generation of cytotoxic reactive oxygen species (ROS) under 808 nm laser irradiation, thus achieving photodynamic therapy (PDT) for cancers at the same time. Enhanced in vitro breast cancer therapy through the combination of photothermal therapy (PTT) and PDT is clearly proved by using the MoS2:Eu3+ nanosheet as a multifunctional nanoprobe. The unique MoS2:Eu3+ works as a promising nanoprobe for PDT/PTT cancer therapies, and also provides a novel strategy for PCE improvement of the 2D-MoS2.

2523 Background: LAG-3 is an immune checkpoint receptor expressed on activated T cells to negatively regulate these cells, resulted in tumor immune escape. LBL-007, a novel anti-LAG-3 antibody, was developed by screening of a human antibody phage display library and demonstrated specific binding to human LAG-3, stimulation of IL-2 release and blockage of LAG-3 binding to its ligands including MHC II. It has shown that LBL-007 significantly inhibited tumor growth in a mouse MC38 tumor model in hLAG-3 knock-in mice with more pronounced tumor inhibition when combined with an anti-PD-1 antibody. Methods: A phase I, multicenter, open-label and first-in-human study was conducted to evaluate the safety, tolerability, and PK in patients with advanced solid tumors. The dose escalation phase was designed with 6 dose cohorts of LBL-007 at 0.05, 0.25, 1, 3, 6 and 10 mg/kg (iv every 2 weeks), using a modified 3+3 design. Key inclusion criteria included: age≥18 years, histologically/cytologically confirmed advanced solid tumors, failed ≥2 lines of prior standard therapies, ECOG of 0-1, and adequate hematologic, renal, hepatic, and cardiac function. Patients who received anticancer or immunotherapy 4 weeks from first dose of LBL-007 were excluded. The primary endpoints were tolerability and safety. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Any potential efficacy was assessed by objective response rate (ORR) evaluated by CT/MRI per RECIST 1.1. Results: From March 12th, 2020 to Feb 9th, 2021, 17 patients were evaluated in this study. There were no dose limiting toxicities (DLTs) at any dose cohorts, and patients were tolerated very well. Overall, there were 129 adverse events (AEs), and 8 events were serious adverse event (SAE), of which 5 were defined as suspected unexpected serious adverse reaction (SUSAR), but most unlikely treatment related AEs (TRAEs). All AEs regardless of attribution included anemia, hypocalcemia, and flu related respiratory infection, etc. The most common AEs were anemia (14, 10.9%), hypocalcemia (6, 4.7%) and thrombocytopenia (4, 3.1%). Totally, there were 8 patients without disease progression, defined as SD at the first evaluation and sustained for 3.5-9 months. The target lesions in 2 of these 8 patients were reduced by 18.9% and 23.2% (both in esophagus cancer). The progression-free survival of these 2 patients was 4.4 and 9.0 months, respectively. Patients are also being enrolled into the indication exploratory phase (3 and 6 mg/kg), testing the combination therapy with an anti-PD-1 antibody in patients with melanoma and other solid tumors. Conclusions: The dose escalation part of the study revealed tolerability of LBL-007 with an impressive safety profile, and potentially some encouraging signs of anti-tumor activities. Clinical trial: Chinaclinicaltrials.org.cn (1900025904). Clinical trial information: CTR20210196.

e19549 Background: Unlike BCL2 translocation ( BCL2TR), limited data about the prognostic significance of BCL2 mutations ( BCL2MUT) and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) is available, especially in the era of immunochemotherapy. Predicting outcomes at the time of diagnosis is of extreme importance. Methods: In this study, we performed probe capture-based high resolution sequencing on 191 Chinese patients with de novo DLBCL, attempting to comprehensively describe BCL2 genetic alterations and several other genes. We also examined correlation between genetic alterations and outcomes in 164 patients treated with R-CHOP. BCL2, MYC and BCL6 protein was determined by immunochemistry. Results: Of all the 191 patients, BCL2 gain/amplificatio n ( BCL2GA/AMP) and BCL2MUT occurred in 9.4% and 8.9% of patients, respectively, and only 4.2% of cases harbored BCL2TR. As a result, BCL2 alteration, comprised of the above three genetic alterations, was observed in 18.3% of patients. Compared to patients with the absence of BCL2 alteration, the 5-year progression-free survival (PFS) (13.7% vs 40.8%, P= 0.003) and overall survival (OS) (34.0% vs 70.9%, P= 0.036) were significantly inferior in cases that harbored BCL2 alteration. Importantly, patients who harbored BCL2GA/AMP also had remarkably inferior PFS (5-year PFS, 11.1% vs 38.3%, P< 0.001) and OS (5-year OS, 22.1% vs 69.6%, P= 0.009) compared to those without BCL2GA/AMP. By contrast, neither BCL2MUT nor BCL2TR were significantly prognostic for survival. Multivariate analysis showed that the presence of BCL2 alterations, especially BCL2GA/AMP, TP53 mutation and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models were constructed based on 3 risk factors, including BCL2 alteration (Model 1) or BCL2GA/AMP (Model 2), TP53 mutation and IPI, stratifying patients into three risk groups with different outcomes. According to Model 1, the 5-year PFS were 65.9%, 25.9%, and 12.9% ( P< 0.001), and 5-year OS were 89.4%, 65.0% and 16.4% ( P< 0.001), respectively, for the low-risk, intermediate-risk and high-risk groups. In Model 2, the 5-year PFS was 56.9% for the low-risk, 24.1% for the intermediate-risk and 14.3% for the high-risk group ( P< 0.001), and 5-year OS were 86.6%, 60.9% and 16.9% for the three risk groups ( P< 0.001), respectively. Conclusions: This study demonstrated that, in patients treated with R-CHOP, the presence of BCL2 alteration, especially BCL2GA/AMP, and TP53 mutation were significantly associated with inferior outcomes independent of IPI. The novel prognostic models we proposed could aid in individual risk prediction for DLBCL patients treated with R-CHOP. Further validation of this prognostic model is warranted.

The prognostic value of pretreatment serum beta-2 microglobulin (B2MG) level in advanced Hodgkin lymphoma (HL) patients treated in the modern era has not been well established. We conducted a retrospective study involving 202 advanced classical HL (cHL) patients treated from 1998.5 to 2015.7 to evaluate the impact of serum B2MG level on prognosis. Multivariate analysis showed that serum B2MG level ≥ 2.5 mg/L was an independent predictor for freedom from progression (FFP) (P = 0.001), lymphoma-specific survival (P = 0.030) and overall survival (P = 0.034). The 5-year FFP of patients with serum B2MG level ≥ 2.5 mg/L was 66.8%, compared with 89.7% in patients with B2MG level < 2.5 mg/L (P < 0.001). The traditionally used International Prognostic Score (IPS) remained prognostic for FFP (P = 0.013) but the predictive range narrowed, with 5-year FFP ranging from 90.9% to 62.3%. The 5-year FFP of the 44 patients with both IPS ≥ 3 and serum B2MG ≥ 2.5 mg/L was 50.7%, which was significantly worse than that of the 87 patients with only one of the two factors (81.9%, P < 0.001) or the 71 patients with both B2MG < 2.5 mg/L and IPS < 3 (91.1%, P < 0.001). The difference of FFP between the latter two groups was smaller but also significant (P = 0.038). In summary, our data suggest pretreatment serum B2MG level ≥ 2.5 mg/L was an independent unfavorable prognostic factor in advanced cHL patients treated in the modern era. It improves IPS in predicting the outcomes as the combination of IPS and B2MG indentified a wider prognostic range than IPS alone with a sizable number of patients in different risk groups.

Hemolymphangioma of the thorax is a very rare benign tumor. There were only three reports of this disease until 2016. Herein, we report a case of hemolymphangioma of the thorax with pleural effusion. A 57-year-old woman had been admitted to hospital. Computed tomography also demonstrated a heterogenous mass in the posterior mediastinum and suspected invasion to the artery. Surgery was performed. The mediastinal tumor was soft. The pathological diagnosis was a hemolymphangioma of the posterior mediastinum. Her postoperative course was uneventful and she was discharged on the fifth day after surgery. Major symptoms are chest tightness and short of breath due to the tumor and pleural effusion. However, we experienced a case of hemolymphangioma of the thorax with pleural effusion. This disease is a very rare entity, but should be considered when patients have mass and pleural effusion in the thorax.

Background: There was an unmet medical need for treatment in patients with relapsed/refractory (R/R) peripheral T cell lymphoma (PTCL). This multicenter, open-label, single-arm, phase 2 trial aimed to evaluate the efficacy and safety of Geptanolimab (GB226), an anti-programmed cell death 1 (PD-1) antibody, in patients with R/R PTCL(NCT03502629). Methods: The study was initiated in July 2018 and patients with R/R PTCL were recruited from 32 sites in China. Patients were treated with Geptanolimab (intravenous infusion, 3 mg/kg) once every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR). The secondary endpoints included duration of response (DOR), time to response (TTR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and immunogenicity. Treatment response was assessed according to Lugano 2014 criteria by the independent review committee. Patients were followed up every 6 weeks for the first year, and every 12 weeks thereafter. Results: By Aug 15, 2019, a total of 102 patients were recruited and treated with Geptanolimab. As of Nov 1, 2019, the median follow-up was 3.98 months (0.30,15.63). The ORR was 36.3% (37/102; 95%CI: 26.98%-46.39%), including of 11 (10.8%) patients achieved CR and 26 (25.5%) patients achieved PR. DCR was 55.9% (57/102; 95%CI: 45.71%-65.71%). The median DOR, TTR, and PFS were 6.83 months (95%CI: 5.13-not reached [NR]), 4.04 months (95% CI: 1.48-8.52), and 2.69 months (95%CI: 1.74-4.21), respectively. The median OS has not been reached. Subgroup analyses showed that the efficacy was consistent across different age, gender, clinical stage, and previous treatment lines. Patients could benefit from Geptanolimab after failure of Chidamide (an oral histone deacetylase [HDAC] inhibitor) treatment with an ORR of 33.3% (8/24). The ORR of patients with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALCL ALK-), ALCL ALK+, extranodal NK-/T-cell lymphoma, nasal type (ENKTL), PTCL-not otherwise specified (PTCL-NOS), and other types were 58.3% (7/12), 42.9% (3/7), 40.9% (9/22), 28.2% (11/39), and 31.8% (7/22) respectively. Treatment-related AEs (TRAEs) occurred in 80.4% of patients, with common TRAEs (incidence ≥10%) of white blood cell count reduction (18.6%), fever (14.7%) and anemia (13.7%). The incidence of grade ≥3 TRAEs and treatment-related serious AEs was 23.5% and 15.7%, respectively. Immune-related AEs (irAEs) occurred in 36 (35.3%) patients. 11 (10.8%) patients had grade ≥3 irAEs. Conclusions: Geptanolimab (GB226), an anti-PD-1 antibody, can be an effective treatment for R/R PTCL, with an acceptable safety profile. Citation Format: Yuankai Shi, Jianqiu Wu, Zhen Wang, Liling Zhang, Zhao Wang, Mingzhi Zhang, Hong Cen, Zhigang Peng, Yufu Li, Lei Fan, Ye Guo, Liping Ma, Jie Cui, Yuhuan Gao, Haiyan Yang, Hongyu Zhang, Lin Wang, Weihua Zhang, Huilai Zhang, Liping Xie, Ming Jiang, Hui Zhou, Yuerong Shuang, Hang Su, Xiaoyan Ke, Chuan Jin, Xin Du, Xin Du, Li Liu, Yaming Xi, Zheng Ge, Ru Feng, Yang Zhang, Shengyu Zhou, Fan Xie, Chao Gao. The efficacy and safety of Geptanolimab (GB226) in patients with relapsed/refractory peripheral T cell lymphoma (PTCL): A multicenter, open-label, single-arm, phase 2 trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT041.