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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.

The principle of power determined by heat and the anti-peak-regulation characteristics of wind power output cause the difficulty of peak regulation in the power grid along with the production of the abandon wind. By analyzing the topological differences between power system and thermal system, establishing positive and negative spinning reserve constraints of the district heating network, and considering both the hot and the cold start-up cost of the units as well as the thermoelectric coupling of the CHP units, a unit commitment model of wind power accommodation in combined heat and power system— whose objective function is to minimize the total coal consumption and environmental cost of the units—is presented in this paper. In this model, unit commitment and optimized dispatch are combined, the electric load is shared by all the units, and the heat load is balanced by the local CHP plants respectively. Finally, the optimization results show that while meeting power and heat load demand, the model of this paper can timely start up or shut down units according to load change and spinning reserve demand, reduce total minimum technical output of operating units, and further improve wind power accommodation rate.

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.

Additional file 7: Figure S3. Predictors of plasma VAFs during platinum-based chemotherapy. Plasma VAFs of mutant genes (A, B and C) and Gene express of ROBO2(D) between tumor and normal in TCGA cohort, and function domain altered in gene ROBO2. Each dot represented one samples. Two truncating mutations (including nonsense, nonstop, frameshift deletion, frameshift insertion and splice site) were indicated with hotpink2 dot, ***p

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.

AIM Most epidermal growth factor receptor (EGFR) gene mutations affecting exon 19 (inframe deletions; 19 Del) and 21 (L858R), while the rest (referred as uncommon EGFR mutation) have not been fully described due to their rarity. Here we present a retrospective study that investigated clinical characteristics and outcome of patients with different EGFR mutations. METHODS We retrospectively analyzed the EGFR mutation pattern and its association with clinical-pathological characteristics from 100 cases of nonsmall-cell lung cancer (NSCLC) harboring EGFR mutations, and compiled the genotype response data for NSCLC patients with common and uncommon EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs). Patients with advanced EGFR-mutated NSCLC were enrolled and treated with icotinib (oral administration, 125 mg, thrice per day). RESULTS Among 100 patients, 85 and 15 had common and uncommon mutations, respectively. Four patients had a single mutation in 18 or 20 exon, and 11 had a complex mutation with del-19 or L858R. There was no significant association between the presence of different mutation type and the type of any clinical and pathological characteristics. Prolonged but not significant progression-free survival (PFS) was noted in patients with common EGFR mutations (18.07 [14.00-26.23] vs 12.9 [8.43-23.27], P = 0.056). Patients without brain metastases had increased PFS to icotinib than those with brain metastases (18.07 [95% confidence interval, CI 14.77-27.03] vs 13.17 [95% CI 8.63-22.63], P = 0.038). CONCLUSION Uncommon EGFR mutations comprised 15% of all mutated patients, in which most were complex mutations. Compared with common EGFR mutation, uncommon EGFR mutations were associated with a modest sensitivity to EGFR TKIs. Our findings will be helpful to make clinical decision and select the appropriate therapy for EGFR-mutated NSCLC patients.

Objective: To detect the serum epithelial growth factor receptor (EGFR) gene mutation status in patients with lung cancer via second-generation sequencing and to analyze its correlations with the clinical features of patients and its therapeutic effects. Methods: A total of 110 patients with non-small cell lung cancer (NSCLC) treated in our hospital were recruited as subjects of our study. The distribution of the EGFR gene mutation in patients was detected via second-generation sequencing and then patients were divided into mutant-type EGFR group (n=37) and wild-type EGFR group (n=73). The clinical features and therapeutic effects were compared between the two groups of patients. Results: A total of 5 kinds of EGFR gene mutation [19del (45.95%), L858R (43.24%), L861Q (5.41%), S768I (2.70%), and G719X (2.70%)] were detected via second-generation sequencing. In the mutant-type EGFR group, the proportions of female patients, patients with adenocarcinoma, and those with no history of smoking were high, and the differences were statistically significant (P

Purpose To investigate the efficacy and toxicity profile of sequential intensity modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, and cisplatin (GDP) on previously untreated high-risk, early stage upper aerodigestive tract natural killer/T-cell lymphoma (UADT-NKTCL). Methods and Materials A phase 2 study was designed, and 40 high-risk patients with stage I(E)/II(E) UADT-NKTCL were enrolled between June 2010 and June 2014. High-risk patients were defined as those with at least 1 predefined risk factor: age >60 years, elevated serum lactate dehydrogenase, regional lymph node involvement, B symptoms, and primary tumor invasion. Patients received extended involved-site IMRT and GDP chemotherapy. The primary endpoint was the 2-year progression-free survival rate. Secondary endpoints were the 2-year overall survival rate, overall response rate, and toxicity. Results Median follow-up time was 60.1 months. The overall response rate and complete remission rate were 97.5% and 95.0%, respectively. The 2- and 5-year progression-free survival rates were 84.7% and 79.4%, and the corresponding overall survival rates were 89.9% and 82.1%, respectively. The most frequent radiation-induced toxicities were mild mucositis and skin reaction. Grade 3/4 neutropenia (12 of 40 patients), thrombocytopenia (7 of 40), and anemia (2 of 40) were observed during chemotherapy. Conclusions First-line IMRT followed by GDP represents an effective and well-tolerated protocol for high-risk, early stage UADT-NKTCL.

Background: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. Methods: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. Results: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 10 6 CD34 + cells/kg and 68% had at least 5 × 10 6 CD34 + cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. Conclusion: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.

Univariate analysis of prognostic factors for patients with localized SN-DLBCL and SN-ENKTL. (DOCX 19 kb)

Supplemental methods. (DOCX 12 kb)

Treatment outcomes for patients with localized SN-DLBCL. (A) Overall survival and (B) progression-free survival of chemotherapy followed by involved-field radiotherapy (IFRT, n = 37) and chemotherapy alone (n = 10). (DOCX 40 kb)

Treatment outcomes for patients with localized SN-ENKTL. (A) Overall survival and (B) progression-free survival for all SN-ENKTL patients (n = 211) treated with combined modality therapy (CMT) and radiotherapy alone. (C) Overall survival and (D) progression-free survival for extensive stage I and stage II SN-ENKTL patients (n = 141) treated with combined modality therapy (CMT) and radiotherapy alone. (DOCX 83 kb)

In this study, serum free and total light chains (sFLC/sTLC) were measured in 108 serum samples of therapy-naive patients with DLBCL. Clinicopathologic data and survival outcomes were analyzed according to the results of sFLC/sTLC measurements. Moreover, the association of sFLC/sTLC with absolute monocyte count (AMC) and absolute lymphocyte count (ALC) was evaluated. Elevated sFLC and abnormal κ / λ ratio was present in 42.6% (51/108) and 4.6% (5/108) of patients, respectively. sTLC was successfully measured in 107 serum samples, abnormal sTLC and abnormal κ / λ ratio was found in 28.0% (30/107) and 26.2% (28/107) of patients, respectively. Patients with elevated sFLC more frequently displayed adverse clinical characteristics, including age ( P = 0.001), B symptoms ( P = 0.022), low ALC ( P = 0.024) and hyperglobulinemia ( P = 0.012). Patients with elevated sFLC had an inferior overall survival (OS) ( P = 0.012) and tended to have shorter progression-free survival (PFS) ( P = 0.061) compared to patients with normal sFLC. Abnormal sTLC or abnormal sTLC ratio showed no significant association with clinical outcomes, with exception of abnormal concurrent κ and λ . Only association of sFLC and ALC with survival remained significant after adjusting for the International Prognostic Index (IPI). The measurement of sFLC and ALC at diagnosis might be useful for the prognostic stratification of patients and sTLC measurement was of little prognostic utility in DLBCL.

The aim of this study was to investigate the clinical features of ulcerative colitis (UC) combined with acute interstitial lung disease (ILD). One case with acute UC combined with ILD and airway disease was reported, and the pathological diagnosis of previous cases of UC combined with ILD was retrospectively analyzed according to the corresponding literature. The present case concerned a male patient with UC who presented with dry cough and progressive dyspnea. The chest computed tomography (CT) images showed as normal on the seventh day; diffuse ground-glass shadows were observed on the 11th day and diffuse reticular, patchy, nodular shadows and lung cysts were observed on the 21st day. The results of an open lung biopsy on the 23rd day indicated pleural adhesions, and the pathologies were pulmonary fibrosis and airway inflammation. Glucocorticoid therapy was ineffective in the patient, but cyclophosphamide combined with γ globulin rapidly caused the disease to remit. A total of 24 cases with UC combined with ILD and two cases of UC combined with acute ILD were retrieved through PubMed. UC combined with acute ILD was rare in clinical practice. Patients with dry cough, progressive dyspnea and diffuse ground-glass shadows in pulmonary CT images should be closely monitored. Glucocorticoid therapy should be carefully selected and precautions should be taken against opportunistic infections of the lung. Cyclophosphamide combined with γ globulin may be an effective treatment strategy.

After the railway emergency, how to transport emergency rescue resources to the accident site in time and reduce all kinds of unnecessary losses caused by the accident is the primary purpose. Based on the theory of Geographic Information System (GIS), a calculation model of the shortest path was established. By using ArcMap software, the network data set based on railway network was analyzed and calculated, and the shortest path from emergency rescue point to accident point was solved and visualized. And supposed that an emergency happened in the area under the jurisdiction of Nanchang Railway Administration, and made an empirical analysis of it. It provides reference for the selection of emergency rescue path after railway emergencies.

Background Diffuse large B-cell lymphoma (DLBCL) is heterogenous morphologically, clinically and genetically. Although half of patients could be cured by frontline R-CHOP, approximately 10%-15% are refractory or relapse within the 1st year. Here, we investigated the molecular landscapes of patients with diverse responses to R-CHOP. Methods Targeted sequencing was performed on baseline samples of 105 DLBCL patients. After a median follow-up of 67 months, 63 (60.0%) patients had refractory or relapsed disease. All patients received R-CHOP(-like) regimen as the first-line treatment. After excluding double-hit and primary central system lymphoma, 81 patients with measurable disease before initial treatment and followed over 1 year were included for survival analysis. Patients who received less than a partial remission in the first-line setting or those relapsed within the first 12 months since the initiation of the treatment were defined as having primary refractory. Results Collectively, we identified 1162 mutations spanning 103 genes from this cohort. The most commonly seen mutations included 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 (41.7% vs 7.4%, p = 0.002). For those with TP53 disruptive mutations, primary refractory is also more common (22.9% vs. 0%, p = 0.006). Interestingly, BCL-2 somatic hypermutation (SHM) was only seen in patients without primary refractory disease (p = 0.014). The International prognostic index (IPI) score and other clinical characteristics were comparable between the 2 groups. Furthermore, TP53 mutations were correlated with shorter PFS (p = 0.001) and OS (p = 0.049). Next, we investigated mutation landscape in patients with WT TP53 (n = 58) and found that patients harboring MYD88 L265P had significantly inferior PFS than those with WT or non-265P (p = 0.046). Conclusions We revealed that patients with TP53 mutation are more likely to have primary refractory to standard R-CHOP. This study also showed the prognostic potential of MYD88 L265P in those with WT TP53 and indicated that distinct subgroups could be identified by TP53 and MYD88 L265P mutations. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma—not otherwise specified (PTCL—NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL—NOS. We retrospectively reviewed patients with relapsed or refractory PTCL—NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2–8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p

To analyze the clinicopathological characteristics, treatment protocls and prognostic factors in patients with primary intestinal diffuse large B-cell lymphoma (DLBCL).The clinical data of 54 patients with DLBCL who were treated in Cancer Hospital of Chinese Academy of Medical Sciences in the period from August 2003 to November 2012 were retrospectively analyzed, and the relevant prognostic factors of DLBCL were analyzed.Of the 54 patients, there were 43 males and 11 females (male∶female ratio was 3.91∶1), with a median age of onset of 49 (7-76) years. Most patients (64.8%) were in Lugano stage Ⅰ-Ⅱ. Of all the patients, 50 were followed up for a median of 49 (1-118) months. The 1-, 3- and 5-year overall survival (OS) rates were 82.0%, 69.9% and 60.7%, respectively; the 1-, 3- and 5-year progression-free survival (PFS) rates were 68.0%, 58.0% and 53.4%, respectively. Univariate analysis showed that the factors affecting prognosis of DLBCL patients included Lugano stage, B symptom, International Prognostic Index (IPI) score, lactate dehydrogenase level, β2-microglobulin level, tumor size, and treatment protocols (all P0.05). The 5-year OS rate was 67.1% in the patients treated with surgery plus chemoradiotherapy, and 40.0% in those treated with surgery or chemotherapy alone (P0.05). In the patients treated with chemotherapy combined with rituximab, the 5-year OS rate was higher than in those treated with chemotherapy alone (71.2% vs 47.6%, P0.05). Multivariate analysis indicated that tumor size (RR=7.686, P=0.022) and lactate dehydrogenase level (RR=10.131, P=0.017) were independent prognostic risk factors affecting OS.Primary intestinal DLBCL is a highly heterogeneous malignancy. Surgery combined with chemoradiotherapy and rituximab may help improve the overall prognosis of DLBCL patients.

Optimal chemotherapy regimen for peripheral T-cell lymphomas (PTCL) has not been fully defined. This study aimed to evaluate the optimal chemotherapy regimen in the first-line treatment for PTCL patients.Between 2003 and 2014, 93 consecutive patients with PTCL were enrolled in this study. Of 93 patients, 42 patients received CHOPE, 40 patients with CHOP, and 11 patients with GDP regimen.Response could be evaluated in 88 of 93 patients at the end of primary treatment. The CR rate for patients received CHOP (n = 38), CHOPE (n = 39), and GDP (n = 11) were 28.9, 51.3, and 45.5%, respectively, (P = 0.132) with an ORR of 65.8, 76.9, and 90.9%, respectively, (P = 0.210). The median follow-up time was 17.1 (1.4-108.3) months. Median progression-free survival (PFS) in CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) groups were 6.0, 15.3, and 9.7 months (P = 0.094) with 1-year PFS of 35.0, 54.8, and 45.5%, respectively, (P = 0.078). One-year OS for patients received CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) were 65.0, 83.3, and 100%, respectively, (P = 0.013) (CHOP vs CHOPE, P = 0.030; CHOP vs GDP, P = 0.024; CHOPE vs GDP, P = 0.174).CHOPE has a trend to improve CR rate, 1-year PFS and OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies. Clinical experience presented in this study may serve as reference for future large cohort studies.

Aim Limited data are available to guide the choice of conditioning regimen before autologous hematopoietic stem cell transplantation (AHSCT) for patients with lymphoma. Methods We analyzed 129 non-Hodgkin lymphoma patients who underwent AHSCT from 1996 to 2013 using the most common regimens: CBV (cyclophosphamide, carmustine and etoposide; n = 16), BEAM (carmustine, etoposide, cytarabine and melphalan; n = 36) and BEAC (carmustine, etoposide, cytarabine and cyclophosphamide; n = 77). Results At a median follow-up of 42.5 months, the estimated 5-year overall survival for the CBV, BEAM and BEAC groups was 68.8%, 77.8% and 81.8%, respectively (P = 0.584). The estimated 5-year progression-free survival in the CBV group (43.8%) was relatively inferior to the BEAM (66.7%) and BEAC (67.5%) groups, but the differences were not significant (P = 0.403). Grade 2 or higher mucositis, diarrhea and fever were relatively more common in the BEAM group (P < 0.05). No differences were observed in the time to hematopoietic recovery and the duration of hospitalization. The amount of transfused platelet was significantly less in the CBV. Conclusion CBV, BEAM and BEAC regimens are all optional high-dose chemotherapy before AHSCT for NHL patients.

This study was conducted to evaluate the effectiveness and tolerance of GDP (gemcitabine, dexamethasone, and cisplatin) regimen in patients with newly diagnosed stage IV and relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). The study enrolled 41 ENKTL patients who received GDP regimen at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2008 and January 2015. The disease status was newly diagnosed stage IV in 15 patients and relapsed/refractory in 26 patients. The median number of cycles of chemotherapy per patient was 6 (range, 2–8 cycles). The overall response rate and complete-remission rate were 83.0% (34/41) and 41.5% (17/41), respectively. After a median follow-up of 16.2 months, 1-year progression-free survival rate and 1-year overall survival rate for the whole cohort were 54.5% and 72.7%. Grade 3 to 4 adverse events included neutropenia (34.1%), thrombocytopenia (19.5%), and anemia (14.6%). Our study has suggested high efficacy and low toxicity profile of GDP regimen in patients with newly diagnosed stage IV and relapsed/refractory ENKTL.

To analyze the duration of preventive filgrastim administration as support for chemotherapy and its affecting factors.Single institutional data from a phase Ⅱ clinical trial and a phase Ⅲ clinical trial of pegylated filgrastim were combined. In the two randomized cross-over trials, patients with previously untreated cancer received two cycles of chemotherapy of the same regimen. In the study group, the patients received a single subcutaneous injection of 100 μg/kg pegylated filgrastim, and in the control group, they received daily subcutaneous injections of 5 μg/kg filgrastim.In 53 chemotherapy cycles, the median duration of filgrastim administration was (9.57±2.10)d. 83.0% (44/53) of them received filgrastim for 7-11 days. Patients with baseline absolute neutrophil count of4×10(9)/L or body mass index less than 22 received a longer filgrastim prophylaxis(P0.05). RESULTS of multivariate analysis showed that the baseline absolute neutrophil count is associated with the time of filgrastim administration(P=0.019). The most common adverse event of rhG-CSF was skeletal pain, generally mild and no treatment-related death occurred.The median duration of filgrastim support for chemotherapy was 10 days. Patients with lower baseline neutrophil count require a longer filgrastim prophylaxis.: ClinicalTrials.gov identifier, NCT01285219.

To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma (DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen (R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P = 0.001), Bcl-6-negative patients (P = 0.01), and MUM-1-positive patients (P = 0.003). The risk of disease relapse in patients with non-GCB subtype (P = 0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P = 0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P = 0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.

Background: Factors affecting progenitor cell mobilization in patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) are incompletely understood. The aim of this retrospective study was to determine which factors are crucial for effective mobilization and collection of autologous peripheral blood stem cells (PBSC) prior to transplantation in Chinese patients. Patients and methods: A total of 239 patients with lymphoma (198 NHL and 41 HL patients) underwent PBSC collection after mobilization with granulocyte-colony-stimulating factor (G-CSF) or G-CSF plus chemotherapy priming. Results: Patient characteristics at diagnosis and transplant, including low Eastern Cooperative Oncology Group score (P = 0.013), lack of extranodal invasion (P = 0.034), previously administered radiotherapy regimens (P = 0.040), treatment with platinum prior to mobilization (P = 0.042), previous chemotherapy regimens (P = 0.001) and cycles (P < 0.001), and chemotherapy regimens (P < 0.001) were statistically significant for successful mobilization in multivariate analysis. Premobilization factors, including previous radiotherapy (P = 0.009), previous chemotherapy regimens (P = 0.043) and cycles (P = 0.039), low platelet count prior to mobilization (P = 0.042), and lower CD34+ cells in peripheral blood (PB) (P = 0.050) or bone marrow (BM) (P = 0.007) were considered possibly predictive of poor mobilization. We found the patients who had chemosensitive lymphoma had worse progress-free survival (PFS) than the patients with initial treatment and high risks (P = 0.017). Conclusion: Our analysis showed that high amounts of chemotherapy, radiotherapy, low platelet count, chemosensitive recurrent patients, combination chemotherapy plus G-CSF and low CD34+ cells in BM prior to mobilization could emerged as important predictive factors for mobilization failure in Chinese patients with NHL and HL. J. Clin. Apheresis, 2012. © 2012 Wiley Periodicals, Inc.

Background The clinical course of diffuse large B-cell lymphoma (DLBCL) is variable. Although the prognostic markers and models have been developed and adapted in DLBCL, prognostic indices in relapse and refractory (r/r) DLBCL remain unclear. In order to better guide clinical practice, this study aimed to develop a prognostic nomogram in r/r DLBCL. Patients and methods Among 1858 DLBCL patients treated in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital in China, between 2006 and 2016, 682 were r/r DLBCL, of which 573 patients were treated with enough cycles of first-line anthracycline-based chemotherapy. The clinical data were reviewed and evaluated. Progression free survival (PFS) was defined as the time from first treatment administration to disease progression/relapse. Relapse was defined as progression after initial complete or partial remission, and refractory disease was defined as achieving less than a partial response in the first-line setting. Cell of origin (COO) was assessed at diagnosis via Hans algorithm. The concordance index (C-index) and a calibration curve were used to determine and compare their predictive and discriminatory capacity. Results Overall, the median age at diagnosis was 54 (range 10-91) years old. Among all the patients, 325 (56.7%) were male and 248 (43.3%) were female. There were 255 (45.1%) patients categorized as stage I-II and 310 (54.9%) categorized as stage III-IV at diagnosis. Of all the patients, 145 (27.0%) were germinal center B-cell-like (GCB) and 393 (73.0%) were non-GCB. According to the Eastern Cooperative Oncology Group (ECOG) performance status (PS) score, the majority of patients had a good performance, with 457 (79.8%) of cases presenting with an ECOG PS score of 0-1; 89 (15.5%) presenting with ECOG PS of 2; 27(4.7%) scored ≥3. In the entire group, 563 (98.3%) patients received CHOP or CHOP-like regimen and 301 (52.5%) received rituximab treatment in the first-line setting. There were 200 patients (34.9%) had refractory disease; 203 (35.4%) had relapse in the first year from treatment commence; 91 (15.9%) had relapse in the second year; and 79 (13.8%) had relapse after the first 2 years. The median overall survival (OS) from diagnosis were 12, 17, 46 and 66 months, respectively in the above four groups, and OS in the entire group was shown in Figure 1. A total of 437 patients with complete clinical information were further divided into the primary (n=300) and validation (n=137) cohorts. Based on a multivariate analysis of the primary cohort, four independent prognostic factors including lactate dehydrogenase (LDH) level at diagnosis; response to the first-line treatment (CR with not CR); progression free survival and recurrence location (original with new with both) were identified and entered the nomogram (Figure 2). The calibration curve showed the optimal agreement between nomogram prediction and actual observation. In addition, the C-index of the nomogram for OS prediction was 0.743. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.75 in the internal validation and 0.84 in the external validation. Four risk groups depending the nomogram were further developed and OS were presented in Figure 3. Conclusions Independent predictors of survival in r/r DLBCL have been identified and 4 indicators were used to create a nomogram. This proposed nomogram help with assess individual risks and decide on second-line treatment in clinical practice. Disclosures No relevant conflicts of interest to declare.

e18802Background: Patient characteristics, perceptions and experience concerning cancer clinical trials (CCT) may affect study accrual and quality. Our study aimed to evaluate 1) subjects’ percepti...

e21198Background: Recombinant human endostatin (rh-endostatin) is an inhibitor of tumor angiogenesis that acts on neovascular endothelial cells. Previous studies showed improved clinical outcome fo...

To investigate the clinicopathological characteristics and optimal treatment modalities of primary non-Hodgkin lymphoma (NHL) in the small and large intestine. Forty patients with primary NHL in the small and large intestine were studied retrospectively. All cases were reclassified according to the World Health Organization (WHO) classification of lymphoma in 2001. Fourteen patients had primary disease in the small intestine, which were all of B-cell origin with diffuse large B-cell lymphoma (DLBCL) diagnosed in 5 of 14 (35.7%) patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 8 of 14 (57.1%) patients. Ileum was the most commonly involved site (8 of 14 patients, 57.1%), followed by jejunum (2 of 14 patients, 14.3%) and duodenum (1 of 14 patients, 7.1%). Twenty-five patients had primary colorectal lymphoma, with B-cell origin accounting for 92.0% and T-cell origin for 8.0% of these patients. The ileocaecal region has the highest involved rate (13 of 25 patients, 52.0%), followed by colon (7 of 25 patients, 28.0%) and rectum (3 of 25 patients, 12.0%). Compared with surgery alone, post-operation chemotherapy or chemoradiotherapy can significantly improve DLBCL patients' event-free survival (EFS). However, no post-operation treatment modality can improve OS or EFS for patients with MALT lymphoma. B-cell lymphoma is the most common pathological type of intestinal lymphomas. Chemotherapy-containing treatment modality is an effective way to improve intestinal lymphoma patients' EFS, especially for those with DLBCL subtype.

The beneficial effects of unfractionated heparin and low molecular weight heparin on cancer progression have been reported. In the study, the effect of dalteparin on pulmonary adenocarcinoma A549 cell line was observed in vitro. Our experiments revealed that: (1) dalteparin can inhibit the cell viability dose-dependently and time-dependently; (2) dalteparin can arrest the A549 cells in G(1) phase and induce them to early apoptosis; (3) dalteparin exerts its effects through p21(WAF1) and p27(KIP1) proteins; and (4) the changes of p21(WAF1) and p27(KIP1) proteins caused by dalteparin occurred at posttranscriptional levels.

Background: This study observed and compared the preventive effects of ramosetron and ondansetron on gastrointestinal side effects caused by cisplatin-containing chemotherapy. Methods: Fifty patients with malignant tumors undergoing their first chemotherapy were randomly divided into two groups, and each group received 0.3 mg of ramosetron and 16 mg of ondansetron in a prospective crossover comparison study. Results: Data were collected for analysis of the therapeutic effect in 47 cases and for adverse events in 50 cases. Both drugs showed similar results in regard to chemotherapy-induced gastrointestinal side effects, emesis and appetite loss on day 1, but by day 5, ramosetron was significantly better than ondansetron in terms of controlling appetite loss. From days 3–5, ramosetron tended to be more effective than ondansetron in its antiemetic action. The incidence of headache, fatigue and constipation was the same for both drugs. Conclusions: Ramosetron is a long-lasting and safe antiemetic agent.

To evaluate the efficacy and safety of gemcitabine combined with ifosfamide (GI regimen)in patients with recurrent or metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy.The clinical data of 27 nasopharyngeal carcinoma patients, who received GI regimen between April 2005 and March 2014 after failure of prior platinum-based chemotherapy, were retrospectively reviewed,and relevant prognostic factors were explored.All patients were evaluable for efficacy and toxicity. No patient achieved complete response (CR). Partial response (PR) was achieved in ten patients, stable disease (SD) in thirteen patients, progressive disease (PD) in four patients, with a response rate of 37.0% and an overall disease control rate (PR+SD) of 85.2%. For ten PR patients, the median duration of response was 5.5 months. The median progression-free survival of the whole group was 6.7 months, and the Kaplan-Meier estimate of median overall survival was 17.4 months. The 1-year survival rate was 72.6%. Toxicity was mainly hematological: Grade III or IV anemia, neutropenia and thrombocytopenia were found in 3.7%, 37.0% and 18.5% of all patients, respectively. Univariate and multivariate analyses indicated that dose intensity of gemcitabine was a significant prognostic factor for PFS, whereas salvage treatment after failure of GI regimen was a significant prognostic factor for OS.Gemcitabine and ifosfamide combination is effective and well tolerated by patients with advanced nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Further clinical study is warranted.

To evaluate the Epstein Barr virus (EBV) positive rate in untreated Hodgkin's lymphoma (HL) and investigate the prognostic significance of EBV status.A total of 207 previously untreated patients with histologically confirmed Hodgkin's lymphoma were enrolled in the study. The EBV infection status was confirmed through examining EBV-RNA (EBER) or EBV latent membrane protein-1. The correlation of clinical features and EBV infection status was analyzed, also the prognostic significance of EBV infection.A total of 66 cases were confirmed to be EBV positive Hodgkin's lymphoma (EBV⁺ HL) in all 207 cases, accounting for 31.9%. EBV⁺ HL group had more male patients (46/66, 69.7%) and mixed cellularity subtype (34/66, 51.5%) than EBV negative Hodgkin's lymphoma (EBV⁻ HL) group. The EBV positive rate had two peaks in age, respectively, in the age of 0-15 yeaR-old and60 yeaR-old. During a median follow-up period of 35 months, EBV⁻ HL was significant better than EBV⁺ HL in overall survival (P=0.001), but no significant difference was found in progression-free survival (P=0.763).EBV positive is a poor prognostic factor for overall survival time in HL.

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.

The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma (DLBCL) remains to be defined. We aimed to compare CHOP plus rituximab (R-CHOP) with CHOP alone and determine the value of radiotherapy in these patients.Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study.Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response (CR) rate was 77% both in R-CHOP and CHOP groups (P=0.945). After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival (PFS) (76% vs. 85%; log-rank P=0.215) and 5-year overall survival (OS) (90% vs. 96%; log-rank P=0.175) compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone (86% vs. 71%; log-rank P=0.005). At multivariate analysis, patients who had CR (P=0.008) and received radiotherapy (P=0.003) were significantly associated with superior PFS.CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.