The clinical and pathological features, biomarker characteristics and prognosis analysis of lung adenosquamous carcinoma / 中华肿瘤杂志

Objective@#Adenosquamous carcinoma of lung is an uncommon subtype with more aggressive behavior and poor prognosis than adenocarcinoma and squamous cell carcinoma. This study was aimed to investigate the clinicopathological characteristics and prognostic factors of lung adenosquamous carcinoma.@*Methods@#The pathological features and follow-up data of 133 patients were collected and the prognostic factors of these patients were retrospectively analyzed.@*Results@#Among the 133 patients, 81 cases (60.9%) smoked. Among the 62 patients whose percentage of histological components were identified, 45 cases had >50% adenocarcinoma components, and 17 cases had >50% squamous cell carcinoma components. 55 patients had lymph node metastasis at the first visit. All patients accepted at least one test of tumor driven gene mutation, and the results showed that the mutation rate of EGFR was 50.8% (67/132), the mutation rate of K-ras was 8.6% (11/128), the ALK-positive rate was 4.2% (2/48). The gender, smoking status, and the proportion of pathological components were the main influence factors of EGFR mutation status. The median overall survival was 28 months, the rates of 1-year, 3-year, and 5-year survival were 72.9%, 23.3%, and 9.0%, respectively. EGFR tyrosine kinase inhibitors (TKIs) treatment was an independent risk factor for prognose of these patients (P=0.024).@*Conclusions@#Lung adenosquamous carcinoma is a rare subtype with high malignancy and poor prognosis. Early diagnosis and driven-mutation-based individualized therapy may improve the survival of patients with lung adenosquamous carcinoma.

The efficacy and influence factors analysis of EGFR TKIs on patients with lung adenosquamous carcinoma / 中华肿瘤杂志

Objective@#To investigate the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) on patients with lung adenosquamous carcinoma, and to analyze relative factors.@*Methods@#From August 2007 to July 2017, 40 patients who were pathologically diagnosed as lung adenosquamous carcinoma in our hospital and received EGFR TKIs treatment were retrospectively analyzed. All patients underwent EGFR mutation detection, resulted in 11 wild type, 13 19Del, 13 21L858R mutations, and 3 uncommon EGFR mutations in 20 exon and 19/21 complex mutation. A higher frequency of EGFR mutation was found in non-smokers and patients with adenocarcinoma components over 50.0%.@*Results@#Twenty-six (65.0%) patients had disease progression after EGFR TKIs treatment, with a median progression-free survival (PFS) of 5.5 months (95% CI 0.52-10.49 months). A total of 20 (50.0%) patients died with an median overall survival (OS) of 15 months (95% CI 11.03-18.97 months). Multivariate analysis showed that gender, age, smoking, histopathological subtypes, EGFR mutations, and brain metastasis had no influence on PFS (all P>0.05). Gender, age, smoking, histopathological subtypes, and the presence of brain metastasis during TKI treatment had no influence on OS (P>0.05), while EGFR mutation is the only influencing factor of OS (P<0.05) in the current study.@*Conclusions@#EGFR TKIs had modest efficacy in lung adenosquamous carcinoma, especially in patients with EGFR mutation. Based on the pathological features, EGFR mutation and EGFR TKIs treatment should be introduced into the routine clinical practice to improve the survival of patients with lung adenosquamous carcinoma.

Retrospective analysis of the clinical features and prognostic factors of 370 patients with advanced-stage diffuse large B-cell lymphoma / 中华肿瘤杂志

Objective@#The clinical features and prognosis of diffuse large B-cell lymphoma (DLBCL) were analyzed to optimize the treatment.@*Methods@#We retrospectively collected the clinical data of patients with advanced-stage DLBCL from January 2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic characteristics, clinical stage, histological diagnosis, treatment and prognostic characteristics of these patients were analyzed.@*Results@#A total of 370 patients with median age of 55 years old were recruited in the study. The male-to-female ratio was 1.3∶1. Among the 361 patients who underwent therapy, 280 cases received chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT). The median follow-up period was 89 months, the 5-year overall survival (OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%, 87.5%, respectively. The 5-year OS rate were significantly different between chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed that the age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki-67 index, lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), international prognostic index (IPI), therapeutic manner and chemotherapy combined with rituximab were significantly associated with the prognosis of advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG PS≥1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and β2-MG, and chemotherapy without rituximab were related with the poor prognosis of patients with advanced-stage DLBCL (all P<0.05).@*Conclusions@#Chemotherapy combined with rituximab can improve the outcome of patients with advanced-stage DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5 expression, LDH, β2-MG and chemotherapy combined with rituximab are associated with the prognosis of these patients.

Duration of filgrastim prophylaxis for chemotherapy-induced neutropenia and its predictors / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the duration of preventive filgrastim administration as support for chemotherapy and its affecting factors.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 of <4×10(9)/L or body mass index less than 22 received a longer filgrastim prophylaxis(P<0.05). 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.</p><p><b>CONCLUSIONS</b>The median duration of filgrastim support for chemotherapy was 10 days. Patients with lower baseline neutrophil count require a longer filgrastim prophylaxis.</p><p><b>TRIAL REGISTRATION</b>: ClinicalTrials.gov identifier, NCT01285219.</p>

Retrospective analysis of the clinical features and prognostic factors of 126 patients with primary gastric diffuse large B-cell lymphoma / 中国肿瘤临床

Objective:Primary gastric diffuse large B-cell lymphoma (PGLBCL) is a highly common subtype of extranodal non-Hodgkin lymphoma. We analyzed the disease's clinical features and prognosis to guide better treatment. Methods:We retrospectively collect-ed data from PGLBCL cases seen from January 1999 to March 2012 in one cancer center. We then analyzed the demographic character-istics, clinical stage, histological diagnosis, complications, treatment, and prognostic characteristics of such patients. Results:A total of 126 patients with median age of 49 years old (range:16-81 years) were included in the study. The male-to-female ratio was 68:58. A to-tal of 96 patients were pathologically diagnosed with pure diffuse large B-cell lymphoma (DLBCL), 27 with mucosa-assouated lymphoid (MALT) component, and 3 with plasmacytoid differentiation. Meanwhile, 90%of the patients were in the early stage of the disease. For the early-stage patients, treatment strategy included surgery+chemotherapy ± radiotherapy for 38 cases, chemoradiotherapy for 39 cases, chemotherapy alone for 37 cases, and surgery alone for 1 case. Under a median follow up of 48 months, the 4-year progres-sion free survival (PFS) and overall ourvival (OS) rate of the whole group were 75.6%and 82.7%, respectively. PFS rates for early and advanced stage patients were 77%and 41.7%(P=0.005), respectively. For the early-stage patients treated with chemotherapy alone, chemoradiotherapy, and surgery with therapy, the PFS rates were 67.3%, 77.8%, and 77.8%(P=0.588), respectively. The patients with international prognostic index (IPI) score of 0, 1, and>1 achieved PFS of 85.4%, 74.4%, and 55.6%(P=0.011), respectively. The PFS rates were 81.2%and 66.1%(P=0.018) for stagesⅠandⅡ, respectively, and 86.6%and 63.3%(P=0.006) for the normal and elevated LDH levels, respectively. The pathological type of pure DLBCL or a MALT component, GCB or non-GCB origin, and age more than 60 years old were not associated with prognosis. Conclusion:The majority of the PGLBCL patients were in the early stage of disease, but the outcome of early-stage disease was favorable. Surgery did not improve outcomes. Univariate analysis demonstrated that IPI score>1, stageⅡdisease, and elevated LDH levels were associated with poor prognosis in the early-stage patient.

Pegylated liposomal doxorubicin in CHOP regimen for untreated elderly patients with advanced diffuse large B-cell lymphoma：re-sults from a prospective phase II study / 中国肿瘤临床

Objective:To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in CHOP regimen for un-treated elderly patients with advanced diffuse large B-cell lymphoma (DLBCL). Methods:In a prospective phase II study, we analyzed the feasibility of PLD-modified CHOP regimen in elderly patients with advanced stages of DLBCL. PLD was administered at 30 mg/m2 in combination with cyclophosphamide, vincristine, and prednisone at standard doses every 21 d for six cycles. CD20 positive patients were given option for rituximab treatment. Results:From November 2011 to March 2014, 30 patients with a median age of 70 years (range:63 to 80) were enrolled in this study. Up to 24 cases (80.0%) obtained an International Prognostic Index of≥3. The overall re-sponse rate was 86.7%, and the complete remission rate was 66.7%. With a median follow-up of 20.1 months, the 18-month overall and progression-free survival rates were 82.4%and 70.1%, respectively. The main toxicity was neutropenia, reaching grades 3 to 4 in the 24 cases (80.0%). No significant changes existed in patients' left ventricular ejection fraction and serum troponin-T during the study. Four patients (13.3%) showed asymptomatic abnormal changes in electrocardiogram after PLD infusion. Conclusion:CHOP regimen with PLD is an effective alternative for the treatment of DLBCL in elderly patients, exhibiting an acceptable toxicity.

Efficacy and safety evaluation of gemcitabine combined with ifosfamide in patients with advanced nasopharyngeal carcinoma after failure of platinum-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Autologous peripheral blood stem cell mobilization following dose-adjusted cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy alone or in combination with rituximab in treating high-risk non-Hodgkin's lymphoma / 癌症

<p><b>BACKGROUND</b>The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is an efficient treatment of non-Hodgkin's lymphoma (NHL). This study aimed to assess the efficacy and toxicity of dose-adjusted CHOP alone or in combination with rituximab (R-CHOP) by examining the stem cell mobilization in NHL patients. Factors affecting the collection of CD34+ cells were also explored.</p><p><b>METHODS</b>Our retrospective study included 39 patients eligible for autologous stem cell transplantation: 14 patients who expressed CD20 and were financially eligible received R-CHOP for autologous peripheral blood stem cell (APBSC) mobilization; the remaining 25 patients received CHOP.</p><p><b>RESULTS</b>The median CD34+ cell yield was 7.01×10(6) cells/kg body weight (range 1.49-28.39×10(6) cells/kg body weight), with only two patients failing to meet the target CD34+ cell harvest of ≥2.0×10(6) cells/kg body weight. The median number of apheresis procedures per patient was 1 (range 1-3). The APBSC mobilization yield of the CHOP group appeared to be higher than that of the R-CHOP group (P=0.005), whereas the success rate was similar between groups. R-CHOP elevated the complete response (CR) rate in B cell lymphoma patients as compared with CHOP (P=0.01). No significant differences in toxicity or engraftment were observed between the two groups.</p><p><b>CONCLUSION</b>The present study demonstrated that dose-adjusted CHOP chemotherapy effectively mobilized APBSCs in NHL patients and that the addition of rituximab to dose-adjusted CHOP chemotherapy elevated the CR rate for patients with B-cell lymphoma.</p>

Efficacy analysis of pegylated filgrastim as prophylaxis for chemo-therapy-induced neutropenia / 中国肿瘤临床

Objective:To compare the efficacy of a single injection of pegylated filgrastim with daily doses of filgrastim as pro-phylaxis for chemotherapy-induced neutropenia in Chinese cancer patients. Methods:Single-institution data from a phase 2 study and a phase 3 trial on pegylated filgrastim were combined to analyze the efficacy and safety parameters. In the two randomized crossover tri-als, patients with previously untreated cancers received two cycles of chemotherapy with identical regimen. In the study cycle, the pa-tients received a single subcutaneous injection of pegylated filgrastim (100 μg/kg), whereas those in the control cycle received daily subcutaneous injections of filgrastim (5μg/kg). Results:Among the 56 patients enrolled, 53 were evaluable for efficacy. These patients received one cycle with pegylated filgrastim prophylaxis and one cycle with filgrastim support each. Results indicated that 94.3%(50/53) of the cycles with pegylated filgrastim or filgrastim support did not develop grade 4 neutropenia. Moreover, febrile neutropenia did not occur in the cycles. The incidence rates of antibiotic administration were 7.5%(4/53) and 3.8%(2/53) in the pegylated filgrastim and filgrastim cycles, respectively (P=0.678). The median duration of filgrastim administration was 10 days (3-14 days). Generally, the safety profile of pegylated filgrastim is similar to that of filgrastim, including skeletal pain, pain at the injection site, palpitation, fever, and fatigue. Conclusion:A single dose of pegylated filgrastim demonstrated comparable efficacy with 10 consecutive doses of filgras-tim as prophylaxis for chemotherapy-induced neutropenia.

Clinical features and prognostic analysis of mantle cell lymphoma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical features, therapeutic outcome and prognostic factors of mantle cell lymphoma (MCL).</p><p><b>METHODS</b>Clinical data of a total of 68 patients with MCL admitted from August 2003 to June 2013 in our department were retrospectively analyzed.</p><p><b>RESULTS</b>Of all the patients, the median age was 58.5 years, with marked male predominance (2.8:1), 59 patients (86.8%) were in Ann Arbor stage III/IV. 56 cases (82.4%) primarily showed lymph node involvement, 49 cased showed extranodal involvement and 19 cases (38.8%) had bone marrow involvement. Patients were followed up for 4 to 122 months with a median follow up time of 35 months. The 3- and 5-year overall survival (OS) rates were 78.5% and 64.1%, respectively. The 2- and 3-year progression-free survival (PFS) rates were 41.3% and 23.7%, respectively, and the median time to progression was 20.0 months. The overall response rate (ORR) of CHOP regimen was superior to that of intense regimens (P = 0.036). Univariate analysis showed that stage III/IV,IPI score of 3-5, expression of Ki-67 higher than 30%, elevated LDH, elevated β2-MG, blastic variant, more than 5 lymph nodes involved, and failure to chemotherapy were the negative factors. Multivariate analysis showed that Ki-67 index, LDH and the response to chemotherapy were independent factors affecting survival.</p><p><b>CONCLUSIONS</b>Most patients with MCL were elderly males with advanced stage and usually had bone marrow involvement. Although ORR of CHOP regimen is superior to intense regimens, the prognosis of MCL remains poor.</p>

Efficacy analysis of different follow-up methods in detecting first recurrence of lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This study aimed to evaluate the value of different follow-up methods for the detection of first recurrence in lymphoma patients in first complete remission (CR), and to find reasonable long-term follow-up strategies.</p><p><b>METHODS</b>We retrospectively analyzed 277 lymphoma patients who achieved CR after first-line therapies and subsequently relapsed. All patients were divided into routine surveillance imaging group (group A) and irregular imaging follow-up visit group (group B). To compare the two groups of patients with tumor burden (tumor diameter and number of tumor invasion areas) at the time of relapse, and the number of imaging scans before the relapse. To analyze the main ways of finding lymphoma relapse in the two groups.</p><p><b>RESULTS</b>Among a total of 277 patients, there were 187 patients in the group A and 90 patients in the group B. The tumor recurrence occurred in 120 cases (43.3%) within the first year, and 76 patients (27.4%) in the second year. At the time of diagnosis of recurrence, the average maximum diameter of tumors in the groups A and B were (3.2 ± 2.2) cm and (3.8 ± 2.9) cm, respectively (P = 0.123). The two groups showed slight difference in number of tumor invasion areas (P = 0.050). At the time of diagnosis of recurrence, there were 3 of 121 patients (2.5%) with maximum diameter of tumors more than 8 cm in the group A and 6 of 49 cases (12.2%) in the group B (P = 0.018). In the group A, the patients had in average 4.9 times of imaging scans before recurrence, significantly more than the 0.22 times in the group B (P < 0.001). Among all patients, the diagnosis of recurrence was based on imaging scans only in 59 patients (21.3%).</p><p><b>CONCLUSIONS</b>Most lymphoma patients do not benefit from routine surveillance imaging to detect the tumor recurrence. It indicates that we should not rely solely on imaging examinations at follow-up visits, and should pay more attention on clinical signs and symptoms.</p>

Efficacy and safety evaluation of gemcitabine combined with oxaliplatin in lymphoma patients after failure of multiple chemotherapy regimens / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of gemcitabine combined with oxaliplatin (GEMOX) in lymphoma patients after failure of multiple chemotherapy regimens.</p><p><b>METHODS</b>The clinical data of 27 lymphoma patients, who received GEMOX regimen after failure of two or more prior chemotherapy regimens, were retrospectively reviewed. The predictive factors related to the clinical efficacy of GEMOX regimen were explored.</p><p><b>RESULTS</b>The efficacy could be evaluated in 24 patients. Complete response was obtained in 4 patients (16.7%), partial response in 7 patients (29.1%), stable disease in 6 patients (25.0%), and progressive disease in 7 patients (29.1%), with an overall response rate of 45.8%. Among the eleven CR and PR patients, four patients were with diffuse large B cell lymphoma, four patients with Hodgkin's lymphoma, one with peripheral T cell lymphoma, one with mantle cell lymphoma and one with gastric mucosa-associated lymphoid tissue lymphoma. The median PFS time of the whole group was 8 months (95%CI, 1.6-14.4 months). For 11 CR and PR patients who had response to the GEMOX regimen, the median PFS time was 19 months (95%CI, 11.1-26.8 months). Major adverse response was hematologic toxicity. Among them, grade III or IV neutropenia appeared in 16 patients (59.3%), and grade III or IV thrombocytopenia appeared in 11 patients (40.7%). The sensitivity to the last chemotherapy was related to the efficacy of GEMOX regimen. The response rate was 83.3% in patients who had response to the last chemotherapy, and only 31.2% in the patients who failed to the last chemotherapy (P = 0.001).</p><p><b>CONCLUSIONS</b>GEMOX regimen can get a better response rate in lymphoma patients after failure of multiple chemotherapy regimens, and with a good tolerance and acceptable safety. Some patients can get long-term survival. Patients sensitive to the last chemotherapy are more likely to benefit from GEMOX regimen.</p>

Pharmacokinetics study of albumin-interferon ?-2b fusion protein (HSA-IFN?-2b) in Rhesus Monkey / 中国药理学通报

Aim To investigate the pharmacokinetics of albumin-interferon ?-2b fusion protein(HSA-IFN?-2b) in Rhesus monkeys.Methods Three groups of monkeys were administrated by single injection of HSA-IFN?-2b at 50 ?g?kg-1 iv,50 ?g?kg-1 sc and 300 ?g?kg-1 sc,respectively.Blood samples were taken at 14 different time points from each animal.ELISA was employed to determine the drug concentrations in plasma for all samples.Results Drug was detectable in all of the treated monkeys up to 336 hours after administration.One-compartment model analysis showed that distribution volume was 71 ml?kg-1 in 50 ?g?kg-1 iv group,67 ml?kg-1 in 50 ?g?kg-1 sc group,and 63 ml?kg-1 in 300 ?g?kg-1sc group,respectively.The absorption of HSA-IFN?-2b was relatively slow when given by subcutaneous injection.After 50 ?g?kg-1 sc,the absorption half-life was 19h and elimination half-life was 53h,the bioavailability(F) was approximately 73%,and the apparent clearance(clearance divided by bioavailability,CL/F) was 0.92 ml?h-1?kg-1.Conclusion The result showed that HSA-IFN?-2b may offer the benefits of less frequent dosing and a potentially improved efficacy profile compared with non-albumin fused IFN-alpha.

Lower Respiratory Tract Klebsiella Pneumoniae Infection:Clinical Manifestations and Susceptibility of 96 Cases / 中国药房

OBJECTIVE: To learn the clinical features of patients infected with Klebsiella pneumoniae in our hospital.METHODS: From 2006 and 2007,a total of 96 inpatients in our hospital that were confirmed to be infected with Klebsiella pneumoniae by sputum culture were collected for a study of their clinical features and drug susceptibility test results.RESULTS: Patients with Klebsiella pneumoniae infection represented 12.7% of the total concurrent pulmonary infection cases,of which,57 Klebsiella pneumoniae infection cases had concurrent pulmonary tuberculosis(TB),and 39 Klebsiella pneumoniae infection cases had no concurrent TB.Drug susceptibility tests showed that the resistance rates of Klebsiella pneumoniae to third generation cephalosporins and quinolones were higher than those reported in the literature,and the resistant rate of Klebsiella pneumoniae to quinolones in Klebsiella pneumoniae infection patients complicated with TB was higher than those without TB.CONCLUSION: Klebsiella pneumoniae infection was more common in patients with low body resistance,which has typical clinical manifestations.Recently,the resistance of Klebsiella pneumoniae to the third generation cephalosporin has been increasing,and its resistance to quinolones in patients with pneumonia Klebsiella infection complicated with TB was significantly higher than in those without TB.