Lung cancer, with growing morbidity and mortality worldwide, is one of the most malignant tumors, representing a significant threat to human health and life.The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of nonsmall cell lung cancer (NSCLC).A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor (EGFR) have been identified in NSCLC.While targeted therapeutic successes have been demonstrated in the therapeutic targeting of EGFR and ALK, the majority of NSCLC tumors do not harbor these genomic events.This review looks at the current treatment paradigms for lung adenocarcinomas (LAC) and squamous cell carcinomas, examining genomic aberrations that dictate therapy selection, as well as novel therapeutic strategies for tumors harboring mutations in KRAS and TP53 which, to date, have been considered undruggable.A more thorough understanding of the molecular alterations that govern NSCLC tumorigenesis, aided by next-generation sequencing, will lead to targeted therapeutic options expected to dramatically reduce the high mortality observed in lung cancer.

The human immune system has the regulatory functions of eradicating pathogens and limiting excessive inflammation, which protect the surrounding tissue from being damaged. The immune bal-ance of self-limiting is mainly controlled by complex interactions between antigen-presenting cells ( APCs ) and T cells. However, the immune balance is destroyed in cancer, which results in immune evasion and tumor metastasis or promotes the development of drug resistance. Immune checkpoints play critical roles in the immune system. Therefore, blocking tumor immune evasion by targeting the immune checkpoints has be-come a research focus in the treatment of relapsed or refractory malignant tumors. Currently, in the studies of malignant lymphomas, some phaseⅠ/Ⅱclinical studies of immune checkpoint inhibitors have achieved sur-prising results. This review will discuss the regulation and immunotherapy of immune checkpoints in malig-nant lymphomas.

Histone deacetylase inhibitors (HDACI) can improve the acetylation status of histone N-terminal, which will exert the effect on treatment. The N-terminal of histone modifications belongs to the category of epigenetics. Epigenetics mainly refers to the study of the heritable variation without change in DNA sequence. HDACI had been paid much attention as a new non-cytotoxic an-ti-cancer targeted drug. Thus, the application of this drug in clinical research is widespread. After the U.S. Food and Drug Administra-tion approved two HDACIs for the treatment of cutaneous T-cell lymphoma, the clinical applications of HDACI in other subtypes of T-cell lymphoma have obtained increasing attention. Studies on the mechanism of HDACI provide the theoretical basis for the applica-tion of HDACIs in other subtypes of T-cell lymphoma. In this article, we reviewed the mechanism and clinical trials of HDACIs on the treatment of T-cell lymphoma.

Castleman disease (CD) is a rare polyclonal lymphoproliferative disorder characterized by enlarged hyperplastic lymph node(s). Unicentric Castleman disease (UCD) is an indolent condition often treated by local approaches. On the contrary, pa-tients with multicentric Castleman disease (MCD) have less favorable prognoses and require systemic treatments. Cytotoxic chemother-apy has been widely used to treat MCD with varying degrees of response because of the toxicity risk of the treatment. The pathogenesis remains unknown;however, most pieces of evidence to date point toward human herpes virus 8 (HHV-8) and deregulated overproduc-tion of interleukin (IL-6). Discovery of putative etiologic factors and targets in MCD, particularly HHV-8, CD20, and IL-6, has translat-ed to the use of rituximab, anti-IL-6-based, and antiviral therapy. Good results have been realized through targeting HHV-8 replication, CD20, and IL-6 pathways. In this article, we reviewed the classification, pathogenesis, and current treatments of CD and provided in-sights into future treatment strategies based on disease biology.

Objective To compare the efficacy and adverse reaction of teniposide (VM-26) plus carboplatin (TC regimen) and etoposide (VP-16) plus carboplatin (EC regimen) in treatment of newly diagnosed small cell lung cancer (SCLC), and the possible role of VM-26 on prevention of brain metastasis of SCLC. Methods A total of 102 previously untreated SCLC patients without brain metastasis were divided into VP-16 group received EC regimen (n=64) and VM-26 group received TC regimen(n=38). The carboplatin dosages in two groups were calculated by blood concentration-area under the curve(AUC)=5, and intravenous infusion of 1 h for the first day. In VM-26 group, VM-26 70 mg/m2+normal saline 500 mL was intravenously infused of 2 h for 1-3 days. VP-16 100 mg/m2+normal saline 500 mL was given to VP-16 group, 1 h for 1-3 days. Twenty-one day was for 1 treatment cycle. The curative effect, prognosis and adverse reaction were compared between two groups. Results The overall response rates (ORR) and disease control rates (DCR) were 78.9%(30/38) and 97.4%(37/38) in VM-26 group, respectively, and 76.6%(49/64) and 95.3%(61/64) in VP-16 group, respectively, with no significant differences between the two groups (χ2=0.078 and 0.283, P<0.05). The median progression-free survival (PFS) was 10 months (95%CI 7.4-12.6) in VM-26 group and 9 months (95%CI 6.4-11.6) in VP-16 group (χ2=0.029,P=0.866). The median overall survival (OS) was 18 months (95%CI 16.5-19.5) and 16 months (95%CI 9.9-22.1) in VM-26 group and VP-16 group (χ2=0.217,P=0.642), respectively. The survival rates for 1,2 and 3 years were 73.7%, 36.8%and 18.4%in VM-26 group, and 71.9%, 37.5%and 18.8%in VP-16 group, respectively, with no significant differences between the two groups (P>0.05). The brain metastasis rate was significantly higher in VP-16 group [43.8%(28/64)] than that of VP-26 group [21.1%(8/38),χ2=5.379,P=0.02). The adverse reactions were mainly grade 1/2 bone marrow suppression in two groups. Conclusion TC is a highly active regimen for treatment of SCLC. There is no difference in the ef?fectiveness and adverse reactions versus EC. Application of VM-26 can reduce the incidence of brain metastasis in SCLC patients.

The incidence rate is high in Asia country, accounting for 15 %-20 % of Non-Hodgkin lymphoma. Every phynotype has different heterogeneity, therapeutic effect and prognosis are also different. There is no standard rigemen for T cell lymphoma at present. CHOP like regimen is commonly used. But therapeutic effect is not as good as we expected. Clinical research shows that dose and intensity regimen, such as m-BACOD,ProMACE-CytaBOM, MACOP-B, do not exhibit survival advantage compared with CHOP regimen. New treatment includes cytotoxic drug, such as gemcitabine. As first line therapy for T cell lymphoma or as salvage therapy for refractory or relapsed T cell lymphoma, the therapeutic effect is good. Gemcitabine based regimen is new for PTCL. Alemtuzumab is a humanized CD52 mono-clonal antibody and is expected as good effect on PTCL therapy. Zanolimumab is a humanized mono-clonal antibody which targets CD4 antigen on T cell. Phase Ⅱclinical research has also got good effect. Denileukin difiitox and Pralatrexate also have good effect on PTCL therapy in clinical researches. Autologous stem cell transplantation(ASCT) is also used in PTCL therapy.

Clinical data of 13 patients with primary pulmonary lymphoma(PPL),treated in Tianjin Medical University Cancer Hospital from January 1999 to December 2009,were retrospectively reviewed.There were 8 patients with mucosa-associated lymphoid tissue(MALT)marginal zone lymphoma,2 patients with diffuse large B cell lymphoma,1 patient with NK/T cell lymphoma,1 patient with nodular sclerosis Hodgkin's lymphoma,and 1 patients with lymphocytic predominance Hodgkin's lymphoma.The main clinical symptoms were cough,fever,night sweat and weight loss.Two patients did not have any symptoms.Pulmonary consolidation shadows and multiple nodules were the main findings of CT scan.An air bronchogram was often seen in the consolidation imaging.The overall 5-year survival rate was 9/13 for all patients;while that was 7/8 for MALT marginal gone lymphoma.

Double-hit lymphoma (DHL) is a kind of disease with features intermediated between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL),usually accompanied by myc gene breakpoint with other recurrent chromosomal breakpoint and mainly involving myc and bcl-2 translocation.The presentation of this disease is characterized by elevated serum lactate dehydrogenase levels,B symptoms,bone marrow involvement,advanced stage disease,extranodal involvement,and central nervous system involvement.Because its features are similar with DLBCL and BL,it's difficult to distinguish them by pathological diagnosis.At present,the differential diagnosis is mainly by chromosomal analysis (G-banding),FISH and immunohistochemistry.This subtype received a poor response to conventional chemotherapy for DLBCL,and has a poor prognosis.The median survival time is only 0.2-1.5 years.Currently,the main regimens include RCHOP,RICE,RCVD,methotrexate prophylaxis for central nervous system involvement,high-dose chemotherapy and bone marrow transplantation.

Objective To retrospectively analyze the treatment outcomes and prognostic factors for primary bone lymphomas ( PBL) . Methods Forty patients with PBL who were admitted to our center from 1964 to 2014 were enrolled as subjects. In those patients, 10 were treated with chemotherapy alone, 10 with radiochemotherapy, 10 with postoperative chemotherapy, 9 with postoperative radiochemotherapy, and 1 with surgery alone. The median radiation dose was 36 Gy. The Kaplan?Meier method was used to calculate survival rates . The log?rank test was used for survival difference analysis and univariate prognostic analysis . Results The follow?up rate was 100%. The 3?year sample size was 36. In all patients, the 1?and 3?year overall survival rates were 60% and 42%, respectively, while the 1?and 3?year disease?free survival rates were 45%and 34%, respectively. The univariate analysis showed that no pathological fracture at diagnosis, normal lactate dehydrogenase level, an International Prognostic Index score of ≤1, early clinical stage ( stageⅠE ) , complete response after initial treatment, no less than 6 cycles of chemotherapy, a radiation dose of≥40 Gy, no progression outside radiation field after radiotherapy, and grade<3 bone marrow suppression during the treatment were prognostic factors for survival ( P=0. 027, 0. 037, 0. 000, 0. 016, 0. 000, 0. 000, 0. 022, 0. 014, and 0. 030). Conclusions The incidence of PBL is low. Comprehensive treatment can achieve satisfactory outcomes. As a PBL staging system, Ann Arbor has limitations. The staging of PBL should be based on local bone destruction and metastasis.

Objective To study the clinical features, effects of therapeutic regimen and prognosis of patents with mantle cell lymphoma (MCL). Methods Clinical data of 27 MCL patients admitted in Tianjin Medical University Cancer Institute&Hospital from January 2008 to December 2014 were retrospectively analyzed. Cox regression analysis was used to analyze influencing factors of prognosis of MCL. Results The median age was 68 years old for 27 patients, and the male-to-female ratio was 4.4∶1. Ann Arbor staging showed that 25 cases were stageⅢ-Ⅳ(92.6%), 8 cases were heptosplenomegaly (29.6%), 7 cases showed extranodal involvement (25.9%). ECOG scoring showed that 4 cases with scores of 2-4 (14.8%), 8 cases were 0-3 (29.6%), 14 cases were 4-5 (51.9%) and 5 cases were 6-11 (18.5%). The Ki-67 index≤30%was found in 9 cases (33.3%), and>30%was found in 18 cases (67.7%). Patients with B symptom was found in 10 (37.0%). The elevated lactate dehydrogenase (LDH) was found in 17 cases (63.0%). The increased Beta 2- microglobulin was found in 8 cases (29.6%). Seven patients were found with bone marrow involvement. The total effective rate (ORR) was 81.8%in group with R-CHOP method, and the ORR was 68.8%in group with CHOP method. Multivariate analysis showed that age, LDH and Ki-67 were independent factors influencing the prognosis of MCL (P<0.05). Conclusion Most patients with MCL are found in advanced stage. Patients with age>60 years, elevated LDH and Ki-67 index>30%are with poor prognosis.