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Small cell lung cancer (SCLC) is a highly malignant tumor with a very poor prognosis; therefore, more effective treatments are urgently needed for patients afflicted with the disease. In recent years, emerging molecular classifications based on key transcription factors of SCLC have provided more information on the tumor pathophysiology, metastasis, immune microenvironment, and acquired therapeutic resistance and reflected the intertumoral heterogeneity of the various SCLC phenotypes. Additionally, advances in genomics and single-cell sequencing analysis have further revealed the high intratumoral heterogeneity and plasticity of the disease. Herein, we review and summarize these recent lines of evidence and discuss the possible pathogenesis of SCLC.
Subject(s)
Humans , Small Cell Lung Carcinoma/genetics , Lung Neoplasms/genetics , Prognosis , Genomics , Phenotype , Tumor MicroenvironmentABSTRACT
In order to give full play to the important role of multi-disciplinary treatment (MDT) in oncology teaching in talent training and discipline development, an oncology teaching and research section has been established, the textbook Clinical Oncology has been compiled, excellent teaching workers in affiliated hospitals have been selected to form an MDT teaching team, and a multi-tutorial system has been established for the discipline related to specific tumor types. The multi-tutorial system of disciplines combines lecture-based learning (LBL) with case-based learning (CBL) and problem-based learning (PBL). Students are arranged to observe and participate in clinical MDT consultation during the inter-class practice, and compared with the traditional assessment form, MDT case discussion questions, review writing, classroom simulation of the MDT process and real participation in clinical MDT discussions are added. The questionnaire for students who participated in MDT teaching showed that more than 93% of the students believed that the MDT teaching model was helpful for systematically mastering the knowledge of the chapters they had learned and understanding the cutting-edge progress, improving learning initiative, thinking and problem-solving ability, clinical comprehensive analysis ability and teamwork spirit. The majority of students' expression skills [89%(169/190)] and literature review skills [79%(150/190)] were improved; 94%(178/190) of students expressed their willingness to accept this teaching method. The teaching practice experience of the Department of Oncology of Jilin University based on the MDT model helps to improve the teaching level of oncology.
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Epidermal growth factor receptor ( EGFR ) mutations are common oncogenic driver mutations in patients with non-small cell lung cancer (NSCLC). The application of EGFR-tyrosine kinase inhibitors (TKIs) is beneficial for patients with advanced and early-stage NSCLC. With the development of next-generation sequencing technology, numerous patients have been found to have more than one genetic mutation in addition to a single EGFR mutation; however, the efficacy of conventional EGFR-TKIs and the optimal treatments for such patients remain largely unknown. Thus, we review the incidence, prognosis, and current treatment regimens of EGFR compound mutations and EGFR concomitant mutations to provide treatment recommendations and guidance for patients with these mutations.
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Protein Kinase Inhibitors/pharmacology , Mutation/genetics , ErbB ReceptorsABSTRACT
Immune checkpoint inhibitor (ICI) has become one of the important therapeutic strategies for the patients with advanced non-small cell lung cancer (NSCLC). The latest clinical studies have shown that immunotherapy can bring more survival benefits to patients with early lung cancer and operable patients with locally advanced lung cancer. However, the strategies of neoadjuvant immunotherapy, the timing of operation, the evaluation system of curative effect, predictive markers and other problems still need to be explored in the clinical practice of large samples. This paper reviews the progress of neoadjuvant immunotherapy in NSCLC.
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Immune checkpoint inhibitors (ICIs) therapy is the most commonly used immunotherapy regimen at present. It has been approved for clinical treatment of melanoma, kidney cancer, head and neck cancer, bladder cancer and other tumors. It has made a breakthrough in the treatment of lung cancer and become a new pillar of comprehensive treatment of lung cancer. However, ICIs alone is less effective in non-selective patients, and combination therapy has become a hot topic of exploration. This article focuses on the development of combined immune checkpoint inhibitors and describes how immunotherapy can be used to treat early stage cancer.
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Brain is the most common site of lung cancer metastasis, and the incidenceis are higher if patients have driver gene mutation. Patients with brain metastasis have a poor prognosis; further, different treatment methods affect the disease status and prognosis. In recent years, with the development of precision medicine, gradual progress has been made in treatments for lung cancer patients with brain metastasis, especially for those with driver gene mutations. This review first highlights the challenges of brain metastasis treatments, and then summarizes the research progress regarding targeted therapies for patients with driver gene mutation-positive lung cancer and brain metastasis. This review could help guide clinical decision making for individualized treatment in daily clinical practice.
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Following the development of antineoplastic modalities and improvement in the prognosis of patients with cancer, the oc-currence of cardiotoxicity induced by chemotherapeutic drugs is increasing. Traditional chemotherapeutic drugs, mainly anthracyclines cause varying degrees of direct or indirect damage to the heart, which may even occur several years after the end of treatment. This is-sue is becoming more complicated with the emergence of some new antineoplastic drugs. Treatment options for patients with cancer are limited, and these also have an important effect on patient survival and prognosis. Cardio-oncology is a emerging discipline that in-volves understanding the pathophysiology of cardiotoxicity induced by chemotherapeutic drugs, evaluation of the risks, early detec-tion and systematic management, and optimal drug therapy to reduce the occurrence of cardiotoxicity and to improve the prognosis of patients.
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In recent years, epidermal growth factor receptor tyrosine kinase inhibitors have been recommended by many guidelines as first-line drugs for advanced non-small cell lung cancer (NSCLC) with EGFR gene mutations and no resistance. However, with the prolongation of medication time, most appear acquired resistance. In recent years, breakthroughs in inhibitors of programmed death-1 (PD-1) and its ligand (PD1 ligand, PD-L1) have rapidly changed the therapeutic model of NSCLC. Recent studies have shown that the efficacy of immune checkpoint inhibitors in EGFR-mutant NSCLC patients is not satisfactory, which might be caused by low PD-L1 expression, inhibitory immune microenvironment and low tumor mutation load. This review will elaborate the immune microenvironment of NSCLC patients with EGFR mutation, the latest study progression of immune checkpoint inhibitors and its combined with TKI, expecting to bring new hopes for the treatment of EGFR-mutant NSCLC patients. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Drug Therapy , Genetics , Allergy and Immunology , ErbB Receptors , Genetics , Immune System , Allergy and Immunology , Lung Neoplasms , Drug Therapy , Genetics , Allergy and Immunology , Molecular Targeted Therapy , Methods , MutationABSTRACT
With the advent of the times of immunotherapy and the emergence of a variety of unconventional response patterns such as delayed response and pseudo-progressive disease,a variety of immune-related efficacy evaluation criteria such as immune-related response criteria,immune-related response evaluation criteria in solid tumor and immune response evaluation criteria in solid tumor have been proposed successively.The evaluation principles and judgment results of these criteria are distinctly different from the traditional response evaluation criteria.In particular,the newly proposed immune response evaluation criteria in solid tumor introduces two new concepts of unconfirmed progressive disease and confirmed progressive disease and provides a new response evaluation model for solid tumors,which is expected to provide solutions to some of the most urgent clinical problems under the times of cancer immunotherapy.
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Immune checkpoint signaling pathway mediates tumor immune escape through various mechanisms. In recent years, studies on immune checkpoint inhibitors have made great breakthroughs in various tumors. However, characteristics of the tumor cells, abnormal presentation of the antigens, functional gene mutations, tumor immune microenvironment, internal environment of patients and metabolic factors can all lead to primary or secondary resistance to immunotherapy. The exploration of the molecular mechanism and response strategy of immunotherapy is the key to further expand the beneficial population treated by immune checkpoint inhibitors and realize the accurate treatment.
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Objective:To determine the derivative chromosome 9 by the method of detecting the ASS gene,and to explore the relationship between the deletion of derivative chromosome 9 and the efficacy and prognosis of the chronic myeloid leukemia (CML)patients. Methods:The materials of 34 CML patients with positive BCR-ABL fusion gene whose ASS genes were detected were retrospectively analyzed. All patients were treated with Extra-signal (ES)probe to detect the derivative chromosome 9.All patients were divided into two groups according to whether they carried the derivative chromosome 9.The blastic phase or the accelerated phase rates in two groups were compared by using Fisher exact probability. Results:All patients were detected by FISH (BCR-ABL ES probe),and all the BCR-ABL fusion signals were positive.6 of 34 patients were found the deletion of ASS gene, among them 1 case blonged to chronic phase,and 5 cases developed into blastic phase or accelerated phase. In the patients without ASS gene deletion,there were 22 cases in chronic phase,and 6 cases in plastic phase or accelerate phase,there was significant difference of blastic phase rate/accelated phase rate between them (P 0.05 ). Conclusion:The CML patients with derivative chromosome 9 (ASS gene deletion)prone to get disease progression, and have a higher proportion in the blastic phase or accelerated phase patients.Derivative chromosome 9 is related to the bad treatment efficacy of TKI and the poor prognosis of CML.
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Objective To explore the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with CCAAT/enhancer binding protein α (CEBPA) mutations.Methods 208 patients with de novo AML were retrospectively analyzed with regard to frequency of CEBPA mutations,clinical characteristics,therapeutic response and long-term outcome.Results CEBPA mutations were detected in 37 patients (17.8 ％),with 29 cases of double mutations and 8 cases of single mutation.In 117 cases of patients with normal karyotype,28 cases (23.9 ％) were detected with CEBPA mutations.As compared with no CEBPA mutation,the following characteristics were observed in patients with CEBPA double mutations.Presented with younger age at diagnosis,82.8 ％ (24/29) of the patients were M1 and M2.Presented with higher peripheral white blood cell count,higher hemoglob in and low platelet count.And increases of CD7,CD34 and HLA-DR expression.Compared with those without mutation,patients with biCEBPA mutations had better overall survival (OS) (2-years OS:100 ％ vs 75.1％,P =0.045).Conclusion BiCEBPA mutation is one of the favorable prognosis indicators.
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<p><b>BACKGROUND</b>Rapid clearance of peripheral blood blasts (PBBs) predicts complete remission (CR) and survival in patients with acute myeloid leukemia (AML). We aimed to explore the correlation between induction therapy response, outcome, and the PBB percentage.</p><p><b>METHODS</b>Forty-six consecutive patients with de novo AML (excluding acute promyelocytic leukemia) were enrolled in this study. Flow cytometry was performed to identify cells with a leukemia-associated aberrant immunophenotype in the initial bone marrow aspirate and in peripheral blood on day 7 of induction therapy.</p><p><b>RESULTS</b>The PBB percentage on day 7 (D7PBBP) was significantly lower in patients who achieved CR (0.03% (0.0%, 0.45%)) than in those who did not (10.85% (1.13%, 19.38%); u = -3.92, P < 0.001). The CR rate was significantly higher among patients with a D7PBBP of <0.945% (84.62%, 22/26) than among those with a D7PBBP of = 0.945% (25.0%, 5/20; χ2 = 16.571, P < 0.001). D7PBBP was significantly correlated with overall survival (OS; r = -0.437, P = 0.003) and relapsefree survival (RFS; r = -0.388, P = 0.007). OS and RFS were significantly higher in patients with a D7PBBP of <0.43% than in those with a D7PBBP of ≥ 0.43% (P < 0.001 and P = 0.039, respectively). D7PBBP was also found to be an independent prognostic indicator in multivariate analysis for both OS (P = 0.036) and RFS (P = 0.035).</p><p><b>CONCLUSION</b>D7PBBP may be an important risk factor for the achievement of complete remission, for overall survival, and for relapse-free survival.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Male , Middle Aged , Young Adult , Antineoplastic Agents , Antineoplastic Combined Chemotherapy Protocols , Blast Crisis , Drug Therapy , Cytarabine , Therapeutic Uses , Flow Cytometry , Idarubicin , Therapeutic Uses , Immunophenotyping , Induction Chemotherapy , Leukemia, Myeloid, Acute , Drug Therapy , Mortality , Neoplasm Recurrence, Local , Drug TherapyABSTRACT
Objective To study the cytogenetic features of acute myeloid leukemia (AML) and analyze the association with cytogenetic features and early responses after induction therapy.Methods The karyotypes of 395 patients who had been newly diagnosed with AML were analyzed.These patients were divided into three groups (low-risk,intermediate-risk and high-risk),according to the AML NCCN guidelines.The incidence of different karyotypes in these three groups and the complete remission (CR) rate after the first cycle of induction therapy were analyzed.Results The incidence rates of karyotypes in high-risk,intermediate-risk and low-risk groups were 50.56 ％ (180/356),39.89 ％ (142/356),9.55 ％ (34/356),respectively.All patients with t(15;17) who completed induction therapy reached CR.There was significant difference in the CR rates of t(8;21) groups with or without additional karyotypes [92.00 ％(23/25) vs 50.00 ％(11/22)] (x2 =10.317,P =0.001).There was no significant difference in the CR rates between normal and-Y karyotype group [61.90 ％ (39/63) vs 58.82 ％ (10/17)] (x2 =0.054,P =0.817).Complex cytogenetics ascribed to the low-risk group,of which monosomal karyotype was common,nine of ten patients with monosomal karyotype were associated with an inferior CR rate.Conclusion The cytogenetic features of AML are different from previous reports by other centers.The cytogenetic features of AML patients not only influence the long-term survival,but also the CR rates of induction therapy.
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Objective To evaluate the efficacy and safety of bortezomib-based chemotherapy and MPT regimen in the MM patients who were newly diagnosed or relapsed/refractory. Methods Twenty-seven MM patients were treated with bortezomib-based chemotherapy, median cycles:3 (range 1-5 cycles). Other 30patients received MPT chemotherapy. EBMT and WHO criteria were used to evaluate the therapeutic effects and the adverse effects, respectively. Results Bortezomib group: 21 patients (77.8 %) showed effects after the first cycle chemotherapy and 24 patients (88.8 %) showed effects after the whole therapy. In wich, 15 patients(94.0 %) and 9 patients (82.0 %) were newly diagnosed and relapsed/refractory, respectively. MPT group: 15patients (50.0 %) showed effects after the whole therapy. In wich, 12 patients (44.0 %) were newly diagnosed.And the other 3 were relapsed/refractory patients. The ORR in Bortezomib group was better than MPT group (P ＜0.05). The incidence of peripheral neuropathy, herpes and Ⅲ - Ⅳ grade thrombocytopenia in the bortezomib group was 10 patients (37.0 %), 7patients (26.0 %), 10 patients (37.0 %) respectively,and they were more common than MPT group, but the incidence of Ⅲ-Ⅳgrade anemia was 21 patients (70.0 %) and more comumom in the MPT group. The theraputic efficacy of bortezomib for renal insufficiency and normal renal function patients was similar, and no significant increase in all kinds of adverse effects. In MPT group,there were 4 patients with renal insufficiency, the serum level of creatinine in the 3 patients returned to normal after 5 cycles therapy. Conclusion Bortezomib-based chemotherapy is more effective than MPT regimen in the treatment of MM. The newly diagnosed, relapsed/ refractory and with renal insufficiency patients all can benefit from it. The adverse effects are mild and with better tolerance.