MUC16: The Novel Target for Tumor Therapy / 中国肺癌杂志

Mucin16 (MUC16), also known as carbohydrate antigen 125 (CA125), is a glycoprotein antigen that can be recognized by the monoclonal antibody OC125 detected from epithelial ovarian carcinoma antigen by Bast et al in 1981. CA125 is not present in normal ovarian tissue but is usually elevated in the serum of epithelial ovarian carcinoma patients. CA125 is the most commonly used serologic biomarker for the diagnosis and recurrence monitoring of epithelial ovarian carcinoma. MUC16 is highly expressed in varieties of tumors. MUC16 can interact with galectin-1/3, mesothelin, sialic acid-binding immunoglobulin-type lectins-9 (Siglec-9), and other ligands. MUC16 plays an important role in tumor genesis, proliferation, migration, invasion, and tumor immunity through various signaling pathways. Besides, therapies targeting MUC16 have some significant achievements. Related preclinical studies and clinical trials are in progress. MUC16 may be a potential novel target for tumor therapy. This article will review the mechanism of MUC16 in tumor genesis and progression, and focus on the research actuality of MUC16 in tumor therapy. This article also provides references for subsequent tumor therapy studies targeting MUC16.
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Interpretation for Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China / 中国药房

Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China was published in the British Journal of Clinical Pharmacology in February 2022. The guideline followed the latest definition of clinical practice guideline and the methodology specification for the guideline development of WHO. The Grading of Recommendations Assessment ， Development，and Evaluation （GRADE）approach was applied to rate the quality of evidence and determine the strength of recommendations. Finally ，this guideline presents 28 recommendations covering the whole process of clinical medication of high-dose methotrexate ，involving evaluation prior to administration （liver and renal function ，pleural effusion and ascites ， comedication，genetic testing ），pre-treatment and routine dosing regimen （pretreatment of hydration and alkalization ，urine alkalization，routine dosing regimen ），therapeutic drug monitoring （necessity，method，timing，target concentration ），leucovorin rescue（rescue timing ，rescue regimen ，rescue dose optimization ），and management of toxicities （liver and kidney function monitoring，supportive treatment ，blood purification treatment ）. This article aims to summarize and interpret the recommendations of this guideline ，so as to promote the better promotion and implementation of this guideline and provide comprehensive technical support and suggestions for whole-course individualized administration of high-dose methotrexate in China.

Tumor autoantibodies in the diagnosis and prognosis of prostate cancer / 中华检验医学杂志

Detection of prostate specific antigen (PSA) is the most commonly used screening method for prostate cancer. However, many studies have found that the false positive rate and false negative rate of PSA detection for prostate cancer screening are very high, which easily leads to the overuse of PSA detection. Autoantibodies appear at the early stage of cancer, accompany the occurrence and development of prostate cancer. Autoantibodies have a long half-life and are easy to detect. Existing studies have found that autoantibodies can be used in the diagnosis of prostate cancer, and correlated with some prognostic indicators such as Gleason grade and overall survival (OS) of prostate cancer patients. This paper summarized 8 studies on the role of single autoantibody in the diagnosis and prognosis of prostate cancer. Most of the reported single autoantibodies have better diagnostic performance than PSA, and combined application could improve the diagnostic performance. Some autoantibodies are related to a poor prognosis of prostate cancer.

Response of Lung Adenocarcinoma Harbouring Sensitizing EGFR Mutation to the Fourth-line Combination Treatment of Pembrolizumab and Anlotinib / 中国肺癌杂志

45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy.
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Progress of prognostic factors for Hodgkin lymphoma / 白血病·淋巴瘤

Hodgkin lymphoma (HL) is a type of curable tumor. The treatment strategy of HL is based on staging and risk of recurrence. With the continuous optimization of combined treatment mode, the prognosis of HL has been greatly improved. The predictive value of the prognostic models widely used in HL is lower than before. Therefore, exploring new prognostic factors and enriching existing prognostic models to provide patients with precise and individualized treatment is an important research direction for HL. This article reviews the progress of prognostic factors for HL in recent years.

The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease / 中华肿瘤杂志

Objective@#To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy.@*Methods@#Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI.@*Results@#Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him.@*Conclusions@#The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.

The diagnostic efficacy of FNA-Tg in detecting lymph node metastasis of differentiated thyroid cancer and its influencing factors / 中华检验医学杂志

Differentiated thyroid cancer (DTC) patients are prone to cervical lymph node metastasis, which affects patients′ quality of life. Accurate diagnosis of lymph node metastasis can guide surgical resection and dissection, and improve patient′s prognosis. Since the first use of fine-needle aspiration washout thyroglobulin (FNA-Tg) to diagnose lymph node metastasis in DTC patients, a large number of studies have shown that FNA-Tg has a good diagnostic performance. However, due to the various influencing factors of detection and the lack of uniform detection standards, the results of studies very largely. How to screen suitable patients and establish uniform standards to maximize the efficiency of FNA-Tg detection is an urgent problem to be solved. This article will systematically review and analyze the diagnostic efficacy of FNA-Tg and its influencing factors,and explore the subsequent clinical application and research direction of FNA-Tg.

Advances in Drug Resistance Mechanisms and Prognostic Markers of Targeted Therapy in ALK-positive Non-small Cell Lung Cancer / 中国肺癌杂志

Echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion accounts for 3%-5% of non-small cell lung cancer (NSCLC) patients. With the in-depth study of the EML4-ALK driver gene, ALK inhibitors represented by crizotinib have been gradually developed and applied in the clinic. However, the response to ALK-targeted therapy is heterogeneous among different patients. Most patients with ALK-targeted therapy will inevitably develop drug resistance, leading to tumor progression. Monitoring the efficacy of patients with prognostic markers to change the treatment in time, and selecting individualized follow-up treatment according to the mechanism of drug resistance, can effectively improve the prognosis of patients. This article will review the mechanism of ALK tyrosine kinase inhibitor (ALK-TKI) resistance and related prognostic markers to discuss the prediction for ALK-targeted therapy and the choice of subsequent treatment for drug-resistant patients.
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Clinical research and drug review of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer / 中华肿瘤杂志

Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. The mutation rate of epidermal growth factor receptor (EGFR) gene is relatively high, accounts for 32%~38% of all NSCLC. During the last decade, the application of EGFR specific tyrosine kinase inhibitors (TKI) significantly improved prognosis of NSCLC patients with sensitive EGFR mutations. Thus, the research and development of third generation EGFR-TKI have entered the period of rapid development. The fourth generation EGFR-TKI which targeting EGFR C797S has even begun clinical development in China. This review will discuss the clinical research and drug review of EGFR-TKI from the perspective of drug review.

Immunocheckpoint inhibition in head and neck squamous cell carcinoma: the current status and progress / 中华肿瘤杂志

Over the past decades, although the clinical efficacy of advanced head and neck squamous cell carcinoma (HNSCC) has been moderately improved by the combination of cetuximab and chemotherapy, no remarkable treatment has emerged. The prognosis of HNSCC is still unsatisfied. With the deeper exploration of tumor immunological therapy, immunocheckpoint inhibitors such as monoclonal antibodies targeting on programmed cell death protein 1 (PD-1)/ cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have shown appreciable anti-tumor effect on cancers such as melanoma and non-small cell lung cancer. Some successful clinical studies on HNSCC have also been reported, which provide a new opportunity for the improvement of HNSCC prognosis.Here we systemically review the progress of checkpoint inhibitors and its combination therapy in HNSCC, some immunotherapy efficacy-related biomarkers are also discussed.

The clinical trials of China innovative new anti-cancer drugs / 中华肿瘤杂志

With the support of the national policies, the improvement of research ability and the development of economy and society, China clinical trials have developed rapidly. Many achievements are made in the clinical trials of new anti-cancer drugs during last several decades. Many innovative new drugs have come into the market and gained influence at home and abroad. Those drugs provide more treatment options for Chinese patients. This article reviews the results of new anti-tumor drug clinical trials, with special focus on the challenge and chance for the new anti-cancer drug clinical trials in China.

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.

Progress of inflammatory cytokines as lymphoma biomarkers and molecular targets / 白血病·淋巴瘤

The inflammatory response is involved in the development of most diseases. In recent years, tumor associated inflammatory response in tumor microenvironment has been paid more attention. Inflammation promotes the progress of lymphoma, and the growth and proliferation of lymphoma cells also depend on the inflammatory tumor microenvironment. Inflammatory response plays an important role in the development and treatment of lymphoma. Inflammatory cytokines are main types of inflammatory mediators, their expression levels reflect the inflammatory response state of the body, and have potential to be biomarkers and molecular targets of lymphoma.

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.

Prospect for chimeric antigen receptor-engineered T cell immunotherapy for solid tumors / 中华肿瘤杂志

Chimeric antigen receptor modified T cell (CAR T) cytotherapy is a modified technology of T cell immunotherapy. It has achieved encouraging breakthroughs in the treatment of hematological malignancies. Recent studies had shown that CAR T cells can also be used in the treatment of solid tumors. However, it′s indispensable to understand its bottlenecks, including regulating CAR T cell expansion, survival time, metastasis, and prognosis in vivo, to establish a feasible and effective CART-based solid tumor therapy model. Therefore, we summarized the advances, challenges and possible solutions for CAR T therapy to treat solid tumors, and then prospected in the future clinical treatment.

Considerations for anti-cancer drug application by single arm trials / 中华肿瘤杂志

Single arm trial (SAT) was widely used for new drug application (NDA) of novel anti-cancer drugs in recent years. The listing time was greatly shortened by SAT while comparing with randomized controlled trials (RCT). Thus, the companies intended to get NDA through SAT. To encourage innovation and accelerate the developments of anti-cancer agents, we summarize the background and key issues of SAT, discuss the conditions of accepting SAT for NDA, and systematically elaborate the design and principles of SAT in this review.

China National Lung Cancer Screening Guideline with Low-dose Computed Tomography (2018 version) / 中国肺癌杂志

BACKGROUND@#Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice.@*METHODS@#The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China.@*RESULTS@#Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation.@*CONCLUSIONS@#A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.

Multicenter postmarketing clinical study on using pegylated recombinant human gran-ulocyte-colony stimulating factor to prevent chemotherapy-induced neutropenia / 中国肿瘤临床

Objective: To investigate the efficacy and safety of using pegylated recombinant human granulocyte-colonystimulating factor (PEG-rhG-CSF) in preventing neutropenia in multiple chemotherapy cycles. Methods: A multicenter, prospective, open-label, singlearmstudy was designed. Patients with malignant tumors, such as lung, ovarian, and colorectal cancers, who received multiple cycles of chemotherapy with the prophylactic use of PEG-rhG-CSF for 2-4 consecutive cycles participated in the study. Results: After the prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 4.76% (13/273) in the first cycle to 1.83% (5/273), 1.15% (2/174), and 2.08% (2/96) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 11.36% (31/ 273) in the first cycle to 6.23% (17/273), 2.87% (5/174), and 3.13% (3/96) in subsequent cycles. The incidence of febrile neutropenia (FN) during the first cycle was 0.73% (2/273). The duration of FN was 2 days in one case and 5 days in another case. FN was not observed during the second, third, or fourth cycle. After the secondary prophylactic use of PEG-rhG-CSF, the incidence of grade IV neutropenia decreased from 25% (7/28) to 3.57% (1/28), 0% (0/28), and 6.67% (1/15) in subsequent cycles. Meanwhile, the incidence of grade III neutropenia decreased from 71.43% (20/28) to 10.71% (3/28), 14.29% (4/28), and 0% (0/15) in subsequent cycles. The proportion of patients who received antibiotic therapy during the entire chemotherapy period was 10.48% (44/420). Conclusion: The application of PEG-rhG-CSF once per chemotherapy cycle can effectively reduce the occurrence of neutropenia in patients under multiple cycles of chemotherapy treatment with good safety.

The development of biosimilars in oncology / 中华肿瘤杂志

With the extensive application in clinical practice, biological medicine plays a significant role in both treatment and supportive care in oncology. With the expiration of original drug patents, biosimilars emerge. The biosimilars are defined as biological drugs that are be highly similar but not identical to the biological reference. Their development and evaluation procedure are different from those of small molecular chemical generics. Biosimilars are expected to reduce the health care costs worldwide. The booming developments of biosimilars, such as rituximab, trastuzumab and bevacizumab in medical oncology can optimize the clinical strategies, offer patients more treatment options and reduce the medical expenditure. In this article, we review the advances in the field of biosimilars, especially focus on the challenges and opportunities of biosimilars in clinical oncology.