Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Foods that fight off cancer through anti-inflammation

Background Since the middle of the 19th century,German pathologist Rudolf Virchow proposed that tumors originate from chronic inflammation[1].At present,the medical community has determined that inflammation is closely related to the occurrence,development and efficacy of anti-cancer treatment[2].Recently,an“anti-inflammatory diet”that claims to have functions such as cancer prevention has attracted much attention.To unveil the magic of the“anti-inflammatory diet”,let’s start with the concept of inflammation,which is the core of the“anti-inflammatory diet”.

Chinese clinical practice guidelines for ultrasound-guided irreversible electroporation of liver cancer(version 2022)

Introduction Liver cancer remains a global health challenge,and its incidence is increasing worldwide.It is estimated that by 2025,more than one million individuals will be affected by liver cancer annually[1,2].In recent years,ablation has become a widely accepted treatment option for patients with primary and secondary liver malignancies[3].The commonly used ablation method for liver cancer is thermal ablation,including radiofrequency ablation.

Anti-silencing function 1B knockdown suppresses the malignant phenotype of colorectal cancer by inactivating the phosphatidylinositol 3-kinase/AKT pathway

BACKGROUND Mounting studies have highlighted the pivotal influence of anti-silencing function 1B(ASF1B)on the malignancy of cancers.AIM To explore the influence and mechanism of ASF1B in colorectal cancer(CRC).METHODS Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect mRNA expression of ASF1B.Immunohistochemical staining was performed to detect protein expression of ASF1B and Ki67 in tumor tissues.Western blot analysis was used to determine levels of ASF1B and proliferation/epithelial mesenchymal transition(EMT)/stemness-related proteins.In addition,the proliferation of CRC cells was assessed using Cell Counting Kit-8 and 5-Ethynyl-2’-Deoxyuridine assays.The migration and invasion of CRC cells were evaluated using transwell assays.Stemness of CRC cells was tested using the sphere formation assay.To construct a xenograft tumor model,HCT116 cells were introduced into mouse flanks via subcutaneous injection.RESULTS ASF1B expression was markedly increased in CRC tissues and cells,and it was inversely correlated with overall survival of CRC patients and was positively associated with the tumor node metastasis(TNM)stage of CRC patients.Silencing of ASF1B suppressed proliferation,migration,invasion,stemness and EMT of CRC cells as well as tumorigenesis of xenograft mice.Furthermore,protein levels of Pphosphatidylinositol 3-kinase(p-PI3K)and p-AKT were decreased after silencing of ASF1B in CRC cells.The inhibitory effects of ASF1B knockdown on cell proliferation,stemness and EMT were partly abolished by PI3K activator in CRC cells.CONCLUSION Silencing of ASF1B inactivated the PI3K/AKT pathway to suppress CRC malignancy in vitro.

National guidelines for diagnosis and treatment of gastric cancer 2022 in China(English version)

Contents 1.Overview 2.Diagnosis 2.1 Symptoms 2.2 Signs 2.3 Imaging 2.3.1 X-ray gas-barium double-contrast imaging 2.3.2 Ultrasonography(US)2.3.3 CT 2.3.4 MRI 2.3.5 Positron emission tomography(PET)-CT 2.3.6 Emission computed tomography(ECT)2.3.7 Tumor biomarkers。

Comments on National guidelines for diagnosis and treatment of gastric cancer 2022 in China(English version)

Gastric cancer is one of the most common malignancies in China.According to the latest statistics in 2020,the incidence and mortality of gastric cancer all rank the third among all cancers,which have brought a huge burden to people’s health and social economy.Besides the high morbidity and mortality,the low early diagnosis rate is another dilemma of gastric cancer in China.Early gastric cancer accounts for only 20%of new gastric cancer cases in China.Most cases are already in the advanced stage when discovered,and the overall 5-year survival rate is less than50%(1,2).Over the past decades,China has made great progress in the prevention and treatment of gastric cancer,but it is still a relatively prominent health problem.

Coexistence of tuberculosis and squamous cell carcinoma in the right main bronchus:A case report

BACKGROUND Lung cancer with pulmonary tuberculosis(TB)refers to the occurrence of lesions simultaneously or sequentially in the lung(s)of the same patient,and the pathological examination and sputum TB examination diagnose them as lung cancer and TB,respectively.The occurrence of endobronchial TB(EBTB)with endobronchial tumor sequentially in the same bronchus lesion of the same patient is relatively rare.CASE SUMMARY A 62-year-old female patient was admitted to a local hospital on June 18,2019 after a 3-mo history of dyspnea.She was a farmer and had no history of smoking and alcohol misuse.The patient had neither family nor work contact indicating exposure to TB.Emergency chest computed tomography(CT)examination showed that the right main bronchus was occupied and malignant tumor was possible.Histopathologic examination of a bronchial biopsy showed granulomatous inflammation with caseification and the presence of acid fast bacilli(AFB).However,after 6 mo of antitubercular treatment,repeat bronchoscopy and biopsy histological examination showed squamous cell carcinoma.The patient has started on systemic chemotherapy with carboplatin.After another two cycles of therapy,chest CT showed complete resolution of the lesions.Bronchoalveolar lavage and bronchial aspirate were negative for AFB and cancer cells.CONCLUSION It is not only more likely that a patient presenting with what appears to be TB will concurrently have a pulmonary malignancy than someone who does not have a TB infection,but also that it is of greater urgency to make an expedited diagnosis of the malignancy.

Prediction of syphilis incident rate and number in China based on the GM(1,1)grey model

Objective:To explore the feasibility of using grey model GM(1,1)model to predict syphilis,and to provide a theoretical basis for the health sector to develop corresponding strategies.Methods:GM(1,1)model was used to construct and simulate the incident rate and case number of syphilis in China from 2009 to 2018 to predict the change trend.Results:The GM(1,1)prediction model of syphilis incident rate was x^(1)(k+1)=929.367901 e(0.029413k)-906.297901.The GM(1,1)prediction model for the number of syphilis patients was x^(1)(k+1)=1060.278025 e(0.034280k)-1029.639925.For syphilis incidence model,the posterior difference ratio was 0.19819 and the probability of small error was 1.For the syphilis incident number model,the posterior difference ratio was 0.18450 and the probability of small error was 1.The above models have good fitting accuracy with excellent grade level and can be predicted by extrapolation and predicted that the syphilis incidence in 2019-2021 may be 36.15 per 100,000,37.23 per 100,000 and 38.34 per 100,000,respectively.From 2019 to 2021,the number of incident syphilis cases in China may be 503,406,520,962 and 539,130,respectively.Conclusion:The GM(1,1)model can well fit and predict the change trend of syphilis incidence in time series.The prediction model showed that the incidence of syphilis may continue to increase and the number of syphilis cases per year may continue to increase substantially.More effort is needed to strengthen the prevention and treatment of venereal disease,reduce venereal harm to the population and improve the early detection rate of syphilis.

Gp350-anchored extracellular vesicles: promising vehicles for delivering therapeutic drugs of B cell malignancies

Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is unsatisfactory.Moreover,fatal side effects greatly impede CAR T cell application.Extracellular vesicles(EVs)are excellent carriers of therapeutic agents.Nevertheless,EVs mainly accumulate in the liver when administered without modification.As an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B cells.Here,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage electroporation.The results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to RBC-EVs.After the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,respectively.Moreover,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal Bcells.Therefore,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.

The incidence and prediction of tuberculosis in China

Objective:To explore the incidence trend of tuberculosis in China from 2009 to 2018,and make a short-term prediction,so as to provide reference for scientific formulation of prevention and control measures for tuberculosis and rational allocation of control and prevention resources.Methods:The grey model GM(1,1)model was used to build and predict the incidence of tuberculosis in China by extracting the data from 2009 to 2018 from the Statistical Yearbook of China.Results:The GM(1,1)prediction model was established to predict the incidence of tuberculosis.The GM(1,1)prediction model for tuberculosis incidence was x^(1)(k+1)=-2572.122087 e(-0.029096k)+2653.212087.The grey GM(1,1)prediction model for pulmonary tuberculosis case number was x^(1)(k+1)=-4092.009372 e(-0.024334k)+4199.703172.The above two models with high fitting accuracy were used to predict that the incidence of tuberculosis in 2019-2021 would be 56.77/100,000,55.14/100,000 and 53.56/100,000,respectively.The model predicted that the number of incident tuberculosis cases may be 790,242,771,245 and 752,704 from 2019 to 2021 in China,respectively.Conclusion:The projection shows that the incidence of tuberculosis may decrease,but the annual incident number of tuberculosis is still very high.We should continue to strengthen the prevention and standardized treatment of tuberculosis,and improve the early detection and treatment rates.

Association of a complete breast cancer pathologic response with axillary lymph node metastasis via neoadjuvant chemotherapy:Results from the CSBrS-012 study

To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.

Efficacy analysis of Cheng's GIRAFFE reconstruction after proximal gastrectomy for adenocarcinoma of esophagogastric junction

Objective:Reconstruction of the digestive tract for adenocarcinoma of esophagogastric junction(AEG)is in dispute.This study evaluated Cheng’s gastric tube interposition esophagogastrostomy with reconstruction of His angle and fundus(Cheng’s GIRAFFE anastomosis)in laparoscopic/open proximal gastrectomy for Siewert typeⅡAEG,which was performed at Zhejiang Cancer Hospital and the First Affiliated Hospital of Zhejiang Chinese Medical University.Here,we discuss the preliminary results of gastric emptying and anti-reflux.Methods:From a retrospective database,74 patients with advanced Siewert typeⅡAEG underwent curative proximal gastrectomy with GIRAFFE anastomosis,and their gastric emptying and anti-reflux outcomes were evaluated by the Reflux Disease Questionnaire(RDQ)score,nuclide gastric emptying,24-h impedance-pH monitoring and gastroscopy.Results:Seventy-four patients successfully completed proximal partial gastrectomy with Cheng’s GIRAFFE esophagogastric anastomosis.RDQ score six months after the operation was 2.2±2.5.Results of nuclide gastric emptying examinations showed that the gastric half-emptying time was 67.0±21.5 min,the 1-h residual rate was(52.2±7.7)%,the 2-h residual rate was(36.4±5.1)%,and the 3-h residual rate was(28.8±3.6)%;24-h impedance-p H monitoring revealed that the mean De Meester score was 5.8±2.9.Reflux esophagitis was observed by gastroscopy in 7 patients six months after surgery.Conclusions:Cheng’s GIRAFFE anastomosis is safe and feasible for Siewert typeⅡAEG.

SR-BI expression regulates the gastric cancer tumor immune microenvironment and is associated with poor prognosis

Aim:Scavenger receptor class B,type I(SR-BI)is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies,such as renal cancer,breast cancer,and prostate cancer,and is an independent prognostic factor.However,the clinical value and expression of SR-BI in GC are unknown.Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer(GC).Methods:GC tissues,paracancerous tissues,and clinicopathological data of 149 patients were collected.The expression level of SR-BI,Tumor-infiltrating lymphocytes(TILs),and PD-L1 were evaluated by immunohistochemistry(IHC).The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test.Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors.Kaplan–Meier analyses were performed to plot the survival curve.Results:Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues(p<0.001),and patients with high levels of SR-BI expression had a worse prognosis.Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis.The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+T cells and CD8+T cells(CD4+T cells,p=0.013;CD8+T cells,p=0.021),and positively correlated with PD-L1(p=0.022).Finally,survival analysis revealed that CD4+T cells were associated with the prognosis of GC patients(p=0.019),and the combined survival analysis of SR-BI and CD4+T cells was also statistically significant(p=0.030).Conclusion:SR-BI is highly expressed in GC tissue and associated with poor prognosis.Moreover,SR-BI can also regulate the GC tumor immune microenvironment.

Complete response of a locally advanced pulmonary hepatoid adenocarcinoma patient to perioperative XELOX-containing chemoimmunotherapy

With morphological features resembling hepatocellular carcinoma,hepatoid adenocarcinoma of the lung(HAL)is a rare and aggressive subtype of lung cancer with a 5-year survival of only 8%.1 Most HAL patients present increased serum alpha-fetoprotein(AFP)levels that are commonly related to poor prognosis.Most insights into HAL have come from case series or reports,and TP53 is frequently mutated in HAL.The heterogeneity of HAL complicates the diagnosis.With no established standard,the management of HAL is modeled on that of classical lung adenocarcinoma,although with dismal outcomes.2 Herein,we reported the effective management of a stage IIIb HAL patient with perioperative chemoimmunotherapy and curative-intent surgery.The patient remained disease-free and minimal residual disease(MRD)-negative for more than one year after surgery.

Systemic therapy in gastrointestinal stromal tumors

Gastrointestinal stromal tumors(GISTs)are the most common type of soft tissue sarcoma in the gastrointestinal tract.Most GISTs have been attributed to activated gain-of-function mutations in either KIT or platelet-derived growth factor receptorα,making these molecular features essential targets for therapeutic interventions.Although surgery is the standard treatment for localized GISTs,patients often experience relapse and disease progression even after surgery.In recent years,targeted therapy has significantly improved the prognosis of patients with advanced GISTs.Imatinib mesylate,a KIT inhibitor,is the first-line treatment for advanced GISTs and has revolutionized the treatment of this disease.However,drug resistance remains a major issue with imatinib treatment,as a significant majority of patients become resistant to imatinib either after initiation or after 2–3 years of treatment.Consequently,novel tyrosine kinase inhibitors such as sunitinib,regorafenib,ripretinib,and avapritinib have been introduced to address drug resistance.Immunotherapy has emerged as a potential approach for the treatment of advanced GISTs.This review comprehensively summarizes the pathogenesis of GISTs and the development of targeted therapies and immunotherapies,provides an overview of the emergence of drug resistance in advanced GISTs,and discusses the challenges and prospects associated with the treatment of GISTs.

Recent progress of aptamer-drug conjugates in cancer therapy

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures.Compared to antibody-drug conjugates(ADC),aptamer-drug conjugate(ApDC)is also an efficient,targeted drug for cancer therapy with a smaller size,higher chemical stability,lower immunogenicity,faster tissue penetration,and facile engineering.Despite all these advantages,several key factors have delayed the clinical translation of ApDC,such as in vivo off-target effects and potential safety issues.In this review,we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

Objective:Glioblastomas are highly vascularized malignant tumors.We determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed glioblastoma.Methods:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November 2020.Patients underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/d.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned treatment.The median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant therapy.Five patients discontinued treatment due to AEs.HEG1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter PFS.Conclusions:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable toxicity.HEG1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

Medical expenditures for colorectal cancer diagnosis and treatment: A 10-year high-level-hospital-based multicenter retrospective survey in China, 2002-2011

Objective: Colorectal cancer(CRC) causes a substantial burden of disease in China and the evidence of economic burden triggered is fundamental for priority setting. The aim of this survey was to quantify medical expenditures and the time trends for CRC diagnosis and treatment in China.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 13 provinces across China. For each eligible CRC patient diagnosed from 2002 to 2011, clinical information and expenditure data were extracted using a uniform questionnaire. All expenditure data were reported in Chinese Yuan(CNY)using 2011 values.Results: Of the 14,536 CRC patients included, the average age at diagnosis was 58.2 years and 15.8% were stageI cases. The average medical expenditure per patient was estimated at 37,902 CNY [95 % confidence interval(95%CI): 37,282-38,522], and the annual average increase rate was 9.2% from 2002 to 2011(P for trend <0.001), with a cumulative increase of 2.4 times(from 23,275 CNY to 56,010 CNY). The expenditure per patient in stages Ⅰ, Ⅱ, Ⅲ and Ⅳ were 31,698 CNY, 37,067 CNY, 38,918 CNY and 42,614 CNY, respectively(P<0.001). Expenditure significantly differed within various subgroups. Expenses for drugs contributed the largest proportion(52.6%).Conclusions: These conservative estimates illustrated that medical expenditures for CRC diagnosis and treatment in tertiary hospitals in China were substantial and increased rapidly over the 10 years, with drugs continually being the main expense by 2011. Relatively, medical expenditures are lower for CRC in the earlier stages. These findings will facilitate the economic evaluation of CRC prevention and control in China.

TIGER:A Web Portal of Tumor Immunotherapy Gene Expression Resource

Immunotherapy is a promising cancer treatment method;however,only a few patients benefit from it.The development of new immunotherapy strategies and effective biomarkers of response and resistance is urgently needed.Recently,high-throughput bulk and single-cell gene expression profling technologies have generated valuable resources.However,these resources are not well organized and systematic analysis is difficult.Here,we present TIGER,a tumor immunotherapy gene expression resource,which contains bulk transcriptome data of 1508 tumor samples with clinical immunotherapy outcomes and 11,057 tumor/normal samples without clinical immunotherapy outcomes,as well as single-cell transcriptome data of 2,116,945 immune cells from 655 samples.TIGER provides many useful modules for analyzing collected and user-provided data.Using the resource in TIGER,we identified a tumor-enriched subset of CD4^(+)T cells.Patients with melanoma with a higher signature score of this subset have a significantly better response and survival under immunotherapy.We believe that TIGER will be helpful in understanding anti-tumor immunity mechanisms and discovering effective biomarkers.

New insight into immune checkpoint inhibitors in the treatment of advanced renal cell carcinoma

Kidney cancer,accounting for 4%of all new cancer cases in men and 3%in women,is one of the ten most frequently diagnosed cancer types,of which renal cell carcinoma(RCC)is the most frequent kind of kidney cancer(responsible for70%of adult renal cancer cases).Before the development of immune checkpoint inhibitors(ICIs),RCC was considered an immunoreactive tumor and treated with IL-2 and other immunotherapies.