Pancreatic cancer is a highly malignant digestive tract tumor with hidden symptoms,limited treatment options and rapid progression.With an increasing incidence rate year by year,pancreatic cancer has increasingly become a prominent issue endangering public health,causing a huge social burden.Although there was no significant improvement in survival rates for pancreatic cancer patients in the past two decades,recent progress in epidemiology,basic research and clinical research of pancreatic cancer has accelerated significantly compared to the past.Some findings have already enabled a small proportion of pancreatic cancer patients to achieve better survival.This article provided a review of the significant progress made in research,diagnosis and treatment of pancreatic cancer in 2023.

Background and Purpose:Accurate differentiation of pancreatic ductal adenocarcinoma(PDAC)from mass-forming chronic pancreatitis(MFCP)is clinically significant.The application of dual-layer spectral detector CT(DLCT)in pancreas has been explored.This study aimed to investigate the value of DLCT in distinguishing resectable PDAC from MFCP.Methods:We retrospectively collected data of 33 patients with resectable PDAC and 19 patients with MFCP admitted to Fudan University Shanghai Cancer Center from September 1,2021 to May 31,2023.Prior to surgery,patients underwent enhanced DLCT scans,including arterial phase(AP),parenchymal phase(PP)and venous phase(VP).DLCT quantitative parameters,including attenuation enhancement fraction(AEF),lesion-to-parenchyma ratio(LPR)and iodine enhancement fraction(IEF)were calculated.Difference analysis was conducted using independent sample t-test or chi-square test.Univariate and multivariate analyses were performed using binary logistic regression.Receiver operating characteristic(ROC)curves were used for performance evaluation.P＜0.05 was considered statistically significant.Results:Statistically significant differences were observed between PDAC and MFCP in AEF_AP/PP,LPR40_VP,IEF_PP/VP,carbohydrate antigen 19-9(CA19-9)and double-duct sign(all P＜0.05).The spectral combined model composed of LPR40_VP and IEF_PP/VP exhibited the best discriminatory efficacy,surpassing CA19-9,double-duct sign and AEF_AP/PP(all P＜0.05).The combined model demonstrated an area under curve(AUC)of 0.841,sensitivity of 90%,specificity of 73%,and accuracy of 79%.Conclusion:DLCT has certain potential in differentiating resectable PDAC from MFCP.Spectral quantitative parameters can complement CA19-9 and outcome shortcomings of conventional CT in distinguishing resectable PDAC from MFCP.

Background and Purpose:Primary Ewing sarcoma of the thoracic wall(PEST)is a rare extraosseous Ewing sarcoma that occurs in the chest wall or thoracic cavity with a short survival,poor prognosis and a high rate of recurrence.Early diagnosis and treatment are the best way to prolong survival time since the cause of PEST is not clear.This study aimed to explore the clinicopathologic characteristics,diagnosis and treatment of PEST to improve clinical understanding of this disease.Methods:A total of 21 cases with PEST were treated at The First Affiliated Hospital of Soochow University,and reviews were published from 2018 to 2023.Clinical data,pathological features,treatment and follow-up of the patients were analyzed respectively.The survival was from the start of treatment to the death of the patient or the end of the follow-up.Cumulative survival was estimated by Kaplan-Meier method.Results:A total of 21 cases with PEST(male/female ratio,13∶8;sites of left/right chest ratio,6∶15;median age,20 years;mean age,28 years;median diameter of the tumor,8.0 cm;mean diameter of the tumor,18.1 cm)met the inclusion criteria.65.2%of the patients presented with the pain in the ipsilateral thoracic and abdominal area.In 47.1%of cases,the ipsilateral ribs were invaded with pleural effusion.Pathological morphology microscopy showed most tumor cells were tightly packed or lobular distribution of small blue round cells.In immunohistochemistry,CD99 and vimentin were positive in 100%and 80%cases respectively while neurogenic markers were expressed to varying degrees.EWSR1 separated signal was found by fluorescence in situ hybridization(FISH),and the EWSR1-FLI1 fusion was detected by next-generation sequencing(NGS)in two cases at our hospital.Two cases received neoadjuvant chemotherapy,10 patients received chemotherapy and radiotherapy after operation,5 cases were treated with radiotherapy only,1 case received surgery only,and 3 cases had no surgical data.A total of 14 cases were followed up for 3-38 month while 7 cases were lost to visit.Cumulative survival correlates with age at disease.The mean survival time was 19.98 months,and the median survival time was 13.00 months.Conclusion:Young males,right chest and the mass larger than 8 cm are more often found.Most cases can be initially diagnosed using histopathology and immunohistochemical markers.FISH or NGS of the EWSR1 gene test are a highly accurate method for diagnosis.The prognosis of PEST is extremely poor,and the cumulative survival rate is negatively correlated with the age of onset.Surgery,radiotherapy and chemotherapy are the main treatments for this disease.

Background and purpose:In recent years,domestic radiotherapy equipment and related software have made great progress,and testing the functionality and stability of the equipment and software is an essential step.This paper focused on comparing the differences in intensity-modulated radiation therapy(IMRT)plans dosimetry and organ at risk(OAR)volume calculations for common cancers between uRT-treatment planning system(TPS)and Monaco-TPS,and to evaluate the feasibility of dose calculation for Infinity linac(linear accelerator,Elekta,Sweden)using uRT-TPS.Methods:Twenty cases of rectal cancer,lung cancer,breast cancer and nasopharyngeal carcinoma were selected.The IMRT plans were completed in uRT-TPS and Monaco-TPS.The dose uniformity and conformity,mean dose,maximum dose of planning target volume(PTV)and OAR between two plans under the same prescribed dose of PTV were compared.And the pass rates of two TPS plans validated at the same linear accelerator were compared.Meanwhile,monitor units(MU),source skin distance(SSD)and the volume of OAR in uRT-TPS and Monaco-TPS were compared.Results:Wonderful plans that met the clinical requirements were obtained in uRT-TPS and Monaco-TPS.Comparable uniformity and conformability was received in PTV,and the maximum dose of PTV was reduced by 1.1 Gy for uRT-TPS(P = 0.006).For breast cancer and lung cancer,the dose in lung was lower for Monaco-TPS(P＜0.05).For nasopharyngeal carcinoma,the dose indicators that oral cavity and throat in the uRT-TPS was reduced by 9.2%and 5.1%,respectively.The verification results of absolute point dose(＜3%)and three-dimensional surface dose(＞95%)for both plans met the clinical requirements.The region of interest in uRT-TPS was smaller compared with Monaco-TPS(P＜0.05).Conclusion:A comparable IMRT plan was obtained for common tumors in uRT-TPS and Monaco-TPS.It is feasible to calculate the dose of Infinity linac using uRT-TPS.

Mucinous ovarian cancer(MOC)is a rare pathological type different from epithelial ovarian cancer,and the clinical treatment should refer to serous ovarian cancer(SOC)guidelines.However,since the clinicopathological features of MOC are significantly different from SOC,careful differentiation is needed in diagnosis and treatment.Surgery combined with adjuvant chemotherapy is the standard treatment for MOC.However,due to the low prevalence rate,it is difficult to carry out clinical trials,hence lacking evidence-based medicine and consensus on the indications of intraoperative appendectomy and the choice of postoperative adjuvant chemotherapy.In addition,further translational preclinical studies of targeted therapy and immunotherapy are needed to facilitate the diagnosis and individualized treatment of MOC.

Tumor metastasis is closely related to high mortality rate of cancer.It is well known that glutamine plays an important role in the malignant progression of cancer.Notably,as an important carbon and nitrogen donor,glutamine has been found to be closely related to tumor metastasis in recent years.Glutamine is not only involved in regulating the proliferation of tumor cells,but is also closely related to the migration and invasion of tumor cells.Furthermore,various enzymes along with transporters in the metabolism of glutamine are involved in the process of tumor metastasis through different signaling pathways.This review provided a summary of the role of glutamine in tumor metastasis in recent years and proposed therapeutic targets to provide new strategies for the clinical treatment of tumor metastases.

Breast cancer is the most prevalent malignant tumor among women globally,posing a serious threat to women's health.With the establishment of staging and typing principles for breast cancer diagnosis and treatment,and the development and application of novel antitumor drugs,the survival and quality of life of breast cancer patients have been continuously improving.In China,the large base of breast cancer patients possesses unique incidence characteristics,necessitating ongoing exploration of more appropriate treatment strategies;the volume and level of clinical research are also continuously advancing.In 2023,significant clinical research results were reported for different subtypes of breast cancer.In surgical treatment,clinical trials on targeted axillary lymph node dissection and the establishment of a predictive model BRCA-CRisk for contralateral breast cancer risk provide more evidence for de-escalation in surgical treatment.In the area of human epidermal growth factor receptor 2(HER2)-positive breast cancer,pyrotinib has shown significant efficacy in advanced breast cancer treatment.In triple-negative breast cancer,precision subtype treatment and immunotherapy continue to improve patient survival.For hormone receptor-positive breast cancer,significant research results were obtained in exempting low-risk patients from chemotherapy and exploring alternative options after resistance to endocrine therapy.In the aspect of BRCA mutations,BGB-290-201 further confirmed the therapeutic efficacy and safety of poly(ADP-ribose)polymerase(PARP)inhibitors for the Chinese population.For advanced HER2-negative patients carrying germline BRCA(gBRCA)1/2 mutations,pamiparib will be an ideal treatment choice.This article reviews the important clinical research in the field of breast cancer in China in 2023,summarizes key results,and aims to provide reference ideas for future clinical research.

The comprehensive diagnosis and treatment of advanced breast cancer has entered the era of"accurate classification and precise stratification",and is moving towards the road of personalized precision medicine.In 2023,significant breakthroughs have been achieved in the research on different molecular classifications of advanced breast cancer,influencing clinical guidelines and transforming clinical practice.The primary focus of research for hormone receptor positive advanced breast cancer lies in selecting appropriate treatments for patients who have failed cyclin-dependent kinase 4 and 6(CDK4/6)inhibitors.Advanced breast cancer with low human epidermal growth factor receptor 2(HER2)expression has emerged as a promising treatment direction,with T-DXd being an important therapeutic option.With the release of results from the PHILA study,a new era has begun for first-line treatment of HER2-positive advanced breast cancer.Simultaneously,T-DXd has become the preferred choice in clinical practice following tyrosine kinase inhibitor failure.Research related to immune and targeted therapy for advanced triple-negative breast cancer(TNBC)is also progressing rapidly,yielding positive outcomes in studies such as TORCHILIGHT and BEGONIA.Additionally,ongoing clinical studies on precision treatment based on the"Fudan classification"for TNBC are expected to revolutionize current treatment approaches.This paper summarized major advancements in clinical research on advanced breast cancer in 2023 according to various molecular classifications,aiming to provide improved reference and guidance for clinical management.

The incidence of breast cancer is rising annually.Along with the broader implementation of tumor screening and increased health awareness,there has been a significant uptick in the diagnosis of early-stage breast cancer.Early-stage breast cancer is generalized to breast cancer without distant metastasis,which is compared to the concept of late-stage breast cancer.The aim of treatment for early-stage breast cancer is to achieve a cure.Treatment is guided by evidence-based medicine,following guidelines and consensus to administer personalized and precise therapies to patients.Clinical research,as the foundational evidence for these guidelines and consensus,brings more optimized treatment for breast cancer patients.According to the updates of domestic and international guidelines and consensus between 2022 and 2023,this review summarized and classified the important clinical studies that have changed the clinical practice for early-stage breast cancer.These studies were based on molecular sub-types and categorized into optimization of neoadjuvant and adjuvant treatment of early breast cancer,escalating and de-escalating of adjuvant treatment,and the optimization of local treatment.The studies related to the optimization of neoadjuvant and adjuvant treatment of human epidermal growth factor receptor 2(HER2)-positive breast cancer included the PHEDRA study which aimed at the application of pyrotinib,a small molecule tyrosine kinase inhibitor(TKI),to neoadjuvant treatment,the ExteNET study which investigated adjuvant treatment of neratinib,and FDChina study which confirmed the efficacy and safety of pertuzumab and trastuzumab fixed dose combination subcutaneous injection(PH FDC SC).The primary study addressing the optimization of neoadjuvant and adjuvant therapy in triple-negative breast cancer(TNBC)was the KEYNOTE-522 study.In terms of escalating in adjuvant therapy,the APHINITY study evaluated the efficacy of pertuzumab added to trastuzumab in high-risk HER2-positive breast cancer.MonarchE and NATALEE focused on the efficacy of abemaciclib and ribociclib in patients with hormone receptor-positive breast cancer.The SOFT TEXT study focused on ovarian function suppression(OFS)combining exemestane or tamoxifen in high-risk premenopausal breast cancer.Descending related studies in adjuvant therapy included the PLAN B study confirming 6 cycles of docetaxel in combination with cyclophosphamide in HER2 negative early intermediate to high-risk breast cancer.Among the studies related to the local treatment of breast cancer,the ACOSOG Z11102 study explored the feasibility of breast conservation in multicenter focal breast cancer.The SOUND study explored the exemption from axillary surgery in people with low-risk breast cancer.The PRIMEⅡ study explored the possibility of exemption from radiotherapy after breast conservation in elderly patients with low-risk breast cancer,and the IMPORT HIGH study compared different dose-escalated simultaneous integrated boost radiotherapy regimens after breast conservation surgery.The FAST-Forward study focused on hypofractionated breast radiotherapy.These studies provided robust evidence for the implementation of clinical practice and the formulation of diagnostic and treatment guidelines and consensus.In this review,we focused on the update of domestic and international breast cancer treatment guidelines,and the impact of these studies on the clinical practice for early-stage breast cancer.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.