Effect of Jianpi Bushen formula for colon cancer patients who underwent adjuvant chemotherapy:Statistical analysis plan for a multicenter trial

Background:Patients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions,including nausea,vomiting,and diarrhea,which make it challenging for them to adhere to treatment.As an effective traditional Chinese medicine,the Jianpi Bushen formula has been widely used to alleviate the side effects of chemotherapy.Objective:To evaluate the efficacy and safety of Jianpi Bushen formulae for patients who undergo chemotherapy.This statistical analysis plan(SAP)is intended to enhance the transparency and research quality of our randomized controlled trial.Methods:Our study is a multicenter,double-blind,randomized controlled clinical trial.This trial aimed to compare the completion rate of chemotherapy in colon cancer patients who are using and not using Jianpi Bushen formula.To attenuate possible selection bias in the final report,we declared the overall trial design,outcome measures,subgroup analyses,and safety measures.Also,we described the data management and statistical analysis methods in detail.Conclusion:The SAP provides more detailed information than the trial protocol for data management and statistical analysis methods.Further post-hoc analyses can be performed by referring to the SAP,and possible selection bias can be attenuated.

Liver-directed therapiesfor fibrolamellar carcinoma:Asingle-center experience

Background:This article aims to present the single-institution outcomes of patients with Fibrolamellar Carcinoma(FLC)treated with liver-directed therapies(LDT).Methods:In this single-center retrospective study,all patients diagnosed with FLC who underwent LDT were identified.Between July 2012 and July 2023,six patients were identified.One patient was excluded due to bleeding.Demographic and clinical parameters were recorded.Complications within 30 days of the LDT were evaluated.Radiological treatment responses at 1,6,and 12 months were assessed per mRECIST.Results:A total offive patients,which included three females and two males,were reviewed.Three patients were treated with transarterial hepatic embolization(TAE;n=3),transarterial radioembolization(TARE;n=1),and combined TAE+radiofrequency ablation(n=1).The objective response rate at one month was 80%[CR=2(40%),PR=2(40%),and SD=1(20%)].At 12 months(n=4),two patients demonstrated CR(50%)and two demonstrated PR(50%).Overall survival from LDT atfive years was 50%.There was no 30-day mortality among this group of patients or any adverse event attributable to the LDT.Conclusion:TAE,TARE,and ablation are safe and effective therapeutic options for FLC.Based on this study and previously published case reports,ablation and TARE yielded the most favorable results.

Updates in advanced diffusion-weighted magnetic resonance imaging techniques in the evaluation of prostate cancer

Diffusion-weighted magnetic resonance imaging(DWMRI) is considered part of the standard imaging protocol for the evaluation of patients with prostate cancer.It has been proven valuable as a functional tool for qualitative and quantitative analysis of prostate cancer beyond anatomical MRI sequences such as T2-weighted imaging. This review discusses ongoing controversies in DW-MRI acquisition, including the optimal number of b-values to be used for prostate DWI, and summarizes the current literature on the use of advanced DWMRI techniques. These include intravoxel incoherent motion imaging, which better accounts for the nonmono-exponential behavior of the apparent diffusion coefficient as a function of b-value and the influence of perfusion at low b-values. Another technique is diffusion kurtosis imaging(DKI). Metrics from DKI reflect excess kurtosis of tissues, representing its deviation from Gaussian diffusion behavior. Preliminary results suggest that DKI findings may have more value than findings from conventional DW-MRI for the assessment of prostate cancer.

Dynamic contrast-enhanced magnetic resonance imaging of prostate cancer: A review of current methods and applications

In many areas of oncology, dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) has proven to be a clinically useful, non-invasive functional imaging technique to quantify tumor vasculature and tumor perfusion characteristics. Tumor angiogenesis is an essential process for tumor growth, proliferation, and metastasis. Malignant lesions demonstrate rapid extravasation of contrast from the intravascular space to the capillary bed due to leaky capillaries associated with tumor neovascularity. DCE-MRI has the potential to provide information regarding blood flow, areas of hypoperfusion, and variations in endothelial permeability and microvessel density to aid treatment selection, enable frequent monitoring during treatment and assess response to targeted therapy following treatment. This review will discuss the current status of DCE-MRI in cancer imaging, with a focus on its use in imaging prostate malignancies as well as weaknesses that limit its widespread clinical use. The latest techniques for quantification of DCE-MRI parameters will be reviewed and compared.

Treatment of locally advanced rectal cancer:Controversies and questions

Rectal cancers extending through the rectal wall, or in- volving Iocoregional lymph nodes （T3/4 or N1/2）, have been more difficult to cure. The confines of the bony pelvis and the necessity of preserving the autonomic nerves makes surgical extirpation challenging, which accounts for the high rates of local and distant relapse in this setting. Combined multimodality treatment for rectal cancer stage Ⅱ and Ⅲ was recommended from National Institute of Health consensus. Neoadjuvant chemoradiation using fluoropyrimidine-based regimen prior to surgical resection has emerged as the standard of care in the United States. Optimal time of surgery after neoadjuvant treatment remained unclear and prospective randomized controlled trial is ongoing. Tra- ditionally, 6-8 wk waiting period was commonly used. The accuracy of studies attempting to determine tumor complete response remains problematic. Currently, surgery remains the standard of care for rectal cancer patients following neoadjuvant chemoradiation, where- as observational management is still investigational. In this article, we outline trends and controversies associ- ated with optimal pre-treatment staging, neoadjuvant therapies, surgery, and adjuvant therapy.

Endoscopic advances in the management of gastric cancer and premalignant gastric conditions

Gastric cancer is the fifth most common cancer and in 2018,it was the third most common cause of cancer-related deaths worldwide.Endoscopic advances continue to be made for the diagnosis and management of both early gastric cancer and premalignant gastric conditions.In this review,we discuss the epidemiology and risk factors of gastric cancer and emphasize the differences in early vs latestage gastric cancer outcomes.We then discuss endoscopic advances in the diagnosis of early gastric cancer and premalignant gastric lesions.This includes the implementation of different imaging modalities such as narrow-band imaging,chromoendoscopy,confocal laser endomicroscopy,and other experimental techniques.We also discuss the use of endoscopic ultrasound in the diagnosis and staging of early gastric cancer.We then discuss the endoscopic advances made in the treatment of these conditions,including endoscopic mucosal resection,endoscopic submucosal dissection,and hybrid techniques such as laparoscopic endoscopic cooperative surgery.Finally,we comment on the current suggested recommendations for surveillance of both gastric cancer and its premalignant conditions.

Chemotherapy of ovarian cancer in elderly patients

Epithelial ovarian cancer is primarily a disease of older women. Advanced age is risk factor for decreased survival. Optimal surgery and the safe and effective administration of chemotherapy are essential for prolonged progression-free and overall survival(OS). In this article, the available regimens in both the primary treatment and relapsed setting are reviewed.

A Novel Technique to Validate Dosimetry for Single-Isocenter Multiple-Target VMAT Stereotactic Radiosurgery

Each year, 170,000 cancer patients in the United States develop brain metastases. Many of them present with multiple small lesions. Historically, Linac-based stereotactic radiosurgery (SRS) was used to treat single solitary brain metastasis with a diameter of less than 3.0 cm, while whole brain radiation therapy (WBRT) was used to treat multiple brain metastases mainly as palliative therapy. Evidence-based practices reveal that WBRT results in poor treatment outcomes, with high local recurrence rates, decreased cognitive function, and even the onset of dementia. Recently, volumetric modulated arc therapy (VMAT) SRS has been tested as an alternative treatment to WBRT. Owing to its inherent complexity and high risk, it is imperative to perform rigorous testing prior to its clinical implementation. In this paper, we present a novel technique for dosimetry validation of VMAT SRS.

Considerations and Experience in the Treatment of Lung Cancer with VMAT SBRT + DIBH in Arms-Down Position

The arms-up position is the most common treatment position adopted for lung cancer patients treated with radiation therapy. However, many elderly or frail patients have shoulder problems and cannot tolerate such an overstretched position for an extended period. Therefore, the arms-down position becomes the only alternative for this group of patients during radiation therapy. Even though the arms-down position is not ideal, it does provide a stable and comfortable patient immobilization position for radiation treatments that require a longer delivery time, such as stereotactic body radiation therapy (SBRT). In this study, we designed a protocol to treat lung cancer patients with VMAT stereotactic body radiation therapy (VMAT SBRT) and deep inspiration breath-hold (DIBH) in the arms-down position. Our initial clinical experience with this protocol indicates that it is reliable for patient immobilization and accurate in delivered dosimetry.

Clinical Efficacy and Safety of Oxaliplatin-tegafur,Gimeracil and Oteracil Potassium and Vinorelbine-Pt in the Treatment of Advanced Triple Negative Breast Cancer

The purpose of this study was to investigate the efficacy and safety of oxaliplatin combined with tegafur,gimeracil and oteracil potassium(SOX regimen)and vinorelbine combined with Pt(NP regimen)in the treatment of advanced triple negative breast cancer(TNBC).First of all,88 patients with advanced breast cancer were selected and divided into observation group and control group with 44 cases each by random number method.Both groups received conventional supportive therapy.On this basis,SOX regimen was adopted in the observation group and NP regimen in the control group,and the efficacy,occurrence of toxic and side effects in the two groups were compared.The results showed that the objective effective rates and clinical benefit rates of the two groups were statistically significant(P<0.05).In addition,both groups had hand foot syndrome,diarrhea,liver function damage,decreased platelet(PLT)and other toxic side effects,but the incidence of rash,oral ulcer and pigmentation in the observation group was significantly lower than that in the control group(P<0.05).Therefore,both SOX regimen and NP regimen can effectively treat advanced TNBC adverse reactions,but SOX regimen was more effective.

Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor types.Not all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are limited.AIM To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving chemotherapy.METHODS The National Cancer Database was used to identify patients between 2004-2015.Patients with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were included.Cases with unknown chemotherapy,RT,or nonprimary surgery status were excluded.Kaplan-Meier estimates of OS were calculated.Cox proportional hazards regression models were employed to examine factors influencing survival.RESULTS Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete data.Median age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic center.The majority(72.7%)did not receive other palliative therapies.On both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased mortality.Higher histologic grade and T-stage were also associated with worse OS(P<0.05).CONCLUSION Palliative therapies other than chemotherapy conferred a numerically higher,but not statistically significant difference in OS among patients with metastatic esophageal cancer not receiving chemotherapy.Quality of life metrics,inpatient status,and subgroup analyses are important for examining the role of palliative therapies other than chemotherapy in metastatic esophageal cancer and future studies are warranted.

SREBP2 restricts osteoclast differentiation and activity by regulating IRF7 and limits inflammatory bone erosion

Osteoclasts are multinucleated bone-resorbing cells,and their formation is tightly regulated to prevent excessive bone loss.However,the mechanisms by which osteoclast formation is restricted remain incompletely determined.Here,we found that sterol regulatory element binding protein 2(SREBP2)functions as a negative regulator of osteoclast formation and inflammatory bone loss.Cholesterols and SREBP2,a key transcription factor for cholesterol biosynthesis,increased in the late phase of osteoclastogenesis.

纵隔肿物活检小标本的获取与病理报告指南

目前，胸腺恶性肿瘤治疗方案大多是根据术后病理确定，然而，多数临床治疗决策需要在术前通过活检小标本的病理报告来制定。所以，术前活检小标本的正确获取和病理解读对治疗决策的制定显得非常重要[1]。这些标本包括细针活检标本，带芯穿刺活检标本和手术切取活检标本[2-7]。由于胸腺肿瘤的病理诊断对组织的获取方法和获取量都有较高的要求，加之对病理的描述也没有统一的标准，使得小标本在诊断胸腺瘤方面存在诸多问题。为此，ITMIG在病理科医生和外科医生回顾相关文献和提出初步建议的基础上，经集体讨论制定了活检规范操作流程，提出了对纵隔肿物小活检标本处理和病理报告的建议。旨在为术前患者的治疗提供一个统一和具有循证医学证据的方法；同时，将有利于全球数据之间的比较和开展合作研究，充分利用医疗资源。

Ⅰ期-Ⅲ期非转移性非小细胞肺癌的系统性治疗演变

早期肺癌患者的治疗是以治愈为目标的。针对手术可切除性和可操作性的多学科讨论模式决定了最终的局部治疗方式(手术或放疗)和相关的系统性治疗方案,从而进一步提高患者治愈的可能性。研究证据支持以顺铂为基础的辅助化疗用于切除术后,或与放疗同步使用。共识指南支持以新辅助化疗代替辅助化疗,并支持对不符合顺铂治疗条件的患者采用基于卡铂的治疗方案。由于研究设计效率低下,需要长时间随访来评估生存终点以及对晚期疾病的持续关注,将新药物(现在是IV期肺癌患者的标准药物)纳入以治愈为目标的治疗范式的工作一直滞后。目前正在研究中的替代性终点(例如病理缓解)将可能缩短研究的时间。2018年,抗程序性死亡配体(programmed cell death ligand 1,PD-L1)抗体度伐利尤单抗获批用于治疗同步放、化疗后的Ⅲ期肺癌患者,自那时起,针对早期肺癌患者的靶向治疗和免疫治疗的研究迅速发展。在本篇综述中,我们介绍了对于目前早期肺癌患者治疗方案的考虑因素,探讨并展望非转移性肺癌系统性治疗的临床研究现状和未来。

Visual Analysis of the Daily QA Results of Photon and Electron Beams of a Trilogy Linac over a Five-Year Period

Data visualization technique was applied to analyze the daily QA results of photon and electron beams. Special attention was paid to any trend the beams might display. A Varian Trilogy Linac equipped with dual photon energies and five electron energies was commissioned in early 2010. Daily Linac QA tests including the output constancy, beam flatness and symmetry (radial and transverse directions) were performed with an ionization chamber array device (QA Beam Checker Plus, Standard Imaging). The data of five years were collected and analyzed. For each energy, the measured data were exported and processed for visual trending using an in-house Matlab program. These daily data were cross-correlated with the monthly QA and annual QA results, as well as the preventive maintenance records. Majority of the output were within 1% of variation, with a consistent positive/upward drift for all seven energies (^+0.25% per month). The baseline of daily device is reset annually right after the TG-51 calibration. This results in a sudden drop of the output. On the other hand, the large amount of data using the same baseline exhibits a sinusoidal behavior (period = 12 months;amplitude = 0.8%, 0.5% for photons, electrons, respectively) on symmetry and flatness when normalization of baselines is accounted for. The well known phenomenon of new Linac output drift was clearly displayed. This output drift was a result of the air leakage of the over-pressurized sealed monitor chambers for the specific vendor. Data visualization is a new trend in the era of big data in radiation oncology research. It allows the data to be displayed visually and therefore more intuitive. Based on the visual display from the past, the physicist might predict the trend of the Linac and take actions proactively. It also makes comparisons, alerts failures, and potentially identifies causalities.

Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas

Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.

DNA repair and synthetic lethality

Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination （HR）, are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly （adenosine diphosphate （ADP）-ribose） polymerase （PARP） inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells.

Pre-Metastatic Niche Formation Has Taken Its TOLL

Pre-Metastatic Niches(PMNs)result from communications between primary tumors and the microenvironment of future distant metastasis via tumor-derived factors.In this issue of Cancer Cell,Liu et al.show that TLR3 activation in lung epithelial cells by tumor exosomal RNAs triggers neutrophil recruitment,which contributes to PMN formation and metastasis.

Potential mechanism of Huatan Qushi decoction on improving phlegm-dampness constitution using microRNA array and RT-qPCR targeting on hsa-miR-1237e3p

Background:Metabolic diseases pose considerable burden on the healthcare system worldwide,indicating the significance of prevention and treatment.In constitution theory of traditional Chinese medicine,phlegm-dampness constitution(PDC)is the common basis of metabolic diseases.In clinical practice,Huatan Qushi(HTQS)decoction targeting on PDC can effectively improve metabolic indicators.However,its underlying biochemical mechanism still remains unclear.Methods:Eight PDC participants received HTQS decoction for three months.Their blood was collected at baseline and 1 and 3 months after intervention started.Related biomedical indicators were detected.High-throughput sequencing and RT-qPCR were used for validation.Due to the missing data,repeated measures with missing values in mixed models were used.Results:After 3-month treatment,HDL-C level increased(P<.001)and FBG,FINS,and HbA1c all showed decreasing trend at different time points(all P<.05).After miRNA high-throughput sequencing,compared with the baseline,differential miRNAs at 1 and 3 months were screened,and target gene prediction and KEGG pathway enrichment analysis were performed.The results displayed that metabolic disease-related pathways mainly included pathways in cancer,PI3K-Akt signaling pathway,etc.Further,RT-qPCR showed that hsa-miR-1237e3p differed statistically(P=.008).Then we validated the target genes of hsa-miR-1237e3p in the“Pathways in Cancer”pathway including SDF1,AC,CRK,and HGF,also known as upstream target genes of PI3K/AKT pathway.The results showed that two indicators of CRK and HGF were in statistical significance(P=.045 and P=.036,respectively).Conclusion:PDC serves as a common basis for various metabolic diseases.Through adjusting PDC,HTQS decoction can improve biomedical indicators including blood glucose,HbA1c,insulin,and HDL-C.The target pathway is“Pathways in cancer”.Specifically,HTQS decoction acts on targets of CRK and HGF by regulating hsa-miR-1237e3p,and probably exerts effects on their downstream PI3K/AKT pathway.

Does Checklist Implementation Improve Quantity of Data Transfer: An Observation in Postanesthesia Care Unit (PACU)

Background: Omission of patient information in perioperative communication is closely linked to adverse events. Use of checklists to standardize the handoff in the post anesthesia care unit (PACU) has been shown to effectively reduce medical errors. Objective: Our study investigates the use of a checklist to improve quantity of data transfer during handoffs in the PACU. Design: A cross-sectional observational study. Setting: PACU at Memorial Sloan Kettering Cancer Center (MSKCC);June 13, 2016 through July 15, 2016. Patients, other participants: We observed the handoff reports between the nurses, PACU midlevel providers, anesthesia staff, and surgical staff. Intervention: A physical checklist was provided to all anesthesia staff and recommended to adhere to the list at all observed PACU handoffs. Main outcome measure: Quantity of reported handoff items during 60 pre- and 60 post-implementation of a checklist. Results: Composite value from both surgical and anesthesia reports showed an increase in the mean report of 8.7 items from pre-implementation period to 10.9 post-implementation. Given that surgical staff reported the mean of 5.9 items pre-implementation and 5.5 items post-implementation without intervention, improvements in anesthesia staff report with intervention improved the overall handoff data transfer. Conclusions: Using a physical 12-item checklist for PACU handoff increased overall data transfer.