New approaches for precise response evaluation in hepatocellular carcinoma

With the increasing clinical use of cytostatic and novel biologic targeted agents,conventional morphologic tumor burden assessments,including World Health Organization criteria and Response Evaluation Criteria in Solid Tumors,are confronting limitations because of their difficulties in distinguishing viable tumor from necrotic or fibrotic tissue.Therefore,the investigation for reliable quantitative biomarkers of therapeutic response such as metabolic imaging or functional imaging has been desired.In this review,we will discuss the conventional and new approaches to assess tumor burden.Since targeted therapy or locoregional therapies can induce biological changes much earlier than morphological changes,these functional tumor burden analyses are very promising.However,some of them have not gone thorough all steps for standardization and validation.Nevertheless,these new techniques and criteria will play an important role in the cancer management,and provide each patient more tailored therapy.

Immune response evaluation criteria in solid tumors for assessment of atypical responses after immunotherapy

In 2017,immune response evaluation criteria in solid tumors(iRECIST)were introduced to validate radiologic and clinical interpretations and to better analyze tumor’s response to immunotherapy,considering the different time of following and response,between this new therapy compared to the standard one.However,even if the iRECIST are worldwide accepted,to date,different aspects should be better underlined and well reported,especially in clinical practice.Clinical experience has demonstrated that in a non-negligible percentage of patients,it is challenging to determine the correct category of response(stable disease,progression disease,partial or complete response),and consequently,to define which is the best management for those patients.Approaching radiological response in patients who underwent immunotherapy,a new uncommon kind of target lesions behavior was found.This phenomenon is mainly due to the different mechanisms of action of immunotherapeutic drug.Therefore,new groups of response have been described in clinical practice,defined as“atypical responses,”and categorized into three new groups:pseudoprogression,hyperprogression,and dissociated response.This review summarizes and reports these patterns,helping clinicians and radiologists get used to atypical responses,in order to identify patients that respond best to treatment.

Radiomics in Antineoplastic Agents Development:Application and Challenge in Response Evaluation

The recent spring up of the antineoplastic agents and the prolonged survival bring both challenge and chance to radiological practice.Radiological methods including CT,MRI and PET play an increasingly important role in evaluating the efficacy of these antineoplastic drugs.However,different antineoplastic agents potentially induce different radiological signs,making it a challenge for radiological response evaluation,which depends mainly on one-sided morphological response evaluation criteria in solid tumors(RECIST)in the status quo of clinical practice.This brings opportunities for the development of radiomics,which is promising to serve as a surrogate for response evaluations of anti-tumor treatments.In this article,we introduce the basic concepts of radiomics,review the state-of-art radiomics researches with highlights of radiomics application in predictions of molecular biomarkers,treatment response,and prognosis.We also provide in-depth analyses on major obstacles and future direction of this new technique in clinical investigations on new antineoplastic agents.

Establishing Chinese Medicine Characteristic Tumor Response Evaluation System Is the Key to Promote Internationalization of Chinese Medicine Oncology

The features and advantages of Chinese medicine （CM） in cancer comprehensive treatment have been in the spotlight of experts both at home and abroad. However, how to evaluate the effect of CM more objectively, scientifically and systematically is still the key problem of clinical trial, and also a limitation to the development and internationalization of CM oncology. The change of tumor response evaluation system in conventional medicine is gradually consistent with the features of CM clinical effect, such as they both focus on a combination of soft endpoints （i.e. quality of life, clinical benefit, etc.） and hard endpoints （i.e. tumor remission rate, time to progress, etc.）. Although experts have proposed protocols of CM tumor response evaluation criteria and come to an agreement in general, divergences still exist in the importance, quantification and CM feature of the potential endpoints.Thus, establishing a CM characteristic and wildly accepted tumor response evaluation system is the key to promote internationalization of CM oncology, and also provides a more convenient and scientific platform for CM international cooperation and communication.

Tumor response assessment by the single-lesion measurement per organ in small cell lung cancer

Background： The criterion of two target lesions per organ in the Response Evaluation Criteria in Solid Tumors （RECIST） version I. 1 is an arbitrary one, being supported by no objective evidence. The optimal number of target lesions per organ still needs to be investigated. We compared tumor responses using the RECIST 1.1 （measuring two target lesions per organ） and modified RECIST I. 1 （measuring the single largest lesion in each organ） in patients with small cell lung cancer （SCLC）. Methods： We reviewed medical records of patients with SCLC who received first-line treatment between January 2004 and December 2014 and compared tumor responses according to the two criteria using computed tomography. Results： There were a total of 34 patients who had at least two target lesions in any organ according to the RECIST 1.1 during the study period. The differences in the percentage changes of the sum of tumor measurements between RECIST 1.1 and modified RECIST 1.1 were all within 13%. Seven patients showed complete response and fourteen showed partial response according to the RECIST I.I. The overall response rate was 61.8%. When assessing with the modified RECIST 1.1 instead of the RECIST 1.1, tumor responses showed perfect concordance between the two criteria （k= 1.0）. Conclusions： The modified RECIST 1.I showed perfect agreement with the original RECIST 1.I in the assessment of tumor response of SCLC. Our result suggests that it may be enough to measure the single largest target lesion per organ for evaluating tumor response.

Neoadjuvant treatment of pancreatic ductal adenocarcinoma:Whom,when and how

Pancreatic ductal adenocarcinoma(PDAC),which is notorious for its aggressiveness and poor prognosis,remains an area of great unmet medical need,with a 5-year survival rate of 10%-the lowest of all solid tumours.At diagnosis,only 20%of patients have resectable pancreatic cancer(RPC)or borderline RPC(BRPC)disease,while 80%of patients have unresectable tumours that are locally advanced pancreatic cancer(LAPC)or have distant metastases.Nearly 60%of patients who undergo upfront surgery for RPC are unable to receive adequate adjuvant chemotherapy(CHT)because of postoperative complications and early cancer recurrence.An important paradigm shift to achieve better outcomes has been the sequence of therapy,with neoadjuvant CHT preceding surgery.Three surgical stages have emerged for the preoperative assessment of nonmetastatic pancreatic cancers:RPC,BRPC,and LAPC.The main goal of neoadjuvant treatment(NAT)is to improve postoperative outcomes through enhanced selection of candidates for curative-intent surgery by identifying patients with aggressive or metastatic disease during initial CHT,reducing tumour volume before surgery to improve the rate of margin-negative resection(R0 resection,a microscopic margin-negative resection),reducing the rate of positive lymph node occurrence at surgery,providing early treatment of occult micrometastatic disease,and assessing tumour chemosensitivity and tolerance to treatment as potential surgical criteria.In this editorial,we summarize evidence concerning NAT of PDAC,providing insights into future practice and study design.Future research is needed to establish predictive biomarkers,measures of therapeutic response,and multidisciplinary stra tegies to improve patient-centered outcomes.

Objective response rate assessment in oncology: Current situation and future expectations

The tumor objective response rate(ORR)is an important parameter to demonstrate the efficacy of a treatment in oncology.The ORR is valuable for clinical decision making in routine practice and a significant end-point for reporting the results of clinical trials.World Health Organization and Response Evaluation Criteria in Solid Tumors(RECIST)are anatomic response criteria developed mainly for cytotoxic chemotherapy.These criteria are based on the visual assessment of tumor size in morphological images provided by computed tomography(CT)or magnetic resonance imaging.Anatomic response criteria may not be optimal for biologic agents,some disease sites,and some regional therapies.Consequently,modifications of RECIST,Choi criteria and Morphologic response criteria were developed based on the concept of the evaluation of viable tumors.Despite its limitations,RECIST v1.1 is validated in prospective studies,is widely accepted by regulatory agencies and has recently shown good performance for targeted cancer agents.Finally,some alternatives of RECIST were developed as immune-specific response criteria for checkpoint inhibitors.Immune RECIST criteria are based essentially on defining true progressive disease after a confirmatory imaging.Some graphical methods may be useful to show longitudinal change in the tumor burden over time.Tumor tissue is a tridimensional heterogenous mass,and tumor shrinkage is not always symmetrical;thus,metabolic response assessments using positron emission tomography(PET)or PET/CT may reflect the viability of cancer cells or functional changes evolving after anticancer treatments.The metabolic response can show the benefit of a treatment earlier than anatomic shrinkage,possibly preventing delays in drug approval.Computer-assisted automated volumetric assessments,quantitative multimodality imaging in radiology,new tracers in nuclear medicine and finally artificial intelligence have great potential in future evaluations.

Comparison of RECIST version 1.0 and 1.1 in assessment of tumor response by computed tomography in advanced gastric cancer

Objective： Response Evaluation Criteria in Solid Tumors （RECIST） guideline version 1.0 （RECIST 1.0） was proposed as a new guideline for evaluating tumor response and has been widely accepted as a standardized measure. With a number of issues being raised on RECIST 1.0, however, a revised RECIST guideline version 1.1 （RECIST 1.1） was proposed by the RECIST Working Group in 2009. This study was conducted to compare CT tumor response based on RECIST 1.1 vs. RECIST 1.0 in patients with advanced gastric cancer （AGC）. Methods： We reviewed 61 AGC patients with measurable diseases by RECIST 1.0 who were enrolled in other clinical trials between 2008 and 2010. These patients were retrospectively re-analyzed to determine the concordance between the two response criteria using the κ statistic. Results： The number and sum of tumor diameters of the target lesions by RECIST 1.1 were significantly lower than those by RECIST 1.0 （P〈0.0001）. However, there was excellent agreement in tumor response between RECIST 1.1 and RECIST 1.0 0（κ=0.844）. The overall response rates （ORRs） according to RECIST 1.0 and RECIST 1.1 were 32.7% （20/61） and 34.5% （20/58）, respectively. One patient with partial response （PR） based on RECIST 1.0 was reclassified as stable disease （SD） by RECIST 1.1. Of two patients with SD by RECIST 1.0, one was downgraded to progressive disease and the other was upgraded to PR by RECIST 1.1. Conclusions： RECIST 1.1 provided almost perfect agreement with RECIST 1.0 in the CT assessment of tumor response of AGC.

Imaging response predictors following drug eluting beads chemoembolization in the neoadjuvant liver transplant treatment of hepatocellular carcinoma

BACKGROUND Drug-eluting bead transarterial chemoembolization(DEB-TACE)is an endovascular treatment to release chemotherapeutic agents within a target lesion,minimizing systemic exposure and adverse effects to chemotherapeutics.Therefore,identifying which patient characteristics may predict imaging response to DEB-TACE can improve treatment results while selecting the best candidates.Predictors of the response after DEB-TACE still have not been fully elucidated.This is the first prospective study performed with standardized DEBTACE technique that aim to identify predictors of radiological response,assessing patients clinical and laboratory characteristics,diagnostic imaging and intraprocedure data of the hepatocellular carcinoma treated in the neoadjuvant context for liver transplantation.AIM To identify pre-and intraoperative clinical and imaging predictors of the radiological response of drug-eluting bead transarterial chemoembolization(DEB-TACE)for the neoadjuvant treatment of hepatocellular carcinoma(HCC).METHODS This is prospective,cohort study,performed in a single transplant center,from 2011 to 2014.Consecutive patients with HCC considered for liver transplant who underwent DEB-TACE in the first session for downstaging or bridging purposes were recruited.Pre and post-chemoembolization imaging studies were performed by computed tomography or magnetic resonance.The radiological response of each individual HCC was evaluated by objective response using mRECIST and the percentage of necrosis.RESULTS Two hundred patients with 380 HCCs were examined.Analysis of the objective response(nodule-based analysis)demonstrated that HCC with pseudocapsules had a 2.01 times greater chance of being responders than those without pseudocapsules(P=0.01),and the addition of every 1mg of chemoembolic agent increased the chance of therapeutic response in 4%(P<0.001).Analysis of the percentage of necrosis through multiple linear regression revealed that the addition of each 1mg of the chemoembolic agent caused an average increase of 0.65%(P<0.001)in necrosis in the treated lesion,whereas the hepatocellular carcinoma with pseudocapsules presented 18.27%(P<0.001)increased necrosis compared to those without pseudocapsules.CONCLUSION The presence of a pseudocapsule and the addition of the amount of chemoembolic agent increases the chance of an objective response in hepatocellular carcinoma and increases the percentage of tumor necrosis following drug-eluting bead chemoembolization in the neoadjuvant treatment,prior to liver transplantation.

RAMAN SPECTROSCOPIC STUDY ON PREDICTION OF TREATMENT RESPONSE IN CERVICAL CANCERS

Concurrent chemoradiotherapy(CCRT)is the choice of treatment for locally adv anced cervical cancers;however,tumors exhibit diverse response to treatment.Early prediction of tumor response leads to individualizing treatment regimen.Response evaluation criteria in solid tumors(RECIST),the current modality of tumor response assessment,is often subject ive and carried out at the first visit after treatment,which is about four months.Hence,there is a need for better predictive tool for radioresponse.Optical spectroscopic techniques,sensitive to molecular alteration,are being pursued as potential diagnostic tools.Present pilot study ains to explore the fiber-optic-based Raman spectroscopy approach in prediction of tumor response to CCRT,before taking up extensive in vivo studies.Ex vivo Raman spectra were acquired from biopsies collected from 11 normal(148 spectra),16 tumor(201 spectra)and 13 complete response(151 CR spectra),one partial response(8 PR spectra)and one nonresponder(8 NR spectra)subjects.Data was analyzed using principal component linear discriminant analysis(PC-LDA)followed by leave-one-out cross-validation(LOO-CV).Findings suggest that normal tissues can be efficiently classified from both pre-and post-treated tumor biopsies,while there is an overlap between pre-and post-CCRT tumor tissues.Spectra of CR,PR and NR tissues were subjected to principal component analysis(PCA)and a tendency of classification was observed,corroborating previous studies.Thus,this study further supports the feasibility of Raman spectroscopy in prediction of tumor radioresponse and prospective noninvasive in vivo applications.

Clinical performance evaluation of O-Ring Halcyon Linac:A realworld study

BACKGROUND Radiation therapy,especially the development of linear accelerators,plays a key role in cancer management.The fast-rotating coplanar O-ring Halcyon Linac has demonstrated many advantages.The previous literature has mainly focused on the machine parameters and plan quality of Halcyon,with a lack of relevant research on its clinical application.AIM To evaluate the clinical performance of the O-ring Halcyon treatment system in a real-world application setting.METHODS Data from sixty-one patients who were treated with the Halcyon system throughout the entire radiotherapy process in Peking Union Medical College Hospital between August 2019 and September 2020 were retrospectively reviewed.We evaluated the target tumour response to radiotherapy and irradiation toxicity from 1 to 3 mo after treatment.Dosimetric verification of Halcyon plans was performed using a quality assurance procedure,including portal dosimetry,ArcCHECK and point dose measurements for verification of the system delivery accuracy.RESULTS Of the 61 patients in the five groups,16,12,7 and 26 patients had complete response,partial response,progressive disease and stable disease,respectively.No increase in the irradiated target tumour volume was observed when separately evaluating the local response.Regarding irradiation toxicity,no radiation-induced deaths were observed.Thirty-eight percent(23/61 patients)had no radiation toxicity after radiotherapy,56%(34/61 patients)experienced radiation toxicity that resolved after treatment,and 6%(4/61 patients)had irreversible adverse reactions.The average gamma passing rates with a 2%dose difference and 2-mm distance to agreement for IMRT/VMAT/SRT plans were ArcCHECK at 96.4%and portal dosimetry at 96.7%,respectively.All of the validated clinical plans were within 3%for point dose measurements,and Halcyon’s ArcCHECK demonstrated a high pass rate of 99.1%±1.1%for clinical gamma passing criteria of 3%/3 mm.CONCLUSION The O-ring Halcyon Linac could achieve a better therapeutic effect on the target volume by providing accurate treatment delivery plans with tolerable irradiation toxicity.

Auditory steady-state evoked response in diagnosing and evaluating hearing in infants

BACKGROUND: Auditory steady-state evoked response (ASSR) is one of the new objective electrophysiological methods to test hearing in infants. It can provide a reliable and complete audiogram with specific frequency to help the hearing diagnosis and rehabilitation of hearing and languaging following auditory screening. OBJECTIVE: To compare the response threshold of ASSR with auditory threshold of visual reinforcement audiometry (VRA) in infants failed in the hearing screening for investigating their hearing loss. DESIGN: A comparative observation. SETTINGS: Maternal and child health care hospitals of Guangdong province, Shunde city, Nanhai city and Huadu district. PARTICIPANTS: Totally 321 infants of 0-3 years undergoing ASSR test were selected from the Hearing Center of Guangdong Maternal and Child Health Care Hospital from January 2002 to December 2004. Informed consents were obtained from their guardians. There were 193 cases (60.2%) of 0-6 months, 31 cases (9.7%) of 7-12 months, 17 cases (5.3%) of 13-18 months, 14 cases (4.4%) of 19-24 months, 33 cases of 25-30 months, and 33 cases (10.2%) of 31-36 months. METHODS: ① The 321 infants failed in the hearing screening were tested under sleeping status, the ranges of response threshold distribution in ASSR of different frequencies were analyzed in each age group. ② The infants above 2 years old were also tested with VRA, and their response thresholds were compared between VRA and ASSR. ③ Evaluative standards: The response threshold was < 30 dB for normal hearing, 31-50 dB for mild hearing loss, 51-70 dB for moderate hearing loss, 71-90 dB for severe hearing loss, and > 91 dB for extremely severe hearing loss. MAIN OUTCOME MEASURES: ① ASSR results of the infants failed in the screening; ② Proportion of cases of each response threshold in each age group; ③ Comparison of ASSR response thresholds and VRA auditory thresholds in the infants of 2-3 years old. RESULTS: ①The response threshold was < 30 dB in 47.4% of the 321 infants failed in the initial hearing screening and secondary screening after 42 days. ② Severe to extremely severe hearing loss was detected in only 16 cases (8.3%) of the 193 infants of 0-6 months, in 9 cases (27.3%) of the 33 infants of 25-30 months, and 13 cases (39.4%) of the 33 infants of 31-36 months. Of the 193 infants of 0-6 months old who failed in the initial screening and the second screening after 42 days, the ASSR auditory threshold was < 30 dB in 97 cases (50.26%), 31-50 dB in 63 cases (32.6%), 51-70 dB in 17 cases (8.8%), 71-90 dB in 7 cases (3.6%), and > 91 dB in 9 cases (4.7%). ③ Among the 321 infants failed in the screening, the auditory threshold in the 6 age groups was < 30 dB in 47.4%, 31-50 dB in 27.1%, 51-70 dB in 8.4%, 71-90 dB in 6.2%, and > 91 dB in 10.9%. ④ The difference between ASSR response threshold and VRA auditory thresholds was 6-18 dB in the normal hearing group, mild and moderate hearing loss groups, and there was high correlation between them. The difference of ASSR and VRA thresholds was less than 5 dB between extremely severe and severe hearing loss groups, 5-13 dB between extremely severe and moderate-to-severe hearing loss groups (P < 0.05), and there was no significant differences between severe and moderate-to-severe hearing loss groups (P > 0.05). CONCLUSION: ① The hearing was normal in about half of the infants, although they failed in the primary screening and secondary screening. ② The proportion of the severity of hearing loss was increased along with aging. ③ Mild and moderate hearing losses are dominant in infants. ④ ASSR is reliable to evaluate the hearing of infants.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.

How to assess the efficacy or failure of targeted therapy:deciding when to stop sorafenib in hepatocellular carcinoma

Sorafenib is thus far the only systemic treatment for hepatocellular carcinoma(HCC) based on the results of two randomized controlled trials performed in Western and in Eastern countries, despite a poor response rate(from 2% to 3.3%) following conventional evaluation criteria. It is now recognized that the criteria(European Association of the Study of the Liver criteria, modified response evaluation criteria in solid tumors) based on contrast enhanced techniques(computed tomography scan, magnetic resonance imaging) aimed to assess the evolution of the viable part of the tumor(hypervascularized on arterial phase) are of major interest to determine the efficacy of sorafenib and of most antiangiogenic drugs in patients with HCC. The role of alphafetoprotein serum levels remains unclear. In 2016, in accordance with the SHARP and the Asia-Pacific trials, sorafenib must be stopped when tolerance is poor despite dose adaptation or in cases of radiological and symptomatic progression. This approach will be different in cases of available second-line therapy trials. Some recent data(in renal cell carcinoma) revealed that despite progression in patients who received sorafenib, this drug can still decrease tumor progression compared to drug cessation. Then, before deciding to continue sorafenib post-progression or shift to another drug, knowing other parameters of post-progression survival(Child-Pugh class, Barcelona Clinic Liver Cancer, alphafetoprotein, post-progression patterns in particular, the development of extrahepatic metastases and of portal vein thrombosis) will be of major importance.

Challenges of evaluating immunotherapy efficacy in solid tumors

Immunotherapy is one of the most promising treatments for multiple tumor types.The significant clinical benefits and durable responses of immunotherapy have led to the emergence of various immune-related clinical response patterns that extend beyond those achieved with cytotoxic agents.Various studies investigated the efficacy of immunotherapy,including the effect on tumor size,long-term survival benefits,and the ability to overcome the particularly challenging survival curves tailing phenomenon.The current immune-related methods guidelines,such as immune-related Response Criteria(irRC),immune-related Response Evaluation Criteria in Solid Tumors(irRECIST),immune Response Evaluation Criteria in Solid Tumors(iRECIST),and immune-modified Response Evaluation Criteria in Solid Tumors(imRECIST),could be well-adapted to identify the heterogeneity of responses that appear in patients receiving immunotherapy,such as pseudoprogression(PsPD)and hyperprogressive disease(HPD),and to some extent to overcome the limitation of evaluating the efficacy of immunotherapy on tumor size by imaging.Additionally,a second type of evaluation method was proposed based on survival,which includes milestone analysis and restricted mean survival time.Currently,milestone analysis is a complementary tool to summarize and interpret trial results along with more conventional measures of survival and other less established metrics.A golden standard evaluation method to distinguish the efficacy of immunotherapy may improve the process of imaging and aid survival-based efficacy evaluation in patients with solid tumors.

Assessment of circulating levels of microRNA-326,microRNA-424,and microRNA-511 as biomarkers for hepatocellular carcinoma in Egyptians

BACKGROUND Hepatocellular carcinoma(HCC)is the fifth most common cancer.Differential expression of microRNAs(miRNAs)-326,miRNA-424,and miRNA-511 has been associated with the diagnosis and prognosis of HCC in different populations.However,limited information is available regarding their expression in Egyptian HCC patients.AIM To assess the role of circulating miRNAs-326,miRNA-424,and miRNA-511 in Egyptian HCC patients.METHODS This prospective observational study included 70 HCC patients and 25 healthy controls.The circulating levels of these three miRNAs were evaluated by real-time PCR.Receiver operating characteristic curve analysis was used to test the diagnostic accuracy of micro RNA expression levels.RESULTS All miRNAs were differentially expressed in HCC patients;miRNAs326 and miRNA-424 were upregulated,while miRNA-511 was downregulated.Both miRNA-326 and miRNA-424 showed sensitivity and specificity of 97%,71.4%,and 52%,60%,respectively,to differentiate HCC from controls.Moreover,miRNA-326 was associated with survival and could differentiate between Child grades(A vs B);miRNA-424 significantly differentiated early vs intermediate stages of HCC;while miRNA-511 was significantly correlated with response to modified Response Evaluation Criteria in Solid Tumors(m RECIST).CONCLUSION We conclude that miRNA-326,miRNA-424,and miRNA-511 have diagnostic and prognostic roles in Egyptian patients with hepatitis C virus-related HCC and should be considered for better disease management.

Utility of positron emission tomography-computed tomography scan in detecting residual hepatocellular carcinoma post treatment:Series of case reports

BACKGROUND Multi-phase computed tomography(CT)or magnetic resonance imaging(MRI)has been the standard of care for hepatocellular carcinoma(HCC)diagnosis for years.CASE SUMMARY We report a case series of four patients in whom positron emission tomographycomputed tomography(PET-CT)scan complemented the conventional CT/MRI scans in evaluating treatment response.In these four cases the conventional multi-phase CT and MRI failed to identify residual HCC disease post-treatment,while PET-CT complemented and aided in treatment response evaluation.In each case,the addition of PET-CT identified and located residual HCC disease,allowed retreatment,and altered medical management.CONCLUSION This case series suggests that PET-CT should perhaps play a role in the HCC management algorithm,in addition to the conventional contrast-enhanced multiphase scans.

Lenvatinib for large hepatocellular carcinomas with portal trunk invasion:Two case reports

BACKGROUND In a phase III trial of lenvatinib as first-line treatment for advanced unresectable hepatocellular carcinoma(uHCC),the drug proved non-inferior to sorafenib in terms of the overall survival,but offered better progression-free survival.However,the effects of lenvatinib in uHCC patients with a tumor thrombus in the main portal vein and/or a high tumor burden(tumor occupancy more than 50%of the total liver volume),remain unclear,because these were set as exclusion criteria in the aforementioned trial.CASE SUMMARY A 53-year-old man(case 1)and 66-year-old woman(case 2)with uHCC presented to us with a tumor thrombus in both the main portal vein and inferior vena cava,a high tumor burden accompanied by a tumor diameter greater than>100 mm,and distant metastasis,with the residual liver function classified as grade 2A according to the modified Albumin–Bilirubin grading.We started both patients on lenvatinib.The therapeutic effect,as evaluated by the modified Response Evaluation Criteria in Solid Tumors,was rated as partial response in both case 1 and case 2(at 8 wk and 4 wk after the start of lenvatinib administration,respectively).The therapeutic effect was sustained for 6 mo in case 1 and 20 mo in case 2.Fever occurred as an adverse event in both case 1 and 2,and hyperthyroidism and thrombocytopenia in only case 2,neither of which,however,necessitated treatment discontinuation.CONCLUSION Even in hepatocellular carcinoma patients with poor prognostic factors,if the liver function is well-preserved,lenvatinib is effective and safe.

外语课堂的师生话语轮换与外语课堂教学

建立一个师生积极互动的外语教学模式是外语教学一直追求的目标。本文观察了两个英语教学课堂的师生话语轮换的分配状况,分析了它们的特征;建议采取多样化的话语轮换模式,给学生足够的机会用目标语进行交流。

Effectiveness of dynamic contrast-enhanced magnetic resonance imaging in evaluating clinical responses to neoadjuvant chemotherapy in breast cancer

Background Use of neoadjuvant chemotherapy necessitates assessment of response to cytotoxic drugs.The aim of this research was to investigate the effectiveness of dynamic contrast-enhanced magnetic resonance imaging （MRI） for evaluating clinical responses to neoadjuvant chemotherapy in breast cancer patients.Methods We examined patients receiving neoadjuvant chemotherapy for primary breast cancer between October 2007and September 2008.Dynamic contrast-enhanced MRI was used to examine breast tumors prior to and after neoadjuvant chemotherapy.The MRI examination assessed tumors using Response Evaluation Criteria in Solid Tumors （RECIST）.The Miller-Payne grading system was used as a histopathological examination to assess the effect of the treatment.We examined the relationship between the results of RECIST and histopathological criteria.In addition,we used time-signal intensity curves （MRI T-SI） to further evaluate the effects of neoadjuvant chemotherapy on tumor response.Results MRI examination of patients completing four three-week anthracycline-taxanes chemotherapy treatment revealed that no patients had complete responses （CR）,58 patients had partial responses （PR）,29 patients had stable disease （SD）,and four with progressive disease （PD）.The effectiveness of neoadjuvant chemotherapy （CR ＋ PR） was 63.7% （58/91）.The postoperative histopathological evaluations revealed the following：seven G5 （pCR） cases （7.7%）,39G4 cases （42.9%）,16 G3 cases （17.6%）,23 G2 cases （25.3%）,and six G1 cases （6.6%）.The effectiveness （G5 ＋ G4 ＋G3） was 68.1% （62/91）.MRI T-SI standards classified 53 responding cases,29 stable cases,and nine progressing cases.These results indicated that the treatment was 58.2% effective （53/91） overall.Conclusions Dynamic contrast-enhanced MRI and histopathological standards were highly correlated.Importantly,MRI T-SI evaluation was found to be useful in assessing the clinical effectiveness of neoadjuvant chemotherapy.