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.

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (<400 ng/ml) (Odds ratio=3.3) and PR as best response to TACE (Odds ratio=6.7) were significantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents.

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.

Predictive factors of tumor response to trans-catheter treatment in cirrhotic patients with hepatocellular carcinoma:A multivariate analysis of pre-treatment findings

AIM： To elucidate the pre-treatment clinical and imaging findings affecting the tumor response to the transcatheter treatment of unresectable hepatocellular carcinoma （HCC）. METHODS： Two hundred cirrhotic patients with HCC received a total of 425 transcatheter treatments. The tumor response was evaluated by helical CT and a massive necrosis （MN） was defined as a necrosis 〉 90%. Twenty-five clinical and imaging variables were analyzed： uninodular/multinodular HCC, unilobar/bilobar, tumor capsula, hypervascular lesion, portal vein thrombosis, portal hypertension, ascites, platelets count, aspartate transaminases/alanine transaminases （AST/ALT）, alfa- fetoprotein （AFP） 〉 100, AFP 〉 400, serum creatinine, virus hepatitis C （VHC） cirrhosis, performance status, age, Okuda stage, ChUd-Pugg stage, sex, CLIP （Cancer of the Liver Italian Program） score, serum bilirubin, constitutional syndrome, serum albumine, prothrombin activity, BCLC （Barcelona Clinic Liver Cancer） stage. Prognostic factors of response were subjected to univariate analysis and thereafter, when significant, to the multivariate analyses. RESULTS： On imaging analysis, complete response wasobtained in 60 （30%） patients, necrosis 〉 90% in 38 （19%） patients, necrosis 〉 50% in 44 （22%） patients, and necrosis 〈 50% in 58 （29%） patients. Ninety-eight （49%） of the 200 patients were considered to have a MN. In univariate analysis, significant variables （P 〈 0.01） were： uninodular tumor, unilobar, tumor size 2-6 cm, CLIP score 〈 2, absence of constitutional syndrome, and BCLC stage 〈 2. In a multivariate analysis, the variables reaching statistical significance were： presence of tumor capsule （P 〈 0.0001）, tumor size 2-6 cm （P 〈 0.03）, CLIP score 〈 2 （P 〈 0.006）, and absence of constitutional syndrome （P 〈 0.03）. Kaplan-Mayer cumulative survival at 12 mo was 80% at 24 mo was 56%. MN was associated with a longer survival （P 〈 0.0001）. CONCLUSION： MN after transcatheter treatment is more common in the presence of tumor capsule, maximum diameter of the main lesion between 2 and 6 cm, CLIP score 〈 2 and absence of constitutional syndrome. The ability to predict which patients will respond to transcatheter treatment may be useful in the clinical decision-making process, and in stratifying the randomization of patients in clinical trials.

Influence of tumor response on the survival of patients with extensive-stage small-cell lung cancer treated with the etoposide plus cisplatin chemotherapy regimen

Objective In this study, we evaluated the difference of progression-free survival （PFS） and overall survival （OS） between extensive-stage small-cell lung cancer （ES-SCLC） patients who acquired partial response （PR） or complete remission （CR） after two cycles of first-line chemotherapy with the etoposide plus cisplatin （EP） regimen and those who acquired PR or CR after four or six cycles. Methods A total of 106 eligible patients treated with the EP chemotherapy regimen for two to six cycles, at The General Hospital of Shenyang Military Region （China） between November 2004 and Way 2011, were enrolled in this study. RECIST version 1.1 was used for the evaluation of chemotherapy efficiency. We followed up all eligible patients every 4 weeks. All statistical data were analyzed by using SPSS 21.0 statistical package for Windows. Results After a median follow-up of 293 days （range, 62-1531 days）, all patients had died by the cutoff date. Fifty-one patients acquired PR or CR after two cycles of chemotherapy; the median PFS reached 6.0 months （95% CI, 5.1-6.9）, and the median OS was 10.5 months （95% CI, 8.6-12.4）. Twenty-eight patients acquired PR or CR after four or six cycles; the median PFS was 4.8 months （95% CI, 4.4-5.2）, and the median OS was 7.5 months （95% CI, 6.8-8.2）. Both PFS and OS showed a statistical difference between the two groups. Conclusion ES-SCLC patients who acquired PR or CR after two cycles of the EP regimen as first-line therapy had longer PFS and OS than those who acquired PR or CR after four or six cycles.

Computed Tomography Evaluation of Tumor Response in Oncology in Togo

Cancer is common in our setting and represents a real public health concern in sub-Saharan Africa. This work aimed to assess the role of computed tomography in the follow-up of patients treated for cancer in Togo. This was a retrospective descriptive study carried out over a period of one year, on patients with cancer, treated in the medical oncology unit of CHU Sylvanus Olympio and having undergone at least two CT scans after cancer treatment. Computed tomography evaluation was performed according to the RECIST 1.1 guidelines. We had found 46 patients. The mean age of the patients was 54.22 years with a female predominance (sex ratio 1:2.5). Cancers mainly involved the urogenital system (60.8%) followed by the digestive system (28.3%). Carcinoma represented 93.5% of cases, mainly adenocarcinoma (45.7%). 74 target lesions were present at baseline, with 18.9% and 11.6% disappearing at the first and second assessments respectively. 36 non-target lesions were present at baseline, with 25% and 22.2% disappearing at the first and second assessments respectively. New lesions were found in the abdominal region in 54.5% of cases and in the thoracic region in 41.3% at the first and second assessments respectively. 58.7% of patients had a stable disease at the first assessment and 39.1% had progression at the second assessment. 50% of them had received chemotherapy in combination with surgery. Computed tomography using the RECIST 1.1 guidelines is a necessity in monitoring tumor extensions and in the follow-up of cancer patients.

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.

Stochastic responses of tumor-immune system with periodic treatment

We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and immune system under external fluctuations and periodic treatment is established based on the stochastic differential equation. Then, sufficient conditions for extinction and persistence of the tumor cells are derived by constructing Lyapunov functions and Ito＇s formula. Finally, numerical simulations are introduced to illustrate and verify the results. The results of this work provide the theoretical basis for designing more effective and precise therapeutic strategies to eliminate cancer cells, especially for combining the immunotherapy and the traditional tools.

Role of imaging in evaluating the response after neoadjuvant treatment for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive malignancy.Despite the development of multimodality treatments,including surgical resection,radiotherapy,and chemotherapy,the long-term prognosis of patients with PDAC remains poor.Recently,the introduction of neoadjuvant treatment(NAT)has made more patients amenable to surgery,increasing the possibility of R0 resection,treatment of occult micro-metastasis,and prolongation of overall survival.Imaging plays a vital role in tumor response evaluation after NAT.However,conventional imaging modalities such as multidetector computed tomography have limited roles in the assessment of tumor resectability after NAT for PDAC because of the similar appearance of tissue fibrosis and tumor infiltration.Perfusion computed tomography,using blood perfusion as a biomarker,provides added value in predicting the histopathologic response of PDAC to NAT by reflecting the changes in tumor matrix and fibrosis content.Other imaging technologies,including diffusion-weighted imaging of magnetic resonance imaging and positron emission tomography,can reveal the tumor response by monitoring the structural changes in tumor cells and functional metabolic changes in tumors after NAT.In addition,with the renewed interest in data acquisition and analysis,texture analysis and radiomics have shown potential for the early evaluation of the response to NAT,thus improving patient stratification to achieve accurate and intensive treatment.In this review,we briefly introduce the application and value of NAT in resectable and unresectable PDAC.We also summarize the role of imaging in evaluating the response to NAT for PDAC,as well as the advantages,limitations,and future development directions of current imaging techniques.

Quantitative dual-energy computed tomography texture analysis predicts the response of primary small hepatocellular carcinoma to radiofrequency ablation

Background:Radiofrequency ablation(RFA)is one of the effective therapeutic modalities in patients with hepatocellular carcinoma(HCC).However,there is no proper method to evaluate the HCC response to RFA.This study aimed to establish and validate a clinical prediction model based on dual-energy com-puted tomography(DECT)quantitative-imaging parameters,clinical variables,and CT texture parameters.Methods:We enrolled 63 patients with small HCC.Two to four weeks after RFA,we performed DECT scanning to obtain DECT-quantitative parameters and to record the patients’clinical baseline variables.DECT images were manually segmented,and 56 CT texture features were extracted.We used LASSO al-gorithm for feature selection and data dimensionality reduction;logistic regression analysis was used to build a clinical model with clinical variables and DECT-quantitative parameters;we then added texture features to build a clinical-texture model based on clinical model.Results:A total of six optimal CT texture analysis(CTTA)features were selected,which were statis-tically different between patients with or without tumor progression(P<0.05).When clinical vari-ables and DECT-quantitative parameters were included,the clinical models showed that albumin-bilirubin grade(ALBI)[odds ratio(OR)=2.77,95%confidence interval(CI):1.35-6.65,P=0.010],λAP(40-100 keV)(OR=3.21,95%CI:3.16-5.65,P=0.045)and IC AP(OR=1.25,95%CI:1.01-1.62,P=0.028)were asso-ciated with tumor progression,while the clinical-texture models showed that ALBI(OR=2.40,95%CI:1.19-5.68,P=0.024),λAP(40-100 keV)(OR=1.43,95%CI:1.10-2.07,P=0.019),and CTTA-score(OR=2.98,95%CI:1.68-6.66,P=0.001)were independent risk factors for tumor progression.The clinical model,clinical-texture model,and CTTA-score all performed well in predicting tumor progression within 12 months after RFA(AUC=0.917,0.962,and 0.906,respectively),and the C-indexes of the clinical and clinical-texture models were 0.917 and 0.957,respectively.Conclusions:DECT-quantitative parameters,CTTA,and clinical variables were helpful in predicting HCC progression after RFA.The constructed clinical prediction model can provide early warning of potential tumor progression risk for patients after RFA.

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.

Gemcitabine-induced peripheral vascular disease and prolonged response in a patient with metastatic pancreatic adenocarcinoma:A case report

BACKGROUND Gemcitabine is an antimetabolite used in the treatment of pancreatic cancer.One of the side effects of gemcitabine is vascular toxicity.Here,we report the case of a patient treated with gemcitabine who had peripheral vascular disease concomi-tant with a prolonged antitumor response.CASE SUMMARY A 75-year-old man was diagnosed with locally recurrent pancreatic cancer.Partial response was achieved after 9 mo of gemcitabine.At the same time,the patient reported peripheral vascular disease without necrosis.Chemotherapy was suspended,and after one month the Positron Emission Tomography(PET)scan showed locoregional tumor recurrence.Gemcitabine was resumed and partial response was obtained,but peripheral vascular disease occurred.CONCLUSION Our results suggest that the appearance of peripheral vascular disease may be related to a prolonged response to gemcitabine.

Tumor irradiation may facilitate the detection of tumor-specific mutations in plasma

BACKGROUND The mutation-based analysis of circulating tumor DNA(ctDNA)is a promising diagnostic tool for clinical oncology.However,it has low success rate because many cancer patients do not have detectable ctDNA in the bloodstream.AIM To evaluate whether preoperative tumor irradiation results in a transient increase of plasma ctDNA concentration due to the induction of apoptosis in radiationexposed cells.METHODS This study focused on patients with locally advanced rectal cancer,because preoperative tumor irradiation is a part of their standard treatment plan.Nine subjects,whose tumors contained KRAS,NRAS or BRAF mutations,donated serial blood samples 1 h prior to the first fraction of irradiation(at baseline),immediately after the first fraction(time 0),and 1,3,6,12,24,36,48,72 and 96 h after the first fraction.The amount of mutated gene copies was measured by droplet digital PCR.RESULTS Five out of nine patients were mutation-negative by ctDNA test at baseline;two of these subjects demonstrated an emergence of the mutated DNA copies in the bloodstream within the follow-up period.There were 4 patients,who had detectable ctDNA in the plasma at the start of the experiment;three of them showed an evident treatment-induced increase of the content of mutated RAS/RAF alleles.CONCLUSION Local tumor irradiation may facilitate the detection of tumor-specific DNA in the bloodstream.These data justify further assessment of the clinical feasibility of irradiation-assisted liquid biopsy.

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.

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.

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.

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is limited.AIM To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced HCC.METHODS HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were enrolled.All patients were treated with lenvatinib every day and sintilimab once every 3 wk.Moreover,TACE was performed every 4-6 wk if necessary.The primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse events.RESULTS Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January 2022.With a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,respectively.The ORR and DCR were 45%and 90%,respectively.The median progressive free survival and median OS were not reached.Common complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

Comparative study between Embosphere®and Marine gel®as embolic agents for chemoembolization of hepatocellular carcinoma

BACKGROUND While gelatin sponge particles and calibrated microspheres are commonly used as embolic materials in conventional transarterial chemoembolization(cTACE),direct comparisons between these embolic agents are rare.AIM To compare the efficacy and safety of superselective cTACE using Embosphere®or Marine gel®in patients with early-stage hepatocellular carcinoma(HCC).METHODS This retrospective study included 70 patients with small(<4 cm)HCC who underwent cTACE with Embosphere®(n=33)or Marine gel®(n=37)as the embolic agent at a single center between March 2021 and July 2022.The radiologic images and clinical data were retrospectively reviewed,with an emphasis on tumor response,procedure-related complications,and local tumor recurrence.The primary index tumor was assessed on a 1-mo follow-up image,and local progression-free survival was obtained using the Kaplan-Meier method and was compared by the log-rank test.RESULTS The median tumor size of both groups was 1.5 cm,and 69 patients achieved a complete response one month after cTACE.The cumulative local recurrence rate at 12 mo was 15.5%in the Embosphere®group and 14.4%in the Marine gel®group.The local progression-free survival was not significantly different between the two groups(P=0.83).In the multivariate analysis,high serum alphafetoprotein was the only significant poor prognostic factor for local tumor progression(P=0.01).Postembolization syndrome occurred in 36.4%of the Embosphere®group and 35.1%of the Marine gel®group,and there were no cases of biloma,biliary duct dilation,or liver abscess in either group.CONCLUSION Calibrated gelatin sponge particles(Marine gel®)and calibrated microspheres(Embosphere®)have similar outcomes in terms of tumor response for superselective cTACE of small HCC.

Targeted systemic therapies for hepatocellular carcinoma:Clinical perspectives,challenges and implications

Hepatocellular carcinoma （HCC） is a lethal disease in most patients, due to its aggressive course and a lack of effective systemic therapies for advanced disease. Surgical resection and liver transplantation remain the only curative options for a small subset of patients. Few patients with HCC are diagnosed early enough to be eli- gible for curative treatment. Angiogenesis inhibition is a natural therapeutic target for all solid tumors, but par- ticularly for the highly vascularized HCC tumors. With the approval of the targeted agent sorafenib, there are now additional options for patients with HCC. Although sorafenib does produce some improvement in survival in HCC patients, the responses are not durable. In addi- tion, there are significant dermatologic, gastrointestinal, and metabolic toxicities, and, as importantly, there is still limited knowledge of its usefulness in special sub- populations with HCC. Other angiogenesis inhibitors are in development to treat HCC both in the first-line set- ting and for use following sorafenib failure; the furthest in development is brivanib, a dual fibroblast growth factor pathway and vascular endothelial growth factor receptor inhibitor. Additional agents with antiangiogenic properties also in phase IT and Ⅲ development for the treatment of patients with HCC include bevacizumab, ramucirumab, ABT-869, everolimus and ARQ 197.

Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy

Advanced cholangiocarcinoma is associated with poor prognostic survival and has limited therapeutic options available at present. The importance of angiogenesis and expression of pro-angiogenic factors in intrahepatic forms of cholangiocarcinoma suggest that therapies targeting angiogenesis might be useful for the treatment of this disease. Here we report three cases of patients with advanced intrahepatic cholangiocarcinoma progressive after standard chemotherapy and treated with sunitinib 50 mg/d in 6-wk cycles of 4 wk on treatment followed by 2 wk off treatment(Schedule 4/2). In all three patients, sunitinib treatment was associated with a sustained disease control superior to 4 mo, patients achieving either a partial response or stable disease. A reduction in tumor size and density was observed in all cases, suggesting tumor necrosis as a result of sunitinib treatment in these patients. In addition, sunitinib was generally well tolerated and the occurrence of side effects was managed with standard medical interventions, as required. Our results suggest that sunitinib therapy maybe associated with favorable outcomes and tolerability in patients with advanced cholangiocarcinoma. Those observations contributed to launch a prospective phase Ⅱ multicenter trial investigating sunitinib in advanced intrahepatic cholangiocarcinoma(SUN-CK study; NCT01718327).