Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

Coordination of distinctive pesticide adjuvants and atomization nozzles on droplet spectrum evolution for spatial drift reduction

Pesticide adjuvants,as crop protection products,have been widely used to reduce drift loss and improve utilization efficiency by regulating droplet spectrum.However,the coordinated regulation mechanisms of adjuvants and nozzles on droplet spectrum remain unclear.Here,we established the relationship between droplet spectrum evolution and liquid atomization by investigating the typical characteristics of droplet diameter distribution near the nozzle.Based on this,the regulation mechanisms of distinctive pesticide adjuvants on droplet spectrum were clarified,and the corresponding drift reduction performances were quantitively evaluated by wind tunnel experiments.It shows that the droplet diameter firstly shifts to the smaller due to the liquid sheet breakup and then prefers to increase caused by droplet interactions.Reducing the surface tension of sprayed liquid facilitates the uniform liquid breakup and increasing the viscosity inhibits the liquid deformation,which prolong the atomization process and effectively improve the droplet spectrum.As a result,the drift losses of flat-fan and hollow cone nozzles are reduced by about 50%after adding organosilicon and vegetable oil adjuvants.By contrast,the air induction nozzle shows a superior anti-drift ability,regardless of distinctive adjuvants.Our findings provide insights into rational adjuvant design and nozzle selection in the field application.

TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

New method of local adjuvant therapy with bicarbonate Ringer’s solution for tumoral calcinosis: A case report

BACKGROUND Tumoral calcinosis is a condition characterized by deposits of calcium phosphate crystals in extra-articular soft tissues,occurring in hemodialysis patients.Calcium phosphate crystals are mainly composed of hydroxyapatite,which is highly infilt-rative to tissues,thus making complete resection difficult.An adjuvant method to remove or resolve the residual crystals during the operation is necessary.CASE SUMMARY A bicarbonate Ringer’s solution with bicarbonate ions(28 mEq/L)was used as the adjuvant.After resecting calcium phosphate deposits of tumoral calcinosis as much as possible,while filling with the solution,residual calcium phosphate deposits at the pseudocyst wall can be gently scraped by fingers or gauze in the operative field.A 49-year-old female undergoing hemodialysis for 15 years had swelling with calcium deposition for 2 years in the shoulders,bilateral hip joints,and the right foot.A shoulder lesion was resected,but the calcification remained and early re-deposition was observed.Considering the difficulty of a complete rection,we devised a bicarbonate dissolution method and excised the foot lesion.After resection of the calcified material,the residual calcified material was washed away with bicarbonate Ringer’s solution.CONCLUSION The bicarbonate dissolution method is a new,simple,and effective treatment for tumoral calcinosis in hemodialysis patients.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor organs restricts the availability of this procedure.Therefore,hepatectomy is the most commonly employed curative treatment for resectable HCC.Unfortunately,the 5-year recurrence rate for patients who undergoing hepatectomy ranges from 50%to 70%[2,3].Recurrence of HCC is associated with several risk factors[4],including single nodule>5 cm,vascular invasion,and multiple nodules.Among these factors,microvascular invasion(MVI)is an independent risk factor for recurrence.MVI is defined as the presence of cancer cells in the lumen of endothelium-lined vessels,typically in the small branches of the portal and hepatic veins of the paracancerous liver tissue,visible only under the microscope[5].Previous studies have shown that among HCC patients who underwent hepatectomy,those with MVI had a higher risk of recurrence and shorter overall survival(OS)than those without MVI[6].Several studies have indicated that adjuvant therapy following curative hepatectomy can prevent recurrence and improve OS in HCC patients with MVI.These postoperative adjuvant therapies include transarterial chemoembolization(TACE)[7],sorafenib[8],hepatic artery infusion chemotherapy(HAIC)[9],and radiotherapy(RT)[10].However,the existing studies mostly compare individual adjuvant therapy with hepatectomy alone.Direct or indirect comparisons between the various adjuvant therapies are lacking.Therefore,we performed the network meta-analysis(NMA)to compare the relative efficacy of each adjuvant therapy to determine the optimal treatment.

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity scorematched analysis

BACKGROUND The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma(ESCC)patients remained debatable.AIM To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery.METHODS In this retrospective,propensity score-matched study,we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019.Patients who underwent neoadjuvant therapy were excluded.We collected pa-tients’clinicopathological features and information regarding lymph nodes,in-cluding the total number of resected lymph nodes(NRLN),and pathologically diagnosed positive lymph nodes(RPLN).SPSS and R software were used for statistical analysis.RESULTS Among the included 1042 patients,two cohorts:≤21(n=664)and>21 NRLN(n=378)were identified.The final prognostic model included four variables:T stage,N,venous thrombus,and the number of removed lymph nodes.Among them,NRLN>21 was determined as an independent prognosticator after surgery for esophageal cancer(hazards regression=0.66,95%confidence interval:0.50-0.87,P=0.004).A nomogram was created based on the regression coefficients of the variables in the final model.In the training cohort,the predictive model dis-played an uncorrected five-year overall survival C-index of 0.659,with a bootstrap-corrected C-index of 0.654.In the subgroup analysis,adjuvant chemotherapy was beneficial in the subgroup with NRLN>21 and RPLN≤0.16 and NRLN≤21 and RPLN>0.16.CONCLUSION NRLN>21 was an independent prognostic factor after ESCC surgery.The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

BACKGROUND The benefit of adjuvant chemotherapy(ACT)for patients with no evidence of disease after pulmonary metastasis resection(PM)from colorectal cancer(CRC)remains controversial.AIM To assess the efficacy of ACT in patients after PM resection for CRC.METHODS This study included 96 patients who underwent pulmonary metastasectomy for CRC at a single institution between April 2008 and July 2023.The primary end-point was overall survival(OS);secondary endpoints included cancer-specific survival(CSS)and disease-free survival(DFS).An inverse probability of treat-ment-weighting(IPTW)analysis was conducted to address indication bias.Sur-vival outcomes compared using Kaplan-Meier curves,log-rank test,Cox regre-ssion and confirmed by propensity score-matching(PSM).RESULTS With a median follow-up of 27.5 months(range,18.3-50.4 months),the 5-year OS,CSS and DFS were 72.0%,74.4%and 51.3%,respectively.ACT had no significant effect on OS after PM resection from CRC[original cohort:P=0.08;IPTW:P=0.15].No differences were observed for CSS(P=0.12)and DFS(P=0.68)between the ACT and non-ACT groups.Multivariate analysis showed no association of ACT with better survival,while sublobar resection(HR=0.45;95%CI:0.20-1.00,P=0.049)and longer disease-free interval(HR=0.45;95%CI:0.20-0.98,P=0.044)were associated with improved survival.CONCLUSION ACT does not improve survival after PM resection for CRC.Further well-designed randomized controlled trials are needed to determine the optimal ACT regimen and duration.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Pharmacological adjuvants for diabetic vitrectomy surgery

Diabetic vitrectomy is a highly intricate surgical procedure performed during the advanced stages of diabetic retinopathy(DR).It is used to treat conditions such as tractional or combined retinal detachment,vitreous hemorrhage,and subhyaloid hemorrhage,which are all severe manifestations of proliferative DR.The results of the surgery are uncertain and variable.Vitreoretinal surgery has made significant progress since the early stages of vitrectomy.In the past ten years,advancements in intravitreal pharmacotherapy have emerged,offering new possibilities to improve the surgical results for our patients.Within the realm of medical terminology,an"adjunct"refers to a pharmaceutical or substance employed to aid or expedite the primary therapeutic intervention for a particular ailment.Their introduction has broadened the range of therapeutic choices that are accessible prior to,during,and following surgical procedures.This review article will specifically analyze the pharmacological adjuncts used in diabetic vitrectomy surgery,with a focus on their role in facilitating or aiding specific steps of the procedure.The implementation of this system of categorization offers benefits to the surgeon by allowing them to foresee potential difficulties that may occur during the surgical procedure and to choose the appropriate pharmacological agent to effectively tackle these challenges,thus enhancing surgical success rates.

Current Status and Research Progress of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Gastric cancer is one of the most common malignant tumours worldwide, with a high degree of malignancy and a poor prognosis. While early gastric cancer can be cured by surgical treatment, locally advanced gastric cancer requires neoadjuvant therapy to shrink the tumour, suppress potential metastases, achieve down-staging, and provide patients with the opportunity for radical surgery to prolong their survival. This article reviews the current status and progress of neoadjuvant chemotherapy for locally advanced gastric cancer.

Adjuvant therapy for orbital non-rhabdomyosarcoma soft tissue sarcoma:comparison of long-term outcome between radiotherapy and chemotherapy

AIM:To illustrate clinicopathological features of orbital non-rhabdomyosarcoma soft tissue sarcoma(NRSTS),and to compare the treatment outcome between postoperative radiotherapy(RT) and chemotherapy in a retrospective analysis nearly 20y.METHODS:A retrospective cohort study of 56 patients with orbital NRSTS were reviewed,34 of whom received postoperative RT,and 22 received postoperative chemotherapy.The clinicopathological features,local recurrence,metastases,and survival data were recorded.Survival analysis was performed using the Kaplan-Meier method.RESULTS:During follow-up(111.8mo,ranged 8-233mo) for 56 patients,19 patients of them developed local recurrence,and 7 patients developed distant metastases.Fifteen patients died during follow-up period.Overall survival rates considering the whole study group was 78.57% at 5y,and 72.16% at 10y after the initial diagnosis.Compared with chemotherapy,RT was associated with lower risk of local recurrence [hazard ratio for RT vs chemotherapy,0.263,95% confidence interval(CI),0.095-0.728,P=0.0015];with lower risk of distant metastasis(hazard ratio for RT vs chemotherapy,0.073,95%CI,0.015-0.364,P=0.0014);and with lower risk of death from disease(hazard ratio for RT vs chemotherapy,0.066,95%CI,0.022-0.200,P<0.0001).The 5-year survival rate in RT group was 97.06% compared to 50% in chemotherapy group.CONCLUSION:In patients with orbital NRSTS,postoperative RT provides better control of local recurrence,distant metastasis,and death from disease than chemotherapy.RT is the more preferrable adjuvant therapy compared to chemotherapy possibly.

Effect of postoperative adjuvant chemotherapyon the prognosis of patients with ypT0-3N0 rectalcancer undergoing neoadjuvant chemoradiotherapy

Objective The aim of this study was to investigate the effect of adjuvant chemotherapy (AC) on theprognosis of patients with ypT0-3N0 rectal cancer undergoing neoadjuvant chemoradiotherapy.Methods The study participants were 110 patients with locally advanced rectal cancer. Thirty-fourpatients did not receive postoperative AC treatment, and the other 76 patients received postoperative ACtreatment. The differences in the 5-year overall survival (OS) and disease-free survival (DFS) between thetwo groups were compared.Results Age was an important determinant of the patients’ decision to undergo postoperative treatment.Patients who did not receive AC treatment were significantly older than those who received AC treatment(P < 0.05). The tumor location (distance above anal margin) in the AC group was significantly larger thanthat in the non-AC group (P < 0.05). Moreover, there was no significant difference in the 5-year DFS andOS between the two groups. Postoperative AC did not significantly improve the prognosis of patients withrectal cancer. Age, tumor differentiation, and the number of resected lymph nodes were independent factorsaffecting the OS of patients (P < 0.05). Older patients, patients with lower degree of tumor differentiation,and patients with <12 resected lymph nodes showed worse prognosis (P < 0.05).Conclusion Patients with rectal cancer whose ypT0-3N0 stage is reduced after neoadjuvantchemoradiotherapy, especially those without adverse prognostic factors, do not need AC after surgery.

Intrathecal liproxstatin-1 delivery inhibits ferroptosis and attenuates mechanical and thermal hypersensitivities in rats with complete Freund's adjuvant-induced inflammatory pain

Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model.However,the role of fe rroptosis in inflammatory pain remains inconclusive.Therefore,we aimed to explore whether ferroptosis in the spinal cord and do rsal root ganglion contributes to complete Freund's adjuvant(CFA)-induced painful behaviors in rats.Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats.These changes included iron overload,enhanced lipid peroxidation,disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels,and abnormal morphological changes in mitochondria.Intrathecal treatment of liproxstatin-1(a ferroptosis inhibitor)reve rsed these ferroptosis-related changes and alleviated mechanical and thermal hype rsensitivities in CFA rats.Our study demonstrated the occurrence of fe rroptosis in the spinal cord and do rsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of fe rroptosis inhibitors,such as liproxstatin-1,is a potential therapeutic strategy for treating inflammatory pain.

The effect of adjuvant transarterial chemoembolization for hepatocellular carcinoma after liver resection based on risk stratification

Background:There is currently no standard adjuvant treatment proven to prevent hepatocellular carcinoma(HCC)recurrence.Recent studies suggest that postoperative adjuvant transarterial chemoembolization(PA-TACE)is beneficial for patients at high risk of tumor recurrence.However,it is difficult to select the patients.The present study aimed to develop an easy-to-use score to identify these patients.Methods:A total of 4530 patients undergoing liver resection were recruited.Independent risk factors were identified by Cox regression model in the training cohort and the Primary liver cancer big data transarterial chemoembolization(PDTE)scoring system was established.Results:The scoring system was composed of ten risk factors including alpha-fetoprotein(AFP),albuminbilirubin(ALBI)grade,operative bleeding loss,resection margin,tumor capsular,satellite nodules,tumor size and number,and microvascular and macrovascular invasion.Using 5 points as risk stratification,the patients with PA-TACE had higher recurrence-free survival(RFS)compared with non-TACE in>5 points group(P<0.001),whereas PA-TACE patients had lower RFS compared with non-TACE in≤5 points group(P=0.013).In the training and validation cohorts,the C-indexes of PDTE scoring system were 0.714[standard errors(SE)=0.010]and 0.716(SE=0.018),respectively.Conclusions:The model is a simple tool to identify PA-TACE for HCC patients after liver resection with a favorable performance.Patients with>5 points may benefit from PA-TACE.

Postoperative adjuvant therapy for hepatocellular carcinoma with microvascular invasion

Hepatocellular carcinoma(HCC)is one of the most lethal tumors in the world.Liver resection(LR)and liver transplantation(LT)are widely considered as radical treatments for early HCC.However,the recurrence rates after curative treatment are still high and overall survival is unsatisfactory.Microvascular invasion(MVI)is considered to be one of the important prognostic factors affecting postoperative recurrence and long-term survival.Unfortunately,whether HCC patients with MVI should receive postoperative adjuvant therapy remains unknown.In this review,we summarize the therapeutic effects of transcatheter arterial chemoembolization,hepatic arterial infusion chemotherapy,tyrosine protein kinase inhibitor-based targeted therapy,and immune checkpoint inhibitors in patients with MVI after LR or LT,aiming to provide a reference for the best adjuvant treatment strategy for HCC patients with MVI after LT or LR.

Anti-inflammatory effects of Solanum procumbens on a low dose complete Freund's adjuvant-induced arthritis rat model

Objective:To investigate the anti-inflammatory and analgesic effects of Solanum procumbens on complete Freund’s adjuvantinduced arthritis rat models.Methods:We isolated and identified five compounds in the ethanolsoluble Solanum procumbens extract(SP)with anti-inflammatory effects,including ursolic acid,β-sitosterol,hexadecanoic acid,cisvaccenic acid,and vanillic acid.Additionally,we investigated the anti-inflammatory effects of SP on rheumatoid arthritis symptoms,including paw volumes,local temperatures,withdrawal latency,and mechanical withdrawal threshold at the hind paw and white blood cell(WBC)number from complete Freund’s adjuvant-induced arthritis rat models.Results:We have successfully established a complete Freund’s adjuvant-induced arthritis rat model at a low dose(1 mg/mL).SP extract significantly reduced paw volumes(P<0.05),prolonged withdrawal latencies(P<0.05),decreased local temperature,and increased the mechanical withdrawal threshold(P<0.05),but only SP extract at the dose of 300 mg/kg significantly decreased WBC numbers.Conclusions:SP extract could be a potential medication candidate with anti-inflammatory effects for arthritis,but it requires further investigation into the mechanism of the SP and its effectiveness on other models as well as clinical trials.

Adjuvant therapy for hormone receptor-positive breast cancer: Perspective from a survey on breast cancer physicians' acceptance of practice-changing data

A cross-sectional online survey was conducted.A high proportion of the Chinese breast cancer(BC)physician respondents(n=77)would prescribe extended adjuvant endocrine therapy(AET)with aromatase inhibitors(AI)beyond 5 years for postmenopausal females with BC,especially those with higher risk.Respondents with≥15 years of clinical experience were more likely to prescribe a longer duration of AET for low-risk patients.Half of the respondents considered intermittent letrozole as an acceptable option.Most respondents would prescribe adjuvant chemotherapy to genomic high-intermediate risk[Oncotype DX recurrence score(RS)21-25]females aged≤50 years regardless of the clinical risk classification.

Efficacy and safety of anlotinib as an adjuvant therapy in hepatocellular carcinoma patients with a high risk of postoperative recurrence

Objective:Hepatocellular carcinoma(HCC)has a high rate of postoperative recurrence and lacks an effective treatment to prevent recurrence.This study aims to investigate the efficacy and safety of anlotinib in postoperative adjuvant therapy for HCC patients with high-risk recurrence factors.Methods:For this multicenter,retrospective study,we recruited 63 HCC patients who received either anlotinib(n=27)or transcatheter arterial chemoembolization(TACE)(n=36)from six research centers in China between March 2019 and October 2020.The primary endpoint was disease-free survival(DFS)and the secondary endpoints were overall survival(OS)and safety.Results:In this study,the median follow-up time was 25.9 and 26.8 months in the anlotinib and TACE groups,respectively.There was no significant difference in the median DFS between the anlotinib[26.8 months,95%confidence interval(95%CI):6.8-NE]and TACE groups(20.6 months,95%CI:8.4-NE).The 12-month OS rates in the anlotinib and TACE groups were 96.3%and 97.2%,respectively.In the anlotinib group,19 of 27patients(70.4%)experienced treatment-emergent adverse events,with the most common events(≥10%)being hypertension(22.2%)and decreased platelet count(22.2%).Conclusions:The results indicate that anlotinib,as a new,orally administered tyrosine kinase inhibitor,has the same efficacy as TACE,and side effects can be well controlled.

Azoximer bromide and hydroxyapatite:promising immune adjuvants in cancer

Immune adjuvants are immune modulators that have been developed in the context of infectious vaccinations.There is currently a growing interest in immune adjuvants due to the development of immunotherapy against cancers.Immune adjuvant mechanisms of action are focused on the initiation and amplification of the inflammatory response leading to the innate immune response,followed by the adaptive immune response.The main activity lies in the support of antigen presentation and the maturation and functions of dendritic cells.Most immune adjuvants are associated with a vaccine or incorporated into the new generation of m RNA vaccines.Few immune adjuvants are used as drugs.Hydroxyapatite(HA)ceramics and azoximer bromide(AZB)are overlooked molecules that were used in early clinical trials,which demonstrated clinical efficacy and excellent tolerance profiles.HA combined in an autologous vaccine was previously developed in the veterinary field for use in canine spontaneous lymphomas.AZB,an original immune modulator derived from a class of heterochain aliphatic polyamines that is licensed in Russia,the Commonwealth of Independent States,and Slovakia for infectious and inflammatory diseases,is and now being developed for use in cancer with promising results.These two immune adjuvants can be combined in various immunotherapy strategies.

Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma

BACKGROUND Owing to rarity of disease and lack of prospective studies, data supporting the role of adjuvant chemotherapy in ampulla of Vater(AoV) carcinoma is limited.AIM To evaluate whether adjuvant chemotherapy cases for AoV carcinoma had better disease-free survival(DFS) rates than cases of observation following curative surgery.METHODS We retrospectively analyzed the association between adjuvant chemotherapy and DFS and overall survival(OS) in patients with stage IB-Ⅲ AoV carcinoma who underwent curative surgical resection. Fluorouracil-based adjuvant chemotherapy was administered after surgery at the discretion of the physician. Adjusted multivariate regression models were used to evaluate the association between adjuvant chemotherapy and survival outcomes.RESULTS Of the total 104 patients who underwent curative surgery, 52 received adjuvant chemotherapy. Multivariate analysis revealed that higher histologic grade [hazard ratio(HR) = 2.24, P = 0.046], advanced tumor stage(HR = 1.85, P = 0.030), and vascular invasion(HR = 2.14, P = 0.010) were associated with shorter DFS. Adjuvant chemotherapy improved DFS compared to the observation group(HR =0.50, P = 0.015) and tended to be associated with a longer OS, although the difference was not statistically significant(HR = 0.58, P = 0.098).CONCLUSION Among patients with resected AoV carcinoma, the adjuvant chemotherapy group was not associated with a significant survival benefit compared to the observation group. However, on multivariate analysis adjusting for prognostic factors, adjuvant chemotherapy following surgery was an independent prognostic factor for DFS in patients with resected AoV carcinoma. Further studies are needed to investigate the effectiveness of adjuvant chemotherapy according to histologic phenotype.