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.

Nonoperative management of gastrointestinal malignancies in era of neoadjuvant treatment

Cancers derived from the gastrointestinal(GI)tract are often treated with radical surgery to achieve a cure.However,recent advances in the management of GI cancers involve the use of a combination of neoadjuvant radiation and chemotherapy followed by surgical intervention to achieve improved local control and cure.Interestingly,a small proportion of patients with highly sensitive tumors achieved a pathological complete response(pCR)(no residual tumor cells in the resected specimen)to neoadjuvant chemoradiation therapy(nCRT).The desire for organ preservation and avoidance of surgical morbidity brings the idea of a nonoperative management(NOM)strategy.Because of the different nature of tumor biology,GI cancers present diverse responses to nCRT,ranging from high sensitivity(anal cancer)to low sensitivity(gastric/esophageal cancer).There is an increasing attention to NOM of localized GI cancers;however,without the use of biomarkers/imaging parameters to select such patients,NOM will remain a challenge.Therefore,this review intends to summarize some of the recent updates from the aspect of current nCRT regimens,criteria for patient selection and active surveillance schedules.We also hope to review significant sequelae of radical surgery and the complications of nCRT to clarify the directions for optimization of nCRT and NOM for oncologic outcomes and quality of life.

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.

Neoadjuvant treatment:A window of opportunity for nutritional prehabilitation in patients with pancreatic ductal adenocarcinoma

Patients affected by pancreatic ductal adenocarcinoma(PDAC)frequently present with advanced disease at the time of diagnosis,limiting an upfront surgical approach.Neoadjuvant treatment(NAT)has become the standard of care to downstage non-metastatic locally advanced PDAC.However,this treatment increases the risk of a nutritional status decline,which in turn,may impact therapeutic tolerance,postoperative outcomes,or even prevent the possibility of surgery.Literature on prehabilitation programs on surgical PDAC patients show a reduction of postoperative complications,length of hospital stay,and readmission rate,while data on prehabilitation in NAT patients are scarce and randomized controlled trials are still missing.Particularly,appropriate nutritional management represents an important therapeutic strategy to promote tissue healing and to enhance patient recovery after surgical trauma.In this regard,NAT may represent a new interesting window of opportunity to implement a nutritional prehabilitation program,aiming to increase the PDAC patient’s capacity to complete the planned therapy and potentially improve clinical and survival outcomes.Given these perspectives,this review attempts to provide an in-depth view of the nutritional derangements during NAT and nutritional prehabilitation program as well as their impact on PDAC patient outcomes.

Loss of human epidermal receptor-2 in human epidermal receptor-2+breast cancer after neoadjuvant treatment:A case report

BACKGROUND Human epidermal receptor-2(HER-2)expression has been reported to be discordant between primary tumor and metastatic tissue.CASE SUMMARY We presented a case diagnosed with the HER-2+breast cancer patient who exhibited changes in the expression of HER-2 receptors on tumour samples from surgical specimens obtained after neoadjuvant treatment(NAT)compared with initial biopsy.The patient underwent a HER-2-targeted therapy consequently,in spite of HER+gene loss.After the surgery,the patient subsequently underwent endocrine therapy and radiotherapy.CONCLUSION Changes in HER-2 expression after NAT should be retested by physicians and pathologists before systemic treatment instead of avoiding further HER-2-targeted therapy,and we will perform immunohistochemical multiple-spot biopsy analyses of other important clinical issues to better define prognosis and tailor subsequent adjuvant therapy.

Neoadjuvant Treatment for Esophageal Cancer

Because the con?icting data currently available from the performed randomized trials it is very di?cult to provide strict guidelines for the treatment of patients with locoregional advanced esophageal cancers. Surgery however, remains the standard of care for potentially resectable disease. Preoperative chemotherapy is still controversial with two large randomized trials resulting in two di?erent conclusions regarding the survival bene?t. Preoperative chemoradiation is also controversial since only one randomized trial showed a clear survival bene?t however, the patients treated with surgery alone in this trial had an unusually poor outcome. And the study by Urba et al was not powered enough to show a clear survival bene?t for patients treated with neoadjuvant chemoradiation. The results of three metaanalysis of these randomized studies show lower rate of resection, higher rate of R0-resection, more often postoperative mortality and better prognosis for patients with neoadjuvant radiochemotherapy. As a consequence one may consider o?ering neoadjuvant chemotherapy or neoadjuvant radiochemotherapy to patients with locally- advanced disease under the premise that patients have a good performance status and understand the controversies about this therapeutic option. Larger trials with su?cient power to clearly detect survival bene?ts for patients treated with neoadjuvant chemotherapy or radiochemotherapy are necessary before this therapeutic option will be the standard of care.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Implications of recent neoadjuvant clinical trials on the future practice of radiotherapy in locally advanced rectal cancer

Over the last two decades, the standard treatment for locally advanced rectal cancer(LARC) has been neoadjuvant chemoradiotherapy plus total mesorectal excision followed by adjuvant chemotherapy. Total neoadjuvant treatment(TNT) and immunotherapy are two major issues in the treatment of LARC. In the two latest phase Ⅲ randomized controlled trials(RAPIDO and PRODIGE23), the TNT approach achieved higher rates of pathologic complete response and distant metastasis-free survival than conventional chemoradiotherapy. Phase I/II clinical trials have reported promising response rates to neoadjuvant(chemo)-radiotherapy combined with immunotherapy. Accordingly, the treatment paradigm for LARC is shifting toward methods that increase the oncologic outcomes and organ preservation rate. However, despite the progress of these combined modality treatment strategies for LARC, the radiotherapy details in clinical trials have not changed significantly. To guide future radiotherapy for LARC with clinical and radiobiological evidence, this study reviewed recent neoadjuvant clinical trials evaluating TNT and immunotherapy from a radiation oncologist’s perspective.

Neoadjuvant treatment of pancreatic ductal adenocarcinoma:present and future

Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with a poor prognosis.Effective treatment with acceptable outcomes is yet to be found,with chemo-and radioresistance comprising major impediments towards this goal.Although upfront surgery is the established therapeutic approach for resectable and borderline resectable disease,neoadjuvant treatment has recently monopolized the interest in clinical trials.This also applies to locally advanced pancreatic adenocarcinomas that could potentially be rendered operable.Chemotherapy and chemoradiotherapy are the most utilized therapeutic modalities in the neoadjuvant setting,while immunotherapy and targeting agents have been gaining significant attention.This critical review focuses on the clinical experience gained from retrospective and phase II/III randomized trials,reporting on the outcomes of neoadjuvant chemotherapy and chemoradiotherapy for pancreatic adenocarcinoma.Moreover,the ongoing trials,including those that involve immunotherapy and targeting agents,are summarized.

Predictive value of Ki67 and p53 in locally advanced rectal cancer:Correlation with thymidylate synthase and histopathological tumor regression after neoadjuvant 5-FU-based chemoradiotherapy

AIM: To investigate the predictive value of Ki67 and p53 and their correlation with thymidylate synthase (TS) gene expression in a rectal cancer patient cohort treated according to a standardized recommended neoadjuvant treatment regimen.METHODS: Formalin fixed, paraffin embedded pre-therapeutical tumor biopsies (n = 22) and post-therapeutical resection specimens (n = 40) from patients with rectal adenocarcinoma (clinical UICC stage Ⅱ/Ⅲ) receiving standardized neoadjuvant 5-fluorouracil (5-FU) based chemoradiotherapy were studied for Ki67 and p53 expression by immunohistochemistry and correlated with TS mRNA expression by quantitative TaqMan real-time PCR after laser microdissection. The results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system.RESULTS: Responders (patients with high tumor regression) showed a significantly lower Ki67 expression than non-responders in the pre-therapeutical tumor biopsies (81.2% vs 16.7%; P < 0.05) as well as in the post-therapeutical resection specimens (75.8% vs 14.3%; P < 0.01). High TS mRNA expression was significantly correlated with a high Ki67 index and low TS mRNA expression was significantly correlated with a low Ki67 index in the pre-therapeutical tumor biopsies (corr. coef. = 0.46; P < 0.01) as well as in the post-therapeutical resection specimens (corr. coef. = 0.40; P < 0.05). No significant association was found between p53 and TS mRNA expression or tumor regression.CONCLUSION: Ki67 has, like TS, predictive value in rectal cancer patients after neoadjuvant 5-FU based chemoradiotherapy. The close correlation between Ki67 and TS indicates that TS is involved in active cell cycle processes.

Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review

Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently available neoadjuvant protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or short-course RT, together with improved surgical techniques, have largely reduced the risk of local relapse, with limited impact on distant recurrence. Available results of phase III trials with additional cytotoxic agents combined with standard CT-RT are disappointing, as no significant reduction in the risk of recurrence has been demonstrated. In order to improve the control of micrometastatic disease, integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach. In particular, the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models, and thus may represent a suitable companion in the neoadjuvant treatment of LARC. Preliminary results of phase&#x02005;I-II clinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection: treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules.

Individualized treatment of breast cancer with chronic renal failure: A case report and review of literature

BACKGROUND Studies have shown that patients with chronic renal failure(CRF)are more likely to suffer from breast cancer and other malignant tumors.To our knowledge,CRF can reduce drug excretion,thereby increase drug exposure and lead to increased toxicity,which will limit drug treatment and lead to tumor progression.Currently,there are few successful reports on the combination of docetaxel,trastuzumab,and pertuzumab(THP)as a neoadjuvant treatment regimen for breast cancer patients with CRF.CASE SUMMARY We report a breast cancer(cT2N2M0,Her-2+/HR-)patient with CRF.It was a clinical stage IIIA tumor on the left breast.The patient had suffered from uremia for 2 years,and her heart function was normal.Based on the pathological type,molecular type,and clinical stage of breast cancer,and the patient’s renal function,the clinician analyzed the pharmacological and pharmacokinetic characteristics of the antitumor drugs after consulting the relevant literature,and prescribed the neoadjuvant regimen of THP(docetaxel 80 mg/m²,trastuzumab 8 mg/kg for the first dose,and 6 mg/kg for the maintenance dose with pertuzumab 840 mg for the first dose and 420 mg for the maintenance dose),once every 3 wk,for a total of 6 courses.The neoadjuvant treatment had a good effect,and the patient then underwent surgery which was uneventful.CONCLUSION CRF is not a contraindication for systemic treatment and surgery of breast cancer.The THP regimen without dose adjustment may be a safe and effective neoadjuvant treatment for HER-2 positive breast cancer patients with CRF.

Characterizing gastrointestinal stromal tumors and evaluating neoadjuvant imatinib by sequencing of endoscopic ultrasound-biopsies

AIM To evaluate endoscopic ultrasound(EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors(GIST) to personalize the management of patients.METHODS All patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase(2006-2011), routine fine-needle-aspiration(EUS-FNA) was performed.In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS-FNA and fine-needle-biopsy-sampling(EUS-FNB) for all lesions. c-KIT-and DOG-1-immunostaining was attempted in all samples and a manual count of the Ki-67-index was performed. FNB-sampled tissue and the resected specimens were subjected to Sanger sequencing of the KIT and platelet-derived growth factor alpha(PDGFRA) genes. RESULTS In all, 64 unique patients with GIST were included, and of these, 38 were subjected to pretreatment dual sampling. EUS-FNB had a higher diagnostic sensitivity when compared head-to-head with EUS-FNA(98% vs 58%, P < 0.001) and was more adequate for Ki-67-indexing(Ki-67EUS)(92% vs 40%, P < 0.001). Sequencing of EUS-biopsies was successful in 43/44(98%) patients, and the mutation profiles(KIT-mutation 73%, PDGFRA-mutation 18%, wild-type 7%) were fully congruent with those detected in the corresponding resected specimens. In imatinib-na?ve patients, the Ki-67_(EUS) was comparable with the Ki-67-index in the corresponding surgical specimens(Ki-67_(SURG))(2.7% vs 2.9%, P = 0.68). In patients treated with neoadjuvant imatinib who also carried mutations indicating sensitivity, the Ki-67 EUS was higher than the Ki-67_(SURG)(2.5% vs 0.2%, P = 0.005), with a significant reduction in the Ki-67-index of-91.5%(95%CI:-82.4 to-96.0, P = 0.005). CONCLUSION EUS-guided biopsy sampling is accurate for the pretreatment diagnosis and characterization of GISTs and allows the prediction and evaluation of tumor response to neoadjuvant imatinib therapy.

Relation between skeletal muscle volume and prognosis in rectal cancer patients undergoing neoadjuvant therapy

The prognostic role of body composition indexes,and specifically sarcopenia,has recently been explored in different cancer types.However,conflicting results have been reported.Heterogeneity in cancer type,cancer stage or oncological treatments,as well as different methodology and definition of sarcopenia,could be accounted for different conclusions retrieved from literature.When focusing on colorectal cancer,it clearly appears that colon and rectal cancers are often treated as a single entity though they have different behaviors and treatments.Particularly,patients with advanced rectal cancer represent a peculiar group of patients that according to current guidelines are treated with neoadjuvant chemotherapy and radiotherapy followed by radical surgery.This review was restricted to a homogeneous group of patients with advanced lower rectal cancer and the aim of exploring whether there is a correlation between skeletal muscle depletion and prognosis.Literature was searched for articles related to patients with advanced rectal cancer undergoing neoadjuvant chemo-radiotherapy(NCRT)followed by radical surgery,in whom muscle mass and/or change in muscle mass during neoadjuvant treatment were measured.Eight full-text articles were selected and included in the present review.The main findings of our review were:(1)The majority of the studies defined sarcopenia as muscle mass alone over muscle strength or physical performance;(2)There was a great deal of heterogeneity in the definition and measures of sarcopenia,in the definition of cut-off values,and in the method to measure change in muscle mass;(3)There was not full agreement on the association between sarcopenia at baseline and/or after chemoradiotherapy and prognosis,and only few studies found a significance in the multivariate analysis;and(4)It seems that a loss in skeletal muscle mass during NCRT is associated with the worst outcomes in terms of disease-free survival.In conclusion,analysis of muscle mass might provide prognostic information on patients with rectal cancer,however more robust evidence is needed to define the role of muscle depletion and/or muscle change during neoadjuvant treatments,related to this specific group of patients.If a prognostic role would be confirmed by future studies,the role of preoperative intervention aimed at modifying muscle mass could be explored in order to improve outcomes.

Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations

BACKGROUND Neoadjuvant treatment(NT)with chemotherapy(Ch)is a standard option for resectable stage III(N2)NSCLC.Several studies have suggested benefits with the addition of radiotherapy(RT)to NT Ch.The International Association for the Study of Lung Cancer(IASLC)published recommendations for the pathological response(PHR)of NSCLC resection specimens after NT.AIM To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy(ChRT).METHODS We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020.After NT,all patients were evaluated for radiological response(RR)according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons.All histological samples were examined by the same two pathologists.PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes.RESULTS Forty patients underwent NT ChRT and 27 NT Ch.Fifty-six(83.6%)patients underwent surgery(35 ChRT and 21 Ch).The median time from ChRT to surgery was 6 wk(3-19)and 8 wk(3-21)for Ch patients.We observed significant differences in RR,with disease progression in 2.5%and 14.8%of patients with ChRT and Ch,respectively,and partial response in 62.5%ChRT vs 29.6%Ch(P=0.025).In PHR we observed≤10%viable cells in the tumor in 19(54.4%)and 2 cases(9.5%),and in the resected lymph nodes(RLN)30(85.7%)and 7(33.3%)in ChRT and Ch,respectively(P=0.001).Downstaging was greater in the ChRT compared to the Ch group(80%vs 33.3%;P=0.002).In the univariate analysis,NT ChRT had a significant impact on partial RR[odds ratio(OR)12.5;95%confidence interval(CI):1.21-128.61;P=0.034],a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5%increased probability for achieving downstaging(OR 8;95%CI:2.34-27.32;P=0.001).CONCLUSION We found significant benefits in RR and PHR by adding RT to Ch as NT.A longer follow-up is necessary to assess the impact on clinical outcomes.

Development of preoperative prognostic models including radiological features for survival of singular nodular HCC patients

Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical practice.However,almost half of the patients have tumor recurrence,and there is no reliable prognostic prediction tool.Besides,it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it.It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus,to improve the outcomes of these patients.The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival(RFS)and overall survival(OS)in patients with singular nodular HCC by integrating the clinical data and radiological features.Methods:We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital(EHBH).They all met the surgical indications and underwent radical resection.We randomly divided the patients into the training cohort(n=132)and the validation cohort(n=79).We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS.By analyzing the receiver operating characteristic(ROC)curve,the discrimination accuracy of the models was compared with that of the traditional predictive models.Results:Our RFS model was based on HBV-DNA score,cirrhosis,tumor diameter and tumor capsule in imaging.RFS nomogram had fine calibration and discrimination capabilities,with a C-index of 0.74(95%CI:0.68-0.80).The OS nomogram,based on cirrhosis,tumor diameter and tumor capsule in imaging,had fine calibration and discrimination capabilities,with a C-index of 0.81(95%CI:0.74-0.87).The area under the receiver operating characteristic curve(AUC)of our model was larger than that of traditional liver cancer staging system,Korea model and Nomograms in Hepatectomy Patients with Hepatitis B VirusRelated Hepatocellular Carcinoma,indicating better discrimination capability.According to the models,we fitted the linear prediction equations.These results were validated in the validation cohort.Conclusions:Compared with previous radiography model,the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC.Our models may preoperatively identify patients with high risk of recurrence.These patients may benefit from neoadjuvant therapy which may improve the patients’outcomes.

Contemporary management of locally advanced rectal cancer:Resolving issues, controversies and shifting paradigms

Advancements in rectal cancer treatment have resulted in improvement only in locoregional control and have failed to address distant relapse, which is the predominant mode of treatment failure in rectal cancer. As the efficacy of conventional chemoradiotherapy（CRT） followed by total mesorectal excision（TME） reaches a plateau, the need for alternative strategies in locally advanced rectal cancer（LARC） has grown in relevance. Several novel strategies have been conceptualized to address this issue, including： 1） neoadjuvant induction and consolidation chemotherapy before CRT; 2） neoadjuvant chemotherapy alone to avoid the sequelae of radiation; and 3） nonoperative management for patients who achieved pathological or clinical complete response after CRT. This article explores the issues, recent advances and paradigm shifts in the management of LARC and emphasizes the need for a personalized treatment plan for each patient based on tumor stage, location, gene expression and quality of life.

New standard in locally advanced rectal cancer

In the following review we intend to ascertain the optimal neoadjuvant therapy inpatients with locally advanced rectal cancer. In 2004, a study revealed thatchemoradiotherapy (CRT) resulted in better local control when performedpreoperatively rather than postoperatively, thus neoadjuvant treatment wasestablished as a standard treatment. Subsequently, the Polish study and the Trans-Tasman Radiation Oncology Group showed no statistically significant differencebetween concomitant CRT over 5 wk vs short-course radiotherapy (RT).Therefore, both were established as standard neoadjuvant treatments. Later, theStockholm III study demonstrated that short-course RT had a higher completepathological response than long-course RT. It also showed that a delay betweenRT and surgery presented fewer complications. This opened a window of time toprovide an early and effective systemic treatment to prevent distant metastases.Studies show that short-course RT plus oxaliplatin-based chemotherapy couldachieve this. When comparing this total neoadjuvant treatment (TNT) vsconcomitant CRT, the former showed greater complete pathological response andlower acute toxicity. Studies presented during 2020 have also shown the benefitsof TNT in terms of complete pathological response, as well as disease andmetastasis-free survival. Our review suggests that probably TNT should be thenew standard treatment for these patients. However, we will have to wait for thefull text publications of these studies to confirm this statement.

Borderline resectable pancreatic cancer:Certainties and controversies

Borderline resectable(BR)pancreatic ductal adenocarcinoma(PDAC)is currently a well-recognized entity,characterized by some specific anatomic,biological and conditional features:It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones.The term BR identifies a tumour with an aggressive biological behaviour,on which a neoadjuvant approach instead of an upfront surgery one should be preferred,in order to obtain a radical resection(R0)and to avoid an early recurrence after surgery.Even if during the last decades several studies on this topic have been published,some aspects of BR-PDAC still represent a matter of debate.The aim of this review is to critically analyse the available literature on this topic,particularly focusing on:The problem of the heterogeneity of definition of BR-PDAC adopted,leading to a misinterpretation of published data;its current management(neoadjuvant vs upfront surgery);which neoadjuvant regimen should be preferably adopted;the problem of radiological restaging and the determination of resectability after neoadjuvant therapy;the post-operative outcomes after surgery;and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.

Cancer nanomedicine in preoperative therapeutics:Nanotechnology-enabled neoadjuvant chemotherapy,radiotherapy,immunotherapy,and phototherapy

Surgical resection remains a mainstay in the treatment of malignant solid tumors.However,the use of neoadjuvant treatments,including chemotherapy,radiotherapy,phototherapy,and immunotherapy,either alone or in combination,as a preoperative intervention regimen,have attracted increasing attention in the last decade.Early randomized,controlled trials in some tumor settings have not shown a significant difference between the survival rates in long-term neoadjuvant therapy and adjuvant therapy.However,this has not hampered the increasing use of neoadjuvant treatments in clinical practice,due to its evident downstaging of primary tumors to delineate the surgical margin,tailoring systemic therapy response as a clinical tool to optimize subsequent therapeutic regimens,and decreasing the need for surgery,with its potential for increased morbidity.The recent expansion of nanotechnology-based nanomedicine and related medical technologies provides a new approach to address the current challenges of neoadjuvant therapy for preoperative therapeutics.This review not only summarizes how nanomedicine plays an important role in a range of neoadjuvant therapeutic modalities,but also highlights the potential use of nanomedicine as neoadjuvant therapy in preclinical and clinic settings for tumor management.