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.

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.

The Current Adjuvant Therapies for the Glioblastoma multiforme: Chemotherapy, Targeted Molecular Therapy and Immunogene Therapy

Glioblastoma multiforme (GBM) is by far the most common type of primary brain tumors and regarded as grade IV tumors by WHO classification. Although the treatment strategies including maximal surgical resection, concurrent radiation and chemotherapy with temozolomide are current recommendations to patients with GBM, the prognosis is still poor and the median survival is less than 2 years. Major challenge for the successful treatment of GBM is the diversity of cell types and mutations in the tumor. These tumors are composed of highly heterogeneous cell populations that are often characterized by high chemo-resistance. Furthermore, because a variety of genes may be mutated or overexpressed in different areas of the tumors, no one treatment is likely to destroy the tumor. With advance in the molecular biology in the field of oncology, new critical signaling pathway involved in development and progression of GBM have been discovered, which leads to emergency of new treatment strategies to target these signaling pathways with the goal to increase specific efficacy. These targeted therapies hold the promise of providing new, more effective treatment options with minimal toxicity. In this review, we described current chemotherapeutic modalities for GBM and introduce the new targeted therapies in the context of current treatment options for patients with GBM. In addition, it is also addressed the issue of drug delivery as a factor limiting the efficacy of systemic administration of therapeutics and attempt to overcome this barrier. To improve outcomes of treatment for GBM, future investigation will focus on elucidating the novel molecular signaling pathways and oncogenic mechanisms underlying tumor resistance to treatment and tumor recurrence.

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.

The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma:a systematic review

BACKGROUND: Following curative treatment for hepatocellular carcinoma (HCC), 50%-90% of postoperative death is due to recurrent disease. Intra-hepatic recurrence is frequently the only site of recurrence. Thus, any neoadjuvant or adjuvant therapy, which can decrease or delay the incidence of intra-hepatic recurrence, or any cancer chemoprevention which can prevent a new HCC from developing in the liver remnant, will improve the results of liver resection. This article systematically reviewed the current evidence of neoadjuvant, adjuvant, and chemoprevention in partial hepatectomy of HCC. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed databases for articles from January 1990 to November 2008 using the keywords 'hepatocellular carcinoma', 'hepatectomy', 'adjuvant therapy', 'neoadjuvant therapy', and 'regional therapy'. Additional papers and book chapters were identified by a manual search of the references from the key articles. RESULTS: Neoadjuvant transarterial chemoembolization or adjuvant regional transarterial chemotherapy embolization+systemic chemotherapy did not add benefit. Both adjuvant transarterial radioembolization with (131)I-lipiodol and adjuvant systemic interferon showed promising results. However, there were only a limited number of such studies. CONCLUSIONS: Further randomized controlled studies need to be carried out. Currently, there is no consensus on a standard neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for HCC.

Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2(HER2)-positive early-stage breast cancer: A real-world retrospective study in Chinese patients

Objective: To assess the long-term effectiveness and safety of trastuzumab in adjuvant therapy for Chinese patients with early-stage human epidermal growth factor 2(HER2)-positive breast cancer in a real-world setting.Methods: This retrospective observational study analyzed the medical records of HER2-positive breast cancer patients between 2000 and 2012 at the Chinese Academy of Medical Sciences. Patients who received adjuvant chemotherapy alone or adjuvant chemotherapy followed by/combined with trastuzumab were included. The Kaplan-Meier method was used to estimate disease-free survival(DFS) and overall survival(OS). Hazard ratios(HR) and 95% confidence intervals(95% CI) were calculated using the Cox regression model.Results: Of the 1,348 patients analyzed, 909 received chemotherapy alone and 439 received chemotherapy plus trastuzumab. The 3-year, 5-year and 10-year DFS rates were 83.70%, 76.38% and 68.94%, respectively, in the chemotherapy-alone cohort, and 90.21%, 86.19% and 83.45% in the chemotherapy plus trastuzumab cohort. The3-year, 5-year and 10-year OS rates were 96.10%, 91.40% and 81.88% in the chemotherapy-alone cohort, and98.17%, 94.91% and 90.01% in the chemotherapy plus trastuzumab cohort. The chemotherapy plus trastuzumab group had a significantly lower risk of disease recurrence and death than the chemotherapy-alone group(DFS:HR=0.50, 95% CI, 0.37-0.68;P<0.001;OS: HR=0.53, 95% CI, 0.34-0.81;P=0.004) after adjusting for covariates.In the 439 patients treated with trastuzumab, multivariate analysis suggested that lymph node positivity, higher T stages, and hormone receptor-negative status were significantly associated with higher risks of disease recurrence,and lymph node positivity and hormone receptor-negative status were significantly associated with higher risks of death. Grade 3/4 adverse events(incidence ≥1%) were more common in patients receiving trastuzumab(54.44% vs.15.73%).Conclusions: Early-stage HER2-positive breast cancer patients treated with trastuzumab plus adjuvant chemotherapy have a significant survival benefit compared with chemotherapy-alone in real-world settings. Lymph node positivity, hormone receptor-negative status, and higher T stages may be associated with higher risks of recurrence, and effective therapy for patients with these factors is required.

Adjuvant Chemotherapy of Gemcitabine plus Carboplatin versus Paclitaxel plus Carboplatin in Patients with Resected Non-Small Cell Lung Cancer

Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29;PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%;PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%;PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%;PC: 13/15, 86.7%, p 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.

Comparison of 4-Weekly vs 3-Weekly Gemcitabine as Adjuvant Chemotherapy Following Curative Resection for Biliary Tract Cancer: A Prospective Randomized Controlled Trial

Background: Surgery for biliary tract cancer, including pancreatoduodenectomy and major hepatectomy, is too aggressive and does not allow postoperative gemcitabine to be administered by the usual dosage protocol. We hypothesized that the feasibility of 3-weekly protocol (days 1 and 8, every 3 weeks) of adjuvant gemcitabine therapy may be superior to the usual 4-weekly protocol (days 1, 8, and 15 every 4 weeks). Method: We compared the outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol in a prospective randomized setting. The primary endpoint was the completion rate, and the secondary endpoints were the adverse events and the recurrence-free survival rate. Results: Totally, 27 patients were enrolled. The protocol could be completed without any omittances and/or dose modifications in two patients (14%) of the 4-weekly protocol, and three patients (23%) of the 3-weekly protocol (p = 0.8099);grade 3/4 neutropenia occurred in almost all the remaining (70%) patients. The relative dose intensity was 72% in the 4-weekly protocol and 78% in the 3-weekly protocol. There was no significant difference in the recurrence-free survival rate. Conclusion: The 3-weekly protocol did not yield superior completion, adverse events or recurrence-free survival rates as compared to the 4-week protocol. Trial Registration: UMIN-CTR, UMIN000001020.

Impact of regular enteral feeding via jejunostomy during neo-adjuvant chemotherapy on body composition in patients with oesophageal cancer

BACKGROUND Malnourishment and sarcopenia are well documented phenomena in oesophageal cancer.Patients undergoing neo-adjuvant chemotherapy prior to oesophagectomy have complex nutritional needs.AIM To examine the effect of regular nutritional support via feeding jejunostomy on overall body composition in patients undergoing neo-adjuvant chemotherapy prior to oesophagectomy for oesophageal cancer.METHODS Retrospective data were collected for 15 patients before and after neo-adjuvant chemotherapy.All patients had feeding jejunostomies inserted at staging laparoscopy prior to neo-adjuvant chemotherapy and underwent regular jejunostomy feeding.Changes in body composition were determined by analysis of computed tomography imaging.RESULTS Patient age was 61.3±12.8 years,and 73%of patients were male.The time between start of chemotherapy and surgery was 107±21.6 d.There was no change in weight(74.5±14.1 kg to 74.8±13.1 kg)and body mass index(26.0±3.8 kg/m^2 to 26.1±3.4 kg/m^2).Body composition analysis revealed a statistically significant decrease in lumbar skeletal muscle index despite regular feeding(45.8±8.0 cm^2/m^2 to 43.5±7.3 cm^2/m^2;P=0.045).The proportion of sarcopenic patients increased(33.3% to 60%).Six patients(40%)experienced dose-limiting toxicity during chemotherapy.CONCLUSION Regular jejunostomy feeding during neo-adjuvant chemotherapy can maintain weight and adipose tissue.Feeding alone is not sufficient to maintain muscle mass.Further insight into the underlying processes causing reduced muscle mass in cancer patients may help to provide targeted interventions.

Value of neoadjuvant chemotherapy in advanced ovarian cancer

Data regarding the role of neoadjuvant chemotherapy(NACT) are not definitive. Several randomized trials and meta-analyses demonstrate that this chemotherapy regimen decreases the morbidity and mortality rates and increases complete cytoreduction rates. If combined with hyperthermic intraperitoneal chemotherapy(HIPEC), NACT could potentially further improve upon these already promising results. Moreover the use of NACT could help in evaluating the chemo-sensitivity of the cancer, thus preventing unnecessary HIPEC procedures in chemo-resistant patients. NACT should definitely be considered as a preferred regimen in the management of advanced ovarian cancer, especially in association with cytoreductive surgery + HIPEC procedure in the context of a multidisciplinary team management in an experienced cancer centre.

Prognostic evaluation of postoperative adjuvant therapy for operable cervical cancer:10 years'experience of National Cancer Center in China

Objective： The aim of this study was to investigate the prognostic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. Methods： The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics （FIGO） Ib-[Ia cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The median follow-up was 70 months. Results： Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival （DFS） of 92.1% and 5-year overall survival （OS） of 95.0%. In multivariate analysis, differentiation of G3 （P〈0.05）, lymph node metastasis （LNM, P〈0.05） and lymphovascular space invasion （LVSI, P〈0.05） were independent predictors for OS, while LNM （P〈0.05）, deep stroma invasion （DSI, P〈0.05） and LVSI （P〈0.05） were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma （SCC） was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamons carcinoma （AC/ASC）, differentiation was the independent predictor of OS （P〈0.05）; and LVSI of DFS （P〈0.05）. Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy （CCRT, n=195）, radiotherapy （RT, n=24）, and chemotherapy （CT, n=17）. Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT （P=0.118）, with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. Conclusions： LNM, LVSI, DSI and differentiation were found to be independent prognostic factors for operable cervical cancer. Aggressive postoperative adjuvant therapy based on single risk factors in Chinese National Cancer Center could benefit survival. CCRT＋CT outperformed CCRT in high-risk patients. For patients with single non-high-risk factor, the role of adjuvant therapy needs to be further discussed.

Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma

BACKGROUND The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma(GBC)after curative resection remain unclear.AIM To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy.METHODS Patients with curatively resected advanced gallbladder adenocarcinoma(T3 and T4)were selected from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.A survival prediction model based on Bayesian network(BN)was constructed using the tree-augmented na?ve Bayes algorithm,and composite importance measures were applied to rank the influence of factors on survival.The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3.The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy.RESULTS A total of 818 patients met the inclusion criteria.The median survival time was 9.0 mo.The accuracy of BN model was 69.67%,and the area under the curve value for the testing dataset was 77.72%.Adjuvant radiation,adjuvant chemotherapy(CTx),T stage,scope of regional lymph node surgery,and radiation sequence were ranked as the top five prognostic factors.A survival prediction table was established based on T stage,N stage,adjuvant radiotherapy(XRT),and CTx.The distribution of the survival time(>9.0 mo)was affected by different treatments with the order of adjuvant chemoradiotherapy(cXRT)>adjuvant radiation>adjuvant chemotherapy>surgery alone.For patients with node-positive disease,the larger benefit predicted by the model is adjuvant chemoradiotherapy.The survival analysis showed that there was a significant difference among the different adjuvant therapy groups(log rank,surgery alone vs CTx,P<0.001;surgery alone vs XRT,P=0.014;surgery alone vs cXRT,P<0.001).CONCLUSION The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients.Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.

Adjuvant hormone therapy after radical prostatectomy in highrisk localized and locally advanced prostate cancer: First multicenter, observational study in China

Objective: Potential of combined androgen blockade(CAB) has not been explored extensively in Chinese males with prostate cancer(PCa). Therefore, this study evaluated the 2-year prostate-specific antigen(PSA) recurrence rate and quality of life(Qo L) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy(HT) after radical prostatectomy(RP).Methods: This prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor(preoperative PSA>20 ng/m L or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice.Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate(FACT-P) Qo L scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.Results: A total of 189 patients(mean age: 66.9±6.5 years) were recruited, among which 112(59.3%) patients showed serum PSA>20 ng/m L preoperatively. The highest postoperative pathological advancement noticed was from clinical T2(c T2) to pathological T3(p T3)(43.9%) stage. The majority of the patients(66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence(15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist(LHRHa)(16.1%), and antiandrogen(19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P Qo L score of119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.Conclusions: Adjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in highrisk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens(AA) or LHRHa therapy. Further long-term therapy(>12 months) significantly improved Qo L compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving Qo L.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Development and controversies of adjuvant therapy for pancreatic cancer

BACKGROUND: Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES: A Medline database search was performed to identify relevant articles using the keywords 'pancreatic neoplasm', and 'adjuvant therapy'. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identified. The results for adjuvant regimens based on systemic 5-fluorouracil with or without external radiotherapy were conflicting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS: Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

Curative effect of ganglioside sodium for adjuvant therapy on acute severe craniocerebral injury

Objective: To study the effect of adjuvant therapy of ganglioside sodium on intracranial pressure (ICP), partial pressure of brain tissue oxygen (PbtO2), nerve injury molecules, nerve protection molecules and indexes of oxidative stress in patients with acute severe craniocerebral injury. <br> Methods: Forty-seven patients with severe craniocerebral injury treated in the emergency department of our hospital during the period time from December 2012 to October 2015 were selected for retrospective analyses. They were divided into the ganglioside group and the normal treatment group according to the usage of ganglioside sodium in the process of the emergency treatment. At days 1, 3, 5 and 7 before and after treatment, theICP and PbtO2 in patients of the two groups were measured. After 7 days of treatment, the nerve injury molecules, nerve protection molecules and the indexes of oxidative stress in serum of the patients of the two groups were determined. <br> Results: At days 1, 3, 5 and 7 before and after treatment, theICP in patients of the ganglioside group were all significantly lower than those of the normal treatment group, while the PbtO2 were all significantly higher than those of normal treatment group. After 7 days of treatment, the contents of serum methane dicarboxylic aldehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine urine, S100β, glial fibrillary acidic portein, neuron specific enolase, myelin basic protein, neuroglobin and ubiquitin carboxyl-terminal hydrolase L1 in patients of the ganglioside group were notably lower than those of the normal treatment group, while the contents of superoxidase dismutase, glutathione peroxidase, catalase, nerve growth factor and brain derived neurotrophic factor were significantly higher than those of the normal treatment group. <br> Conclusions: The adjuvant therapy of ganglioside sodium in patients with severe craniocerebral injury can effectively reduceICP, improve PbtO2 and alleviate the injuries of neurons and glial cells caused by oxidative stress.

Advances in postoperative adjuvant therapy for primary liver cancer

Hepatocellular carcinoma(HCC)is a highly heterogeneous,invasive,and conventional chemotherapy-insensitive tumor with unique biological characteristics.The main methods for the radical treatment of HCC are surgical resection or liver transplantation.However,recurrence rates are as high as 50%and 70%at 3 and 5 years after liver resection,respectively,and even in Milan-eligible recipients,the recurrence rate is approximately 20%at 5 years after liver transplantation.Therefore,reducing the postoperative recurrence rate is key to improving the overall outcome of liver cancer.This review discusses the risk factors for recurrence in patients with HCC radical surgical resection and adjuvant treatment options that may reduce the risk of recurrence and improve overall survival,including local adjuvant therapy(e.g.,transcatheter arterial chemoembolization),adjuvant systemic therapy(e.g.,molecular targeted agents and immunotherapy),and other adjuvant therapies(e.g.,antiviral and herbal therapy).Finally,potential research directions that may change the paradigm of adjuvant therapy for HCC are analyzed.

Current status of the adjuvant therapy in uterine sarcoma: A literature review

Uterine sarcomas (US) are rare mesenchymal tumours accounting approximately for 3%–7% of all uterine cancers. Histologically, US are classified into mesenchymal tumours or mixed epithelial and mesenchymal tumours. The group of mesenchymal tumours includes uterine leiomyosarcoma (uLMS, 65% of cases), endometrial stromal sarcoma (ESS, 21%)– traditionally divided into low grade (LG-ESS) and high grade–undifferentiated uterine sarcoma (5%) and other rare subtypes such as alveolar or embryonal rhabdomyosarcoma. Despite the fact that several drugs demonstrated clinical activity in advanced or metastatic settings, the role of postoperative therapy in US remains controversial. In this review, we have summarised the current state of the art, including the chief trials on adjuvant treatment modalities in US, especially focusing on uLMS, LG-ESS and other rare histotypes.

Fertility-sparing surgeries without adjuvant therapy through term pregnancies in a patient with low-grade endometrial stromal sarcoma:A case report

BACKGROUND Low-grade endometrial stromal sarcoma(LGESS)is a rare indolent tumor with a favorable prognosis.With the importance of improving quality of life recognized,fertility-sparing surgery may be an option for those young women.However,most of the reports suggested that stage IA patients might be candidates for fertility-sparing surgery,and adjuvant hormonal treatment was considered a feasible adjuvant therapy for reducing the recurrence risk of patients with LGESS and hysterectomy was recommended after the completion of pregnancy and delivery.CASE SUMMARY A 28-year-old pregnant woman diagnosed with stage IB LGESS was treated by fertility-sparing surgery when term cesarean section delivery was performed.Without any adjuvant treatment,she had the other successful term pregnancy and cesarean section 45 mo after first fertility-sparing surgery.Moreover,only hysteroscopic resection was performed to retain fertility again even when the tumor recurred after 6 years.So far the patient’s fertility and disease-free status have remained for more than 8 years without any adjuvant therapy despite local resection of the sarcoma.And the two babies were in good health.CONCLUSION For young patients with stage I LGESS,it seems that repeated fertility-sparing surgeries could be performed even after two term deliveries and the tumor recurrence,and it might be attempted without adjuvant therapy but the counseling should be considered as mandatory.