Complete response of gallbladder cancer treated with gemcitabine and cisplatin chemotherapy combined with durvalumab:A case report and review of literature

BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.

Effects of Shenqi Xiangyi granules in advanced gastric cancer chemotherapy

BACKGROUND Owing to the absence of specific symptoms in early-stage gastric cancer,most patients are diagnosed at intermediate or advanced stages.As a result,treatment often shifts from surgery to other therapies,with chemotherapy and targeted therapies being the primary options for advanced gastric cancer treatment.A total of 116 patients with advanced gastric cancer,admitted from January 2021 to December 2023,were selected and divided into two groups of 58 each using the random number table method.The control group received FOLFOX4 chemothe-rapy(oxaliplatin+calcium+folinate+5-fluorouracil)combined with intravenous sindilizumab.The observation group received the same treatment as the control group,supplemented by oral administration of Senqi Shiyiwei granules.Both groups underwent treatment cycles of 3 weeks,with a minimum of two cycles.The therapeutic efficacy,immune mechanisms,and treatment-related toxicity and side effects were compared between the groups.The objective remission rate in the observation group(55.17%)was higher than that of the control group(36.21%)(P<0.05).After two treatment cycle,CD3+,CD4+,and CD4+/CD8+levels were higher in the observation group compared to the control group,while CD8+,regulatory T cells,and natural killer cells were lower(P<0.05).Additionally,the incidence of leukopenia,nausea,and vomiting was lower in observed group(P<0.05).No significant differences were observed in the incidence of other adverse reactions(P>0.05).CONCLUSION Adjuvant therapy with Shenqixian granules may enhance the efficacy of simudizumab combined with FOLFOX4 chemotherapy in advanced gastric cancer and the immune function by increasing immune cell counts,making it a valuable option in clinical treatment.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

Screening of Myocardial Cardiotoxicity Induced by Anticancer Chemotherapy and the Importance of Global Longitudinal Strain

Introduction: The improvement of survival in patients with cancer and the expansion of therapeutic options have led to the emergence of a new profile of cardiotoxicity, specifically associated with antimitotic agents. Our study aimed to assess the incidence of chemotherapy-induced myocardial toxicity in patients with cancer. Patients and Methods: We conducted a looking-forward longitudinal cohort study including all patients admitted to the Cardiology departments of Aristide le Dantec Hospital and Dalal Jamm National Hospital Centre for apre-chemotherapy check-up. The included patients did not undergo any pre-existing cardiopathy. Results: Over a period of two years ranging from January 2019 to December 2021, a total of 37 patients were included in the study. Notably, there was a female predominance (92%) with an average age of 49.7 years ± 13.69. Breast cancer accounted for 70% of the neoplasms. Laboratory findings revealed moderate anemia in 19 patients (51%). At inclusion, the left ventricle (LV) was of normal size (LV diastole at 44.46 ± 4.97 mm). The systolic function of the left ventricle was normal in all patients, with an average ejection fraction (EF) of 63.1% ± 5.80 and a mean global longitudinal strain (GLS) of −20.4% ± 2.58. The most commonly used agents were anthracyclines. During follow-up, 3 patients (8.1%) developed clinical symptoms of left heart failure, and LV dysfunction on echocardiography was observed in 5 (13.5%) patients, with a significant decrease in EF Conclusion: The incidence of cardiac toxicity is not negligible, hence the importance of early screening. Strain imaging is an essential tool that should be performed as part of the assessment before chemotherapy and re-evaluated during treatment.

Perioperative chemotherapy improves survival of patients with locally advanced diffuse gastric cancer

BACKGROUND Whether patients with diffuse gastric cancer,which is insensitive to chemo-therapy,can benefit from neoadjuvant or adjuvant chemotherapy has long been controversial.AIM To investigate whether perioperative chemotherapy can improve survival of patients with locally advanced diffuse gastric cancer.METHODS A total of 2684 patients with locally advanced diffuse gastric cancer from 18 population-based cancer registries in the United States were analyzed.RESULTS Compared with surgery alone,perioperative chemotherapy improved the prognosis of patients with locally advanced gastric cancer.Before stabilized inverse probability of treatment weighting(IPTW),the median overall survival(OS)times were 40.0 months and 13.0 months(P<0.001),respectively.After IPTW,the median OS times were 33.0 months and 17.0 months(P<0.001),respectively.Neoadjuvant chemotherapy did not improve the prognosis of patients with locally advanced gastric cancer compared with adjuvant chemotherapy after IPTW.After IPTW,the median OS times were 38.0 months in the neoadjuvant chemotherapy group and 42.0 months in the adjuvant chemotherapy group(P=0.472).CONCLUSION Patients with diffuse gastric cancer can benefit from perioperative chemotherapy.There was no significant difference in survival between patients who received neoadjuvant chemotherapy and those who received adjuvant chemotherapy.

Nutritional Supplement Ocoxin® Combined with Gemcitabine-Based Chemotherapy in Patients with Advanced Pancreatic Adenocarcinoma

Background: the quality of life (QoL) of patients with pancreatic ductal adenocarcinoma (PDAC), with its limited survival, can be affected by chemotherapy-induced toxicity. The main objective was to evaluate the effect of introducing ocoxin oral solution (OOS) in combination with standard therapy on quality of life. Methods: Thirty patients were enrolled in an exploratory, prospective, single-centre clinical trial in the oncology department of “Hermanos Ameijeiras” University Hospital in Havana, Cuba. Quality of life was measured using the EORTC QLQ-C30 questionnaire and toxicity was assessed using the NCI-CTC-AE classification version 5.0. Results: There was stability in the scores over time for overall QoL and the functional scale criteria, while in terms of symptoms, fatigue, pain and loss of appetite were reduced. No grade 3 - 4 adverse events (AEs) were recorded, and only 14.9% of toxicities were classified as grade 2, and these were considered to be unrelated to OOS. Biochemical and nutritional parameters were normalised at 12 months compared to the baseline values. Conclusions: This clinical study is the first report of the use of OOS in patients with advanced pancreatic cancer, and demonstrates that it is able to maintain optimal quality of life with reduced severity of toxicity during and after combination treatment with gemcitabine-based chemotherapy.

Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma:A systematic review and meta-analysis

BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.

Alterations in Serum Lipids and Lipoproteins Induced by Neoadjuvant Chemotherapy in Patients with Osteosarcoma around the Knee Joint:A Retrospective Analysis

Objective To investigate the serum lipid profiles of patients with localized osteosarcoma around the knee joint before and after neoadjuvant chemotherapy.Methods After retrospectively screening the data of 742 patients between January 2007 and July 2020,50 patients aged 13 to 39 years with Enneking stage II disease were included in the study.Serum lipid levels,including total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),lipoprotein-α[Lp(a)],and apolipoprotein A1,B,and E(ApoA1,ApoB,and ApoE),and clinicopathological characteristics were collected before and after neoadjuvant chemotherapy.Results The mean levels of TC,TG,and ApoB were significantly increased following neoadjuvant chemotherapy(16%,38%,and 20%,respectively,vs.pretreatment values;P<0.01).The mean levels of LDL-C and ApoE were also 19%and 16%higher,respectively(P<0.05).No correlation was found between the pretreatment lipid profile and the histologic response to chemotherapy.An increase in Lp(a)was strongly correlated with the Ki-67 index(R=0.31,P=0.023).Moreover,a trend toward longer disease-free survival(DFS)was observed in patients with decreased TG and increased LDL-C following chemotherapy,although this difference was not statistically significant(P=0.23 and P=0.24,respectively).Conclusion Significant elevations in serum lipids were observed after neoadjuvant chemotherapy in patients with localized osteosarcoma.There was no prognostic significance of pretreatment serum lipid levels on histologic response to neoadjuvant chemotherapy.The scale of increase in serum Lp(a)might have a potential prognostic role in osteosarcoma.Patients with increased LDL-C or reduced TG after chemotherapy seem to exhibit a trend toward favorable DFS.

Effectiveness of a theory-based tailored mHealth physical activity intervention for women undergoing chemotherapy for breast cancer:A quasi-experimental study

Objectives:This study aimed to explore the effectiveness of the theory-based tailored mHealth physical activity(PA)intervention among patients with breast cancer undergoing chemotherapy.Methods:A quasi-experimental study design was adopted.A total of 60 breast cancer patients were selected from two tertiary hospitals in Shanghai and Hangzhou City from September 2019 to August 2021.According to the admission order,30 patients werefirst included in the control group,followed by 30 patients in the intervention group.A smartphone application(app)named“Breast Care”was developed based on social cognitive theory,self-efficacy theory,and the theory of planned behavior.The app integrated various functions,including information browsing,PA monitoring and feedback,symptom reporting,and social interaction.Patients in the intervention group received three months of personalized online PA guidance in addition to routine care.The control group received routine care.Baseline and post-intervention investigations after three months were conducted in two groups using the Short Form of International Physical Activity Questionnaire,the Hospital Anxiety and Depression Scale,and the Functional Assessment of Cancer TherapydBreast cancer.Results:After three months of intervention,compared to the control group,breast cancer patients in the intervention group showed significant improvements in walking,moderate PA,and overall PA(P<0.05).Compared to the baseline data,breast cancer patients in the intervention group had significant improvements in walking and overall PA after three months(P<0.05),whereas the control group experienced significant declines in walking,moderate PA,and overall PA after three months(P<0.05).There were statistically differences between the two groups in scores for anxiety,overall quality of life,and its dimensions,such as physical well-being,emotional well-being,and additional breast cancer well-being(P<0.05).Conclusions:The theory-based tailored mHealth PA intervention has demonstrated a positive impact on promoting PA behavior change and emotional management among breast cancer patients.The‘Breast Care’app integrated various practical behavior change strategies,offering valuable guidance for personalized remote rehabilitation support for cancer patients.

Clinical outcomes of second-line chemotherapy in patients with advanced pancreatic adenocarcinoma:a real-world study

Objective:Little progress has been made in recent years using first-line chemotherapy,including gemcitabine combined with nab-paclitaxel,FOLFIRINOX,and NALIRIFOX,for advanced pancreatic adenocarcinoma(APC).In addition,the optimal second-line chemotherapy regimen has not been determined.This study aimed to compare the effectiveness of different types of second-line chemotherapy for APC.Methods:Patients with APC who received first-line treatment from January 2008 to January 2021 were considered eligible for this retrospective analysis.The primary and secondary endpoints were overall survival(OS)and progression-free survival(PFS),respectively.Results:Four hundred and thirty-seven and 617 patients were treated with 5-fluorouracil-and gemcitabine-based chemotherapy as first-line treatment,respectively.Demographic and clinical features,except age and liver metastasis,were comparable between the two groups(P<0.05).The median OS was 8.8 and 7.8 months in patients who received a 5-fluorouracil-and gemcitabine-based combined regimen for first-line therapy,respectively(HR=1.244,95%CI=1.090–1.419;P<0.001).The median OS was 5.6 and 1.9 months in patients who received second-line chemotherapy and supportive care,respectively(HR=0.766,95%CI=0.677–0.867;P<0.001).The median PFS was not significantly differently between gemcitabine or 5-fluorouracil monotherapy and combination therapy.Conclusions:A 5-fluorouracil-or gemcitabine-based combined regimen was shown to be as effective as a single 5-fluorouracil or gemcitabine regimen as second-line therapy for patients with APC.

Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia:Long-term outcomes of a prospective trial(PKUCH-R03 trial)

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF).Methods:This prospective,single-arm phaseⅡtrial was designed and conducted at Peking University Cancer Hospital.The patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR).Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5%of whom experienced grade 3-4 adverse events during NCT.The pCR rate was 17.0%for the entire cohort,and the overall rate of postoperative complications was 37.7%(1.9%of gradeⅢa patients).The 3-year disease-free survival rate was 91.4%,and 23.5%(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major LARS.Conclusions:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable toxicity.With fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

Ganoboninketal C from Ganoderma boninense improves the efficacy of CDDP-based chemotherapy through inhibiting translesion DNA synthesis

Translesion DNA synthesis(TLS)can bypass DNA lesions caused by chemotherapeutic drugs,which usually result in drug resistance.Given its key role in mutagenesis and cell survival after DNA damage,inhibition of the TLS pathway has emerged as a potential target for improving the efficacy of DNA-damaging agents such as cisplatin(CDDP),a widely used anticancer agent.Unfortunately,few suitable natural TLS inhibitors have been reported.Here,we found that a triterpenoid compound Ganoboninketal C(26-3)from Ganoderma boninense,a traditional Chinese medicine,can impair CDDP-induced TLS polymerase eta(Polη)focus formation,PCNA monoubiquitination as well as mutagenesis.Moreover,26-3 can significantly sensitize tumor cells to CDDP killing and reduce the proportion of cancer stem cells in AGS and promote apoptosis after CDDP exposure.Interestingly,26-3 can also sensitize tumor cells to Gefitinib therapy.Mechanistically,through RNA-seq analysis,we found that 26-3 could abrogate the CDDP-induced upregulation of Polηand PIDD(p53-induced protein with a death domain),2 known factors promoting TLS pathway.Furthermore,we found that activating transcription factor 3 is a potential novel TLS modulator.Taken together,we have identified a natural TLS inhibitor 26-3,which can be potentially used as an adjuvant to improve clinical efficacy.

Prognostic value of neutrophil-to-lymphocyte ratio in gastric cancer patients undergoing neoadjuvant chemotherapy:A systematic review and meta-analysis

BACKGROUND In recent studies,accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors.There is a certain correlation of neutrophil-to-lymphocyte ratio(NLR)with the prognosis in gastric cancer(GC)patients undergoing neoadjuvant chemotherapy(NAC).However,the existing research results have remained controversial.AIM To explore the relationship between NLR ratio and prognosis of GC patients receiving NAC.METHODS A thorough systematic search was performed in databases such as PubMed,Embase,Web of Science,and Cochrane Library,the search is available until February 29,2024,and studies exploring the interaction of NLR with clinical outcomes were collected.Relevant studies meeting pre-defined inclusion and exclusion criteria were carefully chosen.The outcomes included progression-free survival(PFS),relapse-free survival,disease-free survival(DFS),and overall survival(OS).The hazard ratio(HR)and its corresponding 95%confidence interval(CI)were utilized for estimation.RESULTS Our analysis encompassed 852 patients and incorporated data from 12 cohort studies.The comprehensive analysis revealed a significant association of high NLR with reduced OS(HR=1.76;95%CI:1.22-2.54,P=0.003),relapsefree survival(HR=3.73;95%CI:1.74-7.96,P=0.0007),and PFS(HR=2.32;95%CI:1.42-3.81,P=0.0008)in patients.However,this correlation in disease-free survival was not significant.NLR demonstrated its crucial role in effectively predicting the OS of GC patients undergoing NAC at different detection times,ages,regions,and NLR thresholds.CONCLUSION In GC patients receiving NAC,an elevated NLR is strongly associated with reduced OS and PFS.NLR has become an effective biomarker for patient prognosis evaluation,providing valuable insights for the treatment strategies of NAC in GC patients.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.