Clinical antiangiogenic effect of recombinant adenovirus-p53 combined with hyperthermia for advanced cancer

Objective： To assess the safety and clinical antiangiogenic effect of recombinant adenovirus-p53 （rAd-p53） combined with hyperthermia plus or not plus radiotherapy in advanced cancer. Methods： Expression of Vascular epithelial growth factor （VEGF） after intratumoral injection of rAd-p53 was assayed by immunohistochemistry （IHC） imaging. Forty-four patients with advanced cancer were enrolled into this clinical study. The patients were intratumorally injected with rAd-p53 （Gendicine） at a dose of 1×1012 vp once a week, with a total of 4-54 （mean 7.7） times. Total of 4-29 （mean 8.5） times of hyperthermia was given to the patients. Among the 44 patients, 30 patients were concurrently added with radiotherapy of a total dose 30-76 Gy/15-38 f/3-8 w （mean 58 Gy）. Results： Before and after intratumoral injection of rAd-p53, the VEGF IHC positive cell scores were 2.80 and 1.50, respectively （P=0.031）. The treatment of rAd-p53 combined with hyperthermia plus or not plus radiotherapy in advanced cancer achieved CR rate of 13.60% （6/44）, and PR rate of 29.6% （13/44）, and thus the effective rate was 43.2%. In addition to 6 patients with CR, 19 patients （19/38, 50.0%） had low density area （LDA） of more than 50% area on CT image within tumor indicating tumor tissue necrosis. Conclusions： Our data indicate that rAd-p53 inhibits VEGF expression and angiogenesis, and promotes tumor necrosis and shrinkage induced by hyperthermia plus or not plus radiotherapy in advanced cancer.

Clinical Trial Protocol: Randomized Controlled Trial of Cancer Pain Monitoring System (CAPAMOS) in Patients with Advanced Cancer

Purpose: This randomized controlled trial (RCT) protocol was designed to evaluate the effectiveness of the Cancer Pain Monitoring System (CAPAMOS), a telenursing system designed to alleviate pain in ambulatory patients with advanced cancer. Methods: The study design involved a randomized controlled trial consisting of an intervention group using CAPAMOS and a control group that received usual care. At the time of enrollment, both groups will be given a questionnaire regarding issues, such as concerns related to cancer pain and self-management of opioid medication. Patients will then receive pain relief education based on the results of the questionnaire. Subjects in the control group will receive a pain diary and pain-relief pamphlet that acts as an educational tool. They could also call the outpatient clinic if they wanted to ask for a nursing consultation. The intervention group will be able to use CAPAMOS to manage their pain and receive video consultation with a telenurse, who is an oncology nursing specialist. Educational tools will be built into CAPAMOS. The study will be conducted for one month. The primary endpoint of this study was to calculate the Japanese Brief Pain Inventory score. The secondary endpoints were to assess the opioid medication self-management, Barriers Questionnaire, Japanese EuroQol 5-dimensions 5-level, and economic evaluation. Assessment items will be evaluated at registration and 2 and 4 weeks after registration. Conclusions: A RCT based on this protocol is expected to validate the efficacy of telenursing using CAPAMOS in patients with advanced cancer and pain.

A phase Ⅰ study of Hemay022, an irreversible dual EGFR/HER2 tyrosine kinase inhibitor in Chinese patients with HER2-positive advanced breast cancer

Objective: Hemay022 is a novel small-molecule and an irreversible tyrosine kinase inhibitor with the target of epidermal growth factor receptor(EGFR)/human epidermal growth factor receptor 2(HER2), which demonstrated anti-tumor activity in preclinical studies. This first-in-human study evaluated the safety, pharmacokinetics,tolerability and preliminary anti-tumor activity of Hemay022 in HER2-positive advanced breast cancer patients.Methods: Heavily pretreated patients with HER2-positive advanced breast cancer were assigned to eight dose cohorts in a 3+3 dose-escalation pattern at doses of 50-600 mg QD and 300 mg BID. Eligible patients were given a single dose of Hemay022 on d 1 in week 0, followed by once daily continuous doses for four weeks in 28-day cycles.Pharmacokinetic samples were obtained on d 1 and d 28. Clinical responses were assessed every eight weeks.Results: Twenty-eight patients with advanced breast cancer were treated with Hemay022. The most frequently reported drug-related adverse events were diarrhoea(85.7%), vomiting(28.6%), nausea(25.0%) and decreased appetite(17.9%). No grade 4 drug-related adverse events were reported. At 50-600 mg doses, steady state areas under the concentration-time curve and peak concentrations increased with doses. One patient achieved complete response(CR), and three achieved partial response(PR). The objective response rate(ORR) and disease control rate(DCR) were 14.3% and 46.4% in 28 patients, respectively. The median progression-free survival(PFS) was3.98 months.Conclusions: Hemay022 at the dose of 500 mg once daily was well tolerated. The pharmacokinetic properties and encouraging anti-tumor activities of Hemay022 in advanced breast cancer patients warranted further evaluation of Hemay022 for treating breast cancer patients in the current phase Ⅲ trial(No. NCT05122494).

Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model

BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Clinical efficacy and safety of erlotinib combined with chemotherapy in the treatment of advanced pancreatic cancer:A meta-analysis

BACKGROUND Advanced pancreatic cancer is resistant to chemotherapeutic drugs,resulting in limited treatment efficacy and poor prognosis.Combined administration of the chemotherapeutic gemcitabine and erlotinib is considered a potential first-line treatment for advanced pancreatic cancer.However,their comparative benefits and potential risks remain unclear.AIM To assess the clinical efficacy and safety of erlotinib combined with other chemotherapy regimens for the treatment of advanced pancreatic cancer.METHODS Literature on the clinical efficacy and safety of erlotinib combined with chemotherapy for advanced pancreatic cancer was retrieved through an online search.The retrieved literature was subjected to a methodological qualitative assessment and was analyzed using the RevMan 5.3 software.Ten randomized controlled trials involving 2444 patients with advanced pancreatic cancer were included in the meta-analysis.RESULTS Compared with chemotherapeutic treatment,erlotinib combined with chemotherapy significantly prolonged the progression-free survival time of pancreatic cancer patients[hazard ratio(HR)=0.78,95%CI:0.66-0.92,P=0.003].Meanwhile,the overall survival(HR=0.99,95%CI:0.72-1.37,and P=0.95)and disease control rate(OR=0.93,95%CI:0.45-0.91,P=0.84)were not significantly favorable.In terms of safety,the erlotinib and chemotherapy combination was associated with a significantly higher risk of diarrhea(OR=3.59,95%CI:1.63-7.90,P<0.05)and rash(OR=3.63,95%CI:1.64-8.01,P<0.05)compared with single-agent chemotherapy.Moreover,the risk of vomiting(OR=1.27,95%CI:0.62-2.59,P=0.51),regurgitation/anorexia(OR=1.61,95%CI:0.25-10.31,P=0.62),and infection(OR=0.72,95%CI:0.28-1.87,P=0.50)were not significant in either group.CONCLUSION Compared with a single chemotherapeutic modality,erlotinib combined with gemcitabine can prolong progression-free survival in pancreatic cancer,but does not improve survival benefit or disease control rate,and can increase the risk of diarrhea and rash.

Survey on hospice care attitude of family members of advanced cancer patients at different ages

BACKGROUND Hospice care plays an important role in improving the quality of life of advanced cancer patients,but controversy remains over whether age affects the attitudes of family members toward hospice care.AIM To investigate the attitudes of family members of advanced cancer patients of different ages toward hospice care.METHODS The study participants were 175 family members of patients with advanced cancer from January 2020 and October 2022.The participants were divided into youth(<40 years,n=65),middle-aged(40–60 years,n=59),and elderly(>60 years,n=51)groups.Researchers investigated and compared the degree of awareness regarding hospice care,attitudes,and whether the family members of patients would choose hospice care.RESULTS Among the family members of 175 patients,approximately 28%(49/175)were aware of hospice care.Awareness of hospice care,the proportion of hospice care acceptance and adaptation attitudes,and the proportion of those who chose hospice care in the youth group were higher in the middle-aged and elderly groups(P<0.05).No statistically significant difference was found in these three indicators between the middle-aged and elderly groups(P>0.05).Hospice care was chosen mainly to relieve pain and reduce unnecessary treatment,whereas the reasons for not choosing hospice care were mainly distrust and ethical concerns.CONCLUSION The family members of patients with advanced cancer had relatively low awareness of hospice care,while youth had a higher awareness of hospice care,acceptance,and adaptation attitudes,and were more willing to choose hospice care.

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.

Nomogram model including LATS2 expression was constructed to predict the prognosis of advanced gastric cancer after surgery

BACKGROUND Gastric cancer is a leading cause of cancer-related deaths worldwide.Prognostic assessments are typically based on the tumor-node-metastasis(TNM)staging system,which does not account for the molecular heterogeneity of this disease.LATS2,a tumor suppressor gene involved in the Hippo signaling pathway,has been identified as a potential prognostic biomarker in gastric cancer.AIM To construct and validate a nomogram model that includes LATS2 expression to predict the survival prognosis of advanced gastric cancer patients following ra-dical surgery,and compare its predictive performance with traditional TNM staging.METHODS A retrospective analysis of 245 advanced gastric cancer patients from the Fourth Hospital of Hebei Medical University was conducted.The patients were divided into a training group(171 patients)and a validation group(74 patients)to deve-lop and test our prognostic model.The performance of the model was determined using C-indices,receiver operating characteristic curves,calibration plots,and decision curves.RESULTS The model demonstrated a high predictive accuracy with C-indices of 0.829 in the training set and 0.862 in the validation set.Area under the curve values for three-year and five-year survival prediction were significantly robust,suggesting an excellent discrimination ability.Calibration plots confirmed the high concordance between the predictions and actual survival outcomes.CONCLUSION We developed a nomogram model incorporating LATS2 expression,which significantly outperformed conven-tional TNM staging in predicting the prognosis of advanced gastric cancer patients postsurgery.This model may serve as a valuable tool for individualized patient management,allowing for more accurate stratification and im-proved clinical outcomes.Further validation in larger patient cohorts will be necessary to establish its generaliza-bility and clinical utility.

Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer

BACKGROUND Currently,there is no standard adjuvant therapy for patients with resected ampulla of Vater(AoV)cancer.AIM To evaluate the effectiveness of adjuvant concurrent chemoradiotherapy(CCRT)in patients with advanced AoV cancer who underwent curative resection.METHODS This single-centered,retrospective study included 29 patients with advanced AoV cancer who underwent pancreaticoduodenectomy between 2006 and 2018.The impact of CCRT on advanced AoV cancer was analyzed.RESULTS The 1-,3-,and 5-yr recurrence-free survival(RFS)rates for patients with advanced AoV cancer were 82.8%,48.3%,and 40.8%,respectively,and the overall survival(OS)rates were 89.7%,62.1%,and 51.7%,respectively.Lymphovas-cular invasion was found to be a significant risk factor for RFS and OS in patients with advanced AoV cancer in the univariate analysis,whereas T stage and lymph node metastasis were significantly associated with OS in the multivariate analysis.Compared to the patients who did not receive adjuvant CCRT,those who received adjuvant CCRT did not show statistically significant improvements in the RFS and OS,although they had a significantly lower average age and significantly higher platelet-to-lymphocyte ratio.CONCLUSION Adjuvant CCRT did not improve survival outcomes in patients with advanced AoV cancer.These findings contribute to existing knowledge on the effectiveness of CCRT in this patient population and provide important insights for clinical decision-making.

Efficacy evaluation and survival analysis of the combination of oxaliplatin plus Teysuno (SOX) with immune checkpoint inhibitors in the conversion therapy of locally advanced gastric cancer

Background:The efficacy of combining immune checkpoint inhibitors(ICIs)with chemotherapy in neoadjuvant therapy for locally advanced gastric cancer has been explored.However,limited research exists on its effectiveness in conversion therapy,and its superiority over standalone chemotherapy remains to be elucidated.This study aims to investigate the efficacy and survival outcomes of patients treated with ICIs in combination with conversion therapy for locally advanced gastric cancer.Methods:Retrospective data from patients with locally advanced gastric cancer treated with either oxaliplatin+S-1(SOX)alone or in combination with ICIs in conversion therapywere collected.Clinical andpathological characteristics,disease-free survival,andefficacy assessments in nonoperable patients were compared between the 2 treatment groups.Efficacy was further evaluated through dynamic changes in serum markers,and patients’quality of life was assessed using the QLQ-STO22(Gastric Cancer–Specific Quality of Life Questionnaire)quality-of-life measurement scale.Results:A total of 140 patients underwent conversion therapy:80 in the SOX alone group and 60 in the SOX combined with the ICIs group.There were no significant differences in baseline characteristics between the 2 groups.Compared with the SOX alone group,the SOX combined with ICIs group exhibited a higher conversion rate(83.3%vs 75%,P=0.23),R0 resection rate(90.0%vs 83.3%,P=0.31),pathological complete response(pCR)rate(18%vs 5%,P=0.02),median disease-free survival(21.4 vs 16.9 months,P=0.007),the objective response rate in nonoperable patients(60%vs 40%,P=0.301),and median progression-free survival time(7.9 vs 5.7 months,P=0.009).The QLQ-STO22 quality-of-life assessment revealed statistically significant improvements in pain,swallowing difficulties,and dietary restrictions in the combination therapy group compared with those in the monotherapy group.The enhanced efficacy of immune combination with SOX is evident,as demonstrated by the significantly prolonged surgical duration in operated patients(206.6±26.6 min vs 197.8±19.8 min,P=0.35)and intraoperative blood loss(158.9±21.2 mL vs 148.9±25.1 mL,P=0.59).No significant differences were observed in postoperative complications.Conclusions:Compared with the SOX conversion therapy regimen,SOX combined with ICIs demonstrated higher conversion rates,R0 resection rates,pathological response rates,and disease-free survival without increasing surgical difficulty or complications.Nonoperable patients also experienced longer progression-free survival and objective response rates.

Investigating the therapeutic efficacy of psilocybin in advanced cancer patients: A comprehensive review and meta-analysis

BACKGROUND Psilocybin,a naturally occurring psychedelic compound found in certain species of mushrooms,is known for its effects on anxiety and depression.It has recently gained increasing interest for its potential therapeutic effects,particularly in patients with advanced cancer.This systematic review and meta-analysis aim to evaluate the effects of psilocybin on adult patients with advanced cancer.AIM To investigate the therapeutic effect of psilocybin in patients with advanced cancer.METHODS A comprehensive search of electronic databases was conducted in PubMed,Cochrane Central Register of Controlled Trials,and Google Scholar for articles published up to February 2023.The reference lists of the included studies were also searched to retrieve possible additional studies.RESULTS A total of 7 studies met the inclusion criteria for the systematic review,comprising 132 participants.The results revealed significant improvements in quality of life,pain control,and anxiety relief following psilocybin-assisted therapy,specifically results on anxiety relief.Pooled effect sizes indicated statistically significant reductions in symptoms of anxiety at both 4 to 4.5 months[35.15(95%CI:32.28-38.01)]and 6 to 6.5 months[33.06(95%CI:28.73-37.40)].Post-administration compared to baseline assessments(P<0.05).Additionally,patients reported sustained improvements in psychological well-being and existential distress fo-llowing psilocybin therapy.CONCLUSION The findings provided compelling evidence for the potential benefits of psilocybin-assisted therapy in improving quality of life,pain control,and anxiety relief in patients with advanced cancer.

Analysis of the Efficacy,Progression-Free Survival,and Safety of Anlotinib in Advanced Lung Cancer Treatment

Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Research progress of integrated traditional Chinese and Western medicine in the treatment of advanced gastric cancer

Gastric cancer(GC)is a malignant tumor originating from the gastric epithelium,and its incidence and mortality rates rank third among all malignant tumors worldwide.It is also one of the most common cancers in China and is treated predominantly by Western medicine in clinical practice.However,with the advancements in medical technology and informatics,the values of traditional Chinese medicine(TCM)in preventing and treating GC and improving prognosis have increasingly been recognized.According to TCM,clinical manifestations of GC can be divided into Yege(dysphagia),regurgitation,stomach pain,and Zhengxia(abdominal mass).Due to the unbalanced distribution of health care resources in China,most GC patients already have progressive or advanced-stage disease at the first diagnosis.As a result,most GC patients have poor physical function,and surgery or chemotherapy alone will aggravate the impairment to the immune function and seriously affect the quality of life.In contrast,TCM therapies have shown promising efficacy in the management of these patients.Here we review the role of the integrated TCM and Western medicine in treating advanced GC.

Systemic treatment for advanced pancreatic cancer

Pancreatic cancer is a deadly disease with an extremely poor 5-year survival rate due to treatment resistance and late-stage detection.Despite numerous years of research and pharmaceutical development,these figures have not changed.Treatment options for advanced pancreatic cancer are still limited.This illness is typically detected at a late stage,making curative surgical resection impossible.Chemotherapy is the most commonly utilized technique for treating advanced pancreatic cancer but has poor efficacy.Targeted therapy and immunotherapy have made significant progress in many other cancer types and have been proven to have extremely promising possibilities;these therapies also hold promise for pancreatic cancer.There is an urgent need for research into targeted treatment,immunotherapy,and cancer vaccines.In this review,we emphasize the founda-tional findings that have fueled the therapeutic strategy for advanced pancreatic cancer.We also address current advancements in targeted therapy,immuno-therapy,and cancer vaccines,all of which continue to improve the clinical outcome of advanced pancreatic cancer.We believe that clinical translation of these novel treatments will improve the low survival rate of this deadly disease.

Immune-related adverse events associated with immune checkpoint inhibitors for advanced gastric and gastroesophageal junction cancer:A meta-analysis

BACKGROUND Immune checkpoint inhibitors(ICIs)have shown promising efficacy in treatment and clinical management of advanced gastric and gastroesophageal junction cancer.However,the inhibitors also cause immune-related adverse events(irAEs).The current systematic review and meta-analysis study aimed to investigate the incidence and nature of irAEs caused by ICIs.AIM To investigate the incidence and nature of irAEs in advanced gastric and gastroesophageal junction cancer.METHODS This systematic review was registered with PROSPERO(Reg.number:CRD42020152291).Data included in this study were collected from patients diagnosed with advanced gastric cancer or gastroesophageal junction cancer and treated with ICIs.A systematic literature search was conducted using the PubMed,EMBASE,and Cochrane Library databases.Meta-analysis was carried out using the single sample rate method.Synthesis and analysis of the data was conducted using Stata/SE and Review Manager Software.RESULTS The patients enrolled in the present study included 14 patients from 14 case reports,326 patients from 6 case series,and 1249 patients from 8 clinical trials.It was found that the overall incidence of irAEs was 16%[95%confidence interval(CI):11-20]for all grades and 3%(95%CI:2-4)for the severe grade.It was evident that the incidence of irAEs varied with the type of inhibitor and organs.A comparative study of the anti-programmed cell death receptor-1(PD-1)and antiprogrammed death receptor-ligand 1(PD-L1)treatments showed that the antiPD-1 group had a higher overall incidence of irAEs(20%)as compared with that of the anti-PD-L1 group(13%).Results of this study showed that the endocrine system experienced the highest incidence of organ-specific irAEs(7.4%),including hypothyroidism,hyperthyroidism,thyroiditis,diabetes,and adrenal insufficiency,followed by gastroenterology(2.2%),pulmonology(1.8%),neurology(1.4%),dermatology(1.4%),hematology(0.8%),and hepatology(0.7%).In clinical trials,it was found that the incidence of death related to irAEs was 1%(95%CI:0-2.0),whereby colitis and interstitial lung diseases were the leading causes of death.CONCLUSION It was evident that the incidence and nature of irAEs are both organ-and inhibitor-specific.The anti-PD-1 group had the highest incidence of all irAEs grades including the severe grades of irAEs.Early identification and management of irAEs allows clinical oncologists to effectively consider the pros and cons and hence enables them to strike a balance.

Short-term efficacy and influencing factors of conventional chemotherapy combined with irinotecan in patients with advanced gastric cancer

BACKGROUND Gastric cancer is one of the most common cancers worldwide, with a 5-year survival rate of only 20%. The age of onset of gastric cancer is in line with the general rule of cancer. Most of them occur after middle age, mostly between 40and 60 years old, with an average age of about 50 years old, and only 5% of patients are under 30 years old. The incidence of male is higher than that of female.AIM To investigate the short-term efficacy and influencing factors of chemotherapy combined with irinotecan in patients with advanced gastric cancer.METHODS Eighty patients with advanced gastric cancer who were treated in our hospital from January 2019 to January 2022 were selected. The patients were divided into an observation group(n = 40) and control group(n = 40) by the envelope method.The control group was given preoperative routine chemotherapy. The observation group was treated with irinotecan in addition to the chemotherapy given to the control group. The short-term efficacy of treatment in the two groups, as well as tumor marker levels and quality of life before and after treatment were evaluated.RESULTS The short-term treatment effect in the observation group was better than that in the control group(P < 0.05), and the total effective rate was 57.50%. The age and proportion of tumor node metastasis(TNM) stage IV patients with ineffective chemotherapy in the observation group were(65.12 ± 5.71) years and 52.94%,respectively, which were notably higher than those of patients with effective chemotherapy(P < 0.05), while the Karnofsky Performance Scale score was(67.70± 3.83) points, which was apparently lower than that of patients with effective chemotherapy(P <0.05). After 3 mo of treatment, the SF-36 scale scores of physiological function, energy, emotional function, and mental health in the observation group were 65.12 ± 8.14, 54.76 ± 6.70, 47.58 ± 7.22,and 66.16 ± 8.11 points, respectively, which were considerably higher than those in the control group(P < 0.05). The incidence rates of grade Ⅲ-Ⅳ diarrhea and grade Ⅲ-Ⅳ thrombocytopenia in the observation group were 32.50% and 25.00%, respectively, which were markedly higher than those in the control group(P < 0.05).CONCLUSION Chemotherapy combined with irinotecan in patients with advanced gastric cancer has a good short-term efficacy and can significantly reduce serum tumor markers and improve the quality of life of patients. The efficacy may be affected by the age and TNM stage of the patients, and its long-term efficacy needs further study.

Clinical implication of naive and memory T cells in locally advanced cervical cancer:A proxy for tumor biology and short-term response prediction

Background:This study was designed to investigate the feasibility of tumor-infiltrating immune cells with different phenotypic characteristics for predicting short-term clinical responses in patients with locally advanced cervical cancer(LACC).Methods:Thirty-four patients who received concurrent chemoradiotherapy and twenty-one patients who merely underwent radiotherapy were enrolled in this study.We retrospectively analyzed the T cell markers(i.e.,CD3,CD4,CD8),memory markers(i.e.,CD45,CCR7),and differentiation markers(i.e.,CD27)in the peripheral blood and tumor tissues of patients with LACC before treatment based on flow cytometry.We also analyzed the relationship of T cell subsets between peripheral blood and tumor tissues,and their correlation with complete response or partial response.Results:The percentage of central memory CD8^(+)TCM(CD8^(+)CD45RA^(−)CD27^(+)CCR7^(+))cells in LACC patients was significantly lower than that of the control group.The percentage of CD8^(+)TN in the peripheral blood of LACC patients was significantly higher than that of tumor tissues.CD8^(+)TEM in the peripheral blood was significantly lower than that of tumor tissues.The percentage of CD8^(+)TN and CD8^(+)TCM in human papillomavirus(HPV)positive samples was significantly higher than that of HPV-negative samples.Similarly,the percentage of CD8^(+)TCM in tumor tissues was significantly higher in cancer tissue samples with lymph nodes compared with those without.Conclusion:A higher proportion of CD4^(+)TCM and a lower proportion of CD8^(+)TN in the tumor microenvironment of LACC may contribute to the therapy response prediction.

Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival:A case report

BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.