Evaluating combined bevacizumab and XELOX in advanced colorectal cancer: Serum markers carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 199 analysis

BACKGROUND Colorectal cancer ranks third and second among common and fatal cancers.The treatment of metastatic colorectal cancer(mCRC)is generally based on XELOX in clinical practice,which includes capecitabine(CAP)and oxaliplatin.Serum tumor markers carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125 and CA199 are prognostic factors for various tumors.AIM To investigate evaluating combined bevacizumab(BEV)and XELOX in advanced colorectal cancer:Serum markers CEA,CA125,CA199 analysis.METHODS In this retrospective study,a total of 94 elderly patients diagnosed with mCRC were recruited and subsequently categorized into two groups based on the distinct treatment modalities they received.The control group was treated with XELOX plus CAP(n=47),while the observation group was treated with XELOX plus CAP and BEV(n=47).Several indexes were assessed in both groups,including disease control rate(DCR),incidence of adverse effects,serum marker levels(CEA,CA125,and CA19)and progression-free survival(PFS).RESULTS After 9 wk of treatment,the serum levels of CEA,CA199 and CA125 in the observation group were significantly lower than those in the control group(P<0.05).Moreover,the PFS of the observation group(9.12±0.90 mo)was significantly longer than that of the control group(6.49±0.64 mo).Meanwhile,there was no statistically significant difference in the incidence of adverse reactions and DCR between the two groups during maintenance therapy(P>0.05).CONCLUSION On the basis of XELOX treatment,the combination of BEV and CAP can reduce serum tumor marker levels and prolong PFS in patients with mCRC.

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.

Mitomycin C and capecitabine: An additional option as an advanced line therapy in patients with metastatic colorectal cancer

BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.

Retrospective efficacy analysis of olaparib combined with bevacizumab in the treatment of advanced colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a highly prevalent malignancy of the digestive tract worldwide,characterized by a significant morbidity and mortality rate and subtle initial symptoms.Diarrhea,local abdominal pain,and hematochezia occur with the development of cancer,while systemic symptoms such as anemia and weight loss occur in patients with advanced CRC.Without timely interventions,the disease can have fatal consequences within a short span.The current therapeutic options for colon cancer include olaparib and bevacizumab,which are widely utilized.This study intends to evaluate the clinical efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC,hoping to provide insights into advanced CRC treatment.AIM To investigate the retrospective efficacy of olaparib combined with bevacizumab in the treatment of advanced CRC.METHODS A retrospective analysis was conducted on a cohort of 82 patients with advanced colon cancer who were admitted to the First Affiliated Hospital of the University of South China between January 2018 and October 2019.Among them,43 patients subjected to the classical FOLFOX chemotherapy regimen were selected as the control group,and 39 patients undergoing treatment with olaparib combined with bevacizumab were selected as the observation group.Subsequent to different treatment regimens,the short-term efficacy,time to progression(TTP),and incidence rate of adverse reactions between the two groups were compared.Changes in serum-related indicators[vascular endothelial growth factor(VEGF),matrix metalloprotein-9(MMP-9),cyclooxygenase-2(COX-2)]and tumor markers[human epididymis protein 4(HE4),carbohydrate antigen 125(CA125),carbohydrate antigen 199(CA199)]levels before and after treatment were compared between the two groups at the same time.RESULTS The objective response rate was discovered to be 82.05%,and the disease control rate was 97.44%in the observation group,which were significantly higher than the respective rates of 58.14%and 83.72%in the control group(P<0.05).The median TTP was 24 mo(95%CI:19.987-28.005)in the control group and 37 mo(95%CI:30.854-43.870)in the observation group.The TTP in the observation group was significantly better than that in the control group,and the difference held statistical significance(log-rank test value=5.009,P=0.025).Before treatment,no substantial difference was detected in serum VEGF,MMP-9,and COX-2 levels and tumor markers HE4,CA125,and CA199 levels between the two groups(P>0.05).Following treatment with different regimens,the above indicators in the two groups were remarkably promoted(P<0.05),VEGF,MMP-9,and COX-2 in the observation group were lower than those in the control group(P<0.05),and HE4,CA125,and CA199 levels were also lower than those in the control group(P<0.05).Visà-vis the control group,the total incidence of gastrointestinal reactions,thrombosis,bone marrow suppression,liver and kidney function injury,and other adverse reactions in the observation group was notably lowered,with the difference considered statistically significant(P<0.05).CONCLUSION Olaparib combined with bevacizumab in the treatment of advanced CRC demonstrates a strong clinical effect of delaying disease progression and reducing the serum levels of VEGF,MMP-9,COX-2 and tumor markers HE4,CA125 and CA199.Moreover,given its fewer adverse reactions,it can be regarded as a safe and reliable treatment option.

Nursing of advanced colorectal cancer patients treated with Cetuximab combined with chemotherapy

Cetuximab is a new medication that has recently been approved for the treatment of advanced colorectal cancer. To date we have had little experience in using this targeted agent. Eleven patients in our hospital with advanced colorectal cancer were treated with cetuximab and chemotherapy. Based on the curative effect of this combination therapy, we have concluded that the following nursing practices make an important contribution to the patients＇ prognosis and wellbeing： to establish a good nurse-patient relationship, to increase patient understanding of the side effects, to standardize the medications, to observe and to deal with the side effects of the medications（for example skin reaction, neutropenia, and diarrhea）, and to provide continuous mental health care support and education.

Effect and safety of Kanglaite injection combined with chemotherapy in the treatment of advanced colorectal cancer:a systematic review and meta-analysis

Objective:To evaluate the clinical efficacy and safety of Kanglaite injection combined with chemotherapy and chemotherapy alone in the treatment of advanced colorectal cancer.Methods:PubMed,Cochrane library,CNKI,VIP,Wanfang database were systematically searched by inputting keywords to explore the efficacy of Kanglaite injection combined with chemotherapy in the treatment of advanced colorectal cancer.A random-effects model was selected to evaluate the treatment outcomes.The screening of literature,the extraction of data and the assessment of methodology were independently undertaken by two reviewers.Meta analysis was performed using Revman5.3 software and stata15.0 software.Results:A total of 12 RCTs were included,with 792 cases.Compared with chemotherapy alone,Metaanalysis suggested that Kanglaite injection combined with chemotherapy can improve clinical efficiency(RR=1.45,95%CI:1.21-1.74,P<0.0001)and improve patients'quality of life(RR=1.55,95%CI:1.32-1.82,P<0.00001),improve the patient's immune function(CD3+cells:SWD=1.42,95%CI:1.11-1.73;CD4+/CD8+cell ratio:SWD=0.95,95%CI:0.66-1.25;NK cell activity:SWD=3.24,95%CI:2.81-3.66,P<0.00001);Leukopenia rate(RR=0.63,95%CI:0.54-0.74,P<0.0001),incidence of gastrointestinal adverse reactions(RR=0.56,95%CI:0.48-0.66,P<0.00001),incidence of peripheral neurotoxicity(RR=0.79,95%CI:0.65-0.96,P=0.02)were lower than the chemotherapy alone group,the difference was statistically significant.In improving the hand-foot syndrome and oral mucositis after chemotherapy,there was some difference between the Kanglaite injection combined with chemotherapy group and the chemotherapy alone group,but the difference was not significant.Puber bias detection and sensitivity analysis were performed with clinically effective relative risk(RR)as indicators.The results suggested that the publication bias was not obvious.The results of this study are stable.Conclusion:Compared with chemotherapy alone group in the treatment of advanced colorectal cancer,Kanglaite injection combined with chemotherapy can improve the effective rate,quality of life,immune function of patients and reduce the incidence of leukopenia after chemotherapy,gastrointestinal adverse reactions and peripheral neurotoxicity.

Professor YANG Yu-fei’s Experience on the Integrated Chinese and Western Medicine Treatment Strategy for Advanced Colorectal Cancer

Colorectal cancer is one of the common malignant tumors in China.It poses a serious threat to the national health of China.For advanced colorectal cancer, the main goal of treatment is to prolong survival and improve quality of life.It complements other advantages, showing good therapeutic results.However, how to grasp the timing of integrated Chinese and Western Medicine for the treatment of advanced colorectal cancer and use the integrated Chinese and Western Medicine treatment methods flexibly contains profound therapeutic art.Prof.YANG Yu-fei is an authoritative expert in the field of integrated Chinese and Western medicine for colorectal cancer.She is good at accurately grasping the timing of treatment of integrated Chinese and Western Medicine, and flexibly adjusts the treatment strategy according to the specific conditions.In this paper, we shared Professor YANG Yu-fei's strategy for treating advanced colorectal cancer with emphasis on integrated Chinese and Western Medicine and attached a typical case, with a view to provide reference for the treatment of advanced colorectal cancer with integrated Chinese and Western Medicine.

Clinical evaluation of Fufangkushen combined with oxaliplatin in the treatment of advanced colorectal cancer

Objective:To systematically evaluate the efficacy and safety of compound Kushen injection combined with oxaliplatin chemotherapy in the treatment of advanced colorectal cancer.Methods:We searched PubMed,EMbase,the Cochrane Library,CNKI,VIP and Wan Fang database,SinoMed to collect compound Kushen injection combined with chemotherapy oxaliplatin into treatment of advanced colorectal cancer in randomised controlled trials;the databases weresearched from inception to December 2020.Meta-analysis of the included studies was performed using RevMan 5.4.Results:A total of 34 randomized controlled trials involving 2664 patients with colorectal cancer were included.Results of Meta-analysis showed that compound Kushen injection combined with oxaliplatin chemotherapy regimen improved the objective response rate of tumor[RR=1.40,95%CI(1.29,1.51),P<0.00001]and disease control rate[RR=1.12,95%CI(1.08,1,16),P 0.00001]improved the quality of life[RR=1.24,95%CI(1.14,1.36),P<0.00001],and significantly reduced the incidence of leukopenia[RR=0.35,95%CI(0.23,0.52),P<0.00001]and the incidence of diarrhea[RR=0.36,95%CI(0.19,0.70),P=0.003],and improved the immune function of patients(CD3+,CD4+,CD4+/CD8+,NK cell levels).However,compared to the control group,the levels of CD8+cells were decreased in the experimental group.Conclusion:Compound Kushen injection combined with oxaliplatin chemotherapy regimen can significantly improve the clinical efficacy of advanced colorectal cancer patients,improve the quality of life of patients,reduce the occurrence of adverse reactions,and has good efficacy and safety comparison with oxaliplatin chemotherapy regimen alone.

Predictive and prognostic implications of 4E-BP1, Beclin-1, and LC3for cetuximab treatment combined with chemotherapy in advanced colorectal cancer with wild-type KRAS: Analysis from real-world data

BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1(P = 0.010) and 4 E-BP1(P = 0.005), pathological grade(P = 0.002), and T stage(P = 0.004) were independent prognostic factors for overall survival(OS).CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy.LC3 is overexpressed in tumor tissues, and Beclin1 and 4 E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.

Brain metastasis in advanced colorectal cancer： results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Objective:Brain metastasis is considered rare in metastatic colorectal cancer(mCRC);thus,surveillance imaging does not routinely include the brain.The reported incidence of brain metastases ranges from 0.6% to 3.2%.Methods:The South Australian mCRC Registry(SAmCRC)was analyzed to assess the number of patients presenting with brain metastasis during their lifetime.Due to small numbers,a descriptive analysis is presented.Results:Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis(1.4%).The clinical characteristics of those with brain metastasis were as follows:the median age was 65.3 years and 51% were female.Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS)mutation status of the tumor was known,the majority harbored a KRAS mutation(55%);31(53%)underwent craniotomy and 55(93%)underwent whole-brain radiotherapy.The median survival time from diagnosis of brain metastasis was 4.2 months(95% confidence interval 2.9–5.5).Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy(8.5 months vs.2.2 months,respectively).Data from the SAmCRC(a population-based registry)confirm that brain metastases are rare and the median time to development is approximately 2 years.Conclusions:Brain metastasis is a rare outcome in advanced CRC.Patients within the registry tended to be female,young in age,and harbored with higher rates of KRAS mutations.Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately,most patients with central nervous system involvement die from their extracranial disease.

Which strategy after first-line therapy in advanced colorectal cancer?

Second-line therapy for advanced colorectal cancer is an integral part of the treatment strategy that needs to be set from the beginning for each patient, bearing in mind the expected toxicities of chosen treatments, the patient's clinical condition, comorbidities, preferences, the aims of the treatment and the molecular status. Furthermore, the distinction between lines of therapy is no longer absolute. The perspective of "continuum of care" includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays" if needed, surgical resection of metastases in selected patients, and seems to allow a tailored treatment, in which patients are more likely to benefit from exposure to all active agents, which is known to correlate with overall survival. The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies(cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents(bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression. The purpose of this review is to summarize the most important scientific data supporting the use of chemotherapy and the new biologic agents in the second-line setting in advanced colorectal cancer.

Clinical laboratory and imaging evidence for effectiveness of agarose-agarose macrobeads containing stem-like cells derived from a mouse renal adenocarcinoma cell population (RMBs) in treatment-resistant, advanced metastatic colorectal cancer:Evaluation of

Objective： The complexity, heterogeneity and capacity of malignant neoplastic cells and tumors for rapid change and evolution suggest that living-cell-based biological-systems approaches to cancer treatment are merited. Testing this hypothesis, the tumor marker, metabolic activity, and overall survival（OS） responses, to the use of one such system, implantable macrobeads [RENCA macrobeads（RMBs）], in phase I and IIa clinical trials in advanced,treatment-resistant metastatic colorectal cancer（m CRC） are described here.Methods： Forty-eight m CRC patients（30 females; 18 males）, who had failed all available, approved treatments,underwent RMB implantation（8 RMB/kg body weight） up to 4 times in phase I and phase IIa open-label trials.Physicals, labs [tumor and inflammation markers, lactate dehydrogenase（LDH）] and positron emission tomography-computed tomography（PET-CT） imaging to measure number/volume and metabolic activity of the tumors were performed pre-and 3-month-post-implantation to evaluate safety and initial efficacy（as defined by biological responses）. PET-CT maximum standard uptake value（SUVmax）（baseline and d 90; SUVmax ≥2.5）, LDH,and carcinoembryonic antigen（CEA） and/or cancer antigen 19-9（CA 19-9） response（baseline, d 30 and/or d 60）were assessed and compared to OS.Results： Responses after implantation were characterized by an at least 20% decrease in CEA and/or CA 19-9 in75% of patients. Fluorodeoxyglucose（FDG）-positive lesions（phase I, 39; 2 a, 82） were detected in 37/48 evaluable patients, with 35% stable volume and stable or decreased SUV（10） plus four with necrosis; 10, increased tumor volume, SUV. LDH levels remained stable and low in Responders（R）（d 0–60, 290.4–333.9）, but increased steadily in Non-responders（NR）（d 0–60, 382.8–1,278.5）（d 60, P=0.050）. Responders to RMBs, indicated by the changes in the above markers, correlated with OS（R mean OS=10.76 months; NR mean OS=4.9 months; P=0.0006）.Conclusions： The correlations of the tumor marker, tumor volume and SUV changes on PET-CT, and LDH levels themselves, and with OS, support the concept of a biological response to RMB implantation and the validity of the biological-systems approach to m CRC. A phase III clinical trial is planned.

Clinical and prognostic significance of expression of phosphoglycerate mutase family member 5 and Parkin in advanced colorectal cancer

BACKGROUND Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer(CRC)cells.Phosphoglycerate mutase family member 5(PGAM5)activates serine/threonine PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy.However,there are few studies on the clinical and prognostic significance of expression of PGAM5 protein and mitophagy-related protein Parkin in patients.AIM To assess the clinical significance of PGAM5 and Parkin proteins,as biomarkers for diagnosis and prognosis of CRC,by studying their expression in advanced CRC tissues and their association with clinicopathological parameters.METHODS The expression of PGAM5 and Parkin in CRC tissues from 100 patients was determined by immunohistochemistry.Each case was evaluated by using a combined scoring method based on signal intensity staining(scored 0-3)and the proportion of positively stained cancer cells(scored 0-4).The final staining score was calculated as the intensity score multiplied by the proportion score.Specimens were categorized as either high or low expression according to the Youden index,and the association between the expression of PGAM5 or Parkin and clinicopathological factors was ascertained.Additionally,we employed western blot to measure PGAM5 and Parkin protein expression in six matched pairs of CRC and adjacent non-tumor tissues.RESULTS Immunohistochemical and western blot findings showed that both PGAM5 and Parkin protein expression in tumor tissues was significantly higher than that in the adjacent tissues:PGAM5 and Parkin were mainly expressed in the cytoplasm of colonic epithelial cells.PGAM5 and Parkin protein levels were significantly positively correlated in advanced CRC tissues.Moreover,reduced Parkin protein expression was an independent prognostic factor for overall survival and progression-free survival in CRC patients as evinced by multivariate analysis.CONCLUSION The expression of PGAM5 protein and mitophagy-related protein Parkin has diagnostic significance for CRC and may become new biomarkers.Parkin may be a potential marker for the survival of CRC patients.

Role of sex on psychological distress,quality of life,and coping of patients with advanced colorectal and non-colorectal cancer

BACKGROUNDPatients with advanced gastrointestinal cancer must cope with the negative effects of cancer and complications.AIM To evaluate psychological distress,quality of life,and coping strategies in patients with advanced colorectal cancer compared to non-colorectal cancer based on sex.METHODS A prospective,transversal,multicenter study was conducted in 203 patients;101(50%)had a colorectal and 102(50%)had digestive,non-colorectal advanced cancer.Participants completed questionnaires evaluating psychological distress(Brief Symptom Inventory-18),quality of life(EORTC QLQ-C30),and coping strategies(Mini-Mental Adjustment to Cancer)before starting systemic cancer treatment.RESULTS The study included 42.4%women.Women exhibited more depressive symptoms,anxiety,functional limitations,and anxious preoccupation than men.Patients with non-colorectal digestive cancer and women showed more somatization and physical symptoms than subjects with colorectal cancer and men.Men with colorectal cancer reported the best health status.CONCLUSION The degree of disease acceptance in gastrointestinal malignancies may depend on sex and location of the primary digestive neoplasm.Future interventions should specifically address sex and tumor site differences in individuals with advanced digestive cancer.

Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture

BACKGROUND Angiogenesis inhibitors(AIs)combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer(CRC).Aflibercept(AFL)is an option for second-line treatment of CRC,according to the‘VELOUR’trial.Currently,we can choose from three AIs,including bevacizumab,ramucirumab,and AFL.Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action.We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.AIM To determine and compare the efficacy and safety profiles of AFL in the secondline and salvage therapy settings.METHODS Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan(FOLFIRI)regimen were collected retrospectively from six institutions in Japan,for the period from May 2017 to March 2019.Patient characteristics collected included age,sex,tumor location,RAS and RAF status,metastatic sites,number of previous treatment cycles,therapeutic response,adverse events,duration of previous AI treatment,and survival time.The end points were time to AFL treatment failure(aTTF)and median survival time post-AFL(aMST).Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting,which was defined as the days since the end of secondline therapy.RESULTS All 41 patients who received AFL+FOLFIRI for advanced CRC had metastatic or unresectable cancer.Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting.The patient characteristics were similar in the two groups,except for two factors.The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients(144 d vs 323 d,P=0.006).In the second-line and salvage therapy groups,the objective response rates were 11%and 0%,respectively(P=0.50),and the disease control rates were 53%and 50%,respectively(P=1.00).In the second-line and salvage therapy groups,the aTTF(123 d vs 71 d,respectively),aMST(673 d vs 396 d,respectively),and incidence of adverse events of grade 3[8(36%)vs 9(47%)]were not significantly different between the two groups.CONCLUSION AFL can be used to treat advanced CRC patients,with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.

Dynamic monitoring of carcinoembryonic antigen,CA19-9 and inflammation-based indices in patients with advanced colorectal cancer undergoing chemotherapy

BACKGROUND The roles of carcinoembryonic antigen(CEA)and carbohydrate antigen(CA19-9)in monitoring the patient response to chemotherapy for metastatic colorectal cancer(mCRC)are not clearly defined,and inflammatory indices,including the neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR)and systemic immune-inflammation index(SII),have been sparsely investigated for this purpose.AIM To aim of this study was to evaluate the relationship between the kinetics of CEA,CA19-9,NLR,LMR,PLR and SII in serum and patient response to chemotherapy estimated by computed tomography(CT)in patients with unresectable mCRC.METHODS Patients with mCRC treated with a 1st-line and 2nd-line chemotherapy underwent at least 3 whole-body spiral CT scans during response monitoring according to the Response Evaluation Criteria in Solid Tumour 1.1(RECIST 1.1),and simultaneous determination of CEA,CA19-9,neutrophil,lymphocyte,platelet and monocyte levels was performed.The kinetics of changes in the tumour markers and inflammatory indices were calculated as the percentage change from baseline or nadir,while receiver operating characteristic curves were drawn to select the thresholds to define patients with progressive or responsive disease with the highest sensitivity(Se)and specificity(Sp).The correlation of tumour marker kinetics with inflammatory index changes and RECIST response was determined by univariate and multivariate logistic regression analysis and the clinical utility index(CUI).RESULTS A total of 102 patients with mCRC treated with chemotherapy were included.Progressive disease(PD),defined as a CEA increase of 25.52%,resulted in an Se of 80.3%,an Sp of 84%,a good CUI negative[CUI(Ve-)]value of 0.75 and a good fraction correct(FC)value of 81.2;at a CEA cut-off of-60.85%with an Se of 100%and an Sp of 35.7%for PD,CT could be avoided in 25.49%of patients.The 21.49%CA19-9 cut-off for PD had an Se of 66.5%,an Sp of 87.4%,an acceptable CUI(Ve-)value of 0.65 and an acceptable FC value of 75.An NLR increase of 11.5%for PD had an Se of 67%and an Sp of 66%;a PLR increase of 5.9%had an Se of 53%and an Sp of 69%;an SII increase above-6.04%had an Se of 72%and an Sp of 63%;and all had acceptable CUI(Ve-)values at 0.55.In the univariate logistic regression analysis,CEA(P<0.001),CA19-9(P<0.05),NLR(P<0.05),PLR(P<0.05)and SII(P<0.05)were important predictors of tumour progression,but in the multivariate logistic regression analysis,CEA was the only independent predictor of PD(P<0.05).CONCLUSION CEA is a useful marker for monitoring the chemotherapy response of patients with unresectable mCRC and could replace a quarter of CT examinations.CA19-9 has poorer diagnostic characteristics than CEA but could be useful in some clinical circumstances,particularly when CEA is not increased.Dynamic changes in the inflammatory indices NLR,PLR and SII could be promising for further investigation as markers of the chemotherapy response.

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea

BACKGROUND The incidence of colorectal cancer(CRC)and preinvasive CRC(e.g.,early colon cancer and advanced adenoma)is gradually increasing in several countries.AIM To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea.METHODS This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC,and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies.Colonoscopy-related complications by age group were also determined.RESULTS The incidence of CRC showed a rapid increase,then decreased after 2012 in the 50-75 year-age group.During the study period,the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age.Since 2009,the increase has been rapid,showing a pattern similar to the increase in colonoscopies.The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007.The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age.CONCLUSION The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed.As the risk of colonoscopy-related hospitalization and death is high in the elderly,if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75,colonoscopy-related complications can be reduced for those aged 76 years or over.

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.

Clinical Efficacy of Laparoscopic Radical Colorectal Cancer Treatment for Colorectal Cancer and Its Effect on Immune Function

Objective:To explore the therapeutic effect of laparoscopic radical colorectal cancer treatment in colorectal cancer patients.Methods:A total of 50 colorectal cancer patients treated between August 2018 and August 2023 were randomly divided into two groups:Group A underwent laparoscopic radical colorectal cancer surgery,while Group B received open surgery.Clinical indicators,inflammatory factors,immune function indicators,and complications were compared between the two groups.Results:Group A showed significantly shorter operation times,faster recovery times,and reduced hospital stays compared to Group B.Additionally,Group A had less abdominal drainage and intraoperative bleeding(P<0.05).Levels of interleukin(IL)-4,IL-6,ultrasensitive C-reactive protein(hs-CRP),and tumor necrosis factor-alpha(TNF-α)were lower in Group A compared to Group B(P<0.05).Furthermore,immune function indicators,including CD3+,CD4+,CD8+,and CD4+/CD8+ratios,were better in Group A(P<0.05).The complication rate in Group A was also lower than in Group B(P<0.05).Conclusion:Laparoscopic radical treatment for colorectal cancer is efficient and feasible,causing minimal immune function impairment and inflammatory response.It also shortens postoperative recovery time.

Increased expression of tumor necrosis factor-a is associated with advanced colorectal cancer stages

AIM:To detect the expression of tumor necrosis factor-a(TNF-a)in colorectal cancer(CRC)cells among Saudi patients,and correlate its expression with clinical stages of cancer.METHODS:Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital.Patient demographic information,including age and gender,tumor sites,and histological type of CRC,was recorded.To measure TNF-a m RNA expression in CRC,total RNA was extracted from tumor formalin-fixed,paraffinembedded,and adjacent normal tissues.Reverse transcription and reverse transcription polymerase chain reaction were performed.Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-a by immunohistochemistry.RESULTS:The relative expression of TNF-a m RNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue.High TNF-a gene expression was associated with StageⅢandⅣneoplasms when compared with earlier tumor stages(P=0.004).Eighty-three percent of patients(25/30)showed strong TNF-a positive staining,while only 10%(n=3/30)of patients showed weak staining,and 7%(n=2/30)were negative.We showed the presence of elevated TNF-a gene expression in cancer cells,which strongly correlated with advanced stages of tumor.CONCLUSION:High levels of TNF-a expression could be an independent diagnostic indicator of colorectal cancer,and targeting TNF-a might be a promising prognostic tool by assessment of the clinical stages of CRC.