Study protocol of the Asian XELIRI ProjecT(AXEPT):a multinational,randomized,non-inferiority,phase Ⅲ trial of second-line chemotherapy for metastatic colorectal cancer, comparing the eicacy and safety of XELIRI with or without bevacizumab versus FOLFIRI w

Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.

Raltitrexed + irinotecan as second-line chemotherapy in elderly patients with advanced colorectal cancer

Aims and Background: Irinotecan is a standard option for relapsed/refractory advanced colo- rectal cancer. Combination with raltitrexed and irinotecan at lower than MTD doses should preserve disease stabilisation while decreasing toxicity. Patients and Methods: From January 2004 to April 2009, we analyzed, retrospectively, our data on irinotecan + raltitrexed, fixed doses, as a second-line chemotherapy in elderly pa- tients (>70 years) with advanced colorectal can- cer after failure of oxaliplatin based chemothera- py twenty-three patients were evaluated. Iri- notecan 350 mg + raltitrexed 2.6 mg were given every 3 weeks. Tumo r measurements were ob- tained after every third course of therapy. Toxic- ity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, ver- sion 2. Results: The median number of treatment courses received per patient was 4 (range, 1 - 8). All pa-tients were assessable for toxicity and 21 for response. The most frequently observed severetoxicities were diarrhea (grade 2, 13%) No cases of significant neutropenia occurred. Ob- jective partial responses were observed in 3 pa- tients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time- to-progression of 4.3 months and a median sur- vival of 8.3 months. Conclusions: A three weekly irinotecan + raltitrexed administration can indu- ce tumor control in elderly patients with advanc- ed colorectalcancer that has progressed during or shortly after oxaliplatin-based chemotherapy. The diarrhea by irinotecan, seems mitigated by coad-ministration of a smaller dose of

Comparing effectiveness and safety of paclitaxel plus raltitrexed vs. paclitaxel alone in second-line palliative chemotherapy for metastatic gastric adenocarcinoma: A randomized phase Ⅱ clinical trial

Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.

Chemotherapy beyond second-line in advanced gastric cancer

Patients with advanced gastric cancer(AGC) can be treated with multiple lines of chemotherapy. Although several randomized trials have demonstrated the benefit of second-line chemotherapy compared with best supportive care, there is no evidence that further lines of chemotherapy will result in substantial prolongation of survival. Despite this, the practice of offering chemotherapy beyond second-line agents to AGC patients is not uncommon if their performance status is well-preserved and they are willing to receive subsequent active treatments. The choice of chemotherapeutic agents depends on the patient's prior regimens. However, there are important controversial issues in the salvage setting of AGC, including a subset of patients who may benefit from chemotherapy, that still remain unanswered. This report reviews the available evidence regarding the impact of third- and subsequent lines of chemotherapy on survival and quality of life in patients with AGC.

Oral chemotherapy for second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer

BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.

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.

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.

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.

The Construction of Integrated Nursing Model Prevention of Oxaliplatin Chemotherapy-Induced Peripheral Nerve Injury

Objective: To investigate the effect of the integrated nursing model in the prevention of chemotherapy-induced peripheral injury. Methods: A total of 60 tumor patients receiving oxaliplatin for 1 - 6 cycles of chemotherapy from January to September 2023 were selected. 30 patients were selected from January to March and divided into the control group, and 30 patients were selected from July to 9 as the experimental group. The control group received conventional chemotherapy nursing, while the experimental group received integrated nursing. Anxiety, peripheral nerve toxicity stage and quality of life score were compared between the two groups before and after intervention. Results: After intervention, the scores of the self-rating Anxiety Scale (SAS) and the total scores of the oxaliplatin Levi specific sensory neurotoxicity scale in the experimental group were significantly lower than those in the control group, and the differences were statistically significant (P< 0.05);The Quality of Life Scale (FACT-G) score of cancer patients was higher than that of control group, and the difference was statistically significant (P< 0.05). Conclusion: The integrated nursing model can effectively reduce the anxiety of patients, reduce the incidence of peripheral nerve injury and improve the quality of life of patients.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.

Development of a novel staging classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy

BACKGROUND Stage classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction(AEG)treated with neoadjuvant chemotherapy(NAC)has not been established.AIM To investigate the optimal stage classification for Siewert Ⅱ AEG with NAC.METHODS A nomogram was established based on Cox regression model that analyzed variables associated with overall survival(OS)and disease-specific survival(DSS).The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test,Akaike information criterion,Harrell concordance index,time-receiver operating characteristic curve,and decision curve analysis.RESULTS Data from 725 patients with Siewert type Ⅱ AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate analyses revealed that sex,marital status,race,ypT stage,and ypN stage were independent prognostic factors of OS,whereas sex,race,ypT stage,and ypN stage were independent prognostic factors for DSS.These factors were incorporated into the OS and DSS nomograms.Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer.Finally,a user-friendly web application was developed for clinical use.CONCLUSION The nomogram established specifically for patients with Siewert type Ⅱ AEG receiving NAC demonstrated good prognostic performance.Validation using external data is warranted before its widespread clinical application.

Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

TRIANGLE operation,combined with adequate adjuvant chemotherapy,can improve the prognosis of pancreatic head cancer:A retrospective study

BACKGROUND The TRIANGLE operation involves the removal of all tissues within the triangle bounded by the portal vein-superior mesenteric vein,celiac axis-common hepatic artery,and superior mesenteric artery to improve patient prognosis.Although previously promising in patients with locally advanced pancreatic ductal adenocarcinoma(PDAC),data are limited regarding the long-term oncological outcomes of the TRIANGLE operation among resectable PDAC patients undergoing pancreaticoduodenectomy(PD).AIM To evaluate the safety of the TRIANGLE operation during PD and the prognosis in patients with resectable PDAC.METHODS This retrospective cohort study included patients who underwent PD for pancreatic head cancer between January 2017 and April 2023,with or without the TRIANGLE operation.Patients were divided into the PD_(TRIANGLE)and PD_(non-TRIANGLE)groups.Surgical and survival outcomes were compared between the two groups.Adequate adjuvant chemotherapy was defined as adjuvant chemotherapy≥6 months.RESULTS The PD_(TRIANGLE)and PD_(non-TRIANGLE) groups included 52 and 55 patients,respectively.There were no significant differences in the baseline characteristics or perioperative indexes between the two groups.Furthermore,the recurrence rate was lower in the PD_(TRIANGLE) group than in the PD_(non-TRIANGLE) group(48.1%vs 81.8%,P<0.001),and the local recurrence rate of PDAC decreased from 37.8%to 16.0%.Multivariate Cox regression analysis revealed that PD_(TRIANGLE)(HR=0.424;95%CI:0.256-0.702;P=0.001),adequate adjuvant chemotherapy≥6 months(HR=0.370;95%CI:0.222-0.618;P<0.001)and margin status(HR=2.255;95%CI:1.252-4.064;P=0.007)were found to be independent factors for the recurrence rate.CONCLUSION The TRIANGLE operation is safe for PDAC patients undergoing PD.Moreover,it reduces the local recurrence rate of PDAC and may improve survival in patients who receive adequate adjuvant chemotherapy.

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.

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of debate.AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database Article.Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected.RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival.The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than nCRT.Moreover,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for LAEC.However,nCT exhibited better performance in terms of postoperative complications.

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.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status

BACKGROUND Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability(MSI)(MSI-H)metastatic colorectal cancer.However,the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI(MSI-L),and microsatellite stable(MSS)metastatic colorectal cancer remains unclear.AIM To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer,and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months.METHODS We conducted a retrospective cohort study using the National Cancer Database(NCDB)to evaluate the overall survival(OS)of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy.The study population was stratified by MSI status(MSI-H,MSI-L,and MSS).Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS,adjusting for potential confounders.RESULTS A total of 21951 patients with metastatic colorectal cancer were included in the analysis,of which 2358 were MSI-H,and 19593 were MSI-L/MSS.In the MSI-H cohort,immunotherapy treatment(n=142)was associated with a significantly improved median OS compared to chemotherapy(n=860).After adjusting for potential confounders,immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort[adjusted hazard ratio(aHR):0.57,95%confidence interval(95%CI):0.43-0.77,P<0.001].In the MSS cohort,no significant difference in median OS was observed between immunotherapy treatment and chemotherapy(aHR:0.94,95%CI:0.69-1.29,P=0.715).CONCLUSION In this population-based study using the NCDB,immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer,but not in those with MSI-L/MSS metastatic colorectal cancer.Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Chemotherapy and radiotherapy:Could they contribute to the development of new tumors and metastases?

Objective: Both chemotherapy and radiotherapy have demonstrated high effectiveness as the best mechanisms in the fight against cancer;however, various studies seem to confirm that they could also favor the development of other unwanted effects of great importance for the patient. The main objective of this study is to find out the possible existence of this type of links. Method: This is a systematic literature review that seeks to find out which and how long cases of late interactions related to chemotherapy and radiotherapy treatments have been known. The bibliographic review was carried out based on references published in the last five years. Results: Various studies confirm the possible relationship between chemotherapy and radiotherapy treatments with the development of new undesirable side effects, especially as a consequence of the hepatotoxicity generated in the case of chemotherapy and radiation in radiotherapy. However, in this last type of treatment, the problems raised are really few. Conclusions: The existence of a risk of suffering new unwanted side effects after different types of treatment seems to have been demonstrated, especially in the case of chemotherapy. In the case of radiotherapy, adverse effects are practically non-existent, although they are no less important.