First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L150%or more(EMPOWER-Lung 1):35-month follow-up from a multicentre,open-label,randomised,phase 3 trial

肺癌是全球癌症相关死亡的主要原因,非小组胞肺癌(NSCLC)占所有肺癌病例的80%-85%。随着分子生物学的发展,针对驱动基因突变(如EGFR、ALK等)的靶向药物治疗已成为晚期NSCLC的标准一线治疗。但大多数NSCLC并没有可检测到的驱动基因突变,传统的铂类化疗效果不佳。免疫检查点抑制剂的出现极大地改变了这一领域的治疗格局。PD-1/PD-L1抑制剂已被证实可以显著提高NSCLC患者的疗效和生存期,特别是PD-L1表达阳性率≥50%的人群。

Serum basic fibroblast growth factor and interleukin-1βpredict the effect of first-line chemotherapy in patients with advanced gastric cancer

BACKGROUND The incidence and mortality rates of gastric cancer in China are the second-highest in the world,and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis.AIM To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1βlevels for the effect of first-line chemotherapy in patients with advanced gastric cancer.METHODS From the gastric cancer patients admitted to our hospital from May 2019 to April 2023,84 patients were selected and randomly and equally assigned to the experimental or control group.The FLOT group received the FLOT chemotherapy regimen(composed of oxaliplatin+calcium folinate+fluorouracil+paclitaxel),while the SOX group received the SOX chemotherapy regimen(composed of oxaliplatin+tiga capsules).The clinical efficacy,tumor marker levels,adverse reactions,and survival rates of the two groups were compared 7 days after the end of the relevant treatments.RESULTS The target effective rate of the FLOT group was 54.76%,which was much higher than that of the SOX group(33.33%;P<0.05).After treatment,both the groups demonstrated lower levels of cancer antigen(CEA),carbohydrate antigen 199(CA199),and peptide tissue antigen(TPS).For several patients before treatment(P<0.05).Third and fourth grades.In terms of adverse reactions,the level of white blood cells in both the groups was lower.Moreover,the incidence of hand-foot skin reactions in these two study groups was lower(P<0.05),while those of peripheral neuritis,vomiting,diarrhea,and abnormal liver function were significant(P<0.05).No statistically significant difference was noted between the two groups(P<0.05).The 1-year survival rate was higher in the FLOT group(P<0.05).CONCLUSION The FLOT regimen was effective in reducing the serum CEA,CA199,and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability,making it worthy of clinical promotion and application.

Zimberelimab plus chemotherapy as the first-line treatment of malignant peritoneal mesothelioma:A case report and review of literature

BACKGROUND Malignant peritoneal mesothelioma(MPeM)is a rare cancer with a poor prognosis at advanced stage,and the standard first-line treatment for inoperable patients is chemotherapy.Although combining programmed cell death 1(PD-1)inhibitors with chemotherapy is generally considered safe and effective in several malignant solid tumors,there are few reports regarding initial immunochemotherapy in advanced MPeM.CASE SUMMARY Here,to our knowledge,we present the first case of a patient with epithelioid subtype MPeM,who was treatment-naïve and benefited from initial PD-1 inhibitor plus standard chemotherapy with a prolonged progression-free survival(PFS)and good tolerance.A 49-year-old man was admitted to our hospital for a persistent burning sensation in the abdomen.Computed tomography revealed a solid mass in the lower abdomen,which was subsequently diagnosed histologically as epithelioid subtype MPeM by core needle biopsy.The patient received eight cycles of pemetrexed 800 mg(day 1),cisplatin 60/50 mg(day 1–2),and zimberelimab(PD-1 inhibitor)240 mg(day 1)every 3 wk.He achieved significant reduction of peritoneal tumors with remarkable improvement in symptoms.The best tumor response was partial remission with a final PFS of 7 mo.No immunerelated adverse event occurred during the combination treatment.CONCLUSION The outcome of the present case demonstrates the promising anti-tumor activity of immunochemotherapy to treat inoperable MPeM in the future.

Hormonal therapy might be a better choice as maintenance treatment than capecitabine after response to first-line capecitabine-based combination chemotherapy for patients with hormone receptor-positive and HER2-negative,metastatic breast cancer

Background:Both hormonal therapy(HT) and maintenance capecitabine monotherapy(MCT) have been shown to extend time to progression(TTP) in patients with metastatic breast cancer(MBC) after failure of taxanes and anthracycline?containing regimens.However,no clinical trials have directly compared the efficacy of MCT and HT after response to first?line capecitabine?based combination chemotherapy(FCCT) in patients with hormone receptor(HR)?positive and human epidermal growth factor receptor 2(HER2)?negative breast cancer.Methods:We retrospectively analyzed the charts of 138 HR?positive and HER2?negative MBC patients who were in non?progression status after FCCT and who were treated between 2003 and 2012 at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences,in Beijing,China.The median number of first?line chemotherapy cycles was 6(range,4–8);combined agents included taxanes,vinorelbine,or gemcitabine.Of these 138 patients,79 received MCT,and 59 received HT.Single?agent capecitabine was administered at a dose of 1250 mg/m2 twice daily for 14 days,followed by a 7?day rest period,repeated every 3 weeks.Of the 59 patients who received HT,37 received aromatase inhibitors(AIs),8 received selective estrogen receptor modulators(SERMs),and 14 received goserelin plus either AIs or SERMs.We then compared the MCT group and HT group in terms of treatment efficacy.Results:With a median follow?up of 43 months,patients in the HT group had a much longer TTP than patients in the MCT group(13 vs.8 months,P ease?free surviv= 0.011).When TTP was adjusted for age,menopausal status,Karnofsky performance status score,disal,site of metastasis,number of metastatic sites,and response status after FCCT,extended TTP was still observed for patients in the HT group(hazard ratio:0.63;95% confidence interval:0.44–0.93;P = 0.020).We also observed a trend of overall survival advantage for patients in the HT group vs.patients in the MCT group,but the difference was not significant(43 vs.37 months,P tients in the MCT g= 0.400).In addition,patients in the HT group gen?erally tolerated the treatment well,whereas paroup experienced grades 3–4 adverse events,the most frequent of which were hand?foot syndrome(15.8%) and hematologic abnormalities(7.6%).Conclusion:For HR?positive and HER2?negative MBC patients,HT might be considered a treatment after response to FCCT but prior to MCT as a long?term administration.

Efficacy and safety of trastuzumab combined with chemotherapy for first-line treatment and beyond progression of HER2-overexpressing advanced breast cancer

Objective： To observe the efficacy and safety of trastuzumab combined with chemotherapy in patients with human epidermal growth factor receptor 2 （HER2）-overexpressing advanced breast cancer. Methods： A total of 90 patients with HER2-overexpressing advanced breast cancer were enrolled in this study. All patients were diagnosed with ductal invasive breast cancer by pathological analysis, and were aged between 31-73 years with a median of 51 years. HER2-positivity was defined as 3（＋） staining in immunochemistry or amplification of fluorescence in situ hybridization （FISH, ratio ≥2.0）. Trastuzumab was administered in combination with chemotherapy as first-line treatment and beyond progression as a second- line, third-line, and above treatment in 90, 34, 14, and 6 patients, respectively. The chemotherapy regimen was given according to normal clinical practice. The response rate was evaluated every two cycles, and the primary endpoints were progression-free survival （PFS） and overall survival （OS）. Survival curves were estimated by using Kaplan-Meier graphs and were compared by using log-rank test statistics. Multivariate analysis was done using Cox＇s proportional hazards regression model, and the level of significance was P〈0.05. Results： All 90 patients received at least one dose of trastuzumab, and efficacy could be evaluated in 85 patients. The median follow-up was 50 months. In total, 72 （80.00%） patients had visceral metastasis, and 43 （47.78%） patients had progressed after one or more extensive chemotherapy regimens for metastatic diseases. The median PFS for first-line trastuzumab was 10 months （range, 2-59 months）, and the median OS after metastasis or initially local advanced disease was 22 months （range, 2-1 16 months）. Conclusions： Trastuzumab combined with chemotherapy was active and well-tolerated as a first-line treatment and even beyond progression in HER2-overexpressing advanced breast cancer as a second-line or third-line treatment. However, its efficacy is certainly less beyond this point.

Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of first-line EGFR-TKIs and platinum-based chemotherapy

Objective： Data on the clinical activity of epidermal growth factor receptor （EGFR） tyrosine kinase inhibitors （TKIs） in patients with non-small-cell lung cancer （NSCLC） and uncommon EGFR mutations remain insufficient. This study aimed to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy in NSCLC patients with uncommon EGFR mutations. Methods： We retrospectively enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and treatment outcomes were collected and compared between patients with common and uncommon EGFR-mutant NSCLC. Results： Seventy patients （13.9%） harboring uncommon EGFR mutations were included. Thirty of these patients received EGFR-TKIs and 40 received platinum-based chemotherapy as first-line therapy. The objective response rate （ORR） and median progression-free survival （mPFS） of patients treated with TKIs in the uncommon mutation group was significantly inferior to that in the common mutation group （ORR： 23.3% vs. 51.8%, P=0.003; mPFS： 7.1 vs. 10.9 months, P〈0.001）. In the uncommon group, mPFS was similar between first-line EGFR-TKIs treatment and platinum-based chemotherapy （7.1 vs. 6.1 months, P=0.893）. In patients with EGFR G719X or L861Q mutations, the mPFS was longer in the first-line EGFR-TKIs treatment group than in the chemotherapy group, but the difference was not statistically significant （G719X： 8.2 vs. 5.8 months, P=0.061; L861Q： 7.6 vs. 4.1 months, P=0.872）. Multivariate analyses identified adenocarcinoma （P=0.003） as the independent predictive factor for PFS in patients with uncommon EGFR mutations who were treated with first-line EGFR-TKIs. Conclusions： The current study demonstrated that the effect of first-line EGFR-TKIs was similar to that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC. Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR-mutant NSCLC patients treated with first-line EGFR- TKIs.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Cyclophosphamide, Thalidomide and Dexamethasone (CTD) as First-Line Therapy in Multiple Myeloma Patients: An Experience in a Clinical Haematology Centre in Dakar, Senegal

Introduction: Induction therapy followed by high-dose chemotherapy with autologous stem cell transplantation remains the gold standard for myeloma patients who can tolerate this treatment approach. In a developing country setting, in the absence of availability of bone marrow transplantation, the CTD protocol is an accessible treatment regimen whose efficacy and lower toxicity compared to the Melphalan Prednisone protocol has been reported. This protocol has been administered since 2018 in first line. It’s against this backdrop we perform this study to assess the efficacy of this CTD protocol in first line therapy. Methods: We conducted a descriptive and analytical study including clinical, paraclinical and evolutionary data of 50 patients with MM treated during the period range from 01 September 2018 and 01 July 2022 with the CTD protocol of cyclophosphamide (500 mg at D1, D8 and D15), dexamethasone (40 mg weekly) and thalidomide (100 mg/day) in 28-day cycles. Survival outcomes were estimated by the Kaplan-Meier method. Results: The mean age was 62.3 ± 9.1 years and the sex ratio was 0.7. An advanced prognostic score at diagnosis was found in 73.5% of patients according to the Salmon and Durie score and in 32% according to the ISS. Overall remission was noted in 64%, of which 34% were in very good partial remission and partial remission in 12% of cases. Progression was noted in 4 patients. Treatment-related side effects were mainly peripheral neuropathy and anaemia in 3 patients respectively. The median survival was 38.4 months. The progression-free survival was 60%. An advanced age (≥65 years) is correlated with negative impact on survival (p = 0.04). Conclusion: Cyclophosphamide, thalidomide and dexamethasone give good outcome with less toxicity. Thus, it remains a first-line treatment alternative for newly diagnosed and low-income patients.

Prognostic significance of peritoneal metastasis from colorectal cancer treated with first-line triplet chemotherapy

BACKGROUND Peritoneal metastasis from colorectal cancer(CRC)carries a poor prognosis in most studies.The majority of those studies used either a single-agent or doublet chemotherapy regimen in the first-line setting.AIM To investigate the prognostic significance of peritoneal metastasis in a cohort of patients treated with triplet chemotherapy in the first-line setting.METHODS We retrospectively evaluated progression-free survival(PFS)and overall survival(OS)in 51 patients with metastatic CRC treated in a prospective clinical trial with capecitabine,oxaliplatin,irinotecan,and bevacizumab in the first-line setting according to the presence and absence of peritoneal metastasis.Furthermore,univariate and multivariate analyses for PFS and OS were performed to assess the prognostic significance of peritoneal metastasis at the multivariate level.RESULTS Fifty-one patients were treated with the above triplet therapy.Fifteen had peritoneal metastasis.The patient characteristics of both groups showed a significant difference in the sidedness of the primary tumor(left-sided primary tumor in 60%of the peritoneal group vs 86%in the nonperitoneal group,P=0.03)and the presence of liver metastasis(40%for the peritoneal group vs 75%for the nonperitoneal group,P=0.01).Univariate analysis for PFS showed a statistically significant difference for age less than 65 years(P=0.034),presence of liver metastasis(P=0.046),lung metastasis(P=0.011),and those who underwent metastasectomy(P=0.001).Only liver metastasis and metastasectomy were statistically significant for OS,with P values of 0.001 and 0.002,respectively.Multivariate analysis showed that age(less than 65 years)and metastasectomy were statistically significant for PFS,with P values of 0.002 and 0.001,respectively.On the other hand,the absence of liver metastasis and metastasectomy were statistically significant for OS,with P values of 0.003 and 0.005,respectively.CONCLUSION Peritoneal metastasis in patients with metastatic CRC treated with first-line triple chemotherapy does not carry prognostic significance at univariate and multivariate levels.Confirmatory larger studies are warranted.

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

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

Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with Chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(P<0.000,1).Median OS was unreached in the combination group,and 27.8 mon in the monotherapy group(P=0.31).According to the Cox multivariate regression analysis,combination therapy was an independent prognostic factor of PFS.Conclusion:In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations,combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

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.

Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy

BACKGROUND A decline in serum carbohydrate antigen 19-9(CA19-9)levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer.Neutrophil-to-lymphocyte ratio(NLR)has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St.Mary’s Hospital.Patients were divided according to CA19-9 positivity(CA19-9-positive vs-negative groups)and pre-and posttreatment NLR levels.To determine cut-off value of NLR and CA19-9 reduction,time-dependent receiver operating characteristic curve was applied.We evaluated overall survival(OS)and progression-free survival(PFS)for each group using Kaplan-Meier method,and we performed multivariate analyses on the entire cohort.RESULTS We included 271 patients in this study.Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%.Multivariate analysis showed that post-treatment NLR<2.62 and reduction of≥18%of baseline CA19-9 were significantly associated with OS and PFS.Post-treatment NLR≥2.62 showed hazard ratio(HR)of 2.47[95%confidence interval(CI):1.84-3.32,P<0.001]and CA19-9 decline(≥18%)showed HR of 0.51(95%CI:0.39-0.67,P<0.001)for OS.When CA19-9-positive patients were divided into groups according to CA19-9 response(responder vs non-responder)and post-treatment NLR(<2.62 vs≥2.62),CA19-9 responder and post-treatment NLR<2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR≥2.62 group(OS 11.0 mo vs 3.9 mo,P<0.001;PFS 6.3 mo vs 2.0 mo,P<0.001).The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group.Within the CA19-9-negative group,the posttreatment NLR<2.62 group showed better survival than the post-treatment NLR≥2.62 group(OS 12.7 mo vs 7.7 mo,P<0.001;PFS 6.7 mo vs 2.1 mo,P<0.001),and post-treatment NLR showed correlation with clinical response.CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy,the combination of post-treatment NLR<2.62 and 18%decline of CA19-9 at the first response evaluation is a good prognostic marker.Post-treatment NLR<2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.

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

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

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in patients with advanced pancreatic cancer: A population-based cohort study

BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.

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.

Beyond first-line chemotherapy for advanced pancreatic cancer:An expanding array of therapeutic options?

While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer,the optimal choice for treatment in the second-line setting and beyond is less well defined.A variety of cytotoxic agents,either alone or in combination,have been evaluated,although primarily in the context of small single-arm or retrospective studies.Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8mo,highlighting the very poor prognosis of patients who are candidates for such treatment.Targeted therapies studied in this chemotherapy-refractory setting,meanwhile,have produced even worse efficacy results.In the current article,we review the clinical evidence for treatment of refractory disease,primarily in patients who have progressed on front-line gemcitabine-based chemotherapy.In the process,we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting,including how to select an appropriate control arm given the absence of a wellestablished reference standard,and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.

Prognostic factors of early recurrence after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BACKGROUND Although cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)offer the potential for long-term survival in peritoneal carcinomatosis,outcomes following CRS/HIPEC vary significantly.AIM To identify the clinical factors associated with progression-free survival(PFS)after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal,ovarian,and gastric cancers.METHODS We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival(OS)in patients recruited between 2015 and 2020.Logistic regression models were used to assess the prognostic factors for the risk of recurrence within 1 year.Kaplan–Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and OS.RESULTS Of the 80 enrolled patients,39 had an unfavorable PFS(<1 year)and 41 had a favorable PFS(≥1 year).Simple logistic models revealed that the patients with a completeness of cytoreduction score of 0(CC-0)or length of CRS≤6 h had a favorable PFS[odds ratio(OR)=0.141,P=0.004;and OR=0.361,P=0.027,respectively].In multiple logistic regression,achieving CC-0 was the strongest prognostic factor for a favorable PFS(OR=0.131,P=0.005).A peritoneal cancer index score>12 was associated with a lower rate of achieving CC-0(P=0.027).The favorable PFS group had a significantly longer OS(median 81.7 mo vs 17.0 mo,P<0.001).CONCLUSION Achieving CC-0 was associated with a lower early recurrence rate and improved long-term survival.This study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis.

Effect of perioperative chemotherapy on resection of isolated pulmonary metastases from colorectal cancer:A single center experience

BACKGROUND Numerous studies have assessed surgical resection as a standard treatment option for patients with colorectal cancer(CRC)and resectable pulmonary metastases(PM).However,the role of perioperative chemotherapy after complete resection of isolated PM from patients with CRC patients remains controversial.We hypothesize that perioperative chemotherapy does not provide significant survival benefits for patients undergoing resection of PM from CRC.AIM To determine whether perioperative chemotherapy affects survival after radical resection of isolated PM from CRC.METHODS We retrospectively collected demographic,clinical,and pathologic data on patients who underwent radical surgery for isolated PM from CRC.Cancerspecific survival(CSS)and disease-free survival were calculated using Kaplan-Meier analysis.Inter-group differences were compared using the log-rank test.For multivariate analysis,Cox regression was utilized when indicated.RESULTS This study included 120 patients with a median age of 61.6 years.The 5-year CSS rate was 78.2%,with 36.7% experiencing recurrence.Surgical resection for isolated PM resulted in a 5-year CSS rate of 50.0% for second metastases.Perioperative chemotherapy(P=0.079)did not enhance survival post-resection.Factors associated with improved survival included fewer metastatic lesions[hazard ratio(HR):2.51,P=0.045],longer disease-free intervals(HR:0.35,P=0.016),and wedge lung resections(HR:0.42,P=0.035).Multiple PM predicted higher recurrence risk(HR:2.22,P=0.022).The log-rank test showed no significant difference in CSS between single and repeated metastasectomy(P=0.92).CONCLUSION Perioperative chemotherapy shows no survival benefit post-PM resection in CRC.Disease-free intervals and fewer metastatic lesions predict better survival.Repeated metastasectomy is warranted for eligible patients.