Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemothe...Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.展开更多
Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this tr...Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry展开更多
Both platinum-based doublet chemotherapy(PBC) and epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer(NSCLC). In early studi...Both platinum-based doublet chemotherapy(PBC) and epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer(NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival(OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials—involving 11,456 adult patients in 32 arms—were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian(predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs(r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations(r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations(r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.展开更多
Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with adv...Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with advanced cancers[124 gastrointestinal(GI)cancer patients,119 lung cancer patients and 54 head and neck cancer(HNC)patients]receiving first-line chemotherapy at Tongji Hospital.The patients’changes in body weight,body mass index(BMI),and biochemical parameters(serum haemoglobin and albumin levels)were compared before and after two chemotherapy cycles.Results More than half[54.88%(163/297)]of the patients had experienced unintentional weight loss in the 6 months before chemotherapy,and weight loss≥5%and≥10%of the body mass was noted in 35.69%and 20.20%of the patients,respectively.After two cycles of platinum-based chemotherapy,the proportions of patients with a>5%reduction in body weight among patients with GI,lung,and head and neck cancers were 47.5%(59/124),44.53%(53/119),and 46.2%(25/54),respectively.The patients with GI and lung cancers were more vulnerable to extreme weight loss(≥10%)than those with HNC(P=0.025).The serum hemoglobin levels were also remarkably decreased relative to those before chemotherapy(all P<0.05).Common GI symptoms reported by all patients included anorexia(61.28%),vomiting(52.53%),and nausea(51.18%).A higher proportion of patients with≥10%weight loss experienced anorexia and vomiting(OR=12.21 and 3.61,P=0.008 and 0.047,respectively).Conclusions For advanced cancer patients receiving platinum-based chemotherapy,the GI symptoms are the major factor related to their nutritional status.Appropriate nutritional screening,evaluation and treatment should be applied during the treatment of cancer in order to reduce GI symptoms and improve the patient’s nutritional status.展开更多
In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and...In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and drug resistance,patients will ultimately develop reduced sensitivity to EGFR-TKIs.How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research.Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs.However,results of pre-clinical and clinical studies have been inconsistent.The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research.Therefore,systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.展开更多
1文献来源
Tetsuya M, Satoshi M, Yasushi Y, et al. Gefitinib versus Cisplatin plus Docetaxel in patients with non-small-cell lung cancer harbouring mutations of theepidermal growth factor receptor （WJTOG3405） ： Ano...1文献来源
Tetsuya M, Satoshi M, Yasushi Y, et al. Gefitinib versus Cisplatin plus Docetaxel in patients with non-small-cell lung cancer harbouring mutations of theepidermal growth factor receptor （WJTOG3405） ： Anopen label, randomised phase 3 trial [J]. LancetOncol,2010, 11（2） ： 121-125.展开更多
Objective： to determine the role of excision repair cross-complementing group 1 gene （ERCC1） and ribonucleotide reductase subunit M1 （RRM1） expression in predicting response and survival in Chinese patients with ...Objective： to determine the role of excision repair cross-complementing group 1 gene （ERCC1） and ribonucleotide reductase subunit M1 （RRM1） expression in predicting response and survival in Chinese patients with advanced stage non-small cell lung cancer （NSCLC） treated with platinum-based chemotherapy. Methods： Formalin-fixed, paraffin-embedded biopsy tissues were retrospectively obtained from 160 advanced NSCLC patients. mRNA expression levels of ERCC1 and RRM1 were determined by real-time PCR. Results： Associations between mRNA expression level of ERCC1 and RRM1 and clinic-pathologic parameters were analyzed. One handred and forty two （88.75%） specimens were successfully amplified. mRNA expression level of ERCC1 and RRM1 was negatively associated with tumor response. ERCC1 expression levels ranged from 0.01 to 78.79 [median 0.63, mean 4.25 and standard deviation （SD） 9.23] and RRM1 from 0.00 to 30.91 （median 0.63, mean 0.87 and SD 3.36）. By adopting cut-off values according to median expression levels, we found that MST in patients with low ERCC1 mRNA levels was significantly longer in overall population than in patients with higher levels （18.63 versus 13.69 months, log-rank 5.73, P=0.017）, but we did not found the survival benefit of the patients with low expression level of RRM1. （19.07 versus 14.88, log-rank 1.66, P=0.197）. Further, in the multivariable Cox regression model analysis we found that low level of ERCC1 expression, the presence of weight loss and target therapy, were significant prognostic factors for survival. Conclusion： ERCC1 expression is associated with patients’ survival in Chinese advanced NSCLC patients treated with platinum-based regimen and may serve as a biomarker in predicting tumor response and clinical outcome in the patient population.展开更多
Hepatocholangiocarcinoma(c HCC-ICC) is a rare primary hepatic tumor defined by the presence of histological features of both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC). Its prevalence range...Hepatocholangiocarcinoma(c HCC-ICC) is a rare primary hepatic tumor defined by the presence of histological features of both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC). Its prevalence ranges from 1%-5% of all primary liver cancers. We report the case of a 55-year-old cirrhotic male patient admitted to our university hospital for dysphagia, revealing a 10 cm lower-third esophageal metastasis of an unresectable c HCC-ICC with stemcell features. Computed tomography and abdominal magnetic resonance imaging scans revealed multiple hepatic lesions combining features of both HCC and ICC, associated with synchronous bone metastasis. Histological and immunohistochemical analyses of biopsies from the esophageal lesion and the hepatic tumor confirmed the diagnosis of c HCC-ICC with a stem cell-subtype, according to the World HealthOrganization classification. After a multidisciplinary meeting, the patient was treated with chemotherapy. He received two cycles of a gemcitabine plus cisplatin regimen before bone progression, and he died 3 mo after the initial diagnosis.展开更多
BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-...BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.展开更多
BACKGROUND Gynecological malignancies represent a major cause of death in women and are often treated with platinum-based regimens.Patients undergoing chemotherapy suffer from alterations in nutritional status which m...BACKGROUND Gynecological malignancies represent a major cause of death in women and are often treated with platinum-based regimens.Patients undergoing chemotherapy suffer from alterations in nutritional status which may worsen gastrointestinal(GI)toxicities,quality of life and affect the overall prognosis.Indeed,assuring a good nutritional status and limiting toxicities during treatment are still major goals for clinicians.AIM To assess the role of Mediterranean Diet(MD)in reducing GI toxicities in patients with gynecological cancers treated with platinum-based regimens.METHODS We conducted an observational study on 22 patients with gynecological tumors treated with a platinum-based chemotherapy at Candiolo Cancer Institute FPO/IRCCS between January 2018 and June 2018.The food and frequency(FFQ)and the Patient-Reported Outcomes Common Terminology Criteria For Adverse Events(PRO-CTCAE)questionnaires were administered at baseline and at every Day 1 of each cycle.To evaluate the differences in GI toxicities the study population was divided in two groups according to the currently validated Mediterranean Diet Serving Score(MDSS)at baseline.RESULTS Patients with high MDSS reported a trend toward lower GI toxicities according to PRO-CTCAE at each timepoint(first evaluation:P=0.7;second:P=0.52;third:P=0.01).In particular,difference in nausea frequency and gravity(P<0.001),stomach pain frequency and gravity(P=0.01 and P=0.02),abdomen bloating frequency and gravity(P=0.02 and P=0.03),and interference with daily activities(P=0.02)were highly statistically significant at the end of treatment.More than 60%of patients changed their food habits during chemotherapy mainly because of GI toxicities.A higher reduction of food intake,both in terms of caloric(P=0.29)and of single nutrients emerged in the group experiencing higher toxicity.CONCLUSION Our results show that adherence to MD possibly reduces GI toxicity and prevents nutritional status impairment during chemotherapy treatment.Bigger studies are needed to confirm our results.展开更多
Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus ca...Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating AGC.Methods:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor EOXregimen.The primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat basis.Results:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two groups.In patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX arm.The rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy.Conclusions:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients.However,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.展开更多
Ovarian cancer is the leading cause of gynecologic cancer death in the United States.Most ovarian cancer patients are diagnosed with advanced-stage disease,which poses a challenge for early detection and effective tre...Ovarian cancer is the leading cause of gynecologic cancer death in the United States.Most ovarian cancer patients are diagnosed with advanced-stage disease,which poses a challenge for early detection and effective treatment.At present,cytoreductive surgery and platinum-based chemotherapy are foundational for patients with newly diagnosed ovarian cancer,but unfortunately,most patients will recur and die of their disease.Therefore,there is a significant need to seek innovative,novel approaches for early detection and to overcome chemoresistance for ovarian cancer patients.The microbiome,comprising diverse microbial communities inhabiting various body sites,is vital in maintaining human health.Changes to the diversity and composition of the microbial communities impact the microbiota-host relationship and are linked to diseases,including cancer.The microbiome contributes to carcinogenesis through various mechanisms,including altered host immune response,modulation of DNA repair,upregulation of pro-inflammatory pathways,altered gene expression,and dysregulated estrogen metabolism.Translational and clinical studies have demonstrated that specific microbes contribute to ovarian cancer development and impact chemotherapy’s efficacy.The microbiome is malleable and can be altered through different approaches,including diet,exercise,medications,and fecal microbiota transplantation.This review provides an overview of the current literature regarding ovarian cancer and the microbiome of female reproductive and gastrointestinal tracts,focusing on mechanisms of carcinogenesis and options for modulating the microbiota for cancer prevention and treatment.Advancing our understanding of the complex relationship between the microbiome and ovarian cancer may provide a novel approach for prevention and therapeutic modulation in the future.展开更多
Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer （NSCLC） patients. To study if pharmacogenetic approach may allow a tailored selection of platinum chemoth...Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer （NSCLC） patients. To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC, we performed a meta-analysis to compare chemosensitivity to platinum with differe4nt ERCC1 Cl18T/ MDR1 C3435T single-nucleotide polymorphism （SNP）. Methods Relevant studies were identified by searching the PubMed, Embase, Cochrane, OVID, Springer, EBSCO and CNKI databases. Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy, an evaluated polymorphism of ERCC/MDIR1 and overall response rate. We excluded duplicate publications, letters and review articles. The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment. Results A total of 11 studies were included in this meta-analysis. For studies evaluating ERCC1 Cl18T, test for heterogeneity was done （X2=13.41, P=0.1）, and the odds ratio （OR） for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 （95% CI 1.09-2.06, P=0.01）. In four studies evaluating MDR1 polymorphism, test for heterogeneity was also done （X2=3.22, P=0.36）, and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 （95% CI 1.44-3.68, P=0.0005）. Conclusions The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 Cl18T and MDR1 C3435T SNP. In further perspective studies, the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.展开更多
基金supported by the National Key Research and Development Plan of China(No.2017YFC1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Scientific Foundation of China(No.81771912,81901910,82072090,and 82001986)。
文摘Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.
基金supported by the National High-tech R&D Program of China(863 Program)(2012AA02A517)National Natural Science Foundation of China(81173129,81202595,81373490,81273595)
文摘Background:Platinum-based chemotherapy is the first-line treatment of non-small cell lung cancer(NSCLC);it is therefore important to discover biomarkers that can be used to predict the efficacy and toxicity of this treatment.Four important transporter genes are expressed in the kidney,including organic cation transporter 2(OCT2),multidrug and toxin extrusion 1(MATEl),ATP-binding cassette subfamily B member 1 {ABCB1),and ATP-binding cassette subfamily C member 2(ABCC2),and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs.This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinumbased chemotherapy response and toxicity in NSCLC patients.Methods:A total of 403 Chinese NSCLC patients were recruited for this study.All patients were newly diagnosed with NSCLC and received at least two cycles of platinum-based chemotherapy.The tumor response and toxicity were evaluated after two cycles of treatment,and the patients' genomic DNA was extracted.Seven single-nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum-based chemotherapy toxicity and response.Results:OCT2 rs316019 was associated with hepatotoxicity(P = 0.026) and hematological toxicity(P = 0.039),and MATEl rs2289669 was associated with hematological toxicity induced by platinum(P = 0.016).In addition,ABCC2rs717620 was significantly associated with the platinum-based chemotherapy response(P = 0.031).ABCB1 polymorphisms were associated with neither response nor toxicity.Conclusion:OCT2 rs316019,MATEl rs2289669,and ABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum-based treatment in NSCLC patients.Trial registration Chinese Clinical Trial Registry
文摘Both platinum-based doublet chemotherapy(PBC) and epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer(NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival(OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials—involving 11,456 adult patients in 32 arms—were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian(predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs(r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations(r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations(r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.
基金the National Natural Science Foundation of China(No.81703215,81974381)Beijing Xisike Clinical Oncology Research Foundation(No.Y-Q201801-059,81974381)。
文摘Objective This study assessed the weight loss changes and gastrointestinal symptoms in patients with advanced tumors receiving platinum-containing chemotherapy.Methods We retrospectively reviewed 297 patients with advanced cancers[124 gastrointestinal(GI)cancer patients,119 lung cancer patients and 54 head and neck cancer(HNC)patients]receiving first-line chemotherapy at Tongji Hospital.The patients’changes in body weight,body mass index(BMI),and biochemical parameters(serum haemoglobin and albumin levels)were compared before and after two chemotherapy cycles.Results More than half[54.88%(163/297)]of the patients had experienced unintentional weight loss in the 6 months before chemotherapy,and weight loss≥5%and≥10%of the body mass was noted in 35.69%and 20.20%of the patients,respectively.After two cycles of platinum-based chemotherapy,the proportions of patients with a>5%reduction in body weight among patients with GI,lung,and head and neck cancers were 47.5%(59/124),44.53%(53/119),and 46.2%(25/54),respectively.The patients with GI and lung cancers were more vulnerable to extreme weight loss(≥10%)than those with HNC(P=0.025).The serum hemoglobin levels were also remarkably decreased relative to those before chemotherapy(all P<0.05).Common GI symptoms reported by all patients included anorexia(61.28%),vomiting(52.53%),and nausea(51.18%).A higher proportion of patients with≥10%weight loss experienced anorexia and vomiting(OR=12.21 and 3.61,P=0.008 and 0.047,respectively).Conclusions For advanced cancer patients receiving platinum-based chemotherapy,the GI symptoms are the major factor related to their nutritional status.Appropriate nutritional screening,evaluation and treatment should be applied during the treatment of cancer in order to reduce GI symptoms and improve the patient’s nutritional status.
文摘In the past decade,the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)has dramatically influenced the therapeutic strategies for treating lung cancer,but with tumor progression and drug resistance,patients will ultimately develop reduced sensitivity to EGFR-TKIs.How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research.Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs.However,results of pre-clinical and clinical studies have been inconsistent.The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research.Therefore,systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.
文摘1文献来源
Tetsuya M, Satoshi M, Yasushi Y, et al. Gefitinib versus Cisplatin plus Docetaxel in patients with non-small-cell lung cancer harbouring mutations of theepidermal growth factor receptor （WJTOG3405） ： Anopen label, randomised phase 3 trial [J]. LancetOncol,2010, 11（2） ： 121-125.
文摘Objective： to determine the role of excision repair cross-complementing group 1 gene （ERCC1） and ribonucleotide reductase subunit M1 （RRM1） expression in predicting response and survival in Chinese patients with advanced stage non-small cell lung cancer （NSCLC） treated with platinum-based chemotherapy. Methods： Formalin-fixed, paraffin-embedded biopsy tissues were retrospectively obtained from 160 advanced NSCLC patients. mRNA expression levels of ERCC1 and RRM1 were determined by real-time PCR. Results： Associations between mRNA expression level of ERCC1 and RRM1 and clinic-pathologic parameters were analyzed. One handred and forty two （88.75%） specimens were successfully amplified. mRNA expression level of ERCC1 and RRM1 was negatively associated with tumor response. ERCC1 expression levels ranged from 0.01 to 78.79 [median 0.63, mean 4.25 and standard deviation （SD） 9.23] and RRM1 from 0.00 to 30.91 （median 0.63, mean 0.87 and SD 3.36）. By adopting cut-off values according to median expression levels, we found that MST in patients with low ERCC1 mRNA levels was significantly longer in overall population than in patients with higher levels （18.63 versus 13.69 months, log-rank 5.73, P=0.017）, but we did not found the survival benefit of the patients with low expression level of RRM1. （19.07 versus 14.88, log-rank 1.66, P=0.197）. Further, in the multivariable Cox regression model analysis we found that low level of ERCC1 expression, the presence of weight loss and target therapy, were significant prognostic factors for survival. Conclusion： ERCC1 expression is associated with patients’ survival in Chinese advanced NSCLC patients treated with platinum-based regimen and may serve as a biomarker in predicting tumor response and clinical outcome in the patient population.
文摘Hepatocholangiocarcinoma(c HCC-ICC) is a rare primary hepatic tumor defined by the presence of histological features of both hepatocellular carcinoma(HCC) and intrahepatic cholangiocarcinoma(ICC). Its prevalence ranges from 1%-5% of all primary liver cancers. We report the case of a 55-year-old cirrhotic male patient admitted to our university hospital for dysphagia, revealing a 10 cm lower-third esophageal metastasis of an unresectable c HCC-ICC with stemcell features. Computed tomography and abdominal magnetic resonance imaging scans revealed multiple hepatic lesions combining features of both HCC and ICC, associated with synchronous bone metastasis. Histological and immunohistochemical analyses of biopsies from the esophageal lesion and the hepatic tumor confirmed the diagnosis of c HCC-ICC with a stem cell-subtype, according to the World HealthOrganization classification. After a multidisciplinary meeting, the patient was treated with chemotherapy. He received two cycles of a gemcitabine plus cisplatin regimen before bone progression, and he died 3 mo after the initial diagnosis.
文摘BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.
基金funded by Italian Ministry of Health, Ricerca Corrente 2019
文摘BACKGROUND Gynecological malignancies represent a major cause of death in women and are often treated with platinum-based regimens.Patients undergoing chemotherapy suffer from alterations in nutritional status which may worsen gastrointestinal(GI)toxicities,quality of life and affect the overall prognosis.Indeed,assuring a good nutritional status and limiting toxicities during treatment are still major goals for clinicians.AIM To assess the role of Mediterranean Diet(MD)in reducing GI toxicities in patients with gynecological cancers treated with platinum-based regimens.METHODS We conducted an observational study on 22 patients with gynecological tumors treated with a platinum-based chemotherapy at Candiolo Cancer Institute FPO/IRCCS between January 2018 and June 2018.The food and frequency(FFQ)and the Patient-Reported Outcomes Common Terminology Criteria For Adverse Events(PRO-CTCAE)questionnaires were administered at baseline and at every Day 1 of each cycle.To evaluate the differences in GI toxicities the study population was divided in two groups according to the currently validated Mediterranean Diet Serving Score(MDSS)at baseline.RESULTS Patients with high MDSS reported a trend toward lower GI toxicities according to PRO-CTCAE at each timepoint(first evaluation:P=0.7;second:P=0.52;third:P=0.01).In particular,difference in nausea frequency and gravity(P<0.001),stomach pain frequency and gravity(P=0.01 and P=0.02),abdomen bloating frequency and gravity(P=0.02 and P=0.03),and interference with daily activities(P=0.02)were highly statistically significant at the end of treatment.More than 60%of patients changed their food habits during chemotherapy mainly because of GI toxicities.A higher reduction of food intake,both in terms of caloric(P=0.29)and of single nutrients emerged in the group experiencing higher toxicity.CONCLUSION Our results show that adherence to MD possibly reduces GI toxicity and prevents nutritional status impairment during chemotherapy treatment.Bigger studies are needed to confirm our results.
基金National Key Research and Development Program of China,Grant/Award Number:2017YFC1308900The clinical research and cultivation project of shanghai Shenkang hospital development center,Grant/Award Number:SHDC12017×01Sun Yat-sen University Xie Tong Chuang Xin Program,Grant/Award Number:ZLYXXTCX201504。
文摘Background:There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer(AGC).We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine(XELOX)and epirubicin,oxaliplatin,plus capecitabine(EOX)regimens in treating AGC.Methods:This phase III trial enrolled previously untreated patients with AGC whowere randomly assigned to receive the XELOXor EOXregimen.The primary endpoint was non-inferiority in progression-free survival(PFS)for XELOX as compared with EOX on an intention-to-treat basis.Results:Between April 10,2015 andAugust 20,2020,448AGCpatientswere randomized to receive XELOX(n=222)or EOX(n=226).The median PFS(mPFS)was 5.0 months(95%confidence interval[CI]=4.5-6.0 months)in the XELOX arm and 5.5 months(95%CI=5.0-6.0 months)in the EOX arm(hazard ratio[HR]=0.989,95%CI=0.812-1.203;P_(non-inferiority)=0.003).There was no significant difference inmedian overall survival(mOS)(12.0 vs.12.0months,P=0.384)or objective response rate(37.4%vs.45.1%,P=0.291)between the two groups.In patients with poorly differentiated adenocarcinoma and liver metastasis,the EOX arm had a significantly longer mOS(P=0.021)and a trend of longer mPFS(P=0.073)than the XELOX arm.The rate of grade 3/4 adverse events(AEs)was 42.2%(90/213)in the XELOX arm and 72.5%(156/215)in the EOX arm(P=0.001).The global health-related quality of life(QoL)score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy.Conclusions:This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients.However,the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.
文摘Ovarian cancer is the leading cause of gynecologic cancer death in the United States.Most ovarian cancer patients are diagnosed with advanced-stage disease,which poses a challenge for early detection and effective treatment.At present,cytoreductive surgery and platinum-based chemotherapy are foundational for patients with newly diagnosed ovarian cancer,but unfortunately,most patients will recur and die of their disease.Therefore,there is a significant need to seek innovative,novel approaches for early detection and to overcome chemoresistance for ovarian cancer patients.The microbiome,comprising diverse microbial communities inhabiting various body sites,is vital in maintaining human health.Changes to the diversity and composition of the microbial communities impact the microbiota-host relationship and are linked to diseases,including cancer.The microbiome contributes to carcinogenesis through various mechanisms,including altered host immune response,modulation of DNA repair,upregulation of pro-inflammatory pathways,altered gene expression,and dysregulated estrogen metabolism.Translational and clinical studies have demonstrated that specific microbes contribute to ovarian cancer development and impact chemotherapy’s efficacy.The microbiome is malleable and can be altered through different approaches,including diet,exercise,medications,and fecal microbiota transplantation.This review provides an overview of the current literature regarding ovarian cancer and the microbiome of female reproductive and gastrointestinal tracts,focusing on mechanisms of carcinogenesis and options for modulating the microbiota for cancer prevention and treatment.Advancing our understanding of the complex relationship between the microbiome and ovarian cancer may provide a novel approach for prevention and therapeutic modulation in the future.
基金This study was supported by a grant ＂from the National Natural Science Foundation of China （No. C 171003） and Doctoral Fund ot Ministry of Education of China.
文摘Background Platinum-based regimens are used as standard first-line chemotherapy in non-small cell lung cancer （NSCLC） patients. To study if pharmacogenetic approach may allow a tailored selection of platinum chemotherapy for advanced NSCLC, we performed a meta-analysis to compare chemosensitivity to platinum with differe4nt ERCC1 Cl18T/ MDR1 C3435T single-nucleotide polymorphism （SNP）. Methods Relevant studies were identified by searching the PubMed, Embase, Cochrane, OVID, Springer, EBSCO and CNKI databases. Inclusion criteria were patients with advanced NSCLC who received platinum-based chemotherapy, an evaluated polymorphism of ERCC/MDIR1 and overall response rate. We excluded duplicate publications, letters and review articles. The RevMan 4.2 and STATA 11 package were used to do comprehensive quantitative assessment. Results A total of 11 studies were included in this meta-analysis. For studies evaluating ERCC1 Cl18T, test for heterogeneity was done （X2=13.41, P=0.1）, and the odds ratio （OR） for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 1.50 （95% CI 1.09-2.06, P=0.01）. In four studies evaluating MDR1 polymorphism, test for heterogeneity was also done （X2=3.22, P=0.36）, and the OR for the wild-type C/C genotype versus the heterozygous C/T and T/T genotypes was 2.30 （95% CI 1.44-3.68, P=0.0005）. Conclusions The results indicated that platinum-based chemotherapy sensitivity was significantly associated with polymorphism of ERCC1 Cl18T and MDR1 C3435T SNP. In further perspective studies, the ERCC1/MDR1 SNPs might serve as simple and less invasive biomarkers for personalized chemotherapy with platinum-based anticancer drugs.
