BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combinat...BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.展开更多
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 chemoth...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.展开更多
Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene expression.Methods:For this study,623 samples were ...Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene expression.Methods:For this study,623 samples were collected from The Cancer Genome Atlas(TCGA)database,comprising tumor mutational burden(TMB),RNA sequencing(RNA-Seq),and clinical data.Differential gene expression analysis,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified genes were conducted using the R package.Additionally,a comparative analysis of immune infiltrating cell composition in metastatic and non-metastatic groups was performed.Hub genes,exhibiting high levels of interaction,were selected using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database.The Drug Gene Interaction Database(DGIdb)was then utilized to estimate drugs targeting the identified hub genes.Results:The transcriptome data of 326 colorectal cancer patients with low TMB were analyzed,comprising 58 patients with metastasis and 268 patients without metastasis.Among the differential expression in 1,111 genes for patients with metastasis compared to those without metastasis,733 genes were upregulated,and 378 genes were downregulated.KEGG and GO enrichment analysis indicated significant differences in gene expression in CRC metastatic patients with low TMB compared to non-metastasis patients with low TMB.Enriched pathways included humoral immune response,immunoglobulin production,and regulation of AMPA receptor activity.Two genes related to interleukin-12 were identified through secondary enrichment for immune-related genes.Analysis of tumor-infiltrating immune cell data revealed significant differences in memory-activated T cell CD4 and T cell CD8.Conclusions:This analysis of RNA sequencing data and immune-filtrating cell data revealed significant differences between metastatic colorectal cancer patients with low TMB and their non-metastatic counterparts.These distinctions suggest the possibility of identifying more effective drugs or therapies for metastatic colorectal cancer patients with low TMB.展开更多
Background: Most newly diagnosed prostate cancers in Benin are metastatic diseases and patients are reluctant to undergo orchiectomy. Still, chemical androgen deprivation therapy is not always available and not every ...Background: Most newly diagnosed prostate cancers in Benin are metastatic diseases and patients are reluctant to undergo orchiectomy. Still, chemical androgen deprivation therapy is not always available and not every patient can afford it. Thus, it will be interesting to evaluate the results of that therapy in the country. Objective: To analyze the survival rate and factors influencing it in metastatic prostate cancer patients who underwent triptorelin-based androgen deprivation therapy at the former Military Teaching Hospital of Cotonou from January 1, 2012, to December 31, 2022. Patients and Method: Metastatic prostate cancer patients received intragluteal injections of triptorelin 11.25 mg every 3 months. We retrospectively collected follow-up data from the patients’ medical records. By means of the software StataTM version 15, we performed a descriptive analysis of qualitative data. We used Kaplan-Meir method to estimate the overall survival rate in the whole cohort and in specific subgroups of patients. We compared survival rates by using the log-rank test. Results: 68 metastatic prostate cancer patients aged 47-86 years (mean = 69.9) with initial PSA ranging from 24.25 to 6334 ng/mL (mean = 666.1) started triptorelin-based castration. The tumor grade in 21 (33.3%), 14 (22.2%), 15 (23.8), 8 (12.7%), and 5 (7.9%) patients was respectively ISUP grade groups 5, 4, 3, 2, and 1. 15 (22.1%), 4 (5.9%), 2 (2.9%), 1 (1.5%), 11 (16.2%), and 7 (10.3%) patients respectively had hypertension, diabetes mellitus, peptic ulcer, asthma, unilateral or bilateral hydronephrosis, and paralysis. The mean nadir PSA level was 22.5 ng/mL (range: 0.01-220.25). The mean time to nadir PSA level was 8.9 months (range: 3-57). The overall survival rate was 42.6%. There was no significant survival difference between age groups (p = 0.475), relating to the presence of diabetes or hypertension (p = 0.757) or to the presence of paralysis or hydronephrosis (p = 0.090). The initial PSA level exerted no significant impact on patients’ survival (p = 0.461). Neither did the time to PSA nadir (p = 0.263). The PSA nadir less than 4 ng/mL (p = 0.005) and the PSA nadir less than 4 ng/mL achieved in 12 months or less (p = 0.002) were predictive of longer survival rate. The difference in survival rate through the ISUP grade groups was not significant (p = 0.061). Conclusion: The overall survival rate was 42.6% at 5 years. Achieving PSA nadir of less than 4 ng/mL in less than 12 months of castration was predictive of longer survival rate in triptorelin-castrated metastatic prostate cancer patients.展开更多
BACKGROUND Cholangiocarcinoma and small intestine cancer are common clinical malignancies,but metastatic cholangiocarcinoma and small intestine cancer are rare,especially simultaneous metastatic cholangiocarcinoma and...BACKGROUND Cholangiocarcinoma and small intestine cancer are common clinical malignancies,but metastatic cholangiocarcinoma and small intestine cancer are rare,especially simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer.Since the clinical presentation of metastatic cholangiocarcinoma and small intestine cancer does not differ from primary tumor,it may lead to misdiagnosis preoperatively.CASE SUMMARY A 66-year-old woman was admitted to our hospital for further treatment due to abdominal pain and jaundice.Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed an occupying lesion of the bile duct,considering a high possibility of primary bile duct tumor.Therefore,we performed a radical bile duct cancer surgery and cholecystectomy,and multiple tumors in the small intestine were found and removed during the surgery process.Postoperative pathology showed metastatic bile duct cancer and small intestine cancer from tumors in other parts.The patient underwent a right total mastectomy and axillary lymph node dissection because of right breast cancer 2 years ago.Combining with the immunohistochemical results,the patient was finally diagnosed as metastatic cholangiocarcinoma and metastatic small intestine cancer from breast cancer.Postoperatively,the patient received four cycles of chemotherapy and targeted therapy with docetaxel,capecitabine and trastuzumab.Unfortunately,the patient eventually died from tumor progression,thoracoabdominal infection,and sepsis 5 mo after surgery.CONCLUSION Simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer are rare and the prognosis is extremely poor.Improving preoperative diagnostic accuracy is beneficial to avoid excessive surgical treatment.Treatment should be aimed at relieving biliary obstruction and abdominal pain,and then supplemented with chemotherapy and targeted therapy to control tumor progression and prolong the patient’s life.展开更多
Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sop...Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC.The development of next-generation sequencing and wholeexome sequencing,which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment,has resulted in tremendous breakthroughs in DNA sequencing technology in recent years.The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage,presence of high-risk pathologic characteristics,microsatellite instability status,patient age,and performance status.Chemotherapy,targeted therapy,and immunotherapy are the main systemic treatments for patients with mCRC.Despite the fact that these novel treatment choices have increased overall survival for mCRC,survival remains optimal for individuals with non-metastatic disease.The molecular technologies currently being used to support our ability to practice personalized medicine;the practical aspects of applying molecular biomarkers to regular clinical practice;and the evolution of chemotherapy,targeted therapy,and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.展开更多
Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of present...Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of presentation and an additional 25%present with localized disease and will subsequently develop metastases3.The treatment of metastatic colorectal cancer(mCRC)is gradually moving towards the era of precision therapy,which involves guided treatment based on individual genetic characteristics4.Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guidelines was published in 2017,the guidelines have been updated annually according to the latest clinical trial findings5-9.Herein we summarize how the CSCO guidelines enable tailor-made treatments of mCRC with different molecular characteristics(Figure 1).展开更多
Pancreatic ductal adenocarcinoma(PDAC)is nowadays the fourth leading cause of cancer-related death worldwide,but according to recent estimations it will become the second leading cause of cancer-related deaths in the ...Pancreatic ductal adenocarcinoma(PDAC)is nowadays the fourth leading cause of cancer-related death worldwide,but according to recent estimations it will become the second leading cause of cancer-related deaths in the USA up to 2030,following lung cancer.The implementation of neoadjuvant chemotherapy during recent years led to an increase of overall survival at 35 months in PDAC after R0 resection[1].However,pancreatic cancer has a particularity that makes it a real challenge for clinicians:only 20%of patients are diagnosed early enough to have a resectable pancreatic cancer,whereas 40%of patients present with locally advanced or non-resectable disease,while the rest present with distant metastases[2].Systemic chemotherapy plays the main role in metastatic PDAC treatment:polychemotherapy regimens such as FOLFIRINOX(folinic acid,5-fluorouracil,irinotecan and oxaliplatin)or combination of gemcitabine/nab-paclitaxel seemed to improve median overall survival from 6.8 to 11.1 months and 6.7 to 8.5 months,respectively[3].展开更多
Dear Editor,Introduction of prostate-specific membrane antigen positron-emission tomography/contrast-enhanced computed tomography(PSMA PET/CECT)for prostate cancer staging and follow-up have increased detection of met...Dear Editor,Introduction of prostate-specific membrane antigen positron-emission tomography/contrast-enhanced computed tomography(PSMA PET/CECT)for prostate cancer staging and follow-up have increased detection of metastases even in non-regional nodes,often in oligometastatic or oligorecurrent state[1].Some of these merit metastases-directed therapy(MDT)such as surgery or radiotherapy(RT)with curative intent.展开更多
Dear Editor,Prostate cancer is the most common cancer among men[1].Androgen deprivation therapy(ADT)has remained the primary treatment of metastatic-hormone-sensitive prostate cancer(mHSPC),providing a temporary disea...Dear Editor,Prostate cancer is the most common cancer among men[1].Androgen deprivation therapy(ADT)has remained the primary treatment of metastatic-hormone-sensitive prostate cancer(mHSPC),providing a temporary disease control in the majority of patients.Despite initial ADT response,castration-resistance prostate cancer(CRPC)still develops.Previous study have attempted to determine possible biomarkers for poor prognosis in patients with CRPC[2].展开更多
BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treat...BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.展开更多
BACKGROUND The purpose of the present study was to examine retrospectively the contribution of 18Fluorodeoxyglucose positron emission tomography computed tomography(18FDG-PET/CT)to the evaluation of response to first-...BACKGROUND The purpose of the present study was to examine retrospectively the contribution of 18Fluorodeoxyglucose positron emission tomography computed tomography(18FDG-PET/CT)to the evaluation of response to first-line gemcitabine plus cispla-tin-based chemotherapy in patients with metastatic bladder cancer.AIM To evaluate the response to Gemcitabine plus Cisplatin-based chemotherapy using 18FDG-PET/CT imaging in patients with metastatic bladder cancer.METHODS Between July 2007 and April 2019,79 patients underwent 18FDG-PET/CT imaging with the diagnosis of Metastatic Bladder Carcinoma(M-BCa).A total of 42 pa-tients(38 male,4 female)were included in the study,and all had been admi-nistered Gemcitabine plus Cisplatin-based chemotherapy.After completion of the therapy,the patients underwent a repeat 18FDG-PET/CT scan and the results were compared with the PET/CT findings before chemotherapy according to European Organisation for the Research and treatment of cancer criteria.Mean age was 66.1 years and standard deviation was 10.7 years(range:41–84 years).RESULTS Of the patients,seven(16.6%)were in complete remission,17(40.5%)were in partial remission,six(14.3%)had a stable disease,and 12(28.6%)had a pro-gressive disease.The overall response rate was 57.1 percent.CONCLUSION 18FDG-PET/CT can be considered as a successful imaging tool in evaluating response to first-line chemotherapy for metastatic bladder cancer.Anatomical and functional data obtained from PET/CT scans may be useful in the planning of secondline and thirdline chemotherapy.展开更多
Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment ...Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.展开更多
BACKGROUND Colon cancer(CC)is one of the leading causes of cancer-related morbidity and mortality worldwide.Traditional Chinese medicine(TCM)is widely used in the treatment of various chronic diseases.CC easily metast...BACKGROUND Colon cancer(CC)is one of the leading causes of cancer-related morbidity and mortality worldwide.Traditional Chinese medicine(TCM)is widely used in the treatment of various chronic diseases.CC easily metastasizes and results in high morbidity and mortality rates.CASE SUMMARY A 71-year-old man with a 12-year history of old myocardial infarction and a 7-year history of type 2 diabetes mellitus was diagnosed with CC and underwent right hemicolectomy 1 year ago.Tumor biopsy revealed moderately poorly differentiated adenocarcinoma.Subsequently,chemotherapy with oxaliplatin and paclitaxel was administered.Anastomosis recurrence and pelvic metastasis were noted 37 d later.The patient received eight 21-d cycles of adjuvant chemotherapy with oxaliplatin and capecitabine after recurrence.However,the tumor persisted,and chemotherapy-related liver damage developed gradually.Thus,he was advised to take TCM for the recurrence and pelvic metastasis.The patient’s metastatic CC was cured after receiving TCM combined with long-term chemotherapy.CONCLUSION TCM may be an effective adjunct therapy in the treatment of patients with metastatic CC.展开更多
BACKGROUND Immunotherapy has revolutionized the treatment of metastatic melanoma,but a significant proportion of patients still experience treatment resistance.Fecal microbiota transplantation(FMT)has emerged as a pot...BACKGROUND Immunotherapy has revolutionized the treatment of metastatic melanoma,but a significant proportion of patients still experience treatment resistance.Fecal microbiota transplantation(FMT)has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.CASE SUMMARY We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with antiprogrammed death-ligand 1(PD-L1)immunotherapy(pembrolizumab).After failing multiple lines of treatment,the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy.Following FMT,the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease.Despite a subsequent recurrence in the small bowel that was resected,the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.CONCLUSION The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.展开更多
Soft tissue sarcomas represent only 1% of all adult cancers;myxofibrosarcoma is the most common type that arises in adult extremities, particularly lower limbs (77%), other less common locations are the trunk (12%) an...Soft tissue sarcomas represent only 1% of all adult cancers;myxofibrosarcoma is the most common type that arises in adult extremities, particularly lower limbs (77%), other less common locations are the trunk (12%) and neck (3%). Usually presenting as a painless, subcutaneous, slow growing mass with tendency for recurrence, they are prone to have higher histological grade and metastatic potential after recurrence;even in optimal multidisciplinary settings patients can have incomplete resections, making metastatic disease more common after misdiagnosis. We present the case of a 69-year-old male patient with a right infraescapular tumor, presenting as a painless 15 × 8 cm, mobile mass, with a slow but progressive growth, history of a previous tumor excised at the same location 5 years prior without histopathological report.展开更多
Background: The majority of breast cancer patients in Tanzania present with advanced disease, and a significant proportion has metastatic breast cancer (MBC) on presentation or develops it during the course of their f...Background: The majority of breast cancer patients in Tanzania present with advanced disease, and a significant proportion has metastatic breast cancer (MBC) on presentation or develops it during the course of their follow-up. With few treatment options to choose from, such patients often benefit from empathic support and access to information to help them make treatment decisions based on their individual circumstances and needs. Patients with MBC have been shown to present with unique physical, social and psychological needs that require additional time, counselling and availability of health care providers in addition to the routine options available to other patients. In resource-limited settings, the needs of such patients are often unknown and unaddressed, which adds to the anxiety associated with the diagnosis and its treatment. Materials and methods: This descriptive qualitative study was conducted using 3 focus group discussions with a total of 17 participants with metastatic breast cancer (MBC) attending Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Participants were purposively selected for the study from outpatient clinics and inpatient wards. A semi-structured FGD guide was used to moderate discussions and analysis was done using a thematic approach. Results: The median age of participants was 51 (range 33 - 81 years) with an average of 4 months (range 1 - 12 months) from diagnosis of BC to the interview. 4 (24%) were diagnosed with MBC on first presentation (denovo). Participants spoke about the importance of accurate BC-related information in allowing timely referral and treatment both in the community and within the health system. They recognized the role of mass and social media in increasing awareness about BC and identified myths surrounding cancer treatment especially mastectomy. Correct and timely information at points of care, through media platforms and via ambassadors/patient support groups was perceived as a means to avoiding delays and securing early and effective treatment. Conclusion: Patients with MBC in Tanzania have many unmet informational needs in relation to their disease. Accurate BC-related information is important in allowing early detection and diagnosis. At the community level, provision of information through established media platforms and the use of patient advocates may help to enable early referral and treatment of patients.展开更多
BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targete...BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS.Among them,23%(n=6),19%(n=5),31%(n=8),and 19%(n=5)were classified as CMS1,CMS2,CMS3,and CMS4,respectively.Additionally,8%of patients(n=2)could not be classified into any of the four CMS categories.The median overall survival of the total sample was 28 mo,and for CMS1,CMS2,CMS3 and CMS4 it was 11,20,30 and 45 mo respectively,with no statistically significant differences between groups.CONCLUSION A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients.This classification process,which divides patients into the four CMS categories,holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.展开更多
Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate bio...Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.展开更多
文摘BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.
文摘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.
文摘Objective:To identify potential drug targets for metastasis colorectal cancer(CRC)patients with low mutational burden by examining differences in immune-related gene expression.Methods:For this study,623 samples were collected from The Cancer Genome Atlas(TCGA)database,comprising tumor mutational burden(TMB),RNA sequencing(RNA-Seq),and clinical data.Differential gene expression analysis,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of the identified genes were conducted using the R package.Additionally,a comparative analysis of immune infiltrating cell composition in metastatic and non-metastatic groups was performed.Hub genes,exhibiting high levels of interaction,were selected using the Search Tool for the Retrieval of Interacting Genes/Proteins(STRING)database.The Drug Gene Interaction Database(DGIdb)was then utilized to estimate drugs targeting the identified hub genes.Results:The transcriptome data of 326 colorectal cancer patients with low TMB were analyzed,comprising 58 patients with metastasis and 268 patients without metastasis.Among the differential expression in 1,111 genes for patients with metastasis compared to those without metastasis,733 genes were upregulated,and 378 genes were downregulated.KEGG and GO enrichment analysis indicated significant differences in gene expression in CRC metastatic patients with low TMB compared to non-metastasis patients with low TMB.Enriched pathways included humoral immune response,immunoglobulin production,and regulation of AMPA receptor activity.Two genes related to interleukin-12 were identified through secondary enrichment for immune-related genes.Analysis of tumor-infiltrating immune cell data revealed significant differences in memory-activated T cell CD4 and T cell CD8.Conclusions:This analysis of RNA sequencing data and immune-filtrating cell data revealed significant differences between metastatic colorectal cancer patients with low TMB and their non-metastatic counterparts.These distinctions suggest the possibility of identifying more effective drugs or therapies for metastatic colorectal cancer patients with low TMB.
文摘Background: Most newly diagnosed prostate cancers in Benin are metastatic diseases and patients are reluctant to undergo orchiectomy. Still, chemical androgen deprivation therapy is not always available and not every patient can afford it. Thus, it will be interesting to evaluate the results of that therapy in the country. Objective: To analyze the survival rate and factors influencing it in metastatic prostate cancer patients who underwent triptorelin-based androgen deprivation therapy at the former Military Teaching Hospital of Cotonou from January 1, 2012, to December 31, 2022. Patients and Method: Metastatic prostate cancer patients received intragluteal injections of triptorelin 11.25 mg every 3 months. We retrospectively collected follow-up data from the patients’ medical records. By means of the software StataTM version 15, we performed a descriptive analysis of qualitative data. We used Kaplan-Meir method to estimate the overall survival rate in the whole cohort and in specific subgroups of patients. We compared survival rates by using the log-rank test. Results: 68 metastatic prostate cancer patients aged 47-86 years (mean = 69.9) with initial PSA ranging from 24.25 to 6334 ng/mL (mean = 666.1) started triptorelin-based castration. The tumor grade in 21 (33.3%), 14 (22.2%), 15 (23.8), 8 (12.7%), and 5 (7.9%) patients was respectively ISUP grade groups 5, 4, 3, 2, and 1. 15 (22.1%), 4 (5.9%), 2 (2.9%), 1 (1.5%), 11 (16.2%), and 7 (10.3%) patients respectively had hypertension, diabetes mellitus, peptic ulcer, asthma, unilateral or bilateral hydronephrosis, and paralysis. The mean nadir PSA level was 22.5 ng/mL (range: 0.01-220.25). The mean time to nadir PSA level was 8.9 months (range: 3-57). The overall survival rate was 42.6%. There was no significant survival difference between age groups (p = 0.475), relating to the presence of diabetes or hypertension (p = 0.757) or to the presence of paralysis or hydronephrosis (p = 0.090). The initial PSA level exerted no significant impact on patients’ survival (p = 0.461). Neither did the time to PSA nadir (p = 0.263). The PSA nadir less than 4 ng/mL (p = 0.005) and the PSA nadir less than 4 ng/mL achieved in 12 months or less (p = 0.002) were predictive of longer survival rate. The difference in survival rate through the ISUP grade groups was not significant (p = 0.061). Conclusion: The overall survival rate was 42.6% at 5 years. Achieving PSA nadir of less than 4 ng/mL in less than 12 months of castration was predictive of longer survival rate in triptorelin-castrated metastatic prostate cancer patients.
文摘BACKGROUND Cholangiocarcinoma and small intestine cancer are common clinical malignancies,but metastatic cholangiocarcinoma and small intestine cancer are rare,especially simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer.Since the clinical presentation of metastatic cholangiocarcinoma and small intestine cancer does not differ from primary tumor,it may lead to misdiagnosis preoperatively.CASE SUMMARY A 66-year-old woman was admitted to our hospital for further treatment due to abdominal pain and jaundice.Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed an occupying lesion of the bile duct,considering a high possibility of primary bile duct tumor.Therefore,we performed a radical bile duct cancer surgery and cholecystectomy,and multiple tumors in the small intestine were found and removed during the surgery process.Postoperative pathology showed metastatic bile duct cancer and small intestine cancer from tumors in other parts.The patient underwent a right total mastectomy and axillary lymph node dissection because of right breast cancer 2 years ago.Combining with the immunohistochemical results,the patient was finally diagnosed as metastatic cholangiocarcinoma and metastatic small intestine cancer from breast cancer.Postoperatively,the patient received four cycles of chemotherapy and targeted therapy with docetaxel,capecitabine and trastuzumab.Unfortunately,the patient eventually died from tumor progression,thoracoabdominal infection,and sepsis 5 mo after surgery.CONCLUSION Simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer are rare and the prognosis is extremely poor.Improving preoperative diagnostic accuracy is beneficial to avoid excessive surgical treatment.Treatment should be aimed at relieving biliary obstruction and abdominal pain,and then supplemented with chemotherapy and targeted therapy to control tumor progression and prolong the patient’s life.
文摘Significant progress has been achieved in the treatment of metastatic colorectal cancer(mCRC)patients during the last 20 years.There are currently numerous treatments available for the first-line treatment of mCRC.Sophisticated molecular technologies have been developed to reveal novel prognostic and predictive biomarkers for CRC.The development of next-generation sequencing and wholeexome sequencing,which are strong new tools for the discovery of predictive molecular biomarkers to facilitate the delivery of customized treatment,has resulted in tremendous breakthroughs in DNA sequencing technology in recent years.The appropriate adjuvant treatments for mCRC patients are determined by the tumor stage,presence of high-risk pathologic characteristics,microsatellite instability status,patient age,and performance status.Chemotherapy,targeted therapy,and immunotherapy are the main systemic treatments for patients with mCRC.Despite the fact that these novel treatment choices have increased overall survival for mCRC,survival remains optimal for individuals with non-metastatic disease.The molecular technologies currently being used to support our ability to practice personalized medicine;the practical aspects of applying molecular biomarkers to regular clinical practice;and the evolution of chemotherapy,targeted therapy,and immunotherapy strategies for the treatment of mCRC in the front-line setting are all reviewed here.
基金supported by the Provincial Key R&D Program of Zhejiang Province(Grant No.2021C03125)the Beijing Xisike Clinical Oncology Research Foundation(Grant No.Y-tongshu2021/ms-0003).
文摘Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of presentation and an additional 25%present with localized disease and will subsequently develop metastases3.The treatment of metastatic colorectal cancer(mCRC)is gradually moving towards the era of precision therapy,which involves guided treatment based on individual genetic characteristics4.Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guidelines was published in 2017,the guidelines have been updated annually according to the latest clinical trial findings5-9.Herein we summarize how the CSCO guidelines enable tailor-made treatments of mCRC with different molecular characteristics(Figure 1).
文摘Pancreatic ductal adenocarcinoma(PDAC)is nowadays the fourth leading cause of cancer-related death worldwide,but according to recent estimations it will become the second leading cause of cancer-related deaths in the USA up to 2030,following lung cancer.The implementation of neoadjuvant chemotherapy during recent years led to an increase of overall survival at 35 months in PDAC after R0 resection[1].However,pancreatic cancer has a particularity that makes it a real challenge for clinicians:only 20%of patients are diagnosed early enough to have a resectable pancreatic cancer,whereas 40%of patients present with locally advanced or non-resectable disease,while the rest present with distant metastases[2].Systemic chemotherapy plays the main role in metastatic PDAC treatment:polychemotherapy regimens such as FOLFIRINOX(folinic acid,5-fluorouracil,irinotecan and oxaliplatin)or combination of gemcitabine/nab-paclitaxel seemed to improve median overall survival from 6.8 to 11.1 months and 6.7 to 8.5 months,respectively[3].
文摘Dear Editor,Introduction of prostate-specific membrane antigen positron-emission tomography/contrast-enhanced computed tomography(PSMA PET/CECT)for prostate cancer staging and follow-up have increased detection of metastases even in non-regional nodes,often in oligometastatic or oligorecurrent state[1].Some of these merit metastases-directed therapy(MDT)such as surgery or radiotherapy(RT)with curative intent.
文摘Dear Editor,Prostate cancer is the most common cancer among men[1].Androgen deprivation therapy(ADT)has remained the primary treatment of metastatic-hormone-sensitive prostate cancer(mHSPC),providing a temporary disease control in the majority of patients.Despite initial ADT response,castration-resistance prostate cancer(CRPC)still develops.Previous study have attempted to determine possible biomarkers for poor prognosis in patients with CRPC[2].
基金The study was reviewed and approved by the Rabin Medical Center Institutional Review Board(Approval No.0639-19-RMC).
文摘BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.
文摘BACKGROUND The purpose of the present study was to examine retrospectively the contribution of 18Fluorodeoxyglucose positron emission tomography computed tomography(18FDG-PET/CT)to the evaluation of response to first-line gemcitabine plus cispla-tin-based chemotherapy in patients with metastatic bladder cancer.AIM To evaluate the response to Gemcitabine plus Cisplatin-based chemotherapy using 18FDG-PET/CT imaging in patients with metastatic bladder cancer.METHODS Between July 2007 and April 2019,79 patients underwent 18FDG-PET/CT imaging with the diagnosis of Metastatic Bladder Carcinoma(M-BCa).A total of 42 pa-tients(38 male,4 female)were included in the study,and all had been admi-nistered Gemcitabine plus Cisplatin-based chemotherapy.After completion of the therapy,the patients underwent a repeat 18FDG-PET/CT scan and the results were compared with the PET/CT findings before chemotherapy according to European Organisation for the Research and treatment of cancer criteria.Mean age was 66.1 years and standard deviation was 10.7 years(range:41–84 years).RESULTS Of the patients,seven(16.6%)were in complete remission,17(40.5%)were in partial remission,six(14.3%)had a stable disease,and 12(28.6%)had a pro-gressive disease.The overall response rate was 57.1 percent.CONCLUSION 18FDG-PET/CT can be considered as a successful imaging tool in evaluating response to first-line chemotherapy for metastatic bladder cancer.Anatomical and functional data obtained from PET/CT scans may be useful in the planning of secondline and thirdline chemotherapy.
文摘Liver malignancy,including primary liver cancer and metastatic liver cancer has become one of the most common causes of cancer-related death worldwide due to the high malignant degree and limited systematic treatment strategy.Radioembolization with yttrium-90(^(90)Y)-loaded microspheres is a relatively novel technology that has made significant progress in the local treatment of liver malignancy.The different steps in the extensive work-up of radioembolization for patients with an indication for treatment with^(90)Y microspheres,from patient selection to follow up,both technically and clinically,are discussed in this paper.It describes the application and development of^(90)Y microspheres in the treatment of liver cancer.
基金Supported by The National Natural Science Foundation of China,No.81904049Beijing Natural Science Foundation,No.7202118+1 种基金The National Traditional Chinese Medicine Inheritance Innovation Project,No.ZYYCXTD-C-202006-9The Basic Scientific Research Foundation of Beijing University of Chinese Medicine,No.2021-JYB-XJSJJ-033.
文摘BACKGROUND Colon cancer(CC)is one of the leading causes of cancer-related morbidity and mortality worldwide.Traditional Chinese medicine(TCM)is widely used in the treatment of various chronic diseases.CC easily metastasizes and results in high morbidity and mortality rates.CASE SUMMARY A 71-year-old man with a 12-year history of old myocardial infarction and a 7-year history of type 2 diabetes mellitus was diagnosed with CC and underwent right hemicolectomy 1 year ago.Tumor biopsy revealed moderately poorly differentiated adenocarcinoma.Subsequently,chemotherapy with oxaliplatin and paclitaxel was administered.Anastomosis recurrence and pelvic metastasis were noted 37 d later.The patient received eight 21-d cycles of adjuvant chemotherapy with oxaliplatin and capecitabine after recurrence.However,the tumor persisted,and chemotherapy-related liver damage developed gradually.Thus,he was advised to take TCM for the recurrence and pelvic metastasis.The patient’s metastatic CC was cured after receiving TCM combined with long-term chemotherapy.CONCLUSION TCM may be an effective adjunct therapy in the treatment of patients with metastatic CC.
文摘BACKGROUND Immunotherapy has revolutionized the treatment of metastatic melanoma,but a significant proportion of patients still experience treatment resistance.Fecal microbiota transplantation(FMT)has emerged as a potential strategy to overcome immunotherapy resistance by modulating the gut microbiome.CASE SUMMARY We present a case report of a 57-year-old male with metastatic melanoma refractory to immunotherapy who received FMT in combination with antiprogrammed death-ligand 1(PD-L1)immunotherapy(pembrolizumab).After failing multiple lines of treatment,the patient underwent a single FMT procedure by colonoscopy using fecal material from a female metastatic melanoma donor who successfully responded to immunotherapy.Following FMT,the patient demonstrated a response with decreased subcutaneous disease and subsequently underwent surgery to remove the residual disease.Despite a subsequent recurrence in the small bowel that was resected,the patient remained on pembrolizumab without evidence of melanoma recurrence at the time of writing.CONCLUSION The favorable clinical and long-lasting effect we saw in our patient without significant toxicity suggests that this procedure should be considered in similar patients with immunotherapy refractory melanomas.
文摘Soft tissue sarcomas represent only 1% of all adult cancers;myxofibrosarcoma is the most common type that arises in adult extremities, particularly lower limbs (77%), other less common locations are the trunk (12%) and neck (3%). Usually presenting as a painless, subcutaneous, slow growing mass with tendency for recurrence, they are prone to have higher histological grade and metastatic potential after recurrence;even in optimal multidisciplinary settings patients can have incomplete resections, making metastatic disease more common after misdiagnosis. We present the case of a 69-year-old male patient with a right infraescapular tumor, presenting as a painless 15 × 8 cm, mobile mass, with a slow but progressive growth, history of a previous tumor excised at the same location 5 years prior without histopathological report.
文摘Background: The majority of breast cancer patients in Tanzania present with advanced disease, and a significant proportion has metastatic breast cancer (MBC) on presentation or develops it during the course of their follow-up. With few treatment options to choose from, such patients often benefit from empathic support and access to information to help them make treatment decisions based on their individual circumstances and needs. Patients with MBC have been shown to present with unique physical, social and psychological needs that require additional time, counselling and availability of health care providers in addition to the routine options available to other patients. In resource-limited settings, the needs of such patients are often unknown and unaddressed, which adds to the anxiety associated with the diagnosis and its treatment. Materials and methods: This descriptive qualitative study was conducted using 3 focus group discussions with a total of 17 participants with metastatic breast cancer (MBC) attending Ocean Road Cancer Institute in Dar es Salaam, Tanzania. Participants were purposively selected for the study from outpatient clinics and inpatient wards. A semi-structured FGD guide was used to moderate discussions and analysis was done using a thematic approach. Results: The median age of participants was 51 (range 33 - 81 years) with an average of 4 months (range 1 - 12 months) from diagnosis of BC to the interview. 4 (24%) were diagnosed with MBC on first presentation (denovo). Participants spoke about the importance of accurate BC-related information in allowing timely referral and treatment both in the community and within the health system. They recognized the role of mass and social media in increasing awareness about BC and identified myths surrounding cancer treatment especially mastectomy. Correct and timely information at points of care, through media platforms and via ambassadors/patient support groups was perceived as a means to avoiding delays and securing early and effective treatment. Conclusion: Patients with MBC in Tanzania have many unmet informational needs in relation to their disease. Accurate BC-related information is important in allowing early detection and diagnosis. At the community level, provision of information through established media platforms and the use of patient advocates may help to enable early referral and treatment of patients.
基金Supported by Agencia Nacional de Investigación y Desarrollo de Chile,Fondo Nacional de Investigación en Salud(FONIS),No.SA20I0059.
文摘BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to determine the specific CMS.Among them,23%(n=6),19%(n=5),31%(n=8),and 19%(n=5)were classified as CMS1,CMS2,CMS3,and CMS4,respectively.Additionally,8%of patients(n=2)could not be classified into any of the four CMS categories.The median overall survival of the total sample was 28 mo,and for CMS1,CMS2,CMS3 and CMS4 it was 11,20,30 and 45 mo respectively,with no statistically significant differences between groups.CONCLUSION A molecular biology workflow and clinical consensus analysis can be used to accurately classify mCRC patients.This classification process,which divides patients into the four CMS categories,holds significant potential for improving research strategies and targeted therapies tailored to the specific characteristics of mCRC.
基金co-first authors:Zeng-Feng Hanco-first authors/Corresponding to:Bin-Xu Sun,Department of Oncology,The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion.No.88 Changling Road,Xiqing District,Tianjin 300381,China.E-mail:sunbinxu@126.comCorresponding to:Shan-Qi Guo,Department of Oncology,The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion.No.88 Changling Road,Xiqing District,Tianjin 300381,China.E-mail:15022476737@163.com.
文摘Retrospective analysis of the progression of a case of metastatic castration-resistant prostate cancer with neuroendocrine differentiation:the patient was a 65 year old man with prostate adenocarcinoma on prostate biopsy,Gleason 4+4 score=8,70%,ISUP4 group,localized invasion of nerves.Progressed to metastatic castration-resistant prostate cancer after 8 months of novel endocrine therapy,persistent elevated PSA after endocrine therapy,chemotherapy,and radiation,abdominal metastasis,brain metastasis,gastric metastasis,and staging as neuroendocrine differentiation after second prostate biopsy,which is a highly malignant subtype and has been concerned as a mechanism of resistance to targeted therapies.We discuss how to choose a more optimal treatment plan and outline the patient's diagnostic and therapeutic course.We provide a reflection for the clinical study of metastatic castration-resistant prostate cancer with neuroendocrine type.
