BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic brea...BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer.There are currently few reports on the pattern of use and value of Pertuzumab in real world settings.Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted.Demographic and clinical data were extracted from electronic medical records.Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.RESULTS Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline therapy.With a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)cardiotoxicity.The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group.The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity.However,the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.展开更多
Background:Malignant bowel obstruction(MBO)is a highly morbid complication of advanced intra-abdominal malignancies.This study aims to identify clinicopathologic factors and intervention strategies associated with imp...Background:Malignant bowel obstruction(MBO)is a highly morbid complication of advanced intra-abdominal malignancies.This study aims to identify clinicopathologic factors and intervention strategies associated with improved survival and reduced rates of re-obstruction.Methods:A single centre,retrospective data analysis was performed for all consecutive patients admitted with MBO to a tertiary cancer centre in Melbourne,Australia over a 2-year period.Results:We identified a total of 102 patients with 137 admission episodes for MBO.Median age was 62 years,and 55 patients(54%)were female.61 patients(60%)had a gastrointestinal primary(colorectal,gastric or appendiceal),while 17 patients(16%)had a gynaecological primary and 24(24%)other primaries.Median overall survival was 120 days(95%confidence interval(CI)[76,167]).41 patients(40%)died within 90 days of initial admission with MBO.Clinicopathological variables associated with reduced 90-day survival included hypoalbuminaemia(odds ratio[OR]=3.33 for serum albumin<30 g/L,95%CI[1.43,7.69])and peritoneal disease(OR=5.80,95%CI[2.26,14.9]).41 patients(40%)received surgical management.We identified no factors significantly associated with the decision for surgical rather than conservative management.Of the 113 total admissions that reached discharge,55(49%)were followed by patient readmission within 90 d.Almost half(48%)of patients were referred to the inpatient palliative care service and this was associated with a reduction in the odds of 90 d readmission(OR=0.31,95%CI[0.14,0.71]).Conclusion:MBO heralds a poor prognosis,with high rates of readmission,morbidity and mortality.Careful patient selection is imperative to identify patients likely to benefit from operative management.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 tr...Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.展开更多
Purpose or objective The COVID-19 pandemic has resulted in significant healthcare implications,with care for can-cer patients compromised due to resource diversion towards battling the pandemic.We aim to investigate t...Purpose or objective The COVID-19 pandemic has resulted in significant healthcare implications,with care for can-cer patients compromised due to resource diversion towards battling the pandemic.We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore,specifically via our nasopharyn-geal carcinoma(NPC)treatment data.This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore.The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy,time to staging scans,time to treatment commencement,due to its clear protocol and algorithms for staging and treatment;thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery.Materials and methods In this retrospective study,we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre.This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore,which may impact on healthcare seeking behaviour.Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays.Electronic medical records(EMR)were accessed.Only newly diagnosed NPC cases were included in our analysis.Patients with second synchronous primary malignancies or NPC disease recurrence were excluded.Data analysis was carried out using a combination of SPSS and Microsoft Excel.Results Significantly,there was a reduction of 37-46.3%in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years.Despite the reduction in numbers of newly diagnosed NPC,there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years.All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines.Conclusion We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time,encourage patient’s confidence in their ability to seek care.With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore,this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization.It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery,as well as survival outcomes.展开更多
The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the cur...The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the current landscape of biomarkers to forecast treatment outcomes in bladder cancer patients.We explore a range of biomarkers,including genetic,epigenetic,proteomic,and transcriptomic indicators,from multiple sample sources,including urine,tumor tissue and blood,assessing their efficacy in predicting responses to chemotherapy,immunotherapy,and targeted therapies.Despite promising developments,the translation of these biomarkers into clinical practice faces significant challenges,such as variability in biomarker performance,the necessity for large-scale validation studies,and the integration of biomarker testing into routine clinical workflows.We also highlight the need for standardized methodologies and robust assays to ensure consistency and reliability.Future directions point towards longitudinal studies and the development of combination biomarker panels to enhance predictive accuracy.This review emphasizes the transformative potential of predictive biomarkers in improving patient outcomes and advocates for continued collaborative efforts to overcome existing barriers in this rapidly evolving field.展开更多
Objectives This study aimed to develop and preliminarily assess the quality of a Mindfulness Breast Care(MBC)App to reduce body image distress and stigma among breast cancer survivors(BCSs).Methods The development pro...Objectives This study aimed to develop and preliminarily assess the quality of a Mindfulness Breast Care(MBC)App to reduce body image distress and stigma among breast cancer survivors(BCSs).Methods The development process of the MBC App involved:1)establishing a research group;2)determining of the content of the MBC App based on Mindfulness-Based Cognitive Therapy and 3)technical exploitation and maintenance.A mixed-methods study was conducted.We selected ten BCSs by a convenience sampling method.After using the APP for three months,five assessed the quality using the Mobile App Rating Scale:User Version(uMARS)and another five were interviewed for process evaluation.Results The MBC App was developed with three modules:1)Library to provide health education information on body image,stigma,mindfulness,recovery and etc;2)Mindfulness Yoga to offer 12 Hatha yoga videos for daily practice;and 3)Mindfulness Practices to have 12 sessions of mindfulness videoconferences.Based on the uMARS data,the MBC App received high ratings for functionality(4.10±0.34),aesthetics(3.93±0.55),information quality(4.10±0.72),and perceived impact(4.03±0.96),as well as moderate ratings for engagement(3.72±0.94)and subjective quality(3.87±0.77).Participants indicated that the MBC App provided reliable knowledge,information,and emotional support.Recommendations from participants included categorizing knowledge in the Library Module,recording videoconferences of mindfulness practice,and adding discussion sessions in the videoconference.Afterward,we optimized the MBC App to enhance the user experience accordingly.Conclusions The MBC App offers online mindfulness interventions specifically for BCSs in China.The preliminary quality assessment indicates that the MBC App may be a promising tool for delivering mindfulness interventions to BCSs.展开更多
Background:Treatment is an important component of a comprehensive cancer control approach and its outcomes strongly depend on infrastructure,equipment,human and financial resources available.Therefore it is imperative...Background:Treatment is an important component of a comprehensive cancer control approach and its outcomes strongly depend on infrastructure,equipment,human and financial resources available.Therefore it is imperative to generate evidence-based tools to assist health policy makers from low resourced countries in planning efficient and equitable treatment services for a defined population based on what it is feasible to these settings.Methods:The intended cancer spe-cific treatment planned and written in the patients’medical record(treatment prescription)of untreated adult cancer cases(≥18 years of age),excluding non-melanoma skin cancer,was recorded in a chronological way from 1 January 2012 onwards in a group of eight comprehensive cancer centres located in middle income countries and offering the main modalities of cancer treatment(surgery,medical oncology and radiotherapy).Results:A total of 17,713 medical records were reviewed,of which 7106(54.2%)met the eligibility criteria.Prescription of main cancer treatment modalities were distributed as follows:57.6%for chemotherapy(n=4093),56.8%for surgery(n=4038),and 46.8%for radiotherapy(n=3327).There was a predominance of plans consisting of combined treatment modalities over monotherapy(55.2%versus 44.8%).At the time of diagnosis 54.3%of the cancer cases had disease that had spread beyond the primary site,41.2%were considered as having local disease and in 4.5%of the cases the information on disease extension was unknown.Conclusions:The results obtained should be seen as an approximation of cancer treatment service demand based on what it is currently practiced and therefore feasible in developing countries,particularly in middle income countries.展开更多
Objective:Laparoscopic distal gastrectomy(LDG)has potential as a surgical treatment option for locally advanced gastric cancer(LAGC).However,there is uncertainty regarding the generalizability of LDG efficacy across d...Objective:Laparoscopic distal gastrectomy(LDG)has potential as a surgical treatment option for locally advanced gastric cancer(LAGC).However,there is uncertainty regarding the generalizability of LDG efficacy across diverse patient populations and treatment settings.This study aimed to assess the outcomes of LDG vs.open distal gastrectomy(ODG)in patients with LAGC despite differences in clinical trial populations and treatment environments.Methods:The KLASS-02 and CLASS-01 trials are multicenter,non-inferiority,open-label,randomized controlled trials for patients with LAGC eligible for distal subtotal gastrectomy in Korea and China,respectively.Some 1,050 patients were enrolled in KLASS-02,and 1,056 patients were enrolled in CLASS-01.Individual patient data(IPD)from KLASS-02 and CLASS-01 were pooled and analyzed.Results:There were 900 patients in the LDG group and 920 in the ODG group.Baseline characteristics were well balanced between groups.The LDG group had better short-term and recovery outcomes than the ODG group,although anastomotic leakage was more frequent.For patients who underwent LDG vs.ODG,5-year overall survival(OS)was 82.7%[95%confidence interval(95%CI),80.2%-85.2%]vs.83.3%(95%CI,80.9%-85.8%)(P=0.706)and 5-year recurrence-free survival(RFS)was 76.9%(95%CI,74.1%-79.7%)vs.77.9%(95%CI,75.2%-80.6%)(P=0.666),respectively,with a median follow-up of 70 months.In the multivariable prognostic IPD meta-analysis,the operative approach was not independently associated with OS[hazard ratio(HR)=1.045,95%CI,0.833-1.311;P=0.706]or RFS(HR=1.044,95%CI,0.859-1.269;P=0.667)for LDG vs.ODG.In the subgroup analysis,LDG demonstrated a significant association with poorer RFS in the p T4 subgroup(HR=1.377,95%CI,1.022-1.760;P=0.034).Conclusions:Despite differences in patient populations,surgical practices,and postoperative treatments between trials,LDG is oncologically safe with the benefit of being minimally invasive for patients with LAGC,except for the p T4 patients.Therefore,LDG could be a good treatment alternative for patients with LAGC;however,caution should be warranted in its application for patients classified as T4.展开更多
The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellu...The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellular vesicles(EVs)inherently function in target-guided intercellular communication.To incorporate the native merits of EVs into STING pathways,i.e.,engineered EV@STING,poor bioavailability and off-target issues that STING activators possess could be significantly overcome.In this review,emerged STING activators such as nitrogen-containing heterocyclic structures and the universal STING activation strategy(uniSTING)are firstly summarized.Diverse EVs sources from mesenchymal stem cells(MSCs)and innate and adaptive immune cells may evoke distinct regulatory results.Concurrently,how the EVs contents including double-stranded DNA(dsDNA),microRNA(miRNA),cyclic GMP-AMP synthase(cGAS)and 2′3′-cyclic GMP-AMP(2′3′-cGAMP)proteins participate in the regulation of STING activation are widely studied.After mastering the two pivotal aspects of EV@STING,their immunomodulatory roles including in pathogen infection,inflammatory diseases,and cancer therapy are comprehensively summed up and discussed.Finally,in cancer study field,therapeutic challenges and clinical translational opportunities of EV@STING are thoroughly evaluated.展开更多
The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials...The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.展开更多
Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We pr...Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.展开更多
Despite declining incidence,gastric cancer remains one of the most common cancers worldwide.Early detection in population-based screening programs has increased the number of cases of early gastric cancer,representing...Despite declining incidence,gastric cancer remains one of the most common cancers worldwide.Early detection in population-based screening programs has increased the number of cases of early gastric cancer,representing approximately 50%of newly detected gastric cancer cases in Asian countries.Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis.Laparoscopic and robotic resections for early gastric cancer,including function-preserving resections,have propagated through advances in technology and surgeon experience.The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer.展开更多
The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A...The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.展开更多
Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stag...Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However,response to chemotherapy varies widely,with some patients presenting no or only minor response to treatment. Hence,chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately,to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment,or that allow modification of chemotherapy resistance. MicroRNAs(miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types,and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC.The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics,and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.展开更多
Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in pati...Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.展开更多
BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial ...BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial issue in the pathogenesis and development of cancer.AIM To evaluate the prognostic value of absolute monocyte count,monocyte to lymphocyte ratio(MLR),the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio(NLR-PLR),and combined platelet and neutrophilto-lymphocyte ratio(PLT-NLR)in peripheral blood samples of patients with colorectal cancer undergoing surgery.METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery,and 42 healthy controls.The status of absolute monocyte count,MLR,NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery.Haematologic factors were examined in correlation with the type of tumour growth,tumour size,histological type,percentage of mucinous component,grade of malignancy,Tumour-Node-Metastasis stage,venous,lymphatic and perineural invasion of cancer cells,status of lymph node invasion and the presence of cancer cell deposits.The Kaplan-Meier method and the long-rank test were used to compare survival curves.To determine independent prognostic factors,univariate and multivariate Cox proportional hazards regression models were applied.RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion(P=0.015;P=-0.174,P=0.037).Moreover,high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component(NLR-PLR:P=0.002;P=0.009;PLR-NLR status:P=0.002;P=0.007).The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery[HR=2.903,95%CI:(1.368-6.158),P=0.005]and the status of lymph node metastasis[HR=0.813,95%CI:(0.653-1.013),P=0.050]were independent prognostic factors in colorectal cancer patients.CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.展开更多
Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In th...Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.展开更多
AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chem...AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers.RESULTS:A total of 108 patients were reviewed.Median age at diagnosis was 60.The majority of the patients(64.8%) had advanced stage Ⅲ and Ⅳ disease(with no distant metastasis).All except 4 patients had D2 gastrectomy.Twenty one patients(19.4%) had positive surgical resection margins.Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone.For the patients in the chemotherapy-only group,all had fluoropyrimidine-based therapy,with added cisplatin in 7 patients and epirubicin in 2 patients.Median recurrence-free survival was longer for the XRT group(52 mo) compared to the 5FU-RT(35 mo) and chemotherapy-only groups(25 mo)(P=0.48).The patients in the XRT group achieved similar median overall survival(53 mo) as the 5FU-RT(54 mo) and the chemotherapy-only groups(44 mo)(P=0.5).CONCLUSION:Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.展开更多
AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorec...AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.展开更多
文摘BACKGROUND Pertuzumab is a humanized anti-human epidermal growth factor receptor 2(HER2)monoclonal antibody found in a Phase III clinical trial to significantly improve median survival in HER2 positive metastatic breast cancer(MBC)when used in combination with a taxane and Trastuzumab,and its clinical efficacy has transformed the therapeutic landscape of HER2-positive breast cancer.There are currently few reports on the pattern of use and value of Pertuzumab in real world settings.Our study describes the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC treated in a tertiary cancer centre in Singapore in a predominantly Asian population.AIM To investigate the clinical efficacy and treatment costs of Pertuzumab in HER2-positive MBC in an Asian population in Singapore.METHODS A retrospective study of 304 HER2-positive MBC patients seen at National Cancer Centre Singapore between 2011-2017 was conducted.Demographic and clinical data were extracted from electronic medical records.Clinical characteristics and billing data of patients who received Pertuzumab were compared with those who did not.RESULTS Thirty-one(62.0%)of the fifty(16.4%)patients who received Pertuzumab as firstline therapy.With a median follow-up of 21.5 mo,there was a statistically significant difference in the median overall survival between Pertuzumab and non-Pertuzumab groups[51.5(95%CI:35.8–60.0)vs 32.9(95%CI:28.1–37.5)mo;P=0.0128].Two(4.88%)patients in the Pertuzumab group experienced grade 3(G3)cardiotoxicity.The median treatment cost incurred for total chemotherapy for the Pertuzumab group was 130456 Singapore Dollars compared to 34523 Singapore Dollars for the non-Pertuzumab group.The median percentage of total chemotherapy costs per patient in the Pertuzumab group spent on Pertuzumab was 50.3%.CONCLUSION This study shows that Pertuzumab use in the treatment of metastatic breast cancer is associated with a significantly better survival and a low incidence of serious cardiotoxicity.However,the proportionate cost of Pertuzumab therapy remains high and further cost-effectiveness studies should be conducted.
文摘Background:Malignant bowel obstruction(MBO)is a highly morbid complication of advanced intra-abdominal malignancies.This study aims to identify clinicopathologic factors and intervention strategies associated with improved survival and reduced rates of re-obstruction.Methods:A single centre,retrospective data analysis was performed for all consecutive patients admitted with MBO to a tertiary cancer centre in Melbourne,Australia over a 2-year period.Results:We identified a total of 102 patients with 137 admission episodes for MBO.Median age was 62 years,and 55 patients(54%)were female.61 patients(60%)had a gastrointestinal primary(colorectal,gastric or appendiceal),while 17 patients(16%)had a gynaecological primary and 24(24%)other primaries.Median overall survival was 120 days(95%confidence interval(CI)[76,167]).41 patients(40%)died within 90 days of initial admission with MBO.Clinicopathological variables associated with reduced 90-day survival included hypoalbuminaemia(odds ratio[OR]=3.33 for serum albumin<30 g/L,95%CI[1.43,7.69])and peritoneal disease(OR=5.80,95%CI[2.26,14.9]).41 patients(40%)received surgical management.We identified no factors significantly associated with the decision for surgical rather than conservative management.Of the 113 total admissions that reached discharge,55(49%)were followed by patient readmission within 90 d.Almost half(48%)of patients were referred to the inpatient palliative care service and this was associated with a reduction in the odds of 90 d readmission(OR=0.31,95%CI[0.14,0.71]).Conclusion:MBO heralds a poor prognosis,with high rates of readmission,morbidity and mortality.Careful patient selection is imperative to identify patients likely to benefit from operative management.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金the National Institute for Health and Care Research(NHR)Manchester Biomedical Research Centre(BRC)(NIHR203308,NIHR-BRC-1215-20007)Astra-Zeneca(ESR-14-10711)+2 种基金CRUK RadNet(C19941/A27801)TMI and CFF are the recipient of an NIHR Senior Investigator Award(NIHR205054 and NIHR205061)CTH is supported by the NIHR University College London Hospitals NHS Foundation Trust BRC,the City of London CRUK RadNet and the CRUK Lung Cancer Centre of Excellence.
文摘Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.
文摘Purpose or objective The COVID-19 pandemic has resulted in significant healthcare implications,with care for can-cer patients compromised due to resource diversion towards battling the pandemic.We aim to investigate the impact of the peak wave of the pandemic in 2020 on the delivery of cancer care in Singapore,specifically via our nasopharyn-geal carcinoma(NPC)treatment data.This study applies real world numbers to the impact of COVID-19 on cancer care delivery in Singapore.The choice of nasopharyngeal cancer allows a good direct estimate of common treatment measures such as time to biopsy,time to staging scans,time to treatment commencement,due to its clear protocol and algorithms for staging and treatment;thus serving as an excellent surrogate for the effectiveness and timeliness of the different aspects of cancer care delivery.Materials and methods In this retrospective study,we included all patients with newly diagnosed NPC from 1st January to 31st May from 2017 to 2020 at our centre.This time period was chosen as it coincided with the period in 2020 during the COVID-19 pandemic where there was the most strain on healthcare resources and the most restrictions on population movement within Singapore,which may impact on healthcare seeking behaviour.Narrowing down the time period to the first 5 months of the 4 respective years also allowed us to reduce the effect of annual seasonal variation in patient numbers seen as a result of holidays and festive periods such as the Lunar New Year and scheduled school holidays.Electronic medical records(EMR)were accessed.Only newly diagnosed NPC cases were included in our analysis.Patients with second synchronous primary malignancies or NPC disease recurrence were excluded.Data analysis was carried out using a combination of SPSS and Microsoft Excel.Results Significantly,there was a reduction of 37-46.3%in newly diagnosed NPC cases during the peak of the COVID-19 pandemic from January to end May 2020 compared to the preceding three years.Despite the reduction in numbers of newly diagnosed NPC,there was no statistically significant differences in delay from biopsy to the first radiation oncology visit and from biopsy to the first day of treatment in 2020 compared to the preceding years.All the patients treated in our centre also received the standard NPC treatment for their disease stage as per international guidelines.Conclusion We recommend a heightened awareness of the dangers of delaying cancer presentation and care in healthcare policies and resource allocation and at the same time,encourage patient’s confidence in their ability to seek care.With the resurgence of new COVID-19 variants and case numbers worldwide and in Singapore,this study focuses upon the need to be aware of the exigencies of other clinical groups in resource utilization.It would be instructive to compare this study with future long term follow up to investigate the trajectory of our cancer care delivery,as well as survival outcomes.
文摘The advent of precision medicine has underscored the importance of biomarkers in predicting therapy response for bladder cancer,a malignancy marked by considerable heterogeneity.This review critically examines the current landscape of biomarkers to forecast treatment outcomes in bladder cancer patients.We explore a range of biomarkers,including genetic,epigenetic,proteomic,and transcriptomic indicators,from multiple sample sources,including urine,tumor tissue and blood,assessing their efficacy in predicting responses to chemotherapy,immunotherapy,and targeted therapies.Despite promising developments,the translation of these biomarkers into clinical practice faces significant challenges,such as variability in biomarker performance,the necessity for large-scale validation studies,and the integration of biomarker testing into routine clinical workflows.We also highlight the need for standardized methodologies and robust assays to ensure consistency and reliability.Future directions point towards longitudinal studies and the development of combination biomarker panels to enhance predictive accuracy.This review emphasizes the transformative potential of predictive biomarkers in improving patient outcomes and advocates for continued collaborative efforts to overcome existing barriers in this rapidly evolving field.
基金supported by the National Natural Science Foundation of China(No.71974162 and No.7231101009).
文摘Objectives This study aimed to develop and preliminarily assess the quality of a Mindfulness Breast Care(MBC)App to reduce body image distress and stigma among breast cancer survivors(BCSs).Methods The development process of the MBC App involved:1)establishing a research group;2)determining of the content of the MBC App based on Mindfulness-Based Cognitive Therapy and 3)technical exploitation and maintenance.A mixed-methods study was conducted.We selected ten BCSs by a convenience sampling method.After using the APP for three months,five assessed the quality using the Mobile App Rating Scale:User Version(uMARS)and another five were interviewed for process evaluation.Results The MBC App was developed with three modules:1)Library to provide health education information on body image,stigma,mindfulness,recovery and etc;2)Mindfulness Yoga to offer 12 Hatha yoga videos for daily practice;and 3)Mindfulness Practices to have 12 sessions of mindfulness videoconferences.Based on the uMARS data,the MBC App received high ratings for functionality(4.10±0.34),aesthetics(3.93±0.55),information quality(4.10±0.72),and perceived impact(4.03±0.96),as well as moderate ratings for engagement(3.72±0.94)and subjective quality(3.87±0.77).Participants indicated that the MBC App provided reliable knowledge,information,and emotional support.Recommendations from participants included categorizing knowledge in the Library Module,recording videoconferences of mindfulness practice,and adding discussion sessions in the videoconference.Afterward,we optimized the MBC App to enhance the user experience accordingly.Conclusions The MBC App offers online mindfulness interventions specifically for BCSs in China.The preliminary quality assessment indicates that the MBC App may be a promising tool for delivering mindfulness interventions to BCSs.
文摘Background:Treatment is an important component of a comprehensive cancer control approach and its outcomes strongly depend on infrastructure,equipment,human and financial resources available.Therefore it is imperative to generate evidence-based tools to assist health policy makers from low resourced countries in planning efficient and equitable treatment services for a defined population based on what it is feasible to these settings.Methods:The intended cancer spe-cific treatment planned and written in the patients’medical record(treatment prescription)of untreated adult cancer cases(≥18 years of age),excluding non-melanoma skin cancer,was recorded in a chronological way from 1 January 2012 onwards in a group of eight comprehensive cancer centres located in middle income countries and offering the main modalities of cancer treatment(surgery,medical oncology and radiotherapy).Results:A total of 17,713 medical records were reviewed,of which 7106(54.2%)met the eligibility criteria.Prescription of main cancer treatment modalities were distributed as follows:57.6%for chemotherapy(n=4093),56.8%for surgery(n=4038),and 46.8%for radiotherapy(n=3327).There was a predominance of plans consisting of combined treatment modalities over monotherapy(55.2%versus 44.8%).At the time of diagnosis 54.3%of the cancer cases had disease that had spread beyond the primary site,41.2%were considered as having local disease and in 4.5%of the cases the information on disease extension was unknown.Conclusions:The results obtained should be seen as an approximation of cancer treatment service demand based on what it is currently practiced and therefore feasible in developing countries,particularly in middle income countries.
基金supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),the Ministry of Health&Welfare,Republic of Korea(No.RS-2023-KH140183)the 2024 intramural research fund of Ajou University Medical Center(No.M-2024-C0460-00083)+3 种基金an Investigator-Initiated Study granted from Ethicon,Inc-Johnson and Johnson Med Tech(No.ENG-2021-04)the Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(No.2020B121201004)Guangdong Provincial Major Talents Project(No.2019JC05Y361)Major Clinical Technology Project in Guangzhou(No.2023P-ZD01)。
文摘Objective:Laparoscopic distal gastrectomy(LDG)has potential as a surgical treatment option for locally advanced gastric cancer(LAGC).However,there is uncertainty regarding the generalizability of LDG efficacy across diverse patient populations and treatment settings.This study aimed to assess the outcomes of LDG vs.open distal gastrectomy(ODG)in patients with LAGC despite differences in clinical trial populations and treatment environments.Methods:The KLASS-02 and CLASS-01 trials are multicenter,non-inferiority,open-label,randomized controlled trials for patients with LAGC eligible for distal subtotal gastrectomy in Korea and China,respectively.Some 1,050 patients were enrolled in KLASS-02,and 1,056 patients were enrolled in CLASS-01.Individual patient data(IPD)from KLASS-02 and CLASS-01 were pooled and analyzed.Results:There were 900 patients in the LDG group and 920 in the ODG group.Baseline characteristics were well balanced between groups.The LDG group had better short-term and recovery outcomes than the ODG group,although anastomotic leakage was more frequent.For patients who underwent LDG vs.ODG,5-year overall survival(OS)was 82.7%[95%confidence interval(95%CI),80.2%-85.2%]vs.83.3%(95%CI,80.9%-85.8%)(P=0.706)and 5-year recurrence-free survival(RFS)was 76.9%(95%CI,74.1%-79.7%)vs.77.9%(95%CI,75.2%-80.6%)(P=0.666),respectively,with a median follow-up of 70 months.In the multivariable prognostic IPD meta-analysis,the operative approach was not independently associated with OS[hazard ratio(HR)=1.045,95%CI,0.833-1.311;P=0.706]or RFS(HR=1.044,95%CI,0.859-1.269;P=0.667)for LDG vs.ODG.In the subgroup analysis,LDG demonstrated a significant association with poorer RFS in the p T4 subgroup(HR=1.377,95%CI,1.022-1.760;P=0.034).Conclusions:Despite differences in patient populations,surgical practices,and postoperative treatments between trials,LDG is oncologically safe with the benefit of being minimally invasive for patients with LAGC,except for the p T4 patients.Therefore,LDG could be a good treatment alternative for patients with LAGC;however,caution should be warranted in its application for patients classified as T4.
基金supported by the National Natural Science Foundation of China(NSFC,Nos.32222090,32101069 and 32171318)Faculty of Health Sciences,University of Macao,the Multi-Year Research Grant(MYRG)of University of Macao and the University of Macao Development Foundation(UMDF)(Nos.MYRG2022-00011-FHS and MYRG-GRG2023-00013-FHS-UMDF)+2 种基金the Science and Technology Development Fund,Macao SAR(Nos.0002/2021/AKP,0133/2022/A3,0009/2022/AKP,and 0006/2023/ITP1)Ministry of Education Frontiers Science Centre for Precision Oncology,University of Macao(No.SP2023-00001-FSCPO)Guangdong Provincial Applied Science and Technology Research and Development Program(No.2024A1515011140).
文摘The stimulator of interferon genes(STING),as a critical innate immune sensor,has been widely and continually explored in immune-related disease treatment.As lipid bilayer-closed particles derived from cells,extracellular vesicles(EVs)inherently function in target-guided intercellular communication.To incorporate the native merits of EVs into STING pathways,i.e.,engineered EV@STING,poor bioavailability and off-target issues that STING activators possess could be significantly overcome.In this review,emerged STING activators such as nitrogen-containing heterocyclic structures and the universal STING activation strategy(uniSTING)are firstly summarized.Diverse EVs sources from mesenchymal stem cells(MSCs)and innate and adaptive immune cells may evoke distinct regulatory results.Concurrently,how the EVs contents including double-stranded DNA(dsDNA),microRNA(miRNA),cyclic GMP-AMP synthase(cGAS)and 2′3′-cyclic GMP-AMP(2′3′-cGAMP)proteins participate in the regulation of STING activation are widely studied.After mastering the two pivotal aspects of EV@STING,their immunomodulatory roles including in pathogen infection,inflammatory diseases,and cancer therapy are comprehensively summed up and discussed.Finally,in cancer study field,therapeutic challenges and clinical translational opportunities of EV@STING are thoroughly evaluated.
文摘The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.
文摘Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.
文摘Despite declining incidence,gastric cancer remains one of the most common cancers worldwide.Early detection in population-based screening programs has increased the number of cases of early gastric cancer,representing approximately 50%of newly detected gastric cancer cases in Asian countries.Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis.Laparoscopic and robotic resections for early gastric cancer,including function-preserving resections,have propagated through advances in technology and surgeon experience.The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer.
基金funded partly by a program grant from the National Health and Medical Research Council of Australia(NH&MRC)supported by Senior Research Fellowships from the NH&MRCsupport of the Pfizer Australia Fellowship
文摘The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.
文摘Gastric cancer(GC) is the fourth most common cancer worldwide and ranks second in global cancer mortality statistics. Perioperative chemotherapy plays an important role in the management and treatment of advanced stage disease. However,response to chemotherapy varies widely,with some patients presenting no or only minor response to treatment. Hence,chemotherapy resistance is a major clinical problem that impacts on outcome. Unfortunately,to date there are no reliable biomarkers available that predict response to chemotherapy before the start of the treatment,or that allow modification of chemotherapy resistance. MicroRNAs(miRNAs) could provide an answer to this problem. miRNAs are involved in the initiation and progression of a variety of cancer types,and there is evidence that miRNAs impact on resistance towards chemotherapeutic drugs as well. This current review aims to provide an overview about the potential clinical applicability of miRNAs as biomarkers for chemoresistance in GC.The authors focus in this context on the potential of miRNAs to predict sensitivity towards different chemotherapeutics,and on the potential of miRNAs to modulate sensitivity and resistance towards chemotherapy in GC.
基金Supported by National Natural Science Foundation of China,No.81220108023,No.81370064 and No.81572329Fundamental Research Funds for the Central Universities,No.20620140729+1 种基金Jiangsu Provincial Program of Medical Sciences,No.BL2012001Distinguished Young Investigator Project of Nanjing,No.JQX12002
文摘Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.
文摘BACKGROUND Colorectal cancer is the third most common malignancy worldwide.Therefore,it is critically important to identify new useful markers that can be easily obtained in routine practice.Inflammation is a crucial issue in the pathogenesis and development of cancer.AIM To evaluate the prognostic value of absolute monocyte count,monocyte to lymphocyte ratio(MLR),the combination of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio(NLR-PLR),and combined platelet and neutrophilto-lymphocyte ratio(PLT-NLR)in peripheral blood samples of patients with colorectal cancer undergoing surgery.METHODS We conducted a retrospective study of 160 patients with colorectal cancer who underwent surgery,and 42 healthy controls.The status of absolute monocyte count,MLR,NLR-PLR and PLT-NLR was calculated on the basis of blood samples obtained before and after surgery.Haematologic factors were examined in correlation with the type of tumour growth,tumour size,histological type,percentage of mucinous component,grade of malignancy,Tumour-Node-Metastasis stage,venous,lymphatic and perineural invasion of cancer cells,status of lymph node invasion and the presence of cancer cell deposits.The Kaplan-Meier method and the long-rank test were used to compare survival curves.To determine independent prognostic factors,univariate and multivariate Cox proportional hazards regression models were applied.RESULTS The PLT-NLR status was correlated with tumour size and the presence of perineural invasion(P=0.015;P=-0.174,P=0.037).Moreover,high NLR-PLR and PLR-NLR ratios in the blood samples obtained after surgery were positively associated with histological type of cancer and percentage of the mucinous component(NLR-PLR:P=0.002;P=0.009;PLR-NLR status:P=0.002;P=0.007).The analysis of 5-year disease-free survival showed that the MLR of whole blood obtained after surgery[HR=2.903,95%CI:(1.368-6.158),P=0.005]and the status of lymph node metastasis[HR=0.813,95%CI:(0.653-1.013),P=0.050]were independent prognostic factors in colorectal cancer patients.CONCLUSION The postoperative MLR in whole blood samples can be used as an independent prognostic factor in patients diagnosed with colorectal cancer.
文摘Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.
文摘AIM:To analyze the outcome of patients who received concurrent capecitabine(Xeloda) and radiation(XRT) compared to the established concurrent 5-fluorouracil(5-FU) with radiation(5FU-RT) and fluoropyrimidine-based chemotherapy alone as adjuvant treatment in gastric cancers.METHODS:All patients with gastric cancers who received adjuvant treatment at the National Cancer Centre Singapore between 1996 and 2006 were reviewed.Treatment outcomes of patients who received XRT were compared with those who had 5FU-RT or chemotherapy alone as adjuvant therapy for gastric cancers.RESULTS:A total of 108 patients were reviewed.Median age at diagnosis was 60.The majority of the patients(64.8%) had advanced stage Ⅲ and Ⅳ disease(with no distant metastasis).All except 4 patients had D2 gastrectomy.Twenty one patients(19.4%) had positive surgical resection margins.Thirty three patients received XRT compared with 52 who had 5FU-RT and 23 who received chemotherapy alone.For the patients in the chemotherapy-only group,all had fluoropyrimidine-based therapy,with added cisplatin in 7 patients and epirubicin in 2 patients.Median recurrence-free survival was longer for the XRT group(52 mo) compared to the 5FU-RT(35 mo) and chemotherapy-only groups(25 mo)(P=0.48).The patients in the XRT group achieved similar median overall survival(53 mo) as the 5FU-RT(54 mo) and the chemotherapy-only groups(44 mo)(P=0.5).CONCLUSION:Capecitabine with concurrent radiation was as effective as concurrent 5FU with radiation or fluoropyrimidine-based chemotherapy alone when used as adjuvant treatment in patients with gastric cancers.
文摘AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained with total mesorectal excision （TME）. METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records. RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）. CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.
