Importance of performance status for treatment outcome in advanced pancreatic cancer

Despite progress in the treatment of advanced and metastatic pancreatic cancer （PC）, the outcome of this disease remains dismal for the majority of patients. Given the moderate efficacy of treatment, prognostic factors may help to guide treatment decisions. Several trials identified baseline performance status as an important prognostic factor for survival. Unfit patients with a Kamofsky performance status （KPS） below 70% only have a marginal benefit from chemotherapy with gemcitabine （Gem） and may often benefit more from optimal supportive care. Once, however, the decision is taken to apply chemotherapy, KPS may be used to select either mono- or combination chemotherapy. Patients with a good performance status （KPS = 90%-100%） may have a significant and clinically relevant survival benefit from combination chemotherapy. By contrast, patients with a poor performance status （KPS ≤ 80%） have no advantage from intensified therapy and should rather receive single-agent treatment.

Endoscopic retrograde cholangiopancreatography for bile duct stones in patients with a performance status score of 3 or 4

BACKGROUND As the aging population grows worldwide,the rates of endoscopic retrograde cholangiopancreatography(ERCP)for common bile duct stones(CBDS)in older patients with a poor performance status(PS)have been increasing.However,the data on the safety and efficacy of ERCP for CBDS in patients with a PS score of 3 or 4 are lacking,with only a few studies having investigated this issue among patients with poor PS.AIM To examine the safety and efficacy of ERCP for CBDS in patients with a PS score of 3 or 4.METHODS This study utilized a retrospective multi-centered design of three institutions in Japan for 8 years to identify a total of 1343 patients with CBDS having native papillae who underwent therapeutic ERCP.As a result,1113 patients with a PS 0-2 and 230 patients with a PS 3-4 were included.One-to-one propensity-score matching was performed to compare the safety and efficacy of ERCP for CBDS between patients with a PS 0-2 and those with a PS 3-4.RESULTS The overall ERCP-related complication rates in all patients and propensity score-matched patients with a PS 0-2 and 3-4 were 9.0%(100/1113)and 7.0%(16/230;P=0.37),and 4.6%(9/196)and 6.6%(13/196;P=0.51),respectively.In the propensity score-matched patients,complications were significantly more severe in the group with a PS 3-4 than in the group with a PS 0-2 group(P=0.042).Risk factors for complications were indications of ERCP and absence of antibiotics in the multivariate analysis.Therapeutic success rates,including complete CBDS removal and permanent biliary stent placement,in propensity score-matched patients with a PS 0-2 and 3-4 were 97.4%(191/196)and 97.4%(191/196),respectively(P=1.0).CONCLUSION ERCP for CBDS can be effectively performed in patients with a PS 3 or 4.Nevertheless,the indication for ERCP in such patients should be carefully considered with prophylactic antibiotics.

Recipient functional status impacts on short and long-term intestinal transplant outcomes in United States adults

BACKGROUND Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart,liver and kidney transplants.However,information on how functional status,before and after transplant impacts post-transplant survival outcomes is lacking.AIM To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults.METHODS We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022.The primary outcome was mortality.Using the Karnofsky Performance Status,functional impairment was categorized as severe,moderate and normal.Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression.RESULTS The median age was 41 years,majority(53.4%)were women.Severe impairment was present in 28.3%of recipients.The median survival time was 906.6 days.The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively.Recipients with severe impairment had a 56%higher risk of mortality at one year[Hazard ratio(HR)=1.56;95%CI:1.23–1.98;P<0.001]and 58%at five years(HR=1.58;95%CI:1.24–2.00;P<0.001)compared to patients with no functional impairment.Recipients with worse functional status after transplant also had poor survival outcomes.CONCLUSION Pre-and post-transplant recipient functional status is an important prognostic indicator for short-and long-term intestinal transplant outcomes.

Prognostic value of ECOG performance status and Gleason score in the survival of castration-resistant prostate cancer:a systematic review

Eastern Cooperative Oncology Group(ECOG)performance status and Gleason score are commonly investigated factors for overall survival(OS)in men with castration-resistant prostate cancer(CRPC).However,there is a lack of consistency regarding their prognostic or predictive value for OS.Therefore,we performed this meta-analysis to assess the associations of ECOG performance status and Gleason score with OS in CRPC patients and compare the two markers in patients under different treatment regimens or with different chemotherapy histories.A systematic literature review of monotherapy studies in CRPC patients was conducted in the PubMed database until May 2019.The data from 8247 patients in 34 studies,including clinical trials and real-world data,were included in our meta-analysis.Of these,twenty studies reported multivariate results and were included in our main analysis.CRPC patients with higher ECOG performance statuses(≥2)had a significantly increased mortality risk than those with lower ECOG performance statuses(<2),hazard ratio(HR):2.10,95%confidence interval(CI):1.68-2.62,and P<0.001.The synthesized HR of OS stratified by Gleason score was 1.01,with a 95%CI of 0.62-1.67(Gleason score≥8 vs<8).Subgroup analysis showed that there was no significant difference in pooled HRs for patients administered taxane chemotherapy(docetaxel and cabazitaxel)and androgen-targeting therapy(abiraterone acetate and enzalutamide)or for patients with different chemotherapy histories.ECOG performance status was identified as a significant prognostic factor in CRPC patients,while Gleason score showed a weak prognostic value for OS based on the available data in our meta-analysis.

Bi-weekly docetaxel and 5-fluorouracil:an effective and feasible treatment for advanced gastric cancer with poor performance status

Background:The survival benefits from cytotoxic chemotherapy have been demonstrated in advanced gastric cancer(AGC).A large proportion of AGC patients initially present poor performance status(PS);however,most of the clinical evidence comes from trials on patients with good PS.A better-designed regimen is greatly needed for AGC patients with poor PS.Objective:To evaluate the efficacy and safety of a modified combination regimen with docetaxel plus 5-fluorouracil(5-FU)every two weeks as first-line treatment in AGC patients with poor PS.Methods:From September 2011 to December 2013,12 patients diagnosed with AGC with Eastern Cooperative Oncology Group(ECOG)PS scores of 3 or 4 were included in this study.All the patients received docetaxel 60 mg/m^(2) on Day 1,5-FU 400mg/m^(2) intravenous(i.v.)bolus on Day 1,and a 46-hour continuous i.v.infusion of 5-FU 2400mg/m^(2) every two weeks,until disease progressed or patients experienced unacceptable toxicity or declined treatment.Detailed clinical,pathologic and survival data were all recorded.Results:Eleven out of 12 patients were assessable for responses,whereas nine cases(75%)achieved partial response,one(8.3%)achieved stabilized disease,and one(8.3%)had progressive disease.The median progression-free survival was 6.5 months(95%CI:4.8–8.2).The median overall survival was 12.0 months(95%CI:9.0–15.0).The most common Grade 3/4 toxicities were anemia in seven patients(58.3%).No patient experienced febrile neutropenia.Conclusion:The novel modification of bi-weekly docetaxel and 5-FU is a promising treatment option for AGC with poor PS,showing great efficacy and acceptable toxicity.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

Malnutrition and Quality of Life in Chinese Cancer Patients: a Clinical Study of 23,994 Subjects

Background Malnutrition is common in patients with cancer,and can negatively impact their quality of life(QoL)and even survival.However,there is currently no large data available on the prevalence of malnutrition in Chinese cancer patients.This study evaluated the prevalence of malnutrition and the QoL of Chinese patients with locoregional,recurrent or metastatic cancer.Methods We conducted a nationwide observational,multi-center,hospital-based cross-sectional study within the Chinese Society of Nutritional Oncology(CSNO)Network.All of the patients were diagnosed with one of the following 18 different types of malignant tumors:lung cancer,gastric cancer,liver cancer,colorectal cancer,breast cancer,esophageal cancer,cervical cancer,endometrial cancer,nasopharyngeal carcinoma,malignant lymphoma,leukemia,pancreatic cancer,ovarian cancer,prostate cancer,bladder cancer,brain cancer,biliary tract malignant tumors or gastrointestinal stromal tumors.These patients were enrolled from 72 hospitals located in different regions of China.The patients’nutritional status was evaluated based on the body mass index(BMI),loss of bodyweight,laboratory measurements and patient generated-subjective global assessment(PG-SGA)scores.The cancer patients’physical status and QoL were assessed by the Karnofsky Performance Status(KPS)questionnaire and the European Organization for Research and Treatment of Cancer(EORTC)QLQ-C30 questionnaire,respectively.Results From December 2013 to April 2016,23,994 patients hospitalized for cancer treatment(such as surgery,chemotherapy or radiotherapy)were enrolled in the study.The patients included 12,494(52.9%)males and 11,124(47.1%)females.The mean age was 55.8±13.7 years.The proportions of patients in cancer stagesⅠ,Ⅱ,Ⅲ,Ⅳand uncertain were 11.5%,20.3%,27.5%,30.2%and 10.5%,respectively.Among the 23,994 inpatients,the proportions of patients who were underweight(BMI<18.5 kg/m2),normal(18.5 kg/m2<BMI<24 kg/m2),overweight(24 kg/m2≤BMI<28 kg/m2)and obese(BMI≥28 kg/m2)were 9.3%,59.9%,26.1%and 4.7%,respectively.A total of 18.3%(4,101/22,424)of patients had lost 5%or more of their bodyweight within the past month and 19.6%(2,463/12,538)of patients had lost 10%or more of their bodyweight within the past 6 months.According to the PG-SGA scores,26.6%of the patients were severely malnourished(score≥9),31.3%were moderately malnourished(scores 4~8).A total of 22.2%of patients had a serum albumin level lower than 35g/L.Only 8.6%(2056/23,991)of the patients had severe KPS scores(≤60).The patients with these severe KPS scores were most frequently among those with cancers of the brain(19.7%),prostate(18.0%),pancreas(15.5%)and bladder(15.0%).Based on the QLQ-C30 score,11.6%of patients had a poor QoL.The PG-SGA score and global QoL were correlated(r=-0.593,P<0.001).Conclusion The prevalence of malnutrition in patients with cancer is relatively high,and is related to a poorer QoL.The present findings should be kept in mind when assessing cancer patients,because addressing the patient’s problems in nutritional status would be expected to improve both the clinical outcomes and QoL in cancer patients with malnutrition.

Gender-Related Survival in Different Stages of Lung Cancer—A Population Study over 20 Years

Introduction: Tumour stage is the most important prognostic factor in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The aim of this study was to evaluate if female gender was a prognostic factor in different tumour stages in relation to histology and given therapy. Methods: From 1989-2008, 1497 patients in eastern Scania, in southern Sweden with 202,000 inhabitants, were referred and prospectively registered. Tumour stage, performance status, lung cancer type and primary therapy were registered. Results: In NSCLC, female patients in stages 1 and 2 who were treated with surgery had a better 5-year survival rate (79.4%), compared to males (60.6%;p = 0.0004). Female patients in stage 3 with active therapy (surgery and/or radiotherapy and/or chemotherapy) had a better 5-year survival than males (20.6% vs. 10.5%, respectively, p = 0.0006). Female patients with adenocarcinoma were favourable in stages 1-3. In stage 4, there was no survival difference between females and males. In SCLC, females with limited disease (LD) and active therapy (chemotherapy ±?radiotherapy ± surgery) had a higher 5-year survival rate (28%) than males (5.6%);p = 0.001. Females with extensive disease (ED) and active therapy (chemotherapy ± radiotherapy) had a better 5-year survival (3.9%) compared to males (0.7%);p = 0.023. In multivariate analyses, patient performance status at diagnosis was also an independent prognostic factor in all tumour stages of lung cancer. Conclusions: This population-based study corroborates a female survival advantage in NSCLC stages 1-3, but not in metastatic stage 4, and this is also demonstrated for the adenocarcinoma subgroup. The study also confirms better prognosis in females with SCLC in both LD and ED. The study also demonstrates the importance of patient performance status as a prognostic factor in all stages of lung cancer.

“Six-and-twelve” score for outcome prediction of hepatocellular carcinoma following transarterial chemoembolization. In-depth analysis from a multicenter French cohort

The“six-and-twelve”(6&12)score is a new hepatocellular carcinoma(HCC)prognostic index designed for recommended transarterial chemoembolization(TACE)candidates.Quick and easy to use by the sum of tumor size(cm)and number,this model identifies three groups with different survival time(the sum is≤6;or>6 but≤12;or>12);a survival benefit with TACE can be expected for HCC patients with a score not exceeding twelve.Recently,Wang ZW et al showed that the“6&12”model was the best system correlated with radiological response after the first TACE.Thus,we wanted to assess its survival prediction ability as well as its prognostic value and compared it to other systems(Barcelona Clinic Liver Cancer,Hong Kong Liver Cancer(HKLC)staging,Albumin-Bilirubin grade,tumor nodularity,infiltrative nature of the tumor,alpha-fetoprotein,Child-Pugh class,and Performance Status score,Cancer of the Liver Italian Program,Model to Estimate Survival for HCC scores,up-to-seven criteria)different from Wang ZW et al study in a multicenter French cohort of HCC including only recommended TACE candidates retrospectively enrolled.As previously demonstrated,we show that the"6&12”score can classify survival within this French cohort,with a prognostic value comparable to that of other systems,except HKLC staging.More importantly,the“6&12”score simplicity and ability in patients’stratification outperform other systems for a routine clinical practice.

Activity and bioavailability of tepotinib for leptomeningeal metastasis of NSCLC with MET exon 14 skipping mutation

Tepotinib is a key drug for cancer patients with mesenchymal-epithelial transition receptor tyrosine kinase proto-oncogene(MET)exon 14 skipping mutation.However,its bioavailability in the cerebrospinal fluid(CSF)in humans has not been fully elucidated.Moreover,information about the efficacy of tepotinib in patients with leptomeningeal metastasis is limited.Here,we present the case of a 56-year-old man who was diagnosed with lung adenocarcinoma with MET exon 14 skipping mutation.He was urgently hospitalized due to leptomeningeal metastasis.We administered tepotinib 500 mg/day as the second-line therapy and observed improvement in leptomeningeal metastasis and performance status.The tepotinib concentrations reached 1,648 ng/mL in the plasma and 30.6 ng/mL in the CSF,with a penetration rate(CSF/plasma)of 1.83%.These demonstrate tepotinib could achieve a high rate of central nervous system transition and could be effective against leptomeningeal metastasis.