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Influence of Different Age Cutoff Points on the Prediction of Prognosis of Cancer Patients Receiving ICIs and Potential Mechanistic Exploration.

ABSTRACT: Age is a potential predictive marker for the prognosis of cancer patients treated with immune checkpoint inhibitors (ICIs), but the appropriate age cutoff point is still controversial. We aimed to explore the influence of different age cutoff points on the prediction of prognosis for patients receiving ICIs and explore the mechanism underlying the appropriate age cutoff point from the aspects of gene mutation and expression, immune cell infiltration and so on. We applied cutoff points of 50, 55, 60, 65, 70, and 75 years old to divide 1660 patients from the Memorial Sloan-Kettering Cancer Center (MSKCC) immunotherapy cohort into older and younger groups and performed survival analysis of the six subgroups. The results showed that older patients had better survival than younger patients in accordance with the cutoff point of 50 years old [median overall survival (OS) (95% CI): 13.0 (10.5-15.5) months vs. 20.0 (16.7-23.3) months; p=0.002; unadjusted hazard ratio (HR) (95% CI): 0.77 (0.65-0.91)], whereas no significant difference was observed with other cutoff points. Further analysis of The Cancer Genome Atlas (TCGA) database and the MSKCC immunotherapy cohort data showed that the tumor mutation burden (TMB), neoantigen load (NAL), DNA damage response and repair (DDR) pathway mutation status, mutation frequencies of most genes (except IDH1, BRAF and ATRX), the expression of most immune-related genes and the degree of infiltration of most immune cells (such as CD8+ T cells and M1 macrophages) were higher in the elderly group (aged ≥50 years).

SUBMITTER: Guan R

PROVIDER: S-EPMC8260982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Optimal cutoff age for predicting prognosis associated with serous epithelial ovarian cancer: what is the best age cutoff?

Project description:ObjectiveElderly age is one of the poor prognostic factors in epithelial ovarian cancer (EOC), but the optimal age cut-off is not known. The present study sought to identify the ideal age cutoff that represents a negative prognostic factor in EOC, considering the geriatric assessment.MethodsHazard ratios (HRs) with p-values were calculated using all possible age cutoffs with stage, histology, grade, optimality and comorbidities as covariates in multivariate Cox regression model. The trends of p-value and HR by age cutoff were further evaluated in a subgroup of histology and in The Cancer Genome Atlas (TCGA) dataset. In addition, propensity score-matching analysis using the identified age cutoff was performed.ResultsAn age of 66 years was shown to be the most significant cutoff for defining old age with independent prognostic power (HR=1.45; 95% confidence interval=1.04-2.03; p=0.027). This result was also observed with the analyses of serous histology subgroup and with the analysis of a TCGA dataset with serous EOC. In survival analysis, patients aged ?66 years had significantly worse overall survival compared with younger individuals (56 months vs. 87 months; p=0.006), even following propensity score matching (57 vs. 78 months; p=0.038).ConclusionAn age of 66 years is the best cutoff to define elderly age in serous EOC patients considering the geriatric assessment, and this information can be used in the administration of individualized therapies in elderly EOC patients.

| S-EPMC6304408 | biostudies-literature

The need to redefine age- and gender-specific overweight and obese body mass index cutoff points.

Project description:For convenience, health practitioners and clinicians are inclined to classify people/patients as overweight or obese based on body mass index (BMI) cutoff points of 25 and 30 kg m(-2) respectively, irrespective of age and gender. The purpose of the current study was to identity whether, for the same levels of adiposity, BMI is the same across different age groups and gender. A two-way ANCOVA revealed significant differences in BMI between different age groups and gender (plus an interaction), using body fat (%) as the covariate, data taken from a random sample of the English population (n=2993). Younger people had greater BMI than older people for the same levels of adiposity (differences ranged by 4 BMI units for males, and 3 BMI units for females). In conclusion, if BMI thresholds for overweight (BMI=25 kg m(-2)) and obese (BMI=30 kg m(-2)) are to reflect the same levels of adiposity across all gender and age groups within a population, then age- and gender-specific BMI adjustments outlined here are necessary to more accurately/fairly reflect the same critical levels of adiposity.

| S-EPMC4672357 | biostudies-other

The Distress Thermometer: Cutoff Points and Clinical Use

Project description:Purpose/objectivesTo establish an optimal cutoff point for the National Comprehensive Cancer Network’s Distress Thermometer (DT) as a screening measure to identify and address psychological distress in individuals with cancer, and to examine whether distress as measured by the DT significantly changes across the treatment trajectory.DesignSecondary analyses of baseline data from a longitudinal parent study examining a computerized psychosocial assessment.SettingThree diverse comprehensive cancer centers across the United States.Sample836 patients with a current or past diagnosis of cancer.MethodsStudy participants were selected from a randomized clinical trial. Patients during any stage of the cancer treatment trajectory were recruited during a chemotherapy infusion or routine oncology appointment.Main research variablesThe Behavioral Health Status Index and the DT were administered and compared using receiver operating characteristic analyses.FindingsResults support a cutoff score of 3 on the DT to indicate patients with clinically elevated levels of distress. In addition, patients who received a diagnosis within the 1–4 weeks prior to the assessment indicated the highest levels of distress.ConclusionsProviders may wish to use a cutoff point of 3 to most efficiently identify distress in a large, diverse population of patients with cancer. In addition, results indicate that patients may experience a heightened state of distress within 1–4 weeks postdiagnosis compared to other stages of coping with cancer.Implications for nursingUsing a brief measure of distress can help streamline the process of screening for psychosocial distress.

| S-EPMC5839660 | biostudies-literature

Sarcopenia: Influence of Regional Skeletal Muscle Cutoff Points and Fat-Free Mass in Older Mexican People-A Pilot Study.

Project description:Background:Variation in the prevalence of sarcopenia is related to the skeletal muscle index cutoff points applied. The objective of this pilot study was to examine the recruitment process for testing different sarcopenia definitions (ASMI cutoffs) in older Mexican adults. It explored whether the prevalence of sarcopenia decreased by applying ethnic- and gender-specific, DXA-derived appendicular skeletal muscle index (ASMI)-cutoff points in the definitions, as well as some associated factors in a sample of community-dwelling older Mexican people. Methods:This is a pilot feasibility study that included a convenience sample of 217 community-dwelling older adults. Volunteers underwent DXA measurements and an assessment of functional status based on hand grip strength and physical performance. Six definitions were formed based on the 2010 EWGSOP criteria, but using different cutoff points for each of the three components, including regional cutoff points for ASMI derived from young Mexican adults. Several risk factors for sarcopenia were also assessed. Results:The prevalence of sarcopenia varied according to the different definitions applied. The lowest level was found with the definition that applied regional ASMI-cutoff points (p < 0.01). The sarcopenic older adults had significant lower body weight, fat mass, and fat-free mass (FFM) than the nonsarcopenic subjects. The risk of sarcopenia increased with age and low FFM (p < 0.001). Conclusion:The present study demonstrates the feasibility of the main study, and our data support the notion that using regional ASMI cutoff points resulted in a low prevalence of sarcopenia. Therefore, it is preferable to estimate the prevalence of this condition using ethnic- and gender-specific cutoff points and to explore associated factors such as low FFM.

| S-EPMC7281843 | biostudies-literature

Deriving ethnic-specific BMI cutoff points for assessing diabetes risk.

Project description:ObjectiveThe definition of obesity (BMI ? 30 kg/m(2)), a key risk factor of diabetes, is widely used in white populations; however, its appropriateness in nonwhite populations has been questioned. We compared the incidence rates of diabetes across white, South Asian, Chinese, and black populations and identified equivalent ethnic-specific BMI cutoff values for assessing diabetes risk.Research design and methodsWe conducted a multiethnic cohort study of 59,824 nondiabetic adults aged ? 30 years living in Ontario, Canada. Subjects were identified from Statistics Canada's population health surveys and followed for up to 12.8 years for diabetes incidence using record linkages to multiple health administrative databases.ResultsThe median duration of follow-up was 6 years. After adjusting for age, sex, sociodemographic characteristics, and BMI, the risk of diabetes was significantly higher among South Asian (hazard ratio 3.40, P < 0.001), black (1.99, P < 0.001), and Chinese (1.87, P = 0.002) subjects than among white subjects. The median age at diagnosis was lowest among South Asian (aged 49 years) subjects, followed by Chinese (aged 55 years), black (aged 57 years), and white (aged 58 years) subjects. For the equivalent incidence rate of diabetes at a BMI of 30 kg/m(2) in white subjects, the BMI cutoff value was 24 kg/m(2) in South Asian, 25 kg/m(2) in Chinese, and 26 kg/m(2) in black subjects.ConclusionsSouth Asian, Chinese, and black subjects developed diabetes at a higher rate, at an earlier age, and at lower ranges of BMI than their white counterparts. Our findings highlight the need for designing ethnically tailored prevention strategies and for lowering current targets for ideal body weight for nonwhite populations.

| S-EPMC3142051 | biostudies-literature

Neck circumference and excess weight: proposal of cutoff points for Brazilian adolescents.

Project description:ObjectiveTo indicate neck circumference (NC) cutoff points to identify excess weight at different stages of somatic maturation and evaluate the association between NC and body mass index (BMI).MethodsCross-sectional study with 1715 adolescents. BMI was classified according to the World Health Organization (WHO) criteria. Somatic maturation was obtained through the peak growth velocity (PGV). To define the cutoff points, curves of the receiver operating characteristic (ROC) model were constructed. The agreement between the anthropometric evaluation instruments was analyzed. The association between the variables was verified.ResultsOf the girls, 93 were in the pre-PGV stage, 266 in the PGV stage, and 481 in the post-PGV stage. Of the boys, 264 were in the pre-PGV stage, 334 in the PGV stage, and 277 in the post-PGV stage. For the pre-PGV group, the cutoff point was 28cm for females and 29cm for males; for the group during PGV, the cutoff points were 30cm for females and 33cm for males; in the post-PGV group the cutoff values were 32cm in females and 35cm in males. The prevalence of excess weight was higher in the pre-PGV stage in males and in the PGV stage in females. The correlation coefficients were higher in the pre-PGV and PGV stages.ConclusionThe cutoff points for NC found in this study showed good sensitivity and specificity to identify excess weight in Brazilian adolescents and can be used as a reference in epidemiological studies.

| S-EPMC9432223 | biostudies-literature

Reconsidering Cutoff Points in the General Method of Empirical Q-Matrix Validation.

Project description:Cognitive diagnosis models (CDMs) are latent class multidimensional statistical models that help classify people accurately by using a set of discrete latent variables, commonly referred to as attributes. These models require a Q-matrix that indicates the attributes involved in each item. A potential problem is that the Q-matrix construction process, typically performed by domain experts, is subjective in nature. This might lead to the existence of Q-matrix misspecifications that can lead to inaccurate classifications. For this reason, several empirical Q-matrix validation methods have been developed in the recent years. de la Torre and Chiu proposed one of the most popular methods, based on a discrimination index. However, some questions related to the usefulness of the method with empirical data remained open due the restricted number of conditions examined, and the use of a unique cutoff point (EPS) regardless of the data conditions. This article includes two simulation studies to test this validation method under a wider range of conditions, with the purpose of providing it with a higher generalization, and to empirically determine the most suitable EPS considering the data conditions. Results show a good overall performance of the method, the relevance of the different studied factors, and that using a single indiscriminate EPS is not acceptable. Specific guidelines for selecting an appropriate EPS are provided in the discussion.

| S-EPMC7328244 | biostudies-literature

Comparison of Mid-Term Prognosis in Intermediate-to-Low-Risk Contemporary Population with Guidelines-Oriented Age Cutoff.

Project description:BackgroundCurrent European guidelines support transcatheter aortic valve implantation (TAVI) in intermediate-to-low-risk patients ≥75 years-old, but its prognostic relevance is unknown.MethodsIntermediate-to-low-risk (The Society of Thoracic Surgeons score <8%) patients enrolled in the HORSE registry were included. We compared the populations aged under 75 with those over 75. The primary endpoint was all-cause mortality.ResultsA total of 2685 patients were included: 280 (8.6%) < 75 and 2405 ≥ 75 years. Through a mean follow-up of 437 ± 381 days, 198 (8.2%) and 23 (8.2%) patients died in the two arms without statistically significant differences (log-rank p = 0.925). At Cox regression analysis, age did not predict the occurrence of all-cause death, neither as a continuous variable (HR 1.01, 95% CI 0.99-1.04, p = 0.294) nor dichotomizing according to the prespecified cutoff of 75 years (HR 0.97, 95% CI 0.63-1.51, p = 0.924). Time-to-event ROC curves showed low accuracy of age to predict all-cause mortality (area under the curve of 0.54 for both 1-year and 2-year outcomes).ConclusionsTAVI has comparable benefits across age strata for intermediate-to-low-risk patients. The age cutoff suggested by the current guidelines is not predictive of the risk of adverse events during hospital stays or of all-cause mortality through a mid-term follow-up.

| S-EPMC10816002 | biostudies-literature

Clinical impact of endocapillary proliferation with modified cutoff points in IgA nephropathy patients.

Project description:Predictive values of mesangial proliferation (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and crescents (C) among 19 validation studies of the Oxford Classification of IgA nephropathy (IgAN) were discrepant, especially in Asian patients. These validation studies indicate that cutoffs of MESC score in the Oxford Classification may not be generalizable. Thus, we aimed to improve the clinical value of MESC scores by modifying the cutoff points. A total of 104 patients with IgAN were diagnosed from 2001 to 2012 vai renal biopsy and retrospectively evaluated at Nagoya University Hospital. The cutoff point for modified (M´E´S´C´) was determined using the receiver operating characteristic curve in association with renal outcome in the training cohort. Clinical values of the Oxford MESTC vs M´E´S´C´ cutoff points were analyzed using Kaplan-Meier and Cox regression in association with poor renal outcome in the validation and the entire cohort. Of 104 patients, 12.5% reached poor renal outcome over a median of 6.25 [4.16-9.61] years of follow-up. The modified cutoffs were defined as ≥40%, ≥10%, ≥20%, and ≥5% in the glomeruli for M´E´S´, and C´ respectively. In univariate analysis, E´, S ´, and T were significantly associated with poor renal outcome, whereas Oxford MESC, M´, and C´ in the training and validation cohort were not associated with poor renal outcome. Using multivariate analysis in the presence of estimated glomerular filtration rate (eGFR), only E´ was a significant predictive factor for poor renal outcome. The E´ with modified cutoff point of 10% significantly improved predictive value for poor renal outcome in IgAN. Therefore, the clinical value of modified cutoff points for M´E´S´C´ scores should be validated with various cohort studies in different regions.

| S-EPMC6440693 | biostudies-literature

Influence of age, gender, and race on nitric oxide release over acupuncture points-meridians.

Project description:This study examined the influence of age, gender and race on nitric oxide (NO) release over acupuncture points, meridian without acupoint, and non-meridian regions of the Pericardium (PC) and Bladder (BL) meridian as well as aging on LU meridian in 61 healthy subjects. Biocapture tubes were attached to the skin surface, and total nitrite and nitrate was biocaptured and quantified using chemiluminescence. In elder ages compared to adults, NO levels over the ventral forearm were significantly decreased over LU on radial regions but not altered over PC on medial regions. Conversely, NO content was elevated over BL regions only in overweight/obesity of elder ages. NO levels over PC regions were marginally elevated in overweight/obese males compared to females but did not alter between races. These results suggest a selective reduction of NO release over LU meridian with aging, which is consistent with a progressive decline in lung function and increase in chronic respiratory disease in elder ages. Increased NO levels along the BL meridian in older obese subjects may reflect a modified NO level along somatic-bladder pathway for counteracting bladder dysfunctions with aging. Both of them support somatic-organ connections in the meridian system associated with potential pathophysiological changes with aging.

| S-EPMC4664911 | biostudies-other

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