Combined Assessment of Preoperative Frailty and Sarcopenia Allows the Prediction of Overall Survival in Patients with Lung Cancer (NSCLC) and Surgically Treated Brain Metastasis.
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SUBMITTER: Ilic I
PROVIDER: S-EPMC8267959 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundTumor tissue as well as regional lymph nodes are removed during curative surgery for early-stage non-small cell lung cancer (NSCLC). These tissues provide a unique snapshot of the immune cell composition at the time of surgery. We investigated the immune landscape in matched tumor tissue, tumor bearing (tb) and non-tumor bearing (ntb) N1 as well as N2 lymph nodes (LNs) in patients with NSCLC and its relation to survival.MethodsInternal hospital databases were screened for surgically treated NSCLC patients for whom tumor tissue, tbLNs as well as N1 and N2 ntbLNs were available. Clinical as well as demographic data were extracted from hospital records. Expression profiling of 770 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies.ResultsWe identified 190 surgically treated patients of whom 16 fulfilled inclusion criteria and had sufficient archived tissue. The Tumor Immune Dysfunction and Exclusion (TIDE) score in N1 tumor-free lymph nodes was associated with OS. TIM-3 expression was inversely correlated with TIDE scores in affected LNs, N1 and N2 ntbLNs. Levels of CD8 expression were significantly higher in TIDE High compared to TIDE Low patients. TIM-3 and PD-L1 were selected for the final model for OS in multivariate regression in more than one tissue.ConclusionLevels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC.
| S-EPMC9271570 | biostudies-literature
Project description:ObjectivePlatelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.DesignUsing a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.ResultsPatients with clinically high platelet count (≥400 × 10(9)/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR] = 1.66, 95 % confidence interval [CI] 1.34-2.05, P = 2.6 × 10(-6), P(log rank) = 1.1 × 10(-11)) and recurrence (HR = 1.90, 1.24-2.93, P = 0.003, P(log rank) = 0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR = 2.81, 1.67-4.74, P = 1.1 × 10(-4), P(log rank) = 2.6 × 10(-6)) but not locoregional recurrence (HR = 0.59, 95 % CI 0.21-1.68, P = 0.325, P(log rank) = 0.152). The findings were internally validated through bootstrap resampling (P < 0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P < 0.0001) and in patients with metastatic recurrence than locoregional (P = 0.004) or nonrecurrent patients (P < 0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.ConclusionOur data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.
| S-EPMC3748145 | biostudies-literature
Project description:BackgroundThis study aimed to comprehensively evaluate the efficacy and toxicity of afatinib in patients with sarcopenia, an important prognostic factor for treatment efficacy and toxicity in patients with cancer.MethodsThe clinical features of patients with advanced NSCLC treated with frontline afatinib between 2014 and 2018 at a medical center in Taiwan were retrospectively reviewed. Sarcopenia was evaluated based on the total cross-sectional area of skeletal muscles assessed by computed tomography (CT) imaging at the L3 level. Baseline characteristics, response rates, survival rates, and adverse events (AEs) were compared between sarcopenic and nonsarcopenic patients.ResultsA total of 176 patients evaluated for sarcopenia by CT and treated with afatinib were enrolled in the current study. Sarcopenia was significantly associated with good performance status, low body mass index (BMI), low body surface area (BSA), and low total mass area (TMA). Sarcopenia did not influence the response rate (69.2% vs. 72.0%, p = 0.299), progression-free survival (median 15.9 vs. 14.9 months, p = 0.791), or overall survival (median 26.5 vs. 27.2 months, p = 0.441). However, BSA ≤ 1.7 and the 40 mg afatinib dose were associated with dose reduction. TMA was the only independent factor for afatinib discontinuation due to AEs.ConclusionSarcopenia was not associated with treatment efficacy or toxicity among patients with NSCLC harboring common mutations treated with afatinib, indicating sarcopenic patients should not be excluded from afatinib treatment. Other factors, such as BSA and TMA, were associated with dose reduction and afatinib discontinuation, respectively, which may require additional evaluations in future studies.
| S-EPMC10481145 | biostudies-literature
Project description:In patients with decompensated cirrhosis, sarcopenia and frailty are prevalent. Although several definitions exist for these terms, in the field of hepatology, sarcopenia has commonly been defined as loss of muscle mass, and frailty has been broadly defined as the phenotypic manifestation of the loss of muscle function. Prompt recognition and accurate assessment of these conditions are critical as they are both strongly associated with morbidity, mortality, poor quality of life and worse post-liver transplant outcomes in patients with cirrhosis. In this review, we describe the complex pathophysiology that underlies the clinical phenotypes of sarcopenia and frailty, their association with decompensation, and provide an overview of tools to assess these conditions in patients with cirrhosis. When available, we highlight data focusing on patients with acutely decompensated cirrhosis, such as inpatients, as this is an area of unmet clinical need. Finally, we discuss management strategies to reverse and/or prevent the development of sarcopenia and frailty, which include adequate nutritional intake of calories and protein, as well as regular exercise of at least moderate intensity, with a mix of aerobic and resistance training. Key knowledge gaps in our understanding of sarcopenia and frailty in decompensated cirrhosis remain, including best methods to measure muscle mass and function in the inpatient setting, racial/ethnic variation in the development and presentation of sarcopenia and frailty, and optimal clinical metrics to assess response to therapeutic interventions that translate into a reduction in adverse outcomes associated with these conditions.
| S-EPMC9125684 | biostudies-literature
Project description:Musculoskeletal aging is a major public health interesting and strain due to the significant demographic modifications in the population, and it is linked to high risk of falls, loss of autonomy in elderly individuals and institutionalization with small health outcomes. Thus, this pathological status is related to high morbidity and health care rates. Bone mass and muscle mass and strength increase during late adolescence and early adulthood but start to reduce noticeably from the fifth decade of life and are closely linked. Bone and muscle tissues were increasingly recognized, as endocrine target organs and endocrine organs themselves, interacting through paracrine and endocrine signals. During growth, bone mineral content closely correlates with muscle mass, and several evidences suggest that osteoporosis and sarcopenia present common pathophysiological factors and show the correlation between low bone mineral density and sarcopenia in both men and women. Then, sarcopenia and osteoporosis, typical features of aging, are often associated with each other and with the frailty syndrome. In particular, sarcopenia and osteoporosis are major contributors to disability and frailty and the common denominators are age-related chronic inflammation, changes in body composition and hormonal imbalance. Frailty syndrome is characterized by a reduced response to stress, triggering the decline of the physiological functioning of the various systems. Frailty syndrome, typical of the older people, is frequently associated with a reduction in the quality of life and mobility. Falls often are the basis of reduced mobility and ability to perform the common functions of daily life and the increase in the number of institutionalizations. Moreover, the reduction of muscle mass, associated with altered muscle composition, fat and fibrous infiltration and alterations in innervations, and the increase in fat mass, have a synergistic effect on the increase in cardiovascular risk. The aim of this review is to analyze the pathophysiological mechanisms underlying the frailty syndrome and its association with sarcopenia and osteoporosis, and investigate possible intervention measures.
| S-EPMC6491670 | biostudies-other
Project description:PurposeWhile several clinical prediction rules (CPRs) of survival exist for patients with symptomatic spinal metastasis (SSM), these have variable prognostic ability and there is no recognized CPR for health related quality of life (HRQoL). We undertook a critical appraisal of the literature to identify key preoperative prognostic factors of clinical outcomes in patients with SSM who were treated surgically. The results of this study could be used to modify existing or develop new CPRs.MethodsSeven electronic databases were searched (1990-2015), without language restriction, to identify studies that performed multivariate analysis of preoperative predictors of survival, neurological, functional and HRQoL outcomes in surgical patients with SSM. Individual studies were assessed for class of evidence. The strength of the overall body of evidence was evaluated using GRADE for each predictor.ResultsAmong 4,818 unique citations, 17 were included; all were in English, rated Class III and focused on survival, revealing a total of 46 predictors. The strength of the overall body of evidence was very low for 39 and low for 7 predictors. Due to considerable heterogeneity in patient samples and prognostic factors investigated as well as several methodological issues, our results had a moderately high risk of bias and were difficult to interpret.ConclusionsThe quality of evidence for predictors of survival was, at best, low. We failed to identify studies that evaluated preoperative prognostic factors for neurological, functional, or HRQoL outcomes in surgical patients with SSM. We formulated methodological recommendations for prognostic studies to promote acquiring high-quality evidence to better estimate predictor effect sizes to improve patient education, surgical decision-making and development of CPRs.
| S-EPMC5321441 | biostudies-literature
Project description:PurposeAnaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib. To determine the outcome of sequential treatment with crizotinb and ceritinib, we retrospectively evaluated a cohort of ALK-positive patients treated with both agents.Experimental designWe identified 73 ALK-positive NSCLC patients treated with crizotinib followed by ceritinib at four institutions. Medical records were reviewed to determine overall survival (OS) and progression-free survival (PFS) on crizotinib and ceritinib.ResultsAmong 73 ALK-positive patients, the median PFS (mPFS) on crizotinib was 8.2 months [95% confidence interval (CI), 7.4-10.6]. The median interval from crizotinib discontinuation to initiation of ceritinib was 25 days (range, 1-694). The mPFS on ceritinib was 7.8 months (6.5-9.1). Among 53 patients with no interval therapies between crizotinib and ceritinib, the mPFS on ceritinib was similar at 7.8 months (5.4-9.8). The median combined PFS for sequential treatment with crizotinib and ceritinib was 17.4 months (15.5-19.4). Among 23 patients who underwent post-crizotinib/pre-ceritinib biopsies, there was no difference in PFS on ceritinib between patients with or without ALK resistance mutations (mPFS 5.8 vs. 6.5 months, respectively; P = 0.510). In the overall study population, median OS was 49.4 months (35.5-63.1).ConclusionsCeritinib has significant antitumor activity in ALK-positive NSCLC-even when crizotinib immediately precedes treatment with ceritinib (median combined PFS 17.0 months). Additional studies are necessary to further define the impact of specific ALK resistance mutations on duration of response to ceritinib.
| S-EPMC4470734 | biostudies-literature
Project description:Sarcopenia and frailty are geriatric syndromes characterized by multisystem decline, which are related to and reflected by markers of skeletal muscle dysfunction. In older people, sarcopenia and frailty have been used for risk stratification, to predict adverse outcomes and to prompt intervention aimed at preventing decline in those at greatest risk. In this review, we examine sarcopenia and frailty in the context of chronic respiratory disease, providing an overview of the common assessments tools and studies to date in the field. We contrast assessments of sarcopenia, which consider muscle mass and function, with assessments of frailty, which often additionally consider social, cognitive and psychological domains. Frailty is emerging as an important syndrome in respiratory disease, being strongly associated with poor outcome. We also unpick the relationship between sarcopenia, frailty and skeletal muscle dysfunction in chronic respiratory disease and reveal these as interlinked but distinct clinical phenotypes. Suggested areas for future work include the application of sarcopenia and frailty models to restrictive diseases and population-based samples, prospective prognostic assessments of sarcopenia and frailty in relation to common multidimensional indices, plus the investigation of exercise, nutritional and pharmacological strategies to prevent or treat sarcopenia and frailty in chronic respiratory disease.
| S-EPMC5720213 | biostudies-literature
Project description:BackgroundFrailty, characterized by vulnerability, reduced reserves and increased susceptibility to severe events, is a significant concern in chronic haemodialysis (HD) patients. Sarcopenia, corresponding to the progressive loss of muscle mass and strength, may contribute to frailty by reducing functional capacity, mobility and autonomy. However, consensus lacks on the optimal bedside frailty index for chronic HD patients. This study investigated the influence of frailty on chronic HD patient survival and explored the associated factors.MethodsA total of 135 patients were enrolled from January to April 2019 and then followed up prospectively until April 2022. At inclusion, frailty was assessed by the Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests including gait speed, standing balance and lower limb muscle strength.ResultsFrom a total of 114 prevalent chronic HD patients (66% men, age 67.6 ± 15.1 years), 30 died during the follow-up period of 23.7 months (range 16.8-34.3). Deceased patients were older, had more comorbidities and a higher sarcopenia prevalence (P < .05). The TUG and SPPB test scores were significantly reduced in patients who had died [SPPB total score: 7.2 ± 3.3 versus 9.4 ± 2.5; TUG time 8.7 ± 5.8 versus 13.8 ± 10.5 (P < .05)]. Multivariate analysis showed that a higher SPPB score (total value >9) was associated with a lower mortality risk [hazard ratio 0.83 (95% confidence interval 0.74-0.92); P < .03). Each component of the SPPB test was also associated with mortality in univariate analysis, but only the SPPB balance test remained protective against mortality in multivariate analysis. Older age, lower handgrip strength and lower protein catabolic rate were associated with SPPB total scores <9, SPPB balance score and TUG time >10 s.ConclusionsScreening for frailty is crucial in chronic HD patients, and incorporating SPPB, especially the balance test, provides valuable insights. Diminished muscle strength and inadequate protein intake negatively influence the SPPB score and balance in chronic HD patients. Effective identification and management of frailty can therefore improve outcomes.Clinical trial registration clinicaltrialsgovNCT03845452.
| S-EPMC11231581 | biostudies-literature
Project description:ObjectivesFrailty and sarcopenia have been related with adverse events, including hospitalization. However, its combined effect with hospitalization-related outcomes, including costs, has not been previously investigated. Our purpose was to explore how frailty, sarcopenia and its interaction could impact on healthcare expenditures.Methods1358 community-dwelling older adults from the Toledo Study of Healthy Ageing (TSHA) were included. Sarcopenia was measured using the Foundation for the National Institutes of Health criteria fitted to our cohort. Frailty was defined according to Frailty Trait Scale 5 (FTS5) and the Frailty Index fitted to the cut-off points of TSHA population. Hospitalization costs were taken from hospital records and costs were attributed according to Diagnostic-Related Groups, using as the cost base year 2015. Two-part regression models were used to analyze the relationship between frailty and sarcopenia and hospital admission, number of hospitalizations, length of stay and hospitalization costs.ResultsSarcopenia was associated only with the probability of being admitted to hospital. Frailty was also associated with higher hospital use, regardless of the frailty tool used, but in addition increased hospital admission costs at follow-up by 23.72% per year and by 19.73% in the full model compared with non-frail individuals. The presence of sarcopenia did not increase the costs of frailty but, by opposite, frailty significantly increased the costs in people with sarcopenia, reaching by 46-56%/patient/year at follow-up. Older adults with frailty and sarcopenia had a higher risk of hospitalization, disregarding the tool used to assess frailty, and higher hospitalization costs (FTS5) in the full model, at the cross-sectional and at the follow-up level.ConclusionsFrailty is associated with increased hospitalization costs and accounts for the potential effects of sarcopenia.
| S-EPMC9469617 | biostudies-literature