scholarly journals Identification of circulating protein biomarkers for pancreatic cancer cachexia

2018 ◽  
Author(s):  
Safi Shahda ◽  
Ashok Narasimhan ◽  
Joshua Kays ◽  
Susan M. Perkins ◽  
Lijun Cheng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Cell Signaling ◽  
B Cell ◽  
Expression Analysis ◽  
Killer Cell ◽  
Model Systems ◽  
Protein Biomarkers ◽  
Skeletal Muscle Index ◽  
Secreted Factors

AbstractBackgroundOver 80% of patients with pancreatic ductal adenocarcinoma (PDAC) suffer from cachexia, characterized by severe muscle and fat loss. Although various model systems have improved our understanding of cachexia, translating the findings to human cachexia has remained a challenge. In this study, our objectives were to i) identify circulating protein biomarkers using serum for human PDAC cachexia, (ii) identify the ontological functions of the identified biomarkers and (iii) identify new pathways associated with human PDAC cachexia by performing protein co-expression analysis.MethodsSerum from 30 patients with PDAC was collected. Body composition measurements of skeletal muscle index (SMI), skeletal muscle density (SMD), total adipose index (TAI) were obtained from computed tomography scans (CT). Cancer associated weight loss (CAWL), an ordinal classification of history of weight loss and body mass index (BMI) was obtained from medical record. Serum protein profiles and concentrations were generated using SOMAscan, a quantitative aptamer-based assay. Ontological analysis of the proteins correlated with clinical variables (r≥ 0.5 and p<0.05) was performed using DAVID Bioinformatics. Protein co-expression analysis was determined using pairwise Spearman’s correlation.ResultsOverall, 111 proteins of 1298 correlated with these clinical measures, 48 proteins for CAWL, 19 for SMI, 14 for SMD, and 30 for TAI. LYVE1, a homolog of CD44 implicated in tumor metastasis, was the top CAWL-associated protein (r= 0.67, p=0.0001). Other proteins such as INHBA, MSTN/GDF11, and PIK3R1 strongly correlated with CAWL. Proteins correlated with cachexia included those associated with proteolysis, acute inflammatory response, as well as B cell and T cell activation. Protein co-expression analysis identified networks such as activation of immune related pathways such as B-cell signaling, Th1 and Th2 pathways, natural killer cell signaling, IL6 signaling, and mitochondrial dysfunction.ConclusionTaken together, these data both identify immune system molecules and additional secreted factors and pathways not previously associated with PDAC and confirm the activation of previously identified pathways. Identifying altered secreted factors in serum of PDAC patients may assist in developing minimally invasive laboratory tests for clinical cachexia as well as identifying new mediators.

scholarly journals Continued Weight Loss and Sarcopenia Predict Poor Outcomes in Locally Advanced Pancreatic Cancer Treated with Chemoradiation

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 709 ◽  
Author(s):  
Patrick Naumann ◽  
Jonathan Eberlein ◽  
Benjamin Farnia ◽  
Thilo Hackert ◽  
Jürgen Debus ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pancreatic Cancer ◽  
Weight Loss ◽  
Muscle Mass ◽  
Muscle Wasting ◽  
Statistical Tests ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Skeletal Muscle Index ◽  
Poor Outcomes

Background: Surgical resection offers the best chance of survival in patients with pancreatic cancer, but those with locally advanced disease (LAPC) are usually not surgical candidates. This cohort often receives either neoadjuvant chemotherapy or chemoradiation (CRT), but unintended weight loss coupled with muscle wasting (sarcopenia) can often be observed. Here, we report on the predictive value of changes in weight and muscle mass in 147 consecutive patients with LAPC treated with neoadjuvant CRT. Methods: Clinicopathologic data were obtained via a retrospective chart review. The abdominal skeletal muscle area (SMA) at the third lumbar vertebral body was determined via computer tomographic (CT) scans as a surrogate for the muscle mass and skeletal muscle index (SMI) calculated. Uni- and multi-variable statistical tests were performed to assess for impact on survival. Results: Weight loss (14.5 vs. 20.3 months; p = 0.04) and loss of muscle mass (15.1 vs. 22.2 months; p = 0.007) were associated with poor outcomes. The highest survival was observed in patients who had neither cachectic weight loss nor sarcopenia (27 months), with improved survival seen in those who ultimately received a resection (23 vs. 10 months; p < 0.001). Cox regression revealed that either continued weight loss or continued muscle wasting (SMA reduction) was predictive of poor outcomes, whereas a sarcopenic SMI was not. Conclusions: Loss of weight and lean muscle in patients with LAPC is prognostic when persistent. Therefore, both should be assessed longitudinally and considered before surgery.

Cancer Cachexia in the Age of Obesity: Skeletal Muscle Depletion Is a Powerful Prognostic Factor, Independent of Body Mass Index

2013 ◽  
Vol 31 (12) ◽  
pp. 1539-1547 ◽  
Author(s):  
Lisa Martin ◽  
Laura Birdsell ◽  
Neil MacDonald ◽  
Tony Reiman ◽  
M. Thomas Clandinin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Mass Index ◽  
Weight Loss ◽  
Body Mass ◽  
Normal Weight ◽  
Cancer Center ◽  
Skeletal Muscle Index ◽  
Patients With Cancer ◽  
C Statistic ◽  
Muscle Attenuation

Purpose Emerging evidence suggests muscle depletion predicts survival of patients with cancer. Patients and Methods At a cancer center in Alberta, Canada, consecutive patients with cancer (lung or GI; N = 1,473) were assessed at presentation for weight loss history, lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). Univariate and multivariate analyses were conducted. Concordance (c) statistics were used to test predictive accuracy of survival models. Results Body mass index (BMI) distribution was 17% obese, 35% overweight, 36% normal weight, and 12% underweight. Patients in all BMI categories varied widely in weight loss, muscle index, and muscle attenuation. Thresholds defining associations between these three variables and survival were determined using optimal stratification. High weight loss, low muscle index, and low muscle attenuation were independently prognostic of survival. A survival model containing conventional covariates (cancer diagnosis, stage, age, performance status) gave a c statistic of 0.73 (95% CI, 0.67 to 0.79), whereas a model ignoring conventional variables and including only BMI, weight loss, muscle index, and muscle attenuation gave a c statistic of 0.92 (95% CI, 0.88 to 0.95; P < .001). Patients who possessed all three of these poor prognostic variables survived 8.4 months (95% CI, 6.5 to 10.3), regardless of whether they presented as obese, overweight, normal weight, or underweight, in contrast to patients who had none of these features, who survived 28.4 months (95% CI, 24.2 to 32.6; P < .001). Conclusion CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.

Clinical Relevance Of Cachexia Assessed By An Anthropometric Tool In Elderly Patients With Diffuse Large B-Cell Lymphoma Treated By Immunochemotherapy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2926-2926
Author(s):  
Helene Lanic ◽  
Jerome Kraut ◽  
Romain Modzelewski ◽  
Florian Clatot ◽  
Jean-Michel Picquenot ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Elderly Patients ◽  
Ct Scan ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background Cancer Cachexia is a metabolic syndrome that can be present even in absence of weight loss and associated with significantly impaired survival. Muscle wasting represents a key-symptom of this syndrome and we recently demonstrated the strong prognosis impact of sarcopenia assessed by computed tomography (CT)-scan in diffuse large B-cell lymphoma (DLBCL) (Lanic et al. Leukemia & Lymphoma 2013). Conversely, the clinical relevance of loss of fat mass (adipopenia) remains unclear. The aim of this study was (i) to investigate the prognostic impact of a multidimensional tool combining a nutritional parameter (albuminemia) and body composition measurements (skeletal muscle and body fat composition) in elderly patients with DLBCL treated by chemotherapy and rituximab (R) (ii) to document the evolution of sarcopenia after immunochemotherapy. Methods This retrospective analysis included 80 DLBCL patients older than 70 years (y) and treated by R-CHOP or R-miniCHOP. Skeletal muscle (SM), visceral (V) and subcutaneal (S) adipose (A) tissues were measured by analysis of stored CT images at the Lumbar vertebrae 3 (L3) level. The surface of the muscular and adipose tissues was selected according to CT Hounsfield unit. Values were normalized for stature to calculate the L3 SM index (LSMI, in cm2/m2), the LVAI and the LSAI and used to define sarcopenia and visceral/subcutaneal adipopenia. Results The characteristics of the patients were as follows: median age = 78 y [70-95]; 36 males; IPI 0-2 = 22, 3-5 = 58; treatment by R-CHOP (n = 45) or R-miniCHOP (n = 35); median body mass index (BMI; in kg/m2) = 23.9. According to the sex-specific defined cut-offs for LSMI (< 55.8 cm²/m² for men and 38.9 cm²/m² for women), 44 DLBCL patients (55 %, 23 males) were considered as sarcopenic. With a median follow-up of 39 months, the 2y overall survival (OS) in the sarcopenic population was 46% as compared to 84% in the non-sarcopenic group (HR = 3.12; CI95%, 1.66-5.88; p=0.0004). The median LSAI was 76.3 cm2/m2 [10-167] in females and 47.4 cm2/m2[22-100] in males. The median LVSAI was 43.5 cm2/m2[3-141] in females and 50.4 cm2/m2[14-159] in males. Adipopenia, defined by a low LVAI and/or a low LSAI was also highly predictive of the outcome. The 2y OS of the low LVAI population was 48% as compared to 82% for the non-adipopenic group (HR = 2.20; CI95%, 1.19-4.05; p=0.01). The 2y OS in the low LSAI population was 48% as compared to 80% in the non-adipopenic group (HR = 2.28; CI95%, 1.23-4.21; p=0.008). A Three-point cachexia score (CS) including adipopenia, sarcopenia and hypo-albuminemia (defined by an albuminemia < 35 g/L) was build and delineates three distinct risk-groups (Figure 1). More importantly the CS remains predictive of the prognosis in a multivariate analysis including BMI (< or >= 25 kg/m2), age (< or >= 80y), IPI and gender (HR=2.5; CI95%= 1.14-5.39; p =0.02). LMSI was subsequently reassessed in thirty seven patients during the routine CT scan follow-up [mean = 10 months after pre-treatment CT scan (range 2.8-19.2)]. 15 (40%) patients displayed a 5% decrease of their LSMI, whereas 13 (35%) and 9 (25%) displayed no significant change or increase (>5%) of the LMSI respectively. Conclusion Our study demonstrates that sarcopenia and adipopenia estimated by CT-scan define cachexia more accurately than BMI or weight loss in elderly DLBCL patients. These factors can be integrated in a cachexia scoring tool which predicts the outcome independently of the BMI and of the IPI. CT scan follow-up indicates that cachexia is a reversible process that should be integrated as part of the therapeutic target in combination with lymphoma treatment. A prospective multicentric trial (registered as NCT01715961/Clinical.gov) is ongoing to validate these anthropometric and nutritional parameters and compare to geriatric assessment scales. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3787
Author(s):  
Ashok Narasimhan ◽  
Safi Shahda ◽  
Joshua K. Kays ◽  
Susan M. Perkins ◽  
Lijun Cheng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Weight Loss ◽  
Plasma Proteins ◽  
Cancer Cachexia ◽  
Ductal Adenocarcinoma ◽  
Cancer Stage ◽  
Protein Biomarkers ◽  
Skeletal Muscle Index ◽  
Novel Proteins ◽  
Upstream Regulator

Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.

Correlation Analysis Between Hematological Toxicity and Body Composition in Patients With Diffuse Large B Cell Lymphoma Treated With CHOP±R Regimen

2020 ◽  
Author(s):  
Wenhao Zhao ◽  
Xuelian Liu ◽  
Xiangliang Liu ◽  
Haimei Yang ◽  
Wei Ji ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Hematologic Toxicity ◽  
Skeletal Muscle Index ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract Purpose: The tolerance of patients withdiffuse large B cell lymphoma（DLBCL） receiving CHOP±R regimen was significantly different, and grade 3~4 hematologic toxicity after chemotherapy in some patients resulted in prolonged hospital stay, increased risk of infection, delayed treatment, and directly or indirectly affected short-term efficacy and long-term prognosis. Lean body mass（LBM）and L3 skeletal muscle index （L3SMI）obtained from abdominal CT of DLBCL patients were analyzed to determine whether they could be used as independent predictors of hematological toxicity of CHOP± R regimen in DLBCL patients.Methods: The patients with DLBCL who underwent CHOP±R regimen at the Cancer Center of the First Hospital of Jilin University from January 2015 to November 2018 were retrospectively analyzed. The abdominal CT of the patient was analyzed by sliceOmatic5.0 software. The third lumbar disc planar imaging was selected, and two consecutive images were taken to calculate LBM and L3SMI. Single factor and multivariate analysis were performed on the correlation of LBM, L3SMIand chemotherapy-related grade 3~4 hematologic toxicity. The ROC curve was drawn to investigate the predictive value of various human indicators on the hematologic toxicity of grade 3~4 related to chemotherapy.Results: The L3 skeletal muscle index is associated with the occurrence of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. Those with lower L3SMI are prone to grade 3~4 hematologic toxicity.LBM is associated with the occurrence of grade 3~4 hematologic toxicity (leukopenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. This with lower LBM is prone to grade 3~4 hematologic toxicity.The L3 skeletal muscle index can be used as an independent predictor of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP ± R regimen. The cut-off value can be defined as 39.91 cm2/m2.Conclusion: We can draw the following conclusions:The L3 skeletal muscle index is associated with the occurrence of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. Those with lower L3SMI are prone to grade 3~4 hematologic toxicity.LBM is associated with the occurrence of grade 3~4 hematologic toxicity (leukopenia) in patients with diffuse large B-cell lymphoma treated with CHOP±R regimen. This with lower LBM is prone to grade 3~4 hematologic toxicity.The L3 skeletal muscle index can be used as an independent predictor of grade 3~4 hematologic toxicity (leukocyte and neutropenia) in patients with diffuse large B-cell lymphoma treated with CHOP ± R regimen. The cut-off value can be defined as 39.91 cm2/m 2.

scholarly journals New genetic signatures associated with cancer cachexia as defined by low skeletal muscle index and weight loss

2016 ◽  
Vol 8 (1) ◽  
pp. 122-130 ◽  
Author(s):  
Neil Johns ◽  
Cynthia Stretch ◽  
Benjamin H.L. Tan ◽  
Tora S. Solheim ◽  
Sveinung Sørhaug ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Cancer Cachexia ◽  
Skeletal Muscle Index ◽  
Genetic Signatures

scholarly journals Body Composition as a Predictor of Toxicity and Prognosis in Patients with Diffuse Large B-Cell Lymphoma Receiving R-CHOP Immunochemotherapy

2021 ◽  
Vol 28 (2) ◽  
pp. 1325-1337
Author(s):  
Jiaxun Guo ◽  
Panpan Cai ◽  
Pengfei Li ◽  
Cong Cao ◽  
Jing Zhou ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Composition ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Adverse Outcomes ◽  
The Body ◽  
Skeletal Muscle Index ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background: Our study measured the body composition of Diffuse large B-cell lymphoma (DLBCL) patients receiving rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimen by computed tomographic (CT) and assessed their correlation with treatment-related toxicity and other adverse outcomes. Methods: We retrospectively analyzed 201 DLBCL patients who underwent pre-treatment abdominal CT examination. CT images were used to assess body composition metrics at the third lumbar vertebrae including fat tissues and muscle. Based on the skeletal muscle area (SMA) and density (SMD), skeletal muscle index (SMI), skeletal muscle gauge (SMG = SMI × SMD) and lean body mass (LBM) were calculated. Also analyzed were the toxicity, adverse events and survival. Results: We found that SMG, SMD, SMI and LBM were correlated with any grade 3–4 toxicity, dose reduction, hospitalization or termination of the treatment due to immunochemotherapy and worse survival. However, multivariate analysis demonstrated SMG [progression-free survival (PFS): hazard ratio (HR), 2.889; 95% CI, 1.401–5.959; p = 0.004; overall survival (OS): HR, 2.655; 95% CI, 1.218–5.787; p = 0.014] was the best predictor of poor prognosis. Conclusions: SMG, SMD, SMI and LBM were identified as predictors of adverse reactions and poor survival. SMG was an innovative and valuable indicator of immunochemotherapy toxicity and other adverse outcomes. Additionally, it can be used to individualize antineoplastic drug dosing.

scholarly journals O-B05 Does rapid or gradual weight loss following bariatric surgery affect lean body mass depreciation?

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Jonathan Sivakumar ◽  
Qianyu Chen ◽  
Matthew Read ◽  
Tom Sutherland ◽  
Salena Ward ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Body Composition ◽  
Lean Body Mass ◽  
Body Mass ◽  
Statistical Significance ◽  
Resting Energy Expenditure ◽  
Skeletal Muscle Index ◽  
The Difference

Abstract Background Controversy exists regarding the influence of the rate of weight loss on long-term body composition. The objective of this study was to compare body composition changes in patients with successful and unsuccessful weight loss 12 months after bariatric surgery. Methods A prospective analysis was completed on patients undergoing bariatric surgery at St Vincent’s Hospital Melbourne between 2017 and 2021. Body composition was measured with dual-energy X-ray absorptiometry immediately before surgery, and at 12 months post-operatively. Fat mass (FM), lean body mass (LBM) and skeletal muscle index (SMI) trajectories were analysed between patients, with either successful weight loss (SWL) or unsuccessful weight loss (USWL) stratified based on an excess weight loss (EWL) threshold of ≥ 50%. Results Thirty-seven patients were included in this series (SWL n = 25, USWL n = 12). Compared to those with USWL, SWL demonstrated a greater mean loss in BMI (12.3 vs 7.3 kg/m2; p &lt; 0.001) and weight (34.4 vs 20.3 kg; p &lt; 0.001). SWL demonstrated a significantly greater reduction in tissue fat% than USWL, with patients losing 7.3% more tissue fat on average. SWL was associated with an improved mean SMI% when compared with USWL (5.5 vs. 2.42%; p &lt; 0.0009). However, the difference in FM:LBM loss ratio between the two groups did not demonstrate statistical significance (7.07 vs 4.62, p = 0.2519). Conclusions This data suggests that SWL is associated with a more optimal body composition outcome than USWL, which is at least partly due to a relative skeletal muscle-sparing effect in this group. Further research is warranted in understanding the implications of these changes on resting energy expenditure and the risk of weight regain.

Cancer cachexia syndrome in the prediction of outcome in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs): Results from a single-institution, prospective, observational study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21644-e21644
Author(s):  
Dimitrios Mavroudis ◽  
Konstantinos Rounis ◽  
Dimitrios Makrakis ◽  
Alexandra Georgiou ◽  
Nikolaos Galanakis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Weight Loss ◽  
Observational Study ◽  
Prospective Observational Study ◽  
Cancer Cachexia ◽  
Lumbar Vertebra ◽  
Response Rates ◽  
Skeletal Muscle Index ◽  
Potential Biomarker ◽  
Cachexia Syndrome

e21644 Background: Cancer cachexia syndrome (CCS) is a multifactorial inflammatory syndrome affecting a large subset of patients (pts) with NSCLC which in preclinical models negatively impairs antitumor immunity. We conducted a prospective, observational study to investigate the effect of CCS and sarcopenia on the efficacy of ICIs in NSCLC. Methods: CCS was defined as weight loss of > 5% in the last 6 months or any degree of weight loss > 2% in combination with BMI < 20% or baseline skeletal muscle index at the level of the 3rd lumbar vertebra consistent with sarcopenia. Skeletal muscle index was calculated using slice-o-matic tomovision software in the abdominal CT scan before starting ICIs. Results: 83 pts were included in the analysis. Median follow up was 9.5 months. Median age was 66 years, 61.4% had non-squamous histology, 20.5% received ICIs as first and the remaining as second-line therapy. 20.5% of pts experienced partial response (PR), 31% had stable disease (SD) and 48.2% had disease progression (PD). Median progression-free survival (PFS) was 4.4 months and median overall survival (OS) was 10.33 months. 43.4% of the whole group were categorized as having CCS, whereas 63.3% of 30 pts evaluated using tomovision had sarcopenia. CCS negatively affected response rates (p = 0.003) but not response duration (p = 0.266). CCS was associated with reduced PFS (2.46 vs 5.77 months, p = 0.006) and OS (4.8 vs 14.53 months, p = 0.001). In the multivariate analysis, CCS independently predicted for shorter OS (HR = 2.01; CI: 1,14-3,54; p = 0.014). Sarcopenia was also associated with reduced OS (5.4 vs 17.9 months, p = 0.012). Analysis on the whole pt population will be presented at the conference. Conclusions: CCS is associated with lower response rates and independently predicts for shorter OS in pts with NSCLC treated with ICIs. Further research on CCS could better define its role as a potential biomarker and a research platform for maximizing immunotherapy efficacy.

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