Comprehensive analysis of radiographic, clinical, and inflammatory markers demonstrating changes in lean muscle correlate with outcome in patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC) who undergo taxane-based chemotherapy (CT).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 349-349
Author(s):  
Daniel H. Ahn ◽  
Chul Ahn ◽  
Veena Nagar ◽  
Anne M. Noonan ◽  
Matthew Farren ◽  
...  

349 Background: MPDAC is associated with a poor prognosis. The mechanisms of carcinogenesis are complex; involve multiple signaling pathways and inflammatory cytokines that may promote cachexia, a major cause of morbidity and mortality in mPDAC. The purpose of this study is to understand factors related to skeletal muscle changes, and its effect on outcomes in pts with mPDAC. Methods: Pt and clinical data were obtained from a recent prospective clinical trial in mPDAC where all pts received first-line taxane-based CT. We examined changes in modified Glasgow prognostic score, neutrophil lymphocyte ratio, a 32-cytokine panel, weight, and skeletal muscle area (SMA), determined by validated methodology with computed tomography, at baseline and cycle 3. We defined > 6cm2 in SMA, correlating to 1kg of skeletal muscle gain (SMG), as significant. Univariate and multivariate Cox regression models were used to determine the association between laboratory, radiographic and clinical findings with progression free survival (PFS) and overall survival (OS). Results: 66 evaluable pts were included. Independent of clinical response, an OS advantage was seen in pts who experienced significant SMG (p = 0.023) and in patients with nominal SMG (p = 0.012). A numerical benefit in PFS was observed with SMG. Decreases in IFN-a (p = 0.024), IFN-g (p = 0.001) and IL-6 (p = 0.042) were inversely associated with SMG. A comprehensive analysis incorporating all relevant laboratory, radiographic and clinical assessments demonstrated a 4.62-month OS advantage in pts with favorable characteristics vs. those with poor prognostic factors (11.47 versus 6.84 mos., p = 0.0029). Conclusions: SMG, or the reversal of cachexia confers an OS advantage in pts with mPDAC treated with taxane-based CT regardless of clinical response. A comprehensive assessment of muscle change is a precise measurement that can identify pts at greatest risk for muscle loss, which could predict for trmt response and pt outcomes. This merits further investigation as a tool and in trials directed at reversing the process of cachexia.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 188-188
Author(s):  
NOELIA TARAZONA ◽  
Elizabeth Catherine Smyth ◽  
Clare Peckitt ◽  
Ian Chau ◽  
David J. Watkins ◽  
...  

188 Background: Paclitaxel is a standard global salvage therapy for pts with advanced refractory OGA. Western pts may differ from Asian pts with respect to chemotherapy metabolism and cancer behaviour, and the benefits associated with paclitaxel in this setting have not been assessed outside of Asia. We examined the efficacy and toxicity associated with salvage paclitaxel for advanced OGA at RM over a 3 year period. Methods: This was a retrospective observational study. We identified all pts with OGA treated with salvage weekly paclitaxel from 01/06/2011 to 21/02/2014 from the electronic pt record at RM. The following data was collected: demographics, metastatic sites, resection status, response/duration of response to prior chemotherapy, ECOG PS, haemoglobin, albumin, alkaline phosphatase (ALP), neutrophil/lymphocyte ratio, CEA, CA19.9, RM prognostic score, CT response and date of progression, death or last follow up. Toxicity was collected as per NCI Common Toxicity Criteria (v4.0). Overall and progression free survival (OS/PFS) were estimated using the Kaplan-Meier method. Multivariate Cox regression analysis examined the association between clinical and laboratory variables with survival. Results: 57 pts were identified. Pts were 74% male; median age 64y; 66% PS 0-1; 91% 2nd line. Median number cycles 3 (range 1-8). Median follow up 13.6m. Response rate was 18.4% in evaluable pts. OS and PFS were 5.8m (95% CI: 4.8 – 6.8m) and 2.6m (95% CI: 1.9 – 3.2m). 2y and 3y survival from start of 1st line treatment were 26% and 13%. In multivariate analyses PS ≥2 [HR 2.28, p = 0.018], and ALP ≥100 U/L, [HR=2.01, p= 0.033] were independent negative prognostic factors for OS. ≥ Grade 3 nausea, diarrhea and neuropathy were uncommon (<2% each), rate of ≥ grade 3 fatigue was 11%. Grade 3-4 neutropenia, leucopenia and thrombocytopenia occurred in 12%, 11% and 2% pts. Conclusions: Advanced OGA pts treated at RM with salvage paclitaxel have an OS equivalent to pts in clinical trials with less hematological toxicity than seen in Asian patients. This may be due to regional pharmacogenetic profiles. As a significant proportion of pts now survive 2-3y with limited toxicity, therapeutic nihilism is unwarranted.


2020 ◽  
Author(s):  
Minoru Oshima ◽  
Keiichi Okano ◽  
Hironobu Suto ◽  
Yasuhisa Ando ◽  
Hideki Kamada ◽  
...  

Abstract BackgroundInflammatory nutritional factors, such as the neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), modified GPS (mGPS), and C-reactive protein/albumin (CRP/Alb) ratio, have prognostic values in many types of cancer. In this study, the prognostic values of inflammatory nutritional scores were evaluated in the patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemoradiotherapy (NACRT).MethodsA total of 49 patients who underwent pancreatectomy after NACRT from September 2009 to May 2016 were enrolled. The NACRT consisted of hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) delivered 5 days/week for 2 weeks before pancreatectomy. Inflammatory nutritional scores were determined before and after NACRT in this series. ResultsThe median NLR increased after NACRT (from 2.067 to 3.302), with statistical difference (p<0.001). In multivariate Cox regression analysis, high pre-NACRT mGPS (2 or 1; p=0.0478) and significant increase in CRP/Alb ratio after NACRT (≧0.077; p=0.0036) were associated with shorter overall survival. All patients were divided into two groups according to the ΔCRP/Alb ratio after NACRT: the group with high ΔCRP/Alb ratio (≧0.077) and the group with low ΔCRP/Alb ratio (<0.077). The group with high ΔCRP/Alb ratio after NACRT (n=13) not only had higher post-NACRT CRP levels (p<0.001) but also had lower post-NACRT Alb levels (p=0.002). Patients in the group with high ΔCRP/Alb ratio lost more body weight during NACRT (p=0.03).ConclusionIn addition to pre-NACRT mGPS, ΔCRP/Alb after NACRT could provide prognostic value in the patients with PDAC treated by NACRT.


2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 133-133
Author(s):  
Justin Lebenthal ◽  
Junting Zheng ◽  
Paul A. Glare ◽  
Eileen Mary O'Reilly ◽  
Andrew S. Epstein

133 Background: The MPS, a composite of the Neutrophil-Lymphocyte Ratio (NLR) and albumin, is an alternative prognostic tool to the Glasgow Prognostic Score (C-reactive protein and albumin). A retrospective analysis (jco.2016.34.26_suppl.36) of patients with PDAC suggested that the MPS predicts survival. This did not control for clinically relevant factors such as performance status (PS), metastatic sites, or cancer therapies. More discriminating prognostic tools are needed. Methods: A retrospective chart review identified patients at MSK with pathology-confirmed stage IV PDAC diagnosed from 2011 to 2014. An MPS scale of 0-2 was utilized: MPS = 0 for albumin ≥ 4 g/dl and NLR ≤ 4 g/dl, MPS = 1 for either albumin < 4 g/dl or NLR > 4 g/dl, and MPS = 2 for albumin < 4 g/dl and NLR > 4 g/dl. PS (ECOG or KPS) was abstracted from outpatient visit notes. Metastatic sites at initial MSK visit were assessed from cross-sectional imaging. Cancer therapies were characterized as 5FU-based, gemcitabine-based, experimental, and radiation to primary or metastatic sites. Thromboembolic (TE) diagnoses were also noted. Time-dependent Cox regression analyses identified clinical variables associated with overall survival (OS). Univariately significant variables were utilized in a multivariable regression model to interrogate their effect on the association of MPS and OS. Results: Univariate analyses in n = 833 stage IV PDAC patients identified higher MPS score, higher CA19-9 at diagnosis (n = 737), chemo, radiation, liver metastases, TE, hospital admission, and lower PS (n = 727) as associated with worse OS (p < 0.05). A multivariate model (n = 727) controlling for radiation, liver metastases, TE, admission, and PS demonstrated that higher MPS scores at diagnosis remained associated with worse OS (p < 0.001). Median OS in patients with MPS 0, 1, and 2 were 14.5 (95%CI: 12.9-17), 10.2 (9-11.6), and 6.2 (5.1-8.1) months, respectively. Conclusions: The MPS is an objective prognostic tool associated with OS in advanced PDAC independent of PS, disease characteristics, and types of cancer therapies. Future directions include prospective evaluation and application of the MPS to other PDAC disease settings and other malignancies.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3594
Author(s):  
Simone Conci ◽  
Tommaso Campagnaro ◽  
Elisa Danese ◽  
Ezio Lombardo ◽  
Giulia Isa ◽  
...  

The relationship between immune-nutritional status and tumor growth; biological aggressiveness and survival, is still debated. Therefore, this study aimed to evaluate the prognostic performance of different inflammatory and immune-nutritional markers in patients who underwent surgery for biliary tract cancer (BTC). The prognostic role of the following inflammatory and immune-nutritional markers were investigated: Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Neutrophil to Lymphocyte ratio (NLR), Platelet to Lymphocyte ratio (PLR), Lymphocyte to Monocyte ratio (LMR), Prognostic Nutritional Index (PNI). A total of 282 patients undergoing surgery for BTC were included. According to Cox regression and ROC curves analysis for survival, LMR had the best prognostic performances, with hazard ratio (HR) of 1.656 (p = 0.005) and AUC of 0.652. Multivariable survival analysis identified the following independent prognostic factors: type of BTC (p = 0.002), T stage (p = 0.014), N stage (p < 0.001), histological grading (p = 0.045), and LMR (p = 0.025). Conversely, PNI was related to higher risk of severe morbidity (p < 0.001) and postoperative mortality (p = 0.005). In conclusion, LMR appears an independent prognostic factor of long-term survival, whilst PNI seems associated with worse short-term outcomes.


Author(s):  
Anna Cho ◽  
Helena Untersteiner ◽  
Dorian Hirschmann ◽  
Fabian Fitschek ◽  
Christian Dorfer ◽  
...  

Abstract Introduction The predictive value of the pre-radiosurgery Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Lymphocyte-to-Monocyte Ratio (LMR) and the modified Glasgow Prognostic Score (mGPS) was assessed for the first time in a homogenous group of NSCLC brain metastaes (BM) patients. Methods We retrospectively evaluated 185 NSCLC-BM patients, who were treated with Gamma Knife Radiosurgery (GKRS). Patients with immunotherapy or targeted therapy were excluded. Routine laboratory parameters were reviewed within 14 days before GKRS1. Results Median survival after GKRS1 was significantly longer in patients with NLR < 5 (p < 0.001), PLR < 180 (p = 0.003) and LMR ≥ 4 (p = 0.023). The Cox regression model for the continuous metric values revealed that each increase in the NLR of 1 equaled an increase of 4.3% in risk of death (HR: 1.043; 95%CI = 1.020–1.067, p < 0.001); each increase in the PLR of 10 caused an increase of 1.3% in risk of death (HR: 1.013; 95%CI = 1.004–1.021; p = 0.003) and each increase in the LMR of 1 equaled a decrease of 20.5% in risk of death (HR: 0.795; 95%CI = 0.697–0.907; p = 0.001). Moreover, the mGPS group was a highly significant predictor for survival after GKRS1 (p < 0.001) with a HR of 2.501 (95%CI = 1.582–3.954; p < 0.001). NLR, PLR, LMR values and mGPS groups were validated as independent prognostic factors for risk of death after adjusting for sex, KPS, age and presence of extracranial metastases. Conclusion NLR, PLR, LMR and mGPS represent effective and simple tools to predict survival in NSCLC patients prior to radiosurgery for brain metastases.


2020 ◽  
Author(s):  
Donogh Maguire ◽  
Marylynne Woods ◽  
Conor Richards ◽  
Ross Dolan ◽  
Jesse Wilson Veitch ◽  
...  

Abstract BackgroundSevere COVID-19 infection results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associated with the development of multiple organ failure. MethodsElectronic patient records for patients who were admitted to an urban teaching hospital during the initial 7-week period of the COVID-19 pandemic in Glasgow, U.K. (17th March 2020 - 1st May 2020) were examined for routine clinical, laboratory and clinical outcome data. Age, sex, BMI and documented evidence of COVID-19 infection at time of discharge or death certification were considered minimal criteria for inclusion.ResultsOf the 224 patients who fulfilled the criteria for inclusion, 52 (23%) had died at 30-days following admission. COVID-19 related respiratory failure (75%) and multiorgan failure (12%) were the commonest causes of death recorded. Age>70 years (p<0.001), past medical history of cognitive impairment (p<0.001), previous delirium (p<0.001), clinical frailty score>3 (p<0.001), hypertension (p<0.05), heart failure (p<0.01), national early warning score (NEWS) >4 (p<0.01), positive CXR (p<0.01), and subsequent positive COVID-19 swab (p<0.001) were associated with 30-day mortality. CRP>80 mg/L (p<0.05), albumin <35g/L (p<0.05), peri-operative Glasgow Prognostic Score (poGPS) (p<0.05), lymphocytes <1.5 109/l (p<0.05), neutrophil lymphocyte ratio (p<0.001), haematocrit (<0.40 L/L (male) / <0.37 L/L (female)) (p<0.01), urea>7.5 mmol/L (p<0.001), creatinine >130 mmol/L (p<0.05) and elevated urea: albumin ratio (<0.001) were also associated with 30-day mortality.On analysis, age >70 years (O.R. 3.9, 95% C.I. 1.4 – 8.2, p<0.001), past medical history of heart failure (O.R. 3.3, 95% C.I. 1.2 – 19.3, p<0.05), NEWS >4 (O.R. 2.4, 95% C.I. 1.1 – 4.4, p<0.05), positive initial CXR (O.R. 0.4, 95% C.I. 0.2-0.9, p<0.05) and poGPS (O.R. 2.3, 95% C.I. 1.1 – 4.4, p<0.05) remained independently associated with 30-day mortality. Among those patients who tested PCR COVID-19 positive (n=122), age >70 years (O.R. 4.7, 95% C.I. 2.0 - 11.3, p<0.001), past medical history of heart failure (O.R. 4.4, 95% C.I. 1.2 – 20.5, p<0.05) and poGPS (O.R. 2.4, 95% C.I. 1.1- 5.1, p<0.05) remained independently associated with 30-days mortality.ConclusionAge > 70 years and severe systemic inflammation as measured by the peri-operative Glasgow Prognostic Score are independently associated with 30-day mortality among patients admitted to hospital with COVID-19 infection.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Minoru Oshima ◽  
Keiichi Okano ◽  
Hironobu Suto ◽  
Yasuhisa Ando ◽  
Hideki Kamada ◽  
...  

Abstract Background Inflammatory nutritional factors, such as the neutrophil/lymphocyte ratio (NLR), Glasgow Prognostic Score (GPS), modified GPS (mGPS), and C-reactive protein/albumin (CRP/Alb) ratio, have prognostic values in many types of cancer. In this study, the prognostic values of inflammatory nutritional scores were evaluated in the patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant chemoradiotherapy (NACRT). Methods A total of 49 patients who underwent pancreatectomy after NACRT from September 2009 to May 2016 were enrolled. The NACRT consisted of hypofractionated external-beam radiotherapy (30 Gy in 10 fractions) with concurrent S-1 (60 mg/m2) delivered 5 days/week for 2 weeks before pancreatectomy. Inflammatory nutritional scores were determined before and after NACRT in this series. Results The median NLR increased after NACRT (from 2.067 to 3.302), with statistical difference (p < 0.001). In multivariate analysis, high pre-NACRT mGPS (2 or 1; p = 0.0478) and significant increase in CRP/Alb ratio after NACRT (≧ 0.077; p = 0.0036) were associated with shorter overall survival. All patients were divided into two groups according to the ΔCRP/Alb ratio after NACRT: the group with high ΔCRP/Alb ratio (≧ 0.077) and the group with low ΔCRP/Alb ratio (< 0.077). The group with high ΔCRP/Alb ratio after NACRT (n = 13) not only had higher post-NACRT CRP levels (p < 0.001) but also had lower post-NACRT Alb levels (p = 0.002). Patients in the group with high ΔCRP/Alb ratio lost more body weight during NACRT (p = 0.03). Conclusion In addition to pre-NACRT mGPS, ΔCRP/Alb after NACRT could provide prognostic value in the patients with PDAC treated by NACRT.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Donogh Maguire ◽  
Marylynne Woods ◽  
Conor Richards ◽  
Ross Dolan ◽  
Jesse Wilson Veitch ◽  
...  

Abstract Background Severe COVID-19 infection results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associated with the development of multiple organ failure. Methods Electronic patient records for patients who were admitted to an urban teaching hospital during the initial 7-week period of the COVID-19 pandemic in Glasgow, U.K. (17th March 2020—1st May 2020) were examined for routine clinical, laboratory and clinical outcome data. Age, sex, BMI and documented evidence of COVID-19 infection at time of discharge or death certification were considered minimal criteria for inclusion. Results Of the 224 patients who fulfilled the criteria for inclusion, 52 (23%) had died at 30-days following admission. COVID-19 related respiratory failure (75%) and multiorgan failure (12%) were the commonest causes of death recorded. Age ≥ 70 years (p < 0.001), past medical history of cognitive impairment (p ≤ 0.001), previous delirium (p < 0.001), clinical frailty score > 3 (p < 0.001), hypertension (p < 0.05), heart failure (p < 0.01), national early warning score (NEWS) > 4 (p < 0.01), positive CXR (p < 0.01), and subsequent positive COVID-19 swab (p ≤ 0.001) were associated with 30-day mortality. CRP > 80 mg/L (p < 0.05), albumin < 35 g/L (p < 0.05), peri-operative Glasgow Prognostic Score (poGPS) (p < 0.05), lymphocytes < 1.5 109/l (p < 0.05), neutrophil lymphocyte ratio (p ≤ 0.001), haematocrit (< 0.40 L/L (male)/ < 0.37 L/L (female)) (p ≤ 0.01), urea > 7.5 mmol/L (p < 0.001), creatinine > 130 mmol/L (p < 0.05) and elevated urea: albumin ratio (< 0.001) were also associated with 30-day mortality. On multivariate analysis, age ≥ 70 years (O.R. 3.9, 95% C.I. 1.4–8.2, p < 0.001), past medical history of heart failure (O.R. 3.3, 95% C.I. 1.2–19.3, p < 0.05), NEWS > 4 (O.R. 2.4, 95% C.I. 1.1–4.4, p < 0.05), positive initial CXR (O.R. 0.4, 95% C.I. 0.2–0.9, p < 0.05) and poGPS (O.R. 2.3, 95% C.I. 1.1–4.4, p < 0.05) remained independently associated with 30-day mortality. Among those patients who tested PCR COVID-19 positive (n = 122), age ≥ 70 years (O.R. 4.7, 95% C.I. 2.0—11.3, p < 0.001), past medical history of heart failure (O.R. 4.4, 95% C.I. 1.2–20.5, p < 0.05) and poGPS (O.R. 2.4, 95% C.I. 1.1–5.1, p < 0.05) remained independently associated with 30-days mortality. Conclusion Age ≥ 70 years and severe systemic inflammation as measured by the peri-operative Glasgow Prognostic Score are independently associated with 30-day mortality among patients admitted to hospital with COVID-19 infection.


2016 ◽  
Vol 31 (4) ◽  
pp. 395-401 ◽  
Author(s):  
Zhu-Lin Liu ◽  
Ting-Ting Zeng ◽  
Xiao-Juan Zhou ◽  
Ya-Nv Ren ◽  
Lei Zhang ◽  
...  

Background Lung cancer ranks first both in morbidity and mortality in malignancies, but prognostic biological markers are lacking. The neutrophil-lymphocyte ratio (NLR) was proposed as a convenient biological marker. This study aimed to explore the prognostic value of NLR in advanced non-small cell lung cancer (NSCLC). Methods This retrospective study screened patients admitted from October 2007 to October 2014. Patients had histopathologically confirmed, treatment-naïve, metastatic NSCLC, and were prescribed platinum doublet chemotherapy. NLR and demographic data were collected, together with the outcome of chemotherapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression model. Results A total of 325 patients were enrolled. The cutoff value for NLR (3.19) was determined by receiver operator characteristic analysis. Patients were dichotomized into high (≥3.19) and low (<3.19) NLR groups. Both groups had similar demographic features. However, the low-NLR group had longer PFS (6.1 months) and OS (22.3 months) than the high-NLR group (5.1 months, p = 0.002; 13.1 months, p<0.001, respectively). Multivariate analysis confirmed that NLR was inversely related to the prognosis of these patients (HR = 1.684, 95%: 1.297-2.185, p<0.001). Conclusions This study argues that NLR is a convenient prognostic biological marker for advanced NSCLC patients treated with first-line chemotherapy and warrants further validation.


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