Clinical Prognostic Scores Research Articles

The diagnostic and prognostic significance of liver histology in alcoholic hepatitis.

Liver biopsy may be of diagnostic and prognostic value but its role in alcoholic hepatitis (AH) has been controversial. To assess the utility of liver biopsy in the assessment of clinically severe AH METHODS: The histological features of alcoholic steatohepatitis (ASH) were recorded and scored in patients enrolled in the Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial who underwent liver biopsy. These features were then assessed relative to outcome and established clinical prognostic scores. The STOPAH trial recruited 1068 patients; biopsies were obtained in 182 (17%). One hundred and sixty-one biopsies were adequate for histological assessment and 140 (87%) were diagnostic for ASH. Only three biopsies (2%) did not have histological features of alcohol-related liver injury. In biopsies performed prior to randomisation, ASH was identified in 92.5% of patients meeting clinical trial definitions of severe AH. In biopsies with ASH, taken before or within 48hours of randomisation, survival differences between Alcoholic Hepatitis Histological Score (AHHS) groups were not significant: comparison of mild / moderate (91%: 21 of 23 patients) with severe (78%: 29 of 37 patients) groups: P=0.18. The AHHS was not superior to clinical scores of prognosis: area under the curve for 28-day mortality was 0.728, compared with 0.799 for the Glasgow alcoholic hepatitis score and 0.728 for the MELD score. Liver histology taken before treatment rarely changes the diagnosis in patients meeting strict criteria for a clinical diagnosis of AH. The AHHS is similar to clinical scores in determining prognosis. Clinical trial registration EudraCT reference number: 2009-013897-42. ISRCTN reference number: 88782125. MREC number: 09/MRE09/59. 9143.

Quantification of Cystic Fibrosis Lung Disease with Radiomics-based CT Scores.

To develop radiomics-based CT scores for assessing lung disease severity and exacerbation risk in adult patients with cystic fibrosis (CF). This two-center retrospective observational study was approved by an institutional ethics committee, and the need for patient consent was waived. A total of 215 outpatients with CF referred for unenhanced follow-up chest CT were evaluated in two different centers between January 2013 and December 2016. After lung segmentation, chest CT scans from center 1 (training cohort, 162 patients [median age, 29 years; interquartile range {IQR}, 24-36 years; 84 men]) were used to build CT scores from 38 extracted CT features, using five different machine learning techniques trained to predict a clinical prognostic score, the Nkam score. The correlations between the developed CT scores, two different clinical prognostic scores (Liou and CF-ABLE), forced expiratory volume in 1 second (FEV1), and risk of respiratory exacerbations were evaluated in the test cohort (center 2, 53 patients [median age, 27 years; IQR, 22-35 years; 34 men]) using the Spearman rank coefficient. In the test cohort, all radiomics-based CT scores showed moderate to strong correlation with the Nkam score (R = 0.57 to 0.63, P < .001) and Liou scores (R = -0.55 to -0.65, P < .001), whereas the correlation with CF-ABLE score was weaker (R = 0.28 to 0.38, P = .005 to .048). The developed CT scores showed strong correlation with predicted FEV1 (R = -0.62 to -0.66, P < .001) and weak to moderate correlation with the number of pulmonary exacerbations to occur in the 12 months after the CT examination (R = 0.38 to 0.55, P < .001 to P = .006). Radiomics can be used to build automated CT scores that correlate to clinical severity and exacerbation risk in adult patients with CF.Supplemental material is available for this article.See also the commentary by Elicker and Sohn in this issue.© RSNA, 2020.

Evaluation of the Different Stratification Models for POD24 Prediction in Patients with Follicular Lymphoma

Evaluation of the Different Stratification Models for POD24 Prediction in Patients with Follicular Lymphoma

COVID-19 Prognostic Score Utilizing Hematological and Inflammatory Markers to Determine Outcomes of Hospitalized Patients

IntroductionCOVID-19 is an ongoing pandemic that has impacted millions of individuals throughout the world. The spectrum of clinical features of COVID-19 can vary from asymptomatic infection to severe multiorgan failure leading to death. There is no single biomarker available that can predict the trajectory of the infected patient. Few clinical reports suggest a correlation between the severity of COVID-19 and elevation of certain hematological and inflammatory markers. We used a novel COVID-19 Prognostic Score (CPS) which included lymphocyte count, elevated lactate dehydrogenase (LDH), C-reactive protein (CRP) and ferritin levels to predict the outcomes of COVID-19 patients.MethodsWe performed a retrospective chart review of COVID-19 patients admitted to New York Presbyterian Brooklyn Methodist Hospital between March and April of 2020. Clinical data was extracted manually from electronic medical records. Patients were divided into 2 cohorts. The first cohort included a combination of low lymphocyte count, elevated LDH, CRP and ferritin. The second cohort included normal lymphocyte count, low LDH, CRP and ferritin. Low lymphocyte count was defined as < 20% of white blood cell count (WBC), high LDH as ≥ 300 U/L, high CRP as ≥50mg/L and high ferritin as ≥600 ng/mL. Statistical analysis was performed by computing odds ratio using a p-value of < 0.05 as statistically significant.ResultsWe analyzed 683 hospitalized patients who were diagnosed with COVID-19 confirmed via viral PCR resting. The median age was 66.5 years, males were 52.2% and blacks were 47.2%. 16.3% had coronary artery disease (CAD), 38.6% had Diabetes Mellitus (DM), 63.1% had hypertension and 21.6% had pulmonary disease. 181 patients (26.5%) were intubated and transferred to ICU. The median LDH was 438 U/L, the median CRP was 107 mg/L and the median ferritin was 687 ng/mL. 4.6% of patients developed a thromboembolic event. The overall inpatient mortality rate was 32.1%. There were 178 patients in the CPS-High cohort while there were 41 patients who qualified for the CPS-Low cohort. The median age of CPS-High was 65 years and the median age of CPS-Low was 58 years. The percentage of CAD, DM, hypertension, pulmonary disease in CPS-High and CPS-Low were 11.8%, 39.3%, 57.9%, 10.7% and 19.5%, 17.1%, 43.9%, 12.2% respectively. In the CPS-High cohort the overall inpatient mortality was 42% while the inpatient mortality rate for CPS-Low was 7.3%. In univariate analysis, patients who had CPS low had significantly reduced inpatient mortality (Odds ratio 0.108, 95% CI 0.03-0.36, p-value = 0.0003).DiscussionOur study suggests that a combination of hematological characteristics and inflammatory markers can be used to assess the severity of illness with COVID-19. This study shows that there is a likelihood of 6-times higher mortality with COVID-19 if all the clinical characteristics are abnormal including lymphocyte count, LDH, CRP, and ferritin. This simple clinical prognostic score can be used at the time of hospital admission to efficiently triage patients, which may likely improve the outcomes of these patients. This prognostic tool needs to be validated in a larger dataset or prospective clinical study.DisclosuresNo relevant conflicts of interest to declare.

Prognostic significance of computed tomography-assessed right ventricular enlargement in low-risk patients with pulmonary embolism: Systematic review and meta-analysis

BackgroundFor patients with acute low-risk pulmonary embolism (PE), determined by a validated clinical prognostic score, the additive prognostic significance of computed tomography (CT)-assessed right ventricular (RV) enlargement is uncertain. MethodsWe performed a systematic review and meta-analysis of studies that enrolled patients with acute low-risk PE to assess the prognostic value of concomitant CT-assessed RV enlargement for 30-day all-cause mortality and PE-related death. We conducted unrestricted searches of PubMed and Embase through December 2019. We used a random-effects model to pool study results; Begg rank correlation method to evaluate for publication bias; and I2 testing to assess for heterogeneity. ResultsOf the 7 cohorts with 2197 participants who had low-risk PE and provided results on the primary outcome, 743 (34%; 95% confidence interval [CI], 32–36%) patients had concomitant RV enlargement. Six of 743 (0.8%; 95% CI, 0.3–1.8%) patients with concomitant RV enlargement died 30-days after the diagnosis of PE compared with 3 of 1454 (0.2%, 95% CI, 0–0.6%) without RV enlargement. CT-assessed RV enlargement did not have a significant association with 30-day all-cause mortality (odds ratio [OR], 2.6; 95% CI, 0.7–9.4; I2 = 0%; P = 0.15) or PE-related mortality (OR, 2.8; 95% CI, 0.7–12.1; I2 = 0%; P = 0.16). ConclusionsCT-assessed RV enlargement occurs in a third of PE patients identified as low-risk by clinical scores. Mortality rate in these patients is low, and CT-assessed RV enlargement was not associated with a significantly increased risk of death within 30 days of PE diagnosis.

The Evaluation of Prognostic Scores in Spontaneous Intracerebral Hemorrhage in an Asian Population: A Retrospective Study

ObjectiveClinical grading scales used for prognostication in spontaneous intracerebral hemorrhage facilitate informed-decision making for resource-intensive interventions. Numerous clinical prognostic scores are available for spontaneous intracerebral hemorrhage. However, these have not been validated well in Asian patients, and the most appropriate scoring system remains debatable. We evaluated the utility of clinical scores in prognosticating 30-day mortality and 90-day functional outcome in patients with spontaneous intracerebral hemorrhage. Materials and MethodsWe conducted a retrospective review of all patients with spontaneous intracerebral hemorrhage admitted to our tertiary center from December 2014 to May 2016. Data on clinical presentation, imaging, and outcomes were extracted from electronic medical records using a standardized form. The data were analyzed for predictors of outcomes. Performance of prognostic scales was compared using receiver-operator characteristic statistics. ResultsA total of 297 patients were included in the study. Mean age was 60.1 (SD 15.2) years and 190 (64.0%) were male. Thirty-two (10.8%) cases died within 30 days and 177 (62.8%) cases had poor functional outcome (modified Rankin scale of 3 or more) at 90 days. Dialysis dependency (OR=33.54, 95%CI=4.21–325.26, p=0.002), Glasgow coma scale (OR=0.76, 95%CI=0.64–0.88, p=0.001), hematoma volume (OR=1.02, 95%CI=1.00–1.04, p=0.027), and surgical evacuation (OR=0.15, 95%CI=0.02–0.66, p=0.024) were independent predictors for 30-day mortality. The original ICH score (0.862) and the ICH-Grading Scale (0.781) had the highest c-statistic for 30-day mortality and 90-day poor functional outcome respectively. ConclusionsCurrent prognostic scores performed acceptable-to-good in our patient cohort. Future studies may be useful to investigate the utility of these scores in clinical decision-making.

Is age an additional factor in the treatment of elderly patients with glioblastoma? A new stratification model: an Italian Multicenter Study.

Approximately half of glioblastoma (GBM) cases develop in geriatric patients, and this trend is destined to increase with the aging of the population. The optimal strategy for management of GBM in elderly patients remains controversial. The aim of this study was to assess the role of surgery in the elderly (≥ 65 years old) based on clinical, molecular, and imaging data routinely available in neurosurgical departments and to assess a prognostic survival score that could be helpful in stratifying the prognosis for elderly GBM patients. Clinical, radiological, surgical, and molecular data were retrospectively analyzed in 322 patients with GBM from 9 neurosurgical centers. Univariate and multivariate analyses were performed to identify predictors of survival. A random forest approach (classification and regression tree [CART] analysis) was utilized to create the prognostic survival score. Survival analysis showed that overall survival (OS) was influenced by age as a continuous variable (p = 0.018), MGMT (p = 0.012), extent of resection (EOR; p = 0.002), and preoperative tumor growth pattern (evaluated with the preoperative T1/T2 MRI index; p = 0.002). CART analysis was used to create the prognostic survival score, forming six different survival groups on the basis of tumor volumetric, surgical, and molecular features. Terminal nodes with similar hazard ratios were grouped together to form a final diagram composed of five classes with different OSs (p < 0.0001). EOR was the most robust influencing factor in the algorithm hierarchy, while age appeared at the third node of the CART algorithm. The ability of the prognostic survival score to predict death was determined by a Harrell's c-index of 0.75 (95% CI 0.76-0.81). The CART algorithm provided a promising, thorough, and new clinical prognostic survival score for elderly surgical patients with GBM. The prognostic survival score can be useful to stratify survival risk in elderly GBM patients with different surgical, radiological, and molecular profiles, thus assisting physicians in daily clinical management. The preliminary model, however, requires validation with future prospective investigations. Practical recommendations for clinicians/surgeons would strengthen the quality of the study; e.g., surgery can be considered as a first therapeutic option in the workflow of elderly patients with GBM, especially when the preoperative estimated EOR is greater than 80%.

Treatment approaches in relapsed or refractory peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare and aggressive non-Hodgkin’s lymphomas. Clinical staging, prognostic scoring, and initial treatment strategies have historically been based on paradigms developed in B-cell lymphomas. Despite primary treatment protocols that are typically anthracycline-based and frequently involve consolidative autologous stem cell transplantation in first remission, many patients develop disease progression. There remains a high unmet medical need for improved treatment strategies in the relapsed or refractory setting. Salvage chemotherapy and stem cell transplantation in those who are suitable has traditionally been the accepted approach, but this remains a minority of the total patient population. As increasing knowledge is gleaned regarding the biological heterogeneity within the various PTCL subtypes, newer targeted agents have been developed, studied, and approved in this small, heterogeneous population of relapsed or refractory disease. Given its success and tolerability in this pretreated population, brentuximab vedotin, an anti-CD30 antibody drug conjugate, was brought earlier in the disease course and is a model for advances in the targeted treatment of PTCL. As others undergo further development in the relapsed setting and successes are brought earlier in the disease course, the outcome for PTCL patients is likely to improve. However, innovative clinical trial designs are crucial for the assessment of targeted agents in this highly heterogeneous population. This review explores the current treatment environment for patients with relapsed and refractory PTCL, including newer strategies such as targeted agents and immunotherapy.

PROGNOSTIC VALUE OF VARIOUS BIOMARKERS FOR SEPSIS AND MULTIPLE ORGAN DYSFUNCTION SYNDROME IN ABDOMINAL SURGERY PATIENTS

Objective: To establish the prognostic value, sensitivity and specificity of various clinical and laboratory parameters and prognostic scores for sepsis and multiple organ dysfunction syndrome (MODS) in patients after abdominal surgery.Material and methods: A prospective cohort study was performed in 431 abdominal surgical patients in whom a number of clinical and laboratory parameters was analyzed during the first three post-operative days. The patients were divided in two groups: Group 1 (n = 255) of patients without signs of MODS and Group 1 (n = 176) of patients with MODS.Results: Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation III (APACHE III) scores showed the greatest prognostic value for MODS in the first three post-operative days (area under the curve [AUC] 0.825-0.899 and AUC 0.690-0.768, respectively). We suggest in abdominal surgery patients on the 1-st day after operations using as screening criteria MODS creatinine (AUC 0.722) and cholesterol (AUC 0.682) levels, on the 2-nd day – albumin (AUC 0.752), cholesterol (AUC 0.671) and creatinine (AUC 0.631) levels, on the 3-rd day – C-reactive protein (AUC 0.772), albumin (AUC 0.690) and cholesterol (AUC 0.688) levels. But creatinine is known as a marker of kidney injury, so its assessment should be carried out in conjunction with other screening predictors.Conclusion: SOFA offers several advantages over APACHE III for predicting MODS. For the purpose of MODS screening, assay of creatinine, albumin, cholesterol and C-reactive protein levels is required in patients admitted to the intensive care unit after abdominal surgery.

P1622GROWTH DIFFERENTIATION FACTOR 15: A BIOMARKER WITH HIGH CLINICAL POTENTIAL IN THE EVALUATION OF KIDNEY TRANSPLANT CANDIDATES

Abstract Background and Aims Kidney transplantation results a significant improvement in patient survival. Nevertheless, mortality the first years after transplant remains relatively high, being mostly related to cardiovascular (CV) events. The selection of patients for kidney transplantation includes a general assessment focused on CV status. In spite of that, due to the complexity and heterogeneity of mechanisms leading to vascular disease in this population (not exclusively related to traditional CV risk factors and pathogenesis), this evaluation remains insufficient and not particularly effective. During the last years different strategies have been studied to stratify potential receptors better and optimize organ allocation, including the development of clinical prognostic scores and novel biomarkers. Growth differentiation factor 15 (GDF-15) is a stress-responsive member of the TGF-β family. Although its mechanism of action is not completely understood, it acts as a cytokine with effects in regulation of inflammation, metabolism and senescence. In the recent years, interest has arisen regarding its use as a biomarker for diagnosis, prognosis and risk stratification in multiple scenarios. Encouraging results have shown its utility as a biomarker of mortality (all cause and CV), heart failure and acute coronary syndrome in different populations. The aim of this work is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. Method 395 kidney transplant recipients between 2005 and 2015 were included. GDF-15 measurements were performed from stored serum samples obtained pretransplant. The concentration of GDF-15 was analyzed using an enzyme-linked immunosorbent assay (Quantikine, R&amp;D Systems). Results Patient characteristics are shown in Table 1. The median GDF-15 was 5331.3 (50.49-16242.3) pg/ml. After a mean of 90.6 ± 41.5 months of follow up 82 (20.8%) patients died. Patients were stratified in tertiles according to GDF-15 levels: low (GDF-15 ≤ 4612.1 pg/ml), medium (GDF-15 4612.1-6296.5 pg/ml) and high risk tertile (GDF-15 &amp;gt; 6296.5 pg/ml). Higher GDF-15 concentrations were significantly associated with mortality: HR 2.16 95%CI (1.14-1.44), p = 0.018 for medium tertile and HR 3.28 95%CI (1.79-6.1), p &amp;lt;0.001 for high risk tertile (Figure 1). After adjusting for age, diabetes, coronary artery disease, peripheral vascular disease, non-renal solid organ transplant and dialysis at the time of transplant, the relation between survival and GDF-15 was significant (HR 2.24 95%CI (1.2-4.16), p = 0.011 for high risk tertile). After adjusting by EPTS (Estimated Post Transplant Survival score) the association with GDF-15 remained significant: HR 3.24 95%CI (1.2-8.8), p = 0.021 for medium risk tertile and HR 4.3 95%CI (1.65-11.54), p = 0.003 for high risk tertile (calculated only in first renal transplants). Mortality at 3 years was 6.9% (27 patients) and it was only related to coronary artery disease and GDF-15 (OR 7.1 95%CI (1.6-32.1), p = 0.01 for high risk tertile) after adjustment. Conclusion In our cohort, higher GDF-15 levels were independently associated with mortality in kidney transplant candidates. This study suggests that GDF-15 may be useful in stratifying recipient risk, adding value to the prognostic tools already available in clinical practice. Further work is needed to confirm these findings and elucidate the mechanisms linking this protein with mortality and CV disease in patients with CKD.

Establishment of clinical features and prognostic scoring model in early-stage hepatitis B-related acute-on-chronic liver failure

Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

DiM: Prognostic Score for Second- or Further-line Immunotherapy in Advanced Non–Small-Cell Lung Cancer: An External Validation

BackgroundOther than the programmed cell death ligand 1 (PD-L1) value, oncologists have only the clinical characteristics of patients with advanced non–small-cell lung cancer (aNSCLC) to determine candidates for immunotherapy. A clinical prognostic score composed of the Eastern Cooperative Oncology Group performance status, sex, histologic type, stage, platinum-based first-line therapy, and response to first-line therapy has categorized 3 prognostic groups for patients undergoing second-line chemotherapy. We sought to validate the same score for patients with aNSCLC treated with second- or further-line immunotherapy. Materials and MethodsWe collected data from 2 Italian centers. A score was generated to divide patients into 3 prognostic groups: best, score < 5; intermediate, score 5 to 9; and worst, score > 9. Overall survival (OS) and progression-free survival (PFS) were the endpoints. ResultsA total of 347 patients were included for analysis. Their median age was 66 years (range, 30-88 years), most were aged < 70 years (67.5%), 70.7% were men, 79.5% were smokers, and 74.6% had had adenocarcinoma. The Eastern Cooperative Oncology Group performance status was 0 for 23%, 1 for 54.5%, and 2 for 22.5%. Of the 347 patients, 28% were in the best prognosis, 51% in the intermediate, and 21% in the worst prognosis group, respectively. The median OS was 18.0 months for the best, 8.5 months for the intermediate (hazard ratio [HR] vs. best, 1.83; 95% confidence interval [CI], 1.35-2.47; P < .001) and 2.6 months for worst (HR vs. best, 5.77; 95% CI, 3.99-8.33; P < .001) group. The median PFS was 3.4 months for the best, 3.7 months for the intermediate (HR vs. best, 1.35; 95% CI, 1.03-1.77; P = .032), and 1.9 months for the worst (HR vs. best, 2.51; 95% CI, 1.80-3.50; P < .001) group. ConclusionsThe prognostic score was able to predict the outcomes of patients with aNSCLC who had received immunotherapy. The worst category showed a dismal life expectancy and probably would not benefit from active systemic therapy. Thus, for these patients, best supportive care could be the best choice.

An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring.

The frailty index (FI) is based on the principle that the more deficits an individual has, the greater their risk of adverse outcomes. It is expressed as a ratio of the number of deficits present to the total number of deficits considered. We developed an MDS-specific FI using a prospective MDS registry and assessed its ability to add prognostic power to conventional prognostic scores in MDS. The 42 deficits included in this FI included measurements of physical performance, comorbidities, laboratory values, instrumental activities of daily living, quality of life and performance status. Of 644 patients, 440 were eligible for FI calculation. The median FI score was 0.25 (range 0.05-0.67), correlated with age and IPSS/IPSS-R risk scores and discriminated overall survival. With a follow-up of 20 months, survival was 27 months (95% CI 24-30.4). By multivariate analysis, age >70, FI, transfusion dependence, and IPSS were significant covariates associated with OS. The incremental discrimination improvement of the frailty index was 37%. We derived a prognostic score with five risk groups and distinct survivals ranging from 7.4 months to not yet reached. If externally validated, the MDS-FI could be used as a tool to refine the risk stratification of current clinical prognostication models.

Clinical prognostic scores for patients with thymic epithelial tumors

Several inflammation-based prognostic scores emerged in various types of cancer to predict clinical outcomes. So far, no accurate pre-treatment scoring systems exist for patients with thymic epithelial tumors (TETs), comprising thymomas and thymic carcinomas (TCs). Therefore, we sought to test the prognostic value of different clinical composite scores and their components, identify optimal cut-off values for TETs as well as combine predictive components to new suitable prognostic scores. One hundred eighty-four patients with TETs undergoing surgical tumor resection were analyzed. A significant advantage in Freedom-from-Recurrence and/or Cause-specific survival (CSS) was evident for patients with high Advanced-Lung- Cancer-Inflammation-Index, low CRP-Fibrinogen-Score (CFS), low Glasgow-Prognostic-Score (GPS), low high-sensitivity-modified GPS, low TET-adapted GPS (TET-aGPS) and low Systemic-Immune-Inflammation Index. On multivariable analysis high TET-aGPS (HR = 14.9;p = 0.001), incomplete resection status (HR = 13.5;p = 0.001) and TC (HR = 26.0;p = 0.001) were significant independent prognostic factors for worse CSS. The CFS had the highest coefficient of determination (R2 = 0.188) to predict tumor recurrence of all composite scores, comprising CRP (R2 = 0.141) and fibrinogen (R2 = 0.158), the best single factor predictors. Inflammation-based prognostic scores and selected components are suitable to predict survival and/or tumor recurrence in TET patients undergoing primary surgery. Due to excellent long-term survival and frequent tumor recurrence, cut-off values were tailored to increase prognostic power.

Recapitulation of Prognostic Mutational Subtyping Utilizing F1H in GOYA and CAVALLI and the Potential to Highlight Benefit of Targeted Therapy in De Novo DLBCL

Introduction: Diffuse large B-cell lymphoma (DLBCL), is a genetically and clinically heterogeneous disease. Building on existing clinical prognostic scores in the era of genomic risk modeling is critical to improve patient (pt) outcomes and inform future trials. With advances in next-generation sequencing, the interrogation of genetic drivers to refine prognostic subgroups over and above histological cell of origin (COO) subtypes has been of keen interest. The application of an unsupervised prognostic clustering approach, non-negative matrix factorization (NMF) algorithm, to whole exome sequence (WES) data has led to identification of six distinct molecular clusters with potential clinical relevance (Chapuy et al. Nature Med, 2018). Here, we applied the NMF clustering approach to targeted exome-sequencing data utilizing the FoundationOne HemeTM panel and analyzed RNA gene expression data from the randomized Phase 3 GOYA and Phase 1b/2 CAVALLI studies in de novo DLBCL. Methods: Biopsy samples, clinical outcomes (overall survival [OS], progression-free survival [PFS]), and targeted exome-sequencing data were available for 499 pts from the GOYA trial (NCT01287741; ITT=1418; obinutuzumab [G]-CHOP vs rituximab [R]-CHOP) and 106 pts from the CAVALLI trial (NCT02055820; ITT=267, venetoclax+[G/R]-CHOP). The FoundationOne HemeTM panel of 465 genes (F1H, Foundation Medicine Inc. [FMI]) was used to define single nucleotide variants, copy number amplifications, and rearrangements. Clustering methodology was implemented using the R package NMF (Gaujoux and Seoighe, BMC Bioinformatics 2010). All models were adjusted for treatment (where applicable), age, International Prognostic Index (IPI), sex, COO (NanoString), and BCL2 by IHC. Results: Applying the NMF algorithm, de novo pts in GOYA clustered similarly into four of the six groups recently reported by Chapuy et al.: MYD88/CD79B, BCL2/EZH2, NOTCH2/TNFAIP3, and no mutations (Fig 1A). The mutation profiles and COO subset distribution were also similar to those previously described. Furthermore, the MYD88/CD79B and BCL2/EZH2 groups remained associated with inferior clinical outcomes (Fig 1B), with observed poor prognosis over the NOTCH2/TNFAIP3 and no mutations groups (OS: hazard ratio [HR], 2.0; 95% CI: 0.97, 3.90; PFS: HR, 1.60; 95% CI: 0.93, 2.80), even when adjusting for known prognostic factors. Application of NMF to pts treated with the BCL2-inhibitor venetoclax in combination with R-CHOP (CAVALLI) yielded only MYD88/CD79B- and BCL2/EZH2-like groups due to enrollment. However, in contrast to the BCL2/EZH2 subgroup reported in both Chapuy et al. and GOYA, these pts demonstrated a trend towards improved outcomes over MYD88/CD79B (OS: HR, 0.12; 95% CI: 0.01, 1.60; PFS: HR, 0.11; 95% CI: 0.01, 1.10; Fig 1D). The difference between studies is potentially explained by the ability of venetoclax treatment to overcome the adverse prognostic impact of BCL2 over-expression. BCL2 IHC positive (BCL2+) pts were enriched in high-risk groups in GOYA (MYD88/CD79B and BCL2/EZH2) (odds ratio [OR], 5.0; 95% CI: 3.13, 8.33) and CAVALLI (MYD88/CD79B) (OR, 2.0; 95% CI: 0.63, 6.67). In GOYA, a prognostic trend for BCL2+ status is observed within low-risk pts (OS BCL2+ HR, 1.9; 95% CI: 0.55, 6.3; PFS BCL2+ HR, 2.7; 95% CI: 1.0, 6.8), but not within high-risk groups (OS BCL2+ HR, 0.55; 95% CI: 0.29, 1.00; PFS BCL2+ HR, 0.76; 95% CI: 0.45, 1.30; Fig 1C). Additional genetic risk models will be presented, e.g. as per Reddy et al. (Cell, 2017), as well as differential expression analysis. Conclusions: Important findings from the present work include: 1) utility of targeted mutational data from F1H in recapitulating molecular clusters, previously identified using WES, that further subclassify established prognostic groups such as COO and IPI; and 2) a trend towards improved survival outcomes for patients in the BCL2/EZH2 cluster upon treatment with the BCL2 inhibitor venetoclax. This highlights the potential for utilizing novel genetic signatures as a means of identifying patients suitable for targeted therapies in the era of personalized health care. Disclosures Kim: Genentech, Inc.: Employment. Fan:Genentech, Inc.: Employment. Bolen:F. Hoffmann-La Roche: Equity Ownership; Genentech, Inc.: Employment. Bazeos:Roche Products Ltd: Employment, Equity Ownership. Jiang:Genentech: Employment, Equity Ownership; F. Hoffman-La Roche: Equity Ownership. Balasubramanian:Roche-Genentech: Employment; F. Hoffman-La Roche: Equity Ownership. Balakrishnan:Genentech, Inc.: Employment. Knapp:F. Hoffmann-La Roche Ltd: Employment. Humphrey:F. Hoffmann-La Roche Ltd: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Venstrom:F. Hoffmann-La Roche Ltd: Employment. Hernandez:Genentech, Inc.: Employment, Equity Ownership. Paulson:F. Hoffman-La Roche: Equity Ownership; Genentech: Employment.

P2669Prognostication in out-of-hospital cardiac arrest

Abstract Background Out-of-hospital cardiac arrest (OOHCA) remains an area where little progress has been made in outcomes despite significant advances in cardiac care. The OOHCA cohort requires a large amount of resources, including primary coronary intervention and intensive care, often with poor eventual outcomes. A clinical prognostic scoring system would allow resources to be focused on OOHCA patients who are likely to survive; rather than expensive and futile treatments in those who are not. Several different scoring systems have been published but have not been compared in a real world cohort of OOHCA patients. Method The Cardiac Arrest Hospital Prognosis (CAHP) score that utilises 7 variables and a simpler three-factor prognostic score derived by Hirt et al were applied retrospectively to a cohort of 157 consecutive OOHCA patients presenting to a regional Centre in our city, UK between 2016 and 2018. For each patient the CAHP score was calculated where a score of &gt;200 predicts a Cerebral Performance Category (CPC) outcome of 3–5 (severe disability, vegetative coma or death). They were also categorised using the Hirt algorithm into “Futile”, “Approaching Futility” and “Non-Futile” groups. CPC outcomes were then compared using both scores and diagnostic accuracy assessed. Results A CAHP score of &gt;200 predicted a CPC outcome of 3–5 with 97% specificity and a positive predictive value of 92%. A CAHP score &gt;200 predicted 30-day mortality with 96% specificity, and a positive predictive value of 89% (Fig. 1A). The same cohort categorised by the Hirt algorithm was less accurate; in those patients sorted into the “futile” category 15% of patients survived, and in the “approaching futility” group survival was 100% (Fig. 1B). The specificity and PPV of predicting futility was 94% and 85% respectively. Conclusion Although a simple three-factor prognostic score as suggested by Hirt et al is attractive in this cohort of OOHCA patients it did not discriminate those patients who were likely to survive and, the CAHP score was more accurate in predicting outcome. Further validation is required in prospective, multi-centre studies to ensure that application of these scores are reproducible in real-world OOHCA populations in decision making for emergency coronary angiography. Acknowledgement/Funding None

PS1171 TELOMERE LENGTH AT DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA PREDICTS THE ACHIEVEMENT OF DEEP MOLECULAR RESPONSE TO IMATINIB

Background:Telomere length (TL) is shortened with every cell division. Critically short telomeres are associated with genetic instability. In chronic myeloid leukemia (CML), increased cellular turnover of clonal BCR‐ABL1‐positive hematopoietic stem and progenitor cells leads to significantly shortened telomeres in myeloid cells from peripheral blood (PB). Retrospective studies have related accelerated telomere shortening in CML to disease stage, clinical risk score at diagnosis as well as cytogenetic remission.So far, no study has considered the possible association between TL at diagnosis of CML and the achievement of deep molecular response (DMR) with imatinib (IM) treatment.Aims:To explore if TL at diagnosis of CML is predictive of DMR achievement with IM as first‐line treatment.Methods:Samples from 100 patients with de novo CML at diagnosis of three different Catalan hospitals between 2004 and 2016 were included. Three patients were considered as missing due to no valid PCR results. All patients provided informed consent. Patients’ median age was 49 yrs (range 24–80 yrs) and 59% were males. Thirty‐one (38%) patients had the e13a2 p210 BCR‐ABL1 isoform whereas 51 (62%) had the e14a2 isoform. According to Sokal and ELTS scores, 48(50%) and 52(60%) patients were low risk, 30(32%) and 24(28%) were intermediate risk while 17(18%) and 10(12%) were high risk, respectively.Patients were treated with first line IM 400 mg QD orally. For the molecular response (MR) analysis, only response to IM was considered. Response during the first year was assessed according to European Leukemia Net 2013 guidelines. DMR was defined as MR4.0 or MR4.5 The median time from IM start to MR4.0 achievement was 16.1 months (5.5, 100.7). Follow‐up was at least 24 months for all patients.For TL determination, DNA was extracted from PB or bone marrow cells. TL was analysed by monochrome multiplex quantitative polymerase chain reaction and the results were expressed as the standardized T/S ratio. Age adaptation of TL, indicated as ΔTL (delta‐TL), was performed using data from 107 healthy controls (age range 16–84 years). The ΔTL for every patient was calculated subtracting the subject's linear predicted TL (linear regression analysis of healthy controls) from the observed TL.Results:Healthy controls showed the expected decline in TL with increasing age (R2 = 0.1693), which was not detectable in CML (R2 = 0.0002), suggesting that telomeres are not age‐dependent in CML at diagnosis.Analysing the clinical data, no significant correlation between ΔTL and clinical prognostic scores (Sokal and ELTS, with p = 0.816 and p = 0.314, respectively) was observed, nor between ΔTL and p210 BCR‐ABL1 onco‐protein isoforms (e13a2 and e14a2, p = 0.981).Finally, focusing on the ΔTL representing the difference between TL expected by age and TL determined in the CML cells, patients with lower ΔTL at diagnosis were significant associated with achievement of MR4.0 and MR4.5 (HR [95%CI]: 0.24 [0.1, 0.74], p = 0.013 and 0.23 (0.1, 0.76), p = 0.016, respectively). In addition, when patients were stratified according to median value of ΔTL (0.40), those with ΔTL&lt;0.40 significantly achieved MR4.0 earlier than patients with ΔTL&gt;0.40 (median in months [95%CI]: 21 [8.2, 33.7] vs 46.2 [23.6, 68.8], p = 0.034) (Fig1).Summary/Conclusion:TL at diagnosis of CML is a predictive biomarker of DMR achievement with IM as first‐line treatment. Acknowledgements: FIS (AES 2016) PI16/01200 and FEHH.image

Keeping prognostic assessment simple: The value of clinical features in normotensive cancer patients with pulmonary embolism

IntroductionAlthough normotensive cancer patients with acute pulmonary embolism (PE) are a heterogeneous population, most validated clinical prognostic scores classify these patients as high-risk individuals, which limits their usefulness in this setting. In this study, we aimed to identify readily available clinical predictors of overall 30-day and one-year mortality in normotensive cancer patients with PE. Methods and ResultsWe performed a retrospective single-center study that included all normotensive cancer patients with PE diagnosed by multidetector computed tomography (MDCT) during emergency department stay between January 2010 and December 2011. Clinical, MDCT and laboratory variables were collected for all patients. A total of 69 patients were included. All-cause mortality was 28% and 55% at 30 days and one year of follow-up, respectively. Lower mean arterial pressure, higher lactate level and a higher Shock Index (SI) at hospital admission were associated with increased all-cause mortality at 30 days and one year of follow-up. The simplified Pulmonary Embolism Severity Index was not a predictor of short- or long-term mortality. An SI of ≥0.7 was found to be associated with lower event-free survival in both short- and long-term follow-up (hazard ratio 7.20 [95% CI, 1.66-31.21, p<0.01] and 3.51 [95% CI, 1.70-7.25, p<0.01], respectively). ConclusionsThis is the first article reporting the value of the SI, a user-friendly and readily available clinical tool, as an independent and accurate predictor of 30-day and one-year all-cause mortality in normotensive cancer patients with symptomatic PE.

Prognostic score for second or further line immunotherapy in advanced non-small cell lung cancer (aNSCLC): An external validation.

e14077 Background: Beyond PD-L1, nowadays oncologists can only use clinical characteristics to candidate patients for immunotherapy (IO). Previously, a clinical prognostic score composed by ECOG performance status (PS), sex, histology, stage, uses of platin-based therapy at first-line (1L) and response to 1L categorized 3 different prognostic groups for patients treated with second-line (2L) chemotherapy (CHT) (Di Maio, EJC. 2010 Mar;46(4):735-43.). The aim of this study is to assess if the same score is able to discriminate the outcome of aNSCLC pts treated in 2L or further-line IO, potentially helping decision making. Methods: We recorded data of patients collected from two institutional databases: Istituto Nazionale Tumori of Milan and IRCCS Oncologico Giovanni Paolo II of Bari, Italy. Overall survival (OS) was the primary endpoint and also progression-free survival (PFS) was assessed. Prognostic score was generated, and pts were divided into 3 prognostic groups: best (B: &lt; 5), intermediate (I:5-9), worst (W: &gt; 9). Results: Overall, 347 pts were included in the analysis (193 from Milan and 154 from Bari). Median age was 66 years (y) (30 – 88y), most were &lt; 70 y (67.5%), male (70.7%), smokers (79.5%) and adenocarcinoma (74.6%). ECOG PS was: 0 (23%), 1 (54.5%) and 2 (22.5%). Pts distribution was: 28%, 51% and 21% in the B, I and W groups, respectively. Median OS was 18.0 months for B group, 8.5 months for I group (HR vs B 1.83, 95%CI 1.35 – 2.47, p &lt; 0.001) and 2.6 months for W group (HR vs B 5.77, 95%CI 3.99 – 8.33, p &lt; 0.001). Median PFS was 3.4 months for B group, 3.7 months for I group (HR vs B 1.35, 95% CI 1.03 – 1.77, p = 0.032) and 1.9 months for W group (HR vs B 2.51. 95% CI 1.80- 3.50, p &lt; 0.001). Similar results were obtained stratifying the model by Institution. Conclusions: This clinical prognostic score, that was generated in patients treated with second-line chemotherapy, is able to highly predict outcomes of patients treated with IO. These results demonstrated that in pre-treated aNSCLC pts, the worst category has a dismal absolute life expectancy, and probably would not benefit from any active systemic therapy (independently if CHT or IO). Perhaps for these pts best supportive care could be the best choice.

Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival.

Optimal techniques and patient selection for salvage reirradiation of high-grade glioma (HGG) are unclear. In this study, we identify prognostic factors for freedom from progression (FFP) and overall survival (OS) after reirradiation, risk factors for high-grade toxicity, and validate clinical prognostic scores. A total of 116 patients evaluated between 2000 and 2018 received reirradiation for HGG (99 WHO grade IV, 17 WHO grade III). Median time to first progression after initial therapy was 10.6 months. Salvage therapies before reirradiation included surgery (31%) and systemic therapy (41%). Sixty-five patients (56%) received single-fraction stereotactic radiosurgery (SRS) as reirradiation. The median biologically effective dose (BED) was 47.25 Gy, and the median planning target volume (PTV) was 4.8 cc for SRS and 95.0 cc for non-SRS treatments. Systemic therapy was given concurrently to 52% and adjuvantly to 74% of patients. Median FFP was 4.9 months, and median OS was 11.0 months. Significant multivariable prognostic factors for FFP were performance status, time to initial progression, and BED; for OS they were age, time to initial progression, and PTV volume at recurrence. High-grade toxicity was correlated to PTV size at recurrence. Three-level prognostic scores were generated for FFP and OS, with cross-validated receiver operating characteristic area under the curve (AUC) of 0.640 and 0.687, respectively. Clinical variables at the time of reirradiation for HGG can be used to prognosticate FFP and OS.