ECOG Scale Research Articles

Substantiation of the method for resolving obstructive jaundice in operable patients with malignant hepatopancreatobiliary tumors

The OBJECTIVE was to determine the best option for decompression of the biliary tract in patients with malignant neoplasms of the hepatopancreatobiliary zone to resolve obstructive jaundice before performing radical surgery.METHODS AND MATERIALS. The study of the results of examination and surgical treatment of 325 patients with mechanical jaundice caused by malignant tumors of the hepatopancreatobiliary zone allowed us to identify 93 (28.6 %) patients who initially underwent drainage operations on the bile ducts, and then radical surgical interventions.RESULTS. Stage I of the oncological process according to the TnM system (8 reconsideration) was determined in 16 (17.2 %) patients, stage II – in 71 (76.3 %) and stage III – in 6 (6.5 %). According to the ECOG scale, I or II scores were determined in all patients before radical surgery. Tumors of the head of the pancreas, common bile duct and large papilla of the duodenum led to the I level of biliary tract blockage in 81.7 % of patients. Tumors of the common bile duct and head of the pancreas (involving the cystic duct), tumors of the gallbladder and Klatskin (Bismuth–Corlette I) caused the II level of biliary tract blockage in 12.9 % of the examined patients. Klatskin tumor (Bismuth–Corlette II, IIIa, IIIb,) caused bile duct blockage of III level (5.4 % of patients). Pancreatoduodenal resection was performed in 85 patients, endoscopic papillectomy – 3, bile duct resection – 2 and bile duct resection in combination with liver resection – 3. The choice of a rational option for decompression of the biliary tract, taking into account the level of their blockage and the severity of the general somatic condition of patients, provides the possibility of performing radical surgery.CONCLUSION. Before performing radical surgery, obstructive jaundice in operable patients with malignant tumors of the hepatopancreatobiliary zone at the blockage of I level can be effectively and safely resolved by cholecystostomy, at the blockage of II level – endoscopic stenting, while the blockage of III level – percutaneous-transhepatic cholangiodrainage.

Prognostic value of symptoms at lung cancer diagnosis: a three-year observational study.

BackgroundLung cancer is mainly diagnosed at advanced or locally advanced stages, usually when symptoms become evident. However, sometimes it may be diagnosed incidentally during routine care, while patients are still asymptomatic. Prognosis differences based on symptomatic presentation have been partially explored. Our aim was to analyze the prognostic value of the initial symptomatic state of the patients in a general lung cancer cohort.MethodsObservational ambispective study including patients consecutively diagnosed with primary lung cancer between January 2016 and December 2018 via the lung cancer Fast Diagnostic Track (FDT). Patients were followed up until death or the end of the study in September 2019. Asymptomatic patients were compared with patients presenting symptoms. Overall survival (OS) of both groups was compared using the log-rank test. Cox regression analysis was performed to clarify the effect of the symptomatic status at diagnosis on survival. Additionally, propensity score (PS) matching analysis was performed.ResultsA total of 267 patients were analyzed; 83.5% were men, with a mean (SD) age at diagnosis of 68 (10.7) years. Incidental diagnosis was ascertained in 24.7% of cases. Asymptomatic patients presented more frequently stage I and II disease compared to symptomatic patients (51.5% vs. 14%), and exhibited a significantly better prognosis, with a 3-year OS of 63.6% (vs. 30.3%) and a median OS that was not reached during follow-up (vs. 10.3 months). With an adjusted multivariate Cox proportional hazard model, we obtained a HR (95% CI) of 2.63 (95% CI, 1.6–4.2; P<0.0001) associated with symptomatic presentation independently of age, sex, stage at diagnosis and ECOG scale. In addition, after performing the propensity score matching analysis, the Cox regression model continued to show a significantly worse prognosis for patients presenting with symptoms (P=0.041).ConclusionsLung cancer patients who are asymptomatic at diagnosis exhibit a significantly better prognosis, regardless of the stage of the disease, underlining the importance of an early diagnosis.

Interim results of a multicenter retrospective-prospective observational post-marketing study of Extimia® BIOCAD (INN: empegfilgrastim) to evaluate safety and efficacy in patients with lymphoproliferative diseases receiving cytotoxic therapy

Aim. To assess the efficacy and safety of using the drug Extimia BIOCAD (international nonproprietary name INN: empegfilgrastim) in order to reduce the frequency and duration of neutropenia, the frequency of febrile neutropenia (FN) and infections manifested by FN in patients with lymphoproliferative diseases receiving myelosuppressive therapy.&#x0D; Materials and methods. This publication presents the interim results of a multicenter retrospective prospective observational post-marketing study of the safety and efficacy of the drug Extimia BIOCAD (INN: empegfilgrastim) in patients with lymphoproliferative diseases receiving cytotoxic therapy (LEGERITY). The interim data analysis included 40 patients with lymphoproliferative diseases (Hodgkins lymphoma, diffuse large B-cell lymphoma, multiple myeloma, primary mediastinal large B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, splenic marginal zone lymphoma), who were treated in ten research centers of the Russian Federation (Moscow, St. Petersburg, regional clinics). The median age of patients was 48 (2172) years, 13/40 (32.5%) patients belonged to the older age group (60 years). Patients had functional status on the ECOG scale of 02 and received at least 2 chemotherapy injections against the background of prophylaxis with empegfilgrastim. Empegfilgrastim was administered at a dose of 7.5 mg subcutaneously once 24 hours after the end of the administration of cytotoxic chemotherapeutic agents. Primary endpoint: frequency of neutropenia 35 degrees of severity; secondary endpoints: frequency of FN; frequency of severe infections (34 stages); frequency of antibiotic prescription; relative dose intensity of therapy of the conducted chemotherapy courses; the incidence of all adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of all serious adverse reactions in patients who received at least one dose of the study drug empegfilgrastim; the incidence of CTCAE 5.0 grade 34 HP in patients who received at least one dose of the study drug empegfilgrastim; discontinuation rate of study drug empegfilgrastim due to adverse reactions.&#x0D; Results. The results of this study demonstrate that the incidence of neutropenia of 3 degree of severity after the 1st cycle of chemotherapy developed in 2/40 patients (5%) and as a result of high-dose therapy (R-DHAP). Neutropenia of any severity was reported in 5/40 patients (12.5%). Cases of FN development have not been registered. Severe infections (mucositis, enteropathy, pneumonia, etc.), as well as the use of antibacterial and antifungal drugs during 1 cycle of chemotherapy and in the inter-course period after 1 cycle of therapy were not recorded in any patient. The next course of myelosuppressive therapy was not delayed due to the development of neutropenia in any of the patients during the study. Adverse events, according to the researcher, associated with the use of empegfilgrastim, were registered in 2/40 patients (5%): moderate generalized pain syndrome (diffuse pain) of 1 severity and in one case ossalgia of 2 severity. No serious adverse reactions were reported.&#x0D; Conclusion. The results of the interim analysis of the study demonstrate the high efficacy of the first Russian original pegylated granulocyte colony-stimulating factor empegfilgrastim after a single administration of a fixed dose in the treatment of patients with aggressive and indolent lymphomas. The drug has a favorable tolerance profile in any age group of patients, especially in elderly patients. Administration of empegfilgrastim as a prophylaxis of neutropenia in patients with lymphoproliferative diseases receiving myelosuppressive therapy of varying intensity can reduce the burden on medical personnel, improve patient adherence to treatment, and contribute to the implementation of the therapeutic plan.

An oncologic emergency case of massive dedifferentiated liposarcoma of the small bowel mesentery

We report the case of a 71-year-old man who complained of abdominal distension, pedal edema, respiratory discomfort, and weight gain. Computed tomography revealed a giant, poorly enhancing tumor occupying the entire abdomen, with abdominal ascites. The tumor was causing hydronephrosis, compression of the inferior vena cava, and elevation of the diaphragm. The patient exhibited deterioration of performance status (PS3 on the ECOG scale) and required oxygen; therefore, emergency surgery was performed. Operative findings included bloody abdominal ascites and peritoneal dissemination. The large tumor arose from the small bowel mesentery, and infiltrated into the cecum and sigmoid colon. Tumor excision with ileocecal resection and sigmoidectomy was performed. Histopathological examination revealed dedifferentiated liposarcoma. The patient was discharged on postoperative day 22, but pre-discharge CT revealed a recurrent liposarcoma in the retroperitoneum. Therefore, chemotherapy was initiated and the treatment has been continued for over 6months after surgery. Due to the rarity of this disease, there is no consensus regarding treatment strategies for DDLPS with peritoneal dissemination or in patients with a poor general condition, especially in the setting of oncologic emergency. In this case, multimodal treatment was used to successfully manage this life-threatening state and obtain satisfactory therapeutic results.

Comparison of prognostic scales for patients with metastatic spine disease.

This is one-centre retrospective study with the aim to identify the scale, which provides the most accurate prediction of life expectancy in patients with metastatic lesions in spine. A retrospective analysis of clinical data of 138 patients with metastatic spinal tumors. Patients underwent spinal cord decompression and instrumented stabilization of affected area. We evaluated the general condition according to the Karnofsky and ECOG scales, the presence of metastases in the visceral organs, spine and other bones, the neurological status and conduction of the medical therapy before spinal surgery. Observed clinical parameters were converted to Tokuhashi, Tomita, and Katagiri scales. For statistical analysis, software environment R 3.4.1 was used. Assessment of prognostic accuracy was performed using ROC analysis. The Tokuhashi scale showed AUC 0.605 (95% CI 0.586-0.616), Tomita scale showed AUC 0.708 (95% CI 0.573-0.842), Katagiri scale showed AUC 0.650 (95% CI 0.508-0.792). The best results for survival rate predicting after surgical treatment for metastatic spinal lesions were shown the Tomita scale.

Influence of chemosensional disorders on taste preferences in cancer patients who are receiving oral nutrition supplements

Chemosensory disorders (CSD) such as disorders of taste and smell are one of the causes of malnutrition in cancer patients. The aim of the research was to evaluate the influence of CSD on taste preferences in cancer patients receiving oral nutritional supplements (ONS). Material and methods. The procedure involves 100 oncological patients (26 men, 74 women; 57.0±1.2 years old). The taste preferences in these patients were assessed using a digital rating scale during ONS. All patients had cancer outside the head and neck area and underwent specific treatment. The functional status on the ECOG scale was 0-II. All patients had indications for DPP (ESMO scale >2 points). Patients were offered a mixture of sweet (banana, coffee, vanilla) and unsweetened (vegetable, chicken soup) tastes in a disposable 30 ml container. The patient was asked to take a sip and evaluate the smell, taste, strength of taste and density (consistency) of the sample on a digital rating scale from 0 to 5 points, where 0 - I do not feel, 5 - I feel excellent. The maximum possible number of points for each sample was 20. Results. Signs of CSD (score <10) were detected in 69% of patients [95% confidence interval (CI) 59.5-77.7]. In this group, the frequency of choosing unsweetened tastes for ONS was 59.4% (95% CI 47.5-70.8), sweet - 40.6% (95% CI 29.2-52.5). In the group of patients without signs of CSD, the frequency of choosing savory tastes was 29.0% (95% CI 14.1-46.7), sweet - 71.0% (95% CI 53.3-85.9) (р=0.0049). Conclusion. The presence of CSD significantly affects the taste preferences of cancer patients and significantly increases the likelihood of choosing products for ONS with unsweetened taste (unsweetened foods).

Risk of Thromboembolic Disease and Hemorrhage in Patients with Multiform Glioblastoma

Background: Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor, with an aggressive course and a short life expectancy despite standard treatment. The possibility of the development of thrombotic events (VTE) with this type of cancer is frequent. Objective: To determine the risk of presenting VTE and haemorrhagic events in patients affected by GBM. Methods: Observational retrospective study of patients with GBM diagnosis at the General University Hospital of Ciudad Real between 2012 and 2015. The demographic characteristics of patients were studied, predictive models were compared, and a survival analysis was performed. Results: 13 (16.9%) out of 77 patients developed symptomatic VTE. The quality of life according to the performance status ECOG scale at the moment of diagnosis was 1 in 42 (15.38%) patients, and at the time of VTE, 5 (41.7%) had a value of 2, and 4 (33.3.3%) registered 3. In the group that developed VTE according to the predictive model of risk for thrombosis in Khorana 5 (38.5%) had low risk and 8 (61.5%) intermediate; on the ASCO 2013 modified scale 5 (38.5%) had an Intermediate risk and 8 (61.5%) high. With a median, 1 year follow-up, 64 (84.2%) patients died, with an average time after diagnosis of 279.09 days (216.6-341.6) (SE 31,8). 2 (2.6%) of the patients presented a greater haemorrhagic event and 7 (7.9%) cerebral haemorrhage, of which 4 (44.4%) had prophylactic Low molecular weight heparins (LMWHs). In the survival analysis, patients who received prophylactic treatment with LMWHs had a higher survival rate with an average of 298.5 days compared to 239.3 of those who did not (p>0.05). There were no significant variables in the multivariate analysis for thrombotic or haemorrhagic events. Conclusion: The demographic and clinical characteristics of our patients were similar to those reported in other publications. The predictive scale of Khorana was not validated in our study, in contrast, the modified ASCO 2013 scale was closer to our results. The creation of a precise predictive model would help to delineate the benefit of prophylactic anticoagulation in high-risk patients. Long-term prophylaxis with LMWHs has demonstrated a reduction of thrombotic events without significantly increasing fatal haemorrhagic episodes, also demonstrating greater long-term survival, independent of thrombotic events. Randomized prospective studies are needed to demonstrate its benefits.

Clinical characteristics and survival analysis of primary intestinal extranodal NK/T-cell lymphoma, nasal type

目的回顾性研究原发肠道结外鼻型NK/T细胞淋巴瘤（ENKTL）患者的临床特征、生存及影响预后的因素。方法收集2009年1月至2019年12月就诊于空军军医大学第一附属医院诊断为肠道淋巴瘤的病例，从中筛选原发肠道ENKTL并收集患者资料进行回顾性分析。结果在210例肠道淋巴瘤患者中，原发肠道ENKTL患者34例（16.2％），其中男26例，女8例，中位年龄45（20～69）岁，年龄≤60岁者占85.3％。主要症状：腹痛（76.5％）、腹泻（20.6％）、便血（29.4％）、腹部包块（2.9％），85.3％伴B症状，73.5％血清LDH升高。病变部位：大肠（52.9％）、小肠（29.4％）、大肠及小肠均受累（17.7％）。内镜分型：隆起型（8.8％）、溃疡型（32.4％）、弥漫型（2.9％）和混合型（55.9％）。Lugano分期Ⅰ/Ⅱ期24例（70.6％），Ⅳ期10例（29.4％）。组织病理免疫组化EBER阳性者占94.1％。中位生存时间为60 d。ECOG评分、血清LDH、IPI评分及是否有并发症影响患者的OS率（P值分别为0.037、0.009、0.002和0.000）。结论原发肠道ENKTL多见于青中年男性，以腹痛最多见，常合并B症状，血清LDH多异常升高，病变多位于大肠，病灶主要呈混合型或溃疡型。IPI评分低危、无并发症者OS率较高。

Survival and consolidative radiotherapy in patients living with HIV and treated for diffuse large B-cell lymphoma.

Current guidelines tend to treat HIV positive (HIV+) patients as their seronegative counterparts with diffuse large B-cell lymphoma (DLBCL) but little is known about their radiotherapy responses differences. A retrospective cohort of all consecutive HIV+ DBCL patients treated with chemotherapy between 2004 and 2018 was assessed. All patients had biopsy-proven lymphomas. They were included if the proposed radical treatment was done without progression or death during chemotherapy and had at least 6 months of follow-up or were followed until death. Fifty-three (53) patients were selected, with a median age at diagnosis of 41.39 years (20-65 years). Median follow-up of 35.16 months (1.4-178.7 months). Male patients accounted for 54.7% and most had a good performance in the ECOG scale at diagnoses (81.1% are ECOG 0-1). Median overall survival was not reached. Mean OS was 41.5 months with 16 deaths. Age had an impact on OS, with patients older than 60 years at more risk (p = 0.044), as did longtime use of HAART, with those that started antiretroviral therapy within the diagnose of the lymphoma at greatest risk (p = 0.044). RT did not have an impact on OS (p = 0.384) or PFS (p = 0.420), although survival curves show better OS in the radiotherapy group. Toxicities were rare, since none of the patients had grade 3 or superior toxicity. RT did not impact survival or progression in our limited sample, but a longer OS may occur after the first-year post RT. RT should be tested in prospective data in the HIV+ population with DLBCL.

1880P Two thousand consecutive parallel evaluations of Karnofsky and ECOG performance status: looking for a correct comparison

Performance status (PS) is a strong, validated prognostic factor across all cancer types, especially in the advanced phase. It is estimated usually by the Karnofsky (KPS) or the ECOG scale, each of them having peculiar features. Two possible way of comparing KPS and ECOG scales are possibile, differing in the attribution of KPS 90,70, 50 and 30% respectively to PS 0,1,2 and 3 or to 1,2,3 and 4. From the limited data available, the latter comparison seems to better adapt to real-world clinical data (Verger E, Cancer 1992). From 1st May 2019 to 19th May 2020 all the consecutive values of KPS and ECOG PS were simultaneously recorded from every clinical evaulation of three medical oncologists from the Lung Cancer Unit. In particular, KPS values were estimated with the help of specific questions involving the domain of daily self-dependence and self-care (Schag CC, JCO 1984). The attribution of KPS 90,70,50 and 30% to PS 0,1,2 and 3 or to PS 1,2,3 and 4 was defined respectively as the BOLD or the CONSERVATIVE comparison. Moreover, data about DISCORDANT cases (i.e. very different KPS and ECOG values) were analyzed. Values of KPS and ECOG PS from two-thousand consecutive clinical evaluations were collected, 86.5% conducted in an outpatient setting and 78.3% in patients affected by NSCLC or SCLC. Median age of patients was 68.2 years, male/female ratio was 2.26. Mean values of KPS and ECOG PS for the entire cohort were 79.98% and 1.1. The distribution of the attribution of KPS 90,70,50 and 30% to the BOLD or to the CONSERVATIVE comparison was:Table: 1880PBOLDKPS (n.)CONSERVATIVEPS 0: 53.3% (309)90% (579)PS 1: 46.7% (270)PS 1: 9,8% (35)70% (357)PS 2: 90,2% (322)PS 2: 2,9% (3)50% (102)PS 3: 97,1% (99)PS 3: 0% (0)30% (8)PS 4: 100% (8) Open table in a new tab Discordant KPS-ECOG values were identified in 16 cases (0.8%): 14 with KPS 60%-PS 3 (all cases with advanced thoracic cancers), 1 with 50%-PS 2, and 1 with 80%-PS 0. In a real-practice population of aggressive cancers the CONSERVATIVE way of comparing ECOG PS and KPS seems to fit better the clinical data, especially when PS worsens (KPS 70, 50 or 30%). Further researches are however needed to improve the correlation of the two PS scales.

Impact of HIV infection on consolidative radiotherapy for non-Hodgkin diffuse large B-cell lymphoma

ObjectivesEven though frequent, it is not known how HIV infection and treatment impact in the consolidation by radiotherapy of non-Hodgkin diffuse large B-cell lymphomas (DBCL). This article aim to assess that difference that HIV makes on radiation treatment.Patients and methodsA retrospective cohort of all DBCL patients treated with chemotherapy and consolidative radiotherapy at a single institution between 2010 and 2018 was assessed. All patients had biopsy-proven lymphoma and were included if radiation was part of the treatment and had at least 6 months of follow-up or were followed until death.ResultsThree-hundred fifty-nine (359) patients were selected, with a median age at diagnosis of 57.7 years (13–90 years). Twenty-eight patients (7.8%) were HIV positive. Median follow-up was 48.0 months. Female patients were 51.3% and most had a good performance in the ECOG scale (78.8% are ECOG 0–1). Median overall survival was not reached, but mean OS was 50.1 months with 86 deaths. Median progression-free survival was 48.7 months. HIV infection had no impact on OS (p = 0.580) or PFS (p = 0.347) among patients treated with RT. HIV positive patients were more frequently staged only with CT (p > 0.05) with no impact on PFS (p = 0.191). No HIV positive patient received rituximab due to local policy restrictions and HIV positive patients were more prone to receive CHOP-like chemotherapy (p < 0.05), specially ones with etoposide (CHOEP). CHOP was associated with better survival (p = 0.015) in the overall population and in the HIV negative population (p = 0.002), but not in the HIV positive population (p = 0.982). RT toxicities were not overall more frequent in the HIV positive population (p = 0.567), except for fatigue (p < 0.05) and hematological toxicities (p = 0.022).ConclusionHIV status did not influence on survival when patients were treated with consolidative radiotherapy. HIV infection was a bias on our sample for staging methods and chemotherapy regimens choices. For HIV positive patients there was an increase in fatigue and hematological toxicities of any grade with radiation.

Clinical experience with the targeted therapy in melanoma patients with brain metastases.

e22009 Background: According to the clinical studies, the frequency of melanoma brains metastasis reaches 43%, and according to autopsy data, this percentage is even higher - up to 75%. New drugs in clinical practice has significantly improved the prognosis of the metastatic melanoma, however, patients with metastases in the brain are often excluded from large clinical studies, which limits the evidence base of the effectiveness of new therapy methods in this category of patients. Methods: 44 patients with advanced melanoma were treated in SPb Clinical Oncology Dispensary from 2012 till now: 19 male and 25 female, median age is 54y.o. (from 26 to 81). 31 (70%) patients received combination of BRAF and MEK inhibitors, 13 (30%) patients received only BRAF inhibitors. 26 (59%) of patients received target therapy (TT) as 1st line of therapy. Initial performance status (PS) assessed by ECOG scale was following; 8 patient had PS = 0 by ECOG, 29 patients – PS = 1 by ECOG and 6 patients had PS = 2/3 status by ECOG. 8 (18%) patients with brain metastasis has radiation before the TT: 6 patients received at least 1 session of stereotactic radiotherapy and 2 patients underwent radiation of the entire brain. Results: Group of patients without brain metastases: median PFS is 10.0 month (95% CI: 6.0;15.0). The average PFS is 16,90 ± 3,19 month (95% CI:10,64;23,16). Median OS is 15.0 months (95% CI: 11.0;64.0). The average OS is 33,16 ± 5,89 month (95% CI: 21,62 – 44,70). Group of patients with brain metastases: median PFS and OS is not reached. The average PFS is 17,86 +/- 3,3 month (95% CI: 11,42-24,33). The average OS is 20,31 ±2,86 month (95% CI: 14,71 - 25,92). Only 3 from 8 patients have PD after TT on the time of analysis. 5 patients are still alive. Conclusions: Our clinical experience demonstrates comparable efficacy of TT (PFS and OS) in patients with melanoma, regardless of the presence of metastatic brain disease. In the treatment of this category of patients, an integrated approach is very important, including both the use of targeted drugs and the conduct of surgical and radiotherapy. An equally important factor is the rapid onset of treatment.

Association Between Cognitive Test Performance and Subjective Cognitive Decline in a Diverse Cohort of Older Adults: Findings From the KHANDLE Study.

Subjective cognitive decline (SCD) may represent a low-burden indicator of dementia risk. The value of SCD as a proxy marker, however, depends on the consistency of associations between subjective and objective cognitive measures across sociodemographic and psychological factors. We evaluated baseline data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study (n=1615). SCD was measured using the 12-item Everyday Cognition (ECog) scale. Using linear regression models with interaction terms, we evaluated 6 potential modifiers (age, sex, race/ethnicity, educational attainment, family history of dementia, and depressive symptoms) of the association between cognitive performance (episodic memory, executive function) and SCD. Lower episodic memory and executive function scores were associated with higher log(ECog scores) (more SCD). Older age and elevated depressive symptoms were associated with higher log(ECog scores). Age (interaction P=0.002) and education (interaction P=0.01) modified the association between executive function and log(ECog scores). Specifically, associations between executive function and log(ECog scores) were stronger among participants with more education and less pronounced among older participants. The association between cognitive performance and log(ECog scores) differed little across sociodemographic and psychological factors. SCD as measured by the ECog may be a valuable proxy for cognitive performance in diverse older adults.

Cognition After Lowering LDL-Cholesterol With Evolocumab

BackgroundThe EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in High Cardiovascular Risk Subjects) trial demonstrated that evolocumab added to a background statin did not affect cognitive performance in a subset of 1,204 patients enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 inhibitors in Subjects With Elevated Risk). ObjectivesThe authors describe patient-reported cognition in the entire FOURIER trial using a self-survey. MethodsFOURIER was a randomized, double-blind, placebo-controlled trial involving patients with atherosclerotic cardiovascular disease and low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dl or non-high-density cholesterol ≥100 mg/dl despite statin therapy. At the final visit, patients completed a 23-item survey on memory and executive domains from the Everyday Cognition (ECog) scale. Patients compared their levels of everyday function at the end of the trial with their levels at the beginning and scored as 1 (no change or improvement), 2 (occasionally worse), 3 (consistently little worse), or 4 (consistently much worse). ECog scores were compared by the 2 randomized treatment arms and by achieved LDL-C at 4 weeks. ResultsA total of 22,655 patients completed ECog after a median duration of 2.2 years. The proportions of patients reporting cognitive decline (ECog score ≥2) at the end of the study were similar for placebo versus evolocumab, both for total score 3.6% versus 3.7% (p = 0.62) and for subdomains (memory, 5.8% vs. 6.0%; total executive, 3.6% vs. 3.7%). The proportion of patients reporting a decline in total cognitive score was similar among the 2,338 patients who achieved very low LDL-C levels (<20 mg/dl) compared to the 3,613 patients with LDL-C ≥100 mg/dl (3.8% vs. 4.5%, p = 0.57). ConclusionsThe addition of evolocumab to maximally tolerated statin therapy had no impact on patient-reported cognition after an average of 2.2 years of treatment, even among patients who achieved LDL-C <20 mg/dl.

Differential Item Functioning of the Everyday Cognition (ECog) Scales in Relation to Racial/Ethnic Groups

The Everyday Cognition (ECog) scales measure cognitively based across domains of everyday abilities that are affected early in the course of neurodegenerative disorders such as Alzheimer's disease. However, the degree to which the ECog may be differentially influenced by ethnic/racial background is unknown. This study evaluates measurement invariance of the ECog across non-Hispanic White (NHW), Black, and Hispanic individuals. Participants included 1177 NHW, 243 Black, and 216 Hispanic older adults from the UC Davis Alzheimer's Disease Center Cohort who had an ECog. Differential item functioning (DIF) for each ECog domain was evaluated separately for Black and Hispanic participants compared to NHW participants. An iterative multiple group confirmatory factor analysis approach for ordinal scores was used to identify items whose measurement properties differed across groups and to adjust scores for DIF. Adjusted scores were then evaluated to test whether they were more strongly associated with cognitive function (concurrent and longitudinal change in cognition) and brain volumes (measured by brain imaging). Varying levels, patterns, and impacts of DIF were found across domains and groups. However, the impact of DIF was relatively small, and DIF effects on scores generally were less than one-half standard error of measurement. There were no meaningful differences in associations with cognition and brain injury between DIF adjusted and unadjusted scores. Varying patterns of DIF were observed across the Black and Hispanic participants across select ECog domains. Overall, DIF effects were relatively small and did not change the relationship between the ECog and other indicators of disease.

Survival in patients with surgically treated spinal metastases.

Background:Despite the various treatment protocols available, survival evaluation is a fundamental criterion for the definition of surgical management; there are still many inconsistencies in the literature on this topic, especially in terms of the value of surgery and its morbidity in patients with very short survival.Objective:The objective was to analyze the association of clinical, oncological, and surgical factors in the survival of patients undergoing spinal surgery for spinal metastases (SM).Materials and Methods:A retrospective cohort of forty patients who were surgically treated at our institution for SM between 2010 and 2018 were included in the study. We applied the prognostic scales of Tomita and Tokuhashi in each patient and evaluated the systemic status using Karnofsky Performance Scale (KPS) and Eastern Cooperative Oncology Group Performance Scale. Survival rate in months was estimated using the Kaplan–Meier curve, with death considered as primary outcome and, for the evaluation of the association between the variables, the Chi-square test, Fisher’s exact test, or Fisher–Freeman–Halton test was applied for better survival. The level of statistical significance was considered as 5% (P ≤ 0.05).Results:The mean survival was 8.4 months. Patients with KPS <70 had a mean survival of 6.36 months, while those with KPS >70 had a mean survival of 14.48 months (P = 0.04). The mean survival of patients classified as ECOG 2 was 7.05 months (95% confidence interval [CI]: 3.4–10.7), and that of patients classified as ECOG 3 and 4 was 1.24 months (95% CI: 0.8–1.59). The mean survival rate among the patients with unresectable metastases in other organs was 6.3 months (95% CI: 3.9–8.9), while the survival rate of those who did not have metastases was 13.8 months (95% CI: 10.0–17.68; P = 0.022).Conclusion:Survival was associated with the preoperative functional status defined by the KPS and ECOG scales and with the presence of nonresectable visceral metastases.

Risk Factors for Infectious Complications after Surgical Treatment of Spinal Metastases in Patients with Breast and Kidney Cancer

Relevance. In patients with the most common malignant new growth such as breast, kidney and lung cancer the rate of spinal metastases amounts to 70%. Increasing number of surgical procedures results in growing frequency of postoperative complications including surgical site infection (SSI) which do not only deteriorate the quality of patient’s life but change the timelines for renewal of therapy for the primary disease. Study design — case control study. Purpose of the study — to identify key risk factors as well as impact of tumor therapy on development of infectious complications in patients with breast and kidney cancer after surgical management of metastatic spine lesion. Materials and Methods. The authors collected and compiled the data on 2023 oncological patients who underwent specialized neuroorthopaedic treatment in the period from 2000 until 2017 due to tumor spine lesions. Inclusion criteria: malignant breast and kidney tumors with spine metastases, continued systemic tumor therapy, decompression and stabilization spine surgery irrespective of used implants. Patients that corresponded to inclusion criteria were divided into two groups. The first (main) group included patients (n = 22) with infectious complications after surgery. The second (control) group (n = 23) was formed by propensity score matching. Results. The analysis of obtained data resulted in identification of severe significant factors (р0.05): diabetes mellitus, postoperative liquorrhea, certain classes by ASA (3, 4) and ECOG (2, 3, 4) scales, volume of blood loss, time of surgery and type of tumor therapy. However, the three latter have the highest statistical significance (р0.01): surgical factors (blood loss volume and time of procedure) and type of tumor therapy. Conclusion. Postoperative SSI remains a common severe complication after surgeries due to metastatic spine lesions. The causes of postoperative infection after tumor resection are compromised immune status of the patient; long time of procedure with heavy blood loss and adjuvant tumor therapy.

HIGH-DOSE CHEMOTHERAPY FOR PRIMARY DIFFUSE LARGE B-CELL LYMPHOMA OF THE CENTRAL NERVOUS SYSTEM. INTERIM RESULTS OF THE CNS-2015 PROTOCOL

Introduction. Induction chemotherapy (CT) for primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is based on the use of methotrexate in high doses. An optimal consolidation strategy involves high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation (auto-HSCT). The most effective conditioning regimen comprises a combination of chemotherapy agents including thiotepa.Aim. To present the authors’ experience of applying auto-HSCT/TBC in patients with primary DLBCL of the CNS.Methods. The prospective study CNS-2015 was carried out among 20 patients aged 20–52 years (median 42 years old) from 2015 to 2019. The male/female ratio came to 13/7. The somatic status of 17 (85 %) patients was 0–1 on the ECOG scale. Only 3 (15 %) patients showed the somatic status of 4 points. According to the criteria of the MSKCC prognostic system, 18 (90 %) and 2 (10 %) patients were assigned to the low-risk and medium-risk groups, respectively.Results. All patients included in the study received 3–5 cycles of chemotherapy with high doses of methotrexate, vincristine, procarbazine and rituximab (R-MPV), as well as underwent auto-HSCT following TBC-based conditioning regimen (thiotepa, busulfan, cyclophosphamide). Prior to auto-HSCT, 15 and 5 out of 20 patients having completed induction chemotherapy achieved complete remission and partial remission, respectively. Following auto-HSCT, complete remission was achieved in 5 patients with an initial partial response to treatment. All patients underwent temozolomide maintenance therapy for 2 years. With a median follow-up of 17 (1–46) months, 18 patients are alive and in remission. Two patients, who relapsed 4 and 5 months after auto-HSCT and achieved no response to the second line of chemotherapy and radiation therapy, died 24 and 26 months after auto-HSCT.Conclusion. R-MPV is an effective treatment for patients with primary DLBCL of CNS, which is not accompanied by severe toxicity. The use of high-dose chemotherapy with TBC allows a high remission rate to be achieved. The mortality associated with treatment in the group of patients included in the study came to 0 %.

Factors affecting the efficacy of gemcitabine and nab-paclitaxel (paclitaxel + albumin) combination in the Russian patient population: results of a multicenter retrospective study

Introduction . The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods . The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results . 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4), the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings . The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

Genomic profiling of non-oncogene-addicted aNSCLC using liquid biopsy. A single institution Italian experience

Abstract Background cfDNA analysis could represent an alternative to invasive biopsy in patients with NSCLC to better understand disease profile. We report a real-world experience of genomic assessment of an Italian patients’ cohort. Methods We evaluated 58 non-oncogene-addicted aNSCLC patients treated at our Institution from January 2018 to May 2019. All patients were characterized using cfDNA NGS Guardant360® platform (Guardant Health, Redwood City, CA). Association between a positive result (defined as cfDNA detected) and clinical features was assessed using logistic regression test. Using online library dataset (mycancergenome.org) and literature data, we divided patients in genomic clusters and performed a descriptive analysis. Results The median age of patients was 67 (range 38-85), 44 men and 14 women, 8.6% never smokers, 41.4% former and 50% current smokers. 14 patients (24.2%) had squamous cell carcinoma and 44 (75.8%) had non-squamous NSCLC, 50 of 58 at stage IV at the time of testing. Most patients were PS 0-1 per ECOG scale and has been treated with at least one systemic regimen before performing NGS. 47 of 58 patients (81%) has been considered positive at the analysis. No targetable genomic alterations per local authority has been found. More than 40 different mutated genes were detected, the most common alterations involved TP53 (60% of patients), KRAS (34%), PDGFRα (17%), EGFR (15% - not-TKI-sensitive), PI3KCA (15%), CDKN2A (15%). Chemotherapy (but not immunotherapy) and extra-thoracic radiotherapy before testing increased the probability to result positive at NGS of 4.5 and 2 folds respectively. Six mutational clusters have been identified. Most patients had genomic alterations in Replication Stress - DNA damage/repair, cell cycle - (72%) and Tyrosine Kinase Receptor/Growth Factor pathway (62%), less common mutations affected PI3K/AKT/mTOR and Hormone signaling (26% and 9% respectively). Conclusions Our experience demonstrated the feasibility of NGS-based NSCLC patients genomic profiling. The widespread of NGS platforms (and the subsequent reduction of costs) should encourage clinicians to use these methods with all patients to guarantee access to developing therapeutics and clinical trials. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure F. Ciardiello: Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. F. Morgillo: Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.