Unfavorable Disease Research Articles

EZH2 and Endometrial Cancer Development: Insights from a Mouse Model.

Enhancer of zeste homolog 2 (EZH2), a core component of polycomb repressive complex 2, plays an important role in cancer development. As both oncogenic and tumor suppressive functions of EZH2 have been documented in the literature, the objective of this study is to determine the impact of Ezh2 deletion on the development and progression of endometrial cancer induced by inactivation of phosphatase and tensin homolog (PTEN), a tumor suppressor gene frequently dysregulated in endometrial cancer patients. To this end, we created mice harboring uterine deletion of both Ezh2 and Pten using Cre recombinase driven by the progesterone receptor (Pgr) promoter. Our results showed reduced tumor burden in Ptend/d; Ezh2d/d mice compared with that of Ptend/d mice during early carcinogenesis. The decreased Ki67 index in EZH2 and PTEN-depleted uteri versus that in PTEN-depleted uteri indicated an oncogenic role of EZH2 during early tumor development. However, mice harboring uterine deletion of both Ezh2 and Pten developed unfavorable disease outcome, accompanied by exacerbated epithelial stratification and heightened inflammatory response. The observed effect was non-cell autonomous and mediated by altered immune response evidenced by massive accumulation of intraluminal neutrophils, a hallmark of endometrial carcinoma in Ptend/d; Ezh2d/d mice during disease progression. Hence, these results reveal dual roles of EZH2 in endometrial cancer development.

Upregulation of FHL1, SPNS3, and MPZL2 predicts poor prognosis in pediatric acute myeloid leukemia patients with FLT3-ITD mutation

Chromosomal translocations and gene mutations are characteristics of the genomic profile of acute myeloid leukemia (AML). We aim to identify a gene signature associated with poor prognosis in AML patients with FLT3-ITD compared to AML patients with NPM1/CEBPA mutations. RNA-sequencing (RNA-Seq) count data were downloaded from the UCSC Xena browser. Samples were grouped by their mutation status into high and low-risk groups. Differential gene expression (DGE), machine learning (ML) and survival analyses were performed. A total of 471 differentially expressed genes (DEGs) were identified, of which 16 DEGs were used as features for the prediction of mutation status. An accuracy of 92% was obtained from the ML model. FHL1, SPNS3, and MPZL2 were found to be associated with overall survival in FLT3-ITD samples. FLT3-ITD mutation confers an indicative gene expression profile different from NPM1/CEBPA mutation, and the expression of FHL1, SPSN3, and MPZL2 can serve as prognostic indicators of unfavorable disease.

Role of [18F]FDG PET/CT in the management of G1 gastro-entero-pancreatic neuroendocrine tumors

PurposeSince the role of [18F]FDG PET/CT in low-grade gastroenteropancreatic (GEP) neuroendocrine neoplasia (NET) is not well established, this study was aimed to evaluate the role of [18F]FDG PET/CT in grade 1 (G1) GEP-NETs.MethodsThis is a retrospective study including patients with G1 GEP-NETs who underwent [18F]FDG PET/CT.Results55 patients were evaluated, including 24 (43.6%) with pancreatic NETs and 31 (56.4%) with gastrointestinal NETs. At the time of diagnosis, 28 (51%) patients had metastatic disease, and 50 (91%) patients were positive by 68-Ga sstr PET/CT. Overall, 27 patients (49%) had positive findings on [18F]FDG PET/CT. Following [18F]FDG PET/CT, therapeutic management was modified in 29 (52.7%) patients. Progression-free survival was longer in patients with negative [18F]FDG PET/CT compared with positive [18F]FDG PET/CT (median PFS was not reached and 24 months, respectively, p = 0.04). This significance was particularly evident in the pancreatic group (p = 0.008).ConclusionsDespite having low proliferative activity, approximately half of GEP-NETs G1 showed positive [18F]FDG PET/CT, with a corresponding negative impact on patients’ clinical outcomes. These data are in favor of a more “open” attitude toward the potential use of [18F]FDG PET/CT in the diagnostic work-up of G1 GEP-NETs, which may be used in selected cases to detect those at higher risk for an unfavorable disease course.

Evolution of TP53 abnormalities during CLL disease course is associated with telomere length changes

BackgroundTelomeres are protective structures at chromosome ends which shorten gradually with increasing age. In chronic lymphocytic leukemia (CLL), short telomeres have been associated with unfavorable disease outcome, but the link between clonal evolution and telomere shortening remains unresolved.MethodsWe investigated relative telomere length (RTL) in a well-characterized cohort of 198 CLL patients by qPCR and focused in detail on a subgroup 26 patients who underwent clonal evolution of TP53 mutations (evolTP53). In the evolTP53 subgroup we explored factors influencing clonal evolution and corresponding changes in telomere length through measurements of telomerase expression, lymphocyte doubling time, and BCR signaling activity.ResultsAt baseline, RTL of the evolTP53 patients was scattered across the entire RTL spectrum observed in our CLL cohort. RTL changed in the follow-up samples of 16/26 (62%) evolTP53 cases, inclining to reach intermediate RTL values, i.e., longer telomeres shortened compared to baseline while shorter ones prolonged. For the first time we show that TP53 clonal shifts are linked to RTL change, including unexpected RTL prolongation. We further investigated parameters associated with RTL changes. Unstable telomeres were significantly more frequent among younger patients (P = 0.032). Shorter telomeres were associated with decreased activity of the B-cell receptor signaling components p-ERK1/2, p-ZAP-70/SYK, and p-NFκB (P = 0.04, P = 0.01, and P = 0.02, respectively).ConclusionsOur study revealed that changes of telomere length reflect evolution in leukemic subclone proportion, and are associated with specific clinico-biological features of the explored cohort.

Metastasis and Mortality in Men With Low- and Intermediate-Risk Prostate Cancer on Active Surveillance.

Active surveillance (AS) is a safe treatment option for men with low-risk, localized prostate cancer. However, the safety of AS for patients with intermediate-risk prostate cancer remains unclear. We identified men with NCCN-classified low-risk and favorable and unfavorable intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration. We analyzed progression to definitive treatment, metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality using cumulative incidences and multivariable competing-risks regression. The cohort included 9,733 men, of whom 1,007 (10.3%) had intermediate-risk disease (773 [76.8%] favorable, 234 [23.2%] unfavorable), followed for a median of 7.6 years. The 10-year cumulative incidence of metastasis was significantly higher for patients with favorable (9.6%; 95% CI, 7.1%-12.5%; P<.001) and unfavorable intermediate-risk disease (19.2%; 95% CI, 13.4%-25.9%; P<.001) than for those with low-risk disease (1.5%; 95% CI, 1.2%-1.9%). The 10-year cumulative incidence of PCSM was also significantly higher for patients with favorable (3.7%; 95% CI, 2.3%-5.7%; P<.001) and unfavorable intermediate-risk disease (11.8%; 95% CI, 6.8%-18.4%; P<.001) than for those with low-risk disease (1.1%; 95% CI, 0.8%-1.4%). In multivariable competing-risks regression, favorable and unfavorable intermediate-risk patients had significantly increased risks of metastasis and PCSM compared with low-risk patients (all P<.001). Compared with low-risk patients, those with favorable and unfavorable intermediate-risk prostate cancer managed with AS are at increased risk of metastasis and PCSM. AS may be an appropriate option for carefully selected patients with favorable intermediate-risk prostate cancer, though identification of appropriate candidates and AS protocols should be tested in future prospective studies.

COVID-19 Independent Risk Factors for Unfavorable Disease Progression: A Cross-Sectional Study from Romania

COVID-19 Independent Risk Factors for Unfavorable Disease Progression: A Cross-Sectional Study from Romania

The Influence of Endogenous Testosterone Density on Unfavorable Disease and Tumor Load at Final Pathology in Intermediate-Risk Prostate Cancer: Results in 338 Patients Treated with Radical Prostatectomy and Extended Pelvic Lymph Node Dissection

Objective: The aim of this study is to evaluate the influence of endogenous testosterone density (ETD) on features of aggressive prostate cancer (PCa) in intermediate-risk disease treated with radical prostatectomy and extended pelvic lymph node dissection. Materials and Methods: Density measurements included the ratio of endogenous testosterone (ET), prostate-specific antigen (PSA), and percentage of biopsy positive cores (BPC) on prostate volume (ETD, PSAD, and BPCD, respectively). The ratio of percentage of cancer invading the gland (tumor load, TL) on prostate weight (TLD) was also calculated. Unfavorable disease (UD) was defined as tumor upgrading (ISUP >3) and/or upstaging (pT >2) and/or lymph node invasion (LNI). Associations of ETD with features of aggressive PCa, including UD and TLD, were evaluated by logistic and linear regression models. Results: Evaluated cases were 338. Subjects with upgrading, upstaging, and LNI were 61/338 (18%), 73/338 (21%), and 25/338 (7.4%), respectively. TLD correlated with UD (Pearson’s correlation coefficient, r = 0.204; p < 0.0001), PSAD (r = 0.342; p < 0.0001), BPCD (r = 0.364; p < 0.0001), and ETD (r = 0.214; p < 0.0001), which also correlated with BMI (r = −0.223; p < 0.0001), PSAD (r = 0.391; p < 0.0001), and BPCD (r = 0.407; p < 0.0001). TLD was the strongest independent predictor of UD (OR = 2.244; 95% CI = 1.146–4.395; p = 0.018). In the multivariate linear regression model predicting BPCD, ETD was an independent predictor (linear regression coefficient, b = 0.026; 95% CI: 0.016–0.036; p < 0.0001) together with PSAD (b = 1.599; 95% CI: 0.863–2.334; p < 0.0001) and TLD (b = 0.489; 95% CI: 0.274–0.706; p < 0.0001). According to models, TLD increased as ETD increased accordingly, but mean ET levels were significantly lower for patients with UD. Conclusions: As ETD measurements incremented, the risk of large tumors extending beyond the prostate increased accordingly, and patients with lower ET levels were more likely to occult UD. The influence of ETD on PCa biology should be addressed by prospective studies.

Real-world evidence of patients with metastatic castration-resistant prostate cancer treated with cabazitaxel: comparison with the randomized clinical study CARD

BackgroundThe CARD study demonstrated superiority of cabazitaxel over abiraterone/enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who received prior docetaxel and progressed ≤12 months on the alternative androgen-receptor-targeted agent (ARTA). The objective was to compare characteristics and treatment patterns of patients from a real-world dataset with the CARD population.MethodsReal-world data were collected from Medimix Live TrackerTM, a retrospective, global oncology database of healthcare professional-reported electronic patient medical forms (2001–2019), with data from patients from Europe, USA, Brazil and Japan. The database contained patient, tumor and treatment information for 12,140 patients who received ≥1 line of treatment for mCRPC. A CARD-like cohort included patients treated with docetaxel, prior abiraterone/enzalutamide and cabazitaxel.ResultsA large proportion of patients received ≥2 lines of ARTA (35.1%) with 42% of patients who received a first-line ARTA receiving another ARTA in second line. Of the total patients, 452 were eligible for the CARD-like cohort. Median age of the CARD-like cohort was comparable to CARD (73 vs 70 years). The CARD-like cohort had unfavorable disease characteristics vs CARD: ECOG PS ≥ 2 (45% vs 4.7%); metastasis at diagnosis (46% vs 38%) and Gleason 8–10 (65% vs 57%). More patients in the CARD-like cohort received ARTA before docetaxel (48% vs 39%) and received the first ARTA for >12 months (30% vs 17%) compared with CARD. Despite more patients in the CARD-like cohort receiving the lower 20 mg/m2 dose of cabazitaxel (55% vs 21%), cabazitaxel treatment duration was similar (21.9 vs 22.0 weeks).ConclusionsSequential use of ARTA was frequent. Results indicate the CARD population is reflective of routine clinical practice and duration of response to cabazitaxel was similar in a real-world population.

ЕФЕКТИВНІСТЬ ЛІКУВАННЯ ТУБЕРКУЛЬОЗУ ЛЕГЕНЬ В ЗАЛЕЖНОСТІ ВІД ГЕНОТИПУ CYP3A4

Among the factors that can influence the course and effectiveness of the treatment of pulmonary tuberculosis (TB) the genetic characteristics of patients play an important role. It is established that cytochrome (CYP) 3A4/5 is involved in metabolism of more than 30 % of xenobiotics. Consequently, the activity of this enzyme is greatly influenced by responsible genes, such as CYP3А4. The aim of the study was the investigation of prognostic value of CYP3A4 polymorphism on the course and effectiveness of anti-tuberculosis therapy in patients with pulmonary TB. Materials and methods. Using PCR method, a detection of polymorphism of CYP3A4*1B, CYP3A4*1G genes, which determine the activity of CYP3A4 enzyme, was performed in 105 patients with newly diagnosed pulmonary TB. We have revied medical records at the beginning and at the end of inpatient treatment and considered the form, extent, regression rate of TB-lesions, and the rate of smear-positive cases. A statistical analysis of study data, expressed in absolute or relative values, was done using Pearson’s chi-squared test. Results: It was established that out of 105 enrolled TB-patients 84 individuals (80,0%) carried the genotype of “rapid metabolizers” (RA), the rest – 15 (14,3%) and 6 (5,7%) individuals were “intermediate metabolizers” (IM) and “slow metabolizers” (SM) correspondently. According to CYP3A4 genotype in patients with SM and IM the bi-lateral lesions as well as the processes of pulmonary destruction and dissemination, as well as smearpositiveness occurred more frequently than in RM. For example, in IM group the dissemination was observed almost two times more frequently than in RM (Р&lt;0,05; χ2=4,44). At the end of the in-patient treatment in SM remaining TB-infiltrates observed more often, while the resolution of consolidation registered more rarely (66,7%) than in IM and RM (81,0% and 80,0%, correspondently). Also, in SM the TB infiltrates remained more often than in RM (33,3% versus 8,3%, Р&lt;0,05; χ2=4,44). At the same time in IM the smear-positive status remained more often than in other groups. Conclusion. Genotypes of “intermediate metabolizers” and “slow metabolizers” according to CYP3A4 genes were associated with unfavorable pulmonary disease both at initiation and at the end of in-patient phase of the TB treatment. Identification of CYP3A4 genotype in pulmonary TB patients allows allocation of the groups of high risk of unfavorable TB course. Key words: pulmonary tuberculo

ЮВЕНИЛЬНЫЙ ИДИОПАТИЧЕСКИЙ АРТРИТ И СИСТЕМНАЯ КРАСНАЯ ВОЛЧАНКА В ДЕТСКОМ ВОЗРАСТЕ: ЧАСТОТА, ПРИЧИНЫ, КЛАССИФИКАЦИЯ, КЛИНИЧЕСКИЕ ПРОЯВЛЕНИЯ

Juvenile idiopathic arthritis (JIA) is one of the most common and most disabling rheumatic diseases in children. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with unknown etiology, which is based on a genetically determined dysregulation of immunity. In recent years, the view of JIA and SLE as potentially incurable and prognostically unfavorable diseases has been revised. This is largely due to the expansion of the possibilities of early diagnosis of JIA, SLE, which allows starting active therapy at the onset of the disease, the development of a new class of basic anti-inflammatory drugs, and scientific research in the genetics of both diseases. A large number of genes associated with immune responses can, induce an autoimmune response - the leading pathogenetic link in both diseases. The article presents modern data on the possible pathogenesis, spectrum of clinical manifestations of juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE) in children. A brief description of the pathological changes in JIA and SLE is given. Possible factors are considered, incl. genetic, affecting the predisposition to the disease, the process of the formation of organ damage. The issues of assessing the activity of diseases, assessing the quality of life of patients are discussed in detail.

A Comparative Retrospective Study of in Situ Split Plus Portal Vein Ligation (ISLT) Versus Conventional Two-Stage Hepatectomy for Cholangiocellular Carcinoma - Does the ISLT Procedure Have an Oncological Advantage?

Introduction: Cholangiocellular carcinoma (CCA) has a poor prognosis and the mainstay of therapy even in locally advanced cases remains radical surgical resection. This approach however is limited by the future liver remnant (FLR) volume after extensive parenchymal dissection leading to postoperative liver failure and high mortality rates. The aim of this study was to compare the outcome of in situ liver transection with portal vein ligation (ISLT) procedure and conventional two-stage hepatectomy with portal vein embolization (PVE/TSH) in patients with CCA. Methods: All patients with CCA and insufficient FLR considered for either ISLT or PVE/TSH were analyzed for outcomes including postoperative morbidity and mortality as well as overall survival rates (OS). Results: Of the total 24 patients included, 16 patients received ISLT. The remaining 8 patients underwent PVE/TSH. The completion rate of the second stage in the PVE/TSH group was 62% and 100% in the ISLT group (p=0.027). The overall 90-days-morbidity was comparable (PVE/TSH 40% vs. ISLT 69%, p=0.262). OS at follow-up (median: 7 months) did not significantly differ between the two groups (p>0.05). In multivariate analysis, biliary resection and reconstruction was the only risk factor independently associated with significantly higher morbidity and mortality rates (HR=23.33; 95%CI (1.99-273.29); p=0.012). Conclusion: Our results demonstrate comparable outcomes in both groups in a rather prognostically unfavourable disease. The completion rate in the ISLT group was significantly higher than in the PVE/TSH cohort. This work encourages specialized HPB centers in applying the ISLT procedure in selected cases with cholangiocellular carcinoma.

Association of structural changes of the brain with systemic immune activation in schizophrenia

The goal of this work was to investigate the associations between IL-17A levels and structural MRI findings to clarify immune factors of pathogenesis and search for biomarkers of unfavorable disease course. 45 patients with schizophrenia and 30 healthy volunteers were enrolled into the study. The levels of cytokines (IL-1β, IL-4, IL-6, IL-8, IL-17A) and inflammatory markers were determined by ELISA. MRI scans were performed on a Siemens Magnetom Verio 3T MRI scanner. It was found that elevated levels of cytokine IL-17A are associated with morphometric changes in the frontal cortex, signs of systemic inflammation and Th2 activation of the adaptive immune system in the patients. These findings make an important contribution to understanding the role of immune disorders in the pathogenesis of schizophrenia, including brain structure disorders, and indicate that IL-17A may be a biomarker of these disorders. Confirmation of correlations between structural neuroimaging and markers of inflammation may provide the basis for new interdisciplinary approaches to the diagnosis and prognosis of schizophrenia.

Lung cancer incidence and mortality trends in the Republic of Belarus (1990–2019)

Аннотация:&#x0D; &#x0D; Relevance: Lung cancer is one of the most frequent and unfavorable malignant diseases globally. The Republic of Belarus ranks third (8.2%) in cancer incidence and first (21.5%) in cancer mortality.&#x0D; The object of the study was the lung cancer incidence and mortality trends in the Republic of Kazakhstan in 1990-2019.&#x0D; Results: In the study period, the standardized incidence rate decreased from 27.5 to 25.6 per 100 000 population (- 7.1%, p&lt;0.01). In males, it decreased from 62.1 to 54.6 per 100 000 males (- 12.1%, p&lt;0.001); in females, it increased from 5.3 to 6.4 per 100 000 females (+20.7%, p&lt;0.05). The standardized lung cancer mortality rate has decreased over the study period from 23.0 to 18.3 per 100 000 population (- 20.4%, p&lt;0.001). In males, it went down from 53.6 to 40.7 (- 24.1%, p&lt;0.001), and in women it changed slightly from 3.6 to 3.7 (+ 2.8%, p&gt;0.05) per 100 000 of the relevant sex. The average annual increase in standardized mortality decreased eight times&#x0D; faster than the growth in standardized incidence.&#x0D; Conclusion: In the Republic of Belarus, lung cancer incidence is increasing in males and decreasing in females. At that, lung cancer mortality is decreasing. Quality specialized cancer care creates conditions for quicker negative growth of lung cancer standardized mortality vs. incidence

Evaluation of Intensive Care Measures in Children with Severe New Coronavirus Infection in Pediatric Intensive Care Units

Currently, the number of publications on specific features of the clinical course and outcomes of new coronavirus infection COVID-19 in children is steadily increasing, but there are practically no works demonstrating the effectiveness of intensive care interventions, which served as the basis for the present analysis.The objective is to assess the effectiveness of primary intensive care interventions in children with a severe course of new coronavirus infection.Subjects and Methods. 94 patients were examined. Evaluation of intensive care measures was carried out upon admission to ICU.Results. It was found that corticosteroids were used only in 55 (58.5%) patients (χ2 = 5.254, p = 0.022, Pearson conjugation criterion = 0.130). A moderate correlation was established between the unjustified prescription of prednisolone and the unfavorable disease outcome (χ2 = 27.98, p &lt; 0.001, Pearson conjugation criterion = 0.296). The moderate strength of the association between the prescription of antibacterial drugs and the disease outcome was noted (χ2 = 34.01, p &lt; 0.001, Pearson conjugation criterion = 0.331). In all lethal cases, there was volume overload due to excessive intravenous fluid administration (χ2 = 5.14, p = 0.024).Conclusion: individual therapeutic strategies do not have a direct significant impact on outcomes of new coronavirus infection in children, however, the delivery of comprehensive intensive care presented in clinical guidelines is associated with the patient's recovery.

Integrating primary, behavioral and spiritual health care to improve patient outcomes

Background: Residents of Webb County, Texas, along the U.S.-Mexico border suffer from health disparities which stem from extreme poverty, lower levels of educational attainment, and inadequate access to basic health care. The scarcity of primary care and behavioral health service providers is a key factor influencing higher-than-average disease prevalence and unfavorable disease management in the region. In 2015 Mercy Ministries of Laredo became one of eight subgrantees of a grant awarded by the Social Innovation Fund to Methodist Healthcare Ministries of San Antonio to enhance/expand integrated primary care and behavioral health care services in medically underserved areas of South Texas. Methods: Mercy’s project embodied a 3-dimensional model of health and healthcare, to include physical, behavioral and spiritual needs and interventions. With strong support from a research design and analysis group, this small clinic was able to demonstrate statistically significant improved health outcomes of several interventions. A non-randomized quasi experimental design (QED) was used and participants chose whether to participate in the intervention (207) or control (203) group. Common variables for all eight subgrantees included five overarching measures (HbA1C, blood pressure, BMI, PHQ-9 and quality of life score) and depression outcomes were used to statistically power all subgrantee studies. Results: Intervention group participants had significantly greater improvements in quality of life and anxiety symptoms when compared with comparison group participants. Intervention participants had a Duke General Health score 4.01 points higher and a GAD-7 score 0.79 points lower than those in the comparison group. There were also significant improvements for intervention participants over time for these two outcomes as well as depression symptoms. Conclusions: Grant funded resources enhanced health outcomes and prompted this small clinic to expand integrated primary and behavioral health services to serve the entire clinic population and promote integrated primary and behavioral health care for other underserved populations.

Clinical significance of unfavorable findings in intermediate-risk prostate cancer patients for predicting treatment outcomes after contemporary, dose-escalated multimodal radiotherapy.

Few studies have documented the long-term oncological outcomes of favorable and unfavorable intermediate-risk (IR) prostate cancer patients treated via contemporary high-dose irradiation. We analyzed the ultimate clinical outcomes of such patients using the current risk sub-stratification schema. We included 693 patients with localized IR prostate cancer treated via low-dose-rate brachytherapy (LDR-BT) with or without external beam radiation (EBRT) and with or without androgen-deprivation therapy (ADT) in a single institution. Treatment outcomes (biochemical recurrence-free survival [BCRFS] and clinical progression-free survival [CPFS]) were compared according to the numbers of unfavorable findings. Out of the 693 IR patients, 292 (42.1%) exhibited favorable disease; the remaining 401 (57.9%) exhibited unfavorable disease. Compared with favorable IR status, unfavorable IR status was associated with shorter BCRFS and CPFS (p < 0.001 and p < 0.001, respectively). Patients with two to threeunfavorable factors experienced the worst oncological outcomes (p < 0.001 and p < 0.001). Although patients with one or no unfavorable factors responded similarly to LDR-BT monotherapy, this treatment modality was insufficient for preventing biochemical and clinical progression in patients with multiple unfavorable findings. Long-term treatment outcomes indicate that patients with IR disease scheduled for LDR-BT should undergo multimodal irradiation if they exhibit two or more unfavorable factors at diagnosis.

Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis

AimsThere is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure. Materials and methodsIndividual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42–54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan–Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases. ResultsSix hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9–7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5–31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1–311.6, P = 0.003). Conclusion4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.

Characteristics and outcome profile of hospitalized African patients with COVID-19: The Ethiopian context.

BackgroundThe COVID-19 pandemic seems to have a different picture in Africa; the first case was identified in the continent after it had already caused a significant loss to the rest of the world and the reported number of cases and mortality rate has been low. Understanding the characteristics and outcome of the pandemic in the African setup is therefore crucial.AimTo assess the characteristics and outcome of Patients with COVID-19 and to identify determinants of the disease outcome among patients admitted to Millennium COVID-19 Care Center in Ethiopia.MethodsA prospective cohort study was conducted among 1345 consecutively admitted RT-PCR confirmed Patients with COVID-19 from July to September, 2020. Frequency tables, KM plots, median survival times and Log-rank test were used to describe the data and compare survival distribution between groups. Cox proportional hazard survival model was used to identify determinants of time to clinical recovery and the independent variables, where adjusted hazard ratio, P-value and 95% CI for adjusted hazard ratio were used for testing significance and interpretation of results. Binary logistic regression model was used to assess the presence of a statistically significant association between disease outcome and the independent variables, where adjusted odds ratio, P-value and 95% CI for adjusted odds ratio were used for testing significance and interpretation of results.ResultsAmong the study population, 71 (5.3%) died, 72 (5.4%) were transferred and the rest 1202 (89.4%) were clinically improved. The median time to clinical recovery was 14 days. On the multivariable Cox proportional hazard model; temperature (AHR = 1.135, 95% CI = 1.011, 1.274, p-value = 0.032), COVID-19 severity (AHR = 0.660, 95% CI = 0.501, 0.869, p-value = 0.003), and cough (AHR = 0.705, 95% CI = 0.519, 0.959, p-value = 0.026) were found to be significant determinants of time to clinical recovery. On the binary logistic regression, the following factors were found to be significantly associated with disease outcome; SPO2 (AOR = 0.302, 95% CI = 0.193, 0.474, p-value = 0.0001), shortness of breath (AOR = 0.354, 95% CI = 0.213, 0.590, p-value = 0.0001) and diabetes mellitus (AOR = 0.549, 95% CI = 0.337, 0.894, p-value = 0.016).ConclusionsThe average duration of time to clinical recovery was 14 days and 89.4% of the patients achieved clinical recovery. The mortality rate of the studied population is lower than reports from other countries including those in Africa. Having severe COVID-19 disease severity and presenting with cough were found to be associated with delayed clinical recovery of the disease. On the other hand, being hyperthermic is associated with shorter disease duration (faster time to clinical recovery). In addition, lower oxygen saturation, subjective complaint of shortness of breath and being diabetic were associated with unfavorable disease outcome. Therefore, patients with these factors should be followed cautiously for a better outcome.

Treatment Responses, Toxicity and Survival in Patients with Classical Hodgkin Lymphoma Aged 50 Years and Older: A Single-Center Experience over 2 Decades

Introduction: The prognosis of classical Hodgkin lymphoma (cHL) is generally inferior in elderly patients (pts) than in younger pts. Tolerance of conventional therapy decreases in elderly pts, and in addition, treatment-related toxicities and death are more common. While the 5-year overall survival (OS) of pts with cHL is 86.6%, this rate is 57.5% in elderly pts.Objective and Methods: The aim of this study was to retrospectively evaluate the demographic, histopathological, clinical, and laboratory features, prognosis determination according to German Hodgkin Study Group (GHSG) in early-stage, International Prognostic Score (IPS)-3 and IPS-7 in advanced-stage, ECOG (Eastern Cooperative Oncology Group) performance scale (PS), Cumulative Disease Rating Score (CIRS) , Charlson Comorbidity Index (CCI), Adult Comorbidity Evaluation-27 (ACE-27) values, treatment responses, toxicities, and survival among cHL pts aged 50 years and older who were diagnosed between 1999 and 2020.Results: There were 101 pts in total, of which 52 were between 50-59 years of age, and 49 pts were ≥60 years. Sixty-two pts were male, and the most common histopathological subtype was mixed cellularity CHL with 58.4%. Fifty-four pts had advanced-stage disease, while there were 31 and 16 pts with early-stage unfavorable and favorable diseases, respectively. Sixty-one pts (60.4%) had B symptoms (Table 1). ECOG PS, CIRS, CCI, and ACE-27 scores were significantly higher in pts aged ≥60 years than those of 50-59 age group (Table 2). While all pts aged 50-59 years received ABVD as first-line therapy, 79% (n=39) of pts aged ≥60 years had ABVD. Among pts receiving ABVD as a first-line treatment, 82% (n=41) of pts aged 50-59 years and 73.2% (n=30) of pts aged ≥60 years had complete response following first-line treatment (p=0.312). Overall, at interim evaluation, response rates to first-line therapy were significantly higher in pts with IPS-7 value 0-3 (71.8%) than those with IPS-7 value 4-7 (42.9%) (p=0.028). While full-dose treatment was administered to 71 pts (70.3%), 30 pts (29.7%) needed a dose reduction. The percentage of pts needed a dose reduction was 38.8% among pts ≥60 years, whereas this was 21.2% for pts aged 50-59 years (p=0.053). During the follow-up, grades 3-4 hematological and non-hematological toxicities were observed in 50 (49.5%) and 15 pts (14.9%), respectively. Age groups were comparable in terms of hematological and non-hematological toxicities (p=0.369, p=0.127, respectively). None of the pts in the ≥60 age group had received high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDC with AHSCT)/allogeneic hematopoietic stem cell transplantation (allo-HSCT). On the other hand, 8 pts (15.4%) diagnosed between 50-59 years of age underwent HDC with AHSCT, in one patient (1.9%) allo-HSCT was performed, and one patient (1.9%) received both HDC with AHSCT and allo-HSCT (p=0.004). There was no significant difference in terms of OS between those with and without transplantation (p=0.069). In the multivariate analysis, the risk of progression was higher in pts with lymphocyte ≤600/mm 3 and the risk of mortality was higher in pts with B symptoms (p=0.002, p=0.012, respectively). In addition, progression-free survival (PFS) was inferior in pts who were unresponsive to first-line treatment, and worse OS was associated with higher age and CIRS (p<0.001, p=0.001, p=0.038, respectively) (Fig. 1A-C). During their follow-up, 26 pts (25.7%) died, and the causes of death could be determined in 19 of them. The most common cause of death was treatment complications (n=7). Secondary malignancies were detected in 5 pts, of which 3 died. In 2 pts, the cause of death was HL-related, and 7 pts died due to other causes.Conclusion: Although not statistically significant, the percentage of pts needing a dose reduction was higher in pts aged ≥60 years, on the other hand, treatment responses and toxicities were similar in both groups, most probably due to personalized treatment selection and dose reduction according to age, comorbidities, and the performance status. Pts undergoing a transplant had a more favorable outcome than pts without a transplant, but the difference did not reach statistical significance. Response to first-line therapy was associated with superior PFS, and pts with higher age and CIRS had inferior OS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Mortality Trends in Multiple Myeloma after the Introduction of Novel Therapies in the United States

Mortality Trends in Multiple Myeloma after the Introduction of Novel Therapies in the United States