Five-year Survival Probability Research Articles

Combined use of Donepezil and Memantine increases the probability of five-year survival of Alzheimer’s disease patients

BackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.MethodsWe conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. Also, we formally tested for the presence of interaction between these drugs.ResultsHere, we show that the combined use of Donepezil and Memantine significantly elevates the probability of five-year survival. In particular, their combined use increases the probability of five-year survival by 0.050 (0.021, 0.078) (6.4%), 0.049 (0.012, 0.085), (6.3%), 0.065 (0.035, 0.095) (8.3%) compared to no drug treatment, the Memantine monotherapy, and the Donepezil monotherapy respectively. We also identify a significant beneficial additive drug-drug interaction effect between Donepezil and Memantine of 0.064 (0.030, 0.098).ConclusionsBased on our findings, adopting combined treatment of Memantine and Donepezil could extend the lives of approximately 303,000 people with AD living in the USA to be beyond five-years from diagnosis. If these patients instead have no drug treatment, Memantine monotherapy or Donepezil monotherapy they would be expected to die within five years.

Identification of prognostic signatures in remnant gastric cancer through an interpretable risk model based on machine learning: a multicenter cohort study

ObjectiveThe purpose of this study was to develop an individual survival prediction model based on multiple machine learning (ML) algorithms to predict survival probability for remnant gastric cancer (RGC).MethodsClinicopathologic data of 286 patients with RGC undergoing operation (radical resection and palliative resection) from a multi-institution database were enrolled and analyzed retrospectively. These individuals were split into training (80%) and test cohort (20%) by using random allocation. Nine commonly used ML methods were employed to construct survival prediction models. Algorithm performance was estimated by analyzing accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), confusion matrices, five-fold cross-validation, decision curve analysis (DCA), and calibration curve. The best model was selected through appropriate verification and validation and was suitably explained by the SHapley Additive exPlanations (SHAP) approach.ResultsCompared with the traditional methods, the RGC survival prediction models employing ML exhibited good performance. Except for the decision tree model, all other models performed well, with a mean ROC AUC above 0.7. The DCA findings suggest that the developed models have the potential to enhance clinical decision-making processes, thereby improving patient outcomes. The calibration curve reveals that all models except the decision tree model displayed commendable predictive performance. Through CatBoost-based modeling and SHAP analysis, the five-year survival probability is significantly influenced by several factors: the lymph node ratio (LNR), T stage, tumor size, resection margins, perineural invasion, and distant metastasis.ConclusionsThis study established predictive models for survival probability at five years in RGC patients based on ML algorithms which showed high accuracy and applicative value.

Bioelectrical Impedance Phase Angle Value and Prolongations of PR and Corrected QT Intervals in Patients Undergoing Dialysis

Introduction: Phase angle value, derived from bioelectrical impedance analysis, represents the body cell mass and nutritional status of patients undergoing hemodialysis. Although the phase angle value has clinical significance in these patients, its relationship with electrocardiogram (ECG), another clinically relevant bioelectrical examination, has not yet been well clarified. Methods: Two hundred and twenty-four patients undergoing dialysis (80 females and 144 males; mean ± SD, 72.2 ± 12.0 years old; 117 diabetic and 107 nondiabetic patients) were studied retrospectively. Multifrequency bioelectrical impedance analysis was performed immediately after the end of dialysis therapy. The phase shift was geometrically converted into a phase angle value. The ECG was recorded simultaneously, and the upper limits of the PR interval, QRS width, and corrected QT interval (QTc) were set at 0.20, 0.12, and 0.44 s, respectively. The geriatric nutritional risk index (GNRI), a representative nutritional index, was also determined. In addition, we examined the incidence of cardiac events, including heart failure, myocardial infarction, cardiac revascularization procedure, cardiac arrhythmia, and cardiac death, or all-cause death. Results: Of 224 patients undergoing dialysis, the prolongation of the PR interval, QRS width, and QTc was found in 30.7, 17.4, and 62.1%, respectively. The prevalence of QTc prolongation was higher in females and diabetic patients than in males and nondiabetic patients. An inverse relationship between phase angle value and QTc was observed only in males and nondiabetic patients. The relationships of GNRI both with phase angle value and QTc were stronger in males and nondiabetic patients. In addition, PR interval was inversely correlated with a phase angle value only in nondiabetic patients. No significant correlation was found between phase angle value and QRS width. Five-year survival probability for the composite endpoints was significantly worse in patients with lower phase angle values. QTc prolongation was associated with survival in males and nondiabetic patients. Prolonged PR was associated with survival in nondiabetic patients. Discussion: Relationships between phase angle value and ECG findings were demonstrated in patients undergoing dialysis, especially in males and nondiabetic patients. Although the phase angle value has been considered as an index for evaluating nutritional status, another clinical application of phase angle value in predicting cardiac complications seems to be useful.

Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. We used data from the European Renal Association (ERA) Registry on 69854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival. The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

CyberKnife® stereotactic radiation therapy for stage I lung cancer and pulmonary oligometastases: is fiducial implantation still relevant?-a cohort study.

Few studies have investigated whether there is a difference in local control or overall survival rates following treatment with robotic stereotactic body radiation therapy (SBRT) with or without prior fiducial marker implantation. Our study aimed to investigate this in patients with primary or secondary lung tumors. A retrospective study was conducted at the Institut de Cancérologie de Lorraine of patients treated for primary lung cancer or pulmonary oligometastases with SBRT from January 2013 to July 2016. We included patients at least 18 years old who had stage I non-small cell lung cancer (NSCLC) or lung metastases and a follow-up of at least 1 month. A total of 294 patients were included. Tumors included 122 lung metastases, 89 stage I NSCLC, and 83 non-histologically confirmed lung lesions. The tracking methods were Synchrony® in 191 cases (119 gold seeds and 72 coils) and Xsight® Spine with 4D computed tomography in 103 cases. Median follow-up was 31.6 months [interquartile range (IQR), 18.1-50.2 months]. The two- and five-year probability of local control were respectively 92.22% [95% confidence interval (CI): 0.89-0.95] and 85.35% (95% CI: 0.79-0.99). The two- and five-year probability of overall survival were respectively 87.46% and 72.77% (P=0.586). Local control rates did not significantly differ between techniques at 2 and 5 years (P=0.685) (gold seeds, coils or Xsight® Spine) within tumors grouped by location, gross tumor volume (GTV) (respectively P=0.9, P=0.7, and P=0.4), planning target volume (PTV) (respectively P=0.4, P=0.9, and P=0.7), or PTV/GTV ratio (respectively P=0.6, P=0.6, and P=0.5). Metastasis-free survival and Overall survival rates did not significantly differ between techniques at 2 and 5 years (P=0.664 and P=0.586, respectively). There were no grade 4 or 5 toxicities and only one grade 3 pneumonitis and one grade 3 pneumothorax. Fiducial-less SBRT using Xsight® Spine is a safe alternative to Synchrony® using gold seeds or coils, with comparable local control and overall survival rates and a similar toxicity profile.

Is Mixed Chimerism Post-allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Acute Lymphoid Leukemia a Prognostic Factor for Relapse?

Hematopoietic stem cell transplantation (HSCT) has been considered curative for children with high-risk acute leukemia (ALL), offering better survival. Short tandem repeat has been used as a marker of chimerism status after HSCT. The appearance of recipient cells >1% post-allogeneic stem cell transplant is defined as mixed chimerism (MC). Chimeric studies post-HSCT are dynamic. This study aimed to investigate the significance of recipient cells in post-HSCT pediatric ALL patients as a predictor of relapse of their primary disease. The rate of MC was 51.4% (19 out of 37 recipients). It was 48.6% (n = 18) during Day+100 and 12.9% (4 out of 31 recipients) during post-Day+100 follow-up until two years. No significant association was noted between MC and all grade overall acute graft-versus-host disease. A mortality rate of 35.1% (n = 13) and a median follow-up of 56.9 months (95% CI: 39.7-74.2) were observed for all but four (16.7%) of the survivors in remission. Regarding causes of death, transplant-related mortality was recorded in only 2 of 13 expired patients (15.4%); both succumbed to sepsis. No significant association was found between MC and primary causes of death. The cumulative probability of five-year overall survival and event-free survival was not found to be statistically significantly different for MC (≤1.0% vs. > 1.0%). In conclusion, our data did not show MC testing alone as an effective prognostic marker for detecting relapse; molecular and flow cytometric analyses should be considered in children with ALL post-HSCT for monitoring relapse.

#3524 INCIDENCE AND OUTCOMES OF KIDNEY REPLACEMENT THERAPY FOR END-STAGE KIDNEY DISEASE DUE TO PRIMARY GLOMERULONEPHRITIS IN THE ERA REGISTRY

Abstract Background and Aims Primary glomerulonephritis (PGN) is among the leading causes of end-stage kidney disease (ESKD) in patients initiating kidney replacement therapy (KRT). To date, most studies have examined KRT outcomes from all PGN subgroups combined. Using data from the European Renal Association (ERA) Registry we examined trends and outcomes in individuals with PGN and its subgroups commencing KRT. Firstly, we described the incidence of KRT for ESKD due to PGN for all countries combined and by country; and secondly, we compared patient characteristics, survival outcomes, and causes of death. Method We used data from 31 national and regional renal registries providing individual patient data to the ERA Registry for at least three years between 2000-2019. PGN was categorized into six subgroups based on the ERA primary renal disease codes: Immunoglobulin A nephropathy [IgAN], membroproliferative glomerulonephritis [MPGN] (type I and type II), membranous nephropathy [MN], focal segmental glomerulosclerosis [FSGS], crescentic glomerulonephritis [crescentic GN], and other PGN (histologically examined and histologically not examined). The age-and-sex-standardized incidences were estimated using the 2015 EU28 population as a reference. Joinpoint regression analysis was used to determine the annual percentage change (APC) in the incidence. Kaplan Meier and Cox regression analyses were used for the survival analyses. We adjusted for age, sex, KRT initiation era, and country. Results In total, 69,854 individuals started KRT due to PGN between 2000-2019, of whom 27.8% had IgAN, 15.8% FSGS, 8.5% MPGN, 5.8% crescentic GN, and 4.5% MN. The remaining 37.7% were categorized as” other PGN’’ (14.1% not biopsied). The standardized incidence of KRT due to PGN was 16.6 per million population (pmp), ranging from 8.8 pmp in Serbia to 20.0 pmp in France. The incidence was the highest for IgAN (4.6 pmp) and FSGS (2.6 pmp) particularly in age group 65-74 year. The incidence of KRT due to PGN [APC: -1.8% (-2.2; -1.4)] declined between 2000-2013, then it stabilized. Conversely, the incidence of KRT due to IgAN [APC: 5.1% (2.7;7.6)] between 2012-2019 and due to FSGS [APC: 3.1% (2.3-3.8)] between 2000-2019 increased. During a five-year follow-up 8,928 patients died. The five-year survival probabilities varied from 57.0% for crescentic GN to 83.6% for IgAN. The risk of death was highest in crescentic GN [The adjusted hazard ratio: 1.8 (95% confidence interval: 1.6-1.9)] compared to IgAN. Cardiovascular disease was the most common cause of death (33.9%) followed by infection (18.5%). Conclusion The incidence of KRT due to PGN was highest in IgAN and FSGS and varied largely across the European countries. The number of non- histologically examined PGN cases remains high, especially in Eastern Europe, which may reflect a lack of renal biopsy facilities which in turn hamper reporting of the true histological diagnosis. There was an initial decline in the incidence of KRT due to PGN, followed by stabilization. This could imply advances in the management protocols with better prognosis. Further studies are needed to explain the observed difference in the incidence over time and to identify factors leading to less initiation of KRT among patients with PGN.

A Comparison between the Online Prognostic Tool PREDICT and myBeST for Women with Breast Cancer in Malaysia.

The PREDICT breast cancer is a well-known online calculator to estimate survival probability. We developed a new prognostic model, myBeST, due to the PREDICT tool's limitations when applied to our patients. This study aims to compare the performance of the two models for women with breast cancer in Malaysia. A total of 532 stage I to III patient records who underwent surgical treatment were analysed. They were diagnosed between 2012 and 2016 in seven centres. We obtained baseline predictors and survival outcomes by reviewing patients' medical records. We compare PREDICT and myBeST tools' discriminant performance using receiver-operating characteristic (ROC) analysis. The five-year observed survival was 80.3% (95% CI: 77.0, 83.7). For this cohort, the median five-year survival probabilities estimated by PREDICT and myBeST were 85.8% and 82.6%, respectively. The area under the ROC curve for five-year survival by myBeST was 0.78 (95% CI: 0.73, 0.82) and for PREDICT was 0.75 (95% CI: 0.70, 0.80). Both tools show good performance, with myBeST marginally outperforms PREDICT discriminant performance. Thus, the new prognostic model is perhaps more suitable for women with breast cancer in Malaysia.

Minimally invasive interval debulking surgery for advanced ovarian cancer after neoadjuvant chemotherapy

ObjectiveAssess outcomes of interval debulking surgery (IDS) after neoadjuvant chemotherapy via minimally invasive surgery (MIS) compared with laparotomy in patients with advanced epithelial ovarian cancer. MethodsPatients diagnosed with stage IIIC or IV epithelial ovarian cancer between 2013 and 2018 who received neoadjuvant chemotherapy and IDS were identified in the National Cancer Database. Primary outcome was overall survival. Secondary outcomes were 5-year survival, 30- and 90-day postoperative mortality, extent of surgery, residual disease, hospitalization duration, surgical conversions, and unplanned readmissions. Propensity score matching was used to compare MIS and laparotomy for IDS. Association of treatment approach with overall survival was assessed using Kaplan-Meier method and Cox regression. Sensitivity analysis was conducted for effect of unmeasured confounders. ResultsA total of 7897 patients met inclusion criteria; 2021 (25.6%) underwent MIS. Percentage undergoing MIS increased from 20.3%–29.0% over the study period. After propensity score matching, median overall survival was 46.7 months in the MIS group versus 41.0 months in the laparotomy group [hazard ratio (HR) 0.86 (95%CI 0.79–0.94)]. Five-year survival probability was higher in MIS versus laparotomy (38.3% vs 34.8%, p < 0.01). There was lower 30- and 90-day mortality (0.3% vs 0.7% [p = 0.04] and 1.4% vs 2.5% [p = 0.01], respectively), shorter length of stay (median 3 vs 5 days, p < 0.01), lower residual disease (23.9% vs 26.7%, p < 0.01), and lower additional cytoreductive procedures (59.3% vs 70.8%, p < 0.01) in MIS compared to laparotomy, with similar rates of unplanned readmission (2.7% vs 3.1%, p = 0.39). ConclusionsPatients who undergo IDS by MIS have similar overall survival and decreased morbidity compared with laparotomy.

Prevalence and descriptive epidemiology of Turner syndrome in the United States, 2000-2017: A report from the National Birth Defects Prevention Network.

The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 female live births (95% CI=3.0-3.3, program range: 1.0-10.4), and 1.9 for live birth and stillbirth (≥20 weeks gestation) cases (95% CI=1.8-2.1, program range: 0.2-3.9). Prevalence was lowest among cases born to non-Hispanic Black women compared to non-Hispanic White women (PR=0.5, 95% CI=0.4-0.6). Coarctation of the aorta was the most common defect (11.6% of cases), and across the cohort, individuals without hypoplastic left heart had a five-year survival probability of 94.6%. The findings from this population-based study may inform surveillance practices, prenatal counseling, and diagnosis. We also identified racial and ethnic disparities in prevalence, an observation that warrants further investigation.

Racial Disparities in Survival Outcomes of Patients With Serous Epithelial Ovarian Cancer: A Retrospective Cohort Analysis.

To identify racial disparities in five-year survival rates in women affected by serous epithelial ovarian carcinoma in the United States (US). This retrospective cohort study analyzed data from the 2010 to 2016 Surveillance, Epidemiology, and End Results (SEER) program database. Women with a primary malignancy of serous epithelial ovarian carcinoma, using International Classification of Diseases for Oncology (ICD-O) Topography Coding and ICD-O-3 Histology Coding, were included in this study. Race and ethnicity were combined into the following groups: Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Non-Hispanic Asian/Pacific Islander (NHAPI), Non-Hispanic Other (NHO), and Hispanics. Cancer-specific survival was measured at five years post-diagnosis. A comparison of baseline characteristics was assessed using Chi-squared tests. Unadjusted and adjusted Cox regression models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (CI). From 2010 to 2016, there were 9,630 women with a primary diagnosis of serous ovarian carcinoma identified in the SEER database. A higher proportion of Asian/PI women (90.7%) were diagnosed with high-grade malignancy (poorly differentiated/undifferentiated) compared to NHW women (85.4%). NHB women (9.7%) were less likely to undergo surgery when compared to NHW women (6.7%). Hispanic women had the highest proportion of uninsured women (5.9%), while NHW and NHAPI had the lowest (2.2% each). A higher proportion of NHB (74.2%) and Asian/PI (71.3%) women presented with the distant disease compared to NHW women (70.2%). After adjustment for age, insurance, marital status, stage, metastases, and surgical resection, NHB women had the highest hazard of death within five years compared to NHW women (adjusted (adj) HR 1.22, 95% CI 1.09-1.36, p<0.001). Hispanic women also had lower five-year survival probabilities compared to NHW women (adj HR 1.21, 95% CI 1.12-1.30, p<0.001). Patients undergoing surgery had significantly increased survival probability compared to those who did not (p<0.001). As expected, women with Grade III and Grade IV disease both had significantly lower five-year survival probabilities compared to Grade I (p<0.001). This study reveals that there is an association between race and overall survival in patients with serous ovarian carcinoma, with NHB and Hispanic women having the highest hazards of death compared to NHW women. This adds to the existing body of literature as survival outcomes in Hispanic patients relative to NHW patients are not well documented. Because of the potential interplay between overall survival and several factors including race, future studies should aim to investigate other socioeconomic factors that may be impacting survival.

A comparative study of minimally invasive aortic valve replacement with sutureless biological versus mechanical prostheses.

The ministernotomy approach with sutureless aortic bioprosthesis may provide an attractive and safe option for aortic valve disease patients. To assess the early and mid-term outcomes of minimally invasive aortic valve replacement (miniAVR) with sutureless vs. standard prostheses. The study involved 76 consecutive patients (51 males and 25 females) with mean age of 63.2 years who were treated with miniAVR between 2015 and 2022. They were divided into 2 subgroups: group I (n = 40) subjects with sutureless bioprostheses and group II (n = 36) with standard prostheses implanted. Early and mid-term outcomes were evaluated. A probability of survival was estimated by means of the Kaplan-Meier method. No conversion to complete sternotomy was necessary. The median (minimum; maximum) aorta cross clamping and cardio-pulmonary bypass times were 49 (27; 84) and 70 (40; 188) minutes in group I whereas 69 (50; 103) and 95 (69; 170) minutes in group II, respectively (p < 0.001). In-hospital mortality was 5.0% (n = 2) and 2.8% (n = 1) in group I vs. II, respectively (ns). Permanent ICD implantation was performed in 8 (20.0%) in group I and in 3 (8.3%) subjects in group II. In the discharge echocardiography, the function of all prostheses was correct. Five-year probability of survival was much lower in group I (0.75 ±0.10) than in group II (0.94 ±0.04). No wound infection or sternum instability was noted. Intraoperative advantages of miniAVR procedures for aortic valve patients with sutureless bioprostheses do not translate directly into improved early and middle-term outcomes.

BREAST CANCER SURVIVAL: A HOSPITAL-BASED STUDY IN REGIONAL CANCER CENTRE, BENGALURU

Introduction: Breast cancer is one of the most common cancer among Indian Women. The age adjusted rate (AAR) of Breast cancer is 42.1/100000 women in Bengaluru and it is the leading site of cancer in Bengalurian females. The hospital based cancer registry was established in 1983 and is registering around 800 Breast cancer cases per year. Most of them were diagnosed with late stage. The objective of this study is to evaluate Pattern of Care and estimate the Survival rate with respect to different stages, Treatment modalities, ER, PR, HER-2 Status of breast cancer treated only at Kidwai Cancer Institute. A retrospective cohort study was Methodology carried out with 191 Carcinoma Breast cases at a Regional Cancer Centre (Kidwai Memorial Institute of Oncology), Bengaluru. The study started from 2006-2007 and was followed-up until the end of 2020. Five-year survival (60 Months) probabilities were estimated using the Kaplan-Meier and loss adjusted survival analysis method for less than 80% follow-up group for ten years. The log rank test was used to compare the survival between the factors. The overall observed survival rates at 5years Results (60 months) was 72.7%. When analysis was conducted for specic stages, Stage II, Stage III and Stage IV survival rates are 95%, 67% and 17% respectively and is statistically signicant (p&lt;0.001), 39 Patients were dead and 13 Patients were lost for follow-up. The overall survival rate at 10 years was 62.4% and lost for follow-up was 26.5% and death was 27.7%, the Kaplan Meier analysis was unable to be carried out as more than 20% censored cases were seen, hence loss adjusted survival analysis was carried out for 10 years. 89 Patients were alive, 52 patients were dead and 50 patients were lost for follow-up at 10 years. Conclusion: In surgical histopathological nding Estrogen receptor, Progesterone receptor and HER-2 status did not have signicant impact on survival of patients. The post-operative Radiotherapy and combination of modalities of treatment had signicant effect on the long term survival of the patients after adjusting for disease stage.

Sobrevida do câncer colorretal na Grande Cuiabá, Mato Grosso, Brasil

To analyze the specific five-year survival of colorectal cancer (CRC) diagnosed between 2008 and 2013, according to sex and age group, of residents in Greater Cuiabá, state of Mato Grosso, Brazil. This is a retrospective cohort study. Specific survival of CRC was considered as the time between disease diagnosis and death from CRC, in months. Data from the Population-Based Cancer Registry and the Brazilian Mortality Information System were used. To estimate the probability of survival by sex and age group, the Kaplan-Meier estimator was used, and to estimate the effect of age group on the survival of participants, the Cox model stratified by sex was adjusted. From 2008 to 2013, 683 new cases and 193 deaths from CRC were registered. The median time between diagnosis and death from CRC was 44.8 months (95%CI 42.4- 47.3) for women and 46.1 months (95%CI 43.4-48.6) for men, and the five-year survival probabilities of 83.5% (95%CI 79.9-87.2%) and 89.6% (95%CI 86.4-93.0%), respectively. Men aged 70-79 years (HR=2.97; 95%CI 1.11-3.87) and 80 years or older (HR=3.09; 95%CI 1.31-7.27) were at higher risk of mortality, and we verified no difference for women. Women had a shorter time between the diagnosis of CRC and death from the disease as well as a lower probability of survival. Conversely, men were at higher risk of mortality after 70 years of age.

Development of Predictive Models for Survival among Women with Breast Cancer in Malaysia.

Prediction of survival probabilities based on models developed by other countries has shown inconsistent findings among Malaysian patients. This study aimed to develop predictive models for survival among women with breast cancer in Malaysia. A retrospective cohort study was conducted involving patients who were diagnosed between 2012 and 2016 in seven breast cancer centres, where their survival status was followed until 31 December 2021. A total of 13 predictors were selected to model five-year survival probabilities by applying Cox proportional hazards (PH), artificial neural networks (ANN), and decision tree (DT) classification analysis. The random-split dataset strategy was used to develop and measure the models' performance. Among 1006 patients, the majority were Malay, with ductal carcinoma, hormone-sensitive, HER2-negative, at T2-, N1-stage, without metastasis, received surgery and chemotherapy. The estimated five-year survival rate was 60.5% (95% CI: 57.6, 63.6). For Cox PH, the c-index was 0.82 for model derivation and 0.81 for validation. The model was well-calibrated. The Cox PH model outperformed the DT and ANN models in most performance indices, with the Cox PH model having the highest accuracy of 0.841. The accuracies of the DT and ANN models were 0.811 and 0.821, respectively. The Cox PH model is more useful for survival prediction in this study's setting.

Characteristics, Blood Counts, Treatments, and Clinical Outcomes of 5871 Patients with Polycythemia Vera Treated in US Community Practices

Background: Cytoreduction with hydroxyurea (HU) is the recommended first-line (1L) treatment for high-risk polycythemia vera (PV) (age ≥60 years or history of thrombosis), but many patients (pts) have suboptimal response to HU. This study describes characteristics, blood counts, treatments, and clinical outcomes among pts with PV, including those with suboptimal response to HU, in 2 large networks of US community oncology practices. Methods: This was a retrospective observational study of adult pts with a documented new diagnosis of PV in the iKnowMed electronic health record database (01Jan2008-31Jan2020), which is implemented in The US Oncology Network and non-Network practices. Pts with ≥2 postdiagnosis visits during the study observation period (01Jan2008-31Jan2021) were included in the analysis. Suboptimal response to HU was defined as meeting ≥1 of the following criteria after ≥3 months of treatment: (1) white blood cell (WBC) count >10 × 109/L, (2) platelet count >400 × 109/L, and/or (3) hematocrit (HCT) >45%. Data on demographic/clinical characteristics and prior treatment were summarized with descriptive statistics. Duration of therapy and overall survival were assessed via the Kaplan-Meier method, which censored pts without subsequent treatment discontinuation/death records at the end of the study observation period. Results: 5871 pts (The US Oncology Network, n=3022; non-Network, n=2849) met all eligibility criteria and were included in the analysis. Mean (SD) age at diagnosis was 66.1 (13.6) years (70% ≥60 years), 44% of pts were female, 87% were White, and 49% were current or former tobacco users. At diagnosis, 6% of pts had a history of thrombotic event, and 71% had high-risk PV; 38% (1535/4021), 34% (1361/4014), and 67% (2696/4010) of evaluable pts had elevated WBC (>10 × 109/L), platelets (>400 × 109/L), and HCT (>45%), respectively. Over half of pts with high-risk PV (55%; 2303/4185) received a cytoreductive agent as 1L treatment (90% HU), and 45% did not receive cytoreductive therapy. Among those with low-risk PV, 32% (540/1686) received a cytoreductive agent as 1L treatment (89% HU), and 68% did not receive cytoreductive therapy. Five-year survival probability was 82% among all pts, 79% for pts with high-risk PV (age ≥60 years or history of thrombosis), and 96% for those with low-risk PV. Overall, 56% of patients had a suboptimal response for blood count control after 3 months of treatment; this remained roughly the same at 6 months (Table). Among pts who received 1L HU, median (Q1, Q3) time from diagnosis to HU initiation was 29.0 (0.0, 252.5) days for those with high-risk PV and 103.0 (0.0, 683.5) days for those with low-risk PV; median (Q1, Q3) duration of HU was 26.7 (8.1, 54.6) and 35.6 (9.3, 68.5) months, respectively. Among pts treated with 1L HU who had evaluable blood counts, 42% (1078/2548) had a suboptimal response at 3 months, 64% of whom (691/1078) continued to have a suboptimal response at 6 months (WBC >10 × 109/L and/or platelets >400 × 109/L, 50%; HCT >45%, 36%). Median duration of 1L HU treatment for pts with suboptimal response was 26.6 (95% CI: 24.0, 29.3) months. Among pts with suboptimal response to 1L HU, 5-year survival probability was 82% overall (high risk, 78%; low risk, 99%). Pts with suboptimal response appeared to have a lower 5-year survival probability than pts with optimal response (81.5% [95% CI: 77.7%, 85.5%] vs 84.3% [95% CI: 81.2%, 87.4%]). This difference between pts with suboptimal vs optimal response was statistically significant in non-Network (74.5% [95% CI: 67.7%, 82.0%] vs 85.1% [95% CI: 81.1%, 89.3%]; P=0.008) but not in The US Oncology Network practices (86.7% [95% CI: 82.3%, 91.2%] vs 83.6% [95% CI: 79.1%, 88.3%]; P=0.109). Besides this difference observed in the 5-year survival probability, pt characteristics and outcomes were similar between the 2 networks, although additional data (eg, pt/disease characteristics; phlebotomy use, supportive care) are needed to better understand differences between networks. Conclusions: The prevalence of elevated blood counts at diagnosis and follow-up while on HU treatment is consistent with previous real-world evidence. About 1 in 6 pts with a suboptimal response to HU died within 5 years, and there was a trend toward shorter survival among those with suboptimal response compared with pts with blood count control. HU dose adjustments or alternative treatments may be needed for pts with suboptimal response to HU. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comprehensive analyses reveal the role of histone deacetylase genes in prognosis and immune response in low-grade glioma.

Many studies have shown that Histone deacetylases (HDAC) is involved in the occurrence of malignant tumors and regulates the occurrence, proliferation, invasion, and migration of malignant tumors through a variety of signaling pathways. In the present, we explored the role of Histone deacetylases genes in prognosis and immune response in low-grade glioma. Using consensus clustering, we built the new molecular clusters. Using HDAC genes, we constructed and validated the prognostic model in two independent cohort datasets. Patients were divided into high-risk and low-risk groups. Then, we explored the molecular characteristics, clinical characteristics, tumor microenvironment and immune infiltration levels of two clusters and risk groups. Receiver operating characteristic analyses were built for model assessment. We finally detected the expression levels of signature genes between tumor and normal tissues. Low-grade can be separated into two molecular clusters using 11 HDACs genes. Two clusters had different clinical characteristics and prognosis. Nex, we constructed a prognosis model using six HDAC genes (HDAC1, HDAC4, HDAC5, HDAC7, HDAC9, and HDAC10), which was also validated in an independent cohort dataset. Furthermore, multivariate cox regression indicated that the calculated risk score was independently associated with prognosis in low-grade glioma, and risk score can predict the five-year survival probability of low-grade glioma well. High-risk patients can be attributed to multiple complex function and molecular signaling pathways, and the genes alterations of high- and low-risk patients were significantly different. We also found that different survival outcomes of high- and low- risk patients could be involved in the differences of immune filtration level and tumor microenvironment. Subsequently, using signature genes, we identified several small molecular compounds that could be useful for low-grade glioma patients' treatment. Finally, we detected the expression levels of signature genes in tumor tissues. our study uncovers the biology function role of HDAC genes in low-grade glioma. We identified new molecular subtypes and established a prognostic model based on six HDAC genes, which was well applied in two independent cohort data. The regulation of HDAC genes in low-grade glioma involved in multiple molecular function and signaling pathways and immune infiltration levels. Further experiments in vivo and vitro were required to confirm the present findings.

MPN-077 Characteristics, Blood Counts, Treatments, and Clinical Outcomes of 3022 Patients With Polycythemia Vera (PV) Treated in US Community Practices.

Cytoreduction with hydroxyurea (HU) is the recommended first-line (1L) treatment for high-risk PV (age ≥60 years; history of thrombosis), but many patients have a suboptimal response. To describe characteristics, blood counts, treatments, and clinical outcomes among patients with PV. Retrospective observational study of adults in The US Oncology Network iKnowMed electronic health record database with ≥2 post-PV diagnosis visits during the study (01JAN2008-31JAN2021). Suboptimal response was defined as meeting ≥1 of the following criteria after ≥3 months of HU treatment: (1) white blood cell (WBC) count >10×109/L, (2) platelet count >400×109/L, and/or (3) hematocrit (HCT) >45%. Duration of therapy and overall survival were assessed via Kaplan-Meier method. Overall, 3022 patients with PV were included (mean age at diagnosis, 65.8 years [69% ≥60 years]; female, 46%; White, 85%; current/former tobacco users, 49%). At diagnosis, 7% of patients had a history of thrombosis, and 71% had high-risk PV; 37% (886/2413), 32% (778/2411), and 67% (1617/2418) had elevated WBC (>10×109/L), platelets (>400×109/L), and HCT (>45%), respectively. Cytoreductive therapy as 1L treatment was received by 48% of patients (44% HU); phlebotomy data were unavailable. Five-year survival probability was 84% among all patients (low-risk [age <60 years; no history of thrombosis], 97%; high-risk, 81%). Among patients who received 1L HU (n=1317), median (Q1, Q3) time from diagnosis to HU initiation was 19 (0, 189) days; median (Q1, Q3) duration of HU was 30 (9.5, 64.4) months, and 29.5 (9.5, 58.5) and 35.0 (9.5, 77.0) months for high- and low-risk patients, respectively. Among patients on 1L HU with evaluable blood counts, 55% (584/1053) had a suboptimal response (WBC >10×109/L, 26%; platelets >400×109/L, 26%; HCT >45%, 36%) at 3 months; similar findings were seen at 6 months. Among patients with suboptimal response to 1L HU, 5-year survival probability was 87% (low risk, 100%; high risk, 84%). The prevalence of elevated blood counts at diagnosis and follow-up while on HU treatment is consistent with previous real-world experience. About 1 in 8 patients with a suboptimal response to HU died within 5 years.

Characteristics, blood counts, treatments, and clinical outcomes of 3,022 patients (Pts) with polycythemia vera (PV) treated in U.S. community practices.

e19076 Background: Cytoreduction with hydroxyurea (HU) is the recommended first-line (1L) treatment for high-risk PV (age ≥60 y or history of thrombosis), but many pts have a suboptimal response on HU. The objective of this study was to describe characteristics, blood counts, treatments, and clinical outcomes among pts with PV, including those with suboptimal response to HU, in a large network of US community oncology practices. Methods: This was a retrospective observational study of adult pts with a documented diagnosis of PV in The US Oncology Network iKnowMed electronic health record database. Pts with ≥2 post-diagnosis visits during the study observation period (01JAN2008–31JAN2021) were included in the analysis. Suboptimal response to HU was defined as meeting ≥1 of the following criteria after ≥3 months of treatment: (1) white blood cell (WBC) count &gt; 10 × 109/L, (2) platelet count &gt; 400 × 109/L, and/or (3) hematocrit (HCT) &gt; 45%. Data on demographic and clinical characteristics and prior treatment were collected and summarized using descriptive statistics. Duration of therapy and overall survival were assessed via Kaplan-Meier method; pts without subsequent treatment discontinuation/death records were censored. Results: Overall, 3022 pts with PV were included in the analysis; mean age at diagnosis was 65.8 years (69% ≥60 y), 46% of pts were female, 85% were White, and 49% were current/former tobacco users. At diagnosis, 7% of pts had a history of thrombotic event, and 71% had high-risk PV; 37% (886/2413), 32% (778/2411), and 67% (1617/2418) of evaluable pts had elevated WBC (&gt; 10 × 109/L), platelets (&gt; 400 × 109/L), and HCT (&gt; 45%), respectively. Nearly half of pts (48%) received a cytoreductive agent as 1L treatment (44% HU), and 52% did not receive cytoreductive therapy; phlebotomy data were unavailable. Five-year survival probability was 84% among all pts, 97% for low-risk pts (age &lt; 60 y; no history of thrombosis), and 81% for high-risk pts. Among pts who received 1L HU (n = 1317), median (Q1, Q3) time from diagnosis to HU initiation was 19 (0, 189) days; median (Q1, Q3) duration of HU was 30 (9.5, 64.4) months overall, and 29.5 (9.5, 58.5) and 35.0 (9.5, 77.0) months for high- and low-risk pts, respectively. Among pts on 1L HU with evaluable blood counts, 55% (584/1053) had a suboptimal response (WBC &gt; 10 × 109/L, 26%; platelets &gt; 400 × 109/L, 26%; HCT &gt; 45%, 36%) at 3 months; similar findings were seen at 6 months. Among pts with suboptimal response to 1L HU, 5-year survival probability was 87% overall (low risk, 100%; high risk, 84%). Conclusions: The prevalence of elevated blood counts at diagnosis and follow-up while on HU treatment is consistent with previous real-world experience. About 1 in 8 pts with a suboptimal response to HU died within 5 years. HU dose adjustments or alternative treatments may be needed for pts with suboptimal response to HU.

OP0049 FURTHER CHARACTERIZATION OF CLINICAL AND LABORATORY FEATURES OCCURRING IN VEXAS SYNDROME IN A LARGE-SCALE ANALYSIS OF MULTICENTER CASE-SERIES OF 116 FRENCH PATIENTS

BackgroundA new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome.ObjectivesTo describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.MethodsCase-series. Patients referred to a French multicenter registry between November 2020 and May 2021.116 patients with VEXAS syndrome. Frequency and median of parameters and vital status, from diagnosis to the end of the follow-up.ResultsMain clinical features were skin lesions (83.5%), non-infectious fever (63.6%), weight loss (62%), lung involvement (49.6%), ocular symptoms (38.8%), relapsing chondritis (36.4%), venous thrombosis (34.7%), lymph nodes (33.9%), and arthralgia (27.3%). Hematological disease was present in 58 cases (50%), considered as myelodysplastic syndrome (MDS, n= 58) and monoclonal gammapathy of unknown significance (n=12).UBA1 mutations included p.M41T (44.8%), p.M41V (30.2%), p.M41L (18.1%), and splice mutations (6.9%). After a median follow-up of 3.0 years, 18 patients died (15.5%), from infectious origin (n=9) and MDS progression (n=3). Unsupervised analysis identified 3 clusters: cluster 1 (47%) with mild-to-moderate disease; cluster 2 (16%) with underlying MDS and higher mortality rates; cluster 3 (37%) with constitutional manifestations, higher C-reactive protein levels and less frequent chondritis. Five-year probability of survival was 84.2% in cluster 1, 50.5 % in cluster 2, and 89.6% in cluster 3. UBA1 p.Met41Leu mutation was associated with a better prognosis.ConclusionVEXAS syndrome displays a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.Disclosure of InterestsNone declared.