Three-year Patient Survival Research Articles

Personalized three-year survival prediction and prognosis forecast by interpretable machine learning for pancreatic cancer patients: a population-based study and an external validation.

The overall survival of patients with pancreatic cancer is extremely low. We aimed to establish machine learning (ML) based model to accurately predict three-year survival and prognosis of pancreatic cancer patients. We analyzed pancreatic cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2021. Univariate and multivariate logistic analysis were employed to select variables. Recursive Feature Elimination (RFE) method based on 6 ML algorithms was utilized in feature selection. To construct predictive model, 13 ML algorithms were evaluated by area under the curve (AUC), area under precision-recall curve (PRAUC), accuracy, sensitivity, specificity, precision, cross-entropy, Brier scores and Balanced Accuracy (bacc) and F Beta Score (fbeta). An optimal ML model was constructed to predict three-year survival, and the predictive results were explained by SHapley Additive exPlanations (SHAP) framework. Meanwhile, 101 ML algorithm combinations were developed to select the best model with highest C-index to predict prognosis of pancreatic cancer patients. A total of 20,064 pancreatic cancer patients from SEER database was consecutively enrolled. We utilized eight clinical variables to establish prediction model for three-year survival. CatBoost model was selected as the best prediction model, and AUC was 0.932 [0.924, 0.939], 0.899 [0.873, 0.934] and 0.826 [0.735, 0.919] in training, internal test and external test sets, with 0.839 [0.831, 0.847] accuracy, 0.872 [0.858, 0.887] sensitivity, 0.803 [0.784, 0.825] specificity and 0.832 [0.821, 0.853] precision. Surgery type had the greatest effects on three-year survival according to SHAP results. For prognosis prediction, "RSF+GBM" algorithm was the best prognostic model with C-index of 0.774, 0.722 and 0.674 in training, internal test and external test sets. Our ML models demonstrate excellent accuracy and reliability, offering more precise personalized prognostic prediction to pancreatic cancer patients.

Radiogenomics based survival prediction of small-sample glioblastoma patients by multi-task DFFSP model.

In this paper, the multi-task dense-feature-fusion survival prediction (DFFSP) model is proposed to predict the three-year survival for glioblastoma (GBM) patients based on radiogenomics data. The contrast-enhanced T1-weighted (T1w) image, T2-weighted (T2w) image and copy number variation (CNV) is used as the input of the three branches of the DFFSP model. This model uses two image extraction modules consisting of residual blocks and one dense feature fusion module to make multi-scale fusion of T1w and T2w image features as backbone. Also, a gene feature extraction module is used to adaptively weight CNV fragments. Besides, a transfer learning module is introduced to solve the small sample problem and an image reconstruction module is adopted to make the model anatomy-aware under a multi-task framework. 256 sample pairs (T1w and corresponding T2w MRI slices) and 187 CNVs of 74 patients were used. The experimental results show that the proposed model can predict the three-year survival of GBM patients with the accuracy of 89.1 %, which is improved by 3.2 and 4.7 % compared with the model without genes and the model using last fusion strategy, respectively. This model could also classify the patients into high-risk and low-risk groups, which will effectively assist doctors in diagnosing GBM patients.

Long-term follow-up of patients with intermediate-risk neuroblastoma treated with response- and biology-based therapy: A report from the Children's Oncology Group study ANBL0531.

We previously reported excellent three-year overall survival (OS) for patients with newly diagnosed intermediate-risk neuroblastoma treated with a biology- and response-based algorithm on the Children's Oncology Group study ANBL0531. We now present the long-term follow-up results. All patients who met the age, stage, and tumor biology criteria for intermediate-risk neuroblastoma were eligible. Treatment was based on prognostic biomarkers and overall response. Event-free survival (EFS) and OS were estimated by the Kaplan-Meier method. The 10-year EFS and OS for the entire study cohort (n=404) were 82.0% (95% confidence interval (CI), 77.2%-86.9%) and 94.7% (95% CI, 91.8%-97.5%), respectively. International Neuroblastoma Staging System stage 4 patients (n=133) had inferior OS compared with non-stage 4 patients (n=271; 10-year OS: 90.8% [95% CI, 84.5%-97.0%] vs 96.6% [95% CI, 93.9%-99.4%], p=.02). Infants with stage 4 tumors with ≥1 unfavorable biological feature (n=47) had inferior EFS compared with those with favorable biology (n=61; 10-year EFS: 66.8% [95% CI, 50.4%-83.3%] vs 86.9% [95% CI, 76.0%-97.8%], p=.02); OS did not differ (10-year OS: 84.4% [95% CI, 71.8%-97.0%] vs 95.0% [95% CI, 87.7%-100.0%], p=.08). Inferior EFS but not OS was observed among patients with tumors with (n=26) versus without (n=314) 11q loss of heterozygosity (10-year EFS: 68.4% [95% CI, 44.5%-92.2%] vs 83.9% [95% CI, 78.7%-89.2%], p=.03; 10-year OS: 88.0% [95% CI, 72.0%-100.0%] vs 95.7% [95% CI, 92.8%-98.6%], p=.09). The ANBL0531 trial treatment algorithm resulted in excellent long-term survival. More effective treatments are needed for subsets of patients with unfavorable biology tumors.

Quantification of CD44, Epidermal Growth Factor Receptor, E-cadherin, and Vimentin in Oral Squamous Cell Carcinoma as an Indicator for Disease Progression and Survival.

Oral squamous cell carcinoma (OSCC) is commonly associated with early recurrence due to loco-regional spread. Changes at the cellular levels can be studied and are often an early indicator of disease progression, much before clinical symptoms become visible. Identifying parameters indicating an impending recurrence could help the clinician plan for early treatment and thus improve survival. Hence, this study aimed to determine if quantifiable parameters could be established for CD44, epidermal growth factor receptor(EGFR), E-cadherin, and vimentin and if these values could be used as indicators of disease progression on follow-up. A total of 150 cases of OSCC were included in the study and followed up linearly for 36 months. Paraffin-embedded tissues of these cases were subjected to immunohistochemical analysis for reactivity to CD44, EGFR, E-cadherin, and vimentin. The immunohistochemical staining correlated with the tumor's clinical and histological grade. Statistical analysis was done using SPSS Statistics version 17 (IBM Corp., Armonk, NY, USA). The receiver operating characteristics (ROC) were deployed for determining the correlation of recurrence with the immunohistochemistry(IHC) markers, while the Kaplan-Meier curve was employed for survival analysis. A recurrence rate of 70.0% and a survival rate of 66.6% were noted after a follow-up period of three years. It was found that both CD44 and E-cadherin decreased with the grade of tumor, while EGFR and vimentin increased with tumor de-differentiation. The E-cadherin was found to be the best predictor of recurrence and survival among all the four markers. The cut-off values could be identified for all four biomarkers, which on follow-up proved to be a valuable tool with a high sensitivity and specificity for predicting recurrence and three-year survival in patients with OSCC.

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries

ObjectiveSertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. MethodsIndividuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. ResultsIn total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2–99.3%) compared to 67.1% (95% CI: 55.2–81.6%) for all stage IC and 60.6% (95% CI: 40.3–91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99–305.85). ConclusionMost individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

Three-year survival of breast cancer patients attending a one-stop breast care clinic nested within a primary care health facility in sub-Saharan Africa-Zambia.

In Zambia, women with breast symptoms travel through multiple levels of the healthcare system before obtaining a definitive diagnosis. To eradicate this critical barrier to care, we nested a novel breast specialty service platform inside a large public-sector primary healthcare facility in Lusaka, Zambia to offer clinical breast examination, breast ultrasound, and ultrasound-guided core needle biopsy in a one-stop format, tightly linked to referral for treatment. The objective of the study was to determine the life expectancy and survival outcomes of a prospective cohort of women diagnosed with breast cancer who were attended to and followed up at the clinic. The effect of breast cancer stage on prognosis was determined by estimating stage-specific crude survival using the Kaplan-Meier method. Survival analysis was used to estimate mean lifespan according to age and stage at diagnosis. We enrolled 302 women with histologically confirmed breast cancer. The overall 3-year survival was 73%. An increase in patients presenting with early breast cancer and improvements in their survival were observed. Women with early-stage breast cancer had a lifespan similar to the general population, while loss of life expectancy was significant at more advanced stages of disease. Our findings suggest that implementing efficient breast care services at the primary care level can avert a substantial proportion of breast cancer-related deaths. The mitigating factor appears to be stage of disease at the time of diagnosis, the cause of which is multifactorial, with the most influential being delays in the referral process.

Active surveillance for clinical complete responders after chemoradiotherapy for oesophageal squamous cell carcinoma.

Guidelines on the treatment of oesophageal squamous cell carcinoma (SCC) recommend neoadjuvant chemoradiotherapy plus surgery or definitive chemoradiotherapy. The aim of this study was to evaluate the outcome of patients with a cCR after chemoradiotherapy who underwent active surveillance. Patients with oesophageal SCC who were treated with chemoradiotherapy between January 2016 and June 2022 were identified from an institutional database. Survival and recurrence of patients with a cCR who underwent active surveillance were compared with those of patients who underwent planned surgery. Survival was calculated according to the Kaplan-Meier method and compared between groups using the log rank test. The 37 patients who underwent active surveillance were older and tumours were more often located in the middle/upper-third of the oesophagus than in the surgery group of 57 patients. Median follow-up was 28.1 (i.q.r. 17.2-47.1) months for the active surveillance group and 20 (12.9-39.1) months for the surgery group. Overall survival was comparable between the two groups, with 3-year survival rates of 50 (95% c.i. 31 to 67) and 59 (40 to 73)% for the active surveillance and surgery groups respectively (P = 0.55). Three-year progression-free survival for patients who underwent active surveillance was better than in the surgery group: 70 (43 to 85) versus 58 (40 to 72)% (P = 0.02). Overall and progression-free survival was comparable between patients in the active surveillance group and 23 patients in the surgery group who had a pCR (ypT0 N0). The overall recurrence rate was comparable between the groups: 7 of 37 (19.4%) in active surveillance group versus 16 of 49 (32.6%) in surgery group (P = 0.26). Locoregional recurrence was noted more often in the active surveillance group and systemic recurrence in the surgery group. Active surveillance is feasible and safe for patients with oesophageal SCC who have a cCR after chemoradiotherapy.

The Prognostic Value of One-Year Changes in Biventricular Mechanics for Three-Year Survival in Patients with Precapillary Pulmonary Hypertension: A Cardiovascular Magnetic Resonance Feature Tracking Study.

Background and Objectives: The management of patients with pulmonary hypertension (PH) poses a considerable challenge. While baseline cardiac magnetic resonance imaging (cMRI) indices are recognized for survival prognosis in PH, the prognostic value of one-year changes in biventricular mechanics, especially as assessed using feature tracking (FT) technology, remains underexplored. This study aims to assess the predictive value of one-year change in cMRI-derived biventricular function and mechanics parameters, along with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and six-minute walking test (6MWT) results for three-year mortality in precapillary PH patients. Materials and Methods: In this retrospective study, 36 patients diagnosed with precapillary pulmonary hypertension (mPAP 55.0 [46.3-70.5] mmHg, pulmonary capillary wedge pressure 10.0 [6.0-11.0] mmHg) were included. Baseline and one-year follow-up cMRI assessments, clinical data, and NT-proBNP levels were analyzed. FT technology was utilized to assess biventricular strain parameters. Patients were categorized into survival and non-survival groups based on three-year outcomes. Statistical analyses, including univariate logistic regression and Cox regression, were performed to identify predictive parameters. Results: The observed three-year survival rate was 83.3%. Baseline right ventricle (RV) ejection fraction (EF) was significantly higher in the survival group compared to non-survivors (41.0 [33.75-47.25]% vs. 28.0 [23.5-36.3]%, p = 0.044), and values of ≤32.5% were linked to a 20-fold increase in mortality risk. RV septum longitudinal strain (LS) and RV global LS exhibited significant improvement over a one-year period in the survival group compared to the non-survival group (-1.2 [-6.4-1.6]% vs. 4.9 [1.5-6.7]%, p = 0.038 and -3.1 [-9.1-2.6]% vs. 4.5 [-2.1-8.5]%, p = 0.048, respectively). Declines in RV septum LS by ≥2.95% and in RV GLS by ≥3.60% were associated with a 25-fold and 8-fold increase in mortality risk, respectively. Conclusions: The decrease in right ventricular septal and global longitudinal strain over a one-year period demonstrates a significant predictive value and an association with an increased three-year mortality risk in patients with precapillary PH.

Prognostic Relevance of Preoperative "Tumor Marker Index" Values in Patients with Stage III Rectal Adenocarcinoma

Background: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related deaths worldwide. Studies often consider colon and rectal cancers together. The combination of CA 19-9 and CEA markers is used to improve diagnostic accuracy, but there are no reports on the use of this combination as a prognostic predictor for CRC. The study by Kamada et al. was the first to use the "tumor marker index" (TMI), the geometric mean of normalized CEA and CA 19-9 in CRC, demonstrating the prognostic capabilities of this novel marker. However, it is not known how the preoperative value of TMI compares and fits into the current system of prognostic factors for preoperative prediction of overall survival (OS) and disease-free survival (DFS). Objective: The aim was to investigate the significance of preoperatively determined TMI in predicting three-year overall survival (3Y-OS) and three-year disease-free survival (3Y-DFS) in patients with stage III adenocarcinoma of the upper and middle rectum. Methods: Our retrospective cohort study included 93 patients who underwent open anterior resection of the rectum between January 2015 and December 2020. Optimal cut-off values of the markers were determined by ROC analysis. Statistical analysis was performed using IBM SPSS Statistics 22 and R 4.4.0. Results: Patients with TMI ≥1.0158 had a statistically significantly higher likelihood of mortality within three years (p=0.012). Patients with TMI ≥0.979 had a statistically significantly higher likelihood of disease-free survival of less than three years (p=0.003). Compared to CEA and CA 19-9, TMI had the highest AUC for predicting 3Y-OS (0.740, p=0.020) and 3Y-DFS (0.780, p=0.012). Adding TMI to other predictors increased the AUC for predicting both 3Y-OS (from 0.748 to 0.853) (p=0.001) and 3Y-DFS (from 0.711 to 0.850) (p=0.001). Conclusion: Our study confirmed previous findings on the usefulness of preoperative TMI as a prognostic marker, further expanding knowledge about its accuracy by comparing and combining it with established prognostic factors, including CEA and CA 19-9.

Three-Year Overall Survival of Patients With Advanced Non-Small-Cell Lung Cancers With ≥50% PD-L1 Expression Treated With First-Line Pembrolizumab Monotherapy in a Real-World Setting (ESCKEYP GFPC Study).

Outside clinical trials, few data are available on the effect of long-term first-line pembrolizumab in patients with advanced non-small-cell lung cancers with ≥50% of tumor cells expressing programmed cell death ligand 1 (PD-L1). This French, multicenter study included consecutive advanced patients with non-small-cell lung cancer given first-line pembrolizumab alone between May 2017 (authorization date for this indication) and November 2019 (authorization date for pembrolizumab-chemotherapy combination). Information was collected from patients' medical files, with a local evaluation of the response and progression-free survival (PFS). Overall survival (OS) was calculated from pembrolizumab onset using the Kaplan-Meier method. The analysis concerned 845 patients, managed in 33 centers: median age: 65 (range: 59-72) years, 67.8% men, 78.1% Eastern Cooperative Oncology Group performance status 0/1, 38.9%/51.5%/6.6% active, ex or never-smokers, respectively, 10.9%/16.8% taking or recently took corticosteroids/antibiotics, 69.6% nonsquamous histology, 48.9% ≥75% PD-L1-positive, and 20.8% had brain metastases at diagnosis. After a median (95% CI) follow-up of 45 (44.1-45.9) months, respective median (95% CI) PFS and OS lasted 8.2 (6.9-9.2) and 22 (8.5-25.9) months; 3-year PFS and OS rates were 25.4% and 39.4%, respectively. Multivariate analysis retained never-smoker status, adenocarcinoma histology, Eastern Cooperative Oncology Group performance status ≥2, and neutrophil/lymphocyte ratio >4 as being significantly associated with shorter survival, but not brain metastases at diagnosis or <75% PD-L1 tumor-cell expression. These long-term results of pembrolizumab efficacy based on a nationwide "real-world" cohort reproduced those obtained in clinical trials.

Prognosis of older adults with chronic lymphocytic leukemia: A Surveillance, Epidemiology, and End Results-Medicare cohort study

IntroductionWhile prognosis for patients with chronic lymphocytic leukemia (CLL) has improved over time in younger adults, only modest improvements have occurred in older adults. We conducted a descriptive study of prognosis in older adults with CLL. Materials and MethodsWe used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from 2003 to 2016. We identified older adults (≥66 years) diagnosed with primary CLL between 2004 and 2015 (Overall Cohort). A subset who initiated CLL-directed therapy during the year following diagnosis was also identified (Treated Cohort). Both cohorts were matched to Medicare beneficiaries without cancer based on age, sex, and region. For each year from 2004 to 2013, three-year survival for patients with CLL and non-cancer comparators was described using Kaplan-Meier analysis. Inverse probability weighted Cox regression models were used to compare survival in the CLL and non-cancer comparator cohorts, accounting for demographic information and comorbidity and frailty indices. Among older adults with CLL, ten-year cause-specific cumulative mortality was estimated using Aalen-Johansen estimators that accounted for competing risks. Predictors of cause-specific mortality, including comorbidity and frailty burden, were assessed using sub-distribution hazards models. ResultsIn the Overall Cohort, three-year survival increased non-monotonically from 71.4% in 2004 to 73.4% in 2013, with a peak of 74.4% in 2011, and was lower than survival in non-cancer comparators (78.3% in 2004 to 83.2% in 2013). In the Treated Cohort, three-year survival was 56.3% in 2004 and 56.5% in 2013, with a peak of 64.2% in 2011. Cox models suggested that survival in the Treated Cohort was approaching survival in non-cancer comparators after 2011 (hazard ratio = 1.04, 95% confidence interval, 0.93–1.17). Ten-year cumulative mortality was 68.6% in the Overall Cohort and 81.7% in the Treated Cohort, with most deaths attributed to non-CLL causes. In the sub-distribution hazards models, age, year of diagnosis, frailty, and comorbidities were all associated with prognosis. DiscussionPrognosis in older adults has been stable over time and most patients with CLL die from non-CLL causes. CLL-directed treatment decision-making in older adults should consider age-related factors, such as comorbidity and frailty.

Breast Cancer Treatment and Outcomes in Nigeria: A Systematic Review and Meta-analysis

Background: Nigeria has one of the highest age-standardized breast cancer (BC) mortality rates globally and the highest in Africa. Late presentation and diagnosis have been studied extensively as causes of high BC morbidity and mortality, while treatment and outcomes are under-reported. We aggregated data on BC treatment and outcomes in Nigeria to identify gaps in research, challenges, and potential targets for future interventions.Methods: Articles on female BC management in Nigeria published between 2011 and 2021 were reviewed for the prevalence of different treatment modalities and outcomes. The meta-analytical procedure was a random effect model. Results: We identified 15 articles that reported on the treatment and outcomes of 3857 BC patients. The most prevalent treatment modality was chemotherapy alone. The probability of receiving each treatment modality was 85% (95% CI 66-97) for chemotherapy, 62% (95% CI 51-73) for surgery, and 31% (95% CI 8-59) for radiotherapy. Multimodality treatment, including chemotherapy, surgery, and radiation, was administered to 24% (95% CI 10-43) of patients. In studies with available data, nearly half of patients who initiated chemotherapy did not complete the recommended number of doses or received treatments at irregular intervals. The radiotherapy utilization was five times higher when patients received treatment in centers with radiation facilities. Overall survival estimates were 80% at one year, 43% at two years, and 32% at five years. Patients with early-stage (AJCC I/II) disease survived longer, with a 5-year survival difference of 32% compared to patients with late-stage (AJCC III/IV) disease. Patients receiving multimodality therapy survived longer. Three-year survival for patients who received chemotherapy, surgery and radiotherapy was 68%. Whereas it was 43% in patients who received chemotherapy and surgery only. Conclusion: Improving access to complete systemic therapy, surgery, and radiation for breast cancer patients in Nigeria is imperative and should be the target of future interventions.

Surgical treatment of renal tumor with tumor thrombus in the inferior vena cava

Background/Aim. An aggressive approach with radical nephrectomy and thrombectomy is the mainstay of the treatment in patients with renal tumors. The aim of this study was to present the results of such surgical procedures performed in the last 25 years at our institution. Methods. We made a retrospective analysis of radical nephrectomy and thrombectomy in patients with renal tumor and tumor thrombus (TT) extending into the inferior vena cava (IVC) operated on at our institution between January 1995 and October 2021. Results. There were 92 patients (72 males and 20 females) aged 60.5 on average who were operated on in the mentioned period. A predominance of right-sided tumors was present in 73.33% of patients. Patients with TT in the renal vein (levels 0 and I) were not included. TT levels II, III, and IV were present in 32 (34.8%), 52 (56.5%), and 8 (8.7%) patients, respectively. One patient had thrombosis of the right pulmonary artery. Four patients had liver metastases, and ten had lymph node involvement. The surgical approach by subcostal incision was achieved in 8 (8.69%) patients, by chevron incision in only 11 (11.95%) patients, while in 73 (79.34%) patients, we performed median sternotomy and subcostal/chevron incision. Intraoperatively, there was one complication which was pulmonary thromboembolism. Six patient required re-exploration after the surgery due to the IVC hemorrhage. The three-year survival in patients with renal tumors and TT levels II?IV in the IVC was 43%. Conclusion. Surgery will remain the primary cure method in patients with renal tumors and TT in the IVC. Long-term survival in these patients can be achieved by complete surgical removal (radical nephrectomy and thrombectomy).

КОНСОЛИДИРУЮЩАЯ ХИМИОТЕРАПИЯ В РЕЖИМЕ CapOx ПОСЛЕ ХИМИОЛУЧЕВОЙ ТЕРАПИИ УЛУЧШАЕТ ВЫЖИВАЕМОСТЬ ПАЦИЕНТОВ С МЕСТНОРАСПРОСТРАНЕННЫМ РАКОМ ПРЯМОЙ КИШКИ

Purpose: Consideration of the long-term three-year results of combined treatment of patients with locally advanced rectal cancer using preoperative chemoradiotherapy and consolidating chemotherapy. Material and methods: Patients aged &gt;18 with histologycally verified MRI-staged low and medium T3(CRM+)‒4N0‒2M0 rectal cancer were included. In the study group patients received neoadjuvant chemoradiotherapy 52‒56 Gy in 2 Gy fractions with capecitabine 850 mg/m2 per os two times a day and followed by 4 cycles in СapOx regimen. In the control group, similar chemoradiotherapy was performed without consolidating chemotherapy. The study group consisted of 105 patients, and the control group consisted of 99 patients. The median follow-up was 42.4 months. Results: The full planned course of preoperative treatment was carried out in 201 (98.5 %) patients. Progression of the disease after the neoadjuvant therapy was not detected in any patient. A complete pathological response in the tumor was registered in 29 (15.1 %) patients, and a complete clinical response in 12 (6 %) patients. In the study and control groups, these indicators were (20 % vs. 10.3 %, p=0.04) and (9.5 % vs. 2 %, p=0.01), respectively. Local relapses in the study were registered in 18 (8.8 %) patients, and distant metastases in 53 (26 %) patients. In the study and control groups, local relapse and distant metastases developed in 4.8 % vs. 13.1 % (p=0.03) and 20 % vs. 32.3 % (p=0.04), respectively. The overall three-year survival rate in patients in the study group was 92.9 %, in the control group 79.7 % (HR 0.2, 95 % CI 0.03‒0.24, p=0.01). Three-year relapse-free survival in patients in the study group was 75.5 %, and in the control group 59.6 % (HR 0.2, 95 % CI 0.05‒0.32, p=0.01). Conclusion: Up to date, the strategy of combined neoadjuvant treatment seems to be the most promising. With a high degree of probability, this approach in the treatment of patients with locally advanced rectal cancer may become a new standard of therapy with a similar treatment algorithm.

Establishment and validation of individualized clinical prognostic markers for LUAD patients based on autophagy-related genes.

There is considerable heterogeneity in the genomic drivers of lung adenocarcinoma, which has a dismal prognosis. Bioinformatics analysis was performed on lung adenocarcinoma (LUAD) datasets to establish a multi-autophagy gene model to predict patient prognosis. LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database as a training set to construct a LUAD prognostic model. According to the risk score, a Kaplan-Meier cumulative curve was plotted to evaluate the prognostic value. Furthermore, a nomogram was established to predict the three-year and five-year survival of patients with LUAD based on their prognostic characteristics. Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001). The Kaplan-Meier cumulative curve showed that low-risk patients had significantly better overall (P<0.0001). The validation dataset GSE68465 further confirmed the nomogram’s robust ability to assess the prognosis of LUAD patients. A prognosis model of autophagy-related genes based on a LUAD dataset was constructed and exhibited diagnostic value in the prognosis of LUAD patients. Moreover, real-time qPCR confirmed the expression patterns of EIF2AK3 and ITGB1 in LUAD cell lines. Two key autophagy-related genes have been suggested as prognostic markers for lung adenocarcinoma.

Comparison of kidney transplant outcomes in HLA compatible and incompatible transplantation: A national cohort study.

Reports of HLA incompatible (HLAi) kidney transplant outcomes are inconclusive, especially in the context of lower level Donor Specific Antibodies (DSA). Multi-centre national cohort study of HLAi kidney transplant recipients matched in 1:2 ratio with HLA compatible (HLAc) kidney transplant recipients. HLAi defined as DSA identified by Luminex. Antibody mediated rejection (AMR) and transplant-survival were analysed using Kaplan-Meier plots. Propensity score (PS) matching was used to compare recipient and transplant survival between groups. We included 61 HLAi and 122 HLAc recipients; mean age 46 years; 60% female. MFIT0 : 3327 (IQR 1352-6458), 23 (38%) were Flow cytometry crossmatch positive (FC-XMPOS ). DSAPOS /FC-XMPOS transplantation carried an increased risk of AMR at 1year (52%) compared to DSAPOS /FC-XMNEG (27%) and HLAc (0%). Unadjusted death censored graft loss at 3 years was 13% (HLAi) and 8% (HLAc). Three-year patient survival was 95% in HLAc, 84% in DSAPOS /FC-XMNEG and 69% in DSAPOS /FC-XMPOS recipients; 58% of HLAi deaths were infection-related. HLA incompatibility was associated with a decreased 3-year survival in our PS-matched cohort. In kidney transplantation, DSA and positive FC-XM carries an increased risk of AMR. Despite inferior transplant and survival outcomes compared to HLAc transplantation, it remains a realistic option for highly sensitized patients facing prolonged waiting times and reduced survival on dialysis.

NudCD1 as a prognostic marker in colorectal cancer and its role in the upregulation of cellular spindle assembly checkpoint genes and LIS1 pathways

ObjectiveTo investigate the role of NudCD1 in spindle assembly checkpoint regulation and in the prognosis of colorectal cancer. MethodsImmunohistochemical staining was used to detect in situ expression of NudCD1 in 100 colorectal cancer tissue samples. A chi-square test was used to analyse the correlation between the NudCD1 protein expression level of the cancer tissues and clinicopathological features. The Kaplan–Meier survival analysis was used to assess the correlation between the NudCD1 mRNA expression and the three-year survival of patients with colorectal cancer. The impact of NudCD1 on the development of colorectal cancer and the underlying molecular mechanisms were assessed by flow cytometry cell cycle and apoptosis assays after lentiviral overexpression of NudCD1 in two colorectal cancer cell lines. Quantitative real-time PCR was used to assess mRNA expression of the cellular spindle assembly checkpoint genes BUB1, BUBR1, MAD1, CDC20 and MPS1, as well as the downstream genes LIS1, DYNC1H1, and DYNLL1 in the NudC/LIS1/dynein pathway.ResultsCompared with normal intestinal tissue (8.00% with high expression), the expression of NudCD1 protein in colorectal cancer tissue was significantly higher (58.00% with high expression, P < 0.01). In addition, expression of NudCD1 significantly correlated with the degree of tumour differentiation and the TNM staging (P < 0.01), as well as the depth of invasion of the primary tumour and lymph node metastasis (P < 0.05). However, there was no correlation with gender, age, tumour site, gross type, tumour size or distant metastasis. The Kaplan–Meier survival analysis showed that patients with high NudCD1 expression in colorectal cancer tissues had a significantly shorter survival time than those with low expression of NudCD1 (P < 0.01). Compared with the transfection of the empty vector, colon cancer HT-29 cells with overexpressed NudCD1 had significantly increased mRNA levels of BUBR1, MPS1 and LIS1. The DNA synthesis phase (S phase) was significantly shorter in cells overexpressing NudCD1 than in the control group (43.83% ± 1.57%, P < 0.05), while there was no difference in apoptosis in the two groups.ConclusionNudCD1 can serve as a valuable prognostic marker for colorectal cancer. It may be involved in the regulation of spindle-assembly checkpoint-gene expression and the LIS1 pathway of colorectal cancer cells.

Inflammatory Indexes as Prognostic Factors of Survival in Geriatric Patients with Hepatocellular Carcinoma: A Case Control Study of Eight Slovak Centers.

Background and Aims: Hepatocellular cancer (HCC) often occurs in geriatric patients. The aim of our study was to compare overall survival and progression-free survival between geriatric patients (>75 years) and patients younger than 75 years and to identify predictive factors of survival in geriatric patients with HCC. Material and Methods: We performed a retrospective analysis of patients with HCC diagnosed in Slovakia between 2010–2016. Cases (HCC patients ≥75 years) were matched to controls (HCC patients <74 years) based on the propensity score (gender, BCLC stage and the first-line treatment). Results: We included 148 patients (84 men, 57%) with HCC. There were no differences between cases and controls in the baseline characteristics. The overall survival in geriatric patients with HCC was comparable to younger controls (p = 0.42). The one-, two-, and three-year overall survival was 42% and 31%, 19% and 12%, and 12% and 9% in geriatric patients and controls, respectively (p = 0.2, 0.4, 0.8). Similarly, there was no difference in the one- and two-year progression-free survival: 28% and 18% vs. 10% and 7% in geriatric HCC patients and controls, respectively (p = 0.2, 1, -). There was no case–control difference between geriatric HCC patients and younger HCC controls in the overall survival in the subpopulation of patients with no known comorbidities (p = 0.5), one and two comorbidities (p = 0.49), and three or more comorbidities (p = 0.39). Log (CRP), log (NLR), log (PLR), and log (SII) were all associated with the three-year survival in geriatric HCC patients in simple logistic regression analyses. However, this time, only log (NLR) remained associated even after controlling for the age and BCLC confounding (OR 5.32, 95% CI 1.43–28.85). Conclusions. We found no differences in overall survival and progression-free survival between older and younger HCC patients. Parameters of subclinical inflammation predict prognosis in geriatric patients with HCC. A limitation of the study is small number of the treated patients; therefore, further investigation is warranted.

Outcomes of Stable Lung Colorectal Metastases on Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

BackgroundCytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have demonstrated benefit in patients with colorectal peritoneal metastases (CRPM). Traditionally, extraperitoneal disease is considered a contraindication to CRS/HIPEC. Stable lung metastases in patients with colorectal cancer often have an indolent course, while the presence of untreated peritoneal metastases poorly affects short-term survival. We sought to evaluate the outcomes of patients undergoing CRS/HIPEC for peritoneal disease with known stable lung metastases. MethodsWe retrospectively reviewed our prospectively maintained CRS/HIPEC database. In 2017, we adopted a policy of considering patients with stable lung metastases for CRS/HIPEC as part of multidisciplinary treatment. We compared the oncologic outcome and safety of CRS/HIPEC with peritoneal only (PM) against patients with peritoneal and lung metastases (PLM). ResultsOur database includes 570 patients with CRS/HIPEC of which 174 with CRPM that underwent CRS/HIPEC, 18 with preoperatively diagnosed peritoneal and lung metastases. The demographics of the PM and PLM group were similar with the exception of operative time that was longer in the PLM group. Median PCI of the cohort was 7, similar in both groups (p = 0.89). Three-year overall survival (OS) of PLM patients was 68%, compared to 71% in PM (p = 0.277). Three-year progression-free survival (PFS) rate was 20% in PLM and 23% in PM (p = 0.688). ConclusionsPresence of stable lung metastases from colorectal cancer in patients with CRPM does not appear to affect the outcomes of CRS/HIPEC. Patients with stable lung disease should be considered for CRS/HIPEC after multidisciplinary discussion.

110-OR: Excellent Outcome of Solitary Pancreas Transplant Recipients with Brittle Diabetes and without Advanced Nephropathy

Introduction: In contrast to non-pancreatic transplantation, where nephrologists refer patients for kidney and hepatologists for liver transplantation, endocrinologists only rarely refer patients with brittle diabetes for solitary pancreas transplantation. While most pancreas transplants are performed in combination with a kidney graft, solitary pancreas transplants (PTA) without a previous kidney transplant accounted for only 6-7% of pancreas transplants per year although a PTA is the best treatment option to achieve long-term insulin-independence in patients with severe brittle diabetes. Methods: The change in demographics and outcome of 1,636 primary PTAs were analyzed between 20 and 2020 in 5-year intervals. Graft survival was defined as complete insulin-independence. Multivariate analysis was performed to assess factors that impacted outcome and the potential need for a subsequent kidney transplant. Results: Over time, recipient age increased, but donor age and preservation time decreased significantly. Most recipients received induction therapy and maintenance immunosuppression. These changes resulted in significant improvement in patient and pancreas graft survival. Three-year patient survival increased from 92% in 2001-to 96% in 2016-20. Three-year pancreas graft survival improved from 60% in 2001-to 77% in 2016-20 (p&amp;lt;0.0001) . The most influential factors for this decrease were older recipient age and better immunosuppression. The rate of a subsequent kidney transplant declined significantly. It was primarily contingent on native graft function at the time of transplant. If the GFR was as &amp;gt;70ml/min only 1% of patients required a kidney graft. Conclusion: The results of PTA have significantly improved over the past 20 years. A PTA should be strongly considered in brittle diabetic patients before the development of advanced nephropathy. Disclosure A.Gruessner: None.