High Prognostic Score Research Articles

Integrated ubiquitomics characterization of hepatocellular carcinomas.

Patients with aggressive HCC have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic. The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 patients with HCC. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1, and LAMA4 were highly expressed in the disease free survival-poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed cross talk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to protein kinase B-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo. This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC.

Naples Prognostic Score for Graft Functions After Renal Transplantation: A Retrospective Analysis.

BACKGROUND The Naples prognostic score is a comprehensive measure of patients' inflammation and nutritional status, consisting of serum albumin, total cholesterol, neutrophil/lymphocyte ratio (NLR), and lymphocyte/monocyte ratio (LMR). We compared the Naples prognostic scores of kidney transplant patients with a creatinine reduction ratio of less than 30% vs those with greater than 30%. MATERIAL AND METHODS We conducted a retrospective study on 93 patients who received kidney transplants at our hospital from January 2020 to January 2023. Naples prognostic scores were used to calculate the preoperative condition of transplant recipients. The patients were divided into 2 groups based on their creatinine reduction ratio on the second day after surgery. Group A consisted of patients with a ratio above 30%, while group B consisted of those with a ratio below 30%. RESULTS Our analysis revealed that the total cholesterol and albumin values of groups A and B showed no substantial difference. Group B had clearly more patients with Naples prognostic score 3-4 compared to the other group (P=0.032). Multivariate analysis determined that patients with Naples prognostic score 3-4 had a 3.151-fold higher likelihood of experiencing creatinine reduction below 30% (95% CI 1.209-8.215, P value 0.019). CONCLUSIONS The preoperative inflammatory and nutritional status of patients may have an impact on the functioning of grafts during the postoperative period. A high Naples prognostic score may be linked with a decrease in creatinine reduction ratio in post-transplant kidneys, which could lead to graft dysfunction.

Preoperative low muscle mass and malnutrition affect the clinical prognosis of locally advanced gastric cancer patients undergoing radical surgery.

Gastric cancer is a common and highly aggressive malignant tumor of the gastrointestinal tract that poses a serious threat to human life and health. As the clinical symptoms of early gastric carcinoma are not obvious, many patients are diagnosed in the middle or late stages. With the advancement of medical technology, gastrectomy has become a safer surgical procedure, but it still has a high recurrence and mortality rate after surgery. The prognosis of gastric cancer patients after surgery is not only related to tumor-related factors (i.e., tumor stage) but the patient's nutritional status. This study aimed to investigate the effect of preoperative muscle mass combined with the prognostic nutritional index (PNI) on clinical prognosis in locally advanced gastric carcinoma. The clinical data of 136 patients with locally advanced gastric carcinoma diagnosed by pathology and undergoing radical gastrectomy were retrospectively reviewed. To analyze the influencing factors of preoperative low muscle mass and its correlation with the prognostic nutritional index. Patients with both low muscle mass and low PNI (≤46.55) were assigned a score of 2, and those with only one or neither of these abnormalities were assigned a score of 1 or 0, respectively, according to the new prognostic score (PNIS). The relationship between PNIS and clinicopathological characteristics was analyzed. Univariate and multivariate analyses were performed to identify risk factors for overall survival (OS). Low muscle mass was associated with a lower PNI (P < 0.01). The optimal cut-off value of PNI was 46.55, the sensitivity was 48%, and the specificity was 97.1%. There were 53 (38.97%), 59 (43.38%), and 24 patients (17.65%) in the PNIS 0, 1, and 2 groups, respectively. A higher PNIS and advanced age were independent risk factors for postoperative complications (P < 0.01). The overall survival rate in patients with PNIS 2 score was significantly poorer than in patients with scores of 1 or 0 (3-year OS: 45.8% vs 67.8% vs 92.4%, P < 0.001). A Multivariate Cox hazards analysis showed that PNIS 2, depth of tumor invasion, vascular invasion, and postoperative complications were independent predictors of the poor 3-year survival in patients with locally advanced gastric cancer. The combination of muscle mass and the PNI score system can be used to predict the survival outcome of patients with locally advanced gastric cancer.

Biomarkers of Inflammation and Progression During Immunotherapy in Patients With Metastatic Renal Cell Carcinoma.

Biomarkers that would identify patients unlikely to respond to immunotherapy with immune checkpoint inhibitors (ICIs) remain an unmet medical need. In the present study, we have retrospectively evaluated the association between biomarkers of immune activation and outcome in metastatic renal cell carcinoma (mRCC) patients treated with ICIs. The laboratory and clinical data of 79 consecutive patients with histologically confirmed mRCC treated with ICI-based immunotherapy have been analyzed. Patients who progressed or died at 4 months had higher prognostic score, higher serum C-reactive protein (CRP) and neopterin, and urinary neopterin, and lower serum albumin and hemoglobin concentration. Biomarkers of activation of immune response, in particular serum neopterin/creatinine ratio, are associated with outcome in mRCC patients treated with ICI immunotherapy.

RNA 5-Methylcytosine Regulator NSUN3 promotes tumor progression through regulating immune infiltration in head andneck squamous cell carcinoma.

This study aimed to determine whether the RNA, 5-methylcytosine (m5C), is involved in the progression of head and neck squamous cell carcinoma (HNSCC). We used least absolute shrinkage and selection operator to establish a prognostic score (PS) model based on the m5C regulator expression. Immune scores were calculated using the estimation of stromal and immune cells in malignant tumor tissues using expression data. The biological functions of the m5C regulator, NOP2/Sun RNA methyltransferase 3 (NSUN3), were thoroughly investigated in vitro and in vivo. The PS model acted as efficient prognostic factors in HNSCC. The expression of NSUN3, with the maximum weight, was found to be upregulated and indicated a poor prognosis. Meanwhile, NSUN3 knockdown inhibited the tumor proliferation and growth both in vitro and in vivo. High PS status was negatively correlated with CD8+ T, γδ+ T, and M1 macrophage percentages. NSUN3 knockdown increased the infiltration of M1 macrophages but decreased the percentage of M2 macrophages. The PS index is a novel and promising biomarker for predicting the prognosis and immune infiltration microenvironment in HNSCC. Moreover, NSUN3 plays a key role in this process and may serve as a potential therapeutic target for HNSCC.

The Immune-based Prognostic Score for the Immunogenomic Landscape Aanalysis and Application of Chemotherapy in Breast Cancer

Background: Breast cancer is one cancer that develops from breast tissue and one of the major reasons for the death of women all over the world. The tumor infiltrating lymphocytes in tumor immune microenvironment are correlated with the prognosis in breast cancer patients, and play an important role in the occurrence and development of breast cancer. Method: In this study, by integrated the immune gene expression of 20 breast cancer cohorts from the public dataset, an immune-based prognostic score was established. This immune-based prognostic score was found to be correlated with prognosis, stromal score, tumor purity, three famous immune checkpoints, and immune escape mechanism in breast cancer patients. Results: The clinical application of the prognostic score was verified by the breast cancer patients treated with chemotherapy, and good therapeutic benefit of the prognostic score was obtained. In addition, the XGBoost classifier was used to construct for predicting the high and low prognostic score subtypes, and the predictive results indicated that the XGBoost was suitable to predict these two subtypes in breast cancer patients. Conclusion: Based on these results, we believed that the prognostic score may be used as an effective prognostic marker and may provide great help for chemotherapy treatment of breast cancer patients

Analytical Validation of a Novel 6-Gene Signature for Prediction of Distant Recurrence in Estrogen Receptor-Positive, HER2-Negative, Early-Stage Breast Cancer

OncoMasTR is a recently developed multigene prognostic test for early-stage breast cancer. The test has been developed in a kit-based format for decentralized deployment in molecular pathology laboratories. The analytical performance characteristics of the OncoMasTR test are described in this study. Expression levels of 6 genes were measured by 1-step reverse transcription-quantitative PCR on RNA samples prepared from formalin-fixed, paraffin-embedded (FFPE) breast tumor specimens. Assay precision, reproducibility, input range, and interference were determined using FFPE-derived RNA samples representative of low and high prognostic risk scores. A pooled RNA sample derived from 6 FFPE breast tumor specimens was used to establish the linear range, limit of detection, and amplification efficiency of the individual gene expression assays. The overall precision of the OncoMasTR test was high with an SD of 0.16, which represents less than 2% of the 10-unit risk score range. Test results were reproducible across 4 testing sites, with correlation coefficients of 0.94 to 0.96 for the continuous risk score and concordance of 86% to 96% in low-/high-risk sample classification. Consistent risk scores were obtained across a > 100-fold RNA input range. Individual gene expression assays were linear up to quantification cycle values of 36.0 to 36.9, with amplification efficiencies of 80% to 102%. Test results were not influenced by agents used during RNA isolation, by low levels of copurified genomic DNA, or by moderate levels of copurified adjacent nontumor tissue. The OncoMasTR prognostic test displays robust analytical performance that is suitable for deployment by local pathology laboratories for decentralized use.

Anemia in Lymphoma Patients in Indonesia: The Prevalence and Predictive Factors

Background: The burden of lymphoma is intensified with the presence of anemia. The type of anemia in lymphoma is predominantly anemia of chronic disease. Severe anemia is also often associated with advanced stages leading to poor prognosis and survival as well as a worse quality of life. Objective: In this study, we aimed to observe the incidence of anemia in lymphoma and to identify any associated clinical and laboratory factors. Methods: Data from lymphoma patients admitted between 2012 to 2018 with complete hemoglobin (Hb) levels were collected from the medical records in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Clinical and laboratory parameters included were age, sex, nutritional status, Ann Arbor staging, extranodal involvement, number of extranodal sites, Lactate Dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) performance status, platelet count, absolute lymphocyte count (ALC), white blood cell count (WBC), and lymphoma prognostic score (Non-Hodgkin Lymphoma/NHL using Index Prognostic International (IPI), Hodgkin’s Lymphoma/HL using International Prognostic Score (IPS)). Statistical analysis was done to observe the difference in any parameters between patients with anemia and non-anemia. Logistic regression was employed to model the relationship between associated or predictive factors and anemia incidence. Results: Six hundred eleven (611) lymphoma patients were involved in this study, 296 (48.5%) had anemia and 314 (51.5%) did not. Anemia was more prevalent in HL (17/ 33 cases or 51.5%) than in NHL (272/ 564 cases or 48.1%). Patients with anemia frequently presented with mild anemia in 142 (48%), followed by moderate anemia in 139 (46.9%). The incidence of anemia were significantly associated with male sex, advanced Ann Arbor stage (III-IV), underweight, elevated LDH level, abnormal platelet, absolute lymphocyte counts less than 600/mm3, elevated WBC count more than 15,000/mm3, and high total prognostic score (&gt;3). Multivariate analysis demonstrated low or elevated platelet (P=0.044; 95% CI=1.03-8.09) as an independent predictor, meanwhile lymphocytopenia as protective factor (OR=0.05; 95% CI=0.00-0.54; P=0.013). Conclusion: Anemia commonly occurs in Indonesian lymphoma patients. There is an association and increased risk to develop anemia in male, Ann Arbor stage III-IV, underweight, elevated LDH, abnormal platelet, leukocytosis, and high total prognostic score. Abnormal platelet was an independent predictive factor, and lymphocytopenia is one of the protective factor.

A New Prognostic Scoring System to Predict Disease Progression and Mortality in Patients with Newly Diagnosed Primary CNS Lymphoma

▪BackgroundPrimary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin lymphoma (NHL) and counts for about 3% of all CNS neoplasms. Despite advances in treatment, patients' overall survival (OS) is still disastrous. Several prognostic factors have been reported (Ferreri et al . J Clin Oncol. 2003; Abrey et al . J Clin Oncol. 2006; Kreher et al . Ann Hematol. 2015), including age, performance status, serum lactate dehydrogenase, CSF protein level, involvement of deep brain, and intraocular involvement. In the present study, we investigated the risk factors of disease progression and purposed to integrate them into a scoring system for PCNSL.MethodsWe enrolled newly diagnosed PCNSL patients at a national medical center in Taiwan between January 1, 2002 and December 31, 2015. Patients without histological confirmations, or those diagnosed with secondary CNS lymphoma or AIDS were excluded. The cohort was followed up until the end of February, 2017. The risk factors of disease progression and death were identified using univariate and multivariate Cox proportional hazards models. The independent predictors were assigned a value of either 0, if favorable, or 1, if unfavorable, in a prognostic model for risk stratification.ResultsThe study cohort consisted of 101 PCNSL patients, with a median age of 64 years. The median progression-free survival (PFS) and OS were 17.3 (95% confidence interval [CI] 8.4-21.7) months and 100.8 (95% CI 29.5 to not reached) months, respectively. In the multivariate analysis, age ≥ 80 (adjusted hazards ratio [HR] 2.46, 95% CI 1.22-4.99, p= 0.012), involvement of deep brain (adjusted HR 2.57, 95% CI 1.39-4.72, p= 0.003) and ECOG performance status ≥ 2 (adjusted HR 1.87, 95% CI 1.09-3.20, p= 0.024) were identified as independent risk factors of disease progression. The patients were divided into four groups based on the independent predictors. The Kaplan-Meier survival analysis showed the patients with a higher prognostic score had a shorter PFS (log-rank p < 0.001) and OS (log-rank p= 0.005; Figure 1).ConclusionWe identified age ≥ 80, involvement of deep brain, and ECOG ≥ 2 as independent risk factors of disease progression in the PCNSL patients. Our new scoring system demonstrates a good risk stratification for PFS and OS in patients with PCNSL. Identifying patients at a higher prognostic score may help clinicians initiate appropriate management and early treatment. Further validation of our findings in other cohorts is warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic Score Model Based on Ten Differentially Methylated Genes for Predicting Clinical Outcomes in Patients with Adenocarcinoma of the Colon.

PurposeWe aimed to screen novel genetic biomarkers for use in a prognostic score (PS) model for the accurate prediction of survival outcomes for patients with colon adenocarcinoma (COAD).MethodsGene expression and methylation data were downloaded from The Cancer Genome Atlas database, and the samples were randomly divided into training and validation sets for the screening of differentially methylated genes (DMGs) and differentially expressed genes (DEGs). Co-methylated genes were screened using weighted gene co-expression network analysis. Functional enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery. Univariate and multivariate Cox regression analyses were performed to identify prognosis-related genes and clinical factors. Receiver operating characteristic curve analysis was carried out to evaluate the predictive performance of the PS model.ResultsIn total, 1434 DEGs and 1038 DMGs were screened in the training set, among which 284 were found to be overlapping genes. For 127 of these overlapping genes, the methylation and expression levels were significantly negatively correlated. An optimal signature from 10 DMGs was identified to construct the PS model. Patients with a high PS seemed to have worse outcomes than those with a low PS. Moreover, cancer recurrence and the PS model status were independent prognostic factors.ConclusionThis PS model based on an optimal 10-gene signature would help in the stratification of patients with COAD and improve the assessment of their clinical outcomes.

Identification of miR-320 family members as potential diagnostic and prognostic biomarkers in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and the abnormal differentiation of hematopoietic stem cells. An increasing number of researches have demonstrated that microRNAs play crucial roles in the pathogenesis of myelodysplastic syndromes. Herein, we aimed to identify novel potential microRNAs bound up with the diagnosis and prognosis of MDS. MiRNA microarray analysis was used to screen deregulated microRNAs in the bone marrow of MDS patients. qRT-PCR was employed to confirm the microarray results. All members of miR-320 family (miR-320a, miR-320b, miR-320c, miR-320d, and miR-320e) were significantly increased in MDS patients compared to normal control. Although we found no correlation between miR-320 family and most clinical characteristics, high miR-320c and miR-320d expression seemed to be associated with high numbers of bone marrow (BM) blasts and worse karyotype. High expression of all the members of the miR-320 family seemed to be associated with a high prognostic score based on International Prognostic Scoring System (IPSS). The areas under the miR-320 family member ROC curves were 0.9037 (P < 0.0001), 0.7515 (P = 0.0002), 0.9647 (P < 0.0001), 0.8064 (P < 0.0001) and 0.9019 (P < 0.0001). Regarding Kaplan–Meier analysis, high miR-320c and miR-320d expression were related to shorter overall survival (OS). Moreover, multivariate analysis revealed the independent prognostic value of miR-320d for OS in MDS. The expression of miR-320 family members was up-regulated in MDS, and miR-320 family members could serve as candidate diagnostic biomarkers for MDS. High expression of miR-320d was an independent prognostic factor for OS in MDS.

The Risk Factors for Death within 6 Months After Ischemic Stroke in Patients with Cancer

ObjectivesWhile the intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke patients with cancer is recommended when survival of ≥ 6 months is expected, the risk factors for death and stroke recurrence within 6 months after stroke are not well known. Thus, we aimed to identify markers for death and recurrence risks within six months from stroke onset in patients with cancer. Materials and MethodsIn a retrospective cohort study, the subjects comprised acute ischemic stroke patients with cancer hospitalized at St. Marianna University hospital from 2008 through 2019. To evaluate the associations between the clinical factors within 24 h of the initial stroke and death or stroke recurrence events within 6 months from stroke onset, Logistic analysis and Cox proportional hazards regression analysis was used respectively. Next, the optimal cutoff point of markers for different mortality groups was determined using the receiver operating characteristic curve analysis and cumulative outcome rate of each group was compared using the Kaplan–Meier method. ResultsAmong 194 patients with cancer who developed acute stroke, 167 were ultimately selected for analysis. 47 subjects (28.14%) passed away within 6 months following stroke onset, and 20 subjects (11.98%) had stroke recurrence. High D-dimer levels, low fibrinogen levels, high Glasgow prognostic scores (GPS), and multiple vascular territory infarctions was independently associated with death, where higher death rate was significantly confirmed in the group with D-dimer levels of ≥3.95 mg/dl, fibrinogen levels <277.5 mg/dl and GPS scores of 2. Low fibrinogen level, lack of antithrombotic therapy, and the presence of metastasis were associated with stroke recurrence. ConclusionsWhen patients with cancer suffer stroke, D-dimer levels, fibrinogen levels, GPS, and multiple vascular territory infarctions would be associated with the risk of death within 6 months. Low fibrinogen levels, lack of antithrombotic therapy, and the presence of metastasis correlated with high risk of stroke recurrence.

Outcomes of Autologous Stem Cell Transplant Consolidation in Primary Central Nervous System Lymphoma: A Mayo Clinic Experience.

A paucity of randomized phase III clinical trials in primary central nervous system lymphoma (PCNSL) has resulted in no uniform consensus on the optimal strategy for consolidation and conditioning regimens for autologous stem cell transplant (ASCT). The past 2 decades have witnessed a preference for thiotepa (TT)-based conditioning regimens due to superior central nervous system penetration. We retrospectively evaluated outcomes of patients with PCNSL who underwent ASCT at Mayo Clinic, Rochester over the past 2 decades, and the impact of TT-based conditioning regimens. Fifty-six patients underwent transplant for PCNSL, with 25 and 31 patients receiving BEAM (non-thiotepa) and carmustine (BCNU)/TT-based conditioning, respectively. All patients received high-dose methotrexate-based induction therapy. While the BCNU/TT group had higher risk disease features such as high International Extranodal Lymphoma Study Group prognostic score, elevated cerebrospinal fluid protein, and older patient population, there was no significant difference at 2 years post-transplant in progression-free survival (BEAM 68.0% [46.1% to 82.5%] versus BCNU/TT, 65.5% [45.2% to 79.8%], P=.99) or overall survival (OS) (84.0% [62.8% to 93.7%] in the BEAM group versus 81.6% [61.3% to 91.9%] in the BCNU/TT group, P=.95). Disease response status before transplant significantly affected the outcomes as those in complete remission had an OS at 2 years post-transplant of 94.7% (68.1% to 99.2%) in the BEAM group and 90.5% (67.0% to 97.5%) in the BCNU/TT group compared with those in partial response, 57.1% (17.2% to 83.7%) in BCNU/TT group and 50.0% (11.1% to 80.4%) in the BEAM group, respectively (P < .0001). Our retrospective cohort adds to the currently available literature and identifies the disease status before transplant as a significant factor affecting survival.

Correlation between telomerase reverse transcriptase messenger RNA expression and survival of patients with papillary thyroid carcinoma

BackgroundTelomerase reverse transcriptase promoter mutations were recently found to be associated with poorer prognosis in patients with papillary thyroid carcinoma. Correlation between telomerase reverse transcriptase messenger RNA expression and survival of patients with papillary thyroid carcinoma has not been determined. MethodsClinical information, somatic mutations, and RNA sequencing of 492 papillary thyroid carcinoma patients were obtained from The Cancer Genome Atlas. Correlations between messenger RNA expression and clinicopathologic variables were evaluated. Recursive partitioning regression trees were used to find cutoffs predicting survival. Differentially expressed gene analysis was performed by Edge-R, and Database for Annotation, Visualization and Integrated Discovery 6.7 was used to pathway analysis. ResultsTelomerase reverse transcriptase messenger RNA expression was positively correlated with stages II and IV and high MACIS Prognostic Score for Papillary Thyroid Carcinoma. Using a telomerase reverse transcriptase messenger RNA level of 2.854 as a cutoff, patients with higher telomerase reverse transcriptase messenger RNA expression showed poorer overall survival (hazard ratio = 20.7). The higher telomerase reverse transcriptase messenger RNA group showed upregulation of 2,255 genes, with enrichment of carcinogenic pathways. ConclusionHigher telomerase reverse transcriptase messenger RNA expression was associated with poorer survival in patients with papillary thyroid carcinoma and was a better predictor for death than telomerase reverse transcriptase promoter mutations. Measuring telomerase reverse transcriptase messenger RNA expression in thyroid cancer tissue may allow early identification of papillary thyroid carcinoma patients with worse overall survival.

Poor nutritional status and sarcopenia influences survival outcomes in gastric carcinoma patients undergoing radical surgery

BackgroundThe survival impacts of the prognostic nutritional index (PNI) and sarcopenia have been separately investigated in patients with gastric carcinoma (GC), while the prognostic impact of the combination of them remains to be addressed. MethodsIn total, 1166 GC patients undergoing radical gastrectomy were retrospectively reviewed. A new prognostic score (PNIS) was developed based on preoperative PNI and sarcopenia; patients with both low PNI (≤44.8) and sarcopenia were allocated a score of 2, and those with only one or neither of these abnormalities were assigned a score of 1 or 0, respectively. ResultsA lower PNI was independently associated with sarcopenia (P = 0.007). There were 704 (60.4%), 356 (30.5%) and 106 (9.1%) patients in the PNIS 0, 1 and 2 groups, respectively. A higher PNIS was associated with advanced age (P < 0.001) and a higher incidence of postoperative complications (P = 0.01). Patients with PNIS 2 showed significantly poorer overall survival (OS) than those with PNIS 1 or 0 (5-year OS; 57.8% vs. 79.2% vs. 91.6%, P < 0.001). Multivariate Cox hazards analysis showed PNIS 2 to be a powerful predictor of poor OS (HR 5.73, P < 0.001) in patients with pStage I disease, while not being independently associated with OS in those with pStage II/III disease. Patients with PNIS 2 had a markedly higher prevalence of non-GC–related death than those with scores of 0–1. ConclusionThe scoring system combining PNI and sarcopenia is useful for predicting survival outcomes, especially non-GC–related death, in patients with early GC, a population with basically good oncological outcomes.

Epidemiology and outcome of high-surgical-risk patients admitted to an intensive care unit in Brazil.

ObjectiveTo define the epidemiological profile and the main determinants of morbidity and mortality in noncardiac high surgical risk patients in Brazil.MethodsThis was a prospective, observational and multicenter study. All noncardiac surgical patients admitted to intensive care units, i.e., those considered high risk, within a 1-month period were evaluated and monitored daily for a maximum of 7 days in the intensive care unit to determine complications. The 28-day postoperative, intensive care unit and hospital mortality rates were evaluated.ResultsTwenty-nine intensive care units participated in the study. Surgeries were performed in 25,500 patients, of whom 904 (3.5%) were high-risk (95% confidence interval - 95%CI 3.3% - 3.8%) and were included in the study. Of the participating patients, 48.3% were from private intensive care units, and 51.7% were from public intensive care units. The length of stay in the intensive care unit was 2.0 (1.0 - 4.0) days, and the length of hospital stay was 9.5 (5.4 - 18.6) days. The complication rate was 29.9% (95%CI 26.4 - 33.7), and the 28-day postoperative mortality rate was 9.6% (95%CI 7.4 - 12.1). The independent risk factors for complications were the Simplified Acute Physiology Score 3 (SAPS 3; odds ratio - OR = 1.02; 95%CI 1.01 - 1.03) and Sequential Organ Failure Assessment Score (SOFA) on admission to the intensive care unit (OR = 1.17; 95%CI 1.09 - 1.25), surgical time (OR = 1.001, 95%CI 1.000 - 1.002) and emergency surgeries (OR = 1.93, 95%CI, 1.10 - 3.38). In addition, there were associations with 28-day mortality (OR = 1.032; 95%CI 1.011 - 1.052), SAPS 3 (OR = 1.041; 95%CI 1.107 - 1.279), SOFA (OR = 1.175, 95%CI 1.069 - 1.292) and emergency surgeries (OR = 2.509; 95%CI 1.040 - 6.051).ConclusionHigher prognostic scores, elderly patients, longer surgical times and emergency surgeries were strongly associated with higher 28-day mortality and more complications during the intensive care unit stay.

Hodgkin lymphoma detection and survival: findings from the Haematological Malignancy Research Network.

BackgroundHodgkin lymphoma is usually detected in primary care with early signs and symptoms, and is highly treatable with standardised chemotherapy. However, late presentation is associated with poorer outcomes.AimTo investigate the relationship between markers of advanced disease, emergency admission, and survival following a diagnosis of classical Hodgkin lymphoma (CHL).Design & settingThe study was set within a sociodemographically representative UK population-based patient cohort of ~4 million, within which all patients were tracked through their care pathways, and linked to national data obtained from Hospital Episode Statistics (HES) and deaths.MethodAll 971 patients with CHL newly diagnosed between 1 September 2004–31 August 2015 were followed until 18th December 2018.ResultsThe median diagnostic age was 41.5 years (range 0–96 years), 55.2% of the patients were male, 31.2% had stage IV disease, 43.0% had a moderate–high or high risk prognostic score, and 18.7% were admitted via the emergency route prior to diagnosis. The relationship between age and emergency admission was U-shaped: more likely in patients aged <25 years and ≥70 years. Compared to patients admitted via other routes, those presenting as an emergency had more advanced disease and poorer 3-year survival (relative survival 68.4% [95% confidence interval {CI} = 60.3 to 75.2] versus 89.8% [95% CI = 87.0 to 92.0], respectively [P<0.01]). However, after adjusting for clinically important prognostic factors, no difference in survival remained.ConclusionThese findings suggest that CHL survival as a whole could be increased by around 4% if the cancer in patients who presented as an emergency had been detected at the same point as in other patients.

QOLP-05. PREDICTING SURVIVAL WITH THE HEIDELBERG PROGNOSTIC MODEL AFTER SALVAGE STEREOTACTIC RADIOSURGERY OF PREVIOUSLY IRRADIATED PROGRESSIVE HIGH-GRADE GLIOMAS

Abstract BACKGROUND The concept of repeat radiotherapy for previously irradiated, progressive high-grade gliomas (PHGG) is intuitively rational for a disease that has the potential to be a life-threatening illness and seriously affect the quality of remaining life. Recently, a simplified method of prognosis prediction (the Heidelberg prognostic model/HPM) was developed to evaluate survival after re-irradiation of PHGGs. OBJECTIVE This retrospective study aimed to assess whether salvage stereotactic radiosurgery (SSRS) is worthwhile in patients with PHGGs, and to determine which individuals are likely to benefit from retreatment using the HPM. METHODS Three hundred eighty-three people were diagnosed with intracranial glioma between 2000 and 2010 at our institution. From this population, 25 patients (7%) who had a history of prior irradiation and underwent SSRS for PHGGs formed the subjects of this clinical audit. In the HPM system, scores were assigned for clinicopathological features such as age, histology and interval duration between treatments. There were five and 20 patients with HPM determined low and high prognostic scores, respectively. The mean follow-up period was 9.9 months. RESULTS Overall median survival (MS) was 7 months, and the 6, 12- and 24-months crude survival rates (CSR) were 60%, 28% and 16%, respectively. The MS and CSRs for the low scoring patients were 20 months, 100%, 100% and 20%, respectively; for the 20 high-scoring individuals, the corresponding findings were 8 months, 75%, 35% and 10%, respectively. Among the evaluable 11 people, the quality of life was acceptable in approximately half of the cases. Local recurrence rate after SSRS was 12%. Adverse-related events were not observed. CONCLUSION A trend towards improved survival was observed in the HPM low-scoring patients. More documentation of favorable effects is required to support the useful role of SSRS as second line treatment of PHGGs.

Identification and Clinical Validation of a Novel 4 Gene-Signature with Prognostic Utility in Colorectal Cancer.

Colorectal cancer (CRC) is a high burden disease with several genes involved in tumor progression. The aim of the present study was to identify, generate and clinically validate a novel gene signature to improve prediction of overall survival (OS) to effectively manage colorectal cancer. We explored The Cancer Genome Atlas (TCGA), COAD and READ datasets (597 samples) from The Protein Atlas (TPA) database to extract a total of 595 candidate genes. In parallel, we identified 29 genes with perturbations in > 6 cancers which are also affected in CRC. These genes were entered in cBioportal to generate a 17 gene panel with highest perturbations. For clinical validation, this gene panel was tested on the FFPE tissues of colorectal cancer patients (88 patients) using Nanostring analysis. Using multivariate analysis, a high prognostic score (composite 4 gene signature—DPP7/2, YWHAB, MCM4 and FBXO46) was found to be a significant predictor of poor prognosis in CRC patients (HR: 3.42, 95% CI: 1.71–7.94, p < 0.001 *) along with stage (HR: 4.56, 95% CI: 1.35–19.15, p = 0.01 *). The Kaplan-Meier analysis also segregated patients on the basis of prognostic score (log-rank test, p = 0.001 *). The external validation using GEO dataset (GSE38832, 122 patients) corroborated the prognostic score (HR: 2.7, 95% CI: 1.99–3.73, p < 0.001 *). Additionally, higher score was able to differentiate stage II and III patients (130 patients) on the basis of OS (HR: 2.5, 95% CI: 1.78–3.63, p < 0.001 *). Overall, our results identify a novel 4 gene prognostic signature that has clinical utility in colorectal cancer.

A prognostic nomogram to predict the benefit of adjuvant radiotherapy for resected inflammatory breast cancer patients.

e12007 Background: A nomogram is a convenient and reliable tool for individualizing cancer prognosis. Therefore, the purpose of this study was to construct a clinical nomogram for predicting overall mortality (OM) to help clinicians to make individualized estimates of the potential benefit of adjuvant radiotherapy (RT) for resected inflammatory breast cancer (IBC) patients. Methods: We used the Surveillance, Epidemiology, and End Results database to identify 4030 IBS patients treated with surgery between 2004 and 2012, and randomly classified the patients into the discovery (n = 2417) and validation (n = 1613) cohorts. A Cox regression hazards model was used to build a nomogram by determining the prognostic factors for OM in the discovery cohort. The overall accuracy and discriminative ability was measured by Brier score and Harrell's concordance index (c-index). Results: In multivariate analysis, age, race, number of primaries, N stage, estrogen receptor, progesterone receptor status, and marital status, were the independent predictive factors of OM. These variables were selected to generate the nomogram. The calibration curves for 2-, and 5-year OM rate showed excellent agreement between prediction and actual observation. The Brier score and c-index demonstrated the nomogram performed better than the 7th edition TNM staging system for predicting OM possibility. In addition, the nomogram predicted that the magnitude of benefit from adjuvant RT for an individual IBS patient could vary, the certain subgroup of patients (prognostic score: 0-25) would not gain benefit from adjuvant RT, while RT had more pronounced effects in participants with higher prognostic score (prognostic score: ≥25). Conclusions: This nomogram is a reliable prognostic method for predicting OM in IBC patients after surgical resection, which could be used to predict which IBC patients may benefit from adjuvant RT after surgery.