prognostic groups
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2022 ◽  
Vol 63 (1) ◽  
pp. 21
Author(s):  
Leonardo Oliveira Reis ◽  
Luciana S. B. Dal Col ◽  
Diego M. Capibaribe ◽  
Gustavo B. de Mendonça ◽  
Fernandes Denardi ◽  
...  

2021 ◽  
Vol 17 (3) ◽  
pp. 19-28
Author(s):  
M. I. Volkova ◽  
N. L. Vashakmadze ◽  
A. V. Klimov ◽  
A. K. Begaliev ◽  
K. P. Kuznetsov ◽  
...  

Objective: to identify independent risk factors affecting survival of patients with renal cell carcinoma (RCC) and tumor venous thrombosis who have undergone nephrectomy and thrombectomy.Materials and methods. This study included 768 patients with RCC complicated by tumor venous thrombosis who have undergone nephrectomy and thrombectomy. Median age was 58 years (range: 16-82 years); the male to female ratio was 2.3:1. The symptoms of tumor venous thrombosis were identified in 232 patients (30.2 %); laboratory abnormalities at baseline were observed in 456 patients (59.3 %). Grade I and II tumor thrombosis was diagnosed in 456 (59.3 %) and 201 (26.2 %) patients, respectively; grade III and IV thrombosis was found in 171 (22.3 %) and 177 (23.0 %) patients, respectively. One hundred and twenty-nine participants (16.8 %) had infrarenal inferior vena cava thrombosis. Regional metastases were detected in 188 individuals (24.4 %), distant metastases were registered in 274 patients (35.7 %). All patients have undergone surgery: either radical (n = 555; 72.3 %) or cytoreductive (n = 213; 27.7 %). All primary tumors were histologically classified as RCC (G3-4 in 337 cases; 43.9 %). A total of 719 patients (93.6 %) survived the perioperative period; 183 patients with metastasis (23.8 %) received systemic antitumor therapy.Results. The median follow-up was 24 months (range: 1-200 months). The 24-month overall and cancer-specific survival of all patients were 96.9 and 99.7 %, respectively; recurrence-free survival of patients after radical surgery reached 92.9 %. Progression-free survival among those patients who underwent cytoreductive surgery and received first-line therapy/follow-up was 41.7 %. Negative predictive factors of overall survival included hepatomegaly (p = 0.024), ascites (p = 0.033), level IV tumor thrombosis (p <0.0001), infrarenal inferior vena cava thrombosis (p = 0.002), regional metastases (p <0.0001), and cytoreductive surgery (p = 0.012). Depending on the number of risk factors, we have identified 3 prognostic groups: favorable (0 factors), intermediate (1-2 factors), and poor (3-6 factors). Median overall survival differed significantly between the groups and was 128.6 ± 11.8; 40.9 ± 6.7 and 12.3 ± 2.2 months, respectively (p <0.0001 for all).Conclusion. Stratification of patients operated on for RCC and venous tumor thrombosis with their allocation to prognostic groups will ensure the choice of an optimal management strategy.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 225-225
Author(s):  
Shaun Fleming ◽  
Cheng-Hong Tsai ◽  
Hartmut Döhner ◽  
Konstanze Döhner ◽  
Elli Papaemmanuil ◽  
...  

Abstract Genomic profiling contributes to assessment of suitability for allogeneic hematopoietic cell transplant (alloHCT) in Acute Myeloid Leukaemia (AML). The ELN 2017 AML risk classification identifies patients with favorable, intermediate and adverse risk (Döhner 2017). We have used supervised machine learning (ML) to prognostically risk stratify patients with AML and explore whether prognostic groups benefit from alloHCT in first complete remission (CR1) based on pre-treatment stratification. 1961 patients were identified across the German Acute Myeloid Leukemia Study Group (AMLSG, n=1315) and National Taiwan University Hospital (NTUH, n=646) who had sufficient cytogenetic and genomic information available including the ELN 2017 cytogenetic and genomic abnormalities, spliceosome, cohesin complex and the fifteen most common genomic alterations from the Cancer Genome Atlas dataset (Ley 2013). A supervised machine learning model within R (version 4.1.0) employed a combination of random forest analysis (utilising the RandomForestSRC module version 2.11.0) and recursive partitioning (utilising the Rpart module version 4.1-15) to identify prognostic groups categorised into quintiles based upon 4-year overall survival (OS) into very poor, poor, intermediate, good and very good prognostic groups (A). Outcome according to alloHCT in CR1 was then determined by a time-dependent analysis comparing patients who in CR1 who did/or did not receive an alloHCT and were alive at 147 days (median time to transplant in the cohort). The prognostic groups were then validated against a separate AML cohort (Montreal Leucegene cohort) Patients defined by ML classification (figure 1A) to have very poor risk included patients with complex karyotype and either -7, del(7q), -17, del(17p), abn(17p) or TP53 mutations; EVI1 abnormalities (inv(3)/t(3;3)) and combined spliceosome and ASXL1 mutations. These patients had a very poor outcome irrespective of alloHCT in CR1 with a 4yr OS of 13% vs 15% (p=0.24) (alloHCT vs no-alloHCT). Patients with the combination of bi-allelic CEBPA and NRAS mutations, or the combination of NPM1, NRAS and Cohesin mutations had very good prognosis and failed to derive survival benefit from alloHCT in CR1 (4yr OS 80% vs 96% (p&lt;0.05)) (figure 1B). Patients with either good, intermediate and poor prognosis all demonstrated improvement in OS with alloHCT in CR1 (good prognosis 90% vs 74% (p&lt;0.05), intermediate 65% vs 50%mo (p&lt;0.05) and poor 50% vs 31% (p&lt;0.05)(figure 1B). ML AML classification defines two groups of patients who may not benefit from an alloHCT in CR1. Patients with very good prognosis may avoid the toxicity associated with transplantation with expectation of equivalent outcomes to those in receipt of alloHCT. Patients with very poor prognosis also fail to derive survival benefit from transplantation and represent candidates for novel post-remission strategies to improve the natural history of their disease. As this data predates the usage of FLT3 inhibitors and other novel therapies such as liposomal cytarabine/daunorubicin the impact of these therapies on patient outcome will warrant future consideration. Figure 1 Figure 1. Disclosures Fleming: Amgen: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Servier: Honoraria. Döhner: AstraZeneca: Honoraria; GEMoaB: Honoraria; Novartis: Honoraria, Research Funding; Helsinn: Honoraria; Bristol Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria; Agios: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Berlin-Chemie: Honoraria; Astex Pharmaceuticals: Honoraria; Astellas: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Roche: Honoraria; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Oxford Biomedica: Honoraria; Pfizer: Research Funding. Döhner: Abbvie: Consultancy, Honoraria; Jazz Roche: Consultancy, Honoraria; Janssen: Honoraria, Other: Advisory Board; Astellas: Research Funding; Agios and Astex: Research Funding; Daiichi Sankyo: Honoraria, Other: Advisory Board; Celgene/BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Papaemmanuil: Isabl Technologies: Divested equity in a private or publicly-traded company in the past 24 months; Kyowa Hakko Kirin Pharma: Consultancy. Tien: AbbVie: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria. Reynolds: Abbvie: Research Funding; Alcon: Current equity holder in publicly-traded company; Novartis AG: Current equity holder in publicly-traded company. Wei: Abbvie, Amgen, AstraZeneca, Celgene/BMS, Novartis, Servier and F. Hoffmann-La Roche: Research Funding; Abbvie, Amgen, Astellas, AstraZeneca, Celgene/BMS, Genentech, Janssen, MacroGenics, Novartis, Pfizer, and Servier: Honoraria; Former employee of Walter and Eliza Hall Institute: Patents & Royalties: Prof. Andrew Wei is a former employee of the Walter and Eliza Hall Institute and is eligible for a fraction of the royalty stream related to Venetoclax; Novartis, Abbvie, Celgene/BMS: Speakers Bureau; Abbvie, Amgen, Astellas, AstraZeneca, Celgene/BMS, Genentech, Janssen, MacroGenics, Novartis, Pfizer, and Servier: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257949
Author(s):  
Charles Q. Yang ◽  
Huan Wang ◽  
Zhenqiu Liu ◽  
Matthew T. Hueman ◽  
Aadya Bhaskaran ◽  
...  

Background Integrating additional factors into the TNM staging system is needed for more accurate risk classification and survival prediction for patients with cutaneous melanoma. In the present study, we introduce machine learning as a novel tool that incorporates additional prognostic factors to improve the current TNM staging system. Methods and findings Cancer-specific survival data for cutaneous melanoma with at least a 5 years follow-up were extracted from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute and split into the training set (40,781 cases) and validation set (5,390 cases). Five factors were studied: the primary tumor (T), regional lymph nodes (N), distant metastasis (M), age (A), and sex (S). The Ensemble Algorithm for Clustering Cancer Data (EACCD) was applied to the training set to generate prognostic groups. Utilizing only T, N, and M, a basic prognostic system was built where patients were stratified into 10 prognostic groups with well-separated survival curves, similar to 10 AJCC stages. These 10 groups had a significantly higher accuracy in survival prediction than 10 stages (C-index = 0.7682 vs 0.7643; increase in C-index = 0.0039, 95% CI = (0.0032, 0.0047); p-value = 7.2×10−23). Nevertheless, a positive association remained between the EACCD grouping and the AJCC staging (Spearman’s rank correlation coefficient = 0.8316; p-value = 4.5×10−13). With additional information from A and S, a more advanced prognostic system was established using the training data that stratified patients into 10 groups and further improved the prediction accuracy (C-index = 0.7865 vs 0.7643; increase in C-index = 0.0222, 95% CI = (0.0191, 0.0254); p-value = 8.8×10−43). Both internal validation using the training set and temporal validation using the validation set showed good stratification and a high predictive accuracy of the prognostic systems. Conclusions The EACCD allows additional factors to be integrated into the TNM to create a prognostic system that improves patient stratification and survival prediction for cutaneous melanoma. This integration separates favorable from unfavorable clinical outcomes for patients and improves both cohort selection for clinical trials and treatment management.


Author(s):  
Edwin Wong ◽  
Kevin Marchbank ◽  
Hannah Lomax-Browne ◽  
Isabel Pappworth ◽  
Harriet Denton ◽  
...  

Background and objectives: Membranoproliferative Glomerulonephritis (MPGN) and C3 Glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific aetiological data for paediatric MPGN/C3 glomerulopathy are lacking, and outcome data are based upon retrospective studies without aetiological data. Design, setting, participants, and measurements: Eighty prevalent pediatric patients with MPGN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using COX proportional hazards model. Kidney and transplant graft survival was determined using Kaplan-Meier method. Results: Central histology review determined 39 C3 glomerulopathy, 31 immune-complex MPGN and 10 immune-complex glomerulonephritis (GN) cases. Patients were aged 2-15 (median 9 (IQR 7-11) years. Median complement C3 and C4 levels were 0.31g/L and 0.14g/L respectively; acquired (anti-complement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% patients respectively, across all groups including immune-complex GN. Median follow-up was 5.18 (IQR 2.13-8.08) years. Eleven patients (14%) progressed to kidney failure with 9 transplants performed in 8 patients, 2 of which failed due to recurrent disease. Presence of >50% crescents on initial biopsy was the sole variable associated with kidney failure in multivariable analysis (Hazard Ratio 6.2, p = 0.045; 95% CI 1.05 to 36.6). Three distinct C3 glomerulopathy prognostic groups were identified according to presenting eGFR and >50% crescents on initial biopsy. Conclusions: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric MPGN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.


2021 ◽  
pp. 1-17
Author(s):  
Bernhard G. Weiss ◽  
Mahalia Zoe Anczykowski ◽  
Friedrich Ihler ◽  
Mattis Bertlich ◽  
Jennifer L. Spiegel ◽  
...  

BACKGROUND: MicroRNAs constitute promising biomarkers. OBJECTIVE: The aim was to investigate diagnostic and prognostic implications of miR-182-5p and miR-205-5p in p16-positive and p16-negative oropharyngeal squamous cell carcinomas (OPSCCs). METHODS: Expression of miR-182-5p, miR-205-5p were determined via quantitative real-time-PCR in fresh frozen tissues of 26 p16-positive, 19 p16-negative OPSCCs and 18 HPV-negative oropharyngeal controls. Associations between miRNA-expression, clinicopathological characteristics and prognosis were analyzed. RESULTS: Higher miR-182-5p expression was associated with significant inferior disease-specific survival for p16-positive OPSCCs (HR = 1.98E+09, 95% CI 0–Inf; P= 0.028) and a similar trend was observed for p16-negative OPSCCs (HR = 1.56E+09, 95% CI 0–Inf; P= 0.051). Higher miR-205-5p expression was associated with an inferior progression-free survival (HR = 4.62, 95% CI 0.98–21.83; P= 0.034) and local control rate (HR = 2.18E+09, 95% CI 0–Inf; P= 0.048) for p16-positive OPSCCs. CONCLUSIONS: Results indicate that miR-182-5p and miR-205-5p can further stratify patients with p16-positive OPSCC into prognostic groups.


2021 ◽  
Vol 22 (18) ◽  
pp. 10005
Author(s):  
Gábor Hutóczki ◽  
József Virga ◽  
Zsuzsanna Birkó ◽  
Almos Klekner

Although treatment outcomes of glioblastoma, the most malignant central nervous system (CNS) tumor, has improved in the past decades, it is still incurable, and survival has only slightly improved. Advances in molecular biology and genetics have completely transformed our understanding of glioblastoma. Multiple classifications and different diagnostic methods were made according to novel molecular markers. Discovering tumor heterogeneity only partially explains the ineffectiveness of current anti-proliferative therapies. Dynamic heterogeneity secures resistance to combined oncotherapy. As tumor growth proceeds, new therapy-resistant sub clones emerge. Liquid biopsy is a new and promising diagnostic tool that can step up with the dynamic genetic change. Getting a ’real-time’ picture of a specific tumor, anti-invasion and multi-target treatment can be designed. During invasion to the peri-tumoral brain tissue, glioma cells interact with the extracellular matrix components. The expressional levels of these matrix molecules give a characteristic pattern, the invasion spectrum, which possess vast diagnostical, predictive and prognostic information. It is a huge leap forward combating tumor heterogeneity and searching for novel therapies. Using the invasion spectrum of a tumor sample is a novel tool to distinguish between histological subtypes, specifying the tumor grades or different prognostic groups. Moreover, new therapeutic methods and their combinations are under trial. These are crucial steps towards personalized oncotherapy.


2021 ◽  
Vol 11 (9) ◽  
Author(s):  
Zaid H. Abdel-Rahman ◽  
Michael G. Heckman ◽  
Theodora Anagnostou ◽  
Launia J. White ◽  
Sara M. Kloft‐Nelson ◽  
...  

Author(s):  
Kristofs Folkmanis ◽  
Amrou Hajjar ◽  
Elizabete Junk ◽  
Evelīna Merdane ◽  
Valdis Folkmanis ◽  
...  

Abstract Despite the common use of the prostate-specific antigen (PSA) serum level as a tumour marker in diagnosis of prostate cancer, it seems that the PSA doubling time (PSADT) and PSA velocity (PSAV) could be more useful indicators of tumour behaviour and prognosis for patients. The aim of the study was to evaluate the value of PSAV and PSADT in the diagnosis of prostate cancer and their relationship with prostate cancer histopathological characteristics. Eighty-six patients undergoing radical prostatectomy were enrolled in the study. Based on the PSA measurements the PSA dynamic values were calculated: PSADT and PSAV. In addition, clinical and histo-pathological characteristics, including disease stage and prognostic groups were evaluated. The obtained results showed that the first PSA value was 4.29 ng/ml (1.28–13.56), the second PSA value was 7.76 ng/ml (7.60–47.60), and the third PSA value was 9.67 ng/ml (2.56–98.50). The median PSADT was 51.01 months (7.80–311.81) and the median PSAV was 2.66 ng/ml/per year (0.22–4.66). In addition, significant correlations between PSAV and pre- and post-operative Gleason score, and prognostic groups were observed. Significant correlation between PSADT and pre- and pos-toperative Gleason score and prognostic risk groups was demonstrated. This study demonstrated that PSAV and PSADT were significantly correlated with postoperative Gleason score and prognostic risk groups, demonstrating its role in the diagnosis of prostate cancer progression.


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