scholarly journals Immunologic Consequences of Sequencing Cancer Radiotherapy and Surgery

2019 ◽  
pp. 1-16 ◽  
Author(s):  
Juan Carlos López Alfonso ◽  
Jan Poleszczuk ◽  
Rachel Walker ◽  
Sungjune Kim ◽  
Shari Pilon-Thomas ◽  
...  
Keyword(s):  
Statistical Power ◽  
Antitumor Immunity ◽  
Early Stage ◽  
Disease Free Survival ◽  
Immune Memory ◽  
Cervix Uteri ◽  
Model Parameters ◽  
Data Set ◽  
Corpus Uteri ◽  
Study Results

PURPOSE Early-stage cancers are routinely treated with surgery followed by radiotherapy (SR). Radiotherapy before surgery (RS) has been widely ignored for some cancers. We evaluate overall survival (OS) and disease-free survival (DFS) with SR and RS for different cancer types and simulate the plausibility of RS- and SR-induced antitumor immunity contributing to outcomes. MATERIALS AND METHODS We analyzed a SEER data set of early-stage cancers treated with SR or RS. OS and DFS were calculated for cancers with sufficient numbers for statistical power (cancers of lung and bronchus, esophagus, rectum, cervix uteri, corpus uteri, and breast). We simulated the immunologic consequences of SR, RS, and radiotherapy alone in a mathematical model of tumor-immune interactions. RESULTS RS improved OS for cancers with low 20-year survival rates (lung: hazard ratio [HR], 0.88; P = .046) and improved DFS for cancers with higher survival (breast: HR = 0.64; P < .001). For rectal cancer, with intermediate 20-year survival, RS improved both OS (HR = 0.89; P = .006) and DFS (HR = 0.86; P = .04). Model simulations suggested that RS could increase OS by eliminating cancer for a broader range of model parameters and radiotherapy-induced antitumor immunity compared with SR for selected parameter combinations. This could create an immune memory that may explain increased DFS after RS for certain cancers. CONCLUSION Study results suggest plausibility that radiation to the bulk of the tumor could induce a more robust immune response and better harness the synergy of radiotherapy and antitumor immunity than postsurgical radiation to the tumor bed. This exploratory study provides motivation for prospective evaluation of immune activation of RS versus SR in controlled clinical studies.

scholarly journals Retrospective Analysis of Cervical Cancer Treatment Outcomes: Ten Years of Experience with the Vaginal Assisted Radical Laparoscopic Hysterectomy VARLH

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
R. Wojdat ◽  
E. Malanowska
Keyword(s):  
Cervical Cancer ◽  
Radical Hysterectomy ◽  
Early Stage ◽  
Invasive Cervical Cancer ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Laparoscopic Approach ◽  
Laparoscopic Hysterectomy ◽  
Study Results ◽  
Early Stage Cervical Cancer

Background. LACC trial demonstrated inferiority of laparoscopic approach for the treatment of early-stage cervical cancer. There are still limited data from retrospective trials regarding whether survival outcomes after laparoscopic radical hysterectomy are equivalent to those after open abdominal radical hysterectomy. In this study, we present results of combined vaginal radical laparoscopic hysterectomy in the treatment of early-stage cervical cancer. Methods. This retrospective study was carried out at the Department of Gynecology in Mathilden Hospital (Herford, Germany). Between January 2008 and April 2018, all the patients with invasive cervical cancer who underwent combined vaginal assisted radical laparoscopic hysterectomy (VARLH) without the use of any uterine manipulator were enrolled to the study. Results. A total number of 124 patients with diagnosis of invasive cervical cancer were enrolled in the study. All of the patients underwent minimally invasive surgery and were divided according to FIGO 2019: stage IA (25.9%), IB1 (25.0%), IB2-IIB (28.4%), and III/IV (20.7%). Overall, the mean age of the patients was 51.84 years. After a study collection, a median follow-up was 45.6 (range 23.7-76.5) months. The 3- and 5-year disease-free survival rates for early-stage cervical cancer were both 98%, and the 3- and 5-year overall survival rates were 100% and 97%, respectively. We have not observed any recurrence in our study group of patients with early-stage cervical cancer. Conclusions. Combined VARLH can be considered a safe and effective procedure for the treatment of early-stage cervical cancer. Surgical strategy with oncological principles determines the quality and long-term success of the operation in early cervical cancer regardless of laparoscopic approach.

scholarly journals Extending the Basic Local Independence Model to Polytomous Data

Psychometrika ◽  
2020 ◽  
Vol 85 (3) ◽  
pp. 684-715
Author(s):  
Luca Stefanutti ◽  
Debora de Chiusole ◽  
Pasquale Anselmi ◽  
Andrea Spoto
Keyword(s):  
Learning Assessment ◽  
Model Parameters ◽  
Local Independence ◽  
Data Set ◽  
True Parameter ◽  
Independence Model ◽  
Study Results ◽  
Minimum Discrepancy ◽  
Basic Local Independence Model ◽  
Parameter Values

Abstract A probabilistic framework for the polytomous extension of knowledge space theory (KST) is proposed. It consists in a probabilistic model, called polytomous local independence model, that is developed as a generalization of the basic local independence model. The algorithms for computing “maximum likelihood” (ML) and “minimum discrepancy” (MD) estimates of the model parameters have been derived and tested in a simulation study. Results show that the algorithms differ in their capability of recovering the true parameter values. The ML algorithm correctly recovers the true values, regardless of the manipulated variables. This is not totally true for the MD algorithm. Finally, the model has been applied to a real polytomous data set collected in the area of psychological assessment. Results show that it can be successfully applied in practice, paving the way to a number of applications of KST outside the area of knowledge and learning assessment.

scholarly journals The KM-Algorithm Identifies Regulated Genes in Time Series Expression Data

2009 ◽  
Vol 2009 ◽  
pp. 1-10
Author(s):  
Martina Bremer ◽  
R. W. Doerge
Keyword(s):  
Gene Expression ◽  
Time Series ◽  
Statistical Power ◽  
Regulatory Networks ◽  
Real Data ◽  
Model Parameters ◽  
Expression Data ◽  
Data Set ◽  
Gene Expression Time Series ◽  
Expression Time

We present a statistical method to rank observed genes in gene expression time series experiments according to their degree of regulation in a biological process. The ranking may be used to focus on specific genes or to select meaningful subsets of genes from which gene regulatory networks can be built. Our approach is based on a state space model that incorporates hidden regulators of gene expression. Kalman (K) smoothing and maximum (M) likelihood estimation techniques are used to derive optimal estimates of the model parameters upon which a proposed regulation criterion is based. The statistical power of the proposed algorithm is investigated, and a real data set is analyzed for the purpose of identifying regulated genes in time dependent gene expression data. This statistical approach supports the concept that meaningful biological conclusions can be drawn from gene expression time series experiments by focusing on strong regulation rather than large expression values.

EXPONENTIATED HALF-LOGISTIC LOMAX DISTRIBUTION WITH PROPERTIES AND APPLICATION

2019 ◽  
Vol XVI (2) ◽  
pp. 1-11
Author(s):  
Farrukh Jamal ◽  
Hesham Mohammed Reyad ◽  
Soha Othman Ahmed ◽  
Muhammad Akbar Ali Shah ◽  
Emrah Altun
Keyword(s):  
Real Data ◽  
Continuous Model ◽  
Model Parameters ◽  
Data Set ◽  
Lomax Distribution ◽  
Mathematical Properties ◽  
Proposed Model ◽  
Probability Weighted Moment ◽  
Record Statistics ◽  
Maximum Likelihood Criterion

A new three-parameter continuous model called the exponentiated half-logistic Lomax distribution is introduced in this paper. Basic mathematical properties for the proposed model were investigated which include raw and incomplete moments, skewness, kurtosis, generating functions, Rényi entropy, Lorenz, Bonferroni and Zenga curves, probability weighted moment, stress strength model, order statistics, and record statistics. The model parameters were estimated by using the maximum likelihood criterion and the behaviours of these estimates were examined by conducting a simulation study. The applicability of the new model is illustrated by applying it on a real data set.

Identification of Coronary Artery Disease using Artificial Neural Network and Case Based Reasoning

2020 ◽  
Vol 13 ◽  
Author(s):  
Varun Sapra ◽  
M.L Saini ◽  
Luxmi Verma
Keyword(s):  
Neural Network ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Early Stage ◽  
Second Phase ◽  
Case Based Reasoning ◽  
Data Set ◽  
Artery Disease ◽  
Severity Of The Disease ◽  
Case Based

Background: Cardiovascular diseases are increasing at an alarming rate with very high rate of mortality. Coronary artery disease is one of the type of cardiovascular disease, which is not easily diagnosed in its early stage. Prevention of Coronary Artery Disease is possible only if it is diagnosed, at early stage and proper medication is done. Objective: An effective diagnosis model is important not only for the early diagnosis but also to check the severity of the disease. Method: In this paper, a hybrid approach is followed, with the integration of deep learning (multi-layer perceptron) with Case based reasoning to design analytical framework. This paper suggests two phases of the study, one in which the patient is diagnosed for Coronary artery disease and in second phase, if the patient is suffering from the disease then employing Case based reasoning to diagnose the severity of the disease. In the first phase, multilayer perceptron is implemented on reduced dataset and with time-based learning for stochastic gradient descent respectively. Results: The classification accuracy is increase by 4.18 % with reduced data set using deep neural network with time based learning. In second phase, if the patient is diagnosed as positive for Coronary artery disease, then it triggers the Case based reasoning system to retrieve from the case base, the most similar case to predict the severity for that patient. The CBR model achieved 97.3% accuracy. Conclusion: The model can be very useful for medical practitioners as a supporting decision system and thus can save the patients from unnecessary medical expenses on costly tests and can improve the quality and effectiveness of medical treatment.

scholarly journals Improving Risk Stratification of Early Oral Tongue Cancer with TNM-Immune (TNM-I) Staging System

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3235
Author(s):  
Alhadi Almangush ◽  
Ibrahim O. Bello ◽  
Ilkka Heikkinen ◽  
Jaana Hagström ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tongue Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Staging System ◽  
Oral Tongue ◽  
Oral Tongue Cancer ◽  
Important Player ◽  
Infiltrating Lymphocytes

Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio (HR) of 2.87 (95% CI 1.92–4.28; p < 0.001); HR of 2.41 (95% CI 1.26–4.60; p = 0.008) for disease-specific survival; and HR of 1.97 (95% CI 1.13–3.43; p = 0.017) for disease-free survival. The TNM-Immune staging system showed a powerful ability to identify cases with worse survival. The immune response is an important player which can be assessed by evaluating TILs, and it can be implemented in the staging criteria of early OTSCC. TNM-Immune staging forms a step towards a more personalized classification of early OTSCC.

scholarly journals The Treatment Effect of Liver Transplantation versus Liver Resection for HCC: A Review and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3730
Author(s):  
Berend R. Beumer ◽  
Roeland F. de Wilde ◽  
Herold J. Metselaar ◽  
Robert A. de Man ◽  
Wojciech G. Polak ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Resection ◽  
Early Stage ◽  
Disease Free Survival ◽  
Milan Criteria ◽  
Term Survival ◽  
Equal Distribution ◽  
Intention To Treat ◽  
Treat Analysis

For patients presenting with hepatocellular carcinoma within the Milan criteria, either liver resection or liver transplantation can be performed. However, to what extent either of these treatment options is superior in terms of long-term survival is unknown. Obviously, the comparison of these treatments is complicated by several selection processes. In this article, we comprehensively review the current literature with a focus on factors accounting for selection bias. Thus far, studies that did not perform an intention-to-treat analysis conclude that liver transplantation is superior to liver resection for early-stage hepatocellular carcinoma. In contrast, studies performing an intention-to-treat analysis state that survival is comparable between both modalities. Furthermore, all studies demonstrate that disease-free survival is longer after liver transplantation compared to liver resection. With respect to the latter, implications of recurrences for survival are rarely discussed. Heterogeneous treatment effects and logical inconsistencies indicate that studies with a higher level of evidence are needed to determine if liver transplantation offers a survival benefit over liver resection. However, randomised controlled trials, as the golden standard, are believed to be infeasible. Therefore, we suggest an alternative research design from the causal inference literature. The rationale for a regression discontinuity design that exploits the natural experiment created by the widely adopted Milan criteria will be discussed. In this type of study, the analysis is focused on liver transplantation patients just within the Milan criteria and liver resection patients just outside, hereby ensuring equal distribution of confounders.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

scholarly journals Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma

2021 ◽  
Author(s):  
Ignacio Ruz-Caracuel ◽  
Álvaro López-Janeiro ◽  
Victoria Heredia-Soto ◽  
Jorge L. Ramón-Patino ◽  
Laura Yébenes ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Mismatch Repair ◽  
Predictive Value ◽  
Early Stage ◽  
Disease Free Survival ◽  
Low Grade ◽  
Beta Catenin ◽  
Free Survival ◽  
Disease Free ◽  
Risk Of Relapse

AbstractLow-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours. Graphical abstract

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