Predictors of Outcome in Patients with Advanced Nonseminomatous Germ Cell Testicular Tumors

Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches

The real-life efficacy of the second line treatment strategy in advanced pancreas cancer

ABS TRACT Objective: Pancreatic cancer is one of the leading causes of cancer-related death. Despite the introduction of new therapeutic agents, survival rates remain low. Furthermore, few trials have evaluated the options for second-line therapy and the prognostic variables. In this study, we aimed to determine the real-world efficacy and prognostic parameters of second-line treatment for advanced pancreatic cancer. Material and Methods: Patients with advanced pancreatic cancer from different centers who received second-line treatment were enrolled in the study. The patients’ demographic, clinical, and pathological characteristics were retrieved retrospectively. Results: A total of 161 patients were enrolled in the study. The majority of the patients (50.3%) received oxaliplatin plus fluoropyrimidine as second-line treatment. The median progression-free survival and overall survival for the entire cohort were 2.5 months and 4.5 months, respectively. In univariate anal-yses, an Eastern Cooperative Oncology Group performance status ≥2, age ≥65 years, hypoalbuminemia, thrombocytosis, presence of metastatic peritoneal disease, elevated alkaline phosphatase and carcinoembryonic antigen levels, and a neutrophil-lymphocyte ratio (NLR) ≥3 were identified as poor prognostic factors. In multivariable analyses, low albumin level (p=0.031) and high NLR (p=0.05) were found to be independent prognostic factors for overall survival. Conclusion: Pancreatic cancer is a unique malignancy, and advanced disease has a dismal prog-nosis. In univariate analyses, we identified multiple factors that were poor prognostic variables. In particular, the albumin level and NLR were independent prognostic factors for overall survival, and these parameters might be useful in selecting the second-line treatment and pre-dicting the survival of these patients

Predictive factor for lymph node metastasis in non-metastatic colorectal adenocarcinomas

Objectives: To evaluate the predictive factors of lymph node involvement in non-metastatic colorectal adenocarcinomas (nmCRC). Methods: A total of 453 patients diagnosed with nmCRC were analyzed regarding T stage, lymphovascular invasion status, tumor grade and proposed risk score (RS), determined by the combination of these three factors for lymph node metastasis. Results: The median age was 62 (25-90 years), M/F ratio was 1.4:1 and majority of the patients had tumors localized on the left colon (70.6%). The number of excised lymph nodes was ≥12 in 77% of the cases. The postoperative pathological assessments revealed that 57.2% of patie,nts had N0 disease, 29.1% had N1 disease, and 13.7% had N2 disease. The T stages (p=0.007), grade (p<0.001), lymphovascular invasion (p=0.002), RS (p<0.001), and number of excised lymph nodes (p=0.029) were significantly different between N0, N1, and N2 patients. Higher RS was associated with lymph node metastasis (p<0.001). Conclusion: The risk score may predict lymph node metastasis in patients with nmCRC and if validated may be helpful in the decision-making of adjuvant chemotherapy, especially in the elderly and patients with inadequate lymph node dissection

Management of patients with advanced prostate cancer—metastatic and/or castration-resistant prostate cancer: report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022

Background: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. Objective: To present the voting results of the APCCC 2022. Design, setting, and participants: The experts voted on controversial questions where high- level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration- resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. Outcome measurements and statistical analysis: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration- resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. Results and limitations: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. Conclusions: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. Twitter summary: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. Take-home message: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration- resistant prostate cancer is summarised here

Management of Patients with Advanced Prostate Cancer. Part I : Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.publishedVersionPeer reviewe

Management of patients with advanced prostate cancer. Part I: Intermediate-/high-risk and locally advanced disease, biochemical relapse, and side effects of hormonal treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

© 2023 The Authors. Published by Elsevier on behalf of European Association of Urology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.eururo.2022.11.002Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.We gratefully acknowledge the following organisations for providing financial support for the APCCC 2022: The City of Lugano and Movember Foundation. Ros Eeles is supported by a National Institute of Health Research grant to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. We also acknowledge sponsorship from several for-profit organisations for APCCC 2022, including Advanced Accelerator Applications, Amgen, Astellas, AstraZeneca, Bayer Health Care, Debiopharm, MSD, Janssen Oncology, Myovant Sciences, Orion Pharma, Pfizer Oncology, Roche, Telix Innovations SA, Ferring Pharmaceuticals, Lantheus, and Tolmar. These for-profit organisations supported the conference financially but had no input on the scientific content or the final publication.Accepted versio

Management of patients with advanced prostate cancer. Part I: intermediate-/high-risk and locally advanced disease, biochemical relapse, and side effects of hormonal treatment: report of the advanced prostate cancer consensus conference 2022

Background: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective: To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. Patient summary: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions

Cancer modeling via biologically validated genes

The cancer disease is the second most common disease type seen after the frequency of the cardiovascular diseases. The frequency of this genetic disease changes with respect to the gender. Accordingly, the gynecological cancer, which covers ovarian, endometrial or cervical cancer, is the second most common cancer type in women after the breast cancer. Similar to other cancer types, the gynecological cancer is the system disease, meaning that the malfunctions and mutations in the gene regulatory pathways cause this illness. Hereby, in order to diagnoseand treat it, it is crucial to understand the activations and the crosstalk of the biological systems that are affected by this cancer. In this study, to detect the changes in interactions between the genes of the same and the distinct pathways under the gynecological cancer, we comprehensively check the associated literature and make a list of the most affected genes. Then, we consider that these core genes can be represented artificially as an oncogenic network and estimate the strength of their interactions by a mathematical model. Later, we extend our system by adding other proteins within the most affected two regulatory networks, so-called MAPK/ERK and PI3K/AKT pathways, under this illness. In this case, the total number of genes used in the analysis becomes 41 proteins. After we infer the interactions of this complex structure by a mathematical model, we further extend our system by including the proteins affected by the crosstalk between systems resulting in 120 proteins roughly. Finally, we estimatethis largest network. In all these analyses, we use a microarray dataset which is composed of 3171 genes that are collected under various cancer types. On the other hand, in the underlying three-level inference, we apply the Gaussian graphical model in the mathematical description of the systems and estimate the model parameters via the graphical lasso approach. From the first stage of modeling, we obtain promising results which can be fully validated by the knowledge in the databases. For the following two models, part of our findings are validated and the remainings are reported as an interesting list of interactions that can be further studies. As the future work, we consider to combine different datasets to describe a more general view of this oncogenicnetwork and investigate other mathematical models