Association between mpMRI detected tumor apparent diffusion coefficient and 5-year biochemical recurrence risk after radical prostatectomy.

PURPOSE: To assess the ability of tumor apparent diffusion coefficient (ADC) values obtained from multiparametric magnetic resonance imaging (mpMRI) to predict the risk of 5-year biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: This retrospective analysis included 1207 peripheral and 232 non-peripheral zone prostate cancer (PCa) patients who underwent mpMRI before RP (2012-2015), with the outcome of interest being 5-year BCR. ADC was evaluated as a continuous variable and as categories: low (< 850 µm2/s), intermediate (850-1100 µm2/s), and high (> 1100 µm2/s). Kaplan-Meier curves with log-rank testing of BCR-free survival, multivariable Cox proportional hazard regression models were formed to estimate the risk of BCR. RESULTS: Among the 1439 males with median age 63 (± 7) years, the median follow-up was 59 months, and 306 (25%) patients experienced BCR. Peripheral zone PCa patients with BCR had lower tumor ADC values than those without BCR (874 versus 1025 µm2/s, p < 0.001). Five-year BCR-free survival rates were 52.3%, 74.4%, and 87% for patients in the low, intermediate, and high ADC value categories, respectively (p < 0.0001). Lower ADC was associated with BCR, both as continuously coded variable (HR: 5.35; p < 0.001) and as ADC categories (intermediate versus high ADC-HR: 1.56, p = 0.017; low vs. high ADC-HR; 2.36, p < 0.001). In the non-peripheral zone PCa patients, no association between ADC and BCR was observed. CONCLUSION: Tumor ADC values and categories were found to be predictive of the 5-year BCR risk after RP in patients with peripheral zone PCa and may serve as a prognostic biomarker.

A Transcriptomic Analysis of Laryngeal Dysplasia.

This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery. These transcriptional alterations were observed using the RNA-based next-generation sequencing (NGS) panel Oncomine Immune Response Research Assay (OIRRA) to measure the expression of genes associated with lymphocyte regulation, cytokine signaling, lymphocyte markers, and checkpoint pathways. During the analysis, it became apparent that certain alterations divide dysplasia into two categories: progressive or not. In the future, these biological alterations are the first step to provide new treatment modalities with different classes of drugs currently in use in a systemic or local approach, including classical chemotherapy drugs such as cisplatin and fluorouracile, older drugs like fenretinide, and new checkpoint inhibitor drugs such as nivolumab and pembrolizumab, as well as newer options like T cell therapy (CAR-T). Following these observed alterations, it is possible to differentiate which dysplasias progress or not or relapse quickly. This information could, in the future, be the basis for determining a close follow-up, minimizing surgical interventions, planning a correct and personalized treatment protocol for each patient and, after specific clinical trials, tailoring new drug treatments.

Multiparametric MRI-based 5-year Risk Prediction Model for Biochemical Recurrence of Prostate Cancer after Radical Prostatectomy.

Background Current predictive tools to estimate the risk of biochemical recurrence (BCR) after treatment of prostate cancer do not consider multiparametric MRI (mpMRI) information. Purpose To develop a risk prediction tool that considers mpMRI findings to assess the risk of 5-year BCR after radical prostatectomy. Materials and Methods In this retrospective single-center analysis in 1459 patients with prostate cancer who underwent mpMRI before radical prostatectomy (in 2012-2015), the outcome of interest was 5-year BCR (two consecutive prostate-specific antigen [PSA] levels > 0.2 ng/mL [0.2 µg/L]). Patients were randomly divided into training (70%) and test (30%) sets. Kaplan-Meier plots were applied to the training set to estimate survival probabilities. Multivariable Cox regression models were used to test the relationship between BCR and different sets of exploratory variables. The C-index of the final model was calculated for the training and test sets and was compared with European Association of Urology, University of California San Francisco Cancer of the Prostate Risk Assessment, Memorial Sloan-Kettering Cancer Center, and Partin risk tools using the partial likelihood ratio test. Five risk categories were created. Results The median duration of follow-up in the whole cohort was 59 months (IQR, 32-81 months); 376 of 1459 (25.8%) patients had BCR. A multivariable Cox regression model (referred to as PIPEN, and composed of PSA density, International Society of Urological Pathology grade group, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extraprostatic extension score, nodes) fitted to the training data yielded a C-index of 0.74, superior to that of other predictive tools (C-index 0.70 for all models; P ≤ .01) and a median higher C-index on 500 test set replications (C-index, 0.73). Five PIPEN risk categories were identified with 5-year BCR-free survival rates of 92%, 84%, 71%, 56%, and 26% in very low-, low-, intermediate-, high-, and very high-risk patients, respectively (all P < .001). Conclusion A five-item model for predicting the risk of 5-year BCR after radical prostatectomy for prostate cancer was developed and internally verified, and five risk categories were identified. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Aguirre and Ortegón in this issue.

The Genetic and Immunologic Landscape Underlying the Risk of Malignant Progression in Laryngeal Dysplasia.

(1) Background: The development of laryngeal cancer is a multistep process involving structural alterations of the epithelial mucosa, from dysplasia (LDy) to invasive carcinoma. In this study, we define new biomarkers, prognostic for malignant transformation, in patients affected by LDy. (2) Methods: We used targeted next-generation sequencing and immunohistochemical analysis to define the mutational and immunological landscape of 15 laryngeal dysplasia progressing to invasive cancer (progressing dysplasia), as well as 31 cases of laryngeal dysplasia that did not progress to carcinoma (non-progressing dysplasia). Two pathologists independently analyzed the presence of tumor-infiltrating lymphocytes in LDy pre-embedded paraffin-fixed specimens. The RNA-based next-generation sequencing panel OIRRA was used to evaluate the expression of 395 genes related to immune system activation. (3) Results: High TILs are significantly correlated with a higher risk of malignant transformation. The non-brisk pattern was significantly associated with an 86% reduced risk of malignant progression (OR = 0.16, 95% CI: 0.03-0.5, p = 0.008). TILs showed a highly positive correlation with CCR6, CD83, HLA-DPB1, MX1 and SNAI1, and they were inversely correlated with CD48, CIITA, CXCR4, FCER1G, IL1B, LST1 and TLR8. (4) Conclusions: TILs have a great potential to identify high-risk progression dysplasia and thus to define surveillance protocols and prevention programs.

Prediction of the Malignancy of a Breast Lesion Detected on Breast Ultrasound: Radiomics Applied to Clinical Practice.

The study aimed to evaluate the performance of radiomics features and one ultrasound CAD (computer-aided diagnosis) in the prediction of the malignancy of a breast lesion detected with ultrasound and to develop a nomogram incorporating radiomic score and available information on CAD performance, conventional Breast Imaging Reporting and Data System evaluation (BI-RADS), and clinical information. Data on 365 breast lesions referred for breast US with subsequent histologic analysis between January 2020 and March 2022 were retrospectively collected. Patients were randomly divided into a training group (n = 255) and a validation test group (n = 110). A radiomics score was generated from the US image. The CAD was performed in a subgroup of 209 cases. The radiomics score included seven radiomics features selected with the LASSO logistic regression model. The multivariable logistic model incorporating CAD performance, BI-RADS evaluation, clinical information, and radiomic score as covariates showed promising results in the prediction of the malignancy of breast lesions: Area under the receiver operating characteristic curve, [AUC]: 0.914; 95% Confidence Interval, [CI]: 0.876-0.951. A nomogram was developed based on these results for possible future applications in clinical practice.

The Prognostic Impact of Quitting Smoking at or around Diagnosis on the Survival of Patients with Gastrointestinal Cancers: A Systematic Literature Review.

Cigarette smoking is a strong risk factor for the occurrence of gastrointestinal cancers, and a substantial proportion of newly diagnosed patients is made up of active smokers, yet the impact of smoking cessation at or around diagnosis on the clinical course of these cancers (whose prognosis is often unfavourable) has never been summarized to date. We reviewed studies published until 30 April 2022 that investigated whether smoking cessation at or around diagnosis favourably affects the clinical course of gastrointestinal cancers patients. Six studies were included for colorectal cancer patients, which provided limited yet suggestive evidence that quitters may have longer disease-specific survival compared to continued smokers. Only one study each focused on patients with gastric or HBV-positive liver cancer (both reporting a survival advantage for quitters vs. continued smokers), while we found no eligible studies for patients with cancer at other sites within the digestive system. More research is urgently needed to expand the evidence on the topic, given the potentially major clinical implications for these patients. Moreover, health professionals should provide the necessary smoking cessation support to any smoker who is undergoing diagnostic work-up or treatment for gastrointestinal cancer.

Prediction of the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients With MRI-Radiomics: A Systematic Review and Meta-analysis.

We performed a systematic review and a meta-analysis of studies using MRI-radiomics for predicting the pathological complete response in breast cancer patients undergoing neoadjuvant therapy , and we evaluated their methodological quality using the radiomics-quality-score (RQS). Random effects meta-analysis was performed pooling area under the receiver operating characteristics curves. Publication-bias was assessed using the Egger's test and visually inspecting the funnel plot. Forty-three studies were included in the qualitative review and 34 in the meta-analysis. Summary area under the receiver operating characteristics curve was 0,78 (95%CI:0,74-0,81). Heterogeneity according to the I2 statistic was substantial (71%) and there was no evidence of publication bias (P-value = 0,2). The average RQS was 12,7 (range:-1-26), with an intra-class correlation coefficient of 0.93 (95%CI:0.61-0.97). Year of publication, field intensity and synthetic RQS score do not appear to be moderators of the effect (P-value = 0.36, P-value = 0.28 and P-value = 0.92, respectively). MRI-radiomics may predict response to neoadjuvant therapy in breast cancer patients but the heterogeneity of the current studies is still substantial.

Myocardial infarction non-invasively induced in rabbits by administering isoproterenol and vasopressin: protective effects exerted by verapamil.

Myocardial infarction is usually induced in small animals by means of invasive procedures: the aim of this study was to cause heart necrosis lesions by non-invasive means. We injected rabbits with isoproterenol (3 mg/kg, i.p.) and vasopressin (0.3 mg/kg/5 min, i.v.) alone and in combination, and studied their effects on myocardial histology, electrocardiographic profiles, the appearance of the plasma cardiac necrosis marker c-troponin I (c-TPN I), hemodynamic parameters (blood pressure, heart rate), the coagulative process partial throboplastine time (PTT), and plasma nitric oxide (NO) levels. In the rabbits treated with vasopressin alone, the ischemic damage was associated with a decrease in NO values, and the appearance of electrocardiographic T-wave inversion and low plasma c-TPN I levels, whereas the animals treated with isoproterenol alone had necrotic bands in the myocardium, plasma c-TPN I, and electrocardiographic modifications (ST-segment changes and T-wave inversion). Combined treatment increased myocardial alterations such as contraction band necrosis, induced the appearance of specific hypoxic lesions such as areas of coagulative necrosis and leukocyte infiltration, and led to higher plasma c-TPN I levels and altered ECG profiles. Both drugs favored a decrease in plasma NO values and further alterations in hemodynamic parameters, such as higher blood pressure and greater procoagulant activity. The myocardial necrosis and modified cardiovascular parameters were attributed to calcium activated processes and the decrease in NO levels. As this model of myocardial damage involves the use of drugs that facilitate the opening of L-calcium channels, we also investigated their effects on cardiovascular parameters and heart histology after pretreatment with the calcium antagonist verapamil; this drug protected against the appearance of histological myocardial lesions, electrocardiographic alterations and high plasma c-TPN I levels, and prevented the hemodynamic and procoagulation changes, but did not affect the decrease in plasma NO values. The protective effects were attributed to the drug's calcium antagonist activity. In conclusion, the injection of isoproterenol and vasopressin induces a myocardial infarction non-invasively and seems to be suitable for studying early myocardial ischemic lesions and the effects of drugs interfering with myocardial damage and its related phenomena.