Purpose
To assess the role of radiomics parameters in predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer.
Methods
...Seventy-nine patients who had undergone pretreatment staging
18
F-FDG PET/CT and treatment with NAC between January 2010 and January 2018 were included in the study. Primary lesions on PET images were delineated, and extraction of first-, second-, and higher-order imaging features was performed using LIFEx software. The relationship between these parameters and pCR to NAC was analyzed by multiple logistic regression models.
Results
Nineteen patients (24%) had pCR to NAC. Different models were generated on complete information and imputed datasets, using univariable and multivariable logistic regression and least absolute shrinkage and selection operator (lasso) regression. All models could predict pCR to NAC, with area under the curve values ranging from 0.70 to 0.73. All models agreed that tumor molecular subtype is the primary predictor of the primary endpoint.
Conclusions
Our models predicted that patients with subtype 2 and subtype 3 (HER2+ and triple negative, respectively) are more likely to have a pCR to NAC than those with subtype 1 (luminal). The association between PET imaging features and pCR suggested that PET imaging features could be considered as potential predictors of pCR in locally advanced breast cancer patients.
Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the ...repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998-2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen's kappa and Bland and Altman's limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.
Background
Prognostic models for patients with soft tissue sarcoma (STS) of the extremities have been developed from large multi-institutional datasets with mixed results. We aimed to develop ...predictive nomograms for sarcoma-specific survival (SSS) and, for the first time, long-term local recurrence (LR) and distant recurrence (DR) in patients with STS of the extremities treated at our institution.
Patients and methods
Data from patients treated at Humanitas Cancer Center from 1997 to 2015 were analyzed. Variable selection was based on the clinical knowledge and multivariable regression splines algorithm. Perioperative treatments were always included in the model. Prognostic models were developed using Cox proportional hazards model, and model estimates were plotted in nomograms predicting SSS at 5 and 10 years and LR and DR at 2, 5, and 10 years. Model performance was estimated internally
via
bootstrapping, in terms of optimism-corrected discrimination (Harrell C-index) and calibration (calibration plots).
Results
Data on 517 patients were analyzed. At 5 and 10 years, SSS was 68.1% 95% confidence interval (CI), 63.8–72.1 and 55.6% (50.5–60.3), respectively. LR was 79.1% (95% CI, 75.3–82.4), 71.1% (95% CI, 66.7–75.1), and 66.0% (95% CI, 60.7–70.7) at 2, 5, and 10 years, respectively, whereas DR was 65.9% (95% CI, 61.6–69.9), 57.5% (95% CI, 53.0–61.8), and 52.1% (95% CI, 47.1–56.8) at 2, 5, and 10 years, respectively. SSS nomogram included age, gender, margins, tumor size, grading, and histotype. LR and DR nomograms incorporated mostly the same variables, except for age for DR; LR nomogram did not include gender but included anatomic site. The optimism-corrected C-indexes were 0.73 and 0.72 for SSS at 5 and 10 years, respectively; 0.65, 0.64, and 0.64 for LR at 2, 5, and 10 years, respectively; and 0.68 for DR at 2, 5, and 10 years. Predicted probabilities were close to the observed ones for all outcomes.
Conclusions
We developed and validated three nomograms for STS of the extremities predicting the probability of SSS at 5 and 10 years and LR and DR at 2, 5, and 10 years. By accounting for the perioperative treatment, these models allow prediction for future patients who had no perioperative treatment, thus being useful in the clinical decision-making process.
In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide ...registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues.
In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality.
Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids.
To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on ...multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research.
Methods
The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31
st
2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study’s prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks.
Results
The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage.
Discussion
This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.
Numerous pretreatment risk classification tools are available for prostate cancer. Which tool is best in predicting prostate cancer death is unclear.
To systematically compare the prognostic ...performance of the most commonly used pretreatment risk stratification tools for prostate cancer.
A nationwide cohort study was conducted, including 154 811 men in Prostate Cancer data Base Sweden (PCBaSe) 4.0 diagnosed with nonmetastatic prostate cancer during 1998–2016 and followed through 2016.
We compared the D’Amico, National Institute for Health and Care Excellence (NICE), European Association of Urology (EAU), Genito-Urinary Radiation Oncologists of Canada (GUROC), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), and Cambridge Prognostic Groups (CPG) risk group systems; the Cancer of the Prostate Risk Assessment (CAPRA) score; and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting prostate cancer death by estimating the concordance index (C-index) and the observed versus predicted cumulative incidences at different follow-up times.
A total of 139 515 men were included in the main analysis, of whom 15 961 died from prostate cancer during follow-up. The C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval CI: 0.72–0.73) to 0.81 (95% CI: 0.80–0.81) across the compared tools. The MSKCC nomogram (C-index: 0.81, 95% CI: 0.80–0.81), CAPRA score (C-index: 0.80, 95% CI: 0.79–0.81), and CPG system (C-index: 0.78, 95% CI: 0.78–0.79) performed the best. The order of performance between the tools remained in analyses stratified by primary treatment and year of diagnosis. The predicted cumulative incidences were close to the observed ones, with some underestimation at 5 yr. It is a limitation that the study was conducted solely in a Swedish setting (ie, case mix).
The MSKCC nomogram, CAPRA score, and CPG risk grouping system performed better in discriminating prostate cancer death than the D’Amico and D’Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use of these tools may improve clinical decision making.
There are numerous pretreatment risk classification tools that can aid treatment decision for prostate cancer. We systematically compared the prognostic performance of the most commonly used tools in a large cohort of Swedish men with prostate cancer. The Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups performed best in predicting prostate cancer death. The use of these tools may improve treatment decisions.
There are numerous pretreatment risk classification tools for prostate cancer. In a head-to-head comparison, the Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups system performed best in predicting prostate cancer death. The use of these tools may improve clinical decision making.
Background
Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this ...study is to assess the risk of arterial ischemic events during the first year after oncological surgery.
Methods
We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge.
Results
The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24–9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22–7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87–0.93) for myocardial infarction and 1.02 (95% CI 0.99–1.05) for ischemic stroke.
Conclusions
We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects.
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