Grade Group Research Articles

Predicting Metastasis and Mortality Risk in Prostate biopsy using genomics and biopsy related factors

Abstract Introduction/Objective Prostate cancer, the most prevalent cancer among men, is diagnosed through biopsy, yet its predictive accuracy for metastasis and mortality risk remains limited. An approach to stratifying this risk is by combining biopsy data and genetics. The Decipher genomic classifier aids in estimating such risks. This study investigates the correlation between Decipher, biopsy-related factors, and the risk of prostate cancer metastasis or mortality. Methods/Case Report 50 prostatic adenocarcinoma biopsies were analyzed. Patient age, average tumor volume in positive cores, PSA levels, and Gleason score were documented. Employing Tobit regression with maximum likelihood estimation, the study examined the link between various factors and metastasis/mortality risk of prostatic cancer. Dependent variables encompassed 5, 10, and 15-year risks, while the independent variable was patient age, positive to total core ratio, average tumor volume in positive cores, PSA level, and grade group of the prostate cancer. The model integrated three dummy variables-Grade Group 1, 3, and 4, with Grade Group 2 as reference. Coefficients gauged the distinct impact of Level 1, 3, and 4 diagnoses on outcomes relative to Level 2. Statistical significance was tested conventionally. Results (if a Case Study enter NA) Grade Group 1 (Gleason score: 3 + 3): 2.35 percentage point increase in the risk of metastasis within 10 years. 3.51 percentage point increase in the risk of mortality within 15 years. Grade Group 2 Base level for comparison with other grade groups. Grade Group 3 (Gleason score: 4 + 3): No statistically significant difference in the predicting 5 or 10 year risk of metastasis compared to Grade Group 2. No statistically significant difference in the predicting 15 year risk of mortality compared to Grade Group 2. Grade Group 4 (Gleason score: 4 + 4): 10.07 percentage point increase in the risk of metastasis within 5 years. 17.27 percentage point increase in the risk of metastasis within 10 years. 18.48 percentage point increase in the risk of mortality within 15 years. Conclusion The findings suggest combining genomics and grade group can help predict the risk of metastasis and mortality in prostate biopsy. Grade Group 4 diagnosis greatly impacts metastasis and mortality in all timeframes.While Grade Group 1 has a smaller but still significant impact on the 10 and 15 year risk of metastasis and mortality. However, Grade Group 3 diagnosis does not significantly impact the risk of metastasis in any of the timeframes considered.

2022 개정 특수교육 기본 교육과정 수학과 성취기준 분석: Bloom의 신교육목표분류학에 기초하여

Objectives This study aims to provide implications for the achievement standards of the basic curriculum for mathematics in the 2022 Revised Special Education Basic Curriculum by analyzing them based on Bloom's revised taxonomy of educational objectives. Methods To this end, a total of 182 mathematics achievement standards of the revised 2022 special education basic curriculum were analyzed for five grade groups and five mathematics areas based on Bloom's new taxonomy of educational objectives. Results First, the achievement standards for each grade were analyzed. As a result, among Bloom's knowledge dimensions in all grade groups, ‘factual knowledge’ was the highest with 104 (57.1%), and among the cognitive process dimensions, ‘Understanding’ was the highest with 89 (48.9%). A binary classification analysis of knowledge and cognitive process levels, the achievement standards for remembering factual knowledge were found in 55 achievement standards(30.2%). There were no achievement standards for ‘Meta-cognitive knowledge’, ‘Evaluation’, and ‘Create’. Second, as a result of analyzing the achievement standards by mathematics area, ‘Factual knowledge’ was the highest in the knowledge dimension with 45 achievement standards (48.9%) for numbers and operations, 28 (87.5%) for shapes, and 24 (92.2%) for measurement. ‘Conceptual knowledge’ was the highest with 12 (70.5%) in the regularity area and 9 (60%) in the data and probability area. In the cognitive process, ‘Remember’ was the highest with 29 (31.5%) in the number and calculation areas and 18 (56.3%) in the measurement areas was the highest with 17 achievement standards (65.3%), the regularity area with 7 achievement standards (41.1%), and the data and probability area with 9 achievement standards(60.0%). There were no achievement standards for ‘Meta-cognitive knowledge’, ‘Evaluation’, and ‘Create’. Conclusions Based on the results of this study, implications for the development of mathematics achievement standards of the basic curriculum for special education and suggestions for future research were made.

2022 개정 특수교육 기본교육과정 사회과 내 인권교육 관련 성취기준 분석

Objectives The purpose of this study is to analyze the social studies achievement standards of the 2022 revised basic curriculum of special education by content elements of human rights education to check the current status of each school level and human rights education area, and to suggest the direction of human rights education in special education. Methods In this study, the social studies achievement standards of the 2022 special education basic curriculum were analyzed using the analysis framework of previous studies related to human rights education. In addition, in order to confirm the reliability and validity of the analysis results, the reliability between analysts and the validity of the expert content were implemented. Results Elementary school showed the highest frequency, and middle and high school showed the highest frequency of I. respect for human rights in the major area, and I-3. Human rights values and attitudes in the sub-area showed a very high percentage. The analysis results of human rights education by grade group showed that in all grade groups, I. respect for human rights showed the highest frequency, and in the sub-area, I-3. Human rights values and attitudes and II-1. Freedom rights showed the highest frequency, while middle and high school levels showed the highest frequency of human rights values and attitudes. Conclusions The conclusions according to the analysis contents are as follows. First, special teachers need to construct a holistic human rights education through curriculum restructuring. Second, the content elements of human rights education need to be sequenced and connected by grade group of the curriculum.

Using a novel PSMA-PET and PSA-based model to enhance the diagnostic accuracy for clinically significant prostate cancer and avoid unnecessary biopsy in men with PI-RADS ≤ 3 MRI.

The diagnostic evaluation of men with suspected prostate cancer (PCa) yet inconclusive MRI (PI-RADS ≤ 3) presents a common clinical challenge. [68Ga]Ga-labelled prostate-specific membrane antigen ([68Ga]Ga-PSMA) positron emission tomography/computed tomography (PET/CT) has shown promise in identifying clinically significant PCa (csPCa). We aim to establish a diagnostic model incorporating PSMA-PET to enhance the diagnostic process of csPCa in PI-RADS ≤ 3 men. This study retrospective included 151 men with clinical suspicion of PCa and PI-RADS ≤ 3 MRI. All men underwent [68Ga]Ga-PSMA PET/CT scans and ultrasound/MRI/PET fusion-guided biopsies. csPCa was defined as Grade Group ≥ 2. PRIMARY-scores from PSMA-PET scans were evaluated. A diagnostic model incorporating PSMA-PET and prostate-specific antigen (PSA)-derived parameters was developed. The discriminative performance and clinical utility were compared with conventional methods. Internal validation was conducted using a fivefold cross-validation with 1000 iterations. In this PI-RADS ≤ 3 cohort, areas-under-the-curve (AUCs) for detecting csPCa were 0.796 (95%CI, 0.738-0.853), 0.851 (95%CI, 0.783-0.918) and 0.806 (95%CI, 0.742-0.870) for PRIMARY-score, SUVmax and routine clinical PSMA-PET assessment, respectively. The diagnostic model comprising PRIMARY-score, SUVmax and serum free PSA/total PSA (fPSA/tPSA) achieved a significantly higher AUC of 0.906 (95%CI, 0.851-0.961) compared to strategies based on PRIMARY-score or SUVmax (P < 0.05) and markedly superior to conventional strategies typically based on PSA density (P < 0.001). The average fivefold cross-validated AUC with 1000 iterations was 0.878 (95%CI, 0.820-0.954). Theoretically, using a threshold of 21.6%, the model could have prevented 78% of unnecessary biopsies while missing only 7.8% of csPCa cases in this cohort. A novel diagnostic model incorporating PSMA-PET derived metrics-PRIMARY-score and SUVmax-along with serum fPSA/tPSA, has been developed and validated. The integrated model may assist clinical decision-making with enhanced diagnostic accuracy over the individual conventional metrics. It has great potential to reduce unnecessary biopsies for men with PI-RADS ≤ 3 MRI results and warrants further prospective and external evaluations.

Solitary Loss of PMS2 in a patient with Colon carcinoma

Abstract Introduction/Objective In the United States, there are about 150,000 new cases of Colorectal cancer (CRC) and about 50,000 CRC related deaths each year. Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) accounts for 2% - 4% of CRC. It is characterized by germline mutations in mismatch repair (MMR) genes - MLH1, MSH2, MSH6 and PMS2. Patients with Lynch syndrome have up to an 80% lifetime risk (LTR) of CRC and up to 60% LTR of endometrial cancer. Lynch syndrome patients also have an associated LTR of ovarian cancer (38%), upper urologic tract cancer (18%), gastric cancer (13%), small bowel cancer (6%), hepatobiliary tract cancer (4%), and brain tumors (3% - usually glioblastoma). Methods/Case Report A 76-year-old man with history of moderately differentiated colorectal adenosarcoma involving the transverse colon and a recently diagnosed grade group 5 (Gleason 4 + 5) prostate adenocarcinoma, currently being managed at an outside hospital. The case was sent to UAB for DNA MMR/microsatellite instability (MSI) status evaluation testing. Immunostaining showed loss of PMS2 and intact expression of MLH1, MSH2 and MSH6. These results were confirmed by the IdyIIa MSI assay which detected microsatellite instability in 5 of 7 markers and negative for BRAF V600E variant confirming microsatellite instable tumor. Results (if a Case Study enter NA) NA Conclusion Solitary loss of PMS2 in colonic adenocarcinoma is uncommon and may be caused by an underlying germline mutation of MLH-1 or PMS2, thus could represent Lynch Syndrome. Our patient’s age doesn’t favor Lynch syndrome. Next step would be to perform MLH-1 promoter methylation to confirm sporadic nature of carcinoma. Somatic methylation of the MLH1 promoter occurs in approximately 80% of CRC with defective MMR. Prostate cancer is not currently considered a part of Lynch syndrome.

Association between beta-blocker atenolol use and prostate cancer upgrading in active surveillance.

The objective of this study is to investigate the association between the use of beta-adrenergic antagonist atenolol and risk of pathologic upgrade in patients on active surveillance, considering growing literature implicating adrenergic innervation with disease progression mediated through beta-adrenergic signalling. Men with low-risk or favourable intermediate-risk prostate cancer who were placed on an active surveillance protocol between 2006 and 2020 across three diverse urban hospitals were included. Exposure was duration of atenolol use, and outcome was pathologic grade group upgrading (to GG ≥ 3) on final prostate biopsy. Cox proportional hazard regression models were used to determine the associations between atenolol use and risk of upgrading with time, on a per-examination basis. A total of 467 men with initial GG ≤ 2 were included. Postdiagnosis atenolol use was associated with a decreased risk of pathologic upgrade to GG ≥ 3 on final repeat biopsy (HR 0.81, 95% CI 0.39-0.98). Longer duration of postdiagnosis atenolol use (>2years) and greater cumulative atenolol dose (>730 defined daily doses) were associated with a more pronounced decreased risk of upgrade to GG ≥ 3 (HR 0.41, 95% CI 0.05-0.88, and HR 0.32, 95% CI 0.15-0.99, respectively). Initiation of atenolol use prior to prostate cancer diagnosis had a slightly greater protective effect than drug initiation postdiagnosis (HR 0.79, 95% CI 0.43-0.98, and HR 0.83, 95% CI 0.30-0.99, respectively). Beta-adrenergic blockade with atenolol use in men on active surveillance is associated with a reduced risk for clinically significant grade group pathologic upgrade.

The efficacy of different biomarkers and endpoints to refine referrals for suspected prostate cancer: the TARGET study (Tiered integrAted tests for eaRly diaGnosis of clinically significant ProstatE Tumours).

The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. Data and samples from 798 men referred for a raised PSA (≥ 3ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logisticregression models, AUC and decision curve analysis (DCA) plots. The median age and PSA was 65years and 7.13ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raisedPSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used.

Quantitative MRI biomarker for classification of clinically significant prostate cancer: Calibration for reproducibility across echo times.

The purpose of the present study is to develop a calibration method to account for differences in echo times (TE) and facilitate the use of restriction spectrum imaging restriction score (RSIrs) as a quantitative biomarker for the detection of clinically significant prostate cancer (csPCa). This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE ~75ms and once at TE=90ms (TEmin1, TEmin2, and TE90, respectively). A linear regression model was determined to match the C-maps of TE90 to the reference C-maps of TEmin1 within the interval ranging from 95th to 99th percentile of signal intensity within the prostate. RSIrs comparisons were made at the 98th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrsTE90corr) and uncorrected TE90 (RSIrsTE90) to RSIrs from reference TEmin1 (RSIrsTEmin1) and repeated TEmin2 (RSIrsTEmin2). Calibration performance was evaluated with sensitivity, specificity and area under the ROC curve (AUC). Scaling factors for C1, C2, C3, and C4 were estimated as 1.68, 1.33, 1.02, and 1.13, respectively. In non-csPCa cases, the 98th percentile of RSIrsTEmin2 and RSIrsTEmin1 differed by 0.27±0.86SI (mean±standard deviation), whereas RSIrsTE90 differed from RSIrsTEmin1 by 1.82±1.20SI. After calibration, this bias was reduced to -0.51±1.21SI, representing a 72% reduction in absolute error. For patients with csPCa, the difference was 0.54±1.98SI between RSIrsTEmin2 and RSIrsTEmin1 and 2.28±2.06SI between RSIrsTE90 and RSIrsTEmin1. After calibration, the mean difference decreased to -1.03SI, a 55% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrsTEmin1 has a sensitivity of 66% and a specificity of 72%. The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 72% and 55% for non-csPCa and csPCa, respectively.

Is Confirmatory Biopsy Still Necessary for Active Surveillance of Men With Grade Group 1 Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging?

Men diagnosed with prostate cancer (PCa) considering active surveillance (AS) are recommended confirmatory biopsy (CBx). Whether this is necessary in the era of MRI-informed biopsies is questionable. We studied men with Grade Group [GG] 1 PCa at diagnostic biopsy (DBx) considering AS who underwent MRI and CBx (systematic + targeted) within 18 months. Outcomes were grade reclassification to GG ≥ 2, GG ≥ 3, and reclassification to unfavorable intermediate risk disease (UIR). Subset analyses were performed for men with (1) MRI prior to DBx and (2) MRI after DBx. Five hundred twenty-two men had GG1 PCa at DBx. At CBx, 20% reclassified to GG ≥ 2, 12% to UIR, and 5.6% to GG ≥ 3. Of the 306 with positive MRI (PI-RADS > 3), 27% reclassified to GG ≥ 2 and 16% to UIR disease; men with negative MRI experienced these outcomes at rates of 9.2% and 5.5%. There were no differences in reclassification outcomes based on MRI timing (group A vs B), and neither PSA density nor prostate volume added to MRI information. In men with MRI targets, approximately 1/3 of GG > 2 reclassification events were only captured by systematic biopsy core(s). Reclassification rates at CBx were high in men with positive MRI, but < 10% for all reclassification outcomes in men with negative MRI (95% CI 5.8%-14% for GG > 2, 2.9%-10% for UIR, 0.8%-5.3% for GG > 3). Our data support systematic + targeted CBx for men with positive MRI considering AS, while men with GG1 cancer and negative MRI should be able to defer CBx.

When is prostate cancer really cancer?

Prostate cancer (PC) is a major cause of cancer-related deaths worldwide, with far more diagnoses than deaths annually. Recent discussions have challenged whether Grade Group 1 (GG1) PC should be labeled "cancer" due to its indolent nature. To address this question, an international symposium convened stakeholders from various fields. We summarize key discussion points: autopsy studies reveal GG1 is so common in aging males as to be perhaps a normal aspect of aging. Pure GG1 has no capacity to metastasize. Modern diagnostic pathways focus on detecting higher-grade disease, explicitly omitting biopsy if GG 2 or higher is not suspected, so GG1 has effectively become an "incidentaloma." Recent spatial transcriptomics of prostate sections identifies a continuum of genomic changes-including alterations characteristic of malignancy in histologically normal regions, so the designation of cancer based entirely on conventional pathology findings increasingly seems arbitrary at least to an extent. Pathologists discussed heterogeneity and diagnostic challenges, suggesting "acinar neoplasm" as one possible alternative label. GG1 should not be considered "normal," and absolutely requires ongoing active surveillance; whether patients would adhere to surveillance absent a cancer diagnosis is unknown. Patient perspectives highlighted the adverse effects of overtreatment and the burden of a cancer diagnosis. The anticipated impact on screening and treatment varies across health-care systems, but many believe public health would on balance greatly improve if GG1-along with lesions in other organs with no capacity to cause symptoms or threaten life-were labeled something other than "cancer." Ultimately, our goal is to reduce PC mortality while minimizing harms associated with both overdiagnosis and overtreatment.

Cribriform intraductal carcinoma of the prostate may be more aggressive than cribriform conventional/acinar prostatic adenocarcinoma

It remains to be determined if the prognostic value of cribriform morphology (Crib) associated with intraductal carcinoma of the prostate (IDC) is equivalent to that in conventional/acinar prostatic adenocarcinoma (CPA). We herein assessed radical prostatectomy findings and long-term oncologic outcomes in 732 men with Grade Group 2-4 CPA without any Gleason pattern 5. Our cases were divided into 4 cohorts according to the absence or presence of Crib within CPA and/or IDC: Cohort-1) no Crib (n=347; 47.4%); Cohort-2) Crib only in CPA (n=203; 27.7%); Cohort-3) Crib only in IDC (n=17; 2.3%); and Cohort-4) Crib in both CPA and IDC (n=165; 22.5%). Compared with that in CPA only (Cohort-2), Crib in both CPA and IDC (Cohort-4) was significantly associated with adverse histopathological features, including higher tumor grade/stage and larger tumor volume. Univariate analysis revealed significantly higher risks of postoperative recurrence in patients with Crib in IDC only [Cohort-3; hazard ratio (HR) 2.450, P=0.022] or both CPA and IDC (Cohort-4; HR=2.835, P<0.001) than in those with Crib in CPA only (Cohort-2), while the prognosis was analogous between Cohort-3 vs. Cohort-4 (P=0.913). In multivariable analysis [Crib in CPA only (Cohort-2) as a reference], Crib in IDC only (Cohort-3; HR=3.821, P=0.002) or both CPA and IDC (Cohort-4; HR=1.905, P=0.004) showed significantly worse recurrence-free survival. Compared with Crib in CPA only, its presence in both CPA and IDC was thus found to be independently associated with a poorer prognosis, suggesting a potentially greater clinical impact of Crib in IDC than in CPA.

Metastatic prostate adenocarcinoma to the brain – a clinicopathologic analysis of 21 cases

BackgroundBrain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy.DesignA retrospective search spanning 20 years (2003–2022) was conducted on our archives and identified 21 cases diagnosed as “metastatic prostate adenocarcinoma (mPCa)” in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa.ResultThe mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis.ConclusionmPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.

Five-year Oncologic Outcomes Following Primary Partial Gland Cryo-ablation Prospective Cohort Study of Men With Intermediate-risk Prostate Cancer

To assess 5-year oncologic outcomes following primary partial gland cryo-ablation (PPGCA) in intermediate risk prostate cancer. Of 476 men undergoing PPGCA enrolled in our prospective oncologic and functional outcomes study, 313 had MRI concordant intermediate risk prostate cancer with no out-of-field Gleason Grade Group (GGG) ≥2, gross extracapsular extension or extreme apical disease on pre-treatment mpMRI. PSA was monitored every 6 months, and mpMRI at 6-12, 24, 42 and 60 months. Protocol biopsy at 6-12 months and 24 months were discontinued after interim analysis showing low rates of clinically-significant prostate cancer (csPCa) defined as any GGG≥2 disease. Freedom-from-failure (FFF) was defined as no prostate cancer specific mortality, metastatic disease, or whole-gland salvage treatment (WGST) RESULTS: csPCa was detected in 33 (10.5%) subjects. 91 had ≥4.5 years of follow-up data with a mean of 8.9, 3.4, and 2.0 surveillance PSA tests, MRIs, and prostate biopsies; none were lost to follow-up. At 5-years, rates of freedom-from-recurrence of in-field, out-of-field and overall csPCa were 86% (95% CI: 78-96), 85% (95% CI: 63-94), and 70% (95% CI: 57-84). The proportion with freedom-from-failure (FFF) at 5 years was 89% (95% CI: 83-95). None died from prostate cancer, 1 (1%) developed metastasis, 15 (16.5%) underwent WGST, and 15 (16.5%) underwent salvage focal therapy (FT). Only 3 of 91 (3.3%) eligible men were noncompliant with 5-year surveillance protocol. Very encouraging intermediate-term oncological outcomes following PPGCA were observed with very high compliance to a rigorous prospective protocol for identifying recurrent csPCa.

Computed tomography patterns and clinical outcomes of radiation pneumonitis in non-small-cell lung cancer patients.

Radiation pneumonitis (RP) is not an uncommon complication in lung cancer patients undergoing radiation therapy (RT) and symptomatic RP can affect their quality of life. To investigate the CT findings of RP in non-small cell lung cancer (NSCLC) patients and their relationship with clinical outcomes. We reviewed data from 240 NSCLC patients who underwent RT between 2014 and 2022. CT findings of RP were evaluated for parenchymal abnormalities and distribution, which were then classified into three patterns: localized pneumonia (LP), cryptogenic organizing pneumonia (COP), and acute interstitial pneumonia (AIP). Clinical outcomes of RP were evaluated based on Common Terminology Criteria for Adverse Events (CTCAE) grade. Of the 153 patients, 135 developed RP. The most common pattern was LP (n = 78), followed by COP (n = 30) and AIP (n = 25). Among the three CT patterns, CTCAE grade and days between the start of RT and the onset of RP (RT-RP days) were statistically significantly different (p < 0.05). The patients with AIP patterns exhibited higher CTCAE grade, and fewer RT-RP days compared to those with non-AIP patterns (p < 0.05). In these patients, lung-to-lung metastasis and underlying interstitial lung abnormality were observed more frequently (p < 0.05). Underlying pulmonary fibrosis, the AIP pattern, and higher CT extent scores were more frequently observed in higher CTCAE grade group (p < 0.001). In multiple regression analysis, age, bilateral distribution, RT-RP days, and CT extent score ≥3 were independent predicting factors for higher CTCAE grade. RP in NSCLC patients can be classified into LP, COP, and AIP patterns and they exhibit different severities in clinical outcomes.

Five-year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial.

Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival.

A Targeted Methylation-Based Multicancer Early Detection Blood Test Preferentially Detects High-Grade Prostate Cancer While Minimizing Overdiagnosis of Indolent Disease.

Indolent prostate cancer (PCa) is prevalent in the intended use population (adults age 50-79 years) for blood-based multicancer early detection (MCED) tests. We examined the detectability of PCa by a clinically validated, targeted methylation-based MCED test. Detectability by Gleason grade group (GG), clinical stage, association of detection status with tumor methylated fraction (TMeF), and overall survival (OS) were assessed in substudy 3 of Circulating Cell-Free Genome Atlas (CCGA; ClinicalTrials.gov identifier: NCT02889978) and PATHFINDER (ClinicalTrials.gov identifier: NCT04241796) studies. Test sensitivity for PCa in substudy 3 of CCGA was 11.2% (47/420). The test detected 0 (0%) of 58 low-grade (GG1), 3 (1.9%) of 157 favorable intermediate-grade (GG2), 4 (5.1%) of 78 unfavorable intermediate-grade (GG3), and 36 (31.9%) of 113 high-grade (GG4 and 5) cancers and 3 (3.2%) of 95 stage I, 11 (4.7%) of 235 stage II, 7 (14.9%) of 47 stage III, and 22 (81.5%) of 27 stage IV cases. The median TMeF was higher for detected than nondetected cases (2,106.0 parts per million [PPM]; IQR, 349.8-24,376.3 v 24.4 PPM; IQR, 17.8-38.5; P < .05). Nondetected cases had better OS (P < .05; hazard ratio [HR], 0.263 [95% CI, 0.104 to 0.533]) and detected cases had similar survival (P = .2; HR, 0.672 [95% CI, 0.323 to 1.21]) compared with SEER adjusted for age, GG, and stage. Performance was similar in PATHFINDER, with no detected GG1/2 (0/13) or stage I/II (0/16) cases. This MCED test preferentially detects high-grade, clinically significant PCa. Use in population-based screening programs in addition to standard-of-care screening is unlikely to exacerbate overdiagnosis of indolent PCa.

Testosterone Therapy in Men After Radical Prostatectomy for Organ-Confined, Low-Intermediate Prostate Cancer.

Testosterone therapy (TTh) in men with T deficiency who have undergone radical prostatectomy (RP) for prostate cancer remains controversial. We aimed to assess the impact of TTh on biochemical recurrence (BCR) rates after RP in men with low-intermediate organ-confined disease. This study included men who underwent an RP at our institution for organ-confined prostate cancer and had grade groups 1 to 3 on RP pathology. A Cox model was created for time to BCR with T use included as a time-dependent covariate, adjusted for age, preoperative PSA, grade group at RP, and the presence of comorbidities. A landmark analysis was used: Patients were included in the analysis if their last PSA in the 18 weeks postoperatively was undetectable and they had not had BCR or been lost to follow-up by that point, and follow-up for BCR began at 18 weeks. BCR was defined as a PSA ≥ 0.1 ng/mL after RP with a second confirmatory rise ≥ 0.1 ng/mL. The study population included 5199 men after RP, with 198 patients receiving T at any point after RP and 5001 not receiving T. The median age was 59 (IQR, 55-65) and 61 (IQR, 56-66) years, respectively. Men in the T group tended to present with more vascular comorbidities. For those receiving T, clomiphene citrate was prescribed in 49% of men, 32% received transdermal T, and 19% intramuscular T. We found a nonsignificantly decreased risk of BCR associated with the use of T after RP (HR, 0.84; 95% CI, 0.48-1.46; P = .5), and overall rates of BCR were low, with probability of BCR at 5 years less than 2% in both groups. TTh can be given to select men after RP. We found no evidence that administration of TTh after RP causes BCR.

The Impact of Exemplars On The Academic Outcomes For Master’s In Education Online Graduate Students

Annotated exemplars have recently been scrutinized as an academic support strategy in the context of Higher Education Institutes (HEIs). The idea is that using exemplars may front-load the system regarding student academic performance through the provision of meaningful feedback and task-specific comments before formal student submissions. More specifically, The Scholarship of Teaching and Learning (SoTL) research regarding exemplar use has called for the investigation of these exemplars on academic performance for the online graduate student. The purpose of this quantitative, quasi-experimental study was to determine if and to what extent the integration of annotated exemplars impacted the academic outcomes for Masters in Education online graduate students. Academic outcomes were designated as assessment grades and overall course grades. The study methodology and design were quantitative quasi-experimental using traditional pre-/post- techniques regarding this exemplar implementation with a convenience sample. The sample size of the experimental group is n = 17. The control group ranges from n = 25 to n = 27. The objective stated explicitly is to investigate if and to what extent the use of annotated exemplars impacts overarching student outcomes for graduate students at a university in the southwestern United States. The results showed no statistically significant difference between the control group and the experimental group for assignment grades, resulting in a retention of the null hypothesis. The results also indicated that there was a statistically significant difference between the control group and the experimental group for overall course grades, resulting in a rejection of the null hypothesis. Potential areas of future research might include brick-and-mortar settings, larger sample sizes, other student populations, or a qualitative examination of student perceptions about exemplars.

End-to-end [18F]PSMA-1007 PET/CT radiomics-based pipeline for predicting ISUP grade group in prostate cancer.

To develop an end-to-end radiomics-based pipeline for the prediction of International Society of Urological Pathology grade group (ISUP GG) in prostate cancer (PCa). This retrospective study includes 356 patients (241 in training set and 115 in independent test set) with histopathologically confirmed PCa who underwent [18F]PSMA-1007 PET/CT scan. Patients were classified into two groups according to their ISUP GG (1-3 vs. 4-5). Radiomics features were extracted from the whole, automatically segmented prostate on PET/CT images, 30 models were constructed by combining 6 feature selection algorithms and 5 machine learning classifiers. The clinical model incorporated age, total prostate-specific antigen (tPSA), maximum standardized uptake value (SUVmax), and prostate volume. The predictive performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), balanced accuracy (bAcc), and decision curve analysis (DCA). The best-performing radiomics model significantly outperformed clinical model (AUC 0.879 ± 0.041 vs. 0.799 ± 0.051, bAcc 0.745 ± 0.074 vs. 0.629 ± 0.045). On an external independent test set, best-performing radiomics model perform better than clinical model, with an AUC of 0.861 vs. 0.750, p = 0.002 (Delong), and bAcc of 0.764 vs. 0.582, p = 0.043 (McNemar). The learning curve, calibration curve and DCA demonstrated goodness-of-fit and improved benefits in clinical practice. The end-to-end radiomics-based pipeline is an effective non-invasive tool to predict ISUP GG in PCa.

초등 고학년의 자기주도성과 성격특성이 질문행동에 미치는 영향 분석: 혁신학교 사례 중심으로

Objectives This study aims to develop instructional strategies to enhance questioning behavior, a fundamental active learning activity. It examines the impact of self-directed learning variables, validated in prior research, and the often-overlooked personality traits on questioning behavior. Methods This study examined 129 fifth and sixth graders in a metropolitan city, assessing their questioning behavior, self-directedness relating to goal orientation and growth mindset, and BIG 5 personality traits including openness, conscientiousness, neuroticism, and agreeableness. T-tests analyzed gender and grade differences, while correlation and step-wise regression analyses determined the impact of independent variables on the questioning behaviors across different subgroups. Results Significant higher scores in self-directedness were observed in fifth graders compared to sixth graders with no notable gender differences. Except for agreeableness, no significant differences in BIG 5 personality traits were noted between grades or genders. Influential variables on questioning behavior included conscientiousness, openness, and goal orientation, varying significantly across different grade and gender groups. Influential variables on questioning behavior varied; for 5th graders, the order was conscientiousness, openness, and goal orientation, for 6th graders, it was goal orientation, conscientiousness; for boys, it was conscientiousness, openness, and goal orientation, and for girls, it was goal orientation, conscientiousness, openness, and neuroticism. Conclusions This research highlights the importance of motivational and personality factors in influencing students' questioning behaviors and suggests targeted educational strategies to enhance inquiry-based learning. The findings pave the way for further studies into effective teaching and learning methods that foster critical questioning skills.