Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Transfer learning for the generalization of artificial intelligence in breast cancer detection: a case-control study.

BACKGROUND: Some researchers have questioned whether artificial intelligence (AI) systems maintain their performance when used for women from populations not considered during the development of the system. PURPOSE: To evaluate the impact of transfer learning as a way of improving the generalization of AI systems in the detection of breast cancer. MATERIAL AND METHODS: This retrospective case-control Finnish study involved 191 women diagnosed with breast cancer and 191 matched healthy controls. We selected a state-of-the-art AI system for breast cancer detection trained using a large US dataset. The selected baseline system was evaluated in two experimental settings. First, we examined our private Finnish sample as an independent test set that had not been considered in the development of the system (unseen population). Second, the baseline system was retrained to attempt to improve its performance in the unseen population by means of transfer learning. To analyze performance, we used areas under the receiver operating characteristic curve (AUCs) with DeLong's test. RESULTS: Two versions of the baseline system were considered: ImageOnly and Heatmaps. The ImageOnly and Heatmaps versions yielded mean AUC values of 0.82±0.008 and 0.88±0.003 in the US dataset and 0.56 (95% CI=0.50-0.62) and 0.72 (95% CI=0.67-0.77) when evaluated in the unseen population, respectively. The retrained systems achieved AUC values of 0.61 (95% CI=0.55-0.66) and 0.69 (95% CI=0.64-0.75), respectively. There was no statistical difference between the baseline system and the retrained system. CONCLUSION: Transfer learning with a small study sample did not yield a significant improvement in the generalization of the system.

Saliency of breast lesions in breast cancer detection using artificial intelligence.

The analysis of mammograms using artificial intelligence (AI) has shown great potential for assisting breast cancer screening. We use saliency maps to study the role of breast lesions in the decision-making process of AI systems for breast cancer detection in screening mammograms. We retrospectively collected mammograms from 191 women with screen-detected breast cancer and 191 healthy controls matched by age and mammographic system. Two radiologists manually segmented the breast lesions in the mammograms from CC and MLO views. We estimated the detection performance of four deep learning-based AI systems using the area under the ROC curve (AUC) with a 95% confidence interval (CI). We used automatic thresholding on saliency maps from the AI systems to identify the areas of interest on the mammograms. Finally, we measured the overlap between these areas of interest and the segmented breast lesions using Dice's similarity coefficient (DSC). The detection performance of the AI systems ranged from low to moderate (AUCs from 0.525 to 0.694). The overlap between the areas of interest and the breast lesions was low for all the studied methods (median DSC from 4.2% to 38.0%). The AI system with the highest cancer detection performance (AUC = 0.694, CI 0.662-0.726) showed the lowest overlap (DSC = 4.2%) with breast lesions. The areas of interest found by saliency analysis of the AI systems showed poor overlap with breast lesions. These results suggest that AI systems with the highest performance do not solely rely on localized breast lesions for their decision-making in cancer detection; rather, they incorporate information from large image regions. This work contributes to the understanding of the role of breast lesions in cancer detection using AI.

Cancer origin tracing and timing in two high-risk prostate cancers using multisample whole genome analysis: prospects for personalized medicine.

BACKGROUND: Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question. METHODS: We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high-risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones. RESULTS: In patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, 5 years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, 3 years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance the identification of key drivers. Evolutionary analysis' potential impact on therapy selection appears positive in these pilot cases. CONCLUSIONS: PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value.

Unconventional treatment of inoperable biliary IPMN with an oesophageal stent in the common bile duct: case report.

Biliary intraductal papillary mucinous neoplasm (IPMN) is a rare biliary neoplasia preferably treated with oncologic resection. Endoscopic radio frequency (RF) ablation may be used as a palliative measure. We present a rare case, where heavy co-morbidities prevented surgery. Continuous mucus production caused recurrent episodes of severe cholangitis. Several ERCPs (endoscopic retrograde cholangio pancretography) were necessary due to recurrent biliary obstruction. RF ablation was not effective in the dilated common bile duct without a stricture. Standard biliary stents failed due to either migration or occlusion. When other options failed, an exceptional decision was made: a covered large diameter oesophageal stent was inserted in ERCP into the bile duct to secure bile flow and stop mucus production. Digital cholangioscopy was crucial adjunct to standard ERCP in endoscopic management. The palliative treatment method was successful: there were no stent-related adverse events or readmissions for cholangitis. The follow-up in the palliative care lasted until patient's last 10 months of lifetime.

Breast density and the likelihood of malignant MRI-detected lesions in women diagnosed with breast cancer.

OBJECTIVES: To assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant. METHODS: Patients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5th edition of the BI-RADS lexicon. RESULTS: Of 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03-6.86) higher for BI-RADS density category B, 2.68 (1.04-6.92) for category C, and 3.67 (1.36-9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts. CONCLUSION: Women diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions. CLINICAL RELEVANCE STATEMENT: Dense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer. KEY POINTS: • The role of preoperative MRI of patients with dense breasts diagnosed with breast cancer is under debate. • Women with denser breasts have a higher incidence of all MRI-detected incidental breast lesions, but the incidence of malignant MRI-detected incidental lesions is not higher than in women with fatty breasts. • High breast density alone should not indicate preoperative breast MRI.

Neoadjuvant chemotherapy induces an elevation of tumour apparent diffusion coefficient values in patients with ovarian cancer.

OBJECTIVES: Multiparametric magnetic resonance imaging (mMRI) is the modality of choice in the imaging of ovarian cancer (OC). We aimed to investigate the feasibility of different types of regions of interest (ROIs) in the measurement of apparent diffusion coefficient (ADC) values of diffusion-weighted imaging in OC patients treated with neoadjuvant chemotherapy (NACT). METHODS: We retrospectively enrolled 23 consecutive patients with advanced OC who had undergone NACT and mMRI. Seventeen of them had been imaged before and after NACT. Two observers independently measured the ADC values in both ovaries and in the metastatic mass by drawing on a single slice of (1) freehand large ROIs (L-ROIs) covering the solid parts of the whole tumour and (2) three small round ROIs (S-ROIs). The side of the primary ovarian tumour was defined. We evaluated the interobserver reproducibility and statistical significance of the change in tumoural pre- and post-NACT ADC values. Each patient's disease was defined as platinum-sensitive, semi-sensitive, or resistant. The patients were deemed either responders or non-responders. RESULTS: The interobserver reproducibility of the L-ROI and S-ROI measurements ranged from good to excellent (ICC range: 0.71-0.99). The mean ADC values were significantly higher after NACT in the primary tumour (L-ROI p < 0.001, S-ROIs p < 0.01), and the increase after NACT was associated with sensitivity to platinum-based chemotherapy. The changes in the ADC values of the omental mass were associated with a response to NACT. CONCLUSION: The mean ADC values of the primary tumour increased significantly after NACT in the OC patients, and the amount of increase in omental mass was associated with the response to platinum-based NACT. Our study indicates that quantitative analysis of ADC values with a single slice and a whole tumour ROI placement is a reproducible method that has a potential role in the evaluation of NACT response in patients with OC. TRIAL REGISTRATION: Retrospectively registered (institutional permission code: 5302501; date of the permission: 31.7.2020).

Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study.

BACKGROUND: The degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. METHODS: This is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. RESULTS: Out of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0-252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. CONCLUSION: Overall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.

RADIATION DOSE OF THE EYE LENS IN CT EXAMINATIONS OF THE BRAIN IN CLINICAL PRACTICE-THE EFFECT OF RADIOGRAPHER TRAINING TO OPTIMISE GANTRY TILT AND SCAN LENGTH.

Lenses are always exposed to radiation in brain computed tomography (CT) scans. However, the lens dose can be reduced by excluding lens from scanning area by optimising gantry tilt and scan length. The object of this study is to retrospectively analyse if the optimisation by gantry tilt and scan length have been adequate in the CT scan of the brain, and to prospectively analyse the effect of radiographer training to the quality of the CT examinations. This study was conducted in two parts. In all, 329 brain CTs performed in the Tampere University Hospital from 2017 to 2019 were revised retrospectively. The prospective part included 51 brain CT studies conducted in October 2021. Dose to the eye of the lens was modelled using CT-Expo using zero-degree beam angle and scan lengths to expose the lens either to the primary or scattered radiation. Non-zero gantry tilt had been used in a large proportion of the CT examinations in the retrospective setting, 84.8%. However, the lenses were successfully excluded from the scan area in only 1.8% of the examinations. In the prospective part, the gantry tilt was used in 98% of the studies and the proportion of successful examinations rose from 1.8 to 11.8%. The lens dose decreased significantly when the eyes were excluded from the imaging area. The modelled lens dose in the large retrospective part was 25.9 mGy (17.8-49.2 mGy) when the eyes were included and 1.5 mGy (0.4-1.9 mGy) when the eyes were excluded. The lens dose was similar in the small prospective part. Despite the gantry tilt is widely used, unnecessary lens irradiation occurs extensively because of suboptimal gantry tilt and scan length. The training of radiographers reduces the radiation exposure to the lens by more optimal gantry tilt and scan length.

Preoperative measures predicting outcome after pancreatic resection in aged patients.

BACKGROUND AND OBJECTIVE: High-risk surgery on aged patients raises challenging ethical and clinical issues. The aim of this study was to analyze the preoperative factors associated with severe complications and returning home after pancreatic resection among patients aged ⩾ 75 years. PATIENTS AND METHODS: Patients aged ⩾ 75 years undergoing pancreatic resection in 2012-2019 were retrospectively searched from the hospital database. Preoperative indices (Clinical Frailty Scale, Skeletal Muscle Index, Geriatric Nutritional Risk Index, Charlson Comorbidity Index, and National Surgical Quality Improvement Program risk for severe complications) were determined. Postoperative outcome was evaluated by incidence of Clavien-Dindo 3b-5 complications, rate of returning home, and 1-year survival. RESULTS: A total of 95 patients were included. American Society of Anesthesiologists Class 3-4 covered 50%, Clinical Frailty Scale > 3 22%, Charlson Comorbidity Index > 6 53%, and a sarcopenic Skeletal Muscle Index 51% of these patients. The National Surgical Quality Improvement Program risk for severe complications was higher than average among 21% of patients. Geriatric Nutritional Risk Index showed high risk among 3% of them. In total, 19 patients (20%) experienced a severe (Clavien-Dindo 3b-5) complication. However, 30- and 90-day mortality was 2.1%. Preoperative indices were not associated with severe complications. Most patients (79%) had returned home within 8 weeks of surgery. Not returning home was associated with severe complications (p = 0.010). CONCLUSIONS: The short-term outcome after pancreatic resection of fit older patients is similar to that of younger, unselected patient groups. In these selected patients, the commonly used preoperative indexes were not associated with severe complications or returning home.

Population-based randomized trial of screening for clinically significant prostate cancer ProScreen: a pilot study.

OBJECTIVES: To evaluate the feasibility of a population-based screening trial using prostate-specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit. PATIENTS AND METHODS: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score 3-5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies. RESULTS: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA-positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]-positive) had a suspicious MRI finding (PI-RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%. CONCLUSION: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.

Image retrieval-based parenchymal analysis for breast cancer risk assessment.

PURPOSE: This research on breast cancer risk assessment aims to develop models that predict the likelihood of breast cancer. In recent years, the computerized analysis of visual texture patterns in mammograms, namely parenchymal analysis, has shown great potential for risk assessment. However, the visual complexity and heterogeneity of visual patterns limit the performance of parenchymal analysis in large populations. In this work, we propose a method to create individualized risk assessment models based on the radiological visual appearance (radiomic phenotypes) of the mammograms. METHODS: We developed a content-based image retrieval system to stratify mammographic analysis according to the similarities of their radiomic phenotypes. We collected 1144 mammograms from 286 women following a case-control study design. We compared the classical parenchymal analysis with the proposed approach using the area under the ROC curve (AUC) with 95% confidence intervals (CI). Statistical significance was assessed using DeLong's test ( p < $p<$ 0.05). RESULTS: At a patient level, AUC values of 0.504 (95% CI: 0.398-0.611) with classical parenchymal analysis increased to 0.813 (95% CI: 0.734-0.892) when the radiomic phenotypes are incorporated with the proposed method. In risk estimation from individual, standard mammographic views, the highest performance was obtained with the mediolateral oblique view of the right breast (RMLO), with an AUC value of 0.727 (95% CI: 0.634-0.820). Differences in performance among views were statistically significant ( p < 0.05 $p<0.05$ ) CONCLUSIONS: These results indicate that the utilization of radiomic phenotypes increases the performance of computerized risk assessment based on parenchymal analysis of mammographic images. SIGNIFICANCE: The creation of individualized risk assessment models may be leveraged to target personalized screening and prevention recommendations according to the person's risk.

Methodology, clinical applications, and future directions of body composition analysis using computed tomography (CT) images: A review.

PURPOSE OF THE REVIEW: We aim to review the methods, current research evidence, and future directions in body composition analysis (BCA) with CT imaging. RECENT FINDINGS: CT images can be used to evaluate muscle tissue, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) compartments. Manual and semiautomatic segmentation methods are still the gold standards. The segmentation of skeletal muscle tissue and VAT and SAT compartments is most often performed at the level of the 3rd lumbar vertebra. A decreased amount of CT-determined skeletal muscle mass is a marker of impaired survival in many patient populations, including patients with most types of cancer, some surgical patients, and those admitted to the intensive care unit (ICU). Patients with increased VAT are more susceptible to impaired survival / worse outcomes; however, those patients who are critically ill or admitted to the ICU or who will undergo surgery appear to be exceptions. The independent significance of SAT is less well established. Recently, the roles of the CT-determined decrease of muscle mass and increased VAT area and epicardial adipose tissue (EAT) volume have been shown to predict a more debilitating course of illness in patients suffering from severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. SUMMARY: The field of CT-based body composition analysis is rapidly evolving and shows great potential for clinical implementation.

A randomized trial comparing inspiratory training and positive pressure training in immediate lung recovery after minor pleuro-pulmonary surgery.

BACKGROUND: Two respiratory physiotherapy modalities were compared in a randomized controlled trial on patients undergoing minor pleuro-pulmonary surgery. METHODS: Forty-five patients were randomly allocated into positive expiratory pressure (PEP) therapy (n=23) and inspiratory muscle training (IMT) groups (n=22). Individualized group specific physiotherapeutic guidance was administered preoperatively, and once a day postoperatively. Patients also performed independent exercises and kept a logbook. Pain was assessed on a numerical reference scale (NRS). Volumetric pulmonary function values and walking distance were recorded preoperatively, and on first (POD1) and second postoperative days (POD2). Pre- and postoperative values were compared using two-way repeated measures analysis of variance. RESULTS: Patient characteristics and pleuro-pulmonary interventions were similar between the groups. Thoracotomy was performed in 14/45 and video assisted surgery (VATS) in 31/45 of cases. Preoperative volumetric pulmonary functions were normal or slightly decreased in 29/45, and fell significantly (P<0.001) on the first postoperative day (POD1) and improved but remained significantly lower on the second postoperative day. The recovery of mean FEV1, FIV1 and FIVC values was greater in the IMT than in the PEP group between POD1 and POD2, but without significant difference. The corresponding relative to preoperative values were higher in the IMT group, with a significant difference in FEV1 (P=0.045). Also relative PEF and FIV1 values seemed to be slightly higher in the IMT compared to the PEP group, but not significantly. Average NRS values for pain were lower in the IMT group (P=0.010) but only on POD1. Air leak was noted in 4/45 patients, two in each group, on POD1, and two in PEP groups and one in IMT group on POD2. Mean measured walking distances between groups did not differ. Mean hospital stay was 4 days in the PEP group and 3 days in the IMT group. There was no hospital mortality. CONCLUSIONS: Pulmonary function values decreased significantly after minor lung resections, supporting rehabilitative respiratory physiotherapy to avoid postoperative pulmonary complications (PPCs). Both PEP and IMT training were well tolerated and equally efficient when comparing spirometry values at three time points. IMT appeared advantageous regarding relative FEV1 recovery and immediate postoperative pain.

Radiological and pathological assessment of response to neoadjuvant CDK4/6 inhibitor and endocrine treatments in a real-life setting-initial results.

BACKGROUND: Neoadjuvant endocrine therapy is an alternative to neoadjuvant chemotherapy in women with inoperable luminal-like breast cancers. Neoadjuvant cyclin-dependent kinase 4/6 inhibitor treatment combined with endocrine treatment (CDK4/6I + E) is interesting given the combination's utility in the treatment of metastatic breast cancer. Currently, the literature on the radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting is scarce. PURPOSE: To conduct a radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting. MATERIAL AND METHODS: We retrospectively reviewed clinical, pathological, and radiological findings of six patients with luminal-like breast cancers treated with neoadjuvant CDK4/6I + E treatment. The radiological neoadjuvant CDK4/6I + E response was evaluated with the RECIST 1.1 criteria and the pathological residual disease was assessed using the Residual Cancer Burden (RBC) criteria. RESULTS: None of the patients achieved a complete radiological magnetic resonance imaging (MRI)-determined response or a complete pathological response; three (50%) patients had a partial radiological response; in the three others, the disease remained stable radiologically. All of the tumors were rendered susceptible to surgical treatment. Two out of six (33.3%) patients had a moderate response (RBC-II); four (66.7%) had an extensive residual disease (RBC-III) in the final surgical sample. CONCLUSION: Although none of the patients achieved a pathologically complete response, neoadjuvant CDK4/6I + E treatment rendered all tumors operable. MRI appears to be reliable in the assessment of the neoadjuvant CDK4/6I + E treatment response in a real-life setting. Larger studies are warranted to confirm these results.

Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer: Recommendations for Advancing Precision Medicine.

BACKGROUND: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. OBJECTIVE: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials. DESIGN SETTING AND PARTICIPANTS: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature. INTERVENTION: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression. RESULTS AND LIMITATIONS: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of "skeletal-related events" complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study. CONCLUSIONS: The study identified novel outcome subgroups for future validation and provides "vision for mPC precision oncology 2020-2050" draft recommendations for future data collection and biomarker studies. PATIENT SUMMARY: To better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudinal clinical and autopsy records in 33 men. We identified novel outcomes, phenotypes, and aspects of disease burden to be tested and refined in future trials.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

PURPOSE: To prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). METHODS: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. RESULTS: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. CONCLUSION: 18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391.

Perioperative acinar cell count method works well in the prediction of postoperative pancreatic fistula and other postoperative complications after pancreaticoduodenectomy.

BACKGROUND: Earlier we have shown that high frequency of acinar cells in the pancreatic transsection line predicts postoperative pancreatic fistula after pancreaticoduodenectomy (PD). Acinar cell count method (ACM) is fast to perform during operation. In this study our aim was to validate the accuracy of ACM to compare it with other published risk prediction methods. METHODS: 87 patients who underwent PD without any trial including perioperative medications were collected from a single hospital. Data on demographics, surgical details, postoperative complications clinically relevant pancreatic fistulae (CR-POPF) and clinically relevant Clavien-Dindo complications (CR-CDC) were registered. Thirteen previously published risk prediction methods were included in the comparison, such as pancreatic duct diameter, palpable texture of pancreas, Braga score (BC), Fistula Risk Score, Modified Fistula Risk Score, Alternative Fistula Risk Score and multiple radiological parameters. ROC-curves were calculated to compare sensitivity and specificity for identifying high risk patients for CR-POPF and CR-CDC. RESULTS: The three most accurate risk prediction methods for CR-POPF were ACM (sensitivity 88.9%, specificity 52.6%; p = 0.043), BC (87.5%, 56.6%; p = 0.039) and visceral fat area to subcutaneous fat area ratio (75.5%, 80.0%; p = 0.032). In predicting CR-CDC the three most accurate methods were ACM (73.9%, 56.2%; p = 0.033), BC (68.4%, 59.5%; p = 0.036) and TPAI (78.3%, 41.7%; p = 0.012). CONCLUSION: ACM was shown to be as good as the more complicated risk scoring methods in the prediction of CR-POPF. It was good also in predicting all clinically relevant complications. ACM is easy to use during operation and can be recommended as a routine risk prediction method.

Diagnostic efficiency of whole-body 18F-FDG PET/MRI, MRI alone, and SUV and ADC values in staging of primary uterine cervical cancer.

BACKGROUND: The use of PET/MRI for gynecological cancers is emerging. The purpose of this study was to assess the additional diagnostic value of PET over MRI alone in local and whole-body staging of cervical cancer, and to evaluate the benefit of standardized uptake value (SUV) and apparent diffusion coefficient (ADC) in staging. METHODS: Patients with histopathologically-proven cervical cancer and whole-body 18F-FDG PET/MRI obtained before definitive treatment were retrospectively registered. Local tumor spread, nodal involvement, and distant metastases were evaluated using PET/MRI or MRI dataset alone. Histopathology or clinical consensus with follow-up imaging were used as reference standard. Tumor SUVmax and ADC were measured and SUVmax/ADC ratio calculated. Area under the curve (AUC) was determined to predict diagnostic performance and Mann-Whitney U test was applied for group comparisons. RESULTS: In total, 33 patients who underwent surgery (n = 23) or first-line chemoradiation (n = 10) were included. PET/MRI resulted in higher AUC compared with MRI alone in detecting parametrial (0.89 versus 0.73), vaginal (0.85 versus 0.74), and deep cervical stromal invasion (0.96 versus 0.74), respectively. PET/MRI had higher diagnostic confidence than MRI in identifying patients with radical cone biopsy and no residual at hysterectomy (sensitivity 89% versus 44%). PET/MRI and MRI showed equal AUC for pelvic nodal staging (both 0.73), whereas AUC for distant metastases was higher using PET/MRI (0.80 versus 0.67). Tumor SUVmax/ADC ratio, but not SUVmax or ADC alone, was significantly higher in the presence of metastatic pelvic lymph nodes (P < 0.05). CONCLUSIONS: PET/MRI shows higher accuracy than MRI alone for determining local tumor spread and distant metastasis emphasizing the added value of PET over MRI alone in staging of cervical cancer. Tumor SUVmax/ADC ratio may predict pelvic nodal involvement.

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

BACKGROUND: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). OBJECTIVE: To compare standard staging modalities with newer and potentially more accurate imaging modalities. DESIGN, SETTING, AND PARTICIPANTS: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. RESULTS AND LIMITATIONS: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. CONCLUSIONS: Despite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. PATIENT SUMMARY: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.