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Reproducibility of tumor budding assessment in pancreatic cancer based on a multicenter interobserver study.

ABSTRACT: Tumor budding has been reported to be an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Its use in daily diagnostics would improve the prognostic stratification of patients. We performed a multicenter interobserver study to test various budding assessment methods for their reproducibility. Two serial sections of 50 resected, treatment-naïve PDACs were stained for Hematoxylin and Eosin (H&E) and pancytokeratin. Tumor budding was scored by independent observers at five participating centers in Switzerland, Germany, and Canada. Pathologists assessed tumor budding on a digital platform comparing H&E with pancytokeratin staining in 10 high-power fields (10HPF) and one HPF hotspot (1HPF). Additionally, tumor budding was assessed in one H&E hotspot at × 20 magnification, as suggested by the International Tumor Budding Consensus Conference (ITBCC). Correlation coefficients for bud counts between centers ranged from r = 0.58648 to r = 0.78641 for H&E and from r = 0.69288 to r = 0.81764 for pancytokeratin. The highest interobserver agreement across all centers was observed for pancytokeratin 10HPFs (ICC = 0.6). ICC values were 0.49, 0.48, 0.41, and 0.4 for H&E in 1HPF hotspot, H&E in 10HPFs, pancytokeratin in 1HPF, and H&E in one hotspot at ×20, respectively (ITBCC method). This interobserver study reveals a range between moderately poor to moderate agreement levels between pathologists for the different tumor budding assessment methods in PDAC. Acceptable levels of agreement were reached with the pancytokeratin 10HPF method, which can thus be recommended for the assessment of tumor budding in PDAC resection specimens. To improve the levels of interobserver agreement, the implementation of machine learning applications should be considered.

SUBMITTER: Karamitopoulou E

PROVIDER: S-EPMC7990816 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose To determine the interobserver reproducibility of the Prostate Imaging Reporting and Data System (PI-RADS) version 2 lexicon. Materials and Methods This retrospective HIPAA-compliant study was institutional review board-approved. Six radiologists from six separate institutions, all experienced in prostate magnetic resonance (MR) imaging, assessed prostate MR imaging examinations performed at a single center by using the PI-RADS lexicon. Readers were provided screen captures that denoted the location of one specific lesion per case. Analysis entailed two sessions (40 and 80 examinations per session) and an intersession training period for individualized feedback and group discussion. Percent agreement (fraction of pairwise reader combinations with concordant readings) was compared between sessions. κ coefficients were computed. Results No substantial difference in interobserver agreement was observed between sessions, and the sessions were subsequently pooled. Agreement for PI-RADS score of 4 or greater was 0.593 in peripheral zone (PZ) and 0.509 in transition zone (TZ). In PZ, reproducibility was moderate to substantial for features related to diffusion-weighted imaging (κ = 0.535-0.619); fair to moderate for features related to dynamic contrast material-enhanced (DCE) imaging (κ = 0.266-0.439); and fair for definite extraprostatic extension on T2-weighted images (κ = 0.289). In TZ, reproducibility for features related to lesion texture and margins on T2-weighted images ranged from 0.136 (moderately hypointense) to 0.529 (encapsulation). Among 63 lesions that underwent targeted biopsy, classification as PI-RADS score of 4 or greater by a majority of readers yielded tumor with a Gleason score of 3+4 or greater in 45.9% (17 of 37), without missing any tumor with a Gleason score of 3+4 or greater. Conclusion Experienced radiologists achieved moderate reproducibility for PI-RADS version 2, and neither required nor benefitted from a training session. Agreement tended to be better in PZ than TZ, although was weak for DCE in PZ. The findings may help guide future PI-RADS lexicon updates. (©) RSNA, 2016 Online supplemental material is available for this article.

Project description:The present study aimed to analyze the association between tumor budding index (TBI) and microvessel density (MVD) and selected clinicopathological features in female patients with endometrial cancer (EC). The present study included 137 patients, of whom 117 had endometrial endometrioid cancer and 3 had non-endometrioid EC (NEEC). Additionally, 8 cases of simple endometrial hyperplasia and 9 cases of atypical endometrial hyperplasia were included in the present study. Patient age, menopausal status, tumor histological type, grade and International Federation of Gynecologists and Obstetricians (FIGO) clinical stage were investigated. Immunohistochemistry was utilized to detect MVD using a CD34 antibody, and a laminin-5?2 antibody was used for TBI assessment. In nonmalignant endometrial lesions, the TBI was significantly lower than that in patients with EC and NEEC (P=0.002). Significant differences in median TBI (MD-TBI) were also observed between patients with low-grade EC (MD-TBI, 4.5) and high-grade EC (MD-TBI, 16.2; P=0.01). Age, body mass index and tumor FIGO stage were not indicated to be associated with the MD-TBI. Premenopausal patients with EC had lower MD-TBI values than postmenopausal patients (0.3 vs. 11.1; P<0.005). The median MVD-CD34 in the study group was 19 (range, 13-29). Significant differences in MVD-CD34 were observed between malignant and nonmalignant endometrial lesions (P=0.01). Histological grade was markedly associated with tumor MVD-CD34 (P=0.001). The MVD was higher in high-grade cancer (G3; MVD-CD34, 24.9) than in grade G1 and G2 lesions (MVD-CD34, 14 and 18.6, respectively; P=0.01). FIGO clinical stage was not associated with MVD-CD34 in low and high stage lesions (MD, 18.4 for FIGO stage I/II; MD, 17.6 for FIGO stage III/IV; P=0.2). High MVD was markedly associated with high MD-TBI (P=0.0002). In conclusion, TBI could be a valuable indicator of tumor aggressiveness in patients with EC. The presence of the tumor budding phenomenon with increased MVD may have the potential to further refine clinical management decisions when endometrial malignancy is detected.

Project description:Radiomics is a method to mine large numbers of quantitative imaging features and develop predictive models. It has shown exciting promise for improved cancer decision support from early detection to personalized precision treatment, and therefore offers a desirable new direction for pancreatic cancer where the mortality remains high despite the current care and intense research. For radiomics, interobserver segmentation variability and its effect on radiomic feature stability is a crucial consideration. While investigations have been reported for high-contrast cancer sites such as lung cancer, no studies to date have investigated it on CT-based radiomics for pancreatic cancer. With three radiation oncology observers and three radiology observers independently contouring on the contrast CT of 21 pancreatic cancer patients, we conducted the first interobserver segmentation variability study on CT-based radiomics for pancreatic cancer. Moreover, our novel investigation assessed whether there exists an interdisciplinary difference between the two disciplines. For each patient, a consensus tumor volume was generated using the simultaneous truth and performance level expectation algorithm, using the dice similarity coefficient (DSC) to assess each observer's delineation against the consensus volume. Radiation oncology observers showed a higher average DSC of 0.81 ± 0.06 than the radiology observers at 0.69 ± 0.16 (p = 0.002). On a panel of 1277 radiomic features, the intraclass correlation coefficients (ICC) was calculated for all observers and those of each discipline. Large variations of ICCs were observed for different radiomic features, but ICCs were generally higher for the radiation oncology group than for the radiology group. Applying a threshold of ICC > 0.75 for considering a feature as stable, 448 features (35%) were found stable for the radiation oncology group and 214 features (16%) were stable from the radiology group. Among them, 205 features were found stable for both groups. Our results provide information for interobserver segmentation variability and its effect on CT-based radiomics for pancreatic cancer. An interesting interdisciplinary variability found in this study also introduces new considerations for the deployment of radiomics models.

Project description:BackgroundSecuring sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL.MethodA multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion.ResultsFifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04).ConclusionThe surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups.Trial registrationClinicalTrials.gov Identifier: NCT04766060.

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Reproducibility of tumor budding assessment in pancreatic cancer based on a multicenter interobserver study.

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