206 Chapter 15 Post-virtual feedback round In a virtual feedback session, the results of the first two rounds were presented and contained i) overall data: near-unanimous diagnosis, variation in measurements of total tumor size and invasive size and ii) case-specific information: including heatmaps, invasion scores from round 1 and 2, measures of variation in invasion measurement (CV-inv), distribution of pattern scores in both rounds, morphological details of hotspots and other key areas and iii) information about focal invasive growth in biological collapse. To establish the measure of uncertainty about the assessment of invasion one “uncertainty” question was added to each case for the 3rd round: score 1: very uncertain about invasion assignment; score 2: somewhat certain; score 3: neutral; score 4: somewhat certain about invasion (presence or absence); score 5: very certain about presence or absence of invasion. As 29 cases were scored in round 1 and 2 as unanimous invasion, the specific request was to read in the 3rd round the remaining 41 cases. Statistical analysis Statistical analysis was performed in SPSS version 28 (IBM Corp., Armonk, NY, USA) and R Statistical Software version 4.2.1 (R Core Team 2022). P-values <0.05 were considered statistically significant. Invasion scores of first and third and second and third round were compared with the McNemar test. For comparison of coefficient of variation (CV = standard deviation / mean *100%; CVinv: mean) the modified signedlikelihood ratio test in the R CV equality package was used338. This test for comparison coefficient of variations at case level was applied on total tumor size and invasive size measurements as well as for comparison of coefficient of variations between largest invasive size (CV-inv) measurement and the sum of 2 or 3 lines. To obtain an impression about the precision of CV-tot and CV-inv the relative invasive size (ratio invasive size divided by total tumor size) was compared to the mean CV-inv and for case corresponding mean CV-tot. The distribution for ranking the pathologists for the frequency of invasive scores in lowest third, middle and highest third was compared with the region of work using the chi-square test. For Fleisch kappa analysis in the third round the scores from the 29 unanimous invasion cases in the first two rounds were added to the 41 cases. The average pathologists feeling about the decision of invasion was calculated as follows. Four points were assigned to “very uncertain”, 3 points to “somewhat uncertain”, 2 points for “neutral”, and 1 point to “somewhat certain”. The sum of all points divided by the number of pathologists scoring that case resulted in an average uncertainty score per case. For correlation analysis Pearson’s correlation coefficients calculated. For relapse free survival (RFS) and overall survival (OS) KaplanMeier curves were estimated and compared using the log-rank test.
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