Sanja Dacic

Supplementary Table S3 shows the mean intake of cruciferous vegetables for participants in the sulforaphane treated and placebo groups, respectively, at baseline and during the treatment period.

Supplementary Table S7 shows the frequencies of patients with any adverse events in the gastrointestinal, neurological and other body systems of participants in the sulforaphane treated and placebo controlled groups, respectively.

Supplementary Table S4 describes the histopathology score at baseline and the end of treatment period for participants in the sulforaphane treated and placebo groups, respectively.

Supplementary Table S6 shows the number of adverse events grouped by the attribution and severity during the treatment period for participants in the sulforaphane treated and placebo groups, respectively.

Supplementary Table S5 shows mean scores of change in the TUNEL and Caspase-3 from pre- to post-treatment in participants with higher and lower urinary sulforaphane levels in sulforaphane treated and placebo controlled groups

Experimental studies have shown that dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers caspase-3 and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce the Ki-67 index, and/or increase caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 μmol sulforaphane for 12 months. The endpoints were the changes in histopathology scores and Ki-67, caspase-3, and TUNEL indices in post- versus pretreatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology but significantly reduced the Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (P = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (P = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of the Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on the caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced the Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development.Prevention Relevance: High intake of cruciferous vegetables and their sulforaphane is associated with lower incidence of lung cancer in humans and animal models. This clinical trial has demonstrated that oral supplementation of sulforaphane for 12 months significantly reduced the Ki-67 index, a potential surrogate endpoint of biomarkers for lung cancer risk.

Supplementary Table S2 describes the frequencies of lung diseases and measurements of kidney and liver functions at baseline for participants in the sulforaphane treated and placebo groups, respectively.

Supplementary Table S1: describes the representativeness of the study subjects whose distributions of age, sex, and smoking history were in line with the US general population

Experimental studies have shown that dietary isothiocyanates reduced cellular proliferative marker Ki-67 and increased apoptotic markers caspase-3 and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) in animals, but human data are lacking. The present study was to assess whether sulforaphane would stop/reverse the progression of bronchial histopathology, reduce the Ki-67 index, and/or increase caspase-3 and TUNEL indices in humans. A randomized clinical trial (NCT03232138) was conducted in former smokers. Forty-three subjects were randomly assigned to the placebo or the treatment with a potential daily dose of 95 μmol sulforaphane for 12 months. The endpoints were the changes in histopathology scores and Ki-67, caspase-3, and TUNEL indices in post- versus pretreatment bronchial biopsies. Thirty-seven participants (17 in the sulforaphane and 20 in the placebo group) completed the study. Supplementation of sulforaphane did not show significant impact on bronchial histopathology but significantly reduced the Ki-67 index with a 20% decrease in the sulforaphane group and a 65% increase in the placebo (P = 0.014). The difference was even greater in high-density (3+) positive Ki-67, with a 44% decrease in the sulforaphane group compared with a 71% increase in the placebo (P = 0.004). Higher bioavailability of sulforaphane was correlated with greater reduction of the Ki-67 index (P for trend = 0.019). Sulforaphane treatment had no impact on the caspase-3 or TUNEL index in bronchial biopsies. No severe adverse event was observed in the study participants. The findings of oral sulforaphane that significantly reduced the Ki-67 index in bronchial tissue support further development as a potential chemopreventive agent against lung cancer development. Prevention Relevance: High intake of cruciferous vegetables and their sulforaphane is associated with lower incidence of lung cancer in humans and animal models. This clinical trial has demonstrated that oral supplementation of sulforaphane for 12 months significantly reduced the Ki-67 index, a potential surrogate endpoint of biomarkers for lung cancer risk.

Aim: This study evaluates the comparative effectiveness of pathologists versus artificial intelligence (AI) algorithms in scoring PD‐L1 expression in non‐small cell lung carcinoma (NSCLC). Immune‐checkpoint inhibitors have revolutionized NSCLC treatment, with PD‐L1 expression, measured as the tumour proportion score (TPS), serving as a critical predictive biomarker for therapeutic response.Methods and Results: In our analysis, 51 SP263‐stained NSCLC cases were scored by six pathologists using light microscopy and whole‐slide images (WSI), alongside evaluations by two commercially available software tools: uPath software (Roche) and the PD‐L1 Lung Cancer TME application (Visiopharm). The study examined intra‐ and interobserver agreement among pathologists at TPS cutoffs of 1% and 50%, revealing moderate interobserver agreement (Fleiss' kappa 0.558) for TPS <1% and almost perfect agreement (Fleiss' kappa 0.873) for TPS ≥50%. Intraobserver consistency was high, with Cohen's kappa ranging from 0.726 to 1.0. Comparisons between the AI algorithms and the median pathologist scores showed fair agreement for uPath (Fleiss' kappa 0.354) and substantial agreement for the Visiopharm application (Fleiss' kappa 0.672) at the 50% TPS cutoff.Conclusion: These results indicate that while there is strong interobserver concordance among pathologists at higher TPS levels, the performance of AI algorithms is less consistent. The study underscores the need for further refinement of AI tools to match the reliability of expert human evaluation, particularly in critical clinical decision‐making contexts.