Prepregnancy Body Mass Index and Risk of Differentiated Thyroid Cancer: A Prospective Cohort Study of More than 440,000 Danish Women.

Background: High body mass index (BMI) has previously been associated with increased risk of differentiated thyroid cancer (DTC); however, only few studies have investigated the association with BMI in a large cohort assessed at a young age and with sufficient data on confounding factors. We assessed the association between excess body weight and the risk of DTC and papillary thyroid cancer (PTC) in a large cohort of young Danish women with substantial confounder control. Methods: We included all parous Danish women registered with a prepregnancy BMI ≥18.5 kg/m2 during 2004-2016 in the Danish Medical Birth Registry in the study population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) with confidence intervals (CIs) of DTC according to BMI. In subanalyses, we investigated PTC as a separate group. Analyses were adjusted for calendar time, education, smoking status, benign thyroid disease (BTD), type II diabetes, parity, and oral contraceptive use. In addition, we examined the association with increasing BMI stratified for previous BTD. Results: A total of 443,403 women were included in the study population, and the median age at baseline was 30.0 years. Altogether, 463 women were diagnosed with DTC during follow-up. Excess body weight was associated with a higher rate of DTC (overweight, BMI 25-29.9 kg/m2: HR = 1.54; CI 1.25-1.90. Obese, BMI ≥30 kg/m2: HR = 1.32; CI 1.00-1.75) compared with normal weight. Results were similar in PTC. In addition, we found an increased rate of DTC with increasing BMI, when investigating BMI as a continuous variable per 5 kg/m2 increase (HR = 1.17; CI 1.07-1.27). The results were similar in women without previous BTD. Conclusions: Our study confirms that excess body weight is associated with an increased incidence of DTC and PTC in women.

Temporal Trends in Papillary and Follicular Thyroid Cancer Incidence from 1995 to 2019 in Adults in Denmark According to Education and Income.

Background: Thyroid cancer incidence has increased over the past decades. Differences in incidence trends have been observed depending on socioeconomic status. Here, we describe trends in the incidence of papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) in Denmark by level of education and income. Methods: All PTC and FTC cases registered in the Danish Cancer Registry from 1995 to 2019 were identified. Individual-level information on education and income was obtained from nationwide registries. We calculated age-standardized incidence rates according to sex, tumor size, education and income, and estimated incidence trends by average annual percentage change (AAPC) and corresponding confidence intervals [CIs] for the periods 1995 to 2004 and 2005 to 2019 by using Poisson regression models. Results: We identified 3454 cases of PTC and 972 cases of FTC. From 2005 to 2019 among women, the incidence of PTC increased across all levels of education (AAPCshort education = 12.5% [CI 9.8 to 15.3]; AAPCmedium education = 8.1% [CI 6.4 to 9.9]; AAPClong education = 7.3% [CI 5.4 to 9.2]). The same pattern was seen for income. The incidence of FTC increased in all levels of education (AAPCshort education = 10.5% [CI 5.8 to 15.4]; AAPCmedium education = 4.0% [CI 0.9 to 7.3]; AAPClong education = 4.3% [CI 0.6 to 8.1]), with the same pattern for income. Similar trends were observed among men, in both small (≤2 cm) and large (>2 cm) PTCs and from 1995 to 2004 in both sexes. Conclusions: Enhanced detection of thyroid cancer among all levels of education and income cannot be ruled out, and in addition, our results may suggest a true increase in the incidence of differentiated thyroid cancer.

Impact of PD-L1 and T-cell inflamed gene expression profile on survival in advanced ovarian cancer.

OBJECTIVE: Programmed death ligand 1 (PD-L1) expression affects tumor evasion of immune surveillance. The prognostic value and relationship of PD-L1 expression to T-cell-inflamed immune signatures in ovarian cancer are unclear. The purpose of this study is to evaluate the impact of PD-L1 on overall survival and its correlation with an immune-mediated gene expression profile in patients with advanced ovarian cancer. METHODS: PD-L1 expression in tumor and immune cells was assessed by immunohistochemistry, and PD-L1-positive expression was defined as a combined positive score ≥1; a T-cell-inflamed gene expression profile containing interferon γ response genes was evaluated using extracted RNA from surgical samples. Associations between PD-L1 expression, gene expression profile status, and overall survival were analyzed using the Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazards regression models. RESULTS: A total of 376 patients with advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer treated by cytoreductive surgery and platinum-based therapy were included. PD-L1-positive expression was observed in 50.5% of patients and associated with more advanced stage (p=0.047), more aggressive histologic subtype (p=0.001), and platinum sensitivity defined by increasing treatment-free interval from first platinum-based chemotherapy to next systemic treatment (p=0.027). PD-L1-positive expression was associated with longer overall survival in multivariate analyses (adjusted HR 0.72, 95% CI 0.56 to 0.93). In subgroup analyses, this association was most pronounced in patients with partially platinum-sensitive disease (treatment-free interval ≥6 to <12 months). T-cell-inflamed gene expression profile status correlated with PD-L1 expression (Spearman, ρ=0.712) but was not an independent predictor of overall survival. CONCLUSION: PD-L1 expression is associated with longer overall survival among advanced ovarian cancer patients. PD-L1 expression may be an independent prognostic biomarker.

Impact of residual disease on overall survival in women with Federation of Gynecology and Obstetrics stage IIIB-IIIC vs stage IV epithelial ovarian cancer after primary surgery.

INTRODUCTION: The objective of this study was to determine the impact of intra-abdominal residual disease size, type (carcinomatosis, tumor mass or both), and location (upper/lower abdominal/both) on overall survival in women with Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IIIC vs stage IV epithelial ovarian cancer who underwent primary debulking surgery. MATERIAL AND METHODS: Altogether 2092 women diagnosed with advanced epithelial ovarian cancer undergoing primary debulking surgery in Denmark during 2005-2016 were identified in the Danish Gynecological Cancer Database. The impact of residual disease size, type, and location were evaluated using univariate and multivariate analyses. RESULTS: Complete cytoreduction (residual disease = 0) was achieved in 47.3% and 38.4% of women with stage IIIB-IIIC and IV epithelial ovarian cancer, respectively. A benefit in overall survival was observed in women with residual disease = 0 compared with women with residual disease, and among women with residual disease ≤1 cm compared with residual disease >2 cm in both stages IIIB-IIIC and stage IV in multivariate analyses. Multivariate analyses showed an inferior overall survival for women with both residual carcinomatosis and residual tumor mass compared with those with residual tumor mass or residual carcinomatosis only for stage IIIB-IIIC and IV, and an inferior overall survival for women with residual disease located in both the upper and lower abdomen compared with residual disease in the upper abdomen only in stages IIIB-IIIC. CONCLUSIONS: Our results confirm the positive prognostic impact of both complete cytoreduction and residual disease ≤1 cm in stages IIIB-IIIC as well as stage IV epithelial ovarian cancer. Women with stage IV do benefit from cytoreductive surgery and should be considered for primary debulking surgery, if residual disease = 0 can initially be expected.