PurposeA relationship between mean heart dose (MHD) and acute coronary event (ACE) rate was reported in a study of patients with breast cancer (BC). The main objective of our cohort study was to validate this relationship and investigate if other dose-distribution parameters are better predictors for ACEs than MHD.Patients and MethodsThe cohort consisted of 910 consecutive female patients with BC treated with radiotherapy (RT) after breast-conserving surgery. The primary end point was cumulative incidence of ACEs within 9 years of follow-up. Both MHD and various dose-distribution parameters of the cardiac substructures were collected from three-dimensional computed tomography planning data.ResultsThe median MHD was 2.37 Gy (range, 0.51 to 15.25 Gy). The median follow-up time was 7.6 years (range, 0.1 to 10.1 years), during which 30 patients experienced an ACE. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6 to 35.0; P = .042). Analysis showed that the volume of the left ventricle receiving 5 Gy (LV-V5) was the most important prognostic dose-volume parameter. The most optimal multivariable normal tissue complication probability model for ACEs consisted of LV-V5, age, and weighted ACE risk score per patient (c-statistic, 0.83; 95% CI, 0.75 to 0.91).ConclusionA significant dose-effect relationship was found for ACEs within 9 years after RT. Using MHD, the relative increase per Gy was similar to that reported in the previous study. In addition, LV-V5 seemed to be a better predictor for ACEs than MHD. This study confirms the importance of reducing exposure of the heart to radiation to avoid excess risk of ACEs after radiotherapy for BC.

The aim of this study was to investigate classical MHC class I and nonclassical MHC (human leukocyte antigen-G [HLA-G]) expression in a large cohort of patients with endometrial cancer, to determine the prognostic value of these cell surface markers and their relation with clinicopathological variables. Tissue microarrays containing epithelial endometrial carcinoma tissue from 554 patients were stained for classical and nonclassical MHC class I using the following monoclonal antibodies: 4H84 (anti-HLA-G), b2-m (anti-beta-2-microglobulin) and HC-10 (MHC class I antigen heavy chain). Expression data were linked to known clinicopathological characteristics and survival. HLA-G upregulation and MHC class I downregulation in neoplastic cells was observed in 40% and 48%, respectively. Nonendometrioid tumor type, advanced stage disease (FIGO stage !II) and poorly or undifferentiated tumors were associated with MHC class I downregulation. Absence of HLA-G expression was independently associated with MHC class I downregulation. In univariate analysis, MHC class I downregulation was a predictor of worse disease-specific survival. Prognostic unfavorable tumor characteristics were correlated with downregulation of MHC class I expression in endometrial cancer cells. Furthermore, downregulated MHC class I has a negative impact on diseasespecific survival, observed in a large cohort of patients with endometrial cancer. As there seems to be a relation between classical and nonclassical MHC class I molecules (HLA-G), further research is warranted to unravel this regulatory mechanism.Endometrial adenocarcinoma is the most common gynecological malignancy in the developed world.1 In The Netherlands, 1,400 women are diagnosed with endometrial cancer each year, of which the majority is an early stage of disease. Prognosis is good in low-stage endometrial cancer (5-year survival International Federation of Gynecology and Obstetrics [FIGO] Stages I and II: 86% and 66%), but it decreases rapidly in higher stages (5-year survival FIGO Stages III and IV: 44% and 16%).2 Nonendometrioid histological type or Grade 3 endometrioid carcinoma (Type II tumors) have been identified as prognostically worse subgroups.3 Classical surgical approaches in combination with radiotherapy and/or chemotherapy have had only limited success in improving the overall survival in Type II endometrial cancer. In future, immunotherapy might fulfill a role in the treatment of endometrial cancer. Additional investigation is warranted to show that the immune system does play a (prognostic) role in this type of cancer. 4,5 Major histocompatibility complex (MHC) Class I expression might be such a cell surface marker with prognostic significance in endometrial cancer, exemplifying the role of the cellular immune system.All human body cells present antigens to the immune system by means of MHC Class I molecules on the cell surface. MHC Class I antigens comprise the classical (Class Ia) human leukocyte antigen (HLA)-A, -B and -C antigens and the nonclassical (Class Ib) HLA-E...

Toxicity and CO are not impaired after 3D-CRT-SIB. Fibrosis was not significantly associated with radiotherapy parameters. Independent risk factors for fibrosis were chemotherapy after radiotherapy, re-resection, and larger tumor size. Re-resection was most predictive for worse CO. Age had an impact on chest wall pain occurrence.