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Your search keyword '"Horeweg, N"' showing total 3 results
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3 results on '"Horeweg, N"'

1. p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial

Author

Vermij, Lisa, Léon-Castillo, Alicia, Singh, Naveena, Powell, Melanie E., Edmondson, Richard J., Genestie, Catherine, Khaw, Pearly, Pyman, Jan, McLachlin, C. Meg, Ghatage, Prafull, de Boer, Stephanie M., Nijman, Hans W., Smit, Vincent T.H.B.M., Crosbie, Emma J., Leary, Alexandra, Creutzberg, Carien L., Horeweg, Nanda, Bosse, Tjalling, Horeweg, N., de Boer, S.M., Creutzberg, C.L., Bosse, T., Smit, V.T.H.B.M., Kroep, J., Nout, R.A., Nijman, H.W., de Bruyn, M., Powell, M.E., Singh, N., Kitchener, H.C., Crosbie, E., Edmondson, R., Church, D.N., Leary, A., Mileshkin, L., Pollock, P.M., and MacKay, H.

Abstract

Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as the subgroup with the poorest prognosis and the most likely to benefit from adjuvant chemo(radio)therapy. P53abn EC are POLEwildtype, mismatch repair proficient and show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation of routinely performed p53 IHC has therefore become of paramount importance. We aimed to comprehensively investigate abnormal p53 IHC patterns and their relation to clinicopathological and molecular features. Tumor material of 411 molecularly classified high-risk EC from consenting patients from the PORTEC-3 clinical trial were collected. p53 IHC was successful in 408 EC and was considered abnormal when the tumor showed a mutant expression pattern (including subclonal): overexpression, null or cytoplasmic. The presence of pathogenic mutations was determined by next generation sequencing (NGS). Abnormal p53 expression was observed in 131/408 (32%) tumors. The most common abnormal p53 IHC pattern was overexpression (n= 89, 68%), followed by null (n= 12, 9%) and cytoplasmic (n= 3, 2%). Subclonal abnormal p53 staining was observed in 27 cases (21%), which was frequently but not exclusively, associated with POLEmutations and/or MMRd (n= 22/27; p< 0.001). Agreement between p53 IHC and TP53NGS was observed in 90.7%, resulting in a sensitivity and specificity of 83.6% and 94.3%, respectively. Excluding POLEmut and MMRd EC, as per the WHO-endorsed algorithm, increased the accuracy to 94.5% with sensitivity and specificity of 95.0% and 94.1%, respectively. Our data shows that awareness of the abnormal p53 IHC patterns are prerequisites for correct EC molecular classification. Subclonal abnormal p53 expression is a strong indicator for POLEmut and/or MMRd EC. No significant differences in clinical outcomes were observed among the abnormal p53 IHC patterns. Our data support use of the WHO-endorsed algorithm and combining the different abnormal p53 IHC patterns into one diagnostic entity (p53abn EC).

Published
2022
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2. Health-related quality of life of breast cancer patients after accelerated partial breast irradiation using intraoperative or external beam radiotherapy technique.

Author

Jacobs, D.H.M., Horeweg, N., Straver, M., Roeloffzen, E.M.A., Speijer, G., Merkus, J., van der Sijp, J., Mast, M.E., Fisscher, U., Petoukhova, A.L., Zwanenburg, A.G., Marijnen, C.A.M., and Koper, P.C.M.

Subjects
ACCELERATED partial breast irradiation, QUALITY of life, BREAST cancer, CANCER patients, INTRAOPERATIVE radiotherapy, PET therapy, THERAPEUTICS
Abstract

To compare health-related quality of life (HRQL) in elderly breast cancer patients between two types of Accelerated Partial Breast Irradiation: intraoperative radiotherapy (IORT) and external beam APBI (EB-APBI). Between 2011 and 2016 women ≥60 years undergoing breast conserving therapy for early stage breast cancer were included in a prospective multi-centre cohort study. Patients were treated with electron IORT (1 × 23.3 Gy) or photon EB-APBI (10 × 3.85 Gy daily). HRQL was measured by the EORTC-QLQ C30 and BR23 questionnaires before surgery and at several time points until 1 year. HRQoL data was available of 204 IORT and 158 EB-APBI patients. In longitudinal analyses emotional functioning and future perspective were significantly, but not clinically relevantly, worse in IORT-treated patients, and improved significantly during follow-up in both groups. All other aspects of HRQL slightly worsened after treatment and recovered within 3 months with an improvement until 1 year. Cross-sectional analysis showed that postoperatively fatigue and role functioning were significantly worse in IORT patients compared to EB-APBI patients who were not yet irradiated, but the difference was not clinically relevant. At other timepoints there were no significant differences. Multivariable analysis at 1 year identified comorbidity and systemic therapy as risk factors for a worse global health score (GHS). EB-APBI and IORT were well tolerated. Despite a temporary deterioration after treatment, all HRQL scales recovered within 3 months resulting in no clinically relevant differences until 1 year between groups nor compared to baseline levels. • Both external-beam and intraoperative partial breast irradiation were well tolerated. • Most patients experienced mild temporary decrease in quality of life after treatment. • Quality of life (QoL) of patients recovered rapidly within 3 months after treatment. • No significant differences in QoL at 1 year after treatment between groups. • Comorbidity and systemic therapy add more impact than radiation therapy type on QoL. [ABSTRACT FROM AUTHOR]

Published
2019
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