ObjectiveRisk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c... Show moreObjectiveRisk-reducing salpingo-oophorectomy (RRSO) is advised before 40-45 years of age for BRCA1/2 mutation carriers. This study describes the effect of RRSO on lipid determinants, hemoglobin A1c (HbA1c) and C-reactive protein (CRP).MethodsA total of 142 women with increased risk of ovarian cancer were included, 92 premenopausal and 50 postmenopausal. Serum levels of low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol and total cholesterol, triglycerides, HbA1c and CRP were determined at three points in time: before (T0) and 6 weeks (T1) and 7 months (T2) following RRSO. The Hot Flush Rating Scale was administered at the same time points.ResultsIn premenopausal women, levels of HDL-cholesterol, the cholesterol ratio and HBA1c increased significantly over time, although still staying within the reference range. In this group, hot flushes increased over time (p < 0.001). In postmenopausal women, no significant changes were observed following RRSO. At T2, serum LDL-cholesterol, triglycerides, HbA1c and CRP were significantly lower in premenopausal women compared to postmenopausal women, whereas HDL was increased.ConclusionsSeven months after RRSO, the lipid profile in premenopausal women had changed, although still staying within the reference range. For postmenopausal women, we did not observe any significant changes. Our results do not suggest a worsening of cardiovascular risk within 7 months of RRSO. Show less
Winden, L.J. van; Vermeulen, R.F.M.; Noort, V. van den; Gaarenstroom, K.N.; Kenter, G.G.; Brood-van Zanten, M.M.A.; ... ; Rossum, H.H. van 2022
Context: Risk-reducing salpingo-oophorectomy (RRSO) is performed in BRCA1 or 2 mutant carriers to minimize ovarian cancer risk. Although studies have been performed investigating sex steroid levels... Show moreContext: Risk-reducing salpingo-oophorectomy (RRSO) is performed in BRCA1 or 2 mutant carriers to minimize ovarian cancer risk. Although studies have been performed investigating sex steroid levels, menopausal complaints, and sexual functioning in relation to RRSO, their exact relationship remains unknown. Objectives: To investigate the impact of RRSO on serum sex steroid levels and their association with menopausal complaints and sexual functioning. Methods: This prospective observational cohort study included 57 premenopausal and 37 postmenopausal women at risk of ovarian cancer and opting for RRSO. Data collection involved validated questionnaires on sexual functioning and menopausal complaints.Testosterone, androstenedione, estradiol, and estrone levels in serum determined by liquid chromatography-tandem mass spectrometry were obtained 1 day before, 6 weeks, and 7 months after RRSO. Results: In premenopausal women, all 4 steroids were decreased both 6 weeks (P < 0.01) and 7 months (P < 0.01) after RRSO. Furthermore, in these women, decreases in estrogens were associated with a decrease in sexual functioning 7 months after RRSO (P < 0.05). In postmenopausal women, only testosterone was decreased 6 weeks and 7 months (P < 0.05) after RRSO, which was associated with an increase in menopausal complaints at 7 months post-RRSO (P < 0.05). Conclusion: Our results suggest that in premenopausal women, decreases in estrogens are related to a decrease in sexual functioning and that in postmenopausal women, testosterone is decreased after RRSO, which indicates that postmenopausal ovaries maintain some testosterone production. Furthermore, in postmenopausal women, a large decrease of testosterone was associated with more menopausal complaints, indicating that future studies investigating testosterone supplementation are warranted. Show less
Melief, C.J.M.; Welters, M.J.P.; Vergote, I.; Kroep, J.R.; Kenter, G.G.; Ottevanger, P.B.; ... ; Burg, S.H. van der 2020
Therapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16... Show moreTherapeutic cancer vaccines have effectively induced durable regressions of premalignant oncogenic human papilloma virus type 16 (HPV16)-induced anogenital lesions. However, the treatment of HPV16-induced cancers requires appropriate countermeasures to overcome cancer-induced immune suppression. We previously showed that standard-of-care carboplatin/paclitaxel chemotherapy can reduce abnormally high numbers of immunosuppressive myeloid cells in patients, allowing the development of much stronger therapeutic HPV16 vaccine (ISA101)-induced tumor immunity. We now show the clinical effects of ISA101 vaccination during chemotherapy in 77 patients with advanced, recurrent, or metastatic cervical cancer in a dose assessment study of ISA101. Tumor regressions were observed in 43% of 72 evaluable patients. The depletion of myeloid suppressive cells by carboplatin/paclitaxel was associated with detection of low frequency of spontaneous HPV16-specific immunity in 21 of 62 tested patients. Patients mounted type 1 T cell responses to the vaccine across all doses. The group of patients with higher than median vaccine-induced immune responses lived longer, with a flat tail on the survival curve. This demonstrates that chemoimmunotherapy can be exploited to the benefit of patients with advanced cancer based on a defined mode of action. Show less
Purpose: To determine the accuracy of MRI in detecting craniocaudal tumour extension, compared to histopathology, of the hysterectomy specimen in patients with early-stage uterine cervical cancer.... Show morePurpose: To determine the accuracy of MRI in detecting craniocaudal tumour extension, compared to histopathology, of the hysterectomy specimen in patients with early-stage uterine cervical cancer. Three complementary methods were investigated.Materials and methods: Thirty-four patients with early-stage cervical cancer had pre-operative MRI, followed by radical hysterectomy or trachelectomy. 1) craniocaudal tumour extension was measured on MRI by two radiologists and compared to microscopy by a pathologist, 2) to compensate for changes in uterine shape between pre-operative MRI and the surgical specimen, craniocaudal tumour extensions were directly compared and appreciated as being a part of a 3-dimensional tumour by a radiation oncologist and resident, and 3) tumour size on MRI was compared macroscopically after digital non-rigid registration of the uterus, uterine cavity and tumour of both modalities.Results: The craniocaudal tumour extension measured on histopathology minus MRI gives: 1) on average +3 mm difference when measured by a radiologist compared to the microscopic extension (range -13 to +15 mm), 2) -0.2 mm (range -11 to +6.0 mm) when evaluated on MRI by a radiation oncologist compared to the macroscopic tumour; 3) after non-rigid organ registration, a margin of 10 mm around the tumour on MRI would be needed to cover 95% of the tumour in 90% of the patients.Conclusions: Results indicate that microscopic tumour extension towards the uterine fundus is within a margin of 10 mm around the visible tumour on MRI. The major source of measurement uncertainty is post-surgical change of organ shape and form. (C) 2019 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology. Show less
Conclusions: This new study confirms that clinical efficacy of ISA101 vaccination is related to the strength of vaccine-induced HPV16-specific T-cell immunity and is an effective therapy for HPV16... Show moreConclusions: This new study confirms that clinical efficacy of ISA101 vaccination is related to the strength of vaccine-induced HPV16-specific T-cell immunity and is an effective therapy for HPV16-induced high-grade VIN/VaIN. (C) 2016 AACR. Show less
