Lars Fokdal

Background: To better understand the complexity of sexual dysfunction, we aim to construct multi-factorial explanatory models of sexual dysfunction using data from participants enrolled in the Danish cross-sectional Study of latE effects for those liviNg through cErvical CAncer (SENECA). Methods: In a nationwide survey, patient-reported outcomes (PRO) were collected from 2002 cervical cancer survivors treated with surgery and/or radio(chemo)therapy between 2005–2020 and a reference cohort consisting of 7853 women without a history of cancer. PROs in the EORTC C30/CX24 questionnaires were analysed. Bayesian Network models were developed for sexual activity and dyspareunia in reference and cancer survivor cohorts, resulting in four explanatory models. The reference cohort served as a structural prior for the cancer models. Sexual activity models included participants with complete data (6706 reference, 1694 cancer), while dyspareunia models included those reporting sexual activity in the past four weeks (4521 reference, 996 cancer). Results: Respondents were stratified by treatment received: (1) reference group (n = 7853), (2) surgery alone (n = 1285), (3) radio(chemo)therapy (RCT) with/without prior surgery (n = 951). Sexual inactivity was reported by 28%, 29% and 49% of reference, surgery and RCT groups respectively, and dyspareunia by 23%, 39% and 54%. Sexual activity was associated with age, treatment modality and social functioning. Social functioning was associated with cognitive and role functioning, global QoL, and financial difficulties, all of which were associated strongly with fatigue. Dyspareunia was associated with vaginal functioning and soreness. The strong associations observed in the cancer survivor cohort between fatigue and functional outcomes/QoL/sexual activity were absent in the reference cohort. Conclusions: Sexual inactivity and dyspareunia were more common in cervical cancer patients, particularly in those treated with RCT compared with the reference cohort. Differences in explanatory factors between cancer and reference cohorts highlight the need for cancer-specific approaches to sexual rehabilitation.

Background/Objectives: Platinum resistant ovarian cancer represents a treatment challenge due to lack of efficient treatments and the absence of prognostic biomarkers. The circulating tumor DNA (ctDNA), methylated homebox A9 (meth-HOXA9), has been suggested as a biomarker for ovarian cancer, and might have a clinical impact in terms of predicting progression and supporting clinical decision making. Hence, this study investigated the prognostic value of meth-HOXA9 in platinum resistant recurrent ovarian cancer (PR-ROC) treated with bevacizumab and tocotrienol. Methods: Twenty patients with platin-resistant recurrent ovarian cancer were prospectively enrolled in this non-randomized phase II study. The treatment consisted of bevacizumab (Avastin) 10 mg/kg intravenously every three weeks and tocotrienol (Traptol) capsules 300 mg orally three times daily as a continuous treatment. The Level of meth-HOXA9 was measured at baseline and every three weeks. Results: The overall survival (OS) in the cohort was 7.5 months (95% CI 3.0–10.0), and the progression free survival was 4 months (95% CI 1.4–6.6). Comparing meth-HOXA9 ctDNA levels at baseline, there was no statistic significant difference in OS (p = 0.23). Conclusions: Treatment was well tolerated in this heavily pretreated cohort of PR-ROC patients with expected poor prognostic outcomes, with a few individuals showing extraordinary response in terms of progression free survival. The study was not powered to reproduce evidence of potential of meth-HOXA9 as a prognostic biomarker in PR-ROC.

Background: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. Methods: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. Results: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1–2 LVSI-negative disease. For 74–84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. Conclusions: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1–2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.

Methotrexate (MTX) is frequently used as first-line treatment for low-risk gestational trophoblastic neoplasia (GTN). Intravenous and intramuscular (im) routes of administration are the most common methods, although oral administration is used by some Scandinavian centers. The primary aim of this study was to assess the impact of form of administration (im/oral) on resistance to methotrexate (MTX-R) treatment in low-risk GTN. Secondary aims were time to hCG normalization, rates of toxicity-induced treatment switch, and rates of complete remission and recurrence. In total, 170 women treated at Karolinska University Hospital in Sweden and Aarhus University Hospital in Denmark between 1994 and 2018 were included, of whom 107 were given im and 63 oral MTX. MTX-R developed in 35% and 54% in the im and oral groups, respectively (p = 0.01). There was no difference in days to hCG normalization (42 vs. 41 days, p = 0.50) for MTX-sensitive women. Toxicity-induced treatment switch was only seen in the im group. Complete remission was obtained in 99.1% and 100% (p = 0.44), and recurrence rate within one year was 2.8% and 1.6% (p = 0.29). The form of administration of MTX had a significant impact on development of MTX-R and treatment-associated toxicity, but does not affect rates of complete remission, recurrence or survival.