Epigenetic alterations, including aberrant DNA methylation, are now recognized as bone fide hallmarks of cancer, which can contribute to cancer initiation, progression, therapy responses and therapy resistance. Methylation of gene promoters can have a range of impacts on cancer risk, clinical stratification and therapeutic outcomes. We provide several important examples of genes, which can be silenced or activated by promoter methylation and highlight their clinical implications. These include the mismatch DNA repair genes MLH1 and MSH2, homologous recombination DNA repair genes BRCA1 and RAD51C, the TERT oncogene and genes within the P15/P16/RB1/E2F tumour suppressor axis. We also discuss how these methylation changes might occur in the first place – whether in the context of the CpG island methylator phenotype or constitutional DNA methylation. The choice of assay used to measure methylation can have a significant impact on interpretation of methylation states, and some examples where this can influence clinical decision-making are presented. Aberrant DNA methylation patterns in circulating tumour DNA (ctDNA) are also showing great promise in the context of non-invasive cancer detection and monitoring using liquid biopsies; however, caution must be taken in interpreting these results in cases where constitutional methylation may be present. Thus, this review aims to provide researchers and clinicians with a comprehensive summary of this broad, but important subject, illustrating the potentials and pitfalls of assessing aberrant DNA methylation in cancer.
4 November 2024 in International Journal of Gynecological Cancer
Findings from clinical trials have led to advancement of care for patients with gynecologic malignancies. However, restrictive inclusion of patients into trials has been widely criticized for inadequate representation of the real-world population. Ideally, patients enrolled in clinical trials should represent a broader population to enhance external validity and facilitate translation of outcomes across all relevant groups. Specifically, there has been a systematic lack of data for underrepresented groups, with many studies failing to report or differentiate study participants based on sociodemographic domains, such as race and ethnicity. As such, the impact of treatment in these underrepresented groups is poorly understood, and clinical outcomes according to various sociodemographic factors are infrequently assessed. Inclusion of diverse trial participants, with different racial and ethnic background, is essential for the understanding of factors that may impact clinical outcomes. Therefore, we conducted a multi-national meeting of clinical trial groups and industry with the goal of increasing equity, diversity, and inclusion in gynecologic cancer clinical trials and to address barriers to recruitment, participation, and harmonization of data collection and reporting. These Gynecologic Cancer Intergroup (GCIG) statements present recommendations and strategies for the gynecologic cancer research community to improve equity, diversity, and inclusion in gynecologic cancer clinical trials.
Pituitary apoplexy is caused by haemorrhage or infarction of the pituitary gland. Presenting signs and symptoms often include severe headache, visual disturbance, ophthalmoplegia, altered consciousness and impaired pituitary function. The management of pituitary apoplexy has very rarely been described during pregnancy and there is no existing data for further pregnancies of affected women. We present a case of a woman with a recurrent pituitary apoplexy due to haemorrhages in a pituitary adenoma in her third and fourth pregnancies. In both pregnancies, the pituitary apoplexy was managed conservatively, but due to therapy-resistant headaches, a preterm delivery was implemented.
Tying knots during suturing is one of the most challenging tasks in laparoscopic surgery. Therefore, measures aimed at ensuring both the ease and speed of knot tying not only benefit the surgeon but can also reduce operating time significantly. This study compared extracorporeal and intracorporeal knot tying techniques using a Szabo pelvic trainer model from the Gynaecological Endoscopic Surgical Education and Assessment program. The students tied intra- and extracorporeal knots using closed- and open-jaw knot pushers. Using an artificial tissue suturing pad in a certified Szabo pelvic trainer, students tied three knots using each technique according to block randomization. Task completion time, knot strength, knot-spread ability, and number of errors were recorded. The Wilcoxon test and mixed-effects models were used to analyze the results. After completing the exercises, participants answered a questionnaire concerning knot-tying techniques and their performance. University Hospital Basel, which provides tertiary-level clinical care. Fifty-seven medical students with no experience in laparoscopy voluntarily signed up for this study. Open and closed extracorporeal knot tying was significantly faster (p < 0.001, p < 0.001, respectively), more precise (p = 0.007, p = 0.003), and associated with reduced knot-spread ability (p < 0.001, p < 0.001) compared to intracorporeal knot tying. Open- and closed-jaw knot pushers were shown to be equal in terms of speed (p = 0.563), knot-spread ability (p = 0.49), and precision (p = 0.831). The study participants rated open (30 %) and closed (49 %) extracorporeal knot tying as more intuitive than intracorporeal (21 %) knot tying. Improved concentration was significantly correlated with tighter knots (p = 0.011). Students achieved significantly better results using extracorporeal knot-tying techniques than intracorporeal ones, including greater speed, tighter knots, and optimized precision. These results suggest that beginners in the field of laparoscopy should be encouraged to practice extracorporeal knot-tying techniques.
Background: Endocrine therapy is the standard-of-care maintenance treatment for estrogen receptor (ER)-positive breast cancers and is increasingly used in low-grade serous ovarian cancer. However, its therapeutic role in the early maintenance setting for ER-positive high-grade serous ovarian cancer (HGSC) remains undefined. Methods: A retrospective analysis was conducted on clinicopathological data from patients with newly diagnosed ER-positive HGSC following completion of adjuvant chemotherapy. Patients received maintenance therapy either with or without the aromatase inhibitor letrozole, in addition to standard maintenance care. ER expression levels and the administration of letrozole were analyzed, along with outcome measures for the entire cohort, with stratification based on residual disease status. Results: A total of 102 patients with newly diagnosed HGSC were included in the analysis, with 64 (62.7%) receiving letrozole and 38 (37.3%) not receiving letrozole. The median ER expression was 70%, with higher expression observed in the letrozole group compared to the no letrozole group (77.5% vs. 60%). No significant correlation was found between ER expression status and therapy response (p = 0.295 and p = 0.176, respectively). Letrozole therapy was well tolerated with no major adverse effects reported. In the overall cohort, maintenance letrozole therapy did not confer a significant improvement in progression-free survival (median 20.56 months vs. 29.34 months, p = 0.53) or overall survival (OS) (median 79.48 months vs. 46.85 months, p = 0.71) over a median follow-up duration of 23.5 months. However, among patients with no residual disease, maintenance letrozole therapy was associated with a statistically significant improvement in OS compared to those not receiving letrozole (median 114 months vs. 46.9 months, p = 0.006). Conclusions: Maintenance letrozole therapy appears to be a well-tolerated and potentially beneficial intervention in a subset of patients with ER-positive HGSC with no residual disease post-treatment. These findings highlight the need for further validation through prospective randomized trials to comprehensively assess the efficacy of endocrine therapy in this setting and its implications for patient quality of life.
Background Endocrine therapy is standard of care of maintenance treatment for estrogen receptor (ER) positive breast cancers and is increasingly used in low-grade serous ovarian cancer. However, its therapeutic role in the early maintenance setting for ER positive high-grade serous ovarian cancer (HGSC) remains undefined. Methods A retrospective analysis was conducted on clinicopathological data from patients with newly diagnosed ER positive HGSC following completion of adjuvant chemotherapy. Patients received maintenance therapy either with or without aromatase inhibitor letrozole, in addition to standard maintenance care. ER expression levels and the administration of letrozole were analyzed, along with outcome measures for the entire cohort, with stratification based on residual disease status. Results A total of 102 patients with newly diagnosed HGSC were included in the analysis, with 64 (62.7%) receiving letrozole and 38 (37.3%) not receiving letrozole. The median ER expression was 70%, with higher expression observed in the letrozole group compared to the no letrozole group (77.5% vs. 60%). No significant correlation was found between ER expression status and therapy response (P=0.295 and P=0.176, respectively). Letrozole therapy was well tolerated with no major adverse effects reported. In the overall cohort, maintenance letrozole therapy did not confer a significant improvement in progression-free survival (median 20.56 months vs. 29.34 months, P=0.53) or overall survival (OS) (median 79.48 months vs. 46.85 months, P=0.71) over a median follow-up duration of 23.5 months. However, among patients with no residual disease, maintenance letrozole therapy was associated with statistically significant improvement in OS compared to those not receiving letrozole (median 114 months vs. 46.9 months, P=0.006). Conclusions Maintenance letrozole therapy appears to be well tolerated and potentially beneficial intervention in a subset of patients with ER positive HGSC with no residual disease post-treatment. These findings highlight the need for further validation through prospective randomized trials to comprehensively assess the efficacy of endocrine therapy in this setting and its implications for patient quality of life.