‘Our battle for better healthcare is eternal’. Report from the gynocare conference in Sofia, Bulgaria (2nd - 3rd July 2023)

The European Network for Gynaecological Rare Cancer Research: from Concept to Cure (GYNOCARE COST Action CA18117), organized a two-day hybrid conference entitled: ‘Our battle for better healthcare is eternal’. This conference was held at the historic Rectorate at the University of Sofia in Sofia, Bulgaria. The aim of this conference was to highlight the deliverables achieved during the GYNOCARE COST Action especially through international co-operation, both in Europe and beyond. There were 28 invited talks by high-profile international speakers organized over 7 sessions, followed by a final management committee meeting. This was in fact the very final conference of the 4-year long GYNOCARE COST Action, which officially ends on the 11th September 2023.peer-reviewe

‘They are rare, but they are there’. Report from the gynocare training school in Sofia, Bulgaria (29th June - 1st July 2023)

The European Network for Gynaecological Rare Cancer Research: from Concept to Cure (GYNOCARE COST Action CA18117), organized a three-day hybrid training school entitled: ‘They are rare, but they are there’. This training school was held at the historic Rectorate at the University of Sofia in Sofia, Bulgaria. The aim of this training school was to highlight the different aspects of how the management of rare gynecological cancers (RGCs) can be improved through the interdisciplinarity present within the GYNOCARE consortium and collaborators. There were 35 invited talks by high-profile international speakers organized over 6 workshops.peer-reviewe

Electronic brachytherapy for gynecological cancers — a systematic review

Background: The purpose of this manuscript is to provide an in-depth literature review of the management of endometrial and cervical cancers with electronic brachytherapy. Materials and methods: An extensive literature search was performed and 9 articles were selected based on preset criteria. Results: The reviewed studies provided dosimetric and clinical results. Patient populations were diverse and prescribed doses varied. When treatment plans were compared to those using cobalt 60 (60Co) and iridium 192 (192Ir) sources researchers found lower or equivalent doses in organs at risk while the doses at the applicator surface were significantly higher for electronic brachytherapy. In the eligible studies, a total of 72 patients received treatment with AxxentXoft vaginal applicator, 29 were treated with the Intrabeam vaginal applicator, and 8 with AxxentXoft cervical applicator. Conclusions: All authors found that electronic brachytherapy was safe and well tolerated as higher mucosal doses did not present as adverse clinical effects. Electronic brachytherapy for gynecological cancers has the potential to achieve equivalent tumor control while minimizing bowel and urinary toxicity thus improving the quality of life. More clinical data is needed to stratify patients who would benefit the most

Comparative analysis of main clinical features in melanoma patients with and without sentinel lymph node biopsy

Introduction. Sentinel lymph node biopsy is fundamental in the treatment and prognosis of cutaneous malignant melanoma. This study aims to identify differences in baseline clinical characteristics and survival of patients with melanoma with and without a sentinel lymph node biopsy (SLNB) performed.  Material and methods. In 2018, a retrospective study of 151 patients with malignant melanoma (MM) was conducted. The patients were hospitalized at the Second Clinic of University Hospital — Pleven, from 2012 to 2017. The patients were divided into two groups: Group A included 58 (38.4%) patients with SLNB performed; Group B included 93 (61.6%) patients who did not undergo SLNB. A double-detection method was used while performing SLNB.  Results. The incidence of achromatic malignant melanoma is significantly higher in patients without SLNB (12 or 12.9%) than in patients with SLNB (2 or 3.4%) — c2 = 3.796, df = 1, p = 0.051. Of all 151 patients in the study, 46 died, representing 30.5% of patients with melanoma. The mortality rate was higher in the patients without SLNB (32.3% vs. 27.6% in Group A). However, the differences in the two groups are not statistically significant.  Conclusions. Patients with achromatic melanoma have significantly fewer sentinel lymph node (SLN) biopsies performed because of a late diagnosis. Most of our patients are diagnosed at a later stage when lymphatic metastases are already present, which leads to a significant increase in lymph node dissections performed. There is no significant difference in mortality and survival in the SLNB and non-SLNB groups

Cancer of the cervix in Bulgaria : epidemiology of a crisis

Eastern Europe continues to have the highest rates of cancer of the uterine cervix (CUC) and human papillomavirus (HPV) infection in Europe.Aim: The aim of this study was to investigate CUC trends in Bulgaria in the context of a lack of a population-based screening program and a demographic crisis.Methodology: This was a retrospective study of 7861 CUC patients who were registered in the Bulgarian National Cancer Registry (BNCR) between 2013 and 2020 and followed up with until March 2022. We used descriptive statistics and modeling to assess temporal trends in new CUC incidence rates and identify factors associated with survival.Results: Bulgaria’s population has decreased by 11.5% between 2011 and 2021. The CUC incidence rate decreased from 29.5/100,000 in 2013 to 23.2/100,000 in 2020 but remains very high. The proportion of patients diagnosed in earlier stages of CUC has decreased over time. Up to 19% of patients with CUC in Bulgaria are diagnosed between the age of 35 and 44 years. The median survival was 101.5 months, with some improvement in later years (adjusted HR = 0.83 for 2017–2020).Conclusions: In countries with well-established population-based screening, CUC is nowadays considered a rare disease. However, it is not considered rare in Bulgaria. Population-based screening starting at an earlier age is the fastest way to improve outcomes.peer-reviewe

The role of FBXW7 in gynecologic malignancies

The F-Box and WD Repeat Domain Containing 7 (FBXW7) protein has been shown to regulate cellular growth and act as a tumor suppressor. This protein, also known as FBW7, hCDC4, SEL10 or hAGO, is encoded by the gene FBXW7. It is a crucial component of the Skp1-Cullin1-F-box (SCF) complex, which is a ubiquitin ligase. This complex aids in the degradation of many oncoproteins, such as cyclin E, c-JUN, c-MYC, NOTCH, and MCL1, via the ubiquitin-proteasome system (UPS). The FBXW7 gene is commonly mutated or deleted in numerous types of cancer, including gynecologic cancers (GCs). Such FBXW7 mutations are linked to a poor prognosis due to increased treatment resistance. Hence, detection of the FBXW7 mutation may possibly be an appropriate diagnostic and prognostic biomarker that plays a central role in determining suitable individualized management. Recent studies also suggest that, under specific circumstances, FBXW7 may act as an oncogene. There is mounting evidence indicating that the aberrant expression of FBXW7 is involved in the development of GCs. The aim of this review is to give an update on the role of FBXW7 as a potential biomarker and also as a therapeutic target for novel treatments, particularly in the management of GCs.peer-reviewe

An overview of the role of long non-coding RNAs in human choriocarcinoma

Funding: The publication of this manuscript was funded by the European Cooperation in Science & Technology Program (EU COST)–COST Action CA18117: GYNOCARE- “European network for Gynaecological Rare Cancer research: From Concept to Cure”. R.D.F., S.S., A.F., S.A.O., J.J.O., M.P.W., J.B., M.S., P.O., A.Y., M.V.-S., B.E., A.G., and J.C.-A. are Action management committee members and/or form part of Working Groups 1–3, and J.C.-A. is the Chairperson of this Action.Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.publishersversionpublishe

Endometrial carcinoma in patients under 40 years of age : insights from the Bulgarian cancer registry

Objectives: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival.Material and methods: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification.Results: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%.Conclusions: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization.peer-reviewe

Epigenetic silencing of MLH1 as a prognostic factor for endometrial cancer recurrence

Introduction/Background Aberrant DNA methylation is a common phenomenon in different types of cancer, but its patterns, causes, and consequences are poorly defined. Promoter hypermethylation of the DNA mismatch repair (MLH1) has been implicated in prognosis of endometrial cancer (EC). Methodology Fifty women diagnosed with endometrioid-type endometrial adenocarcinoma from 2018–2021 at the Institute of Oncology of Moldova were included in this study. DNA was isolated from plasma, formalin-fixed, paraffin-embedded tumor. The methylation status of the MLH1 gene was determined using the Methylation specific Polymerase Chain Reaction (MS-PCR) method and specific primers for both unmethylated and methylated fragments. (figure 1). Results Clinical and pathological characteristics for the 50 endometrial cancer patients are summarized in table 1. The mean age of the cohort was 59,9 ± 0,64 years (range, 39–87), and most of the patients had early stage (Stage I or II), grade 2 tumors with less than 50% myometrial invasion. The mean tumor size was 4,2 cm and the mean depth of invasion 0,5cm. Myometrial lymphatic/vascular space and perineural invasion was present in nearly half the tumors and was much more common in stage II cases. Overall, 80% of the patients with EC had intact tumors, while 20% had hypermethylation of MLH1 (table 2). The presence of MLH1 epimutation was observed in 22.0% of EC patients in stage I and only in 2 patients in stage II. Conclusion Recent developments in the field of epigenetics, especially studies of DNA methylation, have provided valuable insights for understanding the role of epigenetic alterations in normal cellular processes and abnormal changes leading to endometrial carcinogenesis. Promoter hypermethylation of MLH1 displayed a direct correlation with increasing age, poor differentiation of tumor, presence of myometral and limphovascular invasion. These phenotypes may underlie the different developmental pathways that are known to occur in endometrial cancer.peer-reviewe

Endometrial carcinoma in patients under 40 years of age: insights from the bulgarian cancer registry

Objectives: We aimed to investigate the overall survival (OS) of young women with endometrial cancer (EC) in Bulgaria and the impact of histological type on survival. Material and methods: This is a population-wide retrospective study of patients with EC (≤ 40 years at diagnosis) registered at Bulgarian National Cancer Registry (BNCR) between 1993 and 2020. Patients were re-classified according to the 8th edition of the TNM classification. Results: In total, 30 597 patients were registered and histologically confirmed with malignant tumors of the uterine body. From that, 29 065 of them (95%) had ECs, and the rest had sarcomas. Around 1.64% of all malignant tumors of the uterine body are diagnosed in women under the age of 40. Most of them are diagnosed in the early stage. There was no significant difference in median OS for patients diagnosed before or after 2003. In recent years there was a slight improvement in survival and patients from the last cohort of this study had a 5-year survival rate of 92.5%. Patients with favorable pathology (T1, G1/2) had no lymph node involvement at the time of diagnosis and their 10-year survival rate was 94%. Conclusions: EC in young women is a rare disease. In most cases, patients are diagnosed in early stageT1, G1/2, N0 and their prognosis is excellent. However, the lack of improvement of OS of young patients with EC in the last three decades shows the need for treatment optimization