Lukas Rob

Pretreatment computed tomography L1 attenuation values: Easy reaching predicting factor for radiation-related bone insufficiency fractures in females treated for advanced cervical cancer (prospective study)

Background: Radiotherapy (RT) brings a broad spectrum of side effects that could affect patient well-being. Pelvic insufficiency fractures (PIF) are one of them. Objectives: The aim of our study was to identify easily detectable risk factors for radiation-related PIF. Design: Prospective, single-center study. Methods: We included 104 patients aged 52.9 ± 13.8 years following radical RT for advanced cervical cancer. Patients underwent a pretreatment computed tomography (CT) imaging and a minimally 1-year follow-up by CT or magnetic resonance imaging. We evaluated the association between pretreatment CT attenuation values of L1, their deviation from normative values, age, body mass index, total received radiation dose, smoking habits, and radiation-related bone side effects. Results: In 28 (26.9%) patients PIF were found and first detected at a mean of 16 ± 7 months after RT. Patients with PIF were significantly older; 62.5 ± 10.2 versus 49.4 ± 12.6 years, p  > 0.001; their pretreatment CT L1 attenuation values were significantly lower; 117.5 ± 46.9 HU versus 165.9 ± 44.8 HU, p  < 0.001, as well as more negative deviation from normative values. Age and L1 attenuation values were strongly correlated, p  < 0.001, precluding separation of their independent effects on PIF occurrence. According to logistic regression modeling, a 50-year-old woman had an estimated 16.3% probability of PIF (95% CI [8.6%; 25.9%]); the associated odds ratio increased by approximately 182% [72%; 357%] per 10-year increase in age. Thus, the estimated probability of PIF increased to 34.1% for a 60-year-old and 58.0% for a 70-year-old woman. The pretreatment CT attenuation values of 100 Hounsfield units (HU) were associated with a 51.1% probability of PIF (95% CI [36.2%; 66.5%]), and the probability decreased at higher attenuation values (odds ratio 0.766 [0.663; 0.865] per 10-HU increment). No other variables showed significant associations. Conclusion: Increasing age and lower pretreatment CT L1 attenuation values are strong predictors for radiation-related PIF, reflecting osteoporosis status.

Whole-exome sequencing of epithelial ovarian carcinomas differing in resistance to platinum therapy

Epithelial ovarian carcinoma (EOC) is highly fatal because of the risk of resistance to therapy and recurrence. We performed whole-exome sequencing of blood and tumor tissue pairs of 50 patients with surgically resected EOC. Compared with sensitive patients, platinum-resistant patients had a significantly higher somatic mutational rate inTP53and lower in several genes from the Hippo pathway. We confirmed the pivotal role of somatic mutations in homologous recombination repair genes in platinum sensitivity and favorable prognosis of EOC patients. Implementing the germline homologous recombination repair profile significantly improved the prediction. In addition, distinct mutational signatures, for example, SBS6, and overall mutational load, somatic mutations inPABPC1,PABPC3, andTFAMco-segregated with the resistance status, high-grade serous carcinoma subtype, or overall survival of patients. We generated germline and somatic genetic landscapes of prognostically different subgroups of EOC patients for further follow-up studies focused on utilizing the observed associations in precision oncology.

Malignant transformation of extragenital endometriosis

Endometriosis is a chronic disease characterised by the presence of endometrial tissue outside the uterine cavity, affecting 5–15% of women, especially those of reproductive age. The disease may manifest itself as dysmenorrhoea, dyspareunia, sterility and chronic pelvic pain, among other symptoms. Although it is not malignant, it shares some characteristics with cancer and can lead to epithelial ovarian carcinoma. The risk of malignant transformation of endometriosis is estimated at 1% in premenopausal women and 1–2.5% in postmenopausal women. Our case report describes a 46-year-old female patient with long-standing abdominal pain and a history of surgically confirmed endometriosis. Imaging revealed a cystic mass in the left mesogastrium, which was subsequently surgically removed. Histological examination confirmed the presence of a low-grade endometrioid carcinoma arising from an extragenital endometriosis lesion. Following surgical treatment, the patient underwent adjuvant chemotherapy, after which she was in complete remission. The diagnosis of malignant transformation of endometriosis is complex, requiring a combination of thorough clinical examination, imaging, and histopathological verification. Therapy involves radical surgery and possibly adjuvant chemotherapy, similar to ovarian carcinomas. Despite advances in treatment and research, endometriosis remains a complex disease with unclear aetiology, heterogeneous clinical presentation, and risk of malignant transformation. Key words: endometriosis– malignant transformation – extragenital lesion – diagnosis – treatment

New staging of endometrial carcinoma – FIGO 2023

Aim: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer. Methods and results: The new FIGO 2023 endometrial cancer staging system provides key updates for the diagnosis and treatment of endometrial cancer. An important step in diagnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies. The new staging system, based on the recommendations of the international societies ESGO, ESTRO and ESP, incorporates not only the description of the pathological and anatomical extent of the disease, but also the histopathological characteristics of the tumour, including the histological type and the presence of lymphovascular space invasion. In addition, the staging system uses molecular testing to classify endometrial cancers into four prognostic groups: POLEmut, MMRd, NSMP and p53abn. Each group has its own specific characteristics and prognosis. The most significant changes have occurred in stages I and II, in which the sub-staging better reflects the biological behaviour of the tumour. This update increases the accuracy of prognosis and improves individualized treatment options for patients with endometrial cancer. Conclusion: The updated FIGO staging of endometrial cancer for 2023 incorporates different histologic types, tumour features, and molecular classifications to better reflect the current improved understanding of the complex nature of several endometrial cancer types and their underlying bio logic behaviour. The aim of the new endometrial cancer staging system is to better define stages with similar prognosis, allowing for more precise indication of individualised adjuvant radiation or systemic treatment, including the use of immunotherapy. Key words: endometrial cancer – FIGO – staging – molecular classification – update

Preoperative and postoperative staging in endometrial cancer – a prospective study

Objective: The aim of this study was to determine how often changes the stage of the tumour in definitive histology against preoperative clinical stage in patient cohort with diagnosed endometrial cancer. Methods: We evaluated prospectively a cohort of 166 patients with endometrial cancer. They all underwent abdominal hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node biopsy. Patients with high-risk tumours also pelvic lymfadenectomy. We collected data of preoperative diagnostic biopsy and postoperative definitive histology. The data were statistically processed. Results: Detection of sentinel lymph node was successful in 71.1%, bilateral successful detection was in 40.6%. Discrepancy of tumour grade between preoperative biopsy and definitive histology was generally 31.4%. Upgrading of the tumour was in 22 (14.4%) cases, downgrading in 26 (17%) cases. Upgrade from low-risk to high-risk group of tumours was noticed in eight cases. Histopathological tumour type changed in 6.6%, 4.6% moved to histopathologic high-risk group. The tumour stage changed in definite histology in 57.3%, in 19.2% of cases moved from stage low/intermediate-risk group to intermediate-high/high-risk disease group. Conclusion: Correct assessment of preoperative clinical stage and histological grade of endometrial cancer is burdened with a high inaccuracy rate. A lot of cases is up-staged after surgical staging and moved to intermediate-high/high-risk disease group. Results confirm the importance of oncogynaecologic centre II. evaluation of histopathology findings from diagnostic biopsies made in referring hospitals. Sentinel lymph node biopsy should be performed even in clinically low/intermediate-risk disease group. Key words: endometrial cancer – tumour stage – tumour grade – sentinel lymph node detection

Molecular Classification in Relation to Prevention of Endometrial Cancer Recurrence and Lifestyle Factors

Endometrial cancer (EC) is one of the most prevalent cancers in women worldwide with a significantly increasing incidence, especially in developed countries. One of the reasons for the increase in the incidence of this disease is the rising incidence of obesity as the biggest risk factor for the development of this disease. Other important risk factors are hypertension, diabetes mellitus and the general ageing of the population. These risk factors are not only associated with a higher risk of developing the disease, but also, for example, with post-operative complications affecting the quality of life of patients after surgery. The molecular classification of endometrial cancer, which has been introduced into clinical practice in recent years, is currently helping physicians to make treatment decisions for individual patients and predict prognosis. In this project, we would like to focus on the relationship of this molecular classification with genomic mutational signatures detected by whole-exome sequencing and their association with lifestyle risk factors for endometrial cancer (obesity - BMI, hypertension, diabetes mellitus), including the extent of staging lymphadenectomy. Identification and detailed analysis of dominant mutational profiles associated with a specific molecular subtype of EC and their influence on the presence of lifestyle risk factors may have a major impact on both disease development and prevention of disease recurrence. The possible relationship of the mutational profile with the extent of staging lymphadenectomy may help in deciding the extent of this surgical procedure, which subsequently affects the quality of life of patients, especially in patients with high BMI. Given the widespread prevalence of lifestyle risk factors in the developed world, a detailed understanding of the relationship between the genetic profile, its alterations and the prevalence of these risk factors, with potentially major implications for treatment success, is crutial.