Molecular testing of endometrial carcinoma in real-world clinical practice.

BACKGROUND: Molecular classification has brought significant changes in the management of endometrial cancer (EC). In this article, we aim to analyze our first experience with an implementation of molecular testing into daily clinical practice. MATERIALS AND METHODS: In all newly diagnosed EC, the status of mismatch repair (MMR) and p53 proteins has been evaluated immunohistochemically as a part of the routine histopathological examination since May 2021. In tumors that do not meet clinical criteria for a low risk and those with MMR deficiency or p53 mutation, the molecular genetic testing of the POLE gene is performed as well. Recommendations for adjuvant treatment or follow-up are subsequently made based on the risk of recurrence. Genetic counselling is proposed to all patients with MMR-deficient tumors or family history of cancer. RESULTS: A total of 85 patients with newly diagnosed EC between May 2021 and May 2022 were enrolled in the analysis. The median age was 66 years. The results of molecular testing were as follows: 22 (26%) MMR-deficient, 8 (9%) p53-mutated and none POLE-ultramutated of those 40 tumors with performed POLE sequencing. A total of 46 (51%) patient had a low risk, 2 (2%) intermediate, 14 (16%) high-intermediate and 20 (24%) patients had a high risk of recurrence. Advanced or metastatic diseases were diagnosed in 6 (7%) patients. The median time between surgery and multidisciplinary tumor board decision was 21 days (8-36). A total of 76 (90%) patients underwent the whole treatment plan according to the recurrence risk. At the time of analysis, the results of genetic testing were available in 18 patients and revealed 4 (22%) carriers of a pathogenic variant in any of the genes associated with Lynch syndrome. CONCLUSION: Molecular testing combining immunohistochemical analyses of MMR and p53 proteins in all newly diagnosed EC patients with sequencing analysis of POLE in those with non-low-risk disease is feasible and does not prolong the time needed for treatment decision.

Surgical solution of the extensive post-radiation defect developped 33 years after radiotherapy for breast carcinoma case report.

INTRODUCTION: Damage of the skin and its underlying structures is a common side effect of radiotherapy. These conditions limit further treatment and dealing with these complications is a routine practice of clinical oncologist. The majority of the complications are immediate, with a perspective of healing ad integrum within a few weeks. Less frequently, but sometimes with severe manifestations, chronic toxicity occurs belatedly after months, or even many years after irradiation, in form of post-radiation ulcer, for instance with potential of secondary malignant transformation. Regarding surgery, it might be one of the most challenging chronic wounds to treat. In extreme cases, extensive resection of the entire affected area is needed, inevitably ending with demanding reconstruction of the resulting defect. CASE REPORT: This case report presents a female patient with rapidly progressive post-radiation chest wall defect 33 years after the irradiation, when relatively insignificant skin injury occured. Prior to this sudden deterioration, only long-term, non-progressive changes, without a cutaneous defect, were described during the dispensarisation. After a protracted outpatient treatment with unsatisfactory results, when the patient repeatedly refused mastectomy, the condition inevitably led to the complex surgical procedure with necessary cooperation of breast, plastic and thoracic surgeons. CONCLUSION: Although changes of the similar severity rarely occur even after many years following the treatment, we havent found such a dramatic change of the patients condition three decades after the therapy with urgency of this type of complex,  surgical intervention in current literature.

[Triple-negative breast cancer: analysis of patients diagnosed and/or treated at the Masaryk Memorial Cancer Institute between 2004 and 2009]. / Triple-negativní karcinom prsu: analýza souboru pacientek diagnostikovaných a/nebo lécených v Masarykove onkologickém ústavu v letech 2004 az 2009.

BACKGROUND: Triple-negative breast cancer (TNBC) represents a heterogeneous group of breast cancers that do not express ER-α, PgR and Her-2 receptors. Generally, these tumors are aggressive and more common in younger women, in which an association of TNBC with mutations in the BRCA1 gene was documented. The aim of our study was to create a representative group of patients with TNBC, which could be analyzed and the data gathered to build basic epidemiological, molecular and clinical characteristics of Czech patients with TNBC. PATIENTS AND METHODS: We performed basic clinical-pathologic correlations in a group of 335 patients diagnosed and/or treated for TNBC at the Masaryk Memorial Cancer Institute between 2004 and 2009. We also performed immunohistochemical examination of expression of cytokeratin 5/6, cytokeratin 14 and EGFR to identify the basal-like subset of TNBC. RESULTS: The median age of patients with TNBC was 56 years, range 25-88 years. A total of 9.25% of TNBC cases were diagnosed in patients under the age of 34, and another 15.22% of cases were in the age group of 35 to 44 years. 'Basal-like' carcinomas accounted for 75% of TNBC. We confirmed the aggressive nature of this disease: in the follow-up period we observed a relapse in 25% of patients: 55% of deaths due to disease progression occured within 2 years after diagnosis of the disease. Treatment strategies include chemotherapy, in most cases (88.4%). Chemotherapy was mostly based on regimens with anthracyclines or in combination with taxanes. The most important negative prognostic factors in relation to OS (disease specific OS) were: higher clinical stage (p < 0.0001), pN - positive status (p < 0.0001), high proliferative activity (as measured by Ki-67, cut-off 50%, HR = 0.4740, p = 0.0411) and positive expression of CK5/6 (HR = 0.4274, p = 0.0338). In relation to DFS, the negative prognostic significance was found for these factors: higher clinical stage (p < 0.0001), pN positive status (p < 0.0001), high proliferative activity (Ki-67, cut-off 50%, HR = 0.04993, p = 0.0240). DFS was longer in patients with a higher number of applied cycles of anthracycline-based chemotherapy (> 4 cycles, HR = 1.7273, p = 0.0467). CONCLUSION: TNBC is an aggressive form of breast cancer, which may occur in patients of all ages, but more frequently in younger patients. Only early detection of disease and intensive treatment gives a high chance of cure. Unfortunately, no reliable predictive factors have been identified so far. Better therapeutic results can be expected from targeted therapy.

[Treatment of non small cell lung cancer]. / Lécebné postupy u nemalobunecného karcinomu plic.

According to the recent data lung cancer in Czech republic is the most common malignancy in men (incidence 93/100 000) and is the leading cause of cancer death in men (mortality 90/100 000). In women is the incidence of lung cancer 30/100 000. Non-small-cell lung cancer (NSCLC) accounts for 70% to 75% of all lung cancers, while small-cell lung cancer (SCLC) accounts for 25% to 30% of cases. These two types of lung cance have a different biological characteristics which leads to a different approach in the treatment of NSCLC and SCLC. The treatment of NSCLC is based on clinical stage of disease and different treatment modalities alone or in combination are used: surgery, radiotherapy, chemotherapy and recently a novel treatment strategy--targeted therapy with biologic agents.

Longterm treatment results of childhood medulloblastoma by craniospinal irradiation in supine position.

Medulloblastoma, a primitive neuroectodermal tumor growing in cerebellum, is one of the most sensitive to radiation therapy childhood brain tumors. The radiotherapy is an essential method of treatment for these tumours, but the surgery is the primary treatment of choice in medulloblastoma. I this study between January 1997 and March 2005 were post-operative irradiated a total number of 33 pediatric patients aged under 15 years (median age 8.7 years) with medulloblastoma. All tumors were histologically proved and were localizated infratentorially in the posterior fossa. All of the patients were irradiated with a dose of 24-36 Gy to the whole craniospinal axis and boost with conformal therapy restricted to the tumor bed to the total dose of 50-54 Gy (30-36 Gy "high risk", 24-30 Gy "standard risk" group). Chemotherapy received 26 patients (78%). Patients with craniospinal irradiation were placed in supine position and fixed by a vacuum-form body immobilizer and head mask. Irradiation was performed using standard fractionation (5 fractions per week) with a single dose of 1.5-1.8 Gy for craniospinal axis by photon beam (6 MV) of the linear accelerator. The median overall survival for the whole group was 55.3 months. The median of disease-free survival was 20.6 months, 8 patients (24%) died. In our study the statistical difference in survival rate between standard and high-risk patients with medulloblastoma was not shown. No relationship was found between survival and age, sex or tumor size. Endocrine deficits occurred in 45% (8 patients of the group were hypothyroid, 6 patients needed growth hormone replacement therapy, 1 patient had early puberty). This results (results of overall and disease-free survival) and side-effects of technique of craniospinal axis irradiation in supine position are comparable with results of technique in prone position. Further evaluation of the effectiveness of our therapy is not feasible due to the small number of patients.