Adjuvant accelerated partial-breast irradiation of early-stage breast cancer using stereotactic approach - methodology, technical challenges and early results of prospective randomized trial.

BACKGROUND: The adjuvant radiotherapy (RT) of the early-stage breast cancer patients as local treatment aims to eliminate potential microscopic residual disease in the surgery bed or satellites in its neighborhood. Based on published studies, accelerated partial breast irradiation (APBI) is recommended for strictly selected patients. The aim of this single-institution prospective randomized study was to compare the targeted APBI delivered by stereotactic approach with the currently more commonly used accelerated whole breast irradiation with the boost to the tumor bed in terms of feasibility, safety, tolerance, and cosmetic effects. MATERIALS AND METHODS: Early-stage breast cancer patients after partial mastectomy were screened for eligibility. The inclusion criteria were age > 50 years, non-lobular carcinoma histology, size 2cm, negative margins 2mm, L0, ER-positive, BRCA negative. Enrolled patients were equally randomized into two arms according to radiotherapeutic regiment - external APBI (5× 6 Gy) and accelerated whole breast irradiation with the boost (15× 2,67 Gy + 5× 2 Gy). These preliminary results of the ongoing study evaluated the first 57 from 84 planned patients. RESULTS: The median age was 65 years. The tumors were of grade 1 in 60 % of patients, the median size of 9mm and 70 % were classified as invasive ductal carcinoma. Statistical significant differences between the groups in baseline characteristics were not observed. A total of 29 patients was enrolled in the APBI group by the end of 2020. All enrolled patients were evaluated one month after RT. A total of 40 (70,2 %) a 33 (58 %) had examinations 3 and 6 months after RT, respectively. Toxicity evaluation showed statistically significantly fewer acute adverse events in the APBI group in terms of skin erythema, desquamation, skin tenderness, dryness, edema, pigmentation, breast pain and fatigue. Late toxicity evaluated in 3 and 6 months after RT was significantly higher in the control group. The cosmetic effect (independently evaluated by a physician, nurse and patient) was more favorable to the APBI group. CONCLUSION: The technique using the principles of targeted radiotherapy turned out to be a less toxic and easier feasible approach for adjuvant radiation of early-stage breast cancer patients. Consequently, the presented study increases the level of evidence for RT-indicated patients to the establishment of external APBI into daily clinical practice.

Meigs syndrome.

BACKGROUND: Meigs syndrome is defined by the presence of a benign ovarian tumor, ascites, and pleural effusion (predominantly on the right side). A characteristic sign of Meigs syndrome is the complete disappearance of exudate after surgical resection of the ovarian tumor. CASE REPORT: We present a case report of a 58-year-old patient admitted for an advanced ovarian tumor with pleural effusion, ascites, and tumor marker elevation typical for ovarian cancer. Cytological examination of ascites and pleural effusion was repeatedly negative for malignancy. Histopathological examination of the bio-psied tissue was concluded as low-grade mesenchymal neoplasia. The second opinion of histopathological examination was concluded as low grade fibroblastic pelvic tumor without the possibility of exact specification. Dia-gnoses of desmoid fibromatosis and low-grade fibromyxiod sarcoma (less likely) were considered. Surgical resection was indicated, and a large tumor with numerous adhesions to the uterus, bladder, and thin loops with a noticeably thickened peritoneum were perioperatively described. Histologically, left ovarian fibroma with productive peritonitis and sanguine-induced ascites was dia-gnosed. Due to the clinical findings and the result of the histopathological examination, the case was classified as Meigs syndrome. Two months after the surgery, the ascites and pleural effusion disappeared, and the tumor marker levels normalized. CONCLUSION: The present case report documents that it is always necessary to consider diseases other than those most likely at the outset, as the treatment algorithm and prognosis of these rare diseases may differ significantly.

Pagets disease of the breast - observational retrospective study of the past 20 years.

INTRODUCTION: Pagets disease of the breast (PD) is a rare type of carcinoma that affects the skin of the nipple-areolar complex. Unresolved issues exist regarding its diagnosis and therapy. The aim of the study was to gather data on how the therapy of the disease is approached in clinical practice, and to formulate current diagnostic and therapeutic recommendations. METHODS: Retrospective evaluation of data from medical records of patients with PD who underwent surgery at our department between 2001 and 2020. The data was evaluated using basic statistical methods. RESULTS: Sixty four female patients with the mean age of 62.5 years. In 58 women, PD was confirmed before surgery, with the median of 20 weeks from initial symptoms to diagnosis. Forty seven of the patients were operated for presumed isolated PD; in 38 cases, histopathological evaluation of the specimen revealed an associated malignancy in the mammary gland. Primary breast-conserving surgery (BCS) was performed in 46 patients; surgical revision was indicated in 17 cases. In 6 patients with PD associated with non-invasive breast cancer treated by BCS without radiotherapy (RT), a local recurrence appeared in 3 cases, which is significantly more compared to the group of patients undergoing total mastectomies (p=0.032). No local recurrence appeared in 9 cases of isolated PD treated by BCS, including 6 patients without RT. The tumors associated with PD were mostly ER-negative (44/57) and HER2-positive (22/25). CONCLUSION: In cases where PD is suspected, careful clinical examination and the use of available diagnostic imaging techniques including MRI are appropriate. BCS without RT is not an adequate oncological therapy where an associated malignancy of the breast is found.

Uncommon EGFR Mutations in Non-Small Cell Lung Cancer and Their Impact on the Treatment.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations play an important role in the pathogenesis of non-small cell lung cancer. Because these alterations are so-called targetable mutations, their identification is important in daily clinical practice. The diagnostic standard of EGFR mutations is currently based on polymerase chain reaction methods, particularly the quantitative real-time polymerase chain reaction. In recent years, new generation sequencing has become increasingly important. In patients with EGFR mutations, a significant improvement in therapeutic outcomes was achieved with the administration of targeted therapy using tyrosine kinase inhibitors. EGFR is composed of four domains: extracellular with a ligand binding site, a transmembrane domain, a cytoplasmic tyrosine kinase catalytic domain, and a C-terminal domain. The key structures of the tyrosine kinase domain responsible for signal activation and transmission are encoded within exons 18-21 on chromosome 7. EGFR mutations are highly heterogeneous. About 90% of EGFR mutations are deletions of exon 19 and point mutation L858R in exon 21. These are referred to as classic mutations. Approximately 10% of the total number of EGFR mutations is attributable to less frequent alterations in the EGFR gene. Due to the low incidence of non-small cell lung cancer with less frequent EGFR mutations, information on their predictive significance is still incomplete. Most of the data for the treatment of cases with uncommon mutations were gathered from retrospective analyses and evaluations of small cohorts. PURPOSE: The aim of this review is to summarise the current options for diagnosing and treating non-small cell lung cancer patients with uncommon EGFR mutations. This work was supported by the MEYS - NPS I - LO1413 and MH CR - DRO (MMCI, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 2. 6. 2019 Accepted: 26. 8. 2019.

[Pregnancy after Treatment of Breast Cancer]. / Tehotenství po lécbe karcinomu prsu.

Thanks to improvement in cancer patients treatment results, growing attention has been paid to fertility issues. Physicians should discuss infertility risk and the possibilities of fertility preservation with all patients in reproductive age as soon as possible. Pregnancy in cancer survivors after adequate treatment should not be discouraged, including patients with endocrine-sensitive breast cancer. Embryo and oocyte cryopreservation are standard strategies for fertility cryopreservation. Several randomized clinical trials have addressed the role of LHRHa (luteinizing hormone-releasing hormone analogs) as a way of fertility preservation with conflicting results. A meta-analysis of clinical trials, including also the largest trials POEMS and PROMISE, showed higher odds of achieving pregnancy. These data suggest that giving LHRHa before and during adjuvant chemotherapy could also be a reliable strategy to preserve ovarian function and fertility. The use of ovarian stimulating drugs in standard treatment protocols for ovarian stimulation in female cancer patients is safe according to current data. The meta-analysis of 14 studies did not show negative influence of pregnancy on overall survival of female cancer patients although the optimal interval between breast cancer diagnosis and pregnancy is not known. However, breast cancer patients are in higher risk of preterm labor and low birth weight of infants.Key words: breast neoplasms - fertility preservation - ovarian stimulation - LHRH - pregnancy - tamoxifen - aromatase inhibitors - adjuvant hormonal therapyThis work was supported by MEYS - NPS I - LO1413.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 3. 8. 2016Accepted: 11. 8. 2016.

[Circulating Levels of Estradiol in Breast Cancer Patients Treated with Aromatase Inhibitors and Their Clinical Implications]. / Sledování cirkulujících hladin estradiolu u pacientek s karcinomem prsu lécených inhibitory aromatázy - prínos v klinické praxi.

Adjuvant treatment with aromatase inhibitors improves outcomes in postmenopausal women with hormone-sensitive early breast cancer; however, they should not be used in premenopausal women. Menopausal status is the most important factor in the choice of the hormonal treatment. There is no direct correlation between amenorrhea and ovarian function, as even the patients with amenorrhea may present with premenopausal plasma estradiol levels. The evaluation of hormonal status becomes more complicated in patients taking tamoxifen, which might lead to further increase of plasma estradiol levels. Therefore, its evaluation before and during the treatment with aromatase inhibitors is clinically important. There is a considerable caution needed when indicating aromatase inhibitors in patients with menopause caused by previous adjuvant chemotherapy, while recovery of ovarian function may appear after a certain period. This could take from 4 to 59 months (12 months on average) and it might not be accompanied by menses. This happens typically in women younger than 40 years, who should, therefore, not be treated by aromatase inhibitors alone. This supports the notion that monitoring of plasma estradiol levels is crucial in women from 40 to 50 years of age, especially before the start of aromatase inhibitors treatment.Key words: breast cancer - premenopause - postmenopause - perimenopause - estradiol - aromatase inhibitorsThis work was supported by MEYS - NPS I - LO1413 for RECAMO.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 18. 2. 2016Accepted: 29. 6. 2016.

[Extraoseus Ewings Sarcoma, Primary Affection of Uterine Cervix--Case Report]. / Extraoseální Ewinguv sarkom, primární postizení delozního cípku--kazuistika.

BACKGROUND: Ewing's sarcoma is usually diagnosed in adolescents and young adults, peak of incidence is around 15 years of age. Primary localization is mostly in the skeleton of long bones and chest wall. Primary extraosseous involvement rarely occurs, incidence increases with age. CASE: We present a case report of a 57-year-old patient with locally advanced tumors of the cervix, clinical stage IIB. Due to histological and molecular genetic examination revealing EWS -ERG fusion gene, Ewing's sarcoma was diagnosed. CT revealed pathological pelvic lymphadenopathy and multiple pulmonary bilateral methastases, scintigraphy did not prove any affection of skeleton. The patient underwent a two-stage intensive chemotherapy regimens VIDE (vincristine, ifosfamide, doxorubicin, etoposide) and VAI (vincristine, actinomycin D, ifosfamide). During the second phase, concomitant radiotherapy of pelvis was aplied. According to PET/CT, complete remission was achieved. Whole-lung irradiation was applied in consolidation of the result. CONCLUSION: Primary Ewing's sarcoma of the cervix is an extremely rare disease. To our knowledge, only 12 cases was presented until this time. The average age at time of dia-gnosis was 35 years. Unlike the previous reports, we initially diagnosed distant metastases. The treatment was led according to the protocol Ewing 2008 designed for primary skeletal Ewing's sarcoma. Currently, 18 months after the therapy, the patient is without signs of disease. However, long-term follow-up is necessary.

[The use of lenalidomide in the treatment of multiple myeloma]. / Pouzití lenalidomidu v Iécbe mnohocetného myelomu.

Lenalidomide is a promising new drug in the treatment of patients with multiple myeloma. The analogue of thalidomide was created with the intention of improving the anticancer activity, its immunomodulatory properties as well as reducing the toxicity of the preparation. The mechanism of antitumor action of the preparation appears to be the effect on cells, tumour microenvironment and in particular the regulation of cytokinine production. Performed clinical studies Phase I and II have shown efficacy in patients with relapsed multiple myeloma. Subsequently, large randomized trials demonstrated the benefit of combined therapy in relapsed/refractory multiple myeloma patients with a combination of lenalidomide plus dexamethasone compared with dexamethasone treatment alone. Patients treated with a combination of lenalidomide and dexamethasone had significantly higher therapeutic response and overall survival than patients treated with dexamethasone alone. Profound toxicity seems to be the myelosuppressive effect of lenalidomide. The work gives a summary of the information available on lenalidomide in the treatment of multiple myeloma.

[IKARUS Project--incidence of bone events in breast cancer: retrospective analysis of patients in oncological centres in the Czech Republic and Slovakia]. / Projekt IKARUS--zjistení incidence kostních príhod u karcinomu prsu: retrospektivní analýza nemocných dispenzarizovaných v onkologických centrech Ceské a Slovenské republiky.

BACKGROUND: Bone incidents today represent, in terms of frequency and the overall effect on the quality of life of patients with breast cancer, a serious health problem. In a number of clinical studies bisphosphonates have been shown to have a positive impact on reducing the risk of bone events and therefore to be effective in the prevention of bone events. The primary objective of this project was to identify the incidence of bone events in patients with metastatic breast cancer treated in the Czech and Slovak Republics. SUBJECTS: Retrospective, multi-centre, non-interventional, epidemiological and explorative studies to identify the incidence of bone events in the defined group of patients and a description of the practice of prevention and treatment of skeletal events in the years 2000-2005. Enrolled were patients with advanced metastatic breast cancer diagnosed in 2000. METHODS AND RESULTS: Analysis of overall survival and survival to disease progression, analysis of patterns of treatment of bone events and the practice of the use of bisphosphonates in the prevention of bone events in metastatic skeleton affection in the normal conditions of clinical practice, analysis of patient compliance in the treatment with bisphosphonates, analysis of the time interval between the occurrence of bone metastases and the occurrence of bone events and, last but not least, survival analysis of patients in relation to bone events. CONCLUSION: This work has shown that the practice of treatment with bisphosphonates since 2000 and assessed the survival of patients with metastatic breast cancer.