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Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5–7 weeks of daily treatments, has been reduced to 3–4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes.

Background Management of non-small-cell lung cancer (NSCLC) is affected by regional specificities. The present study aimed at determining diagnostic and therapeutic procedures including outcome of patients with NSCLC stage III in the real-world setting in Central European countries to define areas for improvements. Patients and methods This multicentre, prospective and non-interventional study collected data of patients with NSCLC stage III in a web-based registry and analysed them centrally. Results Between March 2014 and March 2017, patients (n=583) with the following characteristics were entered: 32% females, 7% never-smokers; ECOG performance status (PS) 0, 1, 2 and 3 in 25%, 58%, 12% and 5%, respectively; 21% prior weight loss; 53% squamous carcinoma, 38% adenocarcinoma; 10% EGFR mutations. Staging procedures included chest X-ray (97% of patients), chest CT (96%), PET-CT (27%), brain imaging (20%), bronchoscopy (89%), endobronchial ultrasound (EBUS) (13%) and CT-guided biopsy (9%). Stages IIIA/IIIB were diagnosed in 55%/45% of patients, respectively. N2/N3 nodes were diagnosed in 60%/23% and pathologically confirmed in 29% of patients. Most patients (56%) were treated by combined modalities. Surgery plus chemotherapy was administered to 20%, definitive chemoradiotherapy to 34%, chemotherapy only to 26%, radiotherapy only to 12% and best supportive care (BSC) to 5% of patients. Median survival and progression-free survival times were 16.8 (15.3;18.5) and 11.2 (10.2;12.2) months, respectively. Stage IIIA, female gender, no weight loss, pathological mediastinal lymph node verification, surgery and combined modality therapy were associated with longer survival. Conclusions The real-world study demonstrated a broad heterogeneity in the management o f stage III NSCLC in Central European countries and suggested to increase the rates of PET-CT imaging, brain imaging and invasive mediastinal staging.

Abstract Purpose Male breast cancer (MBC) is a rare, but increasingly common disease, and lacks prospective studies. Collaborative efforts are needed to understand and address MBC, including its prognosis, in different countries. Methods We retrospectively reviewed the clinical, histopathological, and molecular-genetic characteristics, treatments, and survival outcomes of MBC diagnosed between 2007 and 2017 in the Czech Republic. Prognostic factors of overall survival (OS), recurrence-free interval (RFi), and breast cancer-specific mortality (BCSM) were analyzed and indirectly compared to international data. Results We analyzed 256 patients with MBC (median age 66 years), including 12% with de novo metastatic (M1). Of 201 non-metastatic (M0) patients, 6% were <40 years old, 29% had stage I, 55% were cN0, and 54% underwent genetic testing. Overall, 97% of tumors had estrogen receptor expression ≥10%, 61% had high Ki67 index, 40% were high-grade (G3), and 68% were luminal B-like (HER2-negative). Systemic therapies included endocrine therapy (90%) and chemotherapy (53%). Few (5%) patients discontinued adjuvant endocrine therapy for reasons other than disease relapse or death. Patients treated with aromatase inhibitors alone had significantly shorter RFi (P < .001). OS, RFi, and BCSM were associated with disease stage, T stage, N stage, progesterone receptor expression, grade, and Ki67 index. Median OS reached 122 and 42 months in M0 and de novo M1 patients, respectively. Conclusion Due to the rarity of MBC, this study highlights important findings from real clinical practice. Although the number of patients with MBC with unfavorable features was higher in this Czech dataset than in international studies, the prognosis remains consistent with real-world evidence. This study evaluated patient and disease characteristics, treatment, and prognosis of male breast cancer among patients registered with the Complex Oncological Centers in the Czech Republic, and indirectly compared these findings with international data.

The study aimed to evaluate differences in the overall survival of HER2+ breast cancer patients treated with regard to their hormone receptors negativity or positivity. We evaluated a cohort of patients treated with trastuzumab in the Czech Republic. The present study is a retrospective analysis of patients whose data were recorded in a nationwide non-interventional, post-authorisation database BREAST. After propensity score matching of data, the cohort included 4,532 patients. A significant difference in overall survival (OS) of the entire cohort was found between patients with and without hormone dependence. The OS was significantly higher in the group of patients with hormone receptor-positive (HR+) tumours in the following cohorts: patients treated with neoadjuvant therapy, patients with advanced disease, G2 tumours, stage III and IV and in patients with stage II and III of G2 tumours. Increased OS rates were found in several subgroups of patients with HR+/HER2+ tumours compared to those with HR-/HER2+ tumours. Better outcomes of HR+/HER2+ patients were only observed in the first four/five years of follow-up, and the differences disappeared over time.

Image guided radiation therapy (IGRT) enables the achievement of higher precision in radiation delivery, a reduction in safety margins and a reduced risk of toxicity in healthy tissues. The present study investigated the magnitude of safety margins for the radiation boost setup on skin marks or metal clips implanted into the tumor bed during breast cancer surgery. One hundred eighty-four patients after breast conserving surgery with implanted metal clips into tumor bed were analyzed. The present study investigated the difference in safety margin required for the treatment setup on skin marks and metal clips. The skin marks were created using a positioning laser system in the treatment room. Metal clips implanted in the tumor bed were registered using IGRT with kilovoltage X-rays in orthogonal projection. Treatment setup was performed during free breathing. The safety margin corresponding to the planning target volume (PTV) was calculated from the recorded data. Calculated safety margins for the treatment setup on skin marks were 9.4, 11.1 and 11.1 mm in the anteroposterior, craniocaudal, and laterolateral directions, respectively. Corresponding safety margins with the use of IGRT and metal clips registration were 4.7, 5.1 and 5.9 mm, respectively. The safe PTV margin was 12 mm using setup on skin marks without IGRT, whereas a 6-mm margin was sufficient with the use of metal clip-based IGRT with daily online correction. IGRT has been adopted as the standard treatment method within the Oncology Centre of Multiscan and Pardubice Hospital (Pardubice, Czech Republic).

Sacituzumab govitecan (SG), an antibody-drug conjugate targeting TROP-2, demonstrated superior efficacy over standard chemotherapy in heavily pretreated metastatic triple-negative breast cancer (mTNBC) in the ASCENT trial. However, real-world data remain limited. This study evaluated the effectiveness and safety of SG in an unselected multinational cohort of patients with mTNBC. This retrospective analysis included 303 women who initiated SG treatment between August 2021 and April 2025 across 18 oncology centers in Poland, the Czech Republic and Slovakia, within the Central European Breast Cancer Collaboration (CEBCC-102). Primary endpoints were median progression-free survival (mPFS) and overall survival (mOS). Secondary objectives included response pattern, safety and identification of factors influencing outcomes. Adverse events (AEs) were graded using Common Terminology Criteria for AE, version 5.0 and treatment response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median follow-up was 8.8 months (IQR 4.5-14.4). The mPFS was 4.4 months, and mOS was 11.3 months. The overall response rate was 30.7%. The most frequent AEs were hematologic: neutropenia (69.0%) and anemia (39.6%). In multivariate Cox analyses, poor ECOG performance status and liver metastases were independently associated with worse outcomes. Diarrhea and hypersensitivity reactions showed favorable prognostic associations. In this largest real-world cohort, the clinical benefit of SG observed in the ASCENT trial was confirmed under routine practice conditions. Poor performance status and liver metastases predicted inferior outcomes, while certain treatment-related AEs warrant further investigation.

Despite extensive research, the molecular role of AGR2 in the progression and metastasis of colorectal cancer (CRC) has not been fully characterized. We used quantitative mass spectrometry (SWATH MS) to identify differentially expressed proteins in paired CRC cell models of the SW480 and SW620 cell lines in response to AGR2 protein level manipulation. Relying on the results from SWATH MS and subsequent immunochemical validation, we selected NMP3 as the top candidate protein associated with AGR2 in CRC tumour cells in our screen. RT‒qPCR and immunochemical analysis confirmed the involvement of AGR2-mediated regulation of NPM3 at the transcriptional and posttranscriptional levels. Since PD-L1 is a constituent of the NPM3 regulatory axis, we aimed to correlate the changes in PD-L1 to the differential expression of AGR2 in our cell models. We found that AGR2 positively regulates PD-L1 levels in both SW480 and SW620 cell lines; additionally, several different CRC patient transcriptome cohorts confirmed the association of AGR2 with PD-L1. Our work reveals a new AGR2-NPM3 regulatory axis and the involvement of AGR2 in the regulation of PD-L1, which paves the way for the association of AGR2 with immune evasion in CRC cells.

The TGF-β signaling pathway is involved in numerous cellular processes, and its deregulation may result in cancer development. One of the key processes in tumor progression and metastasis is epithelial to mesenchymal transition (EMT), in which TGF-β signaling plays important roles. Recently, AGR2 was identified as a crucial component of the cellular machinery responsible for maintaining the epithelial phenotype, thereby interfering with the induction of mesenchymal phenotype cells by TGF-β effects in cancer. Here, we performed transcriptomic profiling of A549 lung cancer cells with CRISPR-Cas9 mediated AGR2 knockout with and without TGF-β treatment. We identified significant changes in transcripts associated with focal adhesion and eicosanoid production, in particular arachidonic acid metabolism. Changes in transcripts associated with the focal adhesion pathway were validated by RT-qPCR of COL4A1, COL4A2, FLNA, VAV3, VEGFA, and VINC mRNAs. In addition, immunofluorescence showed the formation of stress fibers and vinculin foci in cells without AGR2 and in response to TGF-β treatment, with synergistic effects observed. These findings imply that both AGR2 downregulation and TGF-β have a role in focal adhesion formation and cancer cell migration and invasion. Transcripts associated with arachidonic acid metabolism were downregulated after both AGR2 knockout and TGF-β treatment and were validated by RT-qPCR of GPX2, PTGS2, and PLA2G4A. Since PGE2 is a product of arachidonic acid metabolism, its lowered concentration in media from AGR2-knockout cells was confirmed by ELISA. Together, our results demonstrate that AGR2 downregulation and TGF-β have an essential role in focal adhesion formation; moreover, we have identified AGR2 as an important component of the arachidonic acid metabolic pathway.

Background: In this retrospective study, we analysed clinical, biochemical and molecular genetic data of 47 Czech patients with Single, Large-Scale Mitochondrial DNA Deletions (SLSMD). Methods: The diagnosis was based on the long-range PCR (LX-PCR) screening of mtDNA isolated from muscle biopsy in 15 patients, and from the buccal swab, urinary epithelial cells and blood in 32 patients. Results: A total of 57% patients manifested before the age of 16. We did not find any significant difference between paediatric and adult manifestation in either the proportion of patients that would develop extraocular symptoms, or the timespan of its progression. The survival rate in patients with Pearson Syndrome reached 60%. Altogether, five patients manifested with atypical phenotype not fulfilling the latest criteria for SLSMD. No correlation was found between the disease severity and all heteroplasmy levels, lengths of the deletion and respiratory chain activities in muscle. Conclusions: Paediatric manifestation of Progressive External Ophthalmoplegia (PEO) is not associated with a higher risk of multisystemic involvement. Contrary to PEO and Kearns-Sayre Syndrome Spectrum, Pearson Syndrome still contributes to a significant childhood mortality. SLSMD should be considered even in cases with atypical presentation. To successfully identify carriers of SLSMD, a repeated combined analysis of buccal swab and urinary epithelial cells is needed.