BACKGROUND AND OBJECTIVES: Oligodendrogliomas are primary brain tumors classified as isocitrate deshydrogenase-mutant and 1p19q codeleted in the 2021 World Health Organization Classification of central nervous system tumors. Surgical resection, radiotherapy, and chemotherapy are well-established management options for these tumors. Few studies have evaluated the efficacy of stereotactic radiosurgery (SRS) for oligodendroglioma. As these tumors are less infiltrative than astrocytomas and typically recur locally, focal therapy such as SRS is an appealing option. METHODS: This study was performed through the International Radiosurgery Research Foundation. The objective was to collect retrospective multicenter data on tumor control, clinical response, and morbidity after SRS for oligodendroglioma. Inclusion criteria were age of 18 years or more, single-fraction SRS, and histological confirmation of grade 2 or 3 oligodendroglioma. The primary end points were progression-free survival (PFS) and overall survival from SRS. Secondary end points included clinical evolution and occurrence of adverse radiation events or other complications. Descriptive statistics, Kaplan-Meier analyses, and univariate and multivariate analyses were performed. RESULTS: Eight institutions submitted data for a total of 55 patients. The median follow-up time was 24 months. The median age at SRS was 46 years, and the median Karnofsky Performance Status was 90%. The median marginal dose used was 15 Gy. The median PFS was 17 months, with actuarial rates of 60% at 1 year, 31% at 2 years, and 24% at 5 years after SRS. Factors significantly associated with worsened PFS were World Health Organization grade 3, previous radiotherapy and chemotherapy, and higher marginal dose. The median overall survival post-SRS was 58 months, with actuarial rates of 92% at 1 year, 83% at 2 years, and 49% at 5 years. Karnofsky Performance Status remained stable post-SRS in 51% and worsened in 47% of patients, most often because of tumor progression (73%). Radiation-induced changes occurred in 30% of patients, of which only 4 were symptomatic. CONCLUSION: SRS is a reasonable management option for patients with oligodendroglioma.

• MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory mozku * chirurgie   MeSH
• oligodendrogliom * chirurgie   patologie   MeSH
• radiochirurgie * metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stupeň nádoru MeSH
• Světová zdravotnická organizace * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

• Publikační typ
• souhrny MeSH

BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.

• MeSH
• astrocytom * chirurgie   radioterapie   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory mozku * chirurgie   MeSH
• radiochirurgie * metody   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

• MeSH
• aminopyridiny terapeutické užití   MeSH
• anaplastická lymfomová kináza antagonisté a inhibitory   genetika   MeSH
• klinická studie jako téma MeSH
• laktamy terapeutické užití   MeSH
• lidé MeSH
• nemalobuněčný karcinom plic * farmakoterapie   genetika   patologie   MeSH
• protinádorové látky aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• pyrazoly terapeutické užití   MeSH
• Check Tag
• lidé MeSH

Epitelioidný inflamatórny myofibroblastický sarkóm (EIMS) je zriedkavý variant inflamatórneho myofibroblastického nádoru (IMT). Na rozdiel od klasického IMT sa EIMS typicky vyskytuje intraabdominálne a je charakterizovaný nepriaznivou prognózou v dôsledku svojej agresívnej povahy, vysokej miery recidív a metastatickému potenciálu. Histologicky sa vyznačuje epiteloidnou morfológiou a jedinečným imunohistochemickým profilom, ktorý umožňuje odlíšiť EIMS od iných mezenchýmových nádorov, čím výrazne prispieva k presnej diagnostike. Imunohistochemicky je charakteristická pozitivita ALK proteínu (kináza anaplastického lymfómu) s perinukleárnym alebo membránovým vzorom farbenia. Najčastejšími fúznymi partnermi ALK génu (2p3) sú gény RANBP2, RRBP1 a EML4. Táto genetická aberácia zohráva kľúčovú úlohu v diagnostike a predstavuje potenciálny cieľ pre cielenú terapiu. EIMS je zriedkavá diagnóza, ktorej vzácnosť a agresívne biologické správanie predstavujú významné diagnostické a terapeutické výzvy. V texte prezentujeme prípad 45-ročného muža s diagnózou EIMS primárne pľúcneho origa po hornej lobektómii vpravo, ktorý trpel opakovanými bolesťami hlavy a diplopiou. Zobrazovacie vyšetrenia odhalili metastatické postihnutie mozgu, ktoré napriek cielenej liečbe a opakovaným metastazektómiám recidivovalo v priebehu rokov. Tento prípad poukazuje na mimoriadne agresívnu povahu EIMS a jeho vysoký metastatický potenciál, ktorý komplikuje terapiu pacientov s touto diagnózou. Napriek pokrokom v cielenej liečbe zostáva liečba metastatického EIMS pre onkológa veľkou výzvou.

Epitheloid inflammatory myofibroblastic sarcoma (EIMS) is a rare variant of the inflammatory myofibroblastic tumour (IMT). Unlike the classic IMT, EIMS typically occurs intra-abdominally and is characterized by an adverse prognosis due to its aggressive nature, high rate of recurrence, and metastatic potential. Histologically, it exhibits epitheloid morphology and a unique immunohistochemical profile, which allows to distinguish EIMS from other mesenchymal tumours, thus significantly contributing to diagnostic accuracy. Immunohistochemically, ALK (anaplastic lymphoma kinase) protein positivity is characteristic with perinuclear or membrane staining pattern. The most common fusion partners of the ALK gene (2p3) are the RANBP2, RRBP1, and EML4 genes. This genetic aberration plays a crucial role in diagnosis and represents a potential target for targeted therapy. EIMS is a rare diagnostic entity whose rarity and aggressive biological behaviour pose significant diagnostic and therapeutic challen­ges. The article presents a case of a 45-year-old man diagnosed with EIMS of primary pulmonary origin after right upper lobectomy suffering from repeated headache episodes and diplopia. Imaging studies revealed metastatic brain involvement that, despite targeted therapy and repeated metastasectomies, tended to recur over the years. This case highlights the extremely aggressive nature of EIMS and its high metastatic potential that complicates the treatment of patients with this diagnosis. Despite advancements in targeted therapy, the treatment of metastatic EIMS remains a major challenge for the oncologist.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mozku terapie   MeSH
• nádory plic terapie   MeSH
• plazmocelulární granulom * terapie   MeSH
• přežívající onkologičtí pacienti MeSH
• protokoly protinádorové léčby MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

PURPOSE: This retrospective study aims to show a real-life single-center experience with clinical management of relapsed pediatric ependymomas using results from comprehensive molecular profiling. METHODS: Eight relapsed ependymomas were tested by whole exome sequencing, RNA sequencing, phosphoproteomic arrays, array comparative genome hybridization, and immunohistochemistry staining for PD-L1 expression and treated with an individualized approach implementing targeted inhibitors, immunotherapy, antiangiogenic metronomic treatment, or other agents. Treatment efficacy was evaluated using progression-free survival (PFS), overall survival (OS), survival after relapse (SAR), and PFS ratios. RESULTS: Genomic analyses did not reveal any therapeutically actionable alterations. Surgery remained the cornerstone of patient treatment, supplemented by adjuvant radiotherapy. Empiric agents were chosen quite frequently, often involving drug repurposing. In six patients, prolonged PFS after relapse was seen because of immunotherapy, MEMMAT, or empiric agents and is reflected in the PFS ratio ≥ 1. The 5-year OS was 88%, the 10-year OS was 73%, the 2-year SAR was 88%, and the 5-year SAR was 66%. CONCLUSION: We demonstrated the feasibility and good safety profile. Promising was the effect of immunotherapy on ZFTA-positive ependymomas. However, further research is required to establish the most effective approach for achieving sustained remission in these patients.

• MeSH
• dítě MeSH
• ependymom * terapie   genetika   patologie   MeSH
• imunoterapie MeSH
• individualizovaná medicína * metody   MeSH
• lidé MeSH
• lokální recidiva nádoru * terapie   patologie   genetika   MeSH
• míra přežití MeSH
• mladiství MeSH
• nádory mozku * terapie   genetika   patologie   MeSH
• následné studie MeSH
• předškolní dítě MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Schlafen 11 (SLFN11), a regulator of cell fate following DNA injury, sensitizes tumor cells to DNA-damaging agents. Patients with SLFN11-positive tumors may benefit from DNA-damaging chemotherapies. SLFN11 has been studied in different types of cancer including colorectal carcinomas. However, colorectal carcinomas with diffuse positivity (expression in ≥80% of tumor cells) have not been meticulously characterized. SLFN11 immunostaining of tumor microarrays (TMAs) with 3,300 primary CRCs identified 65 (~2.0%) tumors with focal staining (<10% of tumor nuclei positive), 83 (~2.5%) with patchy (≥10% and <80%) and 51 (~1.5%) with diffuse (≥80%) SLFN11 positivity. The latter was confirmed on full sections from donor blocks in 31 (~1%) cases, which were further studied including evaluation of additional immunohistochemical markers, genotyping with targeted DNA sequencing, and assessment of microsatellite instability. SLFN11-positive carcinomas were mostly (21/31, 68%) right-sided tumors with a female predominance (21/31, 68%) and median age of 67 years. Eighteen of 31 (58%) contained areas of mucinous differentiation. Deficiency of mismatch repair proteins was detected in 65% (20/31) of SLFN11-positive carcinomas. Moreover, MLH1 (n = 2), MSH2, MSH6, and PMS2 germline mutations were identified in 25% (5/20) of patients with mismatch repair deficient tumors. BRAF p.V600E mutation was found in 45% (9/20) of mismatch repair deficient, but only 1 of 11 proficient tumors. Colorectal carcinomas with diffuse SLFN11 positivity were often mismatch repair deficient tumors with their typical clinical, morphological, and molecular characteristics.

• MeSH
• dospělí MeSH
• jaderné proteiny * metabolismus   MeSH
• karcinom * metabolismus   patologie   MeSH
• kolon * metabolismus   patologie   MeSH
• kolorektální nádory * metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrosatelitní nestabilita * MeSH
• nádorové biomarkery metabolismus   MeSH
• oprava chybného párování bází DNA MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Histone deacetylases (HDACs) are frequently deregulated in cancer, and several HDAC inhibitors (HDACi) have gained approval for treating peripheral T cell lymphomas. Here, we investigated the effects of pharmacological or genetic HDAC inhibition on NPM::ALK positive anaplastic large cell lymphoma (ALCL) development to assess the potential use of HDACi for the treatment of this disease. Short-term systemic pharmacological inhibition of HDACs using the HDACi Entinostat in a premalignant ALCL mouse model postponed or even abolished lymphoma development, despite high expression of the NPM::ALK fusion oncogene. To further disentangle the effects of systemic HDAC inhibition from thymocyte intrinsic effects, conditional genetic deletions of HDAC1 and HDAC2 enzymes were employed. In sharp contrast, T cell-specific deletion of Hdac1 or Hdac2 in the ALCL mouse model significantly accelerated NPM::ALK-driven lymphomagenesis, with Hdac1 loss having a more pronounced effect. Integration of gene expression and chromatin accessibility data revealed that Hdac1 deletion selectively perturbed cell type-specific transcriptional programs, crucial for T cell differentiation and signaling. Moreover, multiple oncogenic signaling pathways, including PDGFRB signaling, were highly upregulated. Our findings underscore the tumor-suppressive function of HDAC1 and HDAC2 in T cells during ALCL development. Nevertheless, systemic pharmacological inhibition of HDACs could still potentially improve current therapeutic outcomes.

• MeSH
• anaplastická lymfomová kináza * metabolismus   genetika   MeSH
• anaplastický velkobuněčný lymfom * farmakoterapie   patologie   genetika   metabolismus   MeSH
• benzamidy farmakologie   MeSH
• histondeacetylasa 1 * genetika   antagonisté a inhibitory   fyziologie   metabolismus   MeSH
• histondeacetylasa 2 genetika   MeSH
• inhibitory histondeacetylas * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• myši MeSH
• pyridiny farmakologie   MeSH
• tumor supresorové geny * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Vascular neoplasms with epithelioid cytomorphology encompass a wide spectrum of benign and malignant lesions, including epithelioid hemangioma (EH), cutaneous epithelioid angiomatous nodule (CEAN), epithelioid hemangioendothelioma (EHE), and epithelioid angiosarcoma (EAS). Recently, the first case of a cutaneous hemangioma with epithelioid features harboring a TPM3::ALK fusion was reported. Herein, we report 4 additional cases, including 1 case with an alternate TPM4::ALK fusion, and expand on the clinicopathologic and molecular genetic features of these unusual vascular lesions. Including the previously reported case, 5 tumors occurred in 4 male and 1 female patients with a median age of 14 years (range: 2 to 38 y) and involved the shoulder region (2), the lower extremity (1), trunk (1), and head and neck (1). Clinical follow-up (3 patients; 60%) showed no evidence of disease at the last follow-up (median: 5 mo; range: 1 to 16 mo). Histologically, all tumors showed highly similar morphologic features, including an epidermal collarette, well-formed vascular channels composed of epithelioid endothelial cells with intracytoplasmic vacuoles, and admixed inflammatory cells. Immunohistochemically, all tumors were positive for vascular markers such as ERG and CD31, along with strong and diffuse cytoplasmic expression of ALK. RNA sequencing revealed recurrent TPM3 exon 8 :: ALK exon 20 (4) and TPM4 exon 7 :: ALK exon 20 fusions (1). We conclude that cutaneous hemangiomas with epithelioid features harboring TPM3/4::ALK fusions show consistent morphologic, immunophenotypic, and molecular genetic features. It remains to be determined whether this neoplasm represents a distinct entity or a molecular variant of epithelioid hemangioma.

• MeSH
• anaplastická lymfomová kináza * genetika   MeSH
• dítě MeSH
• dospělí MeSH
• epiteloidní buňky * patologie   MeSH
• fenotyp MeSH
• fúze genů MeSH
• hemangiom * genetika   patologie   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádorové biomarkery * genetika   analýza   MeSH
• nádory kůže * genetika   patologie   MeSH
• předškolní dítě MeSH
• tropomyosin * genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds of structure-activity optimization of Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation of genes involved in oxidative stress response and downregulation of DNA replication genes leading to G2/M arrest and subsequent apoptosis induction. In accordance with this, an unbiased proteomics approach, confocal microscopy and molecular modeling showed that TUBGCP2, member of the centrosomal γ-TuRC complex, is a direct interaction partner of CM14. CM14 overcomes ALK inhibitor resistance in ALCL and is also active in T-cell Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia. Interestingly, CM14 also induced cell death in docetaxel-resistant prostate cancer cells thus suggesting an unexpected role in solid cancers. Thus, we synthesized and thoroughly characterized a novel TUBGCP2 targeting drug that is active in ALCL but has also potential for other malignancies.

• MeSH
• apoptóza * účinky léků   MeSH
• centrozom * účinky léků   metabolismus   MeSH
• fenethylalkohol * analogy a deriváty   farmakologie   chemie   MeSH
• kyseliny kávové * farmakologie   chemie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky * farmakologie   chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH