PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• Gravesova oftalmopatie * farmakoterapie   krev   MeSH
• imunoglobuliny stimulující tyreoideu krev   MeSH
• imunologické faktory terapeutické užití   MeSH
• léková rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rituximab * terapeutické užití   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. METHODS AND MATERIALS: Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up. RESULTS: Three hundred and eighty-three patients (102 DHL, 281 non-DHL, and 44% curative) were treated at 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% of patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post-stem cell transplant. Median biological equivalent dose (alpha/beta: 10) was 28 Gy (range: 3.2-60.0) for palliative and 46.9 Gy (range: 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, the response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI: 1.05-3.67, P = .03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative). CONCLUSIONS: Relapsed/refractory LBCL remains radioresponsive with a 60%-80% response rate to RT. Although DHL pathology does not appear to influence RT response, its presence is associated with higher rates of LR, suggesting that it may be more radioresistant.

• MeSH
• difúzní velkobuněčný B-lymfom * radioterapie   patologie   genetika   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * patologie   MeSH
• mladý dospělý MeSH
• protoonkogenní proteiny c-bcl-2 genetika   MeSH
• protoonkogenní proteiny c-myc genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• translokace genetická MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The FGFR3::TACC3 fusion has been reported in subsets of diverse cancers including urothelial and squamous cell carcinomas (SCC). However, the morphology of FGFR3::TACC3-positive head and neck carcinomas has not been well studied and it is unclear if this fusion represents a random event, or if it might characterize a morphologically distinct tumor type. We describe nine FGFR3::TACC3 fusion-positive head and neck carcinomas affecting six males and three females aged 38 to 89 years (median, 59). The tumors originated in the sinonasal tract (n = 4), parotid gland (n = 2), and one case each in the oropharynx, submandibular gland, and larynx. At last follow-up (9-21 months; median, 11), four patients developed local recurrence and/or distant metastases, two died of disease at 11 and 12 months, one died of other cause, one was alive with disease, and two were disease-free. Three of six tumors harbored high risk oncogenic HPV infection (HPV33, HPV18, one unspecified). Histologically, three tumors revealed non-keratinizing transitional cell-like or non-descript morphology with variable mixed inflammatory infiltrate reminiscent of mucoepidermoid or DEK::AFF2 carcinoma (all were HPV-negative), and three were HPV-associated (all sinonasal) with multiphenotypic (1) and non-intestinal adenocarcinoma (2) pattern, respectively. One salivary gland tumor showed poorly cohesive large epithelioid cells with prominent background inflammation and expressed AR and GATA3, in line with a possible salivary duct carcinoma variant. Two tumors were conventional SCC. Targeted RNA sequencing revealed an in-frame FGFR3::TACC3 fusion in all cases. This series highlights heterogeneity of head and neck carcinomas harboring FGFR3::TACC3 fusions, which segregates into three categories: (1) unclassified HPV-negative category, morphologically distinct from SCC and other entities; (2) heterogeneous group of HPV-associated carcinomas; and (3) conventional SCC. A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.

• MeSH
• dlaždicobuněčné karcinomy hlavy a krku virologie   patologie   genetika   MeSH
• dospělí MeSH
• fenotyp MeSH
• fúzní onkogenní proteiny genetika   MeSH
• infekce papilomavirem * patologie   komplikace   genetika   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory hlavy a krku * patologie   virologie   genetika   MeSH
• proteiny asociované s mikrotubuly genetika   MeSH
• receptor fibroblastových růstových faktorů, typ 3 * genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom patologie   genetika   virologie   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

Pacientce s primárně pokročilým karcinomem vaječníků, u níž nebylo možno ani přes extenzivní chirurgický výkon dosáhnout nulového pooperačního rezidua nádoru, a která tak spadá do kategorie žen s vysokým rizikem relapsu onemocnění, byla v rámci adjuvantní léčby nabídnuta aplikace nejen standardní cílené léčby (bevacizumabu), ale s ohledem na molekulární vyšetření nádoru i výsledek germinálního testování i aplikace udržovací léčby inhibitorem poly (adenosin difosfát-ribóza) polymerázy (PARP) olaparibem. Léčba byla aplikována bez nežádoucích účinků nebo příhod. Rok od zahájení léčby pacientka žije s vynikající kvalitou života bez známek nádorového onemocnění.

A patient with primarily advanced ovarian cancer, in whom it was not possible to achieve zero postoperative tumor residue despite extensive surgery and who therefore falls into the category of women at high risk of disease relapse, was offered not only standard targeted therapy (bevacizumab) as part of adjuvant treatment, but also, based on molecular tumor testing and germline testing results, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. The treatment was administered without adverse effects or incidents. One year after the start of treatment, the patient is living with an excellent quality of life and no signs of cancer.

Karcinom endometria je obvykle diagnostikován v časném stadiu a po primární operační a následné adjuvantní onkologické léčbě má relativně dobrou prognózu. V případě lokální či regionální recidivy v oblasti pánve lze často účinně aplikovat záchrannou léčbu, ať už operační, či léčbu zářením. Pokud ale karcinom endometria recidivuje tak, že jej nelze řešit lokální záchrannou léčbou, nebo pokud metastazuje do vzdálených lokalit, je situace už mnohem vážnější. Díky molekulárně genetickým poznatkům dnes dovedeme nádory endometria lépe kategorizovat a také lépe předpovědět léčebnou odpověď nejen na chemoterapii, ale především na stále rychleji se rozvíjející imunoterapii cílenou na receptor programované buněčné smrti 1 (programmed cell death protein 1, PD-1) a jeho ligandy. Dostarlimab je prvním plně hrazeným tzv. „checkpoint inhibitorem“ v první linii léčby pacientek s rekurentním či metastazujícím MMR (mismatch repair) deficientním karcinomem endometria.

Endometrial cancer is usually diagnosed at an early stage and has a relatively good prognosis after primary surgery and subsequent adjuvant oncological treatment. In the case of local or regional recurrence in the pelvic region, salvage treatment, either surgery or radiation therapy, can often be effectively applied. However, if the endometrial cancer recurs so that it cannot be managed with local salvage treatment, or if it metastasises to distant sites, the situation is much more serious. Thanks to molecular genetic knowledge, we can now better categorize endometrial tumors and more accurately predict the therapeutic response not only to chemotherapy, but also to the rapidly developing immunotherapy targeting the programmed cell death protein 1 (PD-1) receptor and its ligands. Dostarlimab is the first fully reimbursed “checkpoint inhibitor” in the first-line treatment of patients with recurrent or metastatic MMR (mismatch repair) deficient endometrial cancer.

Kazuistika popisuje případ muže narozeného v roce 1955 s uroteliálním karcinomem ureteru přesahujícím do močového měchýře, diagnostikovaným v roce 2018. Vzhledem k rozsahu onemocnění byla primárně zvolena radikální cystektomie a nefroureterektomie s derivací moči podle Brickera, neoadjuvantní režim nebyl volen vzhledem k renální insuficienci. Po dvou letech od operace došlo ke generalizaci nemoci do lymfatických uzlin dutiny břišní. Do první linie byla vybrána studijní léčba NILE (rameno B) - tremeiimumab + durvaiumab + gemcitabin + karbopiatina s násiednou udržovací terapií durvaiumabem do progrese onemocnění. Po progresi onemocnění byla do druhé linie indikována chemoterapie gemcitabinem a karbopiatinou. Po 6 cyklech chemoterapie bylo dosaženo parciální regrese nálezu a dále bylo doporučeno pouze sledování. Po necelém roce sledování došlo k progresi nálezu na výpočetní tomografii a nově metastatickému postižení jater. Do třetí linie léčby byl zvolen enfortumab vedotin jako doporučovaný standard léčby. Po 5 měsících léčby enfortumab vedotinem bylo dosaženo parciální odpovědi na iéčbu a pacient z léčby profitoval celkem 8 měsíců. Nyní probíhá terapie čtvrté linie – rechalienge chemoterapie gemcitabinem a karboplatinou.

The case report describes the case of a man born in 1955 with urothelial carcinoma of the ureter extending into the bladder, diagnosed in 2018. Due to the extent, radical cystectomy and nephroureterectomy with Bricker urinary derivation were chosen, a neoadjuvant chemotherapy was not chosen due to renal insufficiency. Two years after the operation, the disease generalizes to the lymph nodes of the abdominal cavity. The study treatment NILE (arm B) - tremelimumab + durvalumab + gemcitabine + carboplatin was selected as the first line, followed by maintenance therapy with durvalumab until disease progression. After progression the second line gemcitabine/carboplatin chemotherapy was indicated. After 6 cycles of chemotherapy, partial regression of the finding was achieved and only monitoring was recommended. After less than a year, the disease progressed in lymph nodes and there was a new liver metastasis. Enfortumab vedotin was chosen as the third line of treatment, which is the current recommended standard of care in this situation. After 5 months of treatment with enfortumab vedotin, a partial response to treatment was achieved and the patient benefited from the treatment for a total of 8 months. Now, fourth line therapy with rechallenge chemotherapy with gemcitabine and carboplatin is underway.

OBJECTIVES: To compare the drug survival of etanercept to monoclonal tumour necrosis factor-α inhibitors in rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. METHODS: Patients initiating first line biological therapy with tumour necrosis factor-α were propensity score matched and compared for drug survival with a Kaplan-Meier analysis. RESULTS: We matched 657 to 657 patients in rheumatoid arthritis, the median survival time on etanercept was 44.6 months vs. 36.8 months on monoclonal antibody tumour necrosis factor-α inhibitors, with a hazard ratio of 0.94, p = 0.416 We matched 187 to 356 patients in ankylosing spondylitis, the median survival time on etanercept was 75.1 compared to 68.0 months, hazard ratio of 0.78, p = 0.087 We matched 81 to 160 psoriatic arthritis patients, the median survival time on etanercept was 35.8. compared to 65.7 months, hazard ratio 1.61, p = 0.011. Patients treated with etanercept had significantly worse psoriasis scoring during follow up. CONCLUSIONS: We found comparable survival in rheumatoid arthritis and ankylosing spondylitis. In psoriatic arthritis, we found significantly shorter survival on etanercept, possibly due to worse response of skin and nail manifestations.

• MeSH
• adalimumab terapeutické užití   MeSH
• ankylózující spondylitida * farmakoterapie   mortalita   MeSH
• antirevmatika * terapeutické užití   MeSH
• dospělí MeSH
• etanercept * terapeutické užití   MeSH
• infliximab terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• psoriatická artritida * farmakoterapie   mortalita   MeSH
• registrace * MeSH
• revmatoidní artritida * farmakoterapie   mortalita   MeSH
• senioři MeSH
• tendenční skóre * MeSH
• TNF-alfa * antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

Spondyloartritidy jsou heterogenní skupina chronických zánětlivých onemocnění s pestrou škálou projevů, z nichž dominuje postižení axiálního skeletu, periferních kloubů, entezitida a daktylitida, časté jsou též projevy extraskeletální. Lze je dělit podle dominantního postižení na axiální či periferní spondyloartritidy, axiální pak dále podle radiograficky prokazatelných strukturálních změn na sakroiliakálních skloubeních na radiografickou a nonradiografickou formu. Základem léčby nadále zůstávají nesteroidní antirevmatika, významný pokrok však nastal zejména se zavedením biologické léčby, kterou je v současnosti dle mezinárodních doporučení možno nasadit již v druhé linii léčby. Jednou ze základních skupin biologických léčiv jsou inhibitory tumor nekrotizujícího faktoru a, jejichž zástupcem je i certolizumab pegol, humanizovaná monoklonální protilátka, která na rozdíl od ostatních zástupců této skupiny obsahuje pouze Fab fragment molekuly s dvěma navázanými molekulami polyethylenglykolu. Tato struktura minimalizuje transplacentární přestup, a proto je certolizumab pegol s výhodou užíván po celou dobu těhotenství u těhotných pacientek s revmatickým onemocněním. V následujícím textu demonstrujeme účinnost i bezpečnost užití certolizumab pegolu u dvou těhotných pacientek s axiální spondyloartritidou.

Spondyloarthritis is a heterogeneous group of chronic inflammatory diseases with various symptoms that mainly include the damage of axial skeleton, peripheral joints, enthesitis and dactylitis. Extraskeletal manifestations are often as well. Spondyloarthritis can be divided into two groups, axial and peripheral, depending on the dominant involvement. Axial type can be further divided into radiographic and non-radiographic type based on the radiographic evidence of structural damage of sacroiliac joints. Nonsteroidal anti-inflammatory drugs still remain the drug of the first choice, but it was the introduction of biological therapy that led to a significant treatment progress. According to the most recent international recommendations, biological therapy is approved as a second-line treatment of the disease. Tumor necrosis factor a inhibitors are one of the main groups of biologics that include certolizumab pegol, a humanized monoclonal antibody that consists of a single Fab fragment with no Fc portion compared to the other group agents. The Fab fragment is conjugated with two molecules of polyethylene glycol which minimizes the placental transfer. Therefore, certolizumab pegol is successfully used throughout pregnancy in pregnant women with rheumatic diseases. The following text demonstrates both the efficacy and safety of use of certolizumab pegol in two pregnant patients treating for axial spondyloarthritis.

Při léčbě lokálně pokročilého a generalizovaného nemalobuněčného karcinomu plic s mutací genu pro receptor epidermálního růstového faktoru je již standardem zahájení léčby v první linii osimertinibem. Nadále je ale snaha zlepšit celkové přežívání pacientů v souladu s dostatečným zachováním kvality života. Jednou z nových možností léčby je kombinace osimertinibu s chemoterapií. V naší kazuistice předkládáme probíhající léčbu mladého pacienta s adenokarcinomem plic ve IV. stadiu, který podstoupil v úvodu výše uvedenou kombinovanou terapii.

In the treatment of locally advanced and generalized non-small cell lung cancer with a mutation for receptor of the epidermal growth factor, standard of care is to start treatment with osimertinib in the first line. However, the effort to improve overall survival of patients in accordance with sufficient preservation of quality of life continues. One of the new treatment options is the combination of osimertinib with chemotherapy. In our case report, we present the ongoing treatment of a young patient with stage IV lung adenocarcinoma, who initially underwent the combined therapy mentioned above.

Carotid plaque composition represents one of the main risk factors of future ischemic stroke. MRI provides excellent soft tissue contrast that can distinguish plaque characteristics. Our objective was to analyze the diagnostic accuracy of MRI imaging in the detection of carotid plaque characteristics compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis through a systematic review. After prospective registration in PROSPERO (ID CRD42022329690), Medline Ovid, Embase.com, Cochrane Library, and Web of Science Core were searched without any search limitation up to May 27, 2022 to identify eligible articles. Of the 8168 studies, 53 (37 × 1.5 T MRI, 17 × 3 T MRI) evaluated MRI accuracy in the detection of 13 specific carotid plaque characteristics in 169 comparisons. MRI demonstrated high diagnostic accuracy for detection of calcification (3 T MRI: mean sensitivity 92%/mean specificity 90%; 1.5 T MRI: mean sensitivity 81%/mean specificity 91%), fibrous cap (1.5 T: 89%/87%), unstable plaque (1.5 T: 89%/87%), intraplaque hemorrhage (1.5 T: 86%/88%), and lipid-rich necrotic core (1.5 T: 89%/79%). MRI also proved to have a high level of tissue discrimination for the carotid plaque characteristics investigated, allowing potentially for a better risk assessment and follow-up of patients who may benefit from more aggressive treatments. These results emphasize the role of MRI as the first-line imaging modality for comprehensive assessment of carotid plaque morphology, particularly for unstable plaque. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

• MeSH
• arteriae carotides * diagnostické zobrazování   patologie   MeSH
• aterosklerotický plát * diagnostické zobrazování   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• nemoci arterie carotis * diagnostické zobrazování   patologie   MeSH
• reprodukovatelnost výsledků MeSH
• senzitivita a specificita MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH
• systematický přehled MeSH