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

PURPOSE: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) have a poor prognosis. The phase I/II NP30179 study (ClinicalTrials.gov identifier: NCT03075696) evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab. We present data for patients with R/R MCL. METHODS: Eligible patients with R/R MCL (at least one previous therapy) received Gpt (1,000 or 2,000 mg) 7 days before the first glofitamab dose (single dose or split over 2 days if required). Glofitamab step-up dosing was administered once a day on days 8 (2.5 mg) and 15 (10 mg) of cycle 1, with a target dose of 16 or 30 mg once every 3 weeks from cycle 2 day 1 onward, for 12 cycles. Efficacy end points included investigator-assessed complete response (CR) rate, overall response rate (ORR), and duration of CR. RESULTS: Of 61 enrolled patients, 60 were evaluable for safety and efficacy. Patients had received a median of two previous therapies (range, 1-5). CR rate and ORR were 78.3% (95% CI, 65.8 to 87.9) and 85.0% (95% CI, 73.4 to 92.9), respectively. In patients who had received previous treatment with a Bruton tyrosine kinase inhibitor (n = 31), CR rate was 71.0% (95% CI, 52.0 to 85.8) and ORR was 74.2% (95% CI, 55.4 to 88.1). CRS after glofitamab administration occurred in 70.0% of patients, with a lower incidence in the 2,000 mg (63.6% [grade ≥2, 22.7%]) versus 1,000 mg (87.5%; grade ≥2, 62.5%) Gpt cohort. Four adverse events led to glofitamab withdrawal (all infections). CONCLUSION: Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

• MeSH
• dospělí MeSH
• humanizované monoklonální protilátky aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• lymfom z plášťových buněk * farmakoterapie   patologie   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
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH

Patients with testicular lymphoma are at an increased risk of central nervous system (CNS) disease. Optimal strategy for CNS relapse prevention is unknown. We analyzed treatment strategies, cumulative incidence of CNS relapse and prognosis in 229 patients with diffuse large B-cell lymphoma (DLBCL) and testicular involvement: 157 primary testicular lymphomas (PTL) in clinical stages IE/IIE and 72 patients in advanced stages (T-DLBCL) IIIE/IV. Treatments for PTL vs. T-DLBCL included: rituximab-based chemotherapy (80.9% vs. 90.3%), orchiectomy (94.3% vs. 65.3%) and contralateral testicular irradiation (59.8% vs. 44.4%). Majority (84.3%) received CNS prophylaxis with similar rates of prophylactic methotrexate (intravenous 19.1% vs. 16.6%, intrathecal 40.8% vs. 40.4%, or both 24.2% vs. 27.8%) between PTL and T-DLBCL (p = 0.89). Median follow-up was 51.8 months. CNS relapses occurred in 14 (6.1%) of 63 relapsing patients. The 5-year cumulative incidence of CNS relapse in PTL was 4.5% and in T-DLBCL 12.1%. Median time to CNS relapse was 21.9 months. In univariate analyses, orchiectomy was the single significant factor associated with lower risk of CNS relapse in PTL (HR = 0.11 [95% CI, 0-0.124], p = 0.001). Rituximab significantly reduced CNS relapse risk in T-DLBCL (HR = 0.1002, p = 0.0005). Median progression-free survival (PFS) and overall survival (OS) following CNS relapse was dismal in T-DLBCL compared to PTL (PFS 1.6 vs. 37.8 months, p = 0.04 and OS 2.3 vs. 37.8 months, p = 0.05). This study confirmed a favorable impact of rituximab in prevention of CNS relapse in T-DLBCL. Methotrexate prophylaxis did not alter CNS relapse risk. Prognosis of CNS relapse is particularly poor in T-DLBCL.

• MeSH
• difúzní velkobuněčný B-lymfom * terapie   epidemiologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• mladý dospělý MeSH
• nádory centrálního nervového systému * terapie   epidemiologie   prevence a kontrola   mortalita   MeSH
• následné studie MeSH
• orchiektomie MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• rituximab * terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• testikulární nádory * terapie   patologie   epidemiologie   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
• Publikační typ
• časopisecké články MeSH

The characteristics at diagnosis and clinical course of primary extranodal follicular lymphoma (EFL) have not been extensively described. The International Extranodal Lymphoma Study Group (IELSG) conducted an international retrospective survey aimed to describe the clinical features at diagnosis and the outcomes of FL cases with a clinically dominant extranodal component. The dataset included 605 pathologically reviewed cases from 19 different countries, and their outcomes were compared to those of nodal follicular lymphomas. The two most common presentation sites for EFL were the skin (n = 334) and the gastrointestinal tract (n = 72), with 22 cases having primary duodenal localization. These subsets exhibited unique features at diagnosis and significantly different overall survival (OS) patterns. After a median follow-up of 5.5 years, primary cutaneous lymphomas showed a superior outcome [10-year OS: 89% (95% CI, 83%-93%)], while primary gastrointestinal lymphomas had an intermediate outcome [10-year OS: 79% (95% CI, 59%-90%)]. Among the gastrointestinal lymphomas, primary duodenal lymphomas tended toward the best outcome [10-year OS: 95% (95% CI, 69%-99%)]. Other primary extranodal sites had inferior outcomes [10-year OS: 59% (95% CI, 48%-68%)], similar to primary nodal lymphomas [10-year OS: 57% (95% CI, 49%-64%)]. These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics.

• MeSH
• dospělí MeSH
• folikulární lymfom * mortalita   terapie   diagnóza   patologie   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mladý dospělý MeSH
• následné studie MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři 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

Although chronic inflammation is implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL), the mechanisms responsible are unknown. We demonstrate that the overexpression of the collagen receptor, DDR1, correlates with reduced expression of spindle checkpoint genes, with three transcriptional signatures of aneuploidy and with a higher frequency of copy number alterations, pointing to a potential role for DDR1 in the acquisition of aneuploidy in DLBCL. In support of this, we found that collagen treatment of primary germinal centre B cells transduced with DDR1, not only partially recapitulated the aberrant transcriptional programme of DLBCL but also downregulated the expression of CENPE, a mitotic spindle that has a crucial role in preventing chromosome mis-segregation. CENPE expression was also downregulated following DDR1 activation in two B-cell lymphoma lines and was lost in most DDR1-expressing primary tumours. Crucially, the inhibition of CENPE and the overexpression of a constitutively activated DDR1 were able to induce aneuploidy in vitro. Our findings identify a novel mechanistic link between DDR1 signalling and chromosome instability in B cells and provide novel insights into factors driving aneuploidy in DLBCL.

• MeSH
• aneuploidie * MeSH
• B-lymfocyty metabolismus   MeSH
• chromozomální nestabilita * genetika   MeSH
• difúzní velkobuněčný B-lymfom * genetika   patologie   metabolismus   MeSH
• kolagen farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• receptor DDR1 * genetika   metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• signální transdukce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Úvod: Primární tumory a infiltrativní procesy očnice zahrnují poměrně širokou škálu dia gnóz. Nádory a infiltrace, které vycházejí primárně z tkání prostoru očnice ohraničeného periorbitou, označujeme jako primární, zatímco sekundární tumory zasahují do orbity z okolních tkání vně od periorbity. Speciální skupinu tvoří léze metastatické. Cíl: Retrospektivní observační analýza souboru pacientů diagnostikovaných pro primární tumor a primární infiltraci očnice na Klinice otorinolaryngologie a chirurgie hlavy a krku v Nemocnici u sv. Anny v Brně (KOCHHK) v letech 2000– 2023. Metodika: Zařazeni byli pacienti ve věku ≥ 18 let, kteří absolvovali otorinolaryngologické a oftalmologické vyšetření, zobrazovací vyšetření (CT/ MR) a podstoupili stanovenou léčbu. Hodnoceny byly demografické parametry, symptomatologie, diagnostický a terapeutický přístup, histologická charakteristika procesů a efekt léčby. Výsledky: Ve sledovaném souboru byl nejčastějším benigním procesem pseudotumor očnice (12 pacientů, 33 %), z toho jedenáct pacientů podstoupilo kortikoidní terapii. U sedmi pacientů došlo ke kompletní regresi, u jednoho pacienta k parciální regresi, u čtyř byla pozorována recidiva. Z maligních infiltrací byl nejvíce zastoupen lymfom (10 pacientů, 27 %), přičemž u šesti pacientů se jednalo o MALT-lymfom. U devíti pacientů došlo ke kompletní remisi, u jednoho pacienta k remisi parciální. Závěr: Dia gnostika a terapie primárních lézí očnice nevyhnutelně vyžaduje mezioborovou spolupráci oftalmologa, neurochirurga, otorinolaryngologa, radiologa, histopatologa, event. hematoonkologa a dalších. Pro diagnostiku a adekvátní léčbu je klíčové zobrazovací vyšetření doplněno zpravidla i o histologickou verifikaci. Její provedení a event. chirurgické odstranění léze je značně limitováno lokalizací. Prognóza závisí nejen na maligním potenciálu léze, ale významně také na jejím vztahu k okolí a k důležitým strukturám v očnici.

Introduction: Primary tumors and infiltrative processes of the orbit include a fairly wide range of diagnoses. Tumors and infiltrations that arise primarily from the tissues of the orbital space bounded by the periorbita are termed primary, while secondary tumors encroach into the orbit from surrounding tissues outside the periorbita. A special group consists of metastatic lesions. Aim: Retrospective observational analysis of a cohort of patients diagnosed for a primary tumor or infiltration of the orbit at the Department of Otorhinolaryngology and Head and Neck Surgery at St. Anne‘s Hospital in Brno (KOCHHK) between 2000 and 2023. Methods: Patients aged ≥ 18 years who underwent otorhinolaryngological and ophthalmological examinations, imaging (CT/MRI), and treatment were included. Demographic parameters, symptomatology, diagnostic and therapeutic approaches, histological characteristics of the processes, and treatment effect were evaluated. Results: In the study group, the most common benign process was a pseudotumour of the orbit (12 patients, 33%), of which 11 patients underwent corticosteroid therapy. Complete regression was observed in 7 patients, partial regression was in 1 patient, and recurrence was in 4 patients. Lymphoma was the most common malignant infiltration (10 patients, 27%), with 6 patients having MALT-lymphoma. Nine patients had complete remission and 1 patient had partial remission. Conclusion: Diagnosis and therapy of primary lesions of the orbit inevitably require interdisciplinary cooperation of the ophthalmologist, neurosurgeon, otorhinolaryngologist, radiologist, histopathologist, hematooncologist, and others. For diagnosis and adequate treatment, imaging examination is crucial, usually supplemented by histological verification. Its performance, and if necessary, surgical removal of the lesion is limited by localization. Prognosis depends not only on the malignant potential of the lesion, but also significantly on its relationship to the surrounding area and to important structures in the orbit.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfom chirurgie   diagnostické zobrazování   diagnóza   MeSH
• nádory orbity * chirurgie   diagnostické zobrazování   diagnóza   klasifikace   MeSH
• oftalmologické chirurgické výkony metody   MeSH
• orbita diagnostické zobrazování   patologie   MeSH
• poruchy hybnosti oka diagnóza   etiologie   MeSH
• pseudotumor orbity chirurgie   diagnostické zobrazování   diagnóza   klasifikace   MeSH
• retrospektivní studie 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

INTRODUCTION: Pathogenesis of large B-cell lymphomas (LBCL) and follicular lymphomas (FL) is a multistep process associated with the development of diverse DNA alterations and consequent deregulation of critical cellular processes. Detection of tumor-associated mutations within non-tumor compartments (mainly plasma) is the basis of the 'liquid biopsy' concept. Apart from tumor mutational profiling, quantitative analysis of circulating tumor DNA (ctDNA) allows longitudinal assessment of tumor burden. ctDNA-based technologies provide a new tool for tumor diagnostics and treatment personalization. AREAS COVERED: Our review provides a comprehensive overview and summary of available ctDNA studies in LBCL and FL. The accuracy of ctDNA-based detection of lymphoma-associated DNA alterations is correlated to known LBCL and FL molecular landscape. Additionally, we summarized available evidence that supports and justifies the clinical use of ctDNA for lymphoma risk stratification, treatment response evaluation, and treatment response-adapted therapy. Lastly, we discuss other clinically important ctDNA applications: monitoring of lymphoma clonal evolution within resistance and/or relapse development and utilization of ctDNA for diagnostics in non-blood fluids and compartments (e.g. cerebrospinal fluid in primary CNS lymphomas). EXPERT OPINION: Despite certain challenges, including methodological standardization, ctDNA holds promise to soon become an integral part of lymphoma diagnostics and treatment management.

• MeSH
• cirkulující nádorová DNA * krev   genetika   MeSH
• difúzní velkobuněčný B-lymfom * diagnóza   genetika   terapie   krev   MeSH
• folikulární lymfom * diagnóza   genetika   terapie   krev   MeSH
• lidé MeSH
• mutace MeSH
• nádorové biomarkery * krev   genetika   MeSH
• prognóza MeSH
• tekutá biopsie metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL) is a rare but serious condition requiring accurate diagnostics. Cerebrospinal fluid (CSF) analysis plays a crucial role, particularly in cases where biopsy is not feasible, and imaging is inconclusive. AREAS COVERED: Chemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including circulating tumor DNA (ctDNA) analysis and microRNAs (miRNAs), are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data.This review examines both traditional and emerging methods for CSF analysis in diagnosing CNS involvement in DLBCL. Conventional approaches such as cytomorphology, flow cytometry, and biochemical markers have limitations, particularly in low-cellularity samples. Novel molecular techniques, including ctDNA analysis and miRNAs, are gaining prominence for their ability to detect gene mutations at diagnosis and monitor minimal residual disease during follow-up. The sensitivity and specificity of genetic mutations, particularly MYD88 L265P, in combination with interleukin-10 (IL-10) levels, are discussed. The literature search methodology involved reviewing relevant studies and clinical data. EXPERT OPINION: Advancements in CSF biomarker analysis are improving the diagnosis of CNS lymphoma, aiding early detection and personalized treatment approaches. However, further research and broader clinical validation are necessary for their routine implementation.

• MeSH
• cirkulující nádorová DNA mozkomíšní mok   genetika   MeSH
• diagnostické techniky molekulární metody   MeSH
• difúzní velkobuněčný B-lymfom * diagnóza   mozkomíšní mok   genetika   patologie   MeSH
• interleukin-10 genetika   mozkomíšní mok   MeSH
• lidé MeSH
• meningeální nádory * diagnóza   mozkomíšní mok   genetika   MeSH
• mikro RNA genetika   mozkomíšní mok   MeSH
• mutace MeSH
• myeloidní diferenciační faktor 88 genetika   MeSH
• nádorové biomarkery * mozkomíšní mok   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• brentuximab vedotin terapeutické užití   MeSH
• Hodgkinova nemoc diagnóza   terapie   MeSH
• imunoterapie metody   MeSH
• inhibitory kontrolních bodů terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná farmakoterapie MeSH
• kritéria léčebné odpovědi MeSH
• lidé MeSH
• recidiva MeSH
• rizikové faktory MeSH
• staging nádorů MeSH
• transplantace kmenových buněk MeSH
• zohlednění rizika MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Proton beam therapy using pencil beam scanning is an advanced radiotherapy technique that utilises proton beams to precisely target tumours. It is known for its enhanced ability in sparing healthy tissue and potentially reducing toxicity. Clinical experience with pencil beam scanning in the treatment of mediastinal Hodgkin lymphoma remains limited. PATIENTS AND METHODS: This study aimed to evaluate the toxicity and outcomes of a prospectively observed cohort. A total of 162 patients were irradiated between May 2013 and December 2020, with a median age of 32 years (range: 18.4-79.2) and followed up until April 2024. The median applied dose was 30 GyE (range: 20-40). Deep inspiration breath hold was used in 146 patients to enhance targeting precision. RESULTS: The disease-free survival, overall survival and local control rates were 95.1 %, 98.8 % and 98.8 %, respectively. The median follow-up was 59.1 months (range: 4-120.1). The most common acute toxicities observed were oesophageal and skin toxicity. Grade 1 oesophageal mucositis occurred in 76 patients (47 %), grade 2 in 16 patients (10 %). Dermatitis of grade 1 and 2 was observed in 65 (40 %) and 4 (3 %) patients respectively. Grade 1 pulmonary toxicity presented in 8 patients (4.9 %), and grade 2 in one patient (0.6 %). The most predominant late toxicity was grade 2 hypothyroidism in 37 patients (23 %). Three patients (1.8 %) underwent coronary interventions during follow-up, and one patient was diagnosed with hepatocellular carcinoma 3 months post-RT. No unexpected acute or late toxicities were observed. CONCLUSION: Proton beam therapy using pencil beam scanning is a safe and effective technique in terms of toxicity and local control, even when irradiating mediastinal targets.

• MeSH
• celková dávka radioterapie MeSH
• dospělí MeSH
• Hodgkinova nemoc * radioterapie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory mediastina * radioterapie   mortalita   MeSH
• prospektivní studie MeSH
• protonová terapie * škodlivé účinky   metody   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• 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