INTRODUCTION: Combined immuno-oncology (IO) regimens are the cornerstone of the current front-line systemic therapy for metastatic renal cell carcinoma (mRCC). Despite the fact that combined IO regimens show high efficacy, they are often accompanied by a wide spectrum of immune-related adverse effects (irAEs). CASE PRESENTATION: We describe a case of rare irAEs manifested as giant cell temporal arteritis (GCA) followed by severe encephalopathy occurring after continuing immunotherapy in a 66-year-old man with mRCC receiving a combination of ipilimumab and nivolumab in the first line of systemic therapy. GCA occurred 4 months after the initiation of IO and responded promptly to the low-dose prednisone therapy. Four months after the continuation of nivolumab maintenance, the patient was hospitalized due to severe irAE encephalopathy which presented as psycho-behavioral abnormalities and progressive cognitive decline. He was treated with high-dose methylprednisolone which led to complete resolution of the symptoms and IO was permanently discontinued. The patient achieved a durable partial response. CONCLUSION: Both GCA and the subsequent encephalopathy in our patient responded well to the corticosteroid therapy, leading to the complete resolution of the symptoms and the patient achieved a durable partial response. Although the risk of severe neurologic irAEs affecting the central nervous system induced by IO re-administration, following previous discontinuation due to irAE, is not well-defined because of their rarity, this case highlights the need for caution, particularly in cases with a history of previous irAE-associated GCA.

• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathologic features, we performed a multiinstitutional search that yielded 11 cases. The patients ranged in age from 34 to 72 years (mean, 57 years). All tumors arose in the uterine corpus, ranging in size from 6.5 to 32 cm (mean, 15 cm). The most common stage at presentation was pT1b (n = 6), and 3 cases had stage pT1 (unspecified), and 1 case each presented in stages pT2a and pT3b. Most were treated only with hysterectomy and adnexectomy. The follow-up (range, 7-71 months; median, 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three of the 4 remaining patients died of disease within 55 to 71 months, while peritoneal spread developed in the last patient, and the patient was transferred for palliative care at 39 months. Morphologically, the tumors showed a high intertumoral and intratumoral heterogeneity. M-LMS-like and epithelioid leiomyosarcoma-like morphology were present in 3 and 5 primary tumors, respectively, the remaining mostly presented as nondescript ovoid or spindle cell sarcomas. Unusual morphologic findings included prominently hyalinized stroma (n = 3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n = 2), osteosarcomatous differentiation (n = 1), and undifferentiated pleomorphic sarcoma-like areas (n = 1). The mitotic activity ranged from 3 to 24 mitoses per 10 high-power fields (mean, 9); 3 of 10 cases showed necrosis. In 3 of 11 cases, no expression of smooth muscle actin, h-caldesmon, or desmin was noted, whereas 5 of 5 cases expressed PLAG1. By RNA sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n = 2), C15orf29, CD44, MYOCD, FRMD6, PTK2, and TRPS1 (each n = 1). One case only showed PLAG1 gene break by fluorescence in situ hybridization. Our study documents a much broader morphologic spectrum of PLAG1-rearranged uterine sarcomas than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. As it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name "PLAG1-rearranged uterine sarcoma."

• MeSH
• DNA vazebné proteiny * genetika   MeSH
• dospělí MeSH
• fenotyp MeSH
• genová přestavba * MeSH
• imunohistochemie MeSH
• leiomyosarkom * genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory dělohy * genetika   patologie   MeSH
• sarkom * genetika   patologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Východiska: S cílem prokázat proveditelnost implementace konceptu časné nádorové regrese (early tumor shrinkage – ETS) do každodenní klinické praxe v ČR byla provedena neintervenční, multicentrická, jednoramenná, prospektivní studie v reálné klinické praxi. Materiál a metody: Cílem studie bylo sledovat časový interval od data zahájení léčby do data prvního radiologického hodnocení (the first radiographic control – TFRC) a vyhodnotit podíl pacientů, kteří dosáhli ≥ 20 % regrese nádoru během prvních 8 týdnů léčby první linie, a to v reálné klinické praxi. Výsledky: Medián TFRC ve všech jednotlivých zúčastněných centrech byl > 12 týdnů (rozmezí 14,0–36,4 týdnů). TFRC ≤ 8 týdnů byla hlášena pouze u 3 % pacientů v kohortě s první linií léčby a pouze 3 pacienti (1 %) dosáhli regrese nádoru ≥ 20 % do 60. dne (8,6 týdne). Závěr: Tato zjištění naznačují, že základní časový parametr ETS by v rutinní onkologické praxi u pacientů s mCRC v ČR nemohl být reálně využit, pokud by nebyl striktní požadavek na provedení TFRC do 8. týdne od zahájení terapie. Dále byla hodnocena četnost objektivní odpovědi nádoru na první linii léčby cetuximabem + chemoterapií. Na základě relativní regrese součtu průměrů měřitelných metastatických lézí bylo nepotvrzené částečné odpovědi dosaženo u 42,4 % a nepotvrzené úplné odpovědi u 8,6 % pacientů, což dohromady odpovídá celkové četnosti odpovědí 51 % při léčbě první linie. Četnost odpovědí byla vyšší u pacientů s levostrannými než pravostrannými primárními nádory. Zdá se, že režim cetuximab/FOLFOX by mohl být v první linii léčby pravostranného „RAS wild type“ mCRC účinnější než režim cetuximab/FOLFIRI.

Background: With the aim to show the feasibility of early tumor shrinkage (ETS) concept implementation into daily clinical practice in the Czech Republic, a non-interventional, multicentric, single arm, prospective study in real world set-up was performed. Material and methods: The study objectives were to explore the time interval from the treatment starting date to the date of the first radiographic control (TFRC) and evaluate the proportion of patients who achieved ≥ 20% tumor regression within the first 8 weeks of first-line therapy, in the real-world settings. Results: The medians of TFRC in all individual participating centers were > 12 weeks (range 14.0–36.4 weeks). TFRC ≤ 8 weeks was reported for only 3% of patients in the cohort with first-line therapy, and there were only 3 patients (1%) who achieved tumor regression of ≥ 20% by day 60 (8.6 weeks). Conclusion: These findings indicate that the basic time parameter of ETS could not realistically be employed in routine oncology care of patients with metastatic colorectal cancer (mCRC) in the Czech Republic, unless there would be a strict request to perform TRFC by week 8 since the initiation of the therapy. In addition, the frequency of objective tumor response to first-line therapy with cetuximab + chemotherapy was evaluated. Based on the relative regression in the sum of diameters of measurable metastatic lesions, unconfirmed partial responses were achieved in 42.4 % and unconfirmed complete response in 8.6% of patients, altogether corresponding to the overall response rate of 51% with first-line therapy. The frequency of responses was higher among patients with left than right sided primary tumors. It seems that the regimen of cetuximab/FOLFOX might be more active in frontline therapy of right sided RAS wild type mCRC than cetuximab/FOLFIRI.

• MeSH
• cetuximab škodlivé účinky   terapeutické užití   MeSH
• kolorektální nádory * farmakoterapie   prevence a kontrola   MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové procesy * MeSH
• prognóza MeSH
• prospektivní studie MeSH
• rentgendiagnostika MeSH
• statistika jako téma MeSH
• tumor burden MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• klinická studie MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: The introduction of novel hormonal therapies represented by enzalutamide (ENZ) and abiraterone acetate (ABI) has reached a great progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The majority of mCRPC patients are elderly suffering from chronic co-morbidities requiring use of various concomitant medications. In the present study, we focused on impact of concomitant antihypertensive medication on the outcomes of mCRPC patients treated with ENZ or ABI. METHODS: In total, 300 patients were included and their clinical data were retrospectively analyzed. RESULTS: Angiotensin-converting enzyme inhibitors (ACEIs) represented the only concomitant medication significantly associated with survival. The median radiographic progression-free survival (rPFS) and overall survival (OS) for patients using ACEIs were 15.5 and 32.3 months compared to 10.7 and 24.0 months for those not using ACEIs (p = 0.0053 and p = 0.0238, respectively). Cox multivariable analysis revealed the use of ACEIs a significant predictive factor for both rPFS (HR = 0.704, p = 0.0364) and OS (HR = 0.592, p = 0.0185). CONCLUSION: The findings of this study suggest an association between the concomitant use of ACEIs and longer survival of mCRPC patients receiving ENZ or ABI therapy.

• MeSH
• abirateron * terapeutické užití   aplikace a dávkování   MeSH
• antihypertenziva * terapeutické užití   MeSH
• benzamidy * terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• fenylthiohydantoin * terapeutické užití   MeSH
• inhibitory ACE terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   mortalita   patologie   MeSH
• nitrily * terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   škodlivé účinky   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• digitální zdraví * MeSH
• odměny a ceny * MeSH
• Publikační typ
• novinové články MeSH
• rozhovory MeSH