Úvod a cíl: Sarkomy měkkých tkání představují neobvyklý typ malignity v oblasti hlavy a krku. Počet případů je popisován jako nízký. Mnoho autorů popisuje toto maligní onemocnění jako vzácný nádor hlavy a krku u dospělých. Na druhou stranu je sarkom součástí maligních onemocnění se špatnou prognózou v dětském, adolescentním a dospělém věku. Z literárních údajů vyplývá, že počty pacientů se sarkomy nelze přehlížet (27 908 případů za 7 let v Evropě na 500 mil. obyvatel). Sarkomy jsou sice málo častým zhoubným onemocněním, ale nejedná se o vzácné nádory. Proto potřebujeme aktuální poznatky a doporučení pro klinickou praxi v léčbě těchto heterogenních typů zhoubných mezenchymálních nádorů. Metoda: Analyzovali jsme literaturu o sarkomech hlavy a krku s využitím databáze Web of Science. Vyhledali jsme všechny práce popisující všechny typy léčby sarkomů v této oblasti. Tato studie analyzovala diagnostická kritéria sarkomů a léčebné plány sarkomů v oblasti hlavy a krku. Diskuze: Doporučení na základě mnoha faktorů. Sarkomy měkkých tkání v oblasti hlavy a krku jsou vzácné nebo málo časté. Incidence sarkomu měkkých tkání se pohybuje kolem 5 případů na 100 tis. obyvatel ročně. Musíme se zaměřit na nové znaky pro identifikaci rizikových faktorů sarkomu. Zásadní význam má proto patologické vyšetření a rozvoj molekulárních technik. Diagnostika na základě biopsie a histologie, včetně imunohistochemie a detekce specifických nádorových markerů. Doporučené zobrazovací metody: ultrazvuk, CT, HRCT, MR, PET CT. Přesná klasifikace a stratifikace musí být provedena v onkologickém týmu zahrnujícím patologa, onkologa, chirurga, radiologa. V literatuře byla uvedena obecná doporučení pro léčebný protokol a plánování léčby sarkomu hlavy a krku v závislosti na jeho velikosti, lokalizaci a biologickém chování. V literatuře byla popsána analýza údajů o základních léčebných modalitách v onkologické chirurgii, radioterapii a chemoterapii. V současné době nemáme k dispozici údaje o imunoterapii.
Objective: Soft tissue sarcomas represent a unique form of malignancy within the head and neck region, characterized by low incidence. Despite being commonly regarded as rare tumors in adults by numerous authors, sarcomas constitute a subset of malignant diseases associated with poor prognoses across diverse age groups, including children, adolescents, and adults. Recent literature highlights the considerable number of sarcoma cases reported, suggesting that while they may be uncommon, they are not truly rare, with 27,908 cases reported in a seven-year period in Europe among a population of 500 million inhabitants. This emphasizes the importance of recognizing sarcomas as infrequent tumors, rather than being rare. Consequently, it is essential to have up-to-date knowledge and evidence-based recommendations to inform and guide the clinical practice in the management of these heterogeneous types of mesenchymal tumors. Methods: We conducted a literature review about head and neck sarcomas using the Web of Science database. The objective of our review was to identify relevant papers discussing various treatment modalities of sarcomas in the head and neck region. This study analyzed the diagnostic criteria for sarcomas and the therapeutic approach, focusing on the surgical approach for the management of head and neck sarcomas. Discussion: Soft tissue sarcomas of the head and neck are infrequent, with an estimated annual incidence of approximately 5 per 100,000 individuals. Recommendations are based on numerous factors, while directing the attention towards identifying markers implicated as risk factors for sarcomas is crucial. Pathological review coupled with the advancement of molecular techniques is essential for this inquiry. Diagnosis relies heavily on biopsy and histological findings, including immunohistochemistry and the detection of specific tumor markers. Recommended imaging methods include ultrasound, CT, HRCT, MRI, and PET/CT scans. To achieve precise classification and stratification, we must include a multidisciplinary oncological team constructed of pathologists, oncologists, surgeons, and radiologists. Treatment protocol and planning for head and neck sarcomas take into consideration factors such as size, localization, and biological behavior, as described in existing literature. The literature extensively analyzes data connected to fundamental treatment modalities in oncology, including surgery, radiotherapy, and chemotherapy. Radical surgery, ensuring R0 margins, is definite in the treatment approach.
AIMS: Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations. METHODS: A total of 1469 abiraterone plasma levels from 83 healthy volunteers collected in a bioequivalence study were analysed using a nonlinear mixed-effects model. Monte Carlo simulation was used to describe the theoretical distribution of abiraterone pharmacokinetic profiles at a dose of 1000 mg once daily. Adherence of 36 prostate cancer patients treated with abiraterone was then evaluated by comparing the real abiraterone concentration measured in each patient during follow-up visit with the theoretical distribution of profiles based on simulations. Patients whose abiraterone levels were ˂5th or ˃95th percentile of the distribution of simulated profiles were considered to be non-adherent. RESULTS: Based on this evaluation, 13 patients (36%) have been classified as non-adherent. We observed significant association (P = .0361) between richness of the breakfast and rate of non-adherence. Adherent patients reported significantly better overall condition in self-assessments (P = .0384). A trend towards a higher occurrence of adverse effects in non-adherent patients was observed. CONCLUSIONS: We developed an abiraterone population pharmacokinetic model and proposed an advanced approach to medical adherence evaluation. Due to the need for administration under fasting conditions, abiraterone therapy is associated with a relatively high rate of non-adherence.
- MeSH
- adherence k farmakoterapii * statistika a číselné údaje MeSH
- androsteny * farmakokinetika aplikace a dávkování terapeutické užití MeSH
- antitumorózní látky farmakokinetika aplikace a dávkování MeSH
- biologické modely * MeSH
- dospělí MeSH
- interakce mezi potravou a léky MeSH
- lidé středního věku MeSH
- lidé MeSH
- metoda Monte Carlo MeSH
- nádory prostaty * farmakoterapie MeSH
- omezení příjmu potravy MeSH
- prospektivní studie MeSH
- senioři MeSH
- terapeutická ekvivalence MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Avelumab 800 or 1,200 mg was administered continuously every 3 weeks with standard doses of cisplatin + gemcitabine in patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous NSCLC. Dual primary endpoints were dose-limiting toxicity (DLT; phase Ib) and confirmed objective response (phase Ib/II). RESULTS: In phase Ib, urothelial carcinoma and NSCLC cohorts received avelumab 800 mg (n = 13 and n = 6, respectively) or 1,200 mg (n = 6 each) + chemotherapy. In evaluable patients with urothelial carcinoma treated with avelumab 800 or 1,200 mg + chemotherapy, DLT occurred in 1/12 (8.3%) and 1/6 (16.7%), respectively; no DLT occurred in the NSCLC cohort. In phase II, 35 additional patients with urothelial carcinoma received avelumab 1,200 mg + chemotherapy. Across all treated patients, safety profiles were similar irrespective of avelumab dose. Objective response rates (95% confidence internal) with avelumab 800 or 1,200 mg + chemotherapy, respectively, across phase Ib/II, were 53.8% (25.1-80.8) and 39.0% (24.2-55.5) in urothelial carcinoma, and 50.0% (11.8-88.2) and 33.3% (4.3-77.7) in NSCLC. CONCLUSIONS: Preliminary efficacy and safety findings with avelumab + chemotherapy in urothelial carcinoma and NSCLC were consistent with previous studies of similar combination regimens. Conclusions about clinical activity are limited by small patient numbers. SIGNIFICANCE: This phase Ib/II trial evaluated avelumab (immune checkpoint inhibitor) administered concurrently with standard first-line chemotherapy in patients with advanced urothelial carcinoma or advanced nonsquamous NSCLC without actionable mutations. Efficacy and safety appeared consistent with previous studies of similar combinations, although patient numbers were small.
- MeSH
- cisplatina aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- deoxycytidin analogy a deriváty aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- dospělí MeSH
- gemcitabin MeSH
- humanizované monoklonální protilátky * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- karboplatina aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- karcinom z přechodných buněk farmakoterapie patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory plic * farmakoterapie patologie MeSH
- nemalobuněčný karcinom plic * farmakoterapie patologie MeSH
- pemetrexed terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- protokoly antitumorózní kombinované chemoterapie * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- urologické nádory farmakoterapie patologie 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
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.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu u mužů * patologie mortalita terapie farmakoterapie MeSH
- prognóza 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
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- cílená molekulární terapie MeSH
- individualizovaná medicína MeSH
- nádory terapie MeSH
- Publikační typ
- úvodní články MeSH
PURPOSE: Immune checkpoint inhibitors (ICIs) dramatically changed the prognosis of patients with NSCLC. Unfortunately, a reliable predictive biomarker is still missing. Commonly used biomarkers, such as PD-L1, MSI, or TMB, are not quite accurate in predicting ICI efficacy. METHODS: In this prospective observational cohort study, we investigated the predictive role of erythrocytes, thrombocytes, innate and adaptive immune cells, complement proteins (C3, C4), and cytokines from peripheral blood of 224 patients with stage III/IV NSCLC treated with ICI alone (pembrolizumab, nivolumab, and atezolizumab) or in combination (nivolumab + ipilimumab) with chemotherapy. These values were analyzed for associations with the response to the treatment and survival endpoints. RESULTS: Higher baseline Tregs, MPV, hemoglobin, and lower monocyte levels were associated with favorable PFS and OS. Moreover, increased baseline basophils and lower levels of C3 predicted significantly improved PFS. The levels of the baseline immature granulocytes, C3, and monocytes were significantly associated with the occurrence of partial regression at the first restaging. Multiple studied parameters (n = 9) were related to PFS benefit at the time of first restaging as compared to baseline values. In addition, PFS nonbenefit group showed a decrease in lymphocyte count after three months of therapy. The OS benefit was associated with higher levels of lymphocytes, erythrocytes, hemoglobin, MCV, and MPV, and a lower value of NLR after three months of treatment. CONCLUSION: Our work suggests that parameters from peripheral venous blood may be potential biomarkers in NSCLC patients on ICI. The baseline values of Tregs, C3, monocytes, and MPV are especially recommended for further investigation.
- MeSH
- antigeny CD274 MeSH
- biologické markery MeSH
- hemoglobiny terapeutické užití MeSH
- imunofenotypizace MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- lidé MeSH
- nádory plic * MeSH
- nemalobuněčný karcinom plic * MeSH
- nivolumab terapeutické užití MeSH
- prospektivní studie MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
S příchodem imunoterapie v léčbě nemalobuněčného karcinomu plic došlo k prodloužení života velké části nemocných. Pokud organismus nemocného reaguje na léčebné impulsy a podaří se probudit protinádorovou imunitu, je to úspěch. V praxi jsme ale svědkem situací, kdy se to přes veškerou snahu nedaří podle našich plánů a nemocný neprofituje z této léčby. Stále existuje mnoho otázek, proč tomu tak je. Jednou z teorií, proč určitá skupina pacientů má z léčby prospěch, a jiná nikoli, je složení střevního mikrobiomu. Naše kazuistika dokládá krásnou léčebnou odpověď u nemocné s adenokarcinomem, která podstoupila fekální transplantaci. A po roce od diagnózy začínáme být optimisty.
The advent of immunotherapy in the treatment of non-small cell lung cancer has prolonged the lives of a large proportion of patients. If the patient’s body responds to treatment and manages to activate anti-tumor immunity, it is considered a success. However, in practice, we often encounter situations where, despite our best efforts, things do not go as planned and the patient does not benefit from the treatment. Many questions remain as to why this is the case. One theory suggests that the composition of the gut microbiome may determine why certain groups of patients benefit while others do not. Our case report shows a significant treatment response in a patient with adenocarcinoma who underwent fecal transplantation. A year after diagnosis, we are becoming optimistic.
- Klíčová slova
- pembrolizumab,
- MeSH
- fekální transplantace metody MeSH
- imunoterapie klasifikace metody MeSH
- inhibitory kontrolních bodů * farmakologie klasifikace terapeutické užití MeSH
- lidé MeSH
- nemalobuněčný karcinom plic * farmakoterapie MeSH
- senioři MeSH
- střevní mikroflóra účinky léků MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
