STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters? SUMMARY ANSWER: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility. WHAT IS KNOWN ALREADY: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years. STUDY DESIGN, SIZE, DURATION: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy. LIMITATIONS, REASONS FOR CAUTION: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited. WIDER IMPLICATIONS OF THE FINDINGS: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

• MeSH
• analýza spermatu MeSH
• azoospermie farmakoterapie   MeSH
• cyklofosfamid * terapeutické užití   MeSH
• dakarbazin terapeutické užití   MeSH
• dítě MeSH
• doxorubicin terapeutické užití   škodlivé účinky   MeSH
• etoposid terapeutické užití   aplikace a dávkování   MeSH
• folikuly stimulující hormon krev   MeSH
• Hodgkinova nemoc * farmakoterapie   MeSH
• inhibiny krev   MeSH
• lidé MeSH
• mladiství MeSH
• motilita spermií účinky léků   MeSH
• oligospermie farmakoterapie   MeSH
• počet spermií MeSH
• prednison terapeutické užití   aplikace a dávkování   MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• vinkristin terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Východiska: V současné době neexistuje žádná léčba, kterou lze jednoznačně doporučit v indikaci léčby pokročilého melanomu další, tj. 2. nebo 3. linie po selhání moderní imunoterapie a/nebo cílené léčby. Jednou z možností je chemoterapie, jejíž úloha je ale jak z důvodu špatných historických zkušeností, tak z důvodu nedostatku důkazů o účinnosti po předchozí léčbě novodobými preparáty zpochybňována. Soubor pacientů a metody: Na našem pracovišti se nám podařilo shromáždit soubor 23 pacientů s pokročilým kožním melanomem, u kterých došlo v letech 2017–2023 k selhání moderní systémové léčby na bázi imunoterapie anti-PD-1 protilátkou nebo k selhání cílené léčby BRAFi (+MEKi). U všech těchto pacientů byla následně indikována monochemoterapie dakarbazinem. Léčebný efekt byl hodnocen podle kritérií RECIST/iRECIST a máme k dispozici i data o přežití u všech pacientů. Výsledky: V našem souboru jsme prokázali velmi častý výskyt léčebných odpovědí (3× kompletní remise, 6× parciální remise, četnost léčebných odpovědí 39 %, 2× stabilní onemocnění), a také dlouhou dobou jejich trvání. Celkové přežití od zahájení terapie 2., resp. 3. linie dakarbazinem v tomto souboru činí 14,7 měsíce a doba do progrese 9,3 měsíce. V případech, kdy bylo dosaženo klinického benefitu (kompletní remise, parciální remise nebo stabilní onemocnění – 11×, 48 %) pak činí hodnoty přežití bez progrese 16,4 měsíce a celkové přežití 23,3 měsíce. Závěr: Tyto skvělé výsledky ukazují, že úlohu chemoterapie v této indikaci nelze zpochybňovat. Zároveň také vyvolávají otázky, čím jsou tyto až neočekávatelně dobré výsledky způsobeny a zda např. předchozí imunoterapie nemá senzibilizační a potenciační efekt pro následnou chemoterapii.

Background: Currently, there is no standard option that can be routinely recommended for the treatment of advanced melanoma after failure of modern immunotherapy and/or targeted therapy. Chemotherapy is an option, but its role is considered to be questionable. These doubts are based on historical experiences with chemotherapy, however, there is a lack of evidence of chemotherapy effectiveness after previous treatment with modern systemic therapy. Patients and methods: At our institution, we managed to collect a set of 23 patients with advanced cutaneous melanoma who failed modern systemic treatment based on anti-PD-1 antibody immunotherapy or after failure of BRAFi (+MEKi) targeted treatments in the years 2017–2023. Dacarbazine monochemotherapy was indicated as further line systemic treatment for all these patients. The treatment effect was evaluated according to the RECIST/iRECIST criteria, and we also earned survival data for all patients. Results: In our group, we observed substantial treatment response rate (complete remission 3times, partial remission 6times, response rate 39 %, stable disease twice), as well as long duration of those responses. Overall survival from the start of the therapy on second- or third-line dacarbazine in this group was 14.7 months and progression free survival was 9.3 months. In cases where a clinical benefit was achieved (complete remission, partial remission, or stable disease – 11times, 48%), the progression-free survival and overall survival values are 16.4 and 23.3 months respectively. Conclusion: These excellent results show that the role of chemotherapy in this indication should not be doubted. Obviously, this raises questions about the reasons why these unexpectedly good results were achieved. We should seriously consider the possibility that previous immunotherapy does have a sensitizing and potentiating effect for subsequent chemotherapy.

• MeSH
• cílená molekulární terapie MeSH
• dakarbazin * farmakologie   terapeutické užití   MeSH
• imunoterapie MeSH
• lidé MeSH
• melanom * farmakoterapie   MeSH
• neúspěšná terapie MeSH
• pozitronová emisní tomografie metody   MeSH
• Check Tag
• lidé MeSH

Prezentovány jsou dvě kazuistiky pacientů s metastazujícím medulárním karcinomem štítné žlázy, kteří podstoupili léčbu tyrosinkinázovými inhibitory. Srovnávána je účinnost léčby, na jedné straně dlouhodobá léčebná odpověď u pacienta se včasným záchytem metastatického rozsevu a na druhé straně rychlá progrese u nemocného s pozdní diagnózou a velkým rozsahem onemocnění.

Two case reports of patients with metastatic medullary thyroid carcinoma treated with tyrosine kinase inhibitors as a 1st line treatment are presented. The effectiveness of the treatment is compared - long-term treatment response in patient with early detected metastatic disease versus quick progression in patient with late diagnosis of advanced carcinoma and large proportion of metastatic lesions.

• Klíčová slova
• vandetanib, cabozantinib,
• MeSH
• bisfosfonáty terapeutické užití   MeSH
• časná diagnóza MeSH
• cílená molekulární terapie MeSH
• dakarbazin terapeutické užití   MeSH
• dospělí MeSH
• fatální výsledek MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• klinické zhoršení MeSH
• lidé středního věku MeSH
• lidé MeSH
• medulární karcinom * chirurgie   farmakoterapie   radioterapie   MeSH
• metastázy nádorů MeSH
• nádory štítné žlázy * chirurgie   farmakoterapie   radioterapie   MeSH
• opožděná diagnóza MeSH
• paliativní péče MeSH
• progrese nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: To improve the long-term tumour control in early, unfavourable Hodgkin Lymphoma, the German Hodgkin Study Group (GHSG) HD14 trial compared four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with an intensified chemotherapy regimen consisting of two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (escalated BEACOPP) plus two cycles of ABVD. The final analysis of the trial showed a significant advantage in terms of freedom from treatment failure (difference 7·2% [95% CI 3·8-10·5] at 5 years) for patients who received two cycles of escalated BEACOPP and two cycles of ABVD. However, there was no difference in overall survival between the two groups. To evaluate long-term efficacy and toxicity of this strategy, we did a follow-up analysis. METHODS: Patients aged 18-60 years with performance status of 2 or less and primary diagnosis of early, unfavourable Hodgkin lymphoma (all histologies) were included in an international, randomised, open-label, phase 3 trial. Patients were randomly assigned to receive four cycles of ABVD (ABVD group) or two cycles of escalated BEACOPP and two cycles of ABVD (2 + 2 group), both groups also received 30 Gy involved field radiotherapy. The ABVD dosing regimen was doxorubicin 25 mg/m2 (days 1 and 15), bleomycin 10 mg/m2 (days 1 and 15), vinblastine 6 mg/m2 (days 1 and 15), and dacarbazine 375 mg/m2 (days 1 and 15), repeated on day 29. The escalated BEACOPP dosing regimen was cyclophosphamide 1250 mg/m2 (day 1), doxorubicin 35 mg/m2 (day 1), etoposide 200 mg/m2 (days 1-3), procarbazine 100 mg/m2 (days 1-7), prednisone 40 mg/m2 (days 1-14), vincristine 1·4 mg/m2 (day 8; maximum 2 mg), and bleomycin 10 mg/m2 (day 8), repeated on day 22. After closure of the ABVD group according to prespecified rules, patients were assigned to receive two cycles of escalated BEACOPP and two cycles of ABVD (non-randomised 2 + 2 group), which continued until the end of the predefined 5-year recruitment period. In this prespecified long-term follow-up analysis, we aimed to evaluate the secondary endpoints progression-free survival, overall survival, and long-term toxicity. To this end, we did a descriptive intention-to-treat analysis of all qualified HD14 patients and on the predefined subsets of randomised qualified HD14 patients and patients in the non-randomised 2 + 2 group. The trial was registered on the International Standard Randomised Controlled Trial database, 04761296. FINDINGS: Between Jan 28, 2003, and Dec 29, 2009, 1686 patients were randomly assigned to the ABVD group (847 [50·2%] patients) and the 2 + 2 group (839 [49·8%] patients). 370 additional patients were recruited to the non-randomised 2 + 2 group. 1550 (92%) randomly assigned patients (median observation time 112 months [IQR 80-132]) and 339 (92%) patients in the non-randomised 2 + 2 group (median observation time 74 months [58-100]) were included in the qualified analysis set. 10-year overall survival in the randomly assigned patients was 94·1% (95% CI 92·0-95·7) for the ABVD group and 94·1% (91·8-95·7) for the 2 + 2 group (HR 1·0 [95% CI 0·6-1·5]; p=0·88). 8-year overall survival in the non-randomised 2 + 2 group was 95·1% (95% CI 91·6-97·2). 10-year progression-free survival in the randomly assigned patients was 85·6% (95% CI 82·6-88·1) for the ABVD group and 91·2% (88·4-93·3) for the 2 + 2 group (HR 0·5% [95% CI 0·4-0·7]; p=0·0001), accounting for a significant difference of 5·6% (95% CI 1·9-9·2) favouring the 2 + 2 group (p=0·0001). In the non-randomised 2 + 2 group, 8-year progression-free survival was 94·5% (95% CI 91·1-96·6). Standardised incidence ratios of second primary malignancies were similar between the ABVD group (2·3 [95% CI 1·6-3·1]) and the 2 + 2 group (2·5 [1·8-3·4]; Gray's p=0·80). Standardised incidence ratio of second primary malignancies was 3·1 (95% CI 1·7-5·0) in the non-randomised 2 + 2 group. INTERPRETATION: This long-term analysis confirms superior tumour control in the 2 + 2 group compared with the ABVD group without translating into an overall survival difference. At longer follow-up, there is no difference regarding second primary malignancies between groups. In conclusion, the 2 + 2 regimen spares a significant number of patients from the burden of relapse and additional treatment without increased long-term toxicity. FUNDING: Deutsche Krebshilfe eV and Swiss Federal Government.

• MeSH
• bleomycin aplikace a dávkování   terapeutické užití   MeSH
• cyklofosfamid aplikace a dávkování   terapeutické užití   MeSH
• dakarbazin aplikace a dávkování   terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   terapeutické užití   MeSH
• etoposid aplikace a dávkování   terapeutické užití   MeSH
• Hodgkinova nemoc farmakoterapie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• prednison aplikace a dávkování   terapeutické užití   MeSH
• prokarbazin aplikace a dávkování   terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• sekundární malignity epidemiologie   MeSH
• staging nádorů metody   MeSH
• vinblastin aplikace a dávkování   terapeutické užití   MeSH
• vinkristin aplikace a dávkování   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Německo MeSH

Approximately one-third of patients diagnosed with Hodgkin lymphoma presenting with Stage IV disease do not survive past 5 years. We present updated efficacy and safety analyses in high-risk patient subgroups, defined by Stage IV disease or International Prognostic Score (IPS) of 4-7, enrolled in the ECHELON-1 study that compared brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A + AVD) versus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as first-line therapy after a median follow-up of 37.1 months. Among patients treated with A + AVD (n = 664) or ABVD (n = 670), 64% had Stage IV disease and 26% had an IPS of 4-7. Patients with Stage IV disease treated with A + AVD showed consistent improvements in PFS at 3 years as assessed by investigator (hazard ratio [HR], 0.723; 95% confidence interval [CI], 0.537-0.973; p = 0.032). Similar improvements were seen in the subgroup of patients with IPS of 4-7 (HR, 0.588; 95% CI, 0.386-0.894; p = 0.012). The most common adverse events (AEs) in A + AVD-treated versus ABVD-treated patients with Stage IV disease were peripheral neuropathy (67% vs. 40%) and neutropenia (71% vs. 55%); in patients with IPS of 4-7, the most common AEs were peripheral neuropathy (69% vs. 45%), neutropenia (66% vs. 55%), and febrile neutropenia (23% vs. 9%), respectively. Patients in high-risk subgroups did not experience greater AE incidence or severity than patients in the total population. This updated analysis of ECHELON-1 shows a favorable benefit-risk balance in high-risk patients.

• MeSH
• brentuximab vedotin farmakologie   terapeutické užití   MeSH
• dakarbazin farmakologie   terapeutické užití   MeSH
• dospělí MeSH
• doxorubicin farmakologie   terapeutické užití   MeSH
• Hodgkinova nemoc farmakoterapie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• protokoly protinádorové kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• rizikové faktory MeSH
• staging nádorů metody   MeSH
• vinblastin farmakologie   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Prezentujeme případ 72letého muže s leiomyosarkomem funikulus spermaticus. Pacient byl vyšetřen pro bolesti pravého třísla a zvětšení pravého hemiskrota. Fyzikální vyšetření prokázalo tuhou masu, která zasahovala až do dolní poloviny tříselného kanálu. Ultrazvukové vyšetření zjistilo solidní expanzi s heterogenní strukturou a akcentovanou vaskularizací. Byla provedena radikální orchiektomie s vysokou ligací funiculu. Histologicky byl verifikován nízce diferencovaný leiomyosarkom funikulus spermaticus, nádor patřící do skupiny paratestikulárních tumorů. Stagingové CT plic, retroperitonea a malé pánve neodhalilo postižení lymfatik či vzdálené metastázy. Pooperačně nebyla po zvážení na multioborovém semináři indikovaná adjuvantní onkologická terapie. Důvodem byla zejména radikalita chirurgického výkonu. Během dispenzarizace byl po třech letech zjištěn metastatický proces v retroperitoneálních uzlinách.

We present the case of a 72-year-old man with leiomyosarcoma of spermatic cord. The patient presented with pain in his right groin and enlarged right scrotum. Physical examination showed a rigid mass reaching the lower half of the inguinal canal and filling the right scrotum. Ultrasound examination revealed a solid expansion of the heterogeneous structure with accentuated vascularization. A high-ligation radical orchiectomy was performed. Histologic examination verified low-differentiated leiomyosarcoma of spermaticus funiculus belonging to the group of paratesticular tumors. CT scan of the lungs, retroperitoneum and small pelvis showed no metastatic process or lymphadenopathy. The oncologists did not indicate an adjuvant oncological therapy, the reason being radical tumour removal. After 3 years, metastatic process into the retroperitoneal nodes was verified.

• MeSH
• dakarbazin terapeutické užití   MeSH
• doxorubicin terapeutické užití   MeSH
• leiomyosarkom * patologie   MeSH
• lidé MeSH
• nádory mužských pohlavních orgánů * diagnóza   patologie   terapie   MeSH
• orchiektomie MeSH
• progrese nemoci MeSH
• recidiva MeSH
• semenný provazec patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• Klíčová slova
• pazopanib,
• MeSH
• dakarbazin terapeutické užití   MeSH
• doxorubicin terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• metastázy nádorů terapie   MeSH
• neoadjuvantní terapie metody   MeSH
• protinádorové látky terapeutické užití   MeSH
• radiochirurgie metody   MeSH
• sarkom * terapie   MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• souhrny MeSH

V posledních letech došlo k výraznému prodloužení doby přežití pacientů s metastazujícím maligním melanomem díky moderní imunoterapii s využitím protilátek zaměřeným proti kontrolním bodům imunitní reakce a díky zavedení cílené léčby BRAF a MEK inhibitory. První používaná protilátka byla anti-CTLA4 protilátka ipilimumab, která byla následována efektivnějšími anti-PD1 protilátkami (nivolumab, pembrolizumab), a nejnověji jsou testovány anti-PD-L1 protilátky. Ještě lepší léčebnou odpověď potvrzují výsledky klinických studií s kombinacemi jednotlivých protilátek a kombinacemi protilátek s cílenou léčbou.

In recent years, there has been a significant increase in the survival of patients with metastatic malignant melanoma owing to modern immunotherapy using antibodies against immune checkpoints and the introduction of targeted therapy with BRAF and MEK inhibitors. The first antibody used was the anti-CTLA4 antibody ipilimumab which was followed by more effective anti-PD1 antibodies (nivolumab, pembrolizumab); most recently, anti-PD-L1 antibodies have been tested. An even better therapeutic response has been confirmed by the results of clinical trials investigating combinations of individual antibodies and combinations of antibodies with targeted therapy.

• Klíčová slova
• pembrolizumab,
• MeSH
• dakarbazin terapeutické užití   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• ipilimumab aplikace a dávkování   MeSH
• lidé MeSH
• melanom * chirurgie   terapie   MeSH
• metastázy nádorů diagnostické zobrazování   farmakoterapie   radioterapie   terapie   MeSH
• nádory ledvin diagnostické zobrazování   sekundární   MeSH
• počítačová rentgenová tomografie MeSH
• progrese nemoci MeSH
• protinádorové látky imunologicky aktivní aplikace a dávkování   farmakologie   škodlivé účinky   MeSH
• trup diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Primárny slizničný melanóm je v našej populácii zriedkavé onkologické ochorenie. V oblasti hlavy a krku vzniká najčastejšie v sinonazálnom regióne. Autori opisujú prípad 80-ročnej pacientky, ktorá bola prijatá do ORL centra JAS s anamnézou pol roka trva - júceho opakovaného spontánneho krvácania z nosa. Rinoskopicky bol v ľavom nosovom priechode viditeľný polypovitý tumor priemeru 1,5 cm, ktorý vyrastal z prednej tretiny dolnej lastúry. Histopatologické vyšetrenie lézie potvrdilo infiltráciu sliznice melanómom. Pacientka bola zaradená do onkodispenzárnej starostlivosti. Po roku mala v mieste pôvodného tumoru diagnostikovanú lokálnu recidívu. Zároveň mala potvrdené metastázy v krč nej lymfatickej uzline a v pľúcach. Po zahájení systémovej chemoterapie a paliatívnej rádioterapie zakrátko exitovala. Naša kazuistika poukazuje, že melanóm sliznice nosa je agresívny nádor so závažnou prognózou. V dôsledku nešpecifických príznakov pri - chádzajú pacienti často k lekárovi neskoro, čím sa oneskoruje rozpoznanie a liečba ochorenia. Prítomnosť unilaterálnych a progredujúcich symptómov, ako sú krvácanie a pocit obštrukcie nosového priechodu, a to najmä u starších osôb, by mali nútiť myslieť aj na možnú diagnózu melanómu nosovej sliznice.

Primary mucosal melanoma is a rare oncologic disease in our population. In the head and neck region, the majority of them arise from the sinonasal cavity. The authors describe an 80-year-old woman, who was admitted to the ENT centrum with a history of repeated spontaneous bleeding from the nose. It has manifested for six months. Rhinoscopy revealed a polypoid tumor up to 15 mm in diameter, which grew out from the anterior one-third of left inferior nasal concha. Histopathology confirmed a melanoma infiltration of the nasal mucosa. Subsequently, the patient was referred to oncodispensary care. After a year later, a local recurrence occurred at the site of the primary lesion. Furthermore, she was found to have tumor metastases in the cervical lymph node and the lung. She died shortly after the onset of systemic chemotherapy and paliative radiotherapy. Our case report shows, a melanoma of the nasal mucosa is an aggressive tumor with unfavorable prognosis. Due to non-specific symptoms, many patients visit a doctor too late, which results in delay of recognition and treatment of disease. An evidence of unilateral and progressive symptoms, such as epistaxis and nasal airway obstruction, particularly in the elderly, should be suspected also for mucosal melanoma of the nasal cavity

• MeSH
• dakarbazin terapeutické užití   MeSH
• epistaxe MeSH
• lidé MeSH
• melanom chirurgie   mortalita   sekundární   terapie   MeSH
• nádory hlavy a krku * diagnostické zobrazování   diagnóza   farmakoterapie   chirurgie   krev   MeSH
• senioři MeSH
• sliznice * patologie   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Melanoma is one of the most aggressive cancers which has very low response rate and survival rate. Melanoma cells are known to be inherently resistant to the chemotherapy which results in poor outcomes and even failure of the therapy. For this reason, a better understanding of underlying mechanism of melanoma pathogenesis and resistance is required, so that more efficient and novel therapeutic strategies can be developed. Survivin is a protein which is overexpressed in melanoma cells and is known to impart resistance to them against apoptosis. Also, melanoma cells overexpress Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) angiogenic growth factors which lead to aggressive angiogenesis in melanoma cells thereby making the treatment more challenging. This hypothesis presents a combinatorial approach against melanoma where an anti-survivin agent and an anti-angiogenic agent are combined with a chemotherapeutic drug and loaded in surface functionalized liposomes in order to target specific mechanisms of melanoma, thus overcoming its resistance. Thus, the study aims to overcome the resistance of melanoma cells by developing a wise combination of drugs and achieve a higher response rate in resistant melanoma model, which is usually not achieved with the existing treatment modalities.

• MeSH
• antigeny CD44 metabolismus   MeSH
• dakarbazin terapeutické užití   MeSH
• fibroblastový růstový faktor 2 metabolismus   MeSH
• inhibitory angiogeneze chemie   MeSH
• inhibitory apoptózy chemie   MeSH
• lidé MeSH
• liposomy chemie   MeSH
• melanom metabolismus   terapie   MeSH
• nádory kůže terapie   MeSH
• nanočástice chemie   MeSH
• patologická angiogeneze MeSH
• proliferace buněk MeSH
• protinádorové látky chemie   MeSH
• survivin MeSH
• teoretické modely MeSH
• vaskulární endoteliální růstový faktor A metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH