Development and Evaluation of an FDM Printed Nasal Device for CPZ Solid Nanoparticles.

Nasal drug delivery has been a focus of scientific interest for decades. A number of drug delivery systems and devices are available and have been highly successful in providing better and more comfortable therapy. The benefits of nasal drug delivery are not in question. The nasal surface provides an excellent context for the targeted delivery of active substances. In addition to the large nasal surface area and intensive absorption, the active substances delivered through the nose overcome the blood-brain barrier and can be delivered directly to the central nervous system. Formulations for nasal administration are typically solutions or liquid dispersed systems such as emulsions or suspensions. Formulation techniques for nanostructures have recently undergone intensive development. Solid-phase heterogeneous dispersed systems represent a new direction in pharmaceutical formulations. The wide range of possible examples and the variety of excipients allow for the delivery of a wide range of active ingredients. The aim of our experimental work was to develop a solid drug delivery system that possesses all of the above-mentioned advantageous properties. In developing solid nanosystems, we not only exploited the advantages of size but also the adhesive and penetration-enhancing properties of excipients. During formulation, several amphiphilic compounds with adhesion properties and penetration enhancing effects were incorporated. We used chlorpromazine (CPZ), which is mainly used in the treatment of psychotic disorders such as schizophrenia and bipolar disorder. Chlorpromazine has been previously investigated by our team in other projects. With the availability of previous methods, the analytical characterization of the drug was carried out effectively. Due to the frequent and severe side effects of the drug, the need for therapeutic dose reduction is indisputable. In this series of experiments, we succeeded in constructing drug delivery systems. Finely divided Na nanoparticles were formed using a Büchi B90 nanospray dryer. An important step in the development of the drug carrier was the selection of suitable inert carrier compounds. Particle size determination and particle size distribution analysis were performed to characterize the prepared nanostructures. As safety is the most important aspect of any drug formulation, all components and systems were tested with different biocompatibility assays. The tests performed demonstrated the safe applicability of our systems. The bioavailability of chlorpromazine was studied as a function of the ratio of the active ingredient administered nasally and intravenously. As described above, most nasal formulations are liquids, but our system is solid, so there is currently no tool available to accurately target this system. As a supplement of the project, a nasal dosing device was developed, corresponding to the anatomical structure; a prototype of the device was made using 3D FDM technology. Our results lay the foundation for the design and industrial scaling of a new approach to the design and production of a high-bioavailability nasal medicinal product.

Low socioeconomic position is a risk factor for delay to treatment and mortality of testicular cancer patients in Hungary, a prospective study.

BACKGROUND: In Hungary, the mortality rate for testicular germ cell cancer (TGCC) is 0,9/100000 which is significantly higher than the EU average. We prospectively evaluated the effect of socioeconomic position on patient delay and therapy outcomes. METHODS: Questionnaires on subjective social status (MacArthur Subjective Status Scale), objective socioeconomic position (wealth, education, and housing data), and on patient's delay were completed by newly diagnosed TGCC patients. RESULTS: Patients belonged to a relatively high socioeconomic class, a university degree was double the Hungarian average, Cancer-specific mortality in the highest social quartile was 1.56% while in the lowest social quartile 13.09% (p = 0.02). In terms of patient delay, 57.2% of deceased patients waited more than a year before seeking help, while this number for the surviving patients was 8.0% (p = 0.0000). Longer patient delay was associated with a more advanced stage in non-seminoma but not in seminoma, the correlation coefficient for non-seminoma was 0.321 (p < 0.001). For patient delay, the most important variables were the mother's and patient's education levels (r = - 0.21, p = 0.0003, and r = - 0.20, p = 0.0005), respectively. Since the patient delay was correlated with the social quartile and resulted in a more advanced stage in non-seminoma, the lower social quartile resulted in higher mortality in non-seminoma patients (p = 0.005) but not in seminoma patients (p = 0.36) where the patient delay was not associated with a more advanced stage. CONCLUSIONS: Based on our result, we conclude that to improve survival, we should promote testicular cancer awareness, especially among the most deprived populations, and their health care providers.

[Modern treatment of metastatic hormone-sensitive prostate cancer]. / Metasztatikus hormonérzékeny prosztatadaganat korszeru kezelése.

The treatment of metastatic prostate cancer can be divided into two pathophysiological phases: hormone-sensitive and castration-resistant phases. Huggins' observation in the year 1941, which was awarded with the Nobel Prize in 1966, has a key role in treatment during the hormone-sensitive phase, stating that if the testicles are removed, the size of the prostate cancer decreases. Inducing androgen deprivation, i.e., testosterone depletion is the basic treatment of metastatic prostate cancer that patients have to receive life-long. In the past eight years, five new agents have been approved besides docetaxel in the treatment of metastatic castration-resistant prostate cancer: sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, and radium-223. With the sequential application of these agents, significant improvement can be achieved in survival. Besides the latest developments, the hormone-sensitive phase has become the focus of attention, especially in the treatment of patients with de novo metastases and poor prognosis. Many studies have proven the outstanding efficacy of adding early docetaxel and abiraterone to androgen deprivation therapy. The authors give a detailed overview of clinical studies leading to a paradigm change in treatment during the hormone-sensitive phase, and call attention to the difficulties encountered in Hungarian practice. Orv Hetil. 2018; 159(41): 1664-1671.

[The role of steroids in oncological practice]. / Szteroidok szerepe az onkológiai gyakorlatban.

Corticosteroids are a class of steroid hormones that are produced and disengage in the adrenal cortex. Traditionally natural and synthetic corticosteroids are used for diagnosing and treating dysfunctions of the adrenal cortex and treating inflammatory and immunological diseases. Their use is also widespread in oncological practice. Corticosteroids are indispensable in palliative care, in certain urgent oncological cases, as premedication of some chemotherapies and last but not least they have a key role in the secondary hormonal manipulations of metastatic castrate-resistant prostate cancer. The purpose of our review is to describe and compare the effects of different agents in oncological practice, to give a detailed account of the above mentioned indications and would also like to draw attention to the possible side effects of a long-term steroid treatment. Orv Hetil. 2017; 158(42): 1651-1657.

[Androgen receptor-mediated processes in castrate-resistant metastatic prostate cancer]. / Androgénreceptor mediálta folyamatok metasztatikus kasztrációrezisztens prosztatadaganatban.

In the past six years, five new drugs have been approved by the FDA for the treatment of metastatic castrate-resistant prostate cancer. While the disease itself still remains incurable, the sequential use of these drugs can significantly prolong survival while maintaining good quality of life. Research from the past decade made it clear that androgen receptor-mediated processes play a central part in the progression of the disease. Hormonal mechanisms related to androgen-receptors can remain active until late stages of the disease. A deeper understanding of these mechanisms has led to the introduction of new endocrine therapies, which resulted in a change of the nomenclature. The identification and remodelling of androgen receptor mutations that are responsible for primary and secondary resistance developing during the new therapies can pave the way to new and more efficient androgen receptor inhibitor treatments. The aim of the review is to present the pathophysiology of the androgen receptor signaling axis at the receptor level, to review FDA-approved drugs and to draw attention to the most promising developments in the treatment of this disease. Orv. Hetil., 2017, 158(2), 42-49.

[Immunotherapy in the treatment of genitourinary cancers]. / Immunterápia az urológiai daganatok kezelésében.

In this clinical review we provide information regarding advance and main achievements in the immunotherapy of genitourinary, particularly renal cell and prostate cancer. Nivolumab treatment became the new standard of care in locally advanced or metastatic renal cell cancer after failure on tyrosine kinase inhibitor treatment. Sipuleucel-T prolonged survival in patients with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer but had no effect on progression-free survival. Based on the results of phase I/II trials anti-PD-1/PD-L1 monoclonal antibodies are a new hope in the treatment of urothelial bladder cancer. Regarding germ cell tumors basic research is ongoing.

A case study on the potential angiogenic effect of human chorionic gonadotropin hormone in rapid progression and spontaneous regression of metastatic renal cell carcinoma during pregnancy and after surgical abortion.

BACKGROUND: Treatment possibilities of metastatic renal cell carcinoma (mRCC) have recently changed dramatically prolonging the overall survival of the patients. This kind of development brings new challenges for the care of mRCC. CASE PRESENTATION: A 22 year-old female patient with translocation type mRCC, who previously had been treated for nearly 5 years, became pregnant during the treatment break period. Follow-up examinations revealed a dramatic clinical and radiological progression of mRCC in a few weeks therefore the pregnancy was terminated. A few days after surgical abortion, CT examination showed a significant spontaneous regression of the pulmonary metastases, and the volume of the largest manifestation decreased from ca. 30 to 3.5 cm(3) in a week. To understand the possible mechanism of this spectacular regression, estrogen, progesterone and luteinizing hormone receptors (ER, PGR and LHR, respectively) immuno-histochemistry assays were performed on the original surgery samples. Immuno-histochemistry showed negative ER, PGR and positive LHR status suggesting the possible angiogenic effect of human chorionic gonadotropin hormone (hCG) in the background. CONCLUSION: We hypothesize that pregnancy may play a causal role in the progression of mRCC via the excess amount of hCG, however, more data are necessary to validate the present notions and the predictive role of LHR overexpression.

[Treatment strategies for advanced prostate cancer]. / Kezelési stratégiák elorehaladott prosztatadaganatban.

There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer.

Prediction of PSA Response after Dexamethasone Switch during Abiraterone Acetate + Prednisolone Treatment of Metastatic Castration-Resistant Prostate Cancer Patients.

BACKGROUND: The aim was to elaborate a predictive model to find responders for the corticosteroid switch (from prednisolone to dexamethasone) at the first prostate-specific antigen (PSA) progression (≥25% increase) during abiraterone acetate (AA) treatment of metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: If PSA has decreased (≥25%) after switch, patients were considered responders. Logistic regression of 19 dichotomized parameters from routine laboratory and patients' history was used to find the best model in a cohort of 67 patients. The model was validated in another cohort of 42 patients. RESULTS: The model provided 92.5% and 90.5% accuracy in the testing and the validation cohorts, respectively. Overall the accuracy was 91.7%. The AUC of ROC curve was 0.92 (95% CI 0.85-0.96). After a median follow-up of 27.9 (26.3-84) months, the median AA+dexamethasone treatment duration (TD) in non-responders and responders was 4.7 (3.1-6.5) and 11.1 (8.5-12.9) months and the median overall survival (OS) was 23.2 (15.6-25.8) and 33.5 (26.1-38) months, respectively. Multivariate Cox regression revealed that responsiveness was an independent marker of TD and OS. CONCLUSIONS: A high accuracy model was developed for mCRPC patients in predicting cases which might benefit from the switch. For non-responders, induction of the next systemic treatment is indicated.

miR-21, miR-29a, and miR-106b: serum and tissue biomarkers with diagnostic potential in metastatic testicular cancer.

The imperative need for sensitive and precise tools is underscored in cancer diagnostics, with biomarkers playing a pivotal role in facilitating early detection and tumor diagnosis. Despite their classical pathological classification, testicular tumors lack valuable markers, emphasizing the necessity to identify and apply serum tumor markers in clinical management. Unfortunately, existing biomarkers exhibit limited sensitivities and specificities. Recent years have witnessed the discovery of novel RNA molecules, presenting a potential breakthrough as diagnostic tools and promising biomarkers. This report presents compelling evidence supporting the detection of early testicular cancer by applying a set of nine microRNAs (miRNAs), establishing them as valuable serum biomarkers for diagnosis. We developed a standardized serum-based measurement protocol and conducted comprehensive statistical analyses on the dataset to underscore the diagnostic accuracy of the miRNA pool. Notably, with a sensitivity exceeding 93%, miR-21, miR-29a, and miR-106b surpass classical serum tumor markers in the context of testicular cancer. Specifically, these miRNAs are poised to enhance clinical decision-making in testicular cancer detection and hold the potential for assessing tumor growth in monitoring chemotherapy outcomes.

[Mutation frequency of homologous recombination repair genes in prostate adenocarcinomas]. / A homológ rekombinációs hibajavító rendszer szomatikus génmutációinak vizsgálata prosztata-adenokarcinómában, újgenerációs szekvenálással.

The best predictive marker for the expected efficacy of PARP inhibitor therapy is mutations in BRCA1/2 or other homologous recombination repair genes. These tests are part of routine molecular pathology diagnostics. Among 281 patients with prostate adenocarcinoma, somatic pathogenic mutations in one of these genes were identified in 21.4% of patients. In 28.5% of the patients, the test was unsuccessful; the main limitation of successful testing was the age of the paraffin blocks and low DNA concentration. In the case of BRCA1/2 testing, the success rate was significantly reduced for samples older than 5 years, while in tests involving a broader set of homologous recombination repair genes, the success rate was significantly reduced for samples older than 2 years. Therefore, it is very important to test high-risk prostate cancers at the time of primary diagnosis, and probably also liquid biopsy testing of circulating tumor DNA will play an important role in safe diagnosis in the near future.

Complex treatment of residual metastatic germ cell cancer: A single center experience.

BACKGROUND: Testicular cancer is the most common solid malignancy among men aged 15-35. Radical orchiectomy and platinum-based chemotherapy (BEP) are curative in the majority of patients, including advanced, metastatic cases. According to current urooncology guidelines all non-seminoma patients harbouring post-chemotherapy residual masses of ≥ 1 cm should undergo salvage retroperitoneal lymph node dissection (RPLND). However, only 10% of residual tumors contain viable disease. OBJECTIVE: To assess patient outcomes and complications considering different treatment regimens and clinical characteristics. MATERIALS AND METHODS: In a retrospective cross-sectional study patients (n=127) who underwent postchemotherapy RPLND between 2007 and 2023 at our referral center were evaluated. The patients received systemic treatment at various oncology centers. The number of BEP cycles received were occasionally different from standard. Only patients with normal postchemotherapy serum tumor markers and primary testicular or extragonadal germ cell neoplasms were included. Treatment groups were established according to the number of BEP cycles received, and the extent of RPLND (bilateral or modified template). Treatment outcomes and complications were assessed. RESULTS: Standard 3-4 courses of BEP were received by 100 (78,7%) patients, while 11 (8,7%) patients underwent less, and 16 (12,6%) more courses than standard. On histopathologic evaluation viable germ cell tumor, teratoma, and necrosis/fibrosis was present in 26 (20,5%), 67 (52,7%) and 34 (26,8%) of specimen, respectively. In the 5-6 BEP series subgroup high rate of viable disease (37,5%) was found and significantly more nephrectomies were performed, than other chemotherapy subgroups. Extratesticular GCT, viable disease in residual mass or progression after RPLND indicated lower survival. Mild (Clavien-Dindo I-II) or no postoperative complications were reported in 93,7% of cases. CONCLUSIONS: The study suggests no significant benefit from exceeding 3-4 courses of BEP. Timely salvage RPLND should be performed in high volume centers for optimal treatment outcomes with acceptable complication rates. Adherence to the Heidenreich criteria is advisable where practical.

[Immune combination possibilities in the first-line treatment of metastatic renal cell cancer]. / Immunkombinációs lehetoségek a metasztatikus világossejtes vesedaganat elso vonalas kezelésében.

First-line treatment of metastatic renal cancer can be divided into three main phases. The cytokine era was replaced by targeted therapies in 2006 with the introduction of tyrosine kinase inhibitors. Until 2018, the standard first-line therapy was the use of sunitinib or pazopanib. Over the past decade, numerous attempts have been made to combine these drugs, which are already approved or in development, but these attempts have not been successful, primarily because of intolerable toxicity. In 2018, we reached a new stage in the treatment of metastatic renal tumors. This year, the combination immunotherapy of ipilimumab and nivolumab was approved. Since then, the combination of immunotherapy and targeted therapies has led to success. The main objective of our summary is to present in chronological order the clinical trials of combination therapies already approved in Europe, as well as the most recent phase III clinical trials. It is also intended to provide a brief practical guide on how to decide on first-line therapy based on the results of these trials.

A new method to quantify the effect of co-medication on the efficacy of abiraterone in metastatic castration-resistant prostate cancer patients.

Background and Objective: Patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA) have co-morbidities treated with different drugs. The aim was to quantify the potential effect of co-medications on AA treatment duration (TD) and overall survival (OS). Methods: A new parameter, called "individual drug score" (IDS) was calculated by summing the "drug score"-s (DS) of all co-medications for each patient. The DS was determined by quantifying the effect of a given co-drug on enzymes involved in steroidogenesis and metabolism of AA. The correlation between log (IDS) and TD was tested by non-linear curve fit. Kaplan-Meier method and multivariate Cox regression was used for analysis of TD and OS. Results: The IDS and TD of AA+prednisolone showed a dose-response correlation (n = 166). Patients with high IDS had significantly longer TD and OS (p <0.001). In multivariate analysis IDS proved to be an independent marker of TD and OS. The same analysis was performed in a separate group of 81 patients receiving AA+dexamethasone treatment. The previously observed relationships were observed again between IDS and TD or OS. After combining the AA+prednisolone and AA+dexamethasone groups, analysis of the IDS composition showed that patients in the high IDS group not only used more drugs (p <0.001), but their drugs also had a higher mean DS (p = 0.001). Conclusion: The more co-drugs with high DS, the longer the duration of AA treatment and OS, emphasizing the need for careful co-medication planning in patients with mCRPC treated with AA. It is recommended that, where possible, co-medication should be modified to minimize the number of drugs with negative DS and increase the number of drugs with high DS. Our new model can presumably be adapted to other drugs and other cancer types (or other diseases).

Personalized Nasal Protective Devices: Importance and Perspectives.

Nowadays, in addition to diseases caused by environmental pollution, the importance of personalized protection against various infectious agents has become of paramount importance. Besides medicine, several technical and technological studies have been carried out to develop suitable devices. One such revolutionary solution is the use of personalized nasal filters, which allow our body to defend itself more effectively against external environmental damage and pathogens. These filters are small devices that are placed in the nose and specifically filter the inhaled environmental contaminants, allergens, and microorganisms according to individual needs. These devices not only play a key role in maintaining our health but also contribute to environmental protection, reducing the inhalation of pollutants and their harmful impact on the natural environment. Another advantage of personalized filters is that they also provide an opportunity to strengthen our individual immune systems. The use of personalized filters allows medicine to provide optimized protection for everyone, focusing on individual genetic and immunological conditions. The momentum behind the development and research of personalized nasal filters has reached astonishing proportions today. Nowadays, many research groups and medical institutions are working to create new materials, nanotechnologies, and bioinformatics solutions in order to create even more effective personalized nasal filters that can also be shaped easily and safely. Considering the needs of the users is at least as important during development as the efficiency of the device. These two properties together determine the success of the product. Industry research focuses not only on improving the efficiency of devices, but also on making them more responsive to user needs, comfort, and portability. Based on all this, it can be concluded that personalized nasal filters can be a promising and innovative solution for protection against environmental pollutants and pathogens. Through a commitment to the research and development of technology, the long-term impact of such devices on our health and the environment can be significant, contributing to improving people's quality of life and creating a sustainable future. With unique solutions and continuous research, we give hope that in the future, despite the environmental challenges, we can enjoy the protection of our health with even more efficient and sophisticated devices.

[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

[Multicentric Hungarian results of cabozantinib therapy in patients with metastatic kidney cancer based on real-world data]. / Áttétes vesedaganatos betegek kabozantinibterápiájának multicentrikus magyarországi eredményei.

The aim of our analysis was to evaluate the efficacy of cabozantinib in patients with metastatic renal cell carcinoma. Cabozantinib therapy initiated between 01/01/2019 and 31/12/2022 was evaluated based on a retrospective review of data from 14 renal centers in Hungary. The starting dose was 60 or 40 mg. Physical examinations and laboratory tests were performed every 4 weeks and imaging studies 3-monthly. Tumor response was assessed according to RECIST 1.1, and toxicity according to NCI CTCAE 4.0. A total of 230 patient records were evaluated, 201 (87.4%) of them had clear cell RCC. Cabozantinib was administered as third, second and first-line treatment in 48.7%, 38.3% and <5% of cases, respectively. Dose reductions occurred in 62.6% and treatment interruption in 6.5%. Duration of therapy was 10.03 months, which was independent of dose reduction. Overall tumor response rate was 39.2% and clinical benefit was 82.8%. The duration of first-, second-, third- and fourth-line treatment was 11.47, 8.03, 11.57 and 10.13 months, respectively. Overall survival from the start of therapy was 22.0 months. Cabozantinib therapy in daily practice was more beneficial than according to registry study results. Dose reduction did not affect efficacy.

Atezolizumab for the treatment of advanced recurrent basal cell carcinoma and urothelial carcinoma of bladder: a case report.

BACKGROUND: The use of checkpoint inhibitors has become increasingly important in the treatment of different cancers, including advanced muscle-invasive urothelial cancer and even in basal cell carcinoma. We present the case of a patient with advanced basal cell carcinoma and metastatic muscle-invasive urothelial cancer, who was treated with the programmed death-ligand 1 inhibitor, atezolizumab for both cancers. CASE PRESENTATION: A 72-year-old Caucasian female patient, with a history of smoking without any comorbidities developed periocular basal cell carcinoma, which was surgically removed but relapsed 4 years later. Surgical excision was carried out twice, but with positive margins, therefore definitive radiotherapy was given. Subsequently, the patient developed non-muscle-invasive papillary urothelial carcinoma, which was removed by transurethral resection. Follow-up was irregular owing to the patient's inadequate compliance, and within 2 years, the patient's cancer relapsed and histology confirmed muscle-invasive urothelial carcinoma. Definitive radiochemotherapy was not accepted by the patient. Meanwhile, the patient's basal cell carcinoma had also progressed, despite receiving vismodegib therapy. Therefore, the patient was administered epirubicin-cisplatin. Having reached the maximum cumulative dose of epirubicin, treatment with this chemotherapeutic agent could not be continued. The patient developed bladder cancer metastasis in her left suprainguinal lymph nodes. Owing to the presence of both types of tumors, programmed death-ligand 1 inhibitor atezolizumab treatment was chosen. In just over 1 year, the patient received 17 cycles of atezolizumab altogether, which was tolerated well without any adverse or side effects. Follow-up imaging scans indicated complete remission of the metastatic bladder cancer and stable disease of the basal cell carcinoma. The patient subsequently passed away in hospital due to a complication of COVID-19 infection. CONCLUSIONS: Our patient attained stable disease in advanced basal cell carcinoma and complete remission in metastatic muscle-invasive urothelial cancer after receiving programmed death-ligand 1 inhibitor, atezolizumab, therapy. To our knowledge, this is the first paper to report the use of programmed death-ligand 1 inhibitor, atezolizumab, as treatment for advanced basal cell carcinoma. This case may also be of interest for clinicians when treating patients with two synchronous cancers.

[Forward directions for targeted treatment of urothelial tumors]. / Uroteliális daganatok célzott kezelésének eloremutató irányai.

Platinum-based chemotherapy is the standard therapy for inoperable, locally advanced, or metastatic urothelial tumors. Although the initial response rate with combination chemotherapy is very high, the median survival is approximately 15 months. Secondary chemotherapy has had modest clinical benefit and toxicity, with the breakthrough coming from the introduction of checkpoint inhibitory immunotherapies. After chemotherapy and immunotherapy, there is currently no accepted standard of care in the third line. Based on the results of the two phase II and one phase III studies available so far, the use of targeted treatments in tertiary treatment may be a new direction. The purpose of our review is to present these clinical trials, and we would also like to draw attention to promising targeted therapies in the future.

The first experience in Hungary with split-course multimodal treatment in high risk bladder cancer / Az osztott dózisú trimodális kezelés elso hazai alkalmazása nagy kockázatú húgyhólyagdaganat esetében.

Összefoglaló. Az izominvazív vagy nagyon nagy kockázatú, felületes hólyagdaganatok kezelésének arany standardja a radikális húgyhólyag-eltávolítás (cystectomia). Válogatott betegek esetében hasonló hatékonyságú kezelés lehet az osztott dózisú (split-course) trimodális terápia, az endoszkópos tumorreszekció és a kemoirradiáció megszakított ciklusokkal történo alkalmazása. A split-course trimodális terápia a radikális cystectomiához hasonló eredményességu, a késobbi életminoség szempontjából pedig ígéretes kezelési lehetoség lehet megfeleloen kiválasztott betegek esetében. Hazánkban elso alkalommal végzett kezelést ismertetünk a téma szakirodalmi áttekintése mellett. A húgyhólyagtumor transurethralis reszekciója, maximális eradikációja után kemoirradiáció kezdodik, melyet 45 Gy sugárdózis elérésekor ismételt szövettani mintavétel szakít meg. Negatív szövettani eredmény esetén a megkezdett terápia a teljes dózis eléréséig folytatandó. Amennyiben a reszekció során élo tumor észlelheto, a radikális mutét elvégzése javasolt. A korábban transurethralis daganatreszekción négyszer átesett 54 éves beteg lokális immunterápia utáni recidívájának szövettana pT1, 'high grade' urothelialis carcinoma volt. A jól informált, kiváló fizikális statusú beteg kérését figyelembe véve split-course trimodális kezelést végeztünk. Negatív 'staging' vizsgálatok után maximális endoszkópos reszekció, majd kemoirradiáció következett. A 45 Gy besugárzás elérésekor elvégzett ismételt mintavétel azonnal feldolgozott szövettana negatív eredményt mutatott, így késedelem nélkül folytatódott a kemoirradiációs kezelés. Az eddigi kontrollvizsgálatok alapján a beteg komplett remisszióban van. A split-course trimodális terápia a radikális hólyageltávolítás megfelelo alternatívája jól informált, gondosan megválogatott betegek esetében. A szervmegtartó eljárás jobb életminoséget eredményezhet, ugyanakkor a beteget feltétlenül tájékoztatni kell, hogy sikertelenség esetén a radikális mutét is szükségessé válhat. A kezelés sikeres menedzselése csak a társszakmák szoros, jól tervezett együttmuködésével lehetséges. Orv Hetil. 2021; 162(50): 2017-2022. Summary. While radical cystectomy remains the gold standard to treat muscle-invasive or very high risk superficial bladder cancer, well selected patients can be offered split-course multimodal treatment as a similarly effective alternative, combining endoscopic tumor resection and split-course chemoradiotherapy. In highly selected patients, split-course trimodality therapy can lead to survival rates comparable to radical cystectomy with better quality of life outcomes. We present our experience with split-course trimodality treatment used for the very first time in Hungary. Maximal transurethral resection of bladder neoplasm is followed by chemoradiotherapy with repeated bladder biopsy after 45 Gy of irradiation. With negative biopsy results, chemoirradiation should be continued until full dose given. Salvage cystectomy is recommended if viable tumor is detected. Our patient (54), who previously underwent four transurethral bladder tumor resections and local immunotherapy, presented with pT1, high grade urothelial carcinoma recurrence. The well-informed, high performance status patient opted for split-course trimodality treatment. After negative staging scan results, the patient underwent complete endoscopic tumor eradication, followed by chemoradiotherapy. After 45 Gy of irradiation, repeated bladder biopsy was performed. The immediate histopathological examination found no viable tumor, therefore chemoradiotherapy was completed. Follow-up examinations suggest our patient in complete remission. Split-course trimodality treatment can be offered to well-informed and selected patients as a reasonable alternative to radical cystectomy. Though the bladder-sparing approach results in better quality of life, patients must know that in the case of treatment failure, radical cystectomy will likely be offered. Excellent multidisciplinary cooperation is a key to conduct this treatment alternative successfully. Orv Hetil. 2021; 162(50): 2017-2022.