Ozračivanje slezene u bolesnika sa zloćudnim i drugim hematološkim bolestima – iskustva jedne bolničke ustanove

Splenic irradiation has long been known as a palliative treatment modality in patients with various malignant hematologic diseases aiming to ameliorate clinical symptoms of splenomegaly as well as clinical sequels of hypersplenism. It provides considerable effect with low toxicity although exact radiotherapy dose and fractionation schedule are not known. During the 1996-2010 period, eleven patients were treated at our institution with splenic irradiation. They received 16 courses of fractionated radiotherapy. There were six patients with non-Hodgkin’s lymphoma, four with chronic lymphocytic leukemia, and one patient with myelofibrosis. The median of the dose received was 7 Gy, while the median of dose received per fraction was 1 Gy. Both parallel opposed anterior-posterior fields and tangential fields were used. Due to the clinical target volume shrinkage, the treatment field was reduced in 44% of courses. Of the courses initiated for symptom control, 71% resulted in effective palliation, whereas of the courses started to treat hematologic sequels of hypersplenism 50% produced desirable effects. The most common side effects included thrombocytopenia and anemia. Splenic irradiation provides effective and low-toxic palliation of symptoms but it is much less successful in treating hematologic disorders caused by hypersplenism.Ozračivanje slezene je najstariji poznati način palijativnog liječenja bolesnika s različitim zloćudnim hematološkim bolestima. Ima za cilj umanjiti kliničke simptome splenomegalije, kao i posljedice hipersplenizma. Ozračivanje slezene ima značajan učinak uz nisku toksičnost, ali točna radioterapijska doza kao i način frakcioniranja nisu poznati. Između 1996. i 2010. godine 11 bolesnika je liječeno u našoj ustanovi ovim postupkom. Ti bolesnici su primili ukupno 16 aplikacija frakcioniranog zračenja. Šest bolesnika je imalo ne-Hodgkinov limfom, četiri kroničnu limfatičnu leukemiju, a jedan bolesnik je imao mijelofibrozu. Medijan aplicirane tumorske doze bio je 7 Gy, a medijan aplicirane doze po frakciji 1 Gy. Korištena su nasuprotna paralelna te tangencijska radioterapijska polja. Zbog smanjenja kliničkog ciljnog volumena terapijsko polje je tijekom postupka radioterapije smanjeno u 44% radioterapijskih aplikacija. Od radioterapijskih postupaka započetih s ciljem kontrole simptoma 71% ih je rezultiralo uspješnom palijacijom, dok je od postupaka koji su započeti radi popravka hematoloških posljedica hipersplenizma njih 50% izazvalo željeni učinak. Najčešće nuspojave bile su trombocitopenija i anemija. Ozračivanje slezene omogućuje učinkovitu i nisko toksičnu palijaciju simptoma, ali je manje uspješno u liječenju hematoloških poremećaja uzrokovanih hipersplenizmom

Radiation Therapy in Treatment of Fibrodysplasia Ossificans Progressiva: A Case Report and Review of the Literature

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare genetic disorder with diffuse extra-skeletal bone formation. The genetic mutation responsible for FOP has recently been discovered and is connected with excessive activation of bone morphogenetic protein receptor. This disease usually begins with typical ossification pattern in early childhood, causing increasing disability and making patients totally disabled by the age of 30. Ectopic ossification develops spontaneously and can be triggered by any trauma and even intramuscular injections. The symptoms of FOP are often misdiagnosed as cancer, causing unnecessary biopsies, which can precipitate further progressive heterotopic ossification. There is no effective treatment for this severe condition. Radiotherapy can be helpful in impeding ossification, although the strict evidence for that is lacking. There are only two reports in the literature referring to the use of radiotherapy in treatment of FOP. Herein, we present a 35-year-old patient successfully treated with small doses of fractionated radiotherapy in several courses. This case indicates that radiotherapy can be useful in treating patients with FO

Imunoterapija karcinoma bubrega

Targeted therapy has been the standard of care for the treatment of metastatic renal cell carcinoma (mRCC). The current standard of care focuses on tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), antibodies to circulating VEGF receptor (bevacizumab) and m-TOR inhibitors (temsirolimus, everolimus). New immune-based therapies are emerging as a promising treatment for mRCC. Immune checkpoint blockade has shown clinically signifi cant antitumor response. Monoclonal antibodies against immune checkpoint blockade molecules including PD-1 (programmed cell death 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) have become a major focus in the immune-based therapy since it has been reported that they have impressive antitumor eff ects. The most studied inhibitors in the PD-1 pathway are: nivolumab, pembrolizumab and atezolizumab. Based on the results of the phase III clinical trial (CheckMate025) nivolumab, humanized monoclonal IgG4 antibody against PD-1, is the only agent that is approved by the FDA for the second-line treatment of mRCC. Ipilimumab is the fi rst-in-class immunotherapeutic for blockade of CTLA-4. The immunotherapy combinations have demonstrated promising results in a randomized trials. The use of cancer treatment vaccines is another approach to immunotherapy and will be systematically evaluated in the future. Immunotherapy has demonstrated great clinical potential and it represents crucial component of mRCC treatment. Developing immunotherapy to the point of clinical utility presents a number of issue and challenges, and more rigorous studies are needed.Ciljana terapija danas predstavlja osnovicu sistemskog liječenja metastatskog raka bubrega (mRB), a standard liječenja su tirozin-kinazni inhibitori (sunitinib, sorafenib, pazopanib, aksitinib), protutijela na cirkulirajući VEGF receptor (bevacizumab) i m-TOR inhibitori (temsirolimus, everolimus). Noviji imunoterapijski principi predstavljaju značajne iskorake u liječenju mRB. Jedna forma imunoterapije je inhibicija imunoloških kontrolnih točaka (eng. immune checkpoint). Blokiranjemjednog od dva najistraživanija imunološka receptora; antigen 4 povezan s aktivnošću citotoksičnih T-limfocita (CTLA-4) i receptor programirane stanične smrti (PD-1), potenciramo antitumorski imunološki odgovor. Među najistraživanije anti-PD-1 inhibitore ubrajamo: nivolumab, pembrolizumab i avelumab. Nivolumab je ljudsko monoklonalno antitijelo kojega je Američka agencija za hranu i lijekove odobrila u drugoj liniji liječenje mRB, a na osnovi rezultata kliničke studije faze III (CheckMate025). Ipilimumab je prvi registrirani checkpoint inhibitor koji blokira inhibitorni signal (CTLA-4 receptor) na površini citotoksičnih T limfocita. Veliki pomak u imunoterapiji mRB postigut je primjenom konkomitantnih protokola liječenja. Novija istraživanja primjene imunoterapije u liječenju raka bubrega uključuju i pronalaženje cjepiva koje bi prepoznavalo i uništavalo promijenjene tumorske stanice. Imunoterapija ima jasno mjesto i veliki potencijal u liječenju raka bubrega. Ipak, postoji još niz problema i pitanja te su potrebna brojna daljnja istraživanja kako bi se iskoristio njen puni potencijal

Parenhimni angiosarkom poslije zračenja: prikaz slučaja

Secondary angiosarcoma is an aggressive tumor that can develop in breast cancer patients treated with conserving therapy and radiotherapy. The symptoms can be misleading, whereas mammography and fine-needle aspiration (FNA) are typically negative in early stage of the disease. A high grade of clinical suspicion is very important for early diagnosis. A case of angiosarcoma involving breast parenchyma in a patient treated with quadrantectomy and radiotherapy for T1cN1Mx breast carcinoma is presented.Sekundarni angiosarkom je agresivni tumor koji se može razviti kod bolesnica s rakom dojke liječenih terapijom očuvanja i radioterapijom. Simptomi mogu dovesti u zabunu, dok su mamografija i citološka punkcija redovito negativne u ranom stadiju bolesti. Za ranu dijagnozu vrlo je važna visoka klinička sumnja na ovu bolest. Prikazuje se slučaj angiosarkoma koji je zahvatio parenhim dojke u bolesnice liječene kvadrantektomijom i radioterapijom zbog raka dojke T1cN1Mx

Clinical recommendations for diagnosis, treatment and monitoring of patients with bladder cancer

Rak mokraćnog mjehura (RMM) jest, u skladu s podatcima hrvatskog Registra za rak iz 2015. godine, drugi prema učestalosti tumor urinarnog sustava, odmah nakon raka prostate. U 90% slučajeva radi se o urotelnom karcinomu, a razlika u preživljenju kod bolesnika s mišićnoinvazivnim RMM-om (MIRMM) i nemišićnoinvazivnim RMM-om (NMIRMM) znatna je. Liječenje NMIRMM-a usmjereno je na smanjenje recidiva i sprječavanje napredovanja bolesti, a sastoji se od transuretralne resekcije (TUR) tumora i primjene intravezikalne terapije ovisno o procjeni rizika od povrata bolesti. Temelj liječenja bolesnika s MIRMM-om jest radikalno kirurško liječenje, tj. cistektomija kojoj u bolesnika koji su sposobni primiti cisplatinu prethodi neoadjuvantna kemoterapija (NKT). U trenutku postavljanja dijagnoze bolest je kod 4 – 6% bolesnika proširena, dok će se u 50% bolesnika razviti povrat bolesti nakon cistektomije. Metode liječenja proširenje bolesti uključuju: kemoterapiju temeljenu na cisplatini, imunoterapiju, palijativnu radioterapiju te simptomatsko i potporno liječenje. Važno obilježje RMM-a jest prisutnost visoke stope somatskih mutacija koje su omogućile promjenu paradigme u liječenju proširenog RMM-a i dovele do odobravanja niza novih lijekova koji pripadaju inhibitorima PD-1 i PD-L1, tj. inhibitorima nadzornih točaka imunosnog odgovora posredovanog T-stanicama .Bladder cancer is the second most common malignancy of urinary system according to data from the Croatian National Cancer Registry for 2015. In 90% of cases the underlying histology is urothelial carcinoma. Difference in survival in patients with muscle-invasive disease (MIBC) compared to the survival of patients with non-muscle invasive disease (NMIBC) is enormous. Management of NMIBC, traditionally, has been focused on the reduction of subsequent bladder recurrence and prevention of disease progression and is primarily based on transurethral resection (TUR) of the tumor, followed by intravesical therapy based on estimated individual risk of recurrence. Conversely, in patients with MIBC radical cystectomy remains the corne stone of the treatment, optimally in conjunction with neoadjuvant platinum-based chemotherapy in cisplatin-eligible patients. At the moment of diagnosis, 4–6% of patients already have distant metastases, and post cystectomy recurrence could be expected in 50% of patients. Treatment options in metastatic disease range from cisplatin-based chemotherapy, immunotherapy, palliative radiotherapy and finally supportive care. Landmark feature of bladder cancer is the high prevalence of somatic mutations which enabled profound change for decades held treatment paradigm for advanced bladder cancer leading to regulatory approval of whole array of novel immunotherapy agents. These emerging therapeutics (programmed death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1)) belong to the class of inhibitors of checkpoint proteins, which are key targets that regulate T-cell mediated immune response

Kliničke upute za dijagnostiku, liječenje i praćenje bolesnika oboljelih od raka mokraćnog mjehura Hrvatskoga onkološkog društva i Hrvatskoga urološkog društva Hrvatskoga liječničkog zbora [Clinical guidelines for diagnosing, treatment and monitoring patients with bladder cancer - Croatian Oncology Society and Croatian Urology Society, Croatian Medical Association]

Urothelial cancer is the most common bladder cancer. Hematuria is the most common presenting symptom in patients with bladder cancer. The most common diagnostics of bladder cancer is performed by transurethral resection of bladder after which pathohistological diagnosis is set. It is necessary to determine whether the cancer penetrated in muscle layer (muscle-invasive cancer) or not (muscle-noninvasive cancer). Decision on therapeutic modality depends on the clinical stage of disease and on prognostic and risk factors. For muscle non-invasive bladder cancer transurethral resection is preferred with or without intravesical instillation of Bacillus Calmette-Guérin (BCG). For invasive cancer the method of choice is radical cystectomy. Radiotherapy is used in radical and palliative purposes. Metastatic disease is most frequently treated by chemotherapy metotrexate/vinblastine/doxorubicine/cisplatin (MVAC) or gemcitabine/cisplatin (GC). The purpose of this article is to present clinical recommendations to set standards of procedures and criteria in diagnostics, treatment and follow up of patients with bladder cancer in the Republic of Croatia

Clinical guidelines for diagnostics, treatment and monitoring of patients with testicular cancer

Rak testisa najčešći je solidni tumor u muškaraca u dobi od 15. do 34. godine. Incidencija raka testisa u svijetu udvostručena je u posljednjih 40 godina. Tumori zametnih stanica čine 95% svih tumora testisa, a podijeljeni su u dva osnovna histološka tipa: seminomi i neseminomi. Osobito značenje daje im velik postotak izlječivosti i u diseminiranoj fazi bolesti. Tom je uspjehu najviše pridonijela kemoterapija, ali kirurgija je i dalje neizostavan dio uspješnog liječenja. U znatnog dijela bolesnika danas se nastoji odrediti terapijski minimum kojim se izbjegava niz nuspojava, a dovodi do jednakog uspjeha kao i donedavno agresivniji terapijski pristup. U tekstu koji slijedi iznesene su kliničke upute radi standardizacije dijagnostike, liječenja i praćenja bolesnika s tumorima zametnih stanica testisa u Republici Hrvatskoj.Testicular tumors are the most common solid tumors in men between age 15- 34 years. The worldwide incidence of these tumors has doubled in the past 40 years. Germ cell tumors comprise 95% of malignant tumors arising in the testes and they are classified as seminoma and nonseminoma. Testicular cancer has high cure rates even in disseminated stage of disease. The chemotherapy mostly contributed to these results, but surgery is an unavoidable part of this success. In significant number of these patients treatment algorithms today have intention to offer the same cure rates with minimally aggressive therapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for diagnosis, treatment, and follow-up of patients with testicular cancer in the Republic of Croatia