Novosti u imunoterapiji tumora jednjaka i želuca

A high frequency of somatic mutations has been detected in stomach and esophageal cancers which makes them a possible suitable target for the application of immunotherapy. Contemporary immunotherapeutic approaches rely on monoclonal antibodies that inhibit immune checkpoints. The results of early clinical studies are promising, while only a few phase III studies have published their results so far. A particulary promising treatment strategy is the combination of checkpoint inhibitors with other treatment modalities, such as chemotherapy, targeted therapy, radiotherapy or T cells agonists.U karcinoma jednjaka i želuca je nađena visoka učestalost somatskih mutacija što ih čini pogodnom metom za primjenu imunoterapije. Suvremeni pristupi u liječenju imunoterapijom temelje se na inhibiciji imunoloških kontrolnih točaka monoklonskim protutijelima. Rezultati kliničkih studija ranih faza su obećavajući dok je svega nekoliko studija faze III do sada objavilo svoje rezultate. Osobito je obećavajuća strategija liječenja kombinacijom inhibitora kontrolnih točaka s drugim modalitetima liječanja poput kemoterapije, ciljane terapije, radioterapije ili terapije agonistima T stanica

U kojih bolesnika primijeniti radioterapiju u metastatskom hormonalno osjetljivom karcinomu prostate?

The standard of treatment of metastatic hormone-sensitive prostate cancer (mHSPC) is androgen deprivation therapy (ADT ) with docetaxel or abiraterone. However, numerous retrospective studies suggested outcome benefit of prostate radiotherapy. Small randomized trial (HORRAD) showed no overall survival (OS) benefit of the addition of prostate radiotherapy to ADT but there was a trend toward survival benefit in a low volume disease. Although the results of large randomized study (STAMPEDE ) have also not proved improvement of OS in unselected patients, robust improvement of failure-free survival was found. In addition, OS was significantly improved in patients with a low volume disease. In the absence of reliable molecular markers, the extent of metastatic disease has emerged as an important factor for treatment decision making. In this review, we summarize data from non-randomized as well as from randomized studies concerning prostate radiotherapy to contribute to the improvement of treatment tailoring for each individual patient with mHSPC in order to achieve the best possible treatment outcomes.Standard liječenja metastatskog hormonski osjetljivog karcinoma prostate (mHSKP) je androgen deprivirajuća terapija (ADT) s docetakselom ili abirateronom. Međutim, brojne retrospektivne studije su ukazale na korist od radioterapije prostate. Rezultati male randomizirane studije (HORRAD) nisu pokazali poboljšanje ukupnog preživljenja kod primjene radioterapije prostate uz ADT , no uočen je trend ka poboljšanju preživljenja kod bolesnika s malim volumenom metastatske bolesti. Iako rezultati velike randomizirane studije (STAMPEDE ) također nisu pokazali poboljšanje preživljenja u ukupnoj populaciji bolesnika, preživljenje bez neuspjeha liječenja bilo je značajno poboljšano. Pored toga, ukupno preživljenje je bilo značajno poboljšano u bolesnika s malim volumenom metastatske bolesti. U nedostatku pouzdanih molekularnih markera, opseg metastatske bolesti pojavio se kao važan čimbenik kod odlučivanja o liječenju. U ovom preglednom radu iznosimo rezultate ne-randomiziranih i randomiziranih studija o radioterapiji prostate kako bi doprinijeli poboljšanju izbora liječenja za svakog pojedinog bolesnika oboljelog od mHSKP s ciljem postignuća najboljeg mogućeg ishoda liječenja

Larynx Preservation: Advantages and Limitations

For a long time standard treatment approach for resectable squamous cell carcinoma of larynx was surgery with or without subsequent radiotherapy. Surgery, particulary total laryngectomy, has been associated with serious impairment of quallity of life. Between nonsurgical approaches, concurrent cisplatin based chemoradiotherapy has become a very promising treatment modality for larynx preservation. However, concurrent chemotherapy has been associated with serious toxicity. The most recent treatment approach in larynx preservation is related to taxan based induction chemotherapy

Novosti u imunoterapiji tumora jednjaka i želuca

A high frequency of somatic mutations has been detected in stomach and esophageal cancers which makes them a possible suitable target for the application of immunotherapy. Contemporary immunotherapeutic approaches rely on monoclonal antibodies that inhibit immune checkpoints. The results of early clinical studies are promising, while only a few phase III studies have published their results so far. A particulary promising treatment strategy is the combination of checkpoint inhibitors with other treatment modalities, such as chemotherapy, targeted therapy, radiotherapy or T cells agonists.U karcinoma jednjaka i želuca je nađena visoka učestalost somatskih mutacija što ih čini pogodnom metom za primjenu imunoterapije. Suvremeni pristupi u liječenju imunoterapijom temelje se na inhibiciji imunoloških kontrolnih točaka monoklonskim protutijelima. Rezultati kliničkih studija ranih faza su obećavajući dok je svega nekoliko studija faze III do sada objavilo svoje rezultate. Osobito je obećavajuća strategija liječenja kombinacijom inhibitora kontrolnih točaka s drugim modalitetima liječanja poput kemoterapije, ciljane terapije, radioterapije ili terapije agonistima T stanica

Multidisciplinarni tim u liječenju karcinoma glave i vrata - iskustvo KBC-a Zagreb

Head and neck cancers are associated with significant morbidity and mortality despite advancements in treatment in recent decades. A multidisciplinary approach to the treatment of these diseases is thus of essential importance and is becoming the gold standard. Head and neck tumors also endanger relevant structures of the upper aerodigestive tracts, including bodily functions such as voice, speech, swallowing, and breathing. Damage to these functions can significantly influence quality of life. Thus, our study examined not only the roles of head and neck surgeons, oncologists and radiotherapists, but also the importance of the participation of different scientific professions such as anesthesiologists, psychologists, nutritionists, stomatologists, and speech therapists in the work of a multidisciplinary team (MDT). Their participation results in a significant improvement of patient quality of life. We also present our experiences in the organization and work of the MDT as part of the Center for Head and Neck Tumors of the Zagreb Clinical Hospital Center.Karcinomi glave i vrata povezani su sa značajnim morbiditetom i mortalitetom unatoč napretku u liječenju posljednjih desetljeća. Multidisciplinarni pristup liječenju ovih bolesti stoga je od iznimne važnosti i postaje zlatni standard. Tumori glave i vrata također ugrožavaju relevantne strukture gornjeg aerodigestivnog trakta, uključujući funkcije kao što su glas, govor, gutanje i disanje. Oštećenje ovih funkcija može značajno utjecati na kvalitetu života. Stoga je naše istraživanje ispitivalo ne samo ulogu kirurga glave i vrata, onkologa i radioterapeuta, već i važnost sudjelovanja različitih drugih kliničkih profesija poput anesteziologa, psihologa, nutricionista, stomatologa i logopeda u radu multidisciplinarnog tima (MDT). Njihovo sudjelovanje rezultira značajnim poboljšanjem kvalitete života bolesnika. Također predstavljamo svoja iskustva u organizaciji i radu MDT-a u sklopu Centra za tumore glave i vrata KBC-a Zagreb

Primary malignant fibrous histiocytoma of the heart with skeletal muscles metastases

Malignant fibrous histiocytoma is an extremely rare primary malignant tumor of the heart. It is usually diagnosed when it is locally aggressive or has already metastasized. The prognosis is poor with an average survival time of one year. We report a case of recurrent left atrial malignant fibrous histiocytoma initially misdiagnosed as myxoma. The patient underwent repeated surgical resections followed by chemotherapy. Despite adjuvant chemotherapy, 18 months after initial diagnosis, definitive tumor relapse in left atrium was diagnosed. This is the 48th case of primary cardiac fibrous malignant histiocytoma reported in the literature

Immunotherapy of kidney cancer

Rak je bubrega neoplazma koja je razmjerno otporna na postojeću kemoterapiju, hormonsko i iradijacijsko liječenje, stoga se u liječenju bolesnika s rakom bubrega primjenjuju i testiraju lijekovi ili terapije s imunomodulatornim djelovanjem. U kliničkoj praksi, a sa svrhom imunoterapije, najčešće se primjenjuju rekombinantni citokini interferon-alfa (INF-a) i interleukin-2 (IL-2). Ta dva citokina mogu izazvati terapijski odgovor u 10% do 30% bolesnika s metastatskim rakom bubrega. Dugoročno preživljenje ipak je rijetko, nešto češće u bolesnika koji su primali visokodozni IL-2. Kako liječenje raka bubrega usprkos brojnim studijama s različitim terapijama nije zadovoljavajuće, u tijeku su i kliničke studije s drugim imunoterapijskim postupcima.Renal cell carcinoma (RCC) is generally resistant to standard chemotherapy, hormonal or irradiation treatments. Therefore, various drugs or therapies with immunomodulatory action were or are tested in kidney cancer patients. In clinical praxis many approaches have been investigated of which interferon-alpha (INF-") and interleukin-2 (IL-2) are the most extensively studied ones. These two cytokines can achieve response rates in 10% to 30% of patients with metastatic RCC. Long-term survival, however, is achieved only in few patients. More frequently in the ones who have been receiving high-dose IL-2. Consequently, the treatment of RCC is far from being optimal. Therefore, other and novel immunotherapeutic strategies are ongoing or planned to be tested in clinical trials

HORMONAL THERAPY OF PROSTATE CANCER: ARE THERE ANY DILEMMAS LEFT?

Strategija liječenja bolesnika s adenokarcinomom prostate ovisi o procjeni proširenosti bolesti, procjeni rizika od povratka bolesti, dobi, očekivanom trajanju života, komorbiditetima, afinitetima i načinu života. Jedan od standardnih terapijskih modaliteta jest i hormonska terapija. Hormonska terapija raka prostate zapravo je terapija koja suprimira androgen (AST) ili koja terapija deprivira androgen (ADT). Njezinom primjenom dolazi do sniženja razine androgena u krvi, a kako su stanice adenokarcinoma najvećim dijelom (³80%) hormonski ovisne o androgenima, prestanak stimulacije stanica raka androgenima dovodi do njihove apoptoze, usporava se rast tumora i smanjuje se njegova veličina. Stoga se ta vrsta terapije rabi u liječenju karcinoma prostate. Hormonska terapija indicirana je kao prvi terapijski modalitet kod nalaza metastatske bolesti. U slučaju primjene radioterapije na prostatu zahvaćenu rakom s kurativnom namjerom (kod nemetastatske bolesti) preporučuje se primjena terapije koja deprivira androgen u bolesnika sa srednjim i visokim rizikom od povratka bolesti prije, za vrijeme i poslije radioterapije u trajanju od 6 mjeseci ili 2–3 godine ovisno o procijenjenom riziku od povratka bolesti. U vezi s primjenom terapije koja deprivira androgen, a koja se može primijeniti na više načina i u više kombinacija, za određene kliničke situacije ne postoje konačne preporuke. Razloga je više: premalen broj odgovarajućih kliničkih studija, heterogenost bolesnika u studijama što otežava interpretaciju podataka te nekonzistentni rezultati. Također, kako novije dijagnostičke metode i postupci omogućavaju ranije otkrivanje raka prostate, a ranije i sve uspješnije liječenje produžava život bolesnika s metastatskom bolešću, rezultati »ranijih« kliničkih studija mogu gubiti na aktualnosti. Isto tako, sa sve dužim preživljenjem bolesnika sve važnija postaje kvaliteta života, odnosno nuspojave liječenja, kao i procjena koristi u odnosu prema štetnosti same terapije. Cilj je prikaza da upozori na novije spoznaje, kao i na moguće dileme o mjestu i primjeni terapije koja deprivira androgen.The strategy for treating prostate cancer patients depends on the assessment of disease extent, assessment of the risk of disease relapse, assessment of life expectancy, comorbidities, affinities and life-style. Since the activity and survival of prostate cancer cells is at least initially dependent on androgen stimulation, hormonal therapy is one of the several standard treatment modalities. Hormonal therapy is aimed at decreasing this androgen stimulation either by lowering androgen production or by blocking receptor binding. Hormonal therapy is in fact androgen-suppressive therapy (AST) or androgen-deprivation therapy (ADT). If effective, it results in the lack of cancer cell stimulation, thus causing their apoptosis and consequently decline in tumor growth and size. Hormonal therapy is used as a first-line treatment modality for metastatic disease. In addition to this indication, hormonal therapy is also used as an adjunct to radiotherapy with curative intent for patients with non-metastic disease but having an intermediate and high risk of disease relapse. In combination with radiotherapy, hormonal therapy can be applied before, concomitantly and after radiotherapy for the duration of 6 months or 2 to 3 years depending on the risk estimation. Regarding hormonal therapy, it can be applied in combination with other treatments, in several ways, and sometimes there might be several options available. This possible lack of a specific recommendation is a consequence of the fact that there is a limited number of adequate clinical studies which, moreover, may have yielded inconsistent results sometimes simply due to the patients’ heterogeneity. Moreover, thanks to the newer and better diagnostic methods enabling the discovery of prostate cancer in earlier disease stages, as well as to the more effective treatments, there is also a prolongation of relapse-free survival and possibly of overall survival in patients having metastic disease. Consequently, the results of earlier clinical studies might no longer be applicable to the new »generations« of upcoming patients. As regards this improved survival, issues of patient’s quality of life and possible side-effects of hormonal therapy are also becoming increasingly relevant because hormonal adverse events are time-dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, this paper aims to give an overview of the more recent findings, indications and observations regarding hormonal therapy

Gender-Specific Growth Patterns of Transversal Body Dimensions in Croatian Children and Youth (2 to 18 Years of Age)

In a cross-sectional study of growth, 5,260 healthy children of both sexes from Zagreb (Croatia) aged 2 to 18 years were measured. Six transversal body dimensions were studied: biacromial, transverse chest, antero-posterior chest, biiliocristal, bicondylar humerus and bicondylar femur diamters. A significant increase in body diameters has been observed until the age of 14 to 15 in girls and until the age of 16 in boys, showing that girls have a 1 to 2 years shorter period of growth. Compared to boys of the same age, they achieved larger amounts of final transversal bone size throughout the whole growth period. The most pronounced example was the knee diameter that in girls attained 95% of adult size as early as the age of 10. In both genders, the adult size is achieved earlier in widths of the extremities than in those of the trunk. The studied transversal body segments showed different growth dynamics, which is gender-specific. While sexual dimorphism in pelvic and shoulder diameters emerged with pubertal spurt, gender differences in chest and extremities’ diameters started early in life. In all ages, boys had larger chest, elbow and knee diameters. In pubertal age boys gained a significantly larger biacromial diameter (from the age of 13 onwards), while girls exceeded them in biiliocristal diameter (from 10 to 14 years). The findings of gender differences were compared to those reported for other European populations and their growth patters were discussed comparing viewpoints

CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH CANCER OF UNKNOWN PRIMARY SITE

Rak nepoznata primarnog podrijetla obuhvaća vrlo heterogenu skupinu različitih malignih tumora koji se prezentiraju u metastatskoj fazi bolesti. Dijagnoza se postavlja na temelju patohistološke potvrde maligne bolesti uz nemogućnost dokaza postojanja primarnog tumora nijednom dostupnom dijagnostičkom metodom. Iako je općenito loše prognoze, prepoznati su prognostički povoljni klinički entiteti koji čine temeljnu skupinu bolesnika za aktivno onkološko liječenje. U tekstu koji slijedi sadržane su kliničke upute s ciljem standardizacije dijagnostičkih postupaka, liječenja i praćenja bolesnika s nepoznatim primarnim rakom u Republici Hrvatskoj.Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia