SAŽETAK
Rak dojke je najčešći zloćudni tumor u žena koji se može probirom, redovitim kontrolama i zdravstvenim odgojem otkriti u ranim stadijima bolesti i uspješno liječiti. Metode liječenja ...uključuju kirurgiju, kemoterapiju, radioterapiju, endokrinu terapiju, imunoterapiju, ciljanu terapiju te simptomatsko-suportivnu terapiju, koja se primjenjuje ovisno o stadiju bolesti, biološkim obilježjima tumora i općem stanju, dobi i komorbidetima bolesnica. Plan liječenja definira multidisciplinarni tim. S obzirom na pojavnost ove bolesti, mogućnost ranog otkrivanja i mogućeg značajnog učinka terapijskih postupaka na tijek bolesti, potrebno je definirati i pravilno standardizirati pristup u dijagnostici, liječenju i praćenju ovih bolesnica. U tekstu su iznesene smjernice s ciljem primjene standardiziranih postupaka u svakodnevnom radu s bolesnicama s rakom dojke u Republici Hrvatskoj.
Abstract
Diffuse malignant peritoneal mesothelioma (DMPM) is generally an understudied disease, largely because most molecular and clinical studies of mesothelioma have been conducted in patients ...with the more common malignant pleural mesothelioma. We present the case of a 45-year-old male that initially presented with abdominal discomfort and ascites. Diagnostic workup revealed advanced DMPM. Bimodal treatment was stared with cytoreductive surgery and hyperthermic intraperitoneal perfusion with chemotherapy procedure, followed by pemetrexed systemic monotherapy. After the disease progression, and because of a very good previous treatment response to pemetrexed, we decided to rechallenge systemic pemetrexed, along with the introduction of cisplatin. Although the intent behind systemic treatment was atfirst solely palliative, overall survival after the initial diagnosis was 50 months. Treatment based on rechallenging pemetrexed with or without cisplatin in patients with advanced DMPM can result in a quite satisfactory disease control and symptom management.
Nedavni uspješni rezultati više raznih novih imunoterapijskih pristupa u onkoloških bolesnika, kao, primjerice, blokada imunosnih inhibitornih molekularnih interakcija s monoklonskim protutijelima ...protiv molekula kontrolnih točaka, mogu se smatrati medicinskim iskorakom u kliničkoj onkologiji. Cilj je ovoga rada dati pojednostavnjeni prikaz imunosnog uređivanja raka i kliničke primjene monoklonskih protutijela protiv molekula kontrolnih točaka u onkoloških bolesnika. Interakcije između imunosnog sustava i autolognih tumora složene su, ali rezultati dobiveni primjenom monoklonskih protutijela protiv molekula kontrolnih točaka upućuju na prihvatljivu kliničku primjenjivost, učinkovitost i sigurnost u liječenju bolesnika s određenim tipovima raka. Klinička primjena monoklonskih protutijela protiv molekula kontrolnih točaka CTLA-4, PD-1 i PD-L1, ovisno o tome protiv kojih se tumora ta protutijela testiraju i primjenjuju, jest u rasponu od odobrenja regulatornih agencija i primjene u metastatskoj bolesti u bolesnika s određenim vrstama tumora pa do faza testiranja u kliničkim studijama, a radi istraživanja kliničke učinkovitosti i dobivanja odobrenja.
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.
Rak dojke, uz tumore pluća te melanom, najčešći je tumor koji metastazira u središnji živčani sustav. Uslijed razvitka sistemske terapije primarne bolesti, i posljedičnog produljenog preživljenja ...bolesnika, liječenje moždanih metastaza predstavlja sve veći izazov. Dok se novi pristupi sistemskoj terapiji moždanih presadnica tumora dojke fokusiraju na savladavanje prepreke krvno-moždane i krvno-tumorske barijere te na ciljanu terapiju, lokalna terapija ostaje primarna linija liječenja. Odluka o izboru metode liječenja ovisi o broju i volumenu moždanih presadnica, njihovoj lokalizaciji, kliničkom statusu bolesnika, prethodno korištenim metodama liječenja, stadiju uznapredovalosti osnovne bolesti te prognozi bolesnika. U slučajevima kada aktivni pristup liječenju, koji uključuje operaciju i/ili radioterapiju, ne pridonosi kvaliteti života ili ukupnom preživljenju bolesnika, preporuča se najbolja potporna njega.
To immunohistochemically evaluate the expression of MAGE-A1, MAGE-A, and NY-ESO-1 cancer/testis (C/T) tumor antigens in medullary breast cancer (MBC) tumor samples and to analyze it in relation to ...the clinicopathological features.
This retrospective study included samples from 49 patients: 40 with typical MBC and 9 with atypical MBC. Tumor specimens were obtained from patients operated on in the University Hospital for Tumors and the Sisters of Mercy University Hospital, Zagreb, Croatia, from 1999 to 2005. Standard immunohistochemistry was used on archival paraffin-embedded MBC tissues.
MAGE-A1, MAGE-A, and NY-ESO-1 antigens were expressed in 33% (16/49), 33% (16/49), and 22% (11/49) of patients, respectively. No difference between the groups with and without C/T tumor antigen expression in age at diagnosis, tumor size, axillary lymph node metastasis, adjuvant therapy, and HER-2 expression was identified. Significantly more patients died in the MAGE-A-positive group than in the MAGE-A-negative group (P=0.010), whereas a borderline significance was found between MAGE-A1-positive and the MAGE-A1-negative group (P=0.079) and between NY-ESO-1-positive and NY-ESO-1-negative group (P=0.117). Overall survival, as evaluated by the Kaplan-Meier curves, was lower in MAGE-A1- (P=0.031), MAGE-A- (P=0.004), NY-ESO-1-positive groups (P=0.077).
Expression of C/T antigens may represent a marker of potential prognostic relevance in MBC.
Renal transplantation is associated with increased incidence of cancer. We reviewed a large series of renal transplant recipients to determine the incidence and outcome of patients with malignant ...changes located at the head and neck. A total of 1232 renal transplant recipients have been followed at Department of Dialysis University Hospital Centre Zagreb from 1972 to 2009. Demographic data, localization and disease outcome were evaluated in patients who developed cancer. Twenty one patients (1.7%) developed 27 head and neck malignancies. The average time from transplantation to development of cancer was 56.8 months. The mean length of follow-up was 9.4+/-4.8 years. Eighteen malignancies were cutaneous in origin and 9 were noncutaneous. Of cutaneous malignancies, 88.9% were basal cell carcinoma; one patient had Merkell-cell carcinoma and one patient developed squamous cell carcinoma. Six cases of basocellular skin cancer were recorded in one fair-skin patient. Noncutaneous malignancies involved the oral cavity (2 cases of Kaposi's sarcoma and one pharyngeal cancer) and the thyroid gland in 3 patients each. Two patients had post-transplant lymphoproliferative disorder occurring at the head and neck. One patient had brain tumor. Radical surgery, radiation, and/or chemotherapy were necessary in 33.3% of patients. Immunosuppression was reduced in all patients, and 12 patients were switched from the calcineurin-based immunosuppression to sirolimus. They all have stable graft function. None of the patients died from cancer. Immunosuppression was ceased in one patient with Kaposi's sarcoma who returned to dialysis and died 10 years later from heart failure. An increased incidence of cancer occurring in the head and neck was recorded. Careful skin examination and oral examination is mandatory for discovering cancer before dissemination. Sirolimus is safe alternative to calcineurin-based immunosuppression in patients who developed head and neck malignancies.
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.
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