Onkologija
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Karcinom Merklovih celic: novosti v sistemskem zdravljenju
Get PDFMerkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with a poor prognosis in advanced stage. The incidence is increasing with some deviations between different geographic regions. The risk factors are advanced age, immunosuppression, and ultraviolet light exposure. There are associations between MCC and polyomavirus infection, but the exact mechanism that leads to carcinogenesis is yet to be fully understood. For localized disease (when feasible), surgery is the recommended treatment, followed by adjuvant radiation or chemoradiation. In the metastatic setting, chemotherapy has been the standard treatment, but durable responses are rare. As tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, there is rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. However, recently published trials with immune checkpoint inhibitors in the first- and second-line showed promising results with a tolerable safety profile, and these are becoming the standard therapy, already included in international guidelines. The published data showed a high efficacy of avelumab in the metastatic setting.Karcinom Merklovih celic (KMC) je redek, agresiven nevroendokrini kožni rak s slabo prognozo, posebno, ko je v napredovalem stadiju. Incidenca na splošno narašča, čeprav podatki o incidenci kažejo na razlike med geografskimi področji. Med dejavnike tveganja štejemo starost, imunosupresijo in izpostavljenost ultravijoličnemu sevanju. Znana je povezava med MCC in okužbo s poliomavirusom, čeprav natančnega mehanizma, ki vodi v karcinogenezo, še ne razumemo v celoti. Pri lokalizirani bolezni je izbor zdravljenja kirurgija (ko je to mogoče), sledi mu dopolnilno obsevanje ali obsevanje v kombinaciji s kemoterapijo. Pri razsejani bolezni je bila doslej na voljo le kemoterapija, čeprav so dolgotrajni odgovori ob njej redki. Glede na to, da je onkogeneza tumorja povezana z integracijo poliomavirusa Merklovih celic in mutacijami, povzročenih z ultravijoličnim sevanjem, obstaja logična osnova za zdravljenje z imunoterapijo oz. protitelesi, ki ciljajo pot PD-L1/PD-1. Nedavno objavljene raziskave v prvem in drugem redu zdravljenja z inhibitorji imunskih stikal (anti-PD-1/PD-L1-protitelesi) kažejo obetajoče rezultate s sprejemljivim varnostnim profilom zdravljenja, zato tovrstno zdravljenje postaja standardno in je že priporočeno v mednarodnih smernicah za zdravljenje razsejanega raka Merklovih celic. Objavljeni podatki randomiziranih raziskav kažejo na obetajočo učinkovitost teh zdravil pri metastatski bolezni
Tekočinska biopsija pri raku
Get PDFRecently, new exciting developments in oncology have been made in the field of liquid biopsies. In liquid biopsy, samples of blood or other body fluids are analyzed for tumor-derived material. Tumor-derived material comprises cell-free circulating tumor DNA (cf/ctDNA), exosomes released by tumor cells, or circulating tumor cells themselves (CTC). In this review, we highlight the studies that summarize the state of the art in the field of liquid biopsy, and also represent the current challenges which should be addressed in the future to successfully implement liquid biopsy in a clinical setting.V zadnjih letih smo v onkologiji priča hitremu napredku na področju biopsije telesnih tekočin oz. tekočinske biopsije. Tekočinska biopsija predstavlja analizo vzorca odvzete telesne tekočine (v onkologiji je to običajno kri), v katerem iščemo znake navzočnosti raka. V krvi lahko analiziramo cirkulirajočo prosto/cirkulirajočo tumorsko DNA (cf/ctDNA) iz tumorskih celic, eksosome, ki jih v kri sproščajo tumorske celice, in tudi cirkulirajoče tumorske celice (CTC). V pregledu predstavljamo najnovejša dognanja in raziskave na področju tekočinske biopsije pri raku in poleg uporabnosti izpostavljamo tudi njihove omejitve, ki jih bo treba natančno opredeliti, če bomo želeli to metodo uporabljati v vsakodnevni obravnavi bolnikov
Imunoterapija: Nova zdravila, drugačni sopojavi
Get PDFOver the past years, immunotherapy has become an important systemic treatment strategy for cancer patients. We have seen multiple different strategies, and checkpoint blockade is one them. Anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), and programmed death-ligand 1 (PD-L1) are antibodies against checkpoint inhibitors that can increase immune activity against cancer, thus making the immune system stronger against cancer cells. However, the increasing use of these agents has exposed a discrete group of immune-related adverse events (irAEs). Skin, gut, endocrine, lung, and musculoskeletal irAEs are the most common, although every organ can be affected. The majority of irAEs are mild to moderate in severity, however, serious and life-threatening irAEs are reported in literature. Early detection and treatment of irAEs is important, and a multidisciplinary approach is sometimes needed to prevent serious consequences.Imunoterapija je v zadnjih letih postala eden izmed pomembnih načinov sistemskega zdravljenja bolnikov z rakom. Priča smo bili različnim imunskim strategijam, med temi je tudi inhibicija kontrolnih točk. Zdravila proti CTLA-4, PD-1 in PD-L1 so protitelesa proti zaviralcem kontrolnih točk, ki lahko povišajo imunsko aktivnost proti rakavim celicam in tako ojačajo imunski odgovor proti raku. Večja uporaba teh zdravil pa je privedla do pojava posebne vrste imunsko pogojenih neželenih učinkov. Ti se najpogosteje izrazijo na koži, črevesju, žlezah z notranjim izločanjem, pljučih in mišično-skeletnem sistemu, lahko pa je prizadet kateri koli organ. Večina imunsko pogojenih neželenih učinkov je blagih do zmernih, v literaturi pa obstajajo poročila o hudih in življenje ogrožajočih. Pomembna je njihova zgodnja prepoznava in zdravljenje, kakor tudi multidisciplinaren pristop, da preprečimo resne zaplete
Ocena delazmožnosti onkoloških bolnikov – pogled specialista družinske medicine in specialista medicine dela, prometa in športa
Get PDFCancer is among the most common diseases of our time. Each year, about 13.500 people get cancer in Slovenia. The risk of disease increases with age. There are about 100.000 cancer survivors living in Slovenia, meaning cancer can no longer be considered a mortal disease but rather a chronic illness. Population aging and the prolonging length of service put us before a dilemma whether work is harmful or beneficial to a cancer patient. Work is often viewed as an important component of one's self-esteem, a source of social support, and a means of financial income. As work remains a goal for some patients, it requires direct attention by the providers of treatment and rehabilitation. Assessing work ability in cancer survivors is often difficult for a physician because they must decide between the available objective medical records and the individual's perception of and expectations for the disease.Rak spada med najpogostejše bolezni našega časa. V Sloveniji vsako leto zboli za rakom že okoli 13.500 ljudi . S starostjo se nevarnost bolezni povečuje. Toda, ne pozabimo, med nami živi okoli sto tisoč bolnikov in bolnic z rakom, kar pomeni, da rak ni več smrtna, ampak kronična bolezen. Prav staranje prebivalstva in podaljševanje delovne dobe pa nas postavljata pred pomembno dilemo o tem, ali je delo za »onkološkega« bolnika škodljivo ali pa morda celo koristno. Delo lahko človeku predstavlja pomemben del samospoštovanja, mu nudi socialno okolje in finančni zaslužek, kar je treba upoštevati pri načrtovanju zdravljenja in rehabilitacije. Ocenjevanje delazmožnosti bolnika, ki je prebolel raka, je za zdravnika pogosto težavno, saj se mora odločati med dostopnimi objektivnimi medicinskimi izvidi in posameznikovim osebnim doživljanjem bolezni ter njegovimi pričakovanji
Bolnik z rakom v procesu vračanja na delo
Get PDFEarly diagnostics, new terapeutic methods and more successful treatment of cancer patients also enabeled them to return to work at least partly if not completly. For healthcare providers return to work means successful rehabilitation and for the patient and his close once better quality of live. The author of the article is representing a case of a breast cancer pacient who is on sick leave and is returning to work after the process of treatment and rehabilitaion. In the conclusions, she is thinking about what is important for the therapist and for the pacient after the cancer treatment.Zgodnja diagnostika, nove terapevtske možnosti in uspešnejše zdravljenje raka so pripomogli tudi k temu, da se lahko večji delež bolnikov po zdravljenju raka vsaj deloma, če ne v celoti, vrne na delo. Za izvajalce zdravstvene oskrbe pomeni vrnitev na delo uspešen zaključek rehabilitacije, za bolnike in njihove bližnje pa boljšo kakovost življenja. Avtorica članka na primeru začasne nezmožnosti za delo bolnice z rakom dojke predstavlja vračanje na delo po procesu zdravljenja in rehabilitacije. V zaključku razmišlja o tem, kaj je pomembno za terapevta in bolnika po zdravljenju raka
Febrilna nevtropenija in nevtropenija višje stopnje ob adjuvantnem zdravljenju nedrobnoceličnega raka pljuč v vsakodnevni praksi
Get PDFBased on clinical trial data, platinum-based adjuvant chemotherapy (Cht) is an intermediate risk factor for febrile neutropenia in patients with operable non-small-cell lung cancer (NSCLC). This study aims to assess the incidence of febrile neutropenia (FN) and high-grade neutropenia (G 3/4 N) in a group of patients treated in everyday clinical practice, and to determine the groups of patients that are at high risk of developing FN and G 3/4 N. Methods: This observational cohort study included 150 consecutive patient treatments with adjuvant Cht at the University Clinic Golnik, from January 2010 to May 2016. Complete blood counts ware taken on day 1 and day 8 of each cycle, and during each cycle of Cht if clinically indicated. Primary prophylaxis with G-CSF was used based on physician%s decision. The patients and treatment characteristics were collected from the hospital registry data. The average number of Cht cycles was 3.7 (range 1-4). To assess the risk factors, a logistic regression analysis was conducted. Results: Only 6/150 (4%) patients developed FN and 43/150 (29%) patients developed G 3/4 N. None of these patients received primary prophylaxis with G-CSF. Out of the nine risk factors assessed (age, gender, histologic type, stage, performance status, presence of comorbidities, type of surgery, Cht regimen, and year of treatment) only the year of treatment (before/after 2013) appeared to be a significant predictor of FN plus G 3/4 N incidence in the regression model. However, inspecting the frequency table indicates a tendency for higher incidence of FN in the subgroups of patients with pneumonectomy, higher PS, and in those receiving carboplatin. Conclusion: The incidence of FN and G 3/4 N during platinum- -based adjuvant Cht for NSCLC in our daily practice is comparable to the incidence reported in clinical studies. According to our observation, it seems that patients with pneumonectomy, higher performance status, and those receiving carboplatin are those who would benefit most from primary prophylaxis with G-CSF. The decline of FN and G 3/4 N incidence in the second treatment period (after the year 2013) is probably reflecting a more adequate usage of primary prophylaxis with G-CSF at our clinic.Dopolnilna kemoterapija (KT) na bazi platine je srednje močan dejavnik tveganja za pojav febrilne nevtropenije (10- do 20-odstotna incidenca) pri operabilnem raku pljuč. Namen raziskave je bil preveriti pojavnost febrilne nevtropenije (FN) in nevtropenije višje stopnje (N G 3/4) v vsakodnevni klinični praksi napram izsledkom v kliničnih raziskavah ter opredeliti skupine bolnikov, ki imajo višje tveganje za pojav FN in N G 3/4. Metoda: V našo prospektivno, observacijsko raziskavo je bilo vključenih 150 bolnikov s postavljeno diagnozo operabilnega nedrobnoceličnega raka pljuč v obdobju od januarja 2010 do maja 2016 na Kliniki Golnik. Podatke o bolnikih in o zdravljenju smo povzeli iz bolnišničnega registra raka pljuč. Bolniki so bili zdravljeni z dopolnilno KT na bazi platine po radikalni kirurški odstranitvi primarnega pljučnega tumorja. V povprečju so bolniki prejeli 3,7 od predvidenih štirih ciklusov KT. Krvna slika je bila analizirana 1. in 8. dan vsakega cikla KT ter, če je bilo indicirano, kadarkoli v času prejemanja KT. Po presoji zdravnika so bolniki prejeli primarno profilakso z rastnimi dejavniki za nevtrofilne granulocite (pG-CSF). Za analizo dejavnikov tveganja za pojav FN in N G 3/4 smo uporabili logistično regresijo. Rezultati: Febrilno nevtropenijo je utrpelo 4 % (N = 6) bolnikov in N G 3/4 29 % (N = 43) bolnikov, nobeden od njih ni prejel pG-CSF. Od devetih opazovanih dejavnikov tveganja (starost, spol, histološki tip, stadij, stanje zmogljivosti, prisotnost pridruženih obolenj, tip operacije, vrsta KT in obdobje zdravljenja) se je v regresijskem modelu le obdobje zdravljenja izkazalo za statistično pomemben napovednik pojava FN in N G 3/4. Opazili pa smo tudi trend k višji pojavnosti FN pri bolnikih po pulmektomiji, s slabšim stanjem zmogljivosti in pri prejemanju karboplatina v citostatski shemi. Zaključek: V klinični praksi je pojavnost FN in N G 3/4 ob dopolnilni KT operabilnega nedrobnoceličnega raka pljuč primerljiva pojavnosti v kliničnih raziskavah. Bolniki po pulmektomiji, bolniki s slabšim stanjem zmogljivosti in ob prejemanju karboplatina imajo verjetno večjo korist od pG-CSF. Upad pojavnosti FN in N G 3/4 v drugem opazovanem časovnem obdobju (leta 2013-2016) verjetno odraža ustreznejšo uporabo pG-CSF na naši kliniki v tem obdobju
Mesto imunoterapije pri zdravljenju raka
Get PDFThe immunotherapy era began in 1893. Nearly a hundred years later, the first immunotherapy drugs were approved, for instance interferon and interleukin. The role of the immune system in cancer is best represented by the cancer-immunity cycle. In the first step of the cycle, tumor neo-antigens are released and, subsequently, captured by the antigen-presenting cells. In the second step, neo-antigens are presented to the T-cells in the lymph nodes. But additional co-stimulatory signals are needed for the priming and the activation of T cells. At that level, the potential inhibitory signals inhibit or prevent the hyperactivation of T cells and autoimmunity. The activated T cells migrate through circulation into the tumor tissue. A tumor cell is detected by a T-cell receptor. The result of this process is the so-called T-cell killing. A tumor stroma, however, can present different inhibitory signals that inhibit the function of cytotoxic T cells. The article presents the different ways of influencing the cancer-immunity cycle and the readily-approved immunotherapy drugs.Začetni poskusi zdravljena z imunoterapijo segajo v leto 1893. Skoraj stoletje kasneje pa so bila odobrena prva zdravila, ki jih štejemo med imunoterapijo, kot sta interferon in interlevkin. Vlogo imunskega sistema pri raku znanstveniki v zadnjih letih razlagajo s pomočjo protitumorskega imunskega cikla. V prvem koraku tega cikla pride do sproščanja tumorskih antigenov (neoantigenov), ki jih antigen predstavitvene celice spoznajo in ujamejo. V drugem koraku jih v bezgavkah predstavijo celicam T. Za aktivacijo in determinacijo celic T v smeri citotoksičnih T-celic je potreben še dodaten stimulatorni signal. Morebitni inhibitorni signali pa aktivacijo celic T zavirajo oz. preprečujejo čezmerno aktivacijo in avtoimunost. Aktivirane celice T po krvi potujejo v tumor. Tumorsko celico prepoznajo prek T-celičnega receptorja. S tem preide do uničenja tumorske celice. V sami tumorski stromi pa so lahko različni inhibitorni signali, ki delovanje citotoksičnih celic T onemogočijo. V prispevku so predstavljeni možni načini vplivanja na protitumorski imunski cikel in trenutno registrirana zdravila s področja imunoterapije
Sistemsko zdravljenje z interferoni v onkologiji
Get PDFInterferons are an integral part of communication between the cells responsible for triggering the protective defenses of our immune system. In oncology, they are administered in prescribed doses to treat different cancers. They are of utmost importance in adjuvant treatment of malignant melanoma, namely in high doses of interferon α2b. Malignant melanoma is a highly aggressive malignant disease that is curable in more than 80 % of patients, if surgically removed in early stages of the disease. If, upon detection, regional lymph nodes are already positive, an incurable metastatic disease develops in more than 50 % of patients. For patients with a greater possibility of disease recurrence (stages IIB, IIC, and III), adjuvant therapy with a high dose of interferon α2b is recommended in Europe; while for high-risk stage IIIA (node metastasis > 1 mm) and stages IIIB and IIIC, a high dose of the anti-CTLA monoclonal antibody ipilimumab is recommended in the United States. The side effects of a high dose of interferon are manageable with a well-educated and compliant patient.Interferoni so pomembni za komunikacijo med celicami, ki so vključene v obrambo našega imunskega sistema. V onkologiji jih predpisujemo pri zdravljenju različnih rakov, v predpisanih odmerkih. Najpomembnejšo vlogo imajo v adjuvantnem zdravljenju malignega melanoma pri velikih odmerkih z interferonom- -α2b tipa. Maligni melanom je v več kot 80 odstotkih ozdravljiva bolezen, če se kirurško odstranjuje v zgodnjih fazah. V primeru pozitivnih regionalnih bezgavk se v več kot polovici teh bolnikov razvije metastatska bolezen, ki je neozdravljiva. Pri bolnikih z večjo verjetnostjo ponovitve bolezni v stadijih IIB, IIC in III se tako priporoča adjuvantna terapija z visokim odmerkom interferona- α2b v Evropi, v stadiju IIIA z visokim tveganjem (velikost metastaze v regionalni bezgavki > 1 mm) in v stadijih IIIB in IIIC pa v ZDA priporočajo zdravljenje z visokim odmerkom anti-CTLA monoklonalnega protitelesa ipilimumaba. Neželeni učinki visokega odmerka interferona so obvladljivi z dobro edukacijo in s sodelovanjem bolnikov