Today, in the era of precision medicine, the determination of genomic instability or other potentially targetable mutations, along with BRCA 1 and BRCA 2, is a crucial component of the diagnosis and ...treatment management of advanced ovarian cancer. Advanced technologies such as next-generation sequencing (NGS) have enabled comprehensive genomic profiling (CGP) analysis to become more feasible for routine use in daily clinical work. Here, we present the results for the first two years of an analysis of patients with advanced ovarian cancer on a national level. The aim was to establish the position of CGP in the daily clinical practice of treating ovarian cancer. We performed a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients who were newly diagnosed with locally advanced or metastatic ovarian cancer or whose initial disease had progressed from 1 January 2020 to 1 December 2021, and whose tumors underwent CGP analysis. All 86 patients (100%) analyzed with CGP had at least one genomic alteration (GA). The median LOH was 14.6 (IQR 6.8–21.7), with 35 patients (41%) having an LOH ≥ 16. We found BRCA-positive status in 22 patients (26%). Conventional testing, which detects only BRCA mutations, would have opted for therapy with PARP inhibitors in 22 (26%) of our patients. However, CGP revealed the need for PARP inhibitors in 35 patients (41%). The results identified a significantly higher number of women who would achieve a possible benefit from targeted therapy. Hence, we believe that CGP should be a backbone diagnostic tool in the management of ovarian cancer.
Primarni kirurški zahvat i danas se još smatra temeljem liječenja lokalno uznapredovalog epitelnog raka jajnika. Kemoterapija uobičajeno slijedi nakon provedene operacije. No, preživljenje bolesnica ...s uznapredovalim epitelnim rakom jajnika, prema International Federation of Gynecology and Obstetrics (FIGO) stadiji IIIC i IV, koje čine više od 75% svih bolesnica s rakom jajnika još ne zadovoljava. U tih bolesnica često nije moguće provesti adekvatnu resekciju svih promjena u abdomenu (optimalni »debulking« – odstranjenje svih vidljivih tumorskih promjena u abdomenu) pa je učinkovitost citostatika smanjena. Zbog toga se kao mogući optimalni pristup nameće prijeoperativna kemoterapija (neoadjuvantna) koja dovodi do smanjenja primarnog tumora i mogućih presadnica po abdomenu. Takvim pristupom omogućava se kraći i jednostavniji kirurški zahvat nakon 3–4 ciklusa kemoterapije uz veću vjerojatnost optimalnog smanjenja tumorskih masa u abdomenu. Neoadjuvantna kemoterapija (NAC) epitelnog raka jajnika danas je jedna od mogućnosti uspješnog liječenja uz značajno smanjenje postoperativnih komplikacija u bolesnica lošijeg općeg stanja ili primarno inoperabilne bolesti.
Background. Although today it is almost preventable, cervical cancer still represents a significant cancer burden, especially in some developing parts of the world. Since the introduction of ...bevacizumab in the first-line treatment of metastatic disease, improvements of the outcomes were noted. However, results from randomized controlled trials are often hard to recreate in the real-world setting. Objective. To assess the real-world efficacy and safety of bevacizumab as a first-line treatment of advanced cervical cancer. Methods. We conducted a retrospective cohort study on the total population of Croatian patients diagnosed with metastatic cervical cancer from 2016 to 2019 who were treated with bevacizumab in combination with cisplatin and paclitaxel (TCB) in the first line. The comparison group was the consecutive sample of patients treated with chemotherapy alone. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, incidence of adverse events, and the proportion of treatment discontinuation. Results. We enrolled 67 patients treated with TCB and a control group of 62 patients treated with chemotherapy alone. The TCB cohort had significantly longer unadjusted OS with a median of 27.0 (95% CI 18.5; not calculable) months, compared to 15.5 (10.7; 30.1) months in the chemotherapy-alone cohort. Adjusted OS was not significantly different. PFS was significantly longer for the TCB cohort, with a median of 10.6 (95% CI 8.5; 15.4) months, than for the chemotherapy-alone cohort, with a median of 5.4 (95% CI 3.9; 9.1) months, even after adjustment for baseline covariates (HRadjusted = 0.60; 95% CI 0.39; 0.94; p=0.027; false discovery rate <5%). Conclusions. In a real-world setting, TCB as a first-line treatment of metastatic cervical cancer was associated with longer PFS, better objective disease control rate, and acceptable toxicity profile in comparison to chemotherapy alone. These results may indicate its utility and potential applicability in other parts of the developing world.
Rak jajnika i jajovoda, odnosno adneksa, i primarni rak potrbušnice jest šesta po učestalosti zloćudna bolest žena i najsmrtonosniji ginekološki tumor u Hrvatskoj. Histološki je rak jajnika, jajovoda ...i potrbušnice najčešće epitelnog podrijetla, i to seroznog podtipa. Rjeđi su različiti neepitelni tumori jajnika kao i presadnice u jajnike. Posebnu skupinu čine karcinomi niskog zloćudnog potencijala označeni neinvazivnošću, klinički indolentnim tijekom i dobrom prognozom. Klinički su karcinomi u ranim stadijima razvoja uglavnom asimptomatski, tako da se najčešće dijagnosticiraju u kasnijim, uznapredovalim stadijima bolesti. Dijagnoza se potvrđuje patohistološkim nalazom, a iznimno nalazom citološkog bloka nakon provedene dijagnostičke obrade. O liječenju i praćenju bolesnica odlučuje multidisciplinarni tim uzimajući u obzir osobitosti bolesnice (dob, opće stanje i komorbiditete) kao i obilježja samog tumora (stadij bolesti, histološki tip i stupanj zloćudnosti tumora, status homologne rekombinacije, odnosno gena BRCA 1 i 2 kao i odgovor na prethodno liječenje i popratnu toksičnost ako se radi o povratu bolesti). Liječenje primarnog raka jajnika, jajovoda i potrbušnice temelji se na kirurškom liječenju, sistemskoj primjeni kemoterapije, imunoterapije, ciljane terapije i hormonske terapije kao i suportivno-simptomatskih mjera tijekom cijelog liječenja. Terapijski pristup se razlikuje kod rjeđih neepitelnih histoloških tipova ovih tumora jer se češće dijagnosticiraju u ranim stadijima bolesti, imaju indolentniji tijek, drugačiju biologiju bolesti kao i osjetljivost na sistemsko liječenje. U tekstu koji slijedi predstavljene su obnovljene i nadopunjene kliničke upute s ciljem standardizacije postupaka i kriterija postavljanja dijagnoze, liječenja te praćenja bolesnica s rakom jajnika, jajovoda i potrbušnice u Hrvatskoj. Prvo izdanje smjernica za dijagnozu, liječenje i praćenje bolesnica s rakom jajnika objavljeno je 2013. godine.1
Rak vrata maternice, u odnosu na novotvorine drugih ginekoloških sijela, bolest je žena mlađe životne dobi koja se može prevenirati zdravstvenim odgojem i cijepljenjem adolescentske populacije te ...preventivnim i redovitim ginekološkim pregledima, a u ranim stadijima bolesti i učinkovito liječiti. Metode liječenja uključuju kirurgiju, radioterapiju i sistemnu terapiju, ovisno o stadiju bolesti i općem stanju bolesnica. Odluku o liječenju donosi multidisciplinarni tim u koji trebaju biti uključeni ginekolozi, radiolozi, klinički onkolozi, patolozi, citolozi i po potrebi kirurzi i urolozi. Uspjeh liječenja uvelike ovisi o njihovoj međusobnoj suradnji i kvalitetnoj komunikaciji u razmjeni iskustava i nalaza. S obzirom na važnost ove bolesti i posljedice koje ostavlja na obitelj i društvo potrebno je definirati i provoditi standardizirani pristup u dijagnostici, liječenju i praćenju ovih bolesnica. U tekstu koji slijedi iznesene su obnovljene i nadopunjene kliničke smjernice s ciljem implementacije standardiziranih postupaka u radu s bolesnicama s rakom vrata maternice u Republici Hrvatskoj.