Introduction: Bevacizumab is a recombinant humanized anti-VEGF monoclonal antibody. It is an effective treatment for epithelial ovarian cancer, both in primary and recurrent disease. The incidence of ...ovarian cancer increases with advancing age. Despite the high prevalence of the ovarian cancer in elderly, the management of these patients is often less aggressive than in younger patients. In Croatia, from February 2017, we have opportunity to treat patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer with bevacizumab in the first-line and second-line settings. Our aim was to investigate the safety of bevacizumab administration in patients older than 65 years. Methods: We have retrospectively analyzed the archive data of 65 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer who started treatment with bevacizumab in primary advanced and in first relapse setting at the Department of Gynecologic Oncology in the University Hospital Centre Zagreb in the period from January 2017 to December 2018. Patients were divided in two categories according to age: group 1 (≤65 years) and group 2 (>65 years). Results: Our analysis included 65 patients:47 (72.3%) patients in group 1 compared with 18 (27.7%) in group 2. Bevacizumab was administered to 39 (60%) patients as first-line treatment and to 26 (40%) patients as second-line treatment. The median age was 70 years (range 66-76 years) in group 2 and 55 years (range 35-65 years) in group 1. ECOG status 0 had 44.7% of patients in group 1 compared with only 22% in group 2. At the time of diagnosis, elderly patients had presented with at least one comorbidity in 94.4% of the cases, compared with 42.6% in group 1. The median number of cycles of bevacizumab was 9 in elderly patients and 17 cycles in group 1. Among those patients receiving bevacizumab in the first-line setting, median progression free interval (PFI) was 12 months in younger patients versus 7 months in elderly patients. Similarly, among those receiving bevacizumab in the second-line setting PFI was 9 months in younger patients versus 1 months in elderly patients. The occurrence of non-hematological adverse events did not increase in elderly patients; 51.1% of patients in group 1 reported some of non-hematological adverse events versus only 27.8% in elderly patients. Conclusion: Our experience in treating patients with bevacizumab shows good results with acceptable toxicity and our findings suggest that its use in the elderly population should be considered as safe and manageable.
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.
Our objective was to assess the safety and efficacy of olaparib in maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma after the partial or complete response to ...the second or further lines platinum-based chemotherapy in a real-world setting. We performed a multicenter, real-world observational population-based cohort study on the whole population of Croatian patients initiated to olaparib maintenance therapy between 2016 and 2020. The primary endpoints were progression-free survival and the discontinuation of treatment because of adverse events. We enrolled the total population of 69 patients with the median (interquartile range; IQR) age of 53 (48–59), 56 (81%) of them with BRCA1 mutation. The median (IQR) follow-up was 16 (9–25) months. Treatment had to be discontinued because of toxicity in 2 (3%) and temporarily interrupted in 14 (20%), while dose was reduced because of toxicity in 18 (26%) of patients. Toxicity of any grade was observed in 61 (88%) patients and toxicity of grade 3 or 4 in 12 (17%). Median progression-free survival was 21 (95% CI 16-not calculable) months from the introduction of olaparib, and the median overall survival was not reached. Our study confirmed efficacy and safety of olaparib as the maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma. We observed the real-world efficacy and safety comparable to those observed in the randomized controlled trials. We found the interesting observation of better efficacy of 300 mg tablets, compared to 400 mg capsules, an issue that should be addressed on much larger real-world populations.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Comprehensive genomic profiling (CGP) is gradually becoming an inevitable part of the everyday oncology clinical practice. The interpretation and optimal implementation of the results is one of the ...hot topics of modern-day oncology. According to the recent findings, uterine cancer harbors a high level of gene alterations but is still insufficiently explored. The primary goal of this project was to assess the proportion of patients with targetable mutations. Also, the aim was to define and emphasize potential opportunities as well as the problems we have faced in the first year of testing on the national level. We performed a multicentric, retrospective, nested cross-sectional analysis on the total population of Croatian patients with advanced/metastatic uterine cancer where the tumor CGP was performed during 2020. CGP of the tumor tissue of 32 patients revealed clinically relevant genomic alterations (CRGA) in 27 patients (84%) with a median of 3 (IQR 1-4) CRGA per patient. The most common CRGAs were those of phosphatide-inositol-3 kinases (PIK3) in 22 patients (69%), with 13/22 (59%) of those patients harboring PIK3CA mutation. The next most common CGRAs were ARID1A and PTEN mutations in 13 (41%) and 11 (34%) patients, respectively. Microsatellite status was determined as stable in 21 patients (66%) and highly unstable in 10 patients (31%). A high tumor mutational burden (≥10Muts/Mb) was reported in 12 patients (38%). CGP analysis reported some kind of targeted therapy for 28 patients (88%). CGP determined clinically relevant genomic alterations in the significant majority of patients with metastatic uterine cancer, defining it as a rich ground for further positioning and development of precision oncology.
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.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Ovarian and fallopian tube cancer, i.e., adnexal tumours, and primary peritoneal cancer is the sixth most common female cancer and the deadliest gynecologic tumor in Croatia. Hystologically, these ...tumors are most commonly of epithelial origin, a serous subtype. Less common are various non-epithelial ovarian malignancies, as well as ovarian metastases. A special group consists of epithelial carcinomas of low malignant potential characterized by non-invasiveness, clinically indolent course, and good prognosis. Clinically, these cancers are generally asymptomatic in early stages, and therefore usually diagnosed in later, advanced stages. The diagnosis is confirmed by pathological examination, or exceptionally by cell block cytology finding after the completion of diagnostic procedures. Multidisciplinary team makes treatment and follow-up decisions, taking into account patients’ (age, general condition, and comorbidities) and tumor characteristics (stage of disease, histological type and grade, homologous recombination status or BRCA gene 1 and 2 status, as well as the response and toxicity to previous treatment in case of relapse). The treatment of primary ovarian, fallopian tube, and peritoneal cancer is based on surgical procedures, systemic administration of chemotherapy, immunotherapy, targeted therapy and hormone therapy, as well as symptomatic-supportive measures throughout the whole treatment. Treatment approach differs in less frequent non-epithelial histological types of these tumors because they are commonly diagnosed in early stages of the disease, have a more indolent course, different disease biology and sensitivity to systemic treatment. The following text presents the updated and supplemented clinical guidelines in order to standardize procedures and criteria for diagnosis, management, treatment and monitoring of patients with ovarian, fallopian tube, and primary peritoneal cancer in Croatia. The first edition of the guidelines for diagnosis, treatment and monitoring of patients with ovarian cancer was published in 2013.1
Cervical cancer, in comparison with other gynecological malignancies, mainly affects younger women. It can be prevented through educational programs, vaccination, screening and early detection. In ...early stages it can also be effectively treated. Treatment modalities include surgery, radiotherapy and systemic therapy according to stage of the disease and patient condition. Treatment decisions should be made through multidisciplinary team meetings that consist of gynecologists, radiologists, clinical oncologists, pathologists, cytologists and if necessary surgeons and urologists. The success rate of the treatment depends significantly on their good and thorough communication and cooperation. Due to the significance and impact of this disease it is important to define and implement a standardized algorithm and approach for diagnostics, treatment and monitoring. The following text presents up-dated and supplemented clinical guidelines for the standardization of the diagnostic criteria, management, treatment and monitoring of patients with uterine cervical cancer in the Republic of Croatia.
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
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