Non-small cell lung cancer (NSCLC) has become the best example of precision oncology's impact on outcomes in everyday clinical practice, significantly changing the expectations of all stakeholders, ...including medical professionals, society, and most importantly, patients. Consequently, the implementation of the precision oncology concept in medical systems, in order to achieve optimal and proven curative effects in NSCLC, is imperative. In this study, we investigated the development, challenges, and results associated with the implementation of precision oncology in NSCLC on a national level in Croatia. We conducted a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients with metastatic lung cancer, on whose tumors specimen comprehensive genomic profiling (CGP) testing was performed during 2020 and 2021. A total of 48 patients were included in the study. CGP revealed clinically relevant genomic alterations (CRGA) in 37 patients (79%), with a median of 2 (IQR 1-3) CRGA per patient. From the panel of recommended tests,
,
, and
were the most common alterations, detected in 16 (34%), 5 (11%), and 3 (6%) patients, respectively. CGP revealed additional targetable mutations in 29 (60%) patients who would not have been tested (and consequently, whose mutations would not have been detected) according to the existing everyday standard of practice in Croatia. The tumor mutational burden was reported as high (≥10 Muts/Mb) in 19 patients (40%). CGP analysis reported some kind of targeted therapy for 34 patients (72%). CGP revealed other potentially targetable mutations, and it also determined TMB to be high in a significant number of patients. In conclusion, when possible, CGP should be used as an upfront backbone diagnostic and treatment-oriented work-up in patients with NSCLC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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
Background: In modern breast cancer management, SLNB is a standard of care. For the patients with limited sentinel lymph node involvement in the upfront surgery setting, ALND can be safely omitted. ...However, for any sentinel node metastasis detected following neoadjuvant systemic treatment (NST), ALND is still considered a mandatory procedure. Patients and methods: Present retrospective analysis has included all breast cancer patients submitted to surgery following NST in Clinical Hospital Centre (CHC) Rijeka in the period from 2017 till 2020. Results: SLNB was performed in 151 of 222 consecutive patients, and sentinel node metastasis was detected in 49 cases. The risk of non-sentinel lymph node involvement in sentinel node-positive patients was 34.7%, but exclusively for cases with macro-metastatic disease detected in the sentinel node. In addition, for the patients diagnosed with clinically uninvolved axilla, the risk of ypN2-3 status was only 2.8%. Conclusions: ALND following NST is overtreatment in 65.3% of sentinel node-positive patients. Axillary irradiation with the omission of ALND should be considered for the sentinel-positive patients with only micro-metastatic disease detected in the sentinel node following neoadjuvant chemotherapy, as well as for those with low volume macro metastatic disease, diagnosed with the uninvolved axilla.
Background: Following breast cancer treatment recommendations, the conservative approach is accepted and highly respected in the Clinical Hospital Center (CHC) Rijeka. However, we have found that ...institutional follow-up data are lacking. This retrospective analysis aims to update institutional data on survival and disease control rates. Methods: From 2011 till 2014, 915 breast cancer patients underwent surgery at CHC Rijeka, and 615 were included in this analysis. The Institutional Ethics Committee approved the analysis. Results: All patients were female, and the average age was 59 years. In the 5-year postoperative period, local, regional, and distant recurrence-free survival rates and overall survival and disease-free survival were calculated. All rates negatively correlate with a higher T and N status and a higher stage of the disease. The analysis has also demonstrated that in the pT1-3 pN0-1 subgroup, sentinel lymph node biopsy (SLNB) was not inferior to axillary lymph node dissection (ALND) in terms of locoregional control of disease and overall survival. Conclusion: Besides updating institutional data, the analysis confirmed that overall survival and locoregional control of the disease in the upfront-surgery patients are similar between pN0 and pN1 subpopulations and between pN2 and pN3, but statistically significantly different between pN0-1 and pN2-3. Currently ongoing, prospective observational multicenter clinical trial aims to translate the significance of these results into the neoadjuvant era.
Introduction: After the consensus conference in St. Gallen and updated NCCN guidelines, we started doing sentinel lymph node biopsy (SLNB) in May 2017, for breast cancer patients who achieve clinical ...axillary remission following neoadjuvant treatment. This study’s primary goal was to evaluate the clinical impact of SLNB after neoadjuvant therapy in the group mentioned above. Methods: We retrospectively analyzed all neoadjuvant breast cancer patients from May 2016 until May 2018 at Clinical Hospital Center Rijeka. Our preliminary results recorded the appearance of locoregional and distant recurrence. Results: From 65 patients involved in this analysis, 48 patients were node-positive at the time of diagnosis, and 45.83% among those achieved complete pathological axillary remission. After the first postoperative year, there were no locoregional relapses nor statistically significant differences in the prevalence of distant recurrences, regardless of the extent of surgical procedure. However, results showed higher rates of locoregional and distant relapse for the group of patients that did not attain complete axillary remission. Conclusion: SLNB is a reliable alternative to ALND for locoregional and overall disease control for breast cancer patients who achieve complete clinical axillary remission after preoperative systemic treatment. The clinical axillary lymph node status, after neoadjuvant therapy, is a more relevant prognostic factor than the clinical axillary lymph node status at the beginning of the treatment.
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.
The computed tomography has become a standard tool in radiation therapy
treatment planning. Additionally, there is a growing awareness of the dose
delivered to the part of the body outside the target ...volume. The ionizing
radiation carries a stochastic risk of malignancy, therefore, the doses
should be kept as low as reasonably achievable in order to provide an
adequate information needed for the radiotherapy planning. The objective of
this work was to set up the initial diagnostic reference levels and correlate
to the image quality that would be used in the future optimization of
localization scans. To quantify the doses from computed tomography
localization scans at the University Hospital Rijeka, local diagnostic
reference levels were established for five most common procedures of
different anatomical regions; head, head and neck, pelvis, breast and thorax.
The Computed Tomography Dose Index volumetric and the Dose-Length Product
were used as dose indicators and scanning parameters were also recorded. The
image quality assessment was performed for each set of images. The results
were compared to the seldom published data in order to compare the clinical
practice. The image quality for almost all of the body regions are scored as
acceptable in average but require improvement. It is shown that the
optimization of radiotherapy protocols is required. Therefore, these
results will be used as a guideline for that process. The establishment of
the national diagnostic reference levels for computed tomography localization
procedures in radiation therapy is the next step and is currently an ongoing
process.
nema
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
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.
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