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Precision medicine has reached its current peak in non-small cell lung cancer (NSCLC), with a constantly growing number of predictive biomarkers and new targeted therapies that when applied, significantly affect and change outcomes. Hence, the matter in question is how we might optimally detect and implement them in the treatment of our patients in everyday clinical practice. The main problem in the diagnostic workup of NSCLC is the rather limited tumor sample used on many occasions in the classical diagnostic approach, which consists of a series of single-biomarker tests. Consequently, the introduction of comprehensive genomic profiling (CGP) in everyday diagnostic and clinical practice is one of the imperatives that could benefit everybody involved. Here, we present national data and our experiences with the application of comprehensive genomic profiling in NSCLC. The results have shown the utility and potential benefit of comprehensive genomic profiling, but also challenges involved in the implementation of precision oncology in clinical practice. So when possible, CGP should be used as an upfront backbone diagnostic and treatment-oriented work-up in patients with NSCLC.

Adding ovarian function suppression to adjuvant endocrine therapy (AET) lowers the disease recurrence rates among premenopausal women with hormone receptor-positive (HR+) early breast cancer (EBC). However, a detrimental effect on endocrine symptoms burden (ESB) is expected. Therefore, this study aimed to investigate differences in Quality of life (QoL) and endocrine symptoms in premenopausal women prescribed AET, with/without gonadotropin-releasing hormone agonist (GnRH).This study showed that GnRH+AI in premenopausal women with HR+ EBC results in greater ESB and lower QoL compared to patients treated with TAM or GnRH+TAM. Therefore, interventions helping decrease the ESB in patients treated with AI+GnRH should be explored and developed to help patients adhere to and persist in AET.

Serum concentrations of interleukin-17 in patients with liver diseases are elevated in comparsion to healthy population.

Dnevna bolnica Klinike za onkologiju jedna je od ustrojbenih jedinica Klinike za onkologiju namijenjena u prvom redu aplikaciji sustavne onkološke terapije, a potom i simptomatskoj terapiji onkoloških bolesnika. : Putem Dnevne bolnice Klinike za onkologiju na dnevnoj bazi liječi se velik broj onkoloških bolesnika.Budući da se kao najčešće zastupljeno sijelo u Dnevnoj bolnici izdvaja rak dojke, a iza kojeg slijede probavni tumori, planiranje vremenskih i kadrovskih resursa u skladu s navedenim rezultatima povećalo bi kvalitetu zdravstvene skrbi onkoloških bolesnika.

Background and Purpose : So far published data have implicated IL-17 in the promotion of liver fibrosis since it facilitates the influx of inflammatory cells, leading to the expression of profibrogenic growth factors and activation of hepatic stellate cells, so it could be considered to be a profibrotic cytokine. The aim of this study was to investigate the presence and level of interleukin-17 in sera of patients with various liver diseases and healthy controls. Methodology: Two hundred five (205) patients (age 21-84 years ; median 60) with liver disease (33 with hepatocellular carcinoma (HCC), 51 with liver cirrhosis, 43 with viral hepatitis B or C, 50 with autoimmune liver disease (ALD), 21 with non- alcoholic fatty liver disease (NAFLD), 7 pts of non- defined inflammatory liver disease) and 28 healthy controls, were included. Serum interleukin-17 levels were measured by enzyme-linked immunosorbent assay (ELISA). Results and Discussion: Levels of circulating of interleukin-17 in patients with liver disease of any origin (1, 04 -86, 99 pg/ml ; Median 5, 54 pg/ml) were significantly higher than those in healthy controls (1, 04-10, 22 pg/ml ; Median 1, 66). Highest levels were found in patients with liver cirrhosis (1, 98-38, 5 pg/mL ; Median 9, 8) while HCC, autoimmune liver diseases, NAFLD and viral hepatitis had lower levels (1, 27-22 pg/mL ; Median 5, 7, 1.72-72 pg/mL ; Median 3, 5, 1, 02-40, 7 pg/mL ; Median 4, 7, 1, 2-36, 9pg/mL ; Median 3, 73 respectively) but still higher than the healthy controls. Statistically significant difference was found in intrelukin-17 levels between patients with ALD and HCC (P=0.0073) ; ALD, viral hepatitis and HCC and cirrhosis p=0, 0001, p=0.0217, p=0, 0023, respectively. Conclusion: According to those preliminary data circulating IL17 could be a promising prognostic marker of liver inflammation and fibrosis state. Since there was a significantly lower level of IL17 in patients with HCC compared to cirrhosis could we predict the development of HCC with a drop in IL17? Further investigations are surely needed to clarify the role of IL17 in inflammation as well as in organ fibrosis.

Metabolomics is a systems approach in medical research that aims to quantitatively analyze small molecules (less than 1500 Da) in a given biospecimen. Improvement in analytical technologies enabled metabolic research in various fields of medicine including oncology. Metabolic reprogramming is a firmly established hallmark of cancer. It includes changes in tumor cells and in the stromal cells as well. In this review, we focus on metabolomics in the field of cancer research. In the first part, we discuss the main technical approaches. In the second part, we address altered cancer metabolism and additional roles of some metabolites besides energetic and structural roles.

KOncentracije anti-p53 protutijela u serumu bolesnika s bolestima jetre bile su statistički značajno više od zdravih ispitanika.

Metastatski rak dojke je neizlječiva bolest sa skromnim petogodišnjim preživljavanjem. Iako je terapija i dalje palijativne naravi, iskorak u liječenju predstavlja kombinacija CDK4/6 inhibitora i endokrine terapije (ET). U trenutku uvođenja CDK 4/6 inhibitora u standardnu kliničku praksu, veliki udio bolesnica bio je prethodno tretiran drugim terapijskim opcijama te su se CDK 4/6 inhibitori koristili u višim linijama liječenja. Analizom gotovo pet godina, ustanovljen je kontinuiran porast korištenja CDK 4/6 inhibitora u prvoj liniji liječenja metastatskog HR+/HER2– raka dojke.

Evaluation of adherence and associated sociodemographic and clinical factors in patients with metastatic breast cancer treated with CDK 4/6 inhibitors

Od svih bolesnica s novodijagnosticiranim rakom dojke u otprilike 70% njih radi se o hormonski ovisnom raku dojke. Učestalost raka dojke u predmenopauzalnih je bolesnica manja, a njihovi tumori rjeđe su hormonski ovisni te su obično zahtjevniji za liječenje. Predmenopauzalne bolesnice s hormonski ovisnim tumorima obično imaju lošiju prognozu u odnosu na postmenopauzalne s bolešću sličnih karakteristika. Sustavna adjuvantna terapija primjenjuje se kako bi se smanjio rizik od povrata bolesti. Gotovo se sve bolesnice s hormonski ovisnim tumorima dojke liječe adjuvantnom endokrinom terapijom, dok se u visokorizičnih može primijeniti i adjuvantna kemoterapija te produljiti trajanje primjene adjuvantne endokrine terapije. Pri odluci o vrsti sustavne adjuvantne terapije bolesnice je potrebno stratificirati prema klasičnim kliničkopatološkim karakteristikama te prema rezultatima profila ekspresije gena dobivenog multigenskim testovima. U bolesnica mlađih od 50 godina s hormonski ovisnim, HER2 negativnim tumorima i negativnim limfnim čvorovima u pazuhu pri odluci o vrsti adjuvantnog liječenja preporučuje se određivanje genskog profila primjenom testova Oncotype Dx te je, u slučaju zbroja rizika od povrata bolesti RS (recurrence score) < 16, opravdano izostavljanje adjuvantne kemoterapije i primjena samo adjuvantne endokrine terapije. Nadalje, prema trenutno dostupnim literaturnim podacima, predmenopauzalne bolesnice s 1 – 3 pozitivna limfna čvora u pazuhu imaju koristi od primjene adjuvantne kemoterapije neovisno o rezultatima multigenskih testova, stoga primjena istih u potonjem slučaju nije indicirana.

Introduction: According to the 5th ESO-ESMO International Guidelines for Advanced Breast Cancer, primary endocrine resistance is defined as recurrence during the first 2 years of adjuvant endocrine therapy (ET) or disease progression within the first 6 months of first-line ET for metastatic breast cancer (mBC). The same guidelines define secondary endocrine resistance as disease progression during or within 12 months of finishing adjuvant ET but after the first 2 years of treatment or progression after 6 or more months of ET for mBC. CDK 4/6 inhibitors in combination with ET are indicated as treatment for hormone sensitive (HR+) HER2 negative (–) mBC. For endocrine resistant population, the optimal endocrine partner of CDK4/6 inhibitor is fulvestrant. The aim of this study was to determine how much we adhere to the guidelines for treatment of the endocrine-resistant population in everyday clinical practice. Methods: We conducted a retrospective observational cross- sectional study by analyzing UHC Zagreb database for the 203 patients with HR+HER– mBC treated with CDK 4/6 inhibitors (palbociklib, ribociclib and abemaciclib). Of these, 83 were endocrine sensitive, 37 primary endocrine resistant, and 83 secondary resistant. Among the endocrine-resistant patients, we singled out 13 patients for whom the criteria of non-compliance with the guidelines was met. Result: Median patients’ age was 62 years (30–84) and the median follow-up was 12 months (1– 32). Of 120 endocrine-resistant, 13 patients progressed during or within 12 months of finishing adjuvant endocrine therapy, and as an endocrine partner of CDK 4/6 inhibitor an aromatase inhibitor was administered instead of the recommended fulvestrant. Conclusion: A retrospective analysis of endocrine resistant cohort revealed that although optimal endocrine partner of CDK4/6 inhibitor in this population is fulvestrant, this fact was overlooked in 10.8% of patients. A larger number of patients and longer follow-up are needed to analyze progression-free survival in the group of patients whose treatment was inconsistent with the guidelines.

Introduction: According to the current ASCO guidelines, trastuzumab and pertuzumab (TP) in combination with taxanes are indicated as 1st line treatment of HER2 positive metastatic breast cancer, and trastuzumabemtansine (T-DM1) as 2nd line. Due to the prolonged survival of patients with HER2 + breast cancer we occasionally encounter patients whose therapy for metastatic disease was started before the approval of pertuzumab. According to the ASCO guidelines T-DM1 can be used in the 3rd line of treatment if not already used in the 2nd line or pertuzumab if not used in the 1st or 2nd line. The aim of this study was to analyze the efficacy and tolerability of pertuzumab used as 3rd or subsequent line treatment. Methods: We conducted a retrospective chart review using the hospital information system and analyzed 4 patients with HER2 + metastatic breast cancer who received TP + vinorelbin (TPV) in late lines of treatment at the expense of the Department of Oncology at UHC Zagreb. They also received trastuzumab in combination with taxanes in the 1st line because their therapy was started before the approval of pertuzumab. Result: A case series of 4 patients treated with pertuzumab in subsequent lines of therapy, after trastuzumab with taxanes in the 1st line and T-DM1 in the 2nd line, is presented. In two patients, TPV was administered as 4th line treatment. Patient 1 (56) received 12 cycles and patient 2 (61) 10 cycles of TPV therapy until disease progression. Patient 3 (62) received 6 cycles of vinorelbine and 8 cycles of pertuzumab and trastuzumab as 5th line treatment with disease regression, but therapy was discontinued due to heart failure. Patient 4 (43) received 3 cycles in the 3rd line and partial regression of the disease was observed and she still receiving the treatment. Conclusion: In this small series of patients the effectiveness of pertuzumab with trastuzumab and vinorelbine was found despite its use in later treatment lines and earlier exposure to trastuzumab in the 1st line. In some patients who started treatment before the pertuzumab era, dual anti- HER2 blockade may be attempted in late treatment lines in accordance with the ASCO guidelines. This may delay disease progression and provide adequate dual anti-HER2 blockade for a

Introduction: The combination of CDK4/6 inhibitors and endocrine therapy (ET) prolongs survival in patients with HR+/HER2-metastatic breast cancer (mBC). Patients with bone marrow infiltration (BMI) often have low blood count parameters and are therefore an underrepresented group in CDK 4/6 inhibitor registration studies. The trial inclusion criteria include adequate haematopoiesis -absolute neutrophil count ≥ 1.5 × 10^9 / L, platelet count ≥ 100 × 10^9 / L and haemoglobin ≥ 9.0 g / dL. This study analysed the response totherapy and the time to treatment failure (TTF), defined as the interval from therapy initiation to premature discontinuation, in order to determine the safety and efficiency of thetreatment. Methods: Retrospectively, data from the hospital information system for 203 patients, treated with a combination of CDK 4/6 inhibitors and ET with the medianfollow-up of 12 months (1–32 months) was analysed. 16 patients (7.88%) had proven BMI and were analysed separately. Age, endocrine sensitivity, number of previous treatment lines and TTF were determined in this group. Result: The median age was 49.5 (34–78 years). 8 patients had de novo metastatic disease. At the start of treatment, 4 patients (25%) were endocrine- sensitive. CDK 4/6 inhibitors were a first-line treatment in 5 patients (31.25%), 2nd in 7 (43.75%), 3rd in 3 (18.75%) and 4th in one patient (6.25%). All patients treated in the first-line are still receiving the treatment with therapy duration of 3– 19 months. 9 patients (56.25%) with BMI reached TTF and their median TTF is 6 months (2–12). Conclusion: Observing the effects of CDK4/6 inhibitor treatment in patients with HR+ /HER2– mBC with BMI is important because in this subgroup, in everyday clinical practice, we frequently opt for chemotherapy due to the fast onset of action, and also because many consider bone marrow infiltration a manifestation of a visceral crisis. With transfusion support and close monitoring, response to treatment with CDK4/6 inhibitors and disease regression have been reported in most patients in the first-line of treatment, as well as in some patients treated in the subsequent lines. CDK 4/6 inhibitors can significantly affect the quality of life in this subgroup of patients by delaying the start of chemotherapy.

Introduction: Neoadjuvant therapy (NAT) with dual antiHER2 treatment has become standard for most HER2-positive breast cancer patients. Pathological complete response (pCR) has been used as an early surrogate parameter to monitor NAT’s effectiveness since it was found it’s associated with fewer recurrences and better survival. Although the pCR rate is highest for triple-negative and HER2 positive tumors, there are still many of those with residual disease. Based on the Katherine trial result, which showed improved prognostic outcome, trastuzumab emtansine (T-DM1) has become a preferable option for patients with HER2 positive breast cancer with residual tumor after NAT. Case report: A 46 years old premenopausal woman presented with a clinically palpable mass of the right breast and palpable lymph node of the right axilla. MRI revealed a 3.5 cm mass in the right breast, without cious malignant nodes in the axilla. A core needle biopsy was performed, and the histopathology showed triplepositive invasive ductal breast cancer (ER 100%, PR70%, HER2 3+, Ki- 67 30%, grade 2). Cytological analysis of axillary lymph nodes was negative. The patient received a standard NAT protocol with 4 cycle dose-dense doxorubicin/ cyclophosphamide (ddAC) followed by 12 cycle weekly paclitaxel with dual antiHER2 therapy with pertuzumab/ trastuzumab. Following the 4 ddAC cycles, ultrasound and clinical exam showed partial tumor regression. After NAT, complete remission of the tumor was revealed on MRI, and the patient underwent right breastlumpectomy followed by sentinel lymph node biopsy. Histopathological report from the specimen showed a residual tumor with a partial response to NAT (RCB II, ER 80%, PR 0, HER2 1+). Multidisciplinary team decisions included post- neoadjuvant systemic therapy with T-DM1, postoperative radiation therapy of chest wall and regional lymph nodes, and 5-year endocrine treatment with tamoxifen. After 5 cycles of full dose and one cycle with reduced dose, therapy with the T-DM1 agent was discontinued because of grade 3 peripheral neuropathy and she continued with only trastuzumab to complete a one-year treatment course. Conclusion: Postoperative treatment of patients with HER2 positive breast cancer with residual tumor after NAT should be optimized to achieve favorable outcomes.

Introduction: CDK4/6 inhibitors in combination with endocrine therapy have been reimbursed by Croatian Health Insurance Fond in the first line of HR+/HER2– metastatic breast cancer since August 2018. As current experiences with CDK4/6 inhibitors as well as response to subsequent therapies are limited, there are no precise guidelines for post-progression therapy. The aim of this study was to analyse real-world data for the subsequent therapy options after progression on CDK 4/6 inhibitors in University Hospital Centre Zagreb and to compare them with the published data. Methods: We retrospectively analysed data from the hospital information system for 203 patients (200 female and 3 male patients) treated with a combination of endocrine therapy and CDK 4/6 inhibitor. Median age was 62 years (30–87), and median follow-up was 12 months (1– 32). 18 patients were treated with abemaciclib, 106 with palbociklib and 79 with ribociclib. Analysis of treatment options after progression was done on 71 patients who had disease progression by 15. 10. 2020., of whom 31 were treated by first and 40 on a subsequent line of therapy. Result: Of the 71 patients who had disease progression, 55 were switched to a new line of therapy. 39 (70, 91%) received chemotherapy, most often with capecitabine (15) and paclitaxel (13). Endocrine monotherapy was administered in 10 patients (18, 18%) – fulvestrant in 6, an aromatase inhibitor in 3 and tamoxifen in one patient. Targeted therapy was given to 6 patients (10, 91%), 2 of whom got alpelisib with fulvestrant and 4 changed disease biology – therefore atezolizumab for triple- negative and anti-HER2 therapy for HER2 positive disease was given. Conclusion: The choice of first post-progression therapy was predominately chemotherapy, primarily with capecitabine and paclitaxel. Targeted therapy is also a viable choice especially in patients who have a confirmed PIK3CA signal pathway mutation or a conversion to HER2 positive disease. In previous studies, chemotherapy was also the most common choice but more patients received endocrine therapy than in this study (30, 7% to 18, 18%). Since the identification of PIK3CA mutation status has only recently become available in Croatia, in the future alpelisib with fulvestrant is expected to become a reasonable choice for patients with PIK3CA signal pathway mutations.

Introduction: Treatment options for patients with metastatic pancreatic cancer are limited. They are based on systemic chemotherapy whose effects are short limited and eventually pancreatic cancer becomes resistant to conventional therapy. The causes of pancreatic cancer vary and, in many cases, remain unknown. It includes many changes, like inactivation of tumor suppressor genes and mutation of genes which are included in DNA damage repair pathways like BRCA 1 and BRCA 2. Therefore, inhibition of PARP mediated pathway in patients with BRCA1 or BRCA2 mutation represents an important therapeutic option for these patients. The phase III POLO trial showed that maintenance treatment with the poly (ADP ribose) polymerase (PARP) inhibitor olaparib improved progression- free survival vs placebo (7.4 months vs. 3.8 months) among patients with germline BRCA-mutant metastatic pancreatic cancer that had not progressed during first-line platinumbased chemotherapy. Case study: We present interesting case from every day clinical practice. 75year old female was admitted in February 2017. to Department of Internal medicine UHC Zagreb due to severe abdominal pain. After comprehensive diagnostic assessment she was diagnosed with metastatic pancreatic adenocarcinoma. After seeing an oncologist, the patient started combination chemotherapy treatment with gemcitabine and nab- paclitaxel. Until May 2018. she was administrated with 11 cycles of chemotherapy and was regularly evaluated every three months with serum levels of the tumor marker and abdominal, pelvic and thoracic CT scans. Due to progression of liver metastasis in May 2018. she started with second- line chemotherapy with oxaliplatin and capecitabine. Also, Next generation sequencing (NGS) of tumor tissue was performed. From June to December of 2018. six cycles of chemotherapy have been administrated. Control evaluation in December 2018. showed stable disease and NGS results detected somatic mutations in BRCA1 gene. Due to results of NGS patient received maintenance therapy with PARP inhibitor talazoparib from medication donation program. Talazoparib was administrated from February 2019. until April 2020. with occasional disruptions due to thrombocytopenia and neutropenia, in total of 14 months which was significantly longer than median Progression- free survival in POLO trial. Control evaluation showed significantly progression of disease and active anti-cancer treatment was no longer indicated. In July 2020. the patient passed away from complications of progression of primary disease. Conclusion: All proposed molecular mechanisms in pancreatic cancer pathogenesis are still unknown. Additional polygenic tumor sequencing is the future of pancreatic cancer treatment. It is necessary to determine mutational status of BRCA1/2 genes from peripheral blood because standard treatment with PARP inhibitors in this moment requires detection of germ line mutation from peripheral blood. The case we presented shows that it is possible to achieve much longer over-all survival in patients with pancreatic cancer with combination of conventional and target therapy based on new generation sequencing analysis. Younger patients as well as the patients with positive family history for pancreatic cancer should be target group for genetic testing of BRCA1/2 mutations.

CDK 4/6 inhibitors are indicated in combination with fulvestrant or an aromatase inhibitor for the treatment of women with HR-positive HER2-negative advanced or metastatic breast cancer. Although all three CDK 4/6 inhibitors can cause drug-induced liver injury, it tends to be more pronounced with ribociclib. Methods: Clinical data from 79 breast cancer patients treated with ribociclib at the University Hospital Centre Zagreb from August, 2018 till November, 2020 were retrospectively examined. Result: The median age of the patients was 61 years. 33 patients had de novo metastatic breast cancer. 16 patients had liver metastases. An increase in aminotransferase levels (grade 3 or 4) was observed in 7 patients, mean age 62.7 years. Four patients had de novo metastatic breast cancer, 1 had liver metastases. In 1 patient ribociclib was permanently discontinued due to grade 4 hepatotoxicity, without subsequent aminotransferase normalization during follow-up. 6 patients developed grade 3 hepatotoxicity, for which treatment had to be permanently discontinued in 5 of them even after treatment interruption and dose adjustment. All 5 patients were on an aromatase inhibitor in addition to ribociclib and received a median of 4 cycles before discontinuation. Except in one patient in whom aminotransferases were persistently elevated during follow-up, the average time to enzyme recovery in others was 2.5 months. 3 patients switched from ribociclib to palbociclib and fulvestrant, and 1 to abemaciclib and fulvestrant. No hepatotoxicity was observed after the drug switch. Conclusion: Grade 3 and 4 hepatotoxicity occured in 8.8% of patients treated with ribociclib at the University Hospital Centre Zagreb, which is slightly lower than reported in MONALEESA trials (11.4%). In patients who require permanent discontinuation of ribociclib due to drug-induced liver injury, switching to another CDK 4/6 inhibitor could improve the side effects while maintaining the treatment benefit.

Neoadjuvant therapy (NAT) in breast cancer (BC), also called presurgical systemic therapy (PST), refers to systemic therapy administered prior to definitive surgery. In this review we’ll discuss historical, current and future perspective of NAT in BC. It was developed for patients with locally advanced, inoperable BC with the intention of downstaging unresectable tumors, or decreasing the extent of surgical intervention to replace radical mastectomy. These indications were mainly reffered to neoadjuvant chemoterapy (NACT). For patients with inflammatory BC, NACT is considered a standard of care. Nowadays, with advances in the molecular characterization of BC, NACT is being widely used for operable tumors and hold particular relevance in aggressive subtypes like triple negative BC (TNBC) and HER2-positive (HER2+) BC. Combination of anthracycline and taxane-based chemotherapy with pertuzumab and trastuzumab has become a standard NAT regimen for HER2+ disease. Postneoadjuvant treatment for those with residual disease after NACT was also a metter of research with positive KATHERINE trial with trastuzumab emtanzine given postneoadjuvant. In contrast, role of NACT in hormone receptor positive (HR+) HER2– BC is still metter of the debate, mainly due to low rates of pathological complete response (pCR) and lower accuracy of pCR as a surrogate predictor of long-term outcome. Neoadjuvant endocrine therapy (NET) still remains an unused potential in the management of HR+HER2– subtype, with key issues concerning the optimal treatment length, appropriate comparisons with NACTand its use in premenopausal patients. It has gained a central role as a platform to test new drug combinations in treatment naive patients or in „window of opportunity“ trials. Currently, the standard NACT for early-stage TNBC is anthracycline and taxane-based chemotherapy. Several new strategies have been investigated in the NAT of TNBC in order to individualize treatment and achieve higher proportion of pCR. According to the recent trials with checkpoint inhibitors, KEYNOTE-522 and IMpassion 031, the proportion of patients with pCR was significantly higher among those who received pembrolizumab or atezolizumab plus NACT. Strategies without chemo with single agent talazoparib are also under the spot-light for BRCA1/2 mutated tumors.

Background: The pandemic of coronavirus disease 2019 (COVID- 19) was declared in March 2020. The first wave of the pandemic was marked by strict epidemiological measures: lockdown, social distancing, and self- isolation. Cancer patients receiving systemic oncology treatments were considered a high-risk population regarding COVID19. These new circumstances posed possible obstacles for the treatment continuation, which in turn potentially led to an increase in distress. This study aimed to examine the impact of COVID-19 outbreak on a distress level among cancer patients. Methods: A total of 728 cancer patients, in 9 oncology centers, were approached to participate in the study. The study questionnaire with disease and sociodemographic characteristics was completed by 422 patients. Patients were stratified by cancer type: breast, gastrointestinal (colon, gastric, pancreatic), and other cancer types (lung, prostate, ovarian) ; and by disease stage, early or metastatic. All patients had to have an ongoing active oncology treatment which required regular visits to outpatient clinics or inpatient oncology departments. Distress level was measured using the Distress Thermometer with a cut- off value of 4. Results: There were 201 (47%) patients with breast cancer, 130 (32%) patients with gastrointestinal cancer (colon, pancreatic and gastric cancer), and 92 (21%) patients with other types of cancer (lung, prostate, ovarian). A total of 192 (46%) patients had early disease stage while 230 (54%) patients had advanced disease, respectively. A high distress level was reported in 189 (44.8%) of all patients. The breast cancer patients had significantly higher levels of distress when compared with other types of cancer. There was no significant difference in distress level regarding the disease stage. Conclusions: Almost every second cancer patient with ongoing active oncology treatment was highly distressed during the first wave of the COVID- 19 pandemic, regardless of the disease stage. Breast cancer patients tend to have higher levels of distress when compared with other cancer types. When evaluating distress during a pandemic one should take into account the possible impact of various aspects of COVID-19 disease and pandemic on a distress level in cancer patients.

Uvod: Bjelančevina p53 ima brojne funkcije uključujući i poticanje apoptoze. Protutijela na 53 povezana su s mutiranim statusom p53. Kaheksija je kompleksno stanje koje nastaje smanjenjem proteinske mase i masnog tkiva, uslijed promjenjenog metabolizma i smanjenog unosa proteina i kalorija, ali i proinflamatornog zbivanja u okviru patofiziologije kronične bolesti. Čak 80% onkoloških bolesnika u uznapredovaloj fazi bolesti ima razvijenu kaheksiju, a u njih 40% to je i uzrok smrti zbog čega kaheksija predstavlja važan prognostički parametar. Poznato je da su koncentracije TNF-α (tzv. kahetični citokin) povećane u bolesnika s kaheksijom. Istraživanja su pokazala da TNF-α posreduje u inhibiciji miogene diferencijacije kroz p53 PW1 ovisan put. p53 izražen je u matičnim mišićnim stanicama i nedostatak p53 mijenja broj tih stanica. Cilj: U ovom radu analizirali smo prisutnost protutijela na p53 (p53Abs) u serumu i slini bolesnika s različitim karcinomima. Cilj ovog istraživanja bio je odrediti koncentraciju p53Abs u serumu i slini bolesnika s različitim karcinomima i usporediti je s vrijednostima zdravih ispitanika u serumu i slini. Dobivene rezultate usporedili smo s indeksom tjelesne mase (BMI), dobi, odnosno da li su bolesnici bili kahetični ili nisu temeljem konsenzusa o BMI 19 kg/m2 kao graničnoj vrijednosti. Materijali i metode: U istraživanje smo uključili 58 bolesnika s različitim karcinomima i 20 zdravih ispitanika. Uzorci za ispitivanje bili su slina i serum bolesnika i zdravih ispitanika. Trinaest bolesnika imalo je kaheksiju, a četrdeset i pet bolesnika nije. Protutijela na p53 u serumu i slini određivali smo ELISA metodom. Cut-off vrijednosti za p53Abs u serumu i slini određene su ROC krivuljom, te je za slinu 7, 8 U/ml, a za serum 12, 2 U/ml. Rezultati: Bolesnici su imali povišene koncentracije p53Abs u serumu i slini u odnosu na zdrave ispitanike (serum, p=0.0013 ; slina, p=0.0001). Koncentracije p53Abs u slini i serumu bile su statistički povezane (p=0, 0002). Koncentracije p53Abs u slini bile su više (Median 25, 9 ; 95% CI 19, 9 – 43, 4) od koncentracija u serumu (13, 4 ; 95% CI 10, 8 – 16, 6). Analizirali smo i povezanost p53Abs u serumu u kahetičnih i nekahetičnih bolesnika i dobili negativnu statistički značajnu razliku (p=0, 0179) te isto tako i negativnu povezanost koncentracije p53Abs i statusa kaheksje u slini istih bolesnika (p=0.013). Statistički negativna povezanost nađena je između koncentracije p53Abs u serumu i BMI (p=0, 023), kao i koncentracije p53Abs u slini i BMI (0.019). Nismo dobili statističku povezanost koncentracije p53Abs u serumu i slini bolesnika s dobi bolesnika. Zaključak: Naši rezultati upućuju na mogućnost određivanja p53Abs u slini bolesnika s karcinomima, kao i moguće povezanosti povećane koncentracije p53Abs i kaheksije. Ovi rezultati ukazuju i na moguće određivanje p53Abs u slini i/ili serumu kao parametra kaheksije, budući da BMI nije uvijek precizna mjera iste.

Additional file 1. List of genes.

Background: In this study, we focused on communicating with cancer patients on active treatment during the first lockdown due to the COVID- 19 pandemic and the patient’s main sources of pandemic information. Methods: In the first wave of the pandemic, during the first lockdown, we conducted an observational study in 8 of the 13 oncology centers in Croatia. The study is based on an anonymous self-report questionnaire designed for this study. It included 422 oncology patients, older than 18 years, who were in active oncology treatment at the time. To study the correlation between the patient’s perspective on communicating with medical staff during a pandemic, the preferred type of communication, and the main sources of pandemic information relative to clinical and sociodemographic data, we used univariate descriptive and bivariate analyzes. Results: In the first lockdown, our respondents communicated with the oncologist and oncology nurses mostly in-person (77.7% vs. 81%), and with the general practitioner mostly virtually, most often by phone (70.6%). Regardless of the pandemic, the majority of oncology patients (76.1%) prefer to communicate with an oncologist in-person, and most expressed satisfaction with communicating with medical staff during a pandemic. The choice of information sources and type of communication depends on the age, gender, income, education, and the seat of the disease of patients. Conclusions: For most of our respondents, in-person visits were the basic way of communicating with oncologists and oncology nurses. On the other hand, a virtual visit was the basic way to communicate with the general practitioner. As patients stated that, regardless of the pandemic, they prefer to communicate with the oncologist in-person, we can conclude that the virtual visit does not meet the needs of cancer patients who are in active oncology treatment. In our study men showed a tendency to communicate in- person, while women, breast cancer patients, younger people, highly educated people, and people of higher income are more prone to virtual visits and are more inclined to use the Internet as a source of information about a pandemic.

Metastatic breast cancer is an incurable disease with highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. The aim of the study was to determine pathogenic and likely pathogenic variants in a set of highly penetrance genes which can provide new information in the process of treatment decisionmaking. There is still an insufficient number of metastatic patients in our genetic assessment group because of limited resources. Nevertheless, multi-gene testing provided a substantial benefit in clinical management of breast cancer because the small subset of patients were found suitable for the PARP-inhibitor therapy.

Cilj: Pandemija SARS-CoV-2 naglo je i neizmjerno utjecala na onkološku zajednicu širom svijeta. U ovom smo istraživanju analizirali perspektivu pacijenata o utjecaju pandemije COVID-19 na onkološku skrb u Hrvatskoj, komunikaciju s medicinskim osobljem tijekom pandemije kao i utjecaj pandemije COVID-19 na razinu stresa u bolesnica s rakom dojke. Metode: Ova multicentrična opservacijska studija obuhvatila je 422 pacijenta koji su primali sistemsku onkološku terapiju tijekom lockdowna zbog pandemije COVID-19 u Hrvatskoj, neovisno o stadiju maligne bolesti ili trajanju onkološkog liječenja. Pacijenti su ispunili anketu kako bi izrazili svoje stavove o utjecaju pandemije na onkološku skrb u Hrvatskoj, o komunikaciji s medicinskim osobljem tijekom pandemije te o utjecaju pandemije na razinu stresa kod pacijentica s rakom dojke. Provedene su univarijatne deskriptivne i bivarijatne analize kako bi se uvidjela eventualna povezanost ispitivanih parametara te kliničkih i sociodemografskih karakteristika bolesnika. Rezultati: U 10.2% ispitanika došlo je do prestanka ili promjene onkološkog liječenja uslijed pandemije. Većina ispitanika nije promijenila mjesto liječenja zbog lockdowna (97, 6%). 14.7% pacijenata smatra da se kvaliteta njihove onkološke skrbi promijenila tijekom pandemije. Većina naših pacijenata izrazila je zadovoljstvo komunikacijom s medicinskim osobljem u vrijeme pandemije. S onkologom i onkološkim sestrama komunicirali su uglavnom licem u lice (77, 7% vs. 81%), a s liječnikom obiteljska medicine telefonom (70, 6%). Bez obzira na pandemiju, većina onkoloških pacijenata (76.1%) preferira s onkologom komunicirati licem u lice. Izbor izvora informacija i vrsta komunikacije ovisi o osobinama pacijenta. Kod 54.2% bolesnica s rakom dojke zamijećena je visoka razina stresa uslijed pandemije, neovisno o njihovim sociodemografskim karakteristikama. Zaključci: Unatoč povoljnoj epidemiološkoj situaciji u Hrvatskoj u prvim mjesecima pandemije 25% pacijenata s rakom je izvijestilo da je pandemija utjecala na njihovu onkološku skrb. Pacijenti s rakom, čak i u vrijeme pandemije, preferiraju sa svojim onkolozima komunicirati licem u lice. Više od polovice bolesnica s rakom dojke osjećalo je visoku razinu stresa uslijed pandemije COVID-19.

To protect cancer patients from COVID-19 exposure, prioritization strategies are being implemented at global level. Measures include use of telehealth services, deferring elective surgeries, delaying non life-saving therapies, interrupting maintenance and supportive care regimens and suspending screening and regular follow-up visits. Nonetheless, the risk of infection may not always outweigh oncology treatment benefit. Lives of most oncology patients depend on their ability to receive medical, surgical and radiotherapy care. Postponing screening, follow-up and radical surgeries increase patients’ risk of developing metastatic disease. A viral pandemic lasts long time and exhibits seasonal and geographical variations. Though vaccines will be available only in the 2021, a global, aggressive, all-embracing and protracted slowdown of oncologic activities will severely jeopardize patients’ outcomes. A present international oncologists’ panel, ECPC and FAVO, strongly suggest that Hospital measures in a specific geographical area/Nation should be in line with the local epidemic, and restrictions adopted should be adapted and stratified over time.

Breast cancer metastases can be found in almost all organs in the body - but are most commonly found in the lungs, liver, bones, skin and brain. Metastatic breast cancer often occurs years or decades after initial diagnosis and treatment. In this case report, we will present a 62-year-old patient with metastasis of breast cancer which was originally described as primary colorectal cancer.

Genetic testing is a powerful tool that allows detection of BRCA and non-BRCA germline pathogenic variants in breast cancer (BC) patients or in individuals at high risk of BC. Inherited pathogenic variants (PV) in genes related with moderate to high risk of BC may explain up to 50% of familial BC. Although established for BRCA pathogenic variants, indications and interpretations of genetic testing in non-BRCA pathogenic variants are not well defined. The aim of the study was identification of inherited PV of non-BRCA pathogenic variants in BC patients tested at the University Hospital Center (UHC) Zagreb. Identifying germline pathogenic variants in women with BC is important because it can influence their immediate and long-term management and has important implications on other family members. Multigene panel findings are likely to change clinical practice for substantially more patients than BRCA1/2 testing alone. For a large proportion of the genes included in hereditary cancer gene panels, clinical guidelines are to be established.

CDK 4/6 inhibitori indicirani su u kombinaciji s fulvestrantom ili inhibitorom aromataze u liječenju lokalno uznapredovalog ili metastatskog HR+ HER2- raka dojke. Lijekom uzrokovano oštećenje jetre zabilježeno je kod primjene sva tri CDK 4/6 inhibitora, češće kod primjene ribocikliba. Hepatotoksičnost stupnja 3 i 4 zabilježena je kod 8, 8% bolesnica liječenih ribociklibom u KBC Zagreb u promatranom periodu, što je niže nego u MONALEESA studijama (11, 4%). Kod bolesnica kod kojih je zbog lijekom uzrokovanog oštećenja jetre potrebno trajno prekinuti ribociklib, promjenom CDK 4/6 inhibitora mogao bi se izbjeći toksičan učinak lijeka na jetru, a nastaviti učinkovito liječenje.

Introduction: Previous research have pointed to the problem of the availability of diagnostic procedures and utilization of cancer care during the COVID-19 pandemic. Aim of this study is to analyse the number of exams and treatment of adult cancer patients (outpatient and inpatient) over a period of January to November 2020 (including COVID 19 pandemic and time of earthquake in Zagreb), compared to the same time period of two prior years. Methods: This retrospective observational research of electronic patient record included all patients older than 18 years in outpatient and inpatient setting in Oncology Clinic, University Hospital Centre Zagreb. We have analysed the number of outpatient exams, number of outpatient chemotherapies and other therapies, and number of hospital admissions between January 1st and November 5th 2020, compared to the same time period of 2018 and 2019. Results: The study showed decrease in number of hospital admission in Oncology Clinic, University Hospital Centre Zagreb in 2020. The number of all hospital admissions between January 1st and November 5th 2020 (including COVID 19 pandemic and earthquake in Zagreb) was 5133 all hospital admissions. In 2019 in the same time period that number was 6079, and in 2018 it was 5845. Further, the number of outpatient exams in 2020 was increased. For example, number of exams in Outpatient clinic for Breast Cancer was 4570 in 2018 (between January 1st and November 5th) ; 4768 in the same time period in 2019, and 5067 in the same time period in 2020. The number of daily chemotherapies thorough Daily Oncology Hospital was 10473 in 2020, 9242 in 2019, and 8147 in 2018. Conclusion: There is increase in outpatient exams, number of outpatient chemotherapies and other therapies, between January 1st and November 5th 2020 compared to the same time period of two prior years.

Najčešći oblik ranog karcinoma dojke je hormonski osjetljiv, Her2 negativan (HR+/Her2-) koji čini oko 70% svih novo dijagnosticiranih slučajeva. Dijeli se na luminalnom A i luminalnom B sličan surogatni podtip.U svrhu bolje procjene agresivnosti tumora razvijeni su testovi multigenskog profiliranja tumora. Jedan od dostupnih testova je i PROSIGNA test koji na temelju analize izražaja 50 različitih gena, uz veličinu tumora i zahvaćenost limfnih čvorova, svrstava tumor u jedan od dva intrinzička podtipa, luminalni A i luminalni B, te određuje rizik od povrata bolesti (ROR) 10 godina nakon postavljanja dijagnoze. PROSIGNA test multigenskog profiliranja pokazao se korisnim alatom u donošenju odluke o izboru adjuvantnog liječenja u bolesnica čiji su tumori prema imunofenotipu klasificirani kao luminalnom B slični, a preciznije određivanje intrinzičkog podtipa je dovelo do njegove reklasifikacije, a time i do promjene izbora adjuvantnog liječenja.