ABSTRACT
BACKGROUND: There are limited real-world data (RWD) regarding the use of cyclin-dependent kinase (CDK) 4/6 inhibitors in western Balkan. The aim of our study was thus to analyze factors influencing progression-free survival (PFS) and overall survival (OS), along with the differences in adverse effects of CDK 4/6 therapy in a tertiary healthcare center in Croatia. METHODS: We evaluated medical and demographic data for 163 consecutive patients with metastatic breast cancer treated with CDK4/6 inhibitors for at least one month, from October 2018, after the drug became available in Croatia. Eligible patients in our study were those patients who were treated with palbociclib, ribociclib, or abemaciclib. RESULTS: The median PFS of CDK4/6 inhibitors treatment was 2.2 years (95% CI 1.8-3.3), with the longest ongoing treatment for 5.4 years. Treatment with CDK4/6 inhibitors in the first line was associated with a longer PFS compared to the second line or beyond (HR 0.50, 95% CI 0.3-0.9), and patients without liver metastasis exhibited longer survival compared to patients with liver metastasis (HR 0.46, 95% CI 0.2-0.8) (both p < 0.05). Regarding the choice of CDK4/6 inhibitors, ribociclib exhibited longer PFS compared to palbociclib (HR 0.49, 95% CI 0.29-0.82) (p = 0.0032), although the effect was not statistically significant when separating patients who were treated with CDK4/6 inhibitors in the first-line (HR 0.59, 95% CI 0.29-1.2), or second- or later-line therapy (0.49, 95% CI 0.15-1.55); the trend was present in both lines, however. The presence of liver metastasis (p = 0.04), initial luminal A grade (p = 0.039), and time to metastasis up to 5 years from the initial cancer (p = 0.002) were the only factors that remained statistically significant for PFS in multivariate analysis. Median OS since the diagnosis of metastatic disease was 4.5 years (95% CI 3.9-6.3), median OS since the start of CDK4/6 inhibitors treatment was 3.7 years (95% CI 3.4-4.4), while median OS from initial cancer diagnosis was 15.8 years (95% CI 13.8-18.3). There was no difference in OS based on the choice of CDK4/6 inhibitor (p = 0.44) or the adjuvant hormonal therapy (p = 0.12), although a nonsignificant trend for better OS with ribociclib was present for both regardless of whether it was in first- or second/later-line therapies (p > 0.05). In a multivariate analysis, only the presence of liver metastasis (p = 0.0003) and time to metastasis under 5 years from primary breast cancer (p = 0.03) were associated with a worse OS. CONCLUSIONS: Our study provides the RWD with the use of CDK4/6 inhibitors in the treatment of metastatic HR+/HER2- breast cancer. To our best knowledge, there are limited RWD regarding CDK 4/6 inhibitors use in western Balkan; thus, our study provides valuable data from everyday clinical practice for this region of Europe, bridging the gap between randomized clinical trials and clinical reality in western Balkan.
ABSTRACT
BACKGROUND: The development of immunotherapy checkpoint inhibitors (ICIs) has revolutionized cancer care. However, old patients are underrepresented in most clinical trials, although they represent a significant proportion of real-world patients. We aimed to evaluate the effectiveness and safety of ICIs in patients older than the age of 70. METHODS: We performed a retrospective chart review of 145 patients aged 70 or older treated with ICIs for metastatic or unresectable cancer. RESULTS: Median progression-free survival (PFS) was 10.4 months (95% CI 8.6-13.7), with no differences between octogenarians and septuagenarians (p = 0.41). Female gender (p = 0.04) and first-line treatment setting (p < 0.0001) were associated with a longer median PFS. Median overall survival (OS) was 20.7 months (95% CI 13.5-35.0 months), with no difference based on performance status, cancer site, gender, or between septuagenarians and octogenarians (all p > 0.005). Patients treated with ICIs in the first-line setting reported longer OS compared to treatment in the second-line setting (p < 0.001). Discontinuation of ICIs due to adverse effects was associated with both shorter PFS (p = 0.0005) and OS (p < 0.0001). CONCLUSION: The effectiveness of ICIs in older cancer patients primarily depends on the line of treatment and treatment discontinuation. Octogenarians experienced similar treatment responses, PFS, OS, and adverse effects compared to septuagenarians.
ABSTRACT
Prostate cancer (Pca) is among the most common malignant diseases in men and the fourth leading cause of death worldwide. Surgery and radical radiotherapy (RT) remain the gold standard for the treatment of localized or locally advanced prostate cancer. The efficiency of radiotherapy treatment is limited by toxic side effects due to dose escalation. Cancer cells often develop radio-resistant mechanisms that are related to the DNA repair, inhibition of apoptosis or changes in cell cycle. Based on our earlier research on biomarkers that are involved in those cellular mechanisms (p53, bcl-2, NF-kb, Cripto-1 and Ki67 proliferation) and correlation with clinico-pathological parameters (age, PSA value, Gleason score, grade group, prognostic group), we created the numerical index for risk of tumor progression in patients with radioresistant tumors. For each of these parameters, the strength of association with disease progression was statistically assessed, and a specific number of points was assigned proportional to the strength of the correlation. Statistical analysis identified an optimal cut-off score of 22 or more as an indicator of significant risk for progression with a sensitivity of 91.7% and a specificity of 66.7%. The scoring system in the retrospective receiver operating characteristic analysis showed AUC of 0.82. The potential value of this scoring is the possibility of identifying patients with clinically significant radioresistant Pca.
ABSTRACT
Spiritual well-being is a recognized predictor of health-related quality of life in palliative patients. No research in Croatia has yet addressed this field. This study, the first of its kind in Croatia, validated a Croatian translation of the EORTC QLQ-SWB32 measure of spiritual well-being with curative Croatian oncology patients and assessed its use and value. The study was conducted between July 2019 and January 2020 at the Department of Radiotherapy and Oncology, University Hospital Rijeka, with 143 cancer patients, using the linguistically validated Croatian version of the measure. All patients found the measure acceptable. Confirmatory factor analysis aligned with the structure found in previous studies. Cronbach's alpha confirmed internal consistency. Female participants scored higher on the RSG (Relationship with Someone or Something Greater), RG (Relationship with God), and EX (Existential) scales, and on Global-SWB. Patients with breast and gynecological tumors scored higher on RG. Older patients scored lower on RSG, RG and EX. Retirees and those with below-average incomes scored lower on EX. Participants who identified as having no religion scored lower on RSG. Stage I cancer patients scored higher on RG. The Croatian version of the EORTC QLQ-SWB32 is an acceptable, valid, and reliable measure of SWB for Croatian cancer patients.