The relative survival of elderly patients with metastatic colorectal cancer (mCRC) is generally worse than that of younger patients because of more advanced stage at presentation, comorbidity and reduced use of optimal therapy. We conducted a prospective phase II trial of the combination of bevacizumab and capecitabine in elderly patients with mCRC. In total 41 patients aged more than or equal to 70 years with mCRC, who had not received chemotherapy earlier for metastatic disease, were enroled. Patients received capecitabine (1000 mg/m twice daily on days 1-14) and bevacizumab (7.5 mg/kg of body weight on day 1). The treatment cycles were repeated every 3 weeks. The overall response rate was 65%, including 13% of patients with a complete response and 53% of patients with a partial response. A further 13% of patients maintained stable disease. The median progression-free survival was 11.5 months and the median overall survival was 21.2 months. Despite the advanced age of participants, the rate of bevacizumab-related and capecitabine-related adverse events was consistent with that reported earlier in the general mCRC population. The combination of bevacizumab and capecitabine is effective and has a favourable tolerability profile and should be considered as an option for the initial treatment of mCRC in elderly patients.

Optimal first-line chemotherapy for metastatic breast cancer (MBC) is challenging, particularly in patients previously treated with (neo) adjuvant anthracyclines/taxanes. Based on preclinical synergy with mitomycin C (MMC) and capecitabine in human tumor xenografts, we conducted a phase II study of first-line capecitabine and MMC in MBC. Patients received 3-weekly chemotherapy comprising MMC 8 mg/m 2 day 1 and capecitabine 1000 mg/m 2 twice daily, days 1-14. Combination chemotherapy was administered for a maximum six cycles, single-agent capecitabine could be continued until progressive disease or unacceptable toxicity. Thirty patients were included, objective response rate was 65.5%. After a median follow-up of 18.5 months, median time to progression was 8.5 months and median overall survival was 29.8 months. The main adverse events were thrombocytopenia, pneumonitis and hemolytic uremic syndrome. Our data suggest that first-line capecitabine and MMC has good antitumor activity in MBC, but is associated with MMC-specific toxicity.

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.

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, KRAS, MET, and EGFR 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.

Radiotherapy for cervical carcinoma increases the standardized incidence ratios for rectal cancer and soft tissue sarcoma. Unfortunately, the current guidelines on contraindications to radiotherapy appear insufficient as they take into account a very limited number of clinical states and associated conditions, which is in disproportion to the rather high risk of radiation-induced malignancies of 0.45%. Information on the molecular characteristics of human radiation-induced tumors is still of no relevance for everyday clinical practice. Although radiotherapy is one of the most important modalities of oncological treatment, it should be judiciously used in cases where the benefits clearly outweigh the risk of serious untoward effects. In the case of patients undergoing pelvic irradiation, careful follow-up is needed for years.