Background
Our objective was to assess the effects of COVID‐19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers ...in the Republic of Croatia.
Subjects, Materials, and Methods
We performed a retrospective, population‐ and registry‐based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases.
Results
The average monthly percent change after the initial lockdown measures were introduced was −11.0% (95% confidence interval − 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017–2019.
Conclusion
It seems that national health care system measures for controlling the spread of COVID‐19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID‐19 control measures were relaxed, and it has not reoccurred during the second COVID‐19 wave. Although the COVID‐19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020.
Implications for Practice
It is possible to compensate for the adverse effects of COVID‐19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non‐negligible extent.
This article assesses the effects of COVID‐19 on the number of newly diagnosed breast cancer patients in the Republic of Croatia.
The aim of the study was to conduct a retrospective database analysis to understand the current treatment patterns and outcomes to plan potential improvements in therapy delivery and patient ...selection. The electronic patient medical records of 225 patients with advanced gastric and esophagogastric adenocarcinoma treated at two Croatian high-volume tertiary centers from January 2018 to December 2021 were analyzed. Patients ineligible for chemotherapy (66 of 291, 22.7%) due to poor general condition or co-morbidities were not included in the study. The median overall survival (OS) for the whole cohort was 11.0 months (95% confidence interval (CI) 9.7-12.0). Of the 225 patients who received first-line therapy, 47.6%, 16.9%, and 3.1% received second-, third-, and fourth-line therapy, respectively. Survival correlated significantly with the number of treatment lines received (p<0.001), with a median OS from diagnosis of 7.8 (95% CI 6.6-9.4), 12.0 (95% CI 10.0-14.0), and 20.0 months (95% CI 18.0-23.0) for patients receiving 1, 2, and ≥3 lines of treatment, respectively. This study confirmed the positive impact of the number of chemotherapy lines on OS. This highlights the importance of the ratio of patients receiving multiple lines of therapy as well as the availability of new and effective drugs in real-life clinical practice. The selection of optimal therapy for each patient in the first-line therapy is important because a significant number of patients do not receive second-line therapy.
In 2011, we demonstrated that bevacizumab in combination with capecitabine as first-line treatment is effective in elderly patients with metastatic colorectal cancer (mCRC). We present the final ...results of the study with data on tumor molecular biology, sidedness and postprogression therapy. Forty patients with mCRC aged ≥70 years, initially treated with bevacizumab and capecitabine, were followed from the start of the treatment of metastatic disease to death. Tumor tissue samples were retrospectively analyzed for RAS, BRAF and microsatellite status. After a median follow-up time of 20.5 months, the median progression-free survival (PFS) and overall survival (OS) were 9.8 and 20.5 months, respectively and the objective response rate (ORR) was 65%. Twelve patients had mutation in RAS and four patients in BRAF gene, which coexisted with MSI in two cases. Patients with the right-sided tumor had apparently, but not statistically significantly lower PFS (8.6 vs. 13 months, P = 0.14) and statistically significantly lower OS (13 vs. 23.1 months, P = 0.046). Twelve patients with one or more postprogression therapy lines had significantly better ORR (12/12 = 100% vs. 14/28 = 50%, P = 0.003), median PFS (17.2 vs. 8.5 months, P < 0.001) and median OS (42 vs. 13 months, P < 0.001) than patients who received just first-line study treatment. Elderly patients with mCRC responded favorably to bevacizumab and capecitabine, especially the subgroup with the left-sided primary tumor. In the further subset of this group, characterized by RAS/BRAF wild-type and MSS tumors, the application of postprogression therapies was feasible and resulted in significant prolongation of survival.
We assessed the treatment effect of panitumumab plus best supportive care (BSC) vs BSC on overall survival (OS) in patients with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer ...(mCRC) and report the first prospective extended RAS analysis in a phase 3 trial.
Patients with wild-type KRAS exon 2 mCRC were randomised 1 : 1 to panitumumab (6 mg kg
Q2W) plus BSC or BSC. On-study crossover was prohibited. RAS mutation status was determined by central laboratory testing. The primary endpoint was OS in wild-type KRAS exon 2 mCRC; OS in wild-type RAS mCRC (KRAS and NRAS exons 2, 3, and 4) was a secondary endpoint.
Three hundred seventy seven patients with wild-type KRAS exon 2 mCRC were randomised. Median OS was 10.0 months with panitumumab plus BSC vs 7.4 months with BSC (HR=0.73; 95% CI=0.57-0.93; P=0.0096). RAS ascertainment was 86%. In wild-type RAS mCRC, median OS for panitumumab plus BSC was 10.0 vs 6.9 months for BSC (HR=0.70; 95% CI=0.53-0.93; P=0.0135). Patients with RAS mutations did not benefit from panitumumab (OS HR=0.99; 95% CI=0.49-2.00). No new safety signals were observed.
Panitumumab significantly improved OS in wild-type KRAS exon 2 mCRC. The effect was more pronounced in wild-type RAS mCRC, validating previous retrospective analyses.
The aim of this study was to explore the red blood cell changes that occur during neoadjuvant dose-dense chemotherapy (NAC) of breast cancer. Also, we investigated the role of macrocytosis as a ...predictive biomarker for pathological complete response and disease-free survival (DFS) in these patients. A retrospective analysis of 82 breast cancer patients' data treated with anthracycline-cyclophosphamide-paclitaxel (AC-T) NAC in three oncology institutions in south Croatia from 2013 to 2020 was carried out. During chemotherapy mean corpuscular volume increased with time, with a median increase of 7.25 fl. Macrocytosis was induced in 38% of patients overall. Development of macrocytosis did not correlate with DFS hazard ratio = 0.525; 95% confidence interval (CI), 0.074-3.768; P = 0.525. Higher percentage of patients in macrocytosis group achieved PCR, 39% vs. 29% in no macrocytosis group, but this difference was not statistically significant. The relevance of macrocytosis induction during dose-dense neoadjuvant chemotherapy in breast cancer should be further explored.
The aims of this study were to investigate a clinical observation that patients with epithelial ovarian cancer treated with first-line platinum-paclitaxel chemotherapy combination (TP) develop ...macrocytosis and to explore the possible predictive role of macrocytosis in response rate, progression-free survival (PFS), and overall survival. A retrospective analysis of laboratory and clinical data on 184 consecutive ovarian cancer patients treated with first-line TP chemotherapy in a single oncology center from 2004 to 2015 was carried out. Macrocytosis was defined as an increase in mean corpuscular volume of peripheral red blood cells above 97.2 fl during the treatment and/or 30 days after the last chemotherapy cycle. One hundred and forty-one patients were treated with a conventional 3-weekly TP schedule, whereas 43 patients were treated with a dose-dense schedule. Macrocytosis was induced in 35% of patients overall. It was induced significantly more often in patients treated with the dose-dense schedule than in those treated with the 3-weekly schedule (67 vs. 26%, P=1.29×10). Macrocytosis did not correlate with PFS and overall survival in the overall patient population, nor in patients treated with the 3-weekly schedule. It correlated with PFS (hazard ratio=0.42, 95% confidence interval=0.18-0.94, P=0.036) and objective response on therapy in patients treated with the dose-dense schedule (P=0.0285). Dose-dense TP chemotherapy induces macrocytosis significantly more often than does a 3-weekly schedule in ovarian cancer patients. In patients treated with a dose-dense schedule, macrocytosis can potentially be predictive for longer PFS and better response rate. This finding needs further confirmation, preferentially in a prospective study.
Background
There is a steady decline in cancer mortality in Western Europe (WE), but this trend is not so obvious in Central and Eastern Europe (CEE). One of the largest discrepancies between WE and ...CEE is the level of investment in cancer care. The objective of our analysis was to examine the correlation between mortality‐to‐incidence (M/I) ratio and expenditures on oncology drugs in CEE and WE.
Materials and Methods
This cross‐sectional analysis was done on publicly available data. Data on expenditures for oncology drugs were obtained from QuintilesIMS, and data on M/I ratio from Globocan. The main outcome was mortality‐to‐incidence ratio, and the primary analysis was performed by Spearman's rank correlation.
Results
There is a large discrepancy in expenditure on oncology drugs per cancer case between WE and CEE, and within CEE. Average expenditure on oncology drugs per capita as well as per new cancer case was 2.5 times higher in WE than in CEE. Availability of oncology drugs was highest in Germany (100%), relatively similar in WE (average of 91%), but in CEE it ranged from 37% to 86%, with an average of 70%. Annual expenditures on all oncology drugs per new cancer case was significantly negatively correlated with the M/I ratio (Spearman's ρ = −0.90, p < .001).
Conclusion
There is a financial threshold for oncology drugs per cancer case needed to increase survival. Based on significantly lower expenditures for oncology drugs in CEE in comparison with WE, more investment for drugs as well as better, more organized, value‐ oriented consumption is needed.
Implications for Practice
Cancer is not treated equally successfully in Western Europe (WE) and in Central and Eastern Europe (CEE). This study showed that success in treatment of cancer is associated with the amount of money invested in oncology drugs. CEE countries spend on average 2.5 times less than WE countries for oncology drugs per new cancer case. These findings should be used by health care providers and oncologists struggling for more resources and better, more organized, evidence‐based allocation of these resources as well as better oncology outcomes.
This article examines the relationship between expenditures on oncology drugs and the mortality‐to‐incidence ratio in Central and Eastern Europe compared with Western Europe, analyzing the differences in expenditures on oncology drugs.
The standard treatment for locally advanced cervical cancer (LACC) is concomitant chemoradiotherapy. In the majority of patients with LACC after properly executed concomitant chemoradiotherapy local ...control of the disease is achieved, and consequently distant relapse becomes the main cause of death for these patients. In an attempt to improve the outcome of patients with LACC, we designed a regimen of concomitant chemobrachyradiotherapy with cisplatin and ifosfamide followed by consolidation chemotherapy.
Between 1999 and 2012, 118 patients diagnosed with LACC, The International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IVA, regardless of histology, were treated with concomitant chemobrachyradiotherapy and consolidation chemotherapy at our Institution. Chemotherapy consisted of two cycles of cisplatin and ifosfamide applied concomitantly with two intracavitary low-dose rate brachytherapy applications, and of four cycles of the same drug combination as an adjuvant/consolidation part of the treatment. The primary outcome in this analysis was distant disease-specific survival.
A total of 18 patients had documented relapse of cervical cancer, with only three local recurrences observed; 15 patients developed only distant recurrence, and one patient developed both local and distant recurrence. The distant disease-specific survival after a median follow-up of 96 months was 86.4%.
Consolidation or adjuvant chemotherapy that follows concomitant chemoradiotherapy has a potential role in further improving control of the disease, especially distant control of the disease.
In the last decades, the development of high‐throughput molecular assays has revolutionised cancer diagnostics, paving the way for the concept of personalised cancer medicine. This progress has been ...driven by the introduction of such technologies through biomarker‐driven oncology trials. In this review, strengths and limitations of various state‐of‐the‐art sequencing technologies, including gene panel sequencing (DNA and RNA), whole‐exome/whole‐genome sequencing and whole‐transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. This includes the need to assess complex biomarkers, for example microsatellite instability, tumour mutation burden and homologous recombination deficiency, to identify patients suitable for specific therapies, including immunotherapy. Furthermore, the crucial role of biomarker analysis and multidisciplinary molecular tumour boards in selecting patients for trial inclusion is discussed in relation to various trial concepts, including drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics and clinical study inclusion assays, the importance of emerging technologies for multimodal diagnostics, such as proteomics and in vivo drug sensitivity testing, is also discussed. In addition, key regulatory aspects and the importance of patient engagement in all phases of a clinical trial are described. Finally, we propose a set of recommendations for consideration when planning a new precision cancer medicine trial.
Summary
Background
Given the lack of primary and secondary prevention programs and cancer awareness in general, cervical cancer remains one of the main causes of cancer-related death in developing ...countries, such as Bosnia and Herzegovina. Optimization of combinations of external radiation therapy (ERT), brachytherapy and chemotherapy is still needed to improve outcomes in the treatment of advanced cervical cancer.
Patients and methods
We retrospectively analyzed 48 consecutive patients with Fédération Internationale de Gynecologie et d’Obstetrique (FIGO) 2009 stage IB2-IVA, who were treated with primary concomitant chemobrachyradiotherapy (CCBRT) and consolidation chemotherapy at the Department of Oncology, University Hospital Mostar, Bosnia and Herzegovina between December 2012 and June 2020. Patients were treated with ERT plus two cycles of concomitant chemobrachytherapy with ifosfamide and cisplatin and low-dose rate (LDR) brachytherapy followed by four cycles of consolidation chemotherapy at 3‑week intervals. We evaluated local control rate (LCR), disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS) and toxicity.
Results
After 45.5 months (interquartile range, IQR = 47 months) of median follow-up, 5‑year DFS was 72.8% (95% confidence interval. CI 59–78%), OS was 76.6% (95% CI 60–79%), and DSS was 88% (95% CI 71–86%) with acceptable toxicity. LCR was 94%.
Conclusion
Primary CCBRT and consolidation chemotherapy applied in standard clinical practice in the treatment of locally advanced cervical cancer (LACC) produce respectable outcomes.
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