This cost-effectiveness study analyses the expected impacts of activities proposed by the Croatian National Plan Against Cancer (NPAC) on cancer incidence and survival rates, as related to their ...respective costs. We evaluated the impact of the NPAC on two main outcomes, namely, reduced incidence and the improved survival of cancer patients, expressed as life years gained (LYGs), which enabled the calculation of incremental cost-effectiveness ratios (ICERs) in the form of cost per LYG. In the analysis of costs, we considered both the direct costs of NPAC activities as well as the wider indirect societal costs of cancer, thus permitting the calculation of the ICER both from the narrower national health insurer’s perspective (accounting only for the direct costs) and the wider societal perspective (accounting both for the direct and indirect costs). We estimated that on average, for all patients benefiting from the implementation of the NPAC in Croatia, an additional LYG would be yielded at the additional cost of €1.021 (societal perspective). The NPAC can, for some sites, even be considered a dominant intervention due to the negative cost/LYG ratio, meaning that it generates additional LYGs while at the same time, reducing total societal costs. Taking a narrower health insurer’s perspective (i.e., accounting only for the direct costs), the NPAC produces an additional LYG at an additional cost of €1.408. Both cost per LYG estimates can be considered cost-effective investment options.
Introduction
Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancer and can be caused by well-known risk factors, including infection with hepatitis B and C viruses, ...alcohol intake, and metabolic syndrome. The overall prognosis remains poor with a median survival of 1 year for symptomatic advanced-stage cases treated with systemic therapies.
Case description
In July 2020, a 73-year-old male patient presented at our institution with mild abdominal pain and an attack of intense cold. After a radiological workup, the diagnosis of HCC located in the caudate lobe was established. The patient underwent atypical caudate lobe resection, and pathology confirmed the diagnosis of grade 3 HCC. Postoperative MRI showed a new metastasis in the 6th liver segment 1.3 cm in diameter, and a PVT progression which now affected the whole right lobe. The patient was started on sorafenib and demonstrated a complete response which still lasts for more than two years.
Conclusion
We present a rare case of a patient who demonstrated a complete response to sorafenib treatment in advanced HCC with unfavorable prognostic factors.
One of the main features of wasting in cancer is an involuntary weight loss which is most pronounced in gastrointestinal tract tumors and leads to worse clinical outcomes. The aim of this study is to ...analyze the frequency of body weight loss (FBWL) as an additional prognostic factor in the treatment of patients with metastatic colorectal cancer (mCRC).
In this observational, single-center study, data were retrieved for 236 patients treated for mCRC. FBWL was defined as a percent of change in weight divided by weeks of therapy. Patients were stratified into two groups according to the median of FBWL which equaled to the loss of 0.05%/week. Patients who lost >0.05%/week (N = 116) had shorter progression-free survival (PFS) in the first-line treatment, then the ones who lost <0.05%/week (N = 120); 28.3 vs 46.3 weeks, respectively. Cox regression model showed that FBWL and sidedness were significant predictors of PFS, while age, sex and ECOG were not. Significantly more patients with stable weight were also eligible for second-line treatment. In conclusion, stabilization of body weight is important and independent predictor of longer PFS in first-line therapy of patients with mCRC.
There are no recommended biomarkers to identify patients with refractory metastatic colorectal cancer (mCRC) who would benefit the most from trifluridine/tipiracil (TTP). The exploratory analysis of ...the RECOURSE trial revealed that patients with low tumor burden and indolent disease derive greater benefit in terms of both progression-free survival (PFS) and overall survival (OS). Nevertheless, the final answer on the TTP real impact on the well-being of patients with late-stage mCRC will come from real-world data.
The aim of this retrospective exploratory study was to investigate the effectiveness of TTP in mCRC with regard to the duration of standard treatment and other influencing variables. The study included 260 patients from the three largest Croatian oncology centers who began treatment with TTP in the third or fourth line between 2018 and 2020.
The median OS and PFS for the entire cohort were 6.53 and 2.50 months, respectively. Patients with more aggressive disease, defined as those whose time to progression on the first two lines of standard therapy was less than 18 months, had significantly shorter PFS (2.40 vs. 2.57 months, hazard ratio HR 1.34, 95% confidence interval CI: 1.03-1.84). There was also a tendency toward shorter OS (6.10 vs. 6.30 months, HR 1.32, 95% CI: 0.99-1.78) but without statistical significance. Patients with ECOG PS 0, without liver metastases, and with RAS mutation had both longer OS and PFS. No influence was detected from other variables including age, sex, primary tumor location, and tumor burden.
With regard to the results of the previously conducted trials, the study concludes that indolent disease, good general condition, and absence of liver metastases are positive predictive factors for TTP treatment.
Aims
Cancer patients with reduced dihydropyrimidine dehydrogenase (DPD) activity are at increased risk of severe fluoropyrimidine (FP)‐related adverse events (AE). Guidelines recommend FP dosing ...adjusted to genotype‐predicted DPD activity based on four DPYD variants (rs3918290, rs55886062, rs67376798 and rs56038477). We evaluated the relationship between three further DPYD polymorphisms: c.496A>G (rs2297595), *6 c.2194G>A (rs1801160) and *9A c.85T>C (rs1801265) and the risk of severe AEs.
Methods
Consecutive FP‐treated adult patients were genotyped for “standard” and tested DPYD variants, and for UGT1A1*28 if irinotecan was included, and were monitored for the occurrence of grade ≥3 (National Cancer Institute Common Terminology Criteria) vs. grade 0–2 AEs. For each of the tested polymorphisms, variant allele carriers were matched to respective wild type controls (optimal full matching combined with exact matching, in respect to: age, sex, type of cancer, type of FP, DPYD activity score, use of irinotecan/UGT1A1, adjuvant therapy, radiotherapy, biological therapy and genotype on the remaining two tested polymorphisms).
Results
Of the 503 included patients (82.3% colorectal cancer), 283 (56.3%) developed grade ≥3 AEs, mostly diarrhoea and neutropenia. Odds of grade ≥3 AEs were higher in c.496A>G variant carriers (n = 127) than in controls (n = 376) OR = 5.20 (95% CI 1.88–14.3), Bayesian OR = 5.24 (95% CrI 3.06–9.12). Odds tended to be higher in c.2194G>A variant carriers (n = 58) than in controls (n = 432) OR = 1.88 (0.95–3.73), Bayesian OR = 1.90 (1.03–3.56). c.85T>C did not appear associated with grade ≥3 AEs (206 variant carriers vs. 284 controls).
Conclusion
DPYD c.496A>G and possibly c.2194G>A variants might need to be considered for inclusion in the DPYD genotyping panel.
Pancreatic cancer is one of the most lethal malignancies with a rise in mortality rates. FOLFIRINOX and nab-paclitaxel plus gemcitabine demonstrated a survival benefit compared to gemcitabine alone. ...Both protocols are now considered the standard of first-line treatment with no significant difference between them, primarily based on observational studies. Although new therapeutic options have emerged recently, the prognosis remains poor. We conducted a retrospective single-center study on 139 patients treated for metastatic pancreatic adenocarcinoma (mPDAC) with gemcitabine monotherapy (Gem) or nab-paclitaxel + gemcitabine (Nab-P/Gem) in the first line. The aim of our study was to evaluate the effectiveness in terms of overall survival (OS) and progression-free survival (PFS) as well as the influence of patient and disease characteristics on outcomes. Nab-P/Gem resulted in OS of 13.87 months compared to 8.5 months in patients receiving Gem. The same trend was achieved in PFS, 5.37 versus 2.80 months, respectively, but without reaching statistical significance. Furthermore, the 6-month survival in the Nab-P/Gem group was also higher, 78.1% versus 47.8%. In terms of survival, the group of elderly patients, patients of poorer performance, with higher metastatic burden and liver involvement, benefited the most from combination therapy. In our analysis ECOG performance status (p.s.), previous primary tumor surgery, and liver involvement were found to be independent prognostic factors. The addition of nab-paclitaxel to gemcitabine resulted in a significant improvement in the OS of patients with mPDAC. Subgroup analysis demonstrated that patients with some unfavorable prognostic factors benefited the most.
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.
Metastases to the heart and pericardium are rare but more common than primary cardiac tumours and are generally associated with a rather poor prognosis. Most cases are clinically silent and are ...undiagnosed in vivo until the autopsy. We present a female patient with a 27-year-old history of an operated primary breast cancer who was presented with dyspnoea, paroxysmal nocturnal dyspnoea and orthopnoea. The clinical signs and symptoms aroused suspicion of congestive heart failure. However, the cardiac metastases were detected during a routine cardiologic evaluation and confirmed with computed tomography imaging. Additionally, this paper outlines the pathophysiology of molecular and clinical mechanisms involved in the metastatic spreading, clinical presentation, diagnostic procedures and treatment of heart metastases. The present case demonstrates that a complete surgical resection and systemic chemotherapy may result in a favourable outcome for many years. However, a lifelong medical follow-up, with the purpose of a detection of metastases, is highly recommended. We strongly call the attention of clinicians to the fact that during the follow-up of all cancer patients, such heart failure may be a harbinger of the secondary heart involvement.
Objective: The etiology of lung injury following cardiopulmonary bypass (CPB) is multifactorial. Our study focused on quantifying the lactate release from the lungs precipitated by extracorporeal ...circulation at different time points after the insult. This was complemented by an evaluation of the gas exchange at the level of the alveolar–capillary membrane. Methods: Forty consecutive patients (age 61 ± 11 years, EuroScore 4.7 ± 2.7) undergoing CABG were prospectively analyzed. The data are presented as medians and the interquartile range. Results: The pulmonary lactate release (PLR) increased from a baseline value of 0.033 (range −0.077 to 0.170) to 0.465 mmol/min/m2 (range 0.113–0.922), which was seen 6 h postoperatively (P < 0.001). The A-a O2 gradient increased from 12.7 (range 8.8–15) to 39.1 kPa (range 30.3–46.5) upon discontinuation of CPB (P < 0.001). The systemic arterial lactate (LS) concentration increased from 1.22 (range 1–1.44) to 3.03 mmol/l (range 2.29–4.76) 6 h after surgery (P < 0.001). The veno-arterial pCO2 difference (V-A dpCO2) rose from 0.6 (range 0.5–0.9) to 0.9 kPa (range 0.7–1) (P = 0.014). The mortality in the studied group was 5% (2/40). Conclusions: The lungs were found to be a significant source of lactate, and this pulmonary lactate flux was accentuated by CPB. The PLR correlated with systemic hyperlactatemia as well as the A-a O2 gradient, and was found to be higher in patients requiring prolonged mechanical ventilatory support. The duration of CPB had a significant impact on the systemic lactate concentrations, V-A dpCO2 and the A-a O2 gradient, but not on the PLR.
Immunotherapy has improved the prognosis of metastatic melanoma patients, although most patients do not achieve a complete response. While specific gut microbiome and dietary habits might influence ...treatment success, there is a lack of concordance between the studies, potentially due to dichotomizing patients only into responders and non-responders. The aim of this study was to elucidate whether metastatic melanoma patients with complete and sustained response to immunotherapy exhibit differences in gut microbiome composition among themselves, and whether those differences were associated with specific dietary habits. Shotgun metagenomic sequencing revealed that patients who exhibited a complete response after more than 9 months of treatment (late responders) exhibited a significantly higher beta-diversity (
= 0.02), with a higher abundance of
(LDA 3.548,
= 0.010),
(LDA 3.392,
= 0.024), and lower abundance of
(
= 0.04) compared to early responders. Furthermore, late responders exhibited a different diet profile, with a significantly lower intake of proteins and sweets and a higher intake of flavones (
< 0.05). The research showed that metastatic melanoma patients with a complete and sustained response to immunotherapy were a heterogeneous group. Patients with a late complete response exhibited microbiome and dietary habits which were previously associated with an improved response to immunotherapy.
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