Background & Aims
A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for ...HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option.
Methods
Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels.
Results
Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50–0.79), cabozantinib (HR = 0.76, 95% CI = 0.63–0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70–0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36–0.52), regorafenib (HR = 0.46, 95% CI = 0.37–0.56), ramucirumab (HR = 0.54, 95% CI = 0.43–0.68), brivanib (HR = 0.56, 95% CI = 0.42–0.76), S-1 (HR = 0.60, 95% CI = 0.46–0.77), axitinib (HR = 0.62, 95% CI = 0.44–0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57–0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients’ stratification.
Conclusions
The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.
Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a translation factor selectively expressed by heart, skeletal muscle, nervous system and some specialized cells. Its ectopic expression relates with ...tumorigenesis in several types of human cancer. No data are available about the role of eEF1A2 in Triple Negative Breast Cancers (TNBC). This study investigated the relation between eEF1A2 protein levels and the prognosis of TNBC. A total of 84 TNBC diagnosed in the period 2002-2011 were included in the study. eEF1A2 protein level was measured in formalin-fixed paraffin-embedded tissues by immunohistochemistry in a semi-quantitative manner (sum of the percentage of positive cells x staining intensity) on a scale from 0 to 300. Cox regression assessed the association between eEF1A2 levels and disease-free survival (DFS) and breast cancer-specific survival (BCSS). Elevated values of eEF1A2 were associated with older age at diagnosis (p = 0.003), and androgen receptors positivity (p = 0.002). At univariate Cox analysis, eEF1A2 levels were not significantly associated with DFS and BCSS (p = 0.11 and p = 0.08, respectively) whereas adjusting for stage of disease, elevated levels of eEF1A2 protein resulted associated with poor prognosis (HR = 1.05, 95% CI: 1.01-1.11, p = 0.04 and HR = 1.07, 95% CI: 1.01-1.14, p = 0.03 for DFS and BCSS, respectively). This trend was confirmed analyzing negative versus positive samples by using categorized scores. Our data showed a negative prognostic role of eEF1A2 protein in TNBC, sustaining further investigations to confirm this result by wider and independent cohorts of patients.
To evaluate the effect of different first-line chemotherapy durations in patients with metastatic breast cancer (MBC) on overall survival (OS) and progression-free survival (PFS).
We searched ...literature databases to identify randomized controlled trials that compared different chemotherapy durations in the first-line treatment of MBC. Only trials with unconfounded comparisons of additional cycles of chemotherapy were included. The main outcome measures for this analysis were OS and PFS. Published data from retrieved studies were analyzed according to standard meta-analytic techniques.
We found 11 randomized clinical trials including 2,269 patients. Longer first-line chemotherapy duration resulted into a significantly improved OS (hazard ratio HR, 0.91; 95% CI, 0.84 to 0.99; P = .046) and PFS (HR, 0.64; 95% CI, 0.55 to 0.76; P < .001). There were no differences in effects on either OS or PFS between subgroups defined by time of random assignment, study design, number of chemotherapy cycles in the control arm or concomitant endocrine therapy.
Longer first-line chemotherapy duration is associated with marginally longer OS and a substantially longer PFS.
The validated Palliative Prognostic (PaP) score predicts survival in terminally ill cancer patients, assigning patients to three different risk groups according to a 30-day survival probability: ...group A, >70%; group B, 30−70%; and group C, <30%. We aimed to develop and validate a PaP nomogram to provide individualized prediction of survival at 15, 30 and 60 days. Three cohorts of consecutive terminally ill cancer patients were used: one (n = 519) for nomogram development and internal validation, and a second (n = 451) and third (n = 549) for external validation. Multivariate analyses included dyspnea, anorexia, Karnofsky performance status, clinical prediction of survival, total white blood count and lymphocyte percentage. The predictive accuracy of the nomogram was determined by Harrell’s concordance index (95% CI), and calibration plots were generated. The nomogram had a concordance index of 0.74 (0.72−0.75) and showed good calibration. The internal validation showed no departures from ideal prediction. The accuracy of the nomogram at 15, 30 and 60 days was 74% (70−77), 89% (85−92) and 72% (68−76) in the external validation cohorts, respectively. The PaP nomogram predicts the individualized estimate of survival and could greatly facilitate clinical care decision-making at the end of life.
Randomization procedure in randomized controlled trials (RCTs) permits an unbiased estimation of causal effects. However, in clinical practice, differential compliance between arms may cause a strong ...violation of randomization balance and biased treatment effect among those who comply. We evaluated the effect of the consolidation phase on disease-free survival of patients with multiple myeloma in an RCT designed for another purpose, adjusting for potential selection bias due to different compliance to previous treatment phases.
We computed two propensity scores (PS) to model two different selection processes: the first to undergo autologous stem cell transplantation, the second to begin consolidation therapy. Combined stabilized inverse probability treatment weights were then introduced in the Cox model to estimate the causal effect of consolidation therapy miming an ad hoc RCT protocol.
We found that the effect of consolidation therapy was restricted to the first 18 months of the phase (HR: 0.40, robust 95 % CI: 0.17-0.96), after which it disappeared.
PS-based methods could be a complementary approach within an RCT context to evaluate the effect of the last phase of a complex therapeutic strategy, adjusting for potential selection bias caused by different compliance to the previous phases of the therapeutic scheme, in order to simulate an ad hoc randomization procedure.
ClinicalTrials.gov: NCT01134484 May 28, 2010 (retrospectively registered) EudraCT: 2005-003723-39 December 17, 2008 (retrospectively registered).
A retrospective study was conducted among Italian cancer healthcare workers (HCWs) to describe how influenza vaccination attitudes have changed during the COVID-19 pandemic. The analysis was ...conducted on the last three influenza seasons (2018/19, 2019/20 and 2020/21). To account for different relationships and proximity with patients, the study population was grouped into three main professional categories: health personnel, administrative staff and technicians. Moreover, to explore the factors affecting the coverage of influenza vaccine, a multinomial regression analysis was performed.Over the years, the influenza vaccination uptake showed a gradual increase across the overall staff, the highest coverage (53.8%) was observed in the season 2020/21, in particular, for health personnel (57.7%). In general, males resulted in more adherent to vaccination campaigns; nevertheless, this gap decreased in the last season. A total of 28.6% workers were always vaccinated throughout the past three seasons, a remarkable 25.2% (mainly young and females) received for the first time the influenza vaccination in 2020/21.In this dramatic health crisis, the attitudes of HCWs toward flu vaccination have changed. The COVID-19 outbreak increased adherence to flu vaccination, reaching the highest coverage in the campaign 2020/21. However, further efforts should be made to achieve greater vaccination coverage.
Purpose
Cost evaluation is becoming mandatory to support healthcare sustainability and optimize the decision-making process. This topic is a challenge, especially for complex and rapidly evolving ...treatment modalities such as radiotherapy (RT). The aim of the present study was to investigate the cost of RT in the last month of life of patients in an Italian cancer center.
Methods
This was a retrospective study on a cancer population (
N
= 160) who underwent RT or only an RT planning simulation in an end of life (EOL) setting. The cost of RT procedures performed on patients was collected according to treatment status, care setting, and RT technique used. Costs were valued according to the sum of reimbursements relating to all procedures performed and assessed from the perspective of the National Health System.
Results
The total cost of RT in the last month of life was €244,774, with an average cost per patient of €1530. Around 7.7% and 30.3% of the total cost was associated with patients who never started RT or who discontinued RT, respectively, while the remaining 62.0% referred to patients who completed treatment. Costs associated with outpatient and inpatient settings represented 54.3% and 38.6% of the total cost, respectively. The higher average cost per patient for the never-started and discontinued groups was correlated with patients who had a poor ECOG Performance Status.
Conclusion
Improved prognostic accuracy and a better integration between radiotherapy and palliative care units could be a key to a better use of resources and to a reduction in the cost of EOL RT.
Purpose
To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy ...alone in metastatic breast cancer (MBC) patients.
Methods
CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses.
Results
Seventy-two out of 126 randomized patients were evaluated: 57% had ≥ 1 IGF-1R positive CTC and 37.5% ≥ 4 IGF-1R negative cells; 42% had CTC count ≥ 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (
P
= 0.013) and 3.65 (
P
= 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (
P
= 0.322 and
P
= 0.840). The prognostic role of CTC count was confirmed: HR 1.69,
P
= 0.042 for PFS and HR 2.80 for OS,
P
= 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found.
Conclusion
Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. Clinical trial registration: Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26).
Purpose.
Predicting prognosis in advanced cancer aids physicians in clinical decision making and can help patients and their families to prepare for the time ahead.
Materials and Methods.
This ...multicenter, observational, prospective, nonrandomized population‐based study evaluated life span prediction of four prognostic scores used in palliative care: the original Palliative Prognostic Score (PaP Score), a variant of PaP Score including delirium (D‐PaP Score), the Palliative Performance Scale, and the Palliative Prognostic Index.
Results.
A total of 549 patients were enrolled onto the study. Median survival of the entire group was 22 days (95% confidence intervals 95% CI = 19–24). All four prognostic models discriminated well between groups of patients with different survival probabilities. Log‐rank tests were all highly significant (p < .0001). The PaP and D‐PaP scores were the most accurate, with a C index of 0.72 (95% CI = 0.70–0.73) and 0.73 (95% CI = 0.71–0.74), respectively.
Conclusion.
It can be confirmed that all four prognostic scores used in palliative care studies accurately identify classes of patients with different survival probabilities. The PaP Score has been extensively validated and shows high accuracy and reproducibility in different settings.
Predicting prognosis in advanced cancer aids physicians in clinical decision making and can help patients and their families to prepare for the time ahead. It can be confirmed that all four prognostic scores used in palliative care studies accurately identify classes of patients with different survival probabilities. The Palliative Prognostic Score has been extensively validated and shows high accuracy and reproducibility in different settings.
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