Summary Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous ...population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology. This suggests that not all patients with intermediate-stage HCC will derive similar benefit from TACE, and that some patients may benefit from other treatment options. Results of an extensive literature review into the treatment of unresectable HCC with TACE were combined with our own clinical experience to identify factors that may predict survival after TACE. We also report contraindications to TACE and propose a treatment algorithm for the repetition of TACE. In addition, we have constructed a number of expert opinions that may be used as a guide to help physicians make treatment decisions for their patients with intermediate-stage HCC. The data included in the literature review related almost exclusively to conventional TACE, rather than to TACE with drug-eluting beads. Therefore, the findings and conclusions of the literature review are only applicable to the treatment of HCC with conventional TACE. Treating physicians may want to consider other treatment options for patients with intermediate-stage HCC who are not suitable for or do not respond to TACE. By distinguishing those patients who represent good candidates for TACE from those where little or no benefit might be expected, it may be possible to make better use of current treatment options and improve outcomes for patients.
In a phase III trial in patients with advanced, well-differentiated, progressive pancreatic neuroendocrine tumors, sunitinib 37.5 mg/day improved investigator-assessed progression-free survival (PFS) ...versus placebo (11.4 versus 5.5 months; HR, 0.42; P < 0.001). Here, we present PFS using retrospective blinded independent central review (BICR) and final median overall survival (OS), including an assessment highlighting the impact of patient crossover from placebo to sunitinib.
In this randomized, double-blind, placebo-controlled study, cross-sectional imaging from patients was evaluated retrospectively by blinded third-party radiologists using a two-reader, two-time-point lock, followed by a sequential locked-read, batch-mode paradigm. OS was summarized using the Kaplan–Meier method and Cox proportional hazards model. Crossover-adjusted OS effect was derived using rank-preserving structural failure time (RPSFT) analyses.
Of 171 randomized patients (sunitinib, n = 86; placebo, n = 85), 160 (94%) had complete scan sets/time points. By BICR, median (95% confidence interval CI) PFS was 12.6 (11.1–20.6) months for sunitinib and 5.8 (3.8–7.2) months for placebo (HR, 0.32; 95% CI 0.18–0.55; P = 0.000015). Five years after study closure, median (95% CI) OS was 38.6 (25.6–56.4) months for sunitinib and 29.1 (16.4–36.8) months for placebo (HR, 0.73; 95% CI 0.50–1.06; P = 0.094), with 69% of placebo patients having crossed over to sunitinib. RPSFT analysis confirmed an OS benefit for sunitinib.
BICR confirmed the doubling of PFS with sunitinib compared with placebo. Although the observed median OS improved by nearly 10 months, the effect estimate did not reach statistical significance, potentially due to crossover from placebo to sunitinib.
NCT00428597.
Background: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse. Patients and methods: A total of 400 patients ...with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A—LV5FU2 leucovorin 200 mg/m2, 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m2 bolus, 600 mg/m2 22-h continuous infusion, days 1 and 2 or B—LV5FU2 + IRI (irinotecan 180 mg/m2 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS). Results: Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% 95% confidence interval (CI) 53% to 66% and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference was observed hazard ratio (HR) = 1.12, 95% CI 0.85–1.47, P = 0.42 even when adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74–1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53% to 67%) in arms A and B, respectively. Conclusion: Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.
Redox-active ligands have evolved from being considered spectroscopic curiosities - creating ambiguity about formal oxidation states in metal complexes - to versatile and useful tools to expand on ...the reactivity of (transition) metals or to even go beyond what is generally perceived possible. This review focusses on metal complexes containing either catechol,
o
-aminophenol or
o
-phenylenediamine type ligands. These ligands have opened up a new area of chemistry for metals across the periodic table. The portfolio of ligand-based reactivity invoked by these redox-active entities will be discussed. This ranges from facilitating oxidative additions upon d
0
metals or cross coupling reactions with cobalt(
iii
) without metal oxidation state changes - by functioning as an electron reservoir - to intramolecular ligand-to-substrate single-electron transfer to create a reactive substrate-centered radical on a Pd(
ii
) platform. Although the current state-of-art research primarily consists of stoichiometric and exploratory reactions, several notable reports of catalysis facilitated by the redox-activity of the ligand will also be discussed. In conclusion, redox-active ligands containing catechol,
o
-aminophenol or
o
-phenylenediamine moieties show great potential to be exploited as reversible electron reservoirs, donating or accepting electrons to activate substrates and metal centers and to enable new reactivity with both early and late transition as well as main group metals.
The emerging applications of catechol,
o
-aminophenol and
o
-phenylenediamine based redox-active ligands for chemical reactivity and catalysis are highlighted.
Use of chemotherapy near the end of life in patients with metastatic cancer is often ineffective and toxic. Data about the factors associated with its use remain scarce, especially in Europe.
...Nationwide, register-based study including all hospitalized patients aged ≥20 years who died from metastatic solid tumors in France between 2010 and 2013.
A total of 279 846 hospitalized patients who died from metastatic cancer were included. During the last month before death, 19.5% received chemotherapy (including 11.3% during the last 2 weeks). Female sex (OR= 0.96, 95% CI= 0.93–0.98), older age (OR= 0.70, 95% CI= 0.69–0.71 for each 10-year increase) and higher number of chronic comorbidities (OR= 0.83, 95% CI= 0.82–0.84) were independently associated with lower rates of chemotherapy. Although patients with chemosensitive tumors were statistically more likely to receive chemotherapy during the last month before death (OR= 1.21, 1.18–1.25), this association was mostly fueled by testis and ovary tumors and we found no obvious pattern between the expected chemosensitivity of different cancers and the rates of chemotherapy use close to death. Compared with university hospitals, patients who died in for-profit clinics/hospital (OR= 1.40, 95% CI= 1.34–1.45), or comprehensive cancer centers (OR= 1.43, 95% CI= 1.36–1.50) were more likely to receive chemotherapy. Finally, high-volume centers and hospitals without palliative care units reported greater-than-average rates of chemotherapy near the end of life.
among hospitalized patients with cancer, young individuals, treated in comprehensive cancer centers or in high-volume centers without palliative care units were the most likely to receive chemotherapy near the end of life. We found no evident pattern between the expected chemosensitivity of different cancers and the probability for patients to receive chemotherapy close to death.
Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and ...had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC.
The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m2 i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously.
Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively).
The addition of sorafenib to gemcitabine does not improve PFS in APC patients.
A Dynamical Model of General Intelligence van der Maas, Han L. J; Dolan, Conor V; Grasman, Raoul P. P. P ...
Psychological review,
10/2006, Letnik:
113, Številka:
4
Journal Article
Recenzirano
Scores on cognitive tasks used in intelligence tests correlate positively with each other, that is, they display a positive manifold of correlations. The positive manifold is often explained by ...positing a dominant latent variable, the
g
factor, associated with a single quantitative cognitive or biological process or capacity. In this article, a new explanation of the positive manifold based on a dynamical model is proposed, in which reciprocal causation or mutualism plays a central role. It is shown that the positive manifold emerges purely by positive beneficial interactions between cognitive processes during development. A single underlying
g
factor plays no role in the model. The model offers explanations of important findings in intelligence research, such as the hierarchical factor structure of intelligence, the low predictability of intelligence from early childhood performance, the integration/differentiation effect, the increase in heritability of
g
, and the Jensen effect, and is consistent with current explanations of the Flynn effect.
Metastatic colorectal cancer is a particularly frequent and severe cancer. Patients die mainly from metastatic disease; however, the survival of these patients has dramatically improved with the ...progress in chemotherapeutic regimens as new routes of administration and introduction of more potent cytotoxic agents administered in sequential 5-FU-folinic acid-irinotecan/5-FU-folinic acid-oxaliplatine strategies. Biologic therapies have been also developed targeting two different pathways, angiogenesis and the epidermal growth factor receptor. Their combination with chemotherapy leads to improved progression-free survival and overall survival in some cases as the addition of cetuximab in wild-type K-Ras tumors. The objectives of this expert conference were to review the different options, the available prognostic or predictive factors to optimally guide the treatment.
Abstract Objective To assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC). Design Among the 294 patients with ...non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test. Results Among the 216 patients with stage IV CRC (median follow-up, 33 months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p = 0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval CI, 0.4–0.8; p = 0.0002) and OS (HR, 0.4; CI, 0.3–0.6; p < 0.0001). Both median PFS (5.1 4.6–5.6 versus 2.9 2.2–4.1 months; p = 0.001) and OS (16.3 13.7–19.2 versus 9.6 7.4–12.5; p < 0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary ( n = 43). Conclusion Resection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.
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