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from palliative literature, were administered with acceptable safety and tolerability. Off-label treatment practised in the clinic should be identified, reported and serve as inspiration for future scientific research and incentives for extension of marketing authorisations.Individuals with advanced cancer who have accurate prognostic awareness are reported to make more informed decisions about their plan of care. Despite this, it is reported that individuals do not always have accurate prognostic awareness with the rationale for this discordance unclear. The primary aim of the integrative literature review was to identify if there is concordance between actual prognosis and accurate prognostic awareness in individuals with advanced cancer. The secondary aim was to identify the rationale for any discordance between actual prognosis and prognostic awareness in individuals with advanced cancer. This is an integrative literature review using a systematic approach. Literature searches were undertaken in March 2018 in four databases; CINAHL, MEDLINE, PsycINFO and Cochrane Library. Searches were limited to between 2008 and 2018 and those written in the English language. Database searches were supplemented with papers from reference lists of included papers and grey literature. Two reviewers independently completed the literature search and independently reviewed the papers. GSK-3 inhibition Fourteen eligible research papers were identified. The majority of individuals with advanced cancer in the included studies did not have accurate prognostic awareness. When identified, the rationale for discordance relates to the individual not being communicated accurate prognostic information, not being able to recall prognostic conversations or prognosis being discussed in vague terms. As individuals with advanced cancer with accurate prognostic awareness make more informed decisions at a crucial time in their life trajectory, it is imperative that healthcare professionals are equipped to effectively deliver accurate prognostic information, ensuring understanding is assessed.
Patients with haematological malignancies (HM) receive more aggressive treatments near the end-of-life (EOL) than patients with solid tumours. Palliative care (PC) needs are less widely acknowledged in patients with multiple myeloma (MM) than in other HM. The main objective of our study was to describe EOL care and PC referral in a population of older patients with MM.
We retrospectively included deceased inpatients and outpatients with an MM previously diagnosed at the age of 70 and over in two tertiary centres in France. We reported EOL characteristics regarding treatments considered to be aggressive-antimyeloma therapies, hospitalisations, blood product transfusions, intensive care units (ICUs) or emergency admissions-and PC referral.
We included 119 patients. In their last month of life, 75 (63%) were hospitalised for fever, pain, asthenia, anaemia or bleeding, 49 (41%) were admitted in the emergency department and 12 (10%) in ICU, 76 (64%) still received antimyeloma therapy and 45 (38%) had at least two transfusions. Only 24 (20%) received PC intervention for pain, global care, family support, anxiety, social care or confusion. Median follow-up until death was 20 days.
Our study found a high rate of hospitalisations and antimyeloma therapies in the last month of life. The PC referral rate was low, often once specific treatments were stopped. Our results suggest the need for more effective collaboration between PC teams and haematologists in order to respond to the specific needs of these patients and to improve their quality of care at EOL.
Our study found a high rate of hospitalisations and antimyeloma therapies in the last month of life. The PC referral rate was low, often once specific treatments were stopped. Our results suggest the need for more effective collaboration between PC teams and haematologists in order to respond to the specific needs of these patients and to improve their quality of care at EOL.
The safety and preliminary efficacy of MEDI1873, an agonistic IgG1 fusion protein targeting glucocorticoid-induced TNF receptor-related protein (GITR), were evaluated in an open-label, first-in-human, phase I, dose escalation study in previously treated patients with advanced solid tumors.
Two single-patient cohorts at 1.5 and 3 mg i.v. were followed by 3+3 dose escalation in six cohorts at 7.5, 25, 75, 250, 500, and 750 mg, all every 2 weeks, for up to 52 weeks. Primary endpoints were safety and tolerability, dose-limiting toxicities (DLT), and MTD. Secondary endpoints included antitumor activity, pharmacokinetics, immunogenicity, and pharmacodynamics.
Forty patients received MEDI1873. Three experienced DLTs grade 3 worsening tumor pain (250 mg); grade 3 nausea, vomiting, and headache (500 mg); and grade 3 non-ST segment elevation myocardial infarction (750 mg). An MTD was not reached and treatment was well tolerated up to 500 mg. Most common treatment-related adverse events were headache (25%), infusion-related reaction (17.5%), and decreased appetite (17.5%). MEDI1873 exposure was dose proportional. Antidrug-antibody incidence was low. MEDI1873 increased peripheral CD4
effector memory T-cell proliferation as well as cytokines associated with effector T-cell activation at dose levels ≥75 mg. The best response was stable disease (SD) in 17 patients (42.5%), including 1 unconfirmed partial response. Eight patients (20.0%) had SD ≥24 weeks.
MEDI1873 showed acceptable safety up to 500 mg i.v. every 2 weeks with pharmacodynamics activity, and prolonged SD in some patients. However, further development is not planned because of lack of demonstrated tumor response.
MEDI1873 showed acceptable safety up to 500 mg i.v. every 2 weeks with pharmacodynamics activity, and prolonged SD in some patients. However, further development is not planned because of lack of demonstrated tumor response.
Advanced thyroid cancers, including poorly differentiated and anaplastic thyroid cancer (ATC), are lethal malignancies with limited treatment options. The majority of patients with ATC have responded poorly to programmed death 1 (PD1) blockade in early clinical trials. There is a need to explore new treatment options.
We examined the expression of PD-L1 (a ligand of PD1) and intercellular adhesion molecule 1 (ICAM1) in thyroid tumors and ATC cell lines, and investigated the PD1 expression level in peripheral T cells of patients with thyroid cancer. Next, we studied the tumor-targeting efficacy and T-cell dynamics of monotherapy and combination treatments of ICAM1-targeting chimeric antigen receptor (CAR) T cells and anti-PD1 antibody in a xenograft model of ATC.
Advanced thyroid cancers were associated with increased expression of both ICAM1 and PD-L1 in tumors, and elevated PD1 expression in CD8
T cells of circulating blood. The expression of ICAM1 and PD-L1 in ATC lines was regulated by the IFNγ-JAK2 signaling pathway.
