REVISION Flashcards
WHAT WAS THE MAIN TRIAL POPULATION THAT THE DRUG VENETOCLAX WAS INTENDED FOR IN THE NICE STA PROCESS?
RELAPSED OR REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA
HYPERMETHYLATION OF CPG ISLANDS CAN BE USED AS BIOMARKERS TO INFORM DIAGNOSIS, PROGNOSISM AND TREATMENT RESPONSE IN CANCERS. MGMT HYPERMETHYLATION IN PATIENTS WITH GLIOMA IS A GOOD BIOMARKER FOR?
FOR INDICATING THAT PATIENTS WILL RESPOND WELL TO CHEMOTHERAPEUTIC AGENT TEMOZOLOMIDE
RANDOMISATION IN CLINICAL TRIALS IS USED TO:
STOP SELECTION BIAS WHEN ALLOCATING TREATMENTS
ABCDE RULE FOR MELANOMA
The ABCDE Rule of skin cancer is an easy-to-remember system for determining whether a mole or growth may be cancerous:
A Asymmetry of shape of one half of the lesion compared to the other half
B Border of the lesion is irregular, jagged, notched or may blur pigment into the surrounding skin
C Colour of the lesion may be varied with shades of black, brown, blue and white
D Diameter of the lesion is greater than 6 mm, or larger than the end of an eraser
E Evolution of the size, shape, elevation, surface or colour of the lesion has occurred over time
EXAMPLE OF A NON-CANCEROUS SKIN LESION
A lesion that is confined to the epidermis (the outermost skin layer) and has not spread to nearby lymph nodes and other areas of the body
EARLY VS LATE STAGE MELANOMA
.At an early stage (0 to 2), melanoma is only in the skin and there is no sign that it has spread to lymph nodes.
(Stage 0 referred to as melanoma in situ)
At late stages (3 or 4), this generally means melanoma has spread to nearby lymph nodes or elsewhere in the body.
Treating the early stage is mainly by excision surgery to remove the melanoma as well as a margin of normal skin around it, while the late stage is usually treated with wide excision surgery plus adjuvant treatment with immunotherapy or with targeted therapy drugs or radiation therapy.
What makes something cancerous?
key: uncontrollable division AND spread to nearby or distant regions of the body
KINASE INHIBITORS AND MELANOMA
Kinase inhibitors target signalling pathways particularly those driving cell proliferation. They consist of tyrosine kinase inhibitors (receptor and non-receptor tyrosine kinases) and serine/threonine kinase inhibitors.
These mostly target the ERK-MAP kinase pathway through either directly inhibiting receptor tyrosine kinases such as the EGF receptor or downstream components of MAP kinase cascade.
One kinase component of this pathway, BRAF, is mutated in around 50% of melanomas and as consequence becomes hyperactivated. BRAF inhibitors have been designed to target this kinase and block its ability to activate the downstream signalling cascade that results in the proliferation of melanoma cells.
IMMUNE CHECKPOINT INHIBITORS AND MELANOMA
Immune checkpoint inhibition (ICI) is a type of cancer immunotherapy. This therapy uses monoclonal antibodies to block the inhibitory pathways that control T cell activation. T cells are an important component of the anti-tumour immune response and be activated to directly kill cancer cells expressing tumour-associated antigens. (2 marks)
Immune checkpoint pathways normally prevent T cells from becoming hyperactivated which can result in autoimmune disease. Tumour-specific T cells can be inhibited by these same pathways through inhibitory signals received from: (a) antigen presenting cells in lymph nodes via CTLA-4 on the surface of T cells and B7 on the surface of antigen presenting cells and (b) tumour cells at the site of the cancer via PD-1 on the surface of T cells and PD-L1 on the surface of tumour cells. These interactions can be directly blocked by monoclonal antibodies (e.g. Ipilimumab to block CTLA-4, Nivolumab to block PD-1, Avelumab to block PD-L1) and this approach results in significant clinical benefit in patients with various tumours.
In the context of metastatic melanoma, ICI therapy results in an objective clinical response in 35-40% of patients. The lack of response to ICI therapy in some patients with melanoma and in those with other tumours is due to differences in immune responsiveness within the tumour microenvironment (TME).
The more immune responsive tumours have an inflammed TME with many infiltrating T cells and macrophages along with high levels of PD-L1 expression on the tumour cells and a high tumour mutational burden. These factors can be measured as biomarkers in tumour biopsies and used to identify those patients who will respond more effectively to ICI therapy as a form of personalised cancer immunotherapy.
ALMOST 1/2 OF MEDICAL EXPENDITURE IS BEING INCURRED IN THE LAST X DAYS OF A PATIENT’S LIFE?
60 DAYS
CHARACTERISTICS OF SUSTAINABLE HEALTHCARE
- QUALITY
- ACCESSABILITY
- AFFORDABILITY
- ACCEPTABILITY
IF NO ACTION IS MADE, THE GLOBAL TEMPERATURE WILL INCREASE BY X DEGREES BY 2100 (COMPARED TO PREINDUSTRIAL TIMES)
3.6 DEGREES
EN ROADS
En-ROADS is a freely-available online simulator that provides policymakers, educators, businesses, the media, and the public with the ability to test and explore cross-sector climate solutions.
En-ROADS is a global climate simulator that allows users to explore the impact of roughly 30 policies—such as electrifying transport, pricing carbon, and improving agricultural practices—on hundreds of factors like energy prices, temperature, air quality, and sea level rise.
