The goal of this observational study is to to look for changes within the brain, and changes in body-to-brain signals in people with cancer and people who do not have cancer. The main questions it aims to answer are:

1. Are there differences in areas of the brain known to be related to appetite control, food reward and motivation, between participants with cancer related weight loss and healthy volunteers
2. Do responses to questionnaires and computer based tasks suggest participants with cancer related weight loss have reduced appetite and reduced motivation to eat compared to healthy volunteers, and if so, do questionnaires suggest that this is associated with any other symptoms?

Researchers will compare the structure and blood flow in relevant areas of the brain using MRI images between participants with cancer related weight loss and healthy volunteers. Participants will complete questionnaires and computer based tasks to allow researchers to assess areas of the brain which become more active in response to different stimuli. Some computer based tasks will be performed during the MRI scan. This is called functional MRI.

A further objective is to obtain an archive of blood samples which will be stored securely for future analysis if relevant hormones or analytes are identified that may be relevant to metabolism or body composition

Cancer cachexia is a complex disorder involving progressive loss of muscle and fat in people with cancer, which cannot be corrected with dietary supplements. It affects 50-80% of the cancer population, and accounts for up to 20% of cancer related deaths.To date there are no effective treatments for cancer cachexia and further research is needed to highlight possible treatments for this condition.

Previous research into conditions such as obesity and anorexia have shown the importance of signals between the body and the brain in controlling appetite. This study will focus on how cancer affects signals within the body which are communicated to the brain. In people with cancer, these signals may be altered, leading to changes in appetite and less pleasure from eating, ultimately resulting in weight loss (cancer cachexia).

The study will be observational and will be carried out in one centre at the Translational Research Facility, Addenbrookes Hospital. Researchers aim to recruit 50 participants (30 with cancer and weight loss, and 20 healthy volunteers).

Potential participants will be identified by clinical teams in oncology clinics, via recruitment posters and multi-disciplinary team meetings on the hospital site. Participants will attend for one study visit lasting 4 hours. During this time, participants will undergo an MRI scan, complete questionnaires and perform computer based tasks. Researchers will look for changes within the brain, and changes in body-to-brain signals in people with cancer and people who do not have cancer. Researchers will assess attitudes to eating and body perceptions using questionnaires and computer based tasks. This will indicate whether cancer is driving changes in behaviour which may cause weight loss (cachexia). The ultimate goal is to develop treatment strategies in future to prevent weight loss and improve outcomes for people with cancer

Inclusion Criteria:

General inclusion criteria for all groups:

• Written informed consent
• Aged 18 years or over
• Willing and able to comply with study procedures and visits

Additional inclusion criteria for participants with cancer:

• Histological or cytological diagnosis of cancer or confirmed non-intracranial malignancy on imaging.
• Unintended documented weight loss of >5% body weight in 6 months which is felt to be cancer related, OR patient reported weight loss and/or change in appetite

Exclusion Criteria:

General exclusion criteria for all groups:

• Non-fluent English speaker
• Active infection, as determined by the investigator based on clinical symptoms and / or fever and / or requirement for antibiotics
• Women, who are pregnant, plan to become pregnant or are lactating.
• MRI contraindication
• A significant acute, chronic or psychiatric condition which in the judgement of the investigator would place the volunteer at undue risk or interfere with the study
• Metabolically or clinically unstable on day of study visit
• Artificial nutrition
• Taking medications which, as determined by the investigator, may affect appetite or cognition, or otherwise affect completion of study tasks.
• Weight or body circumference above upper threshold for MRI scanner (220kg)
• Unresolved obstructive gastrointestinal (GI) lesion

Additional exclusion criteria for participants with cancer:

• Intracranial cancer or metastatic intracranial involvement of cancer

Additional exclusion criteria for healthy volunteers:

• Have, or be recovering from, any form of cancer
• Unintentional weight loss of >5% body weight or unexplained loss of appetite

A maximum of 50 participants will be recruited to this study over a period of 4 years.

This will include approximately 30 participants with cancer, and 20 healthy volunteers. Participants with cancer will be recruited from oncology outpatient clinics or multi-disciplinary team meetings including palliative care MDT meetings at Addenbrooke's Hospital, Cambridge. Healthy volunteers will be recruited by advertising on site, study recruitment notice boards or through a contact of the participant with cancer. Participants in each group will be matched for age and sex