Pain from advanced pancreatic cancer is often difficult to control. This pain commonly occurs when the cancer affects a network of nerves in the abdomen called the coeliac plexus. Even strong pain medicines, including morphine and related drugs, may not give enough relief. Some patients may have a procedure called a coeliac plexus block, but this is invasive, not widely available, and does not always work.

Radiotherapy is widely used to relieve cancer-related pain in other cancers, but it is not commonly used in the UK for pancreatic cancer pain. Studies carried out in the United States and Amsterdam have investigated the use of radiotherapy to help control pain in pancreatic cancer and have shown benefit for many patients. However, these studies were not specifically designed to target the coeliac plexus nerve region, which is thought to be an important source of pain in pancreatic cancer.

Recent research suggests that radiotherapy directed at this nerve area may reduce pain in many patients with limited side effects. This study is therefore being carried out to investigate whether targeting this nerve area using a short course of radiotherapy can safely and effectively improve pain control in patients with advanced pancreatic cancer.

The radiotherapy in this study will be delivered using a widely available technique called Intensity Modulated Radiotherapy (IMRT). IMRT is an advanced form of radiotherapy that allows radiation beams to be shaped very precisely to the treatment area while reducing radiation exposure to nearby healthy tissues and organs. IMRT is routinely used in the NHS to treat many different types of cancer, including prostate, head and neck, lung, and gastrointestinal cancers. In this study radiotherapy is not being given with the intention of treating the cancer itself, but rather to help alleviate pain related to the cancer.

The main outcome we will measure is whether pain improves by a meaningful amount using a questionnaire called the Brief Pain Inventory (BPI), which assesses pain severity and its impact on daily life. We will also measure changes in pain medication, treatment side effects, overall survival and patients' overall impression of change after treatment. Participants will be followed up for up to 12 months after radiotherapy treatment.

If this study shows a promising signal of benefit, radiotherapy for pancreatic cancer pain could become more widely used across the UK. Because IMRT is available at most radiotherapy centres, many patients could receive treatment closer to home.

Inclusion Criteria:

1. Pain with a BPI score ≥ 2 as a result of pancreatic adenocarcinoma, not sufficiently responding to opiate medication.

2. Primarily unresectable or locally advanced pancreatic adenocarcinoma with or without metastases.

3. Participant is not considered suitable for a potentially radical treatment pathway (including radical chemoradiotherapy, SABR, or surgery with curative intent).

4. Histological or cytological confirmation of adenocarcinoma of the pancreas.

5. Diagnostic CT scan not older than 2 months before study entry.

6. Age ≥ 18 years.

7. If the participant is receiving systemic anti-cancer therapy (SACT), the following minimum washout periods must be achievable:

   1. A minimum interval of 7 days between the last dose of SACT and the start of radiotherapy.
   2. A minimum interval of 7 days between completion of radiotherapy and recommencement of SACT.

8. Able to provide informed consent and has provided written, signed, and dated consent.

9. The ability to answer questionnaires.

Exclusion Criteria:

1. Resectable or borderline resectable tumours without distant metastases.
2. Locally advanced pancreatic adenocarcinoma without distant metastases where a higher dose of radiation delivery for local control is deemed in the participant's best interests.
3. Participants who are unable to have a washout window from their SACT are ineligible for the trial.
4. Pregnant women.
5. Predicted prognosis less than 8 weeks.
6. Prior radiotherapy to the abdomen.