Malignant pancreatic cancers

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The pancreas is a gland just over 15 centimetres long that is located in the upper abdomen, situated transversely and behind the stomach, at the height of the first two lumbar vertebrae.

It basically has two functions:

• Exocrine function: it secretes pancreatic juices- fluids containing the enzymes that are critical for proper digestion
• Endocrine function: it makes different hormones that are used to use or store energy derived from food, including insulin, which regulates blood glucose levels

Different types of tumours can affect the pancreas:

• Adenocarcinoma: it is the most common pancreatic cancer, and it starts in the ducts that carry digestive enzymes. It grows and spreads quickly, and diagnosing it at an early stage is very difficult. The number of cases in Europe is constantly growing: in Italy more than 10,000 people get this disease every year. 
• Endocrine tumours: they originate from hormone-making cells, and they are rare (only 5-10% of pancreatic neoplasms are of endocrine origin). In most cases, these tumours grow slowly and are not very aggressive.
• Cystic tumours: they are also rare and sometimes large; they are sacs filled with fluid. They are often benign or diagnosed when they are still benign.

Causes of malignant pancreatic cancer

Several studies identify some risk factors related to the development of pancreatic cancer:

• Tobacco use: cigarette smoking is the best established risk factor associated with the chances of getting pancreatic cancer
• History of Diabetes
• Chronic pancreatitis (inflammation of the pancreas). People who have suffering from diabetes for a long period of time may have a higher risk of getting the malignancy
• Hereditary factors (previous family history of pancreatic cancer) 
• Obesity. People who are overweight or obese have a slightly higher risk of developing pancreatic cancer.

However, in many cases, the trigger of the tumour cannot be traced or identified. As a matter of fact, many people who get it do not show any of these risk factors, and many who do have one or more do not get sick.

Symptoms of malignant pancreatic cancer

In its early stages, pancreatic cancer is asymptomatic, a characteristic that, unfortunately, can make it difficult to diagnose.

The first evident symptoms appear in the advanced stage of the disease; some of them are very general and, if they are considered individually, they are difficult to attribute to the disease. In general:

• Belly or back pain, which can come and go, worsening when lying down and after eating
• Decreased appetite or increased feeling of satiety
• Unexplained weight loss
• Jaundice (yellowing of the skin and whites of the eye)
• Dark yellow or orange urine
• Light coloured and floating faeces
• Nausea and vomiting
• Weakness or feeling of extreme tiredness

Finally, during the medical visit, the following can be detected:

• Liver enlargement
• Gallbladder enlargement

Diagnosis of malignant pancreatic cancer

When the symptoms listed above occur, and therefore, pancreatic cancer is suspected, there are several tests to check whether the patient has this malignancy or not:

• Computed tomography (spiral or helical scans): to detect pancreatic tumours and possible spread to lymph nodes, liver and bile ducts
• Ultrasound imaging of the abdomen (external), and endoscopically (internal) through the stomach and duodenum.

In the presence of jaundice, three different tests can be performed to check whether the bile ducts are obstructed and whether the obstruction is due to a tumour: 

• Endoscopic retrograde cholangiopancreatography (ERCP)
• Percutaneous transhepatic cholangiography
• Magnetic resonance cholangiography

This last examination is the least invasive and accurately identifies the site of the obstruction, but it does not allow to perform a biopsy in order to investigate the presence of tumour cells, something that can be done with the other two techniques.

In some cases, patients with pancreatic cancer may have increased levels of a protein called CA-19-9. That is the reason why, when an abnormal value is detected, further tests are required.

Treatment of malignant pancreatic cancer

The first therapeutic indication in case of pancreatic cancer is surgery. 
Hadrontherapy is indicated:

• for some locally advanced, inoperable pancreatic tumours 
• in some cases, such as pre-operative treatment (clinical trial)

There is no indication for metastatic cases.

Locally advanced pancreatic tumours are inoperable tumours that have reached large blood vessels; in these cases, chemotherapy cycles are often used. Surgery cannot be performed once the cycles end. 

Given such circumstances, hadrontherapy represents an additional treatment option, which exploits the physical and radiobiological advantages of carbon ions- tissues surrounding the affected area are spared and the resistance to traditional radiation tumours show is overcome.

CNAO is the only Centre in Italy, together with 3 others in Europe, (6 in Japan and 1 in China) that offers hadrontherapy with carbon ions. We are trying to reproduce the results deriving from the extensive Japanese experience, according to which the median survival of patients is 21 months, compared to 16 months in trials with traditional radiation therapies*.

We will also start recruiting patients for an international clinical trial shortly.
'CHIPER' (A Prospective, Multi-Center Randomized Phase 3 Trial of Carbon Ion versus Conventional Photon Radiation Therapy for Locally Advanced, Unresectable Pancreatic Cancer). Patients will be classified into two distinct groups; those belonging to the first group will undergo chemotherapy combined with hadrontherapy with carbon ions; those belonging to the second group will undergo traditional chemotherapy combined with X-ray radiation therapy. The purpose is to understand and prove whether combining chemotherapy and hadrontherapy is better than combining chemotherapy and X-ray radiation therapy. 

*Kawashiro et al; Multi-institutional Study of Carbon-ion Radiotherapy for Locally Advanced Pancreatic Cancer: Japan Carbon-ion Radiation Oncology Study Group (J-CROS) Int J Radiat Oncol Biol Phys. 2018 Aug 1;101(5):1212-1221