Gastrointestinal tumours are often challenging to treat, but there is an encouraging amount of research and development into new treatment options currently taking place.
Because many gastrointestinal cancers have overlapping symptoms and treatment options and by treating a wide range of malignancies, I have personal experience of safely and successfully using therapies developed for one type of cancer on another type of cancer, when there is a strong biological basis for it.
Upper Gastro-intestinal cancers
Upper gastrointestinal cancers include oesophageal cancer, stomach cancer, small bowel cancer, pancreatic cancer, liver cancer and cancers of the biliary system.
Oesophageal cancer
The oesophagus is also known as the gullet or the food pipe and carries food from the mouth to the stomach. Cancer can develop in any part of the oesophagus, and is usually either squamous cell carcinoma, which develops in the lining of the upper oesophagus or adenocarcinoma, which tends to develop at the lower end of the oesophagus. There are other rarer forms of oesophageal cancer. Cancer cells can cause narrowing of the oesophagus, which means difficulty swallowing is a common symptom of oesophageal cancer.
Stomach cancer
Stomach cancer is also known as gastric cancer. The stomach is linked to the oesophagus at the top and the bowel at the bottom, with sphincters at each end to control the movement of food. Cancers can start in any part of the stomach and there are a number of subtypes, including gastric adenocarcinoma, soft tissue sarcoma that begin in the walls of the stomach, non-Hodgkin’s lymphoma that begins in the immune system cells and neuroendocrine cancers that be found in hormone producing cells. Stomach cancer can often asymptomatic in its early stages and when symptoms do exhibit, they can be nonspecific, including indigestion, abdominal pain, nausea, tiredness and weight loss.
Hepatobiliary cancers
The term hepatobiliary cancer refers to primary malignancies, which develop in the liver, either hepatocellular carcinoma , or the intra- and extra-hepatic biliary ductal system giving rise to biliary tract carcinomas.
Pancreatic cancer
The pancreas is a large gland found within the abdomen that creates enzymes to aid digestion, as well as making important hormones, such as insulin. The most common type of cancer is pancreatic ductal adenocarcinoma, a form of exocrine tumour. These begin in the exocrine cells, where enzymes are made. A less common form of pancreatic cancer results from neuroendocrine tumours, which develop in the neuroendocrine cells that produce hormones. Pancreatic cancer is often asymptomatic in the early stages, with symptoms including yellow skin, loss of appetite, weight loss and abdominal pain usually only seen at an advanced stage.
Biliary tract cancer
Biliary tract cancer is a form of cholangiocarcinoma, which develops in the gland cells lining the bile ducts. Bile ducts connect the liver and the gallbladder to the small intestine, allowing bile to pass through and aid the breakdown of fats in food. Tumours can form in different parts of the bile duct, with intrahepatic cholangiocarcinoma forming in the part that sits within the liver, hilar cholangiocarcinoma occurring outside of the liver and distal cholangiocarcinoma occurring in the part that sits near the small intestine. As with pancreatic cancer, symptoms often present at an advanced stage and include jaundice, weight loss, changes to the colour of stools and urine and abdominal pain.
Gallbladder cancer
The gallbladder is a small organ in the abdomen that concentrates and stores the bile made in the liver before it travels through the bile ducts into the small intestine. Gallbladder cancer is rare and is often related to the build-up of gallstones which can lead to calcification of the gallbladder. Symptoms such as abdominal pain and jaundice normally present once the cancer has spread to other organs, but if caught early is highly treatable through surgery and removal of the gallbladder as bile can still travel directly from the liver through bile ducts to the small intestine.
Lower gastrointestinal cancers
Colorectal cancer
Colorectal cancer, also known as bowel cancer, refers to cancer of the colon and rectum, which make up the large intestine. The colon is a 5 feet long tube that connects the small intestine to the rectum. Many colorectal cancers begin as growths, known as polyps, which form on the inner lining of the colon or rectum and continue to grow. There are different types of polyps and some have a higher risk of becoming cancerous over time. Common symptoms include blood in the stool, weight loss, fatigue and a change in the regularity and consistency of bowel movements.
Anal cancer
The anus is at the end of the rectum with an internal and external sphincter controlling the movement of faeces out of the body. Anal cancer is rare but can develop in the lining as squamous cell cancers or as adenocarcinomas in the glandular cells. In some cases, cancer develops known in the skin cells, known as melanoma. Symptoms including blood in the stool, anal discharge and changes to your bowel movements.
Carcinoma of unknown primary
Cancer cells can travel and spread through the body through the blood or lymphatic system, causing a secondary cancer, also known as metastasis. Cancers or carcinoma of unknown primary (CUPs) occur when a patient has metastatic disease, but we cannot diagnose where the cancer came from because the primary tumour site cannot be identified. This may be for a number of reasons. In some cases, the primary cancer is too small or hidden behind the secondary cancer, making it difficult to diagnose. Sometimes the body’s natural immune response has successfully got rid of the primary cancer, despite it spreading.
Treatment Options
Cancer cells grow and divide more quickly than most other cells in the body, which is how tumours grow. Chemotherapy is a conventional form of cancer treatment that attacks the rapidly dividing cancer cells. There are different types of chemotherapy drugs. The type of drug, the dosage and the length of the treatment all depend on the size and location of the tumour and if it has spread, as well as biological factors such as the health, age and medical history of the patient. As a research-active consultant I make every effort to examine the latest data around clinical trials and developments in the field to determine the most effective forms of chemotherapy for each patient.
Chemotherapy can be used on primary and secondary cancers and is usually given intravenously. Although the chemotherapy drugs are used to destroy cancer cells, they can also damage other cells in the body that grow and multiply quickly. This can lead to unpleasant side effects but myself and other members of the multidisciplinary team work closely with patients on how to best manage them.
Most patients require multiple rounds of chemotherapy. As an oncologist, as essential part of my role is careful decision making around the length of treatment. It’s important that chemotherapy is not overprescribed and patients instead receive adequate maintenance therapy that keeps the cancer from coming back.
Immunotherapy is a novel way of treating cancer that works by enhancing the patient’s own immune response. The body’s natural immune response detects and destroys abnormal cells and will work to prevent the growth of cancers. In some cases, however, the cancer grows too aggressively for the immune system to succeed. In other cases, cancel cells have genetic changes or abnormal proteins that that make the immune system less effective at identifying and destroying them.
There are different types of immunotherapy treatment that each support the body’s immune response in different ways. Checkpoint inhibitors for example, work by blocking the immune cells ‘checkpoint protein’, that stops it from attacking cancer cells. Monoclonal antibodies (MABs) work by attaching themselves to cancer cells, making it easier for immune cells to find them.
Immunotherapy often requires initial tests, such as blood tests or a biopsy to understand which treatment will work most effectively for you. Side effects will also vary and depending on the treatment. Immunotherapy may take longer to take affect than conventional therapies, but by supporting the body’s natural immune response, is less likely to damage non-cancerous cells.
Targeted therapies are drugs that attack specific genes and protein within cancer cells. By identifying these specific genetic changes and proteins that are not present in healthy cells, we can target these mutations to either block signals that cause rapid cell growth or destroy the cancer cells entirely.
For example, there is a complex phenomenon found in some tumours known as oncogenic addiction. This happens when the cancer becomes ‘addicted’ or dependent on certain genes or proteins for survival. As a result, by identifying the gene or protein and administering drugs that bind to cell proteins and block their activity, we can destroy cancer cells without damaging normal cells.
There are multiple targeted therapies, each targeting different mutations in the cancer cells but they are not suitable for all types of cancers. They can also be used in combination with other types of therapies and surgery for optimum results. I have been involved in early phrase research of targeted therapies and my knowledge of the development of these drugs informs how I apply them in to my patients in practice.
Medical research has evolved over time and we now know that the use of multiple different therapies can lead to the best possible results when treating cancer. A large part of my own research has been into what happens when we combine both conventional and novel therapies.
There can be a synergistic effect when combining chemotherapy, immunotherapy and targeted therapies, but in each instance I work closely with the patient to ensure that we are optimising the benefits of multiple therapies while limiting the potential side effects of the treatment.
In some cases, we also work with other disciplines such as surgery or interventional radiology to make the tumour more manageable. We first try to achieve systemic control of the cancer before it spreads to other part of the body through combination therapies. Once it has shrunk, what is left of the tumour can be removed either through surgery or through radiofrequency ablation or embolization.
A treatment plan will be developed only after assessing the disease biology and the individual needs and wishes of the patient.
Liquid Biopsy
A liquid biopsy is a minimally invasive technique (taking of a blood sample) that has ability to detect and characterize tumours by analysing biomarkers circulating in the blood. The two most well-developed biomarkers detected by liquid biopsy are circulating tumour cells (CTCs) and circulating cell-free tumour DNA (ctDNA). Analysing of a blood sample to look for the presence of these pieces of DNA from tumour cells, can be used to find cancer at an early stage or help plan treatment or to find out how well treatment is working or if cancer has come back, by enabling a doctor to see the molecular changes taking place in a tumour.
Khurum is an expert in the field of liquid biopsy, with the main focus of his research being using ctDNA from blood samples to gain knowledge about complex molecular mechanisms of cancer. This enables Khurum to tailor cancer therapies for his patients and offer “out-of-box” treatment options. See the case study of Zandra Rhodes for an example of Khurum successfully using this approach.
His hope is that in the future, doctors will be able to perform serial liquid biopsies at clinically relevant intervals such that therapies can be switched at the right times to get the best outcomes for the patients.