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Gastrointestinal Cancers in focus

Introduction to GI cancer

This page provides an overview of gastrointestinal (GI) cancer, the associated disease burden and clinical considerations relating to the most common GI tumour types.

GI tract cancer is a collective term used to describe cancers that affect the digestive system. Worldwide, the most commonly diagnosed GI cancers include: colorectal cancer (CRC); gastric cancer; liver cancers (e.g. hepatocellular carcinoma [HCC]); oesophageal cancer; and pancreatic cancer.1

Less common GI cancers include those affecting the anus, appendix, bile duct, gallbladder and small intestine,2,3 as well as GI neuroendocrine tumours (NETs) and stromal tumours (GISTs), which are characterised by their cell type of origin rather than their location within the GI tract.4,5

Disease burden

GI cancers are responsible for more cancer-related deaths than any other type of cancer.6 In 2018, they accounted for an estimated 3.4 million deaths worldwide, with a further 4.8 million new cases diagnosed in the same year.6

Common GI cancers: global incidence and mortality6

Global GI cancer incidence and mortality

*Global data, both sexes, all ages; **CRC, gastric cancer, oesophageal cancer, pancreatic cancer, liver cancer.

CRC, colorectal cancer; GI, gastrointestinal.

Common types of GI cancer

CRC is the most common type of GI cancer, with 1.85 million new cases diagnosed worldwide in 2018, making it the third most common of all organ cancers, after lung and breast.6

In the same year, gastric (or stomach) and oesophageal cancers were ranked the fifth and seventh most commonly diagnosed cancers (respectively), with 1.03 million new cases of gastric cancer and 0.6 million new cases of oesophageal cancer worldwide.6

Rank order of incident cancer cases in 20186

Rank order of incident cancer cases in 2018

CRC, colorectal cancer; GI, gastrointestinal.

Common GI cancers ‘at a glance’

CRC

CRC occurs when a growth in the lining of the large intestine (colon), or at its end (rectum), becomes cancerous. It is one of the leading causes of cancer-related deaths in men and women, worldwide.6

Approximately 25% of patients with CRC present with metastases at the time of initial diagnosis, and almost a half go on to develop metastases at some point, contributing to its high mortality rate.7

Location of the colon and rectum within the digestive system

Location of the colon and rectum within the digestive system
  • Common symptoms include: changes in bowel habits, general or localised abdominal pain, weight loss without other specific causes, weakness, iron deficiency and anaemia8
  • Risk factors include: age, inflammatory bowel disease, family history, elevated body mass index, reduced physical activity, alcohol consumption and cigarette smoking, as well as a number of dietary factors. High consumption of processed and red meat is thought to contribute to increased risk, while high fruit and vegetable intake is thought to confer protection9
  • Staging: staging of metastatic CRC should include clinical examination, blood counts, liver and renal function tests, carcinoembryonic antigen (CEA) evaluation, and a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the abdomen and chest.7 Additionally, a colonoscopy is often performed as part of initial diagnostic procedures.8 The optimum therapeutic strategy is further determined by an evaluation of the patient’s general condition, organ function and presence of any relevant comorbid (non-malignant) diseases7
  • Management (first-line standard of care):
    • Early-stage disease:
      • Colon cancer: surgery (partial colectomy, with or without lymph node excision) is the standard of care, followed by adjuvant chemotherapy according to the patient’s overall risk profile8
      • Rectal cancer: a curative treatment approach is possible based on surgery, often with chemoradiation10
    • Metastatic disease: the heterogenous nature of CRC means that effective treatment remains a complex and individualised challenge. Numerous genes (tumour protein p53 [TP53]; KRAS and BRAF) and pathways (Wnt, RAS−MAPK, PI3K, TGF-β, p53 and DNA mismatch-repair) are implicated in disease initiation and progression.11,12 Targeted agents are indicated in the majority of patients; the choice of treatment pathway is informed by the molecular profile of the tumour, prior therapy, treatment tolerability and treatment goals7

Gastric cancer

The prevalence of gastric (or stomach) cancer varies significantly around the world.6,13 The highest rates are seen in Eastern Asia, Eastern Europe and South America, and the lowest in North America and Western Europe.13 Over the last 60 years, there has been a gradual decline in new cases across North America and Western Europe and, more recently, in higher-prevalence regions.13

Location of the stomach within the digestive system

Location of the stomach within the digestive system
  • Common symptoms include: weight loss, dysphagia, dyspepsia, vomiting, early satiety and/or iron deficiency anaemia13
  • Risk factors include:13
    • General: male gender (incidence is twice as high as in females), Helicobacter pylori infection, tobacco use, atrophic gastritis, partial gastrectomy and Ménétrier’s disease
    • Anatomical subsite-specific:
      • H. pylori and dietary factors are associated with antral or distal cancers
      • Obesity is associated with cancers of the cardia or proximal stomach
      • Reflux is associated with cancers occurring at the gastroesophageal junction
  • Staging:13
    • Initial staging and risk assessment should include physical examination, blood count and differential, liver and renal function tests, endoscopy, and contrast-enhanced CT scan of the thorax, abdomen and pelvis
    • Laparoscopy is recommended for patients with resectable disease
    • Multidisciplinary planning is strongly recommended before any treatment is administered
  • Management (first-line standard of care):13
    • For very early tumours: endoscopic resection is appropriate
    • For Stage IB–III gastric cancer: radical gastrectomy is indicated and perioperative therapy is recommended
    • For metastatic disease:
      • Doublet or triplet platinum/fluoropyrimidine combinations are recommended for fit patients with advanced gastric cancer
      • Trastuzumab is recommended, in conjunction with platinum- and fluoropyrimidine-based chemotherapy, for patients with HER2-positive advanced gastric cancer

Liver cancer

Liver cancer is the third most common GI cancer.6 There are two major subtypes: HCC and intrahepatic bile duct cancer. HCC is the more common of the two, with rates increasing globally for the last 20 years (and predicted to continue to increase until 2030).14

Location of the liver within the digestive system

Location of the liver within the digestive system

Common symptoms include: pain, fatigue, weight loss and obstructive syndromes, such as ascites and jaundice15

Risk factors include: chronic liver disease, liver cirrhosis, hepatitis infection14

Staging and management: several staging systems have been developed, including the Barcelona Clinic Liver Cancer (BCLC) system. BCLC staging links tumour stage, liver function, cancer-related symptoms and performance status (PS) to an evidence-based treatment algorithm:14

  • BCLC A: patients with early HCC who may benefit from ablative treatment
  • BCLC B: patients with intermediate disease, for whom transarterial chemoembolisation (TACE) may be indicated
  • BCLC C: patients with advanced disease, for whom the kinase inhibitor sorafenib may be suitable
  • BCLC D: for patients with end-stage disease, best supportive care (BSC) is recommended (end-stage liver function; ECOG PS 3 or 4)

Oesophageal cancer

There are two main subtypes of oesophageal cancer – squamous cell carcinoma (SCC) and adenocarcinoma. SCC occurs more frequently in the upper and middle parts of the oesophageal tract, while adenocarcinoma usually occurs in the lower part of the oesophagus, near the junction with the stomach.16

Although SCC accounts for approximately 90% of cases of oesophageal cancer, adenocarcinoma is associated with a higher mortality rate. Indeed, adenocarcinoma mortality rates have now surpassed those of SCC in some countries.16,17

Location of the oesophagus within the digestive system

Location of the oesophagus within the digestive system
  • Common symptoms include: difficult or painful swallowing, progressive weight loss, nausea, vomiting, loss of appetite, chest pain and hoarseness16
  • Risk factors include:17
    • Smoking and alcohol consumption for SCC
    • Chronic gastro-oesophageal reflux and obesity for adenocarcinoma
  • Staging should include:17
    • A complete clinical examination and a CT scan of the neck, chest and abdomen. In candidates for surgical resection, endoscopic ultrasonography should be carried out to evaluate T and N tumour categories; in candidates for oesophagectomy, 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) should be performed
    • Multidisciplinary planning is strongly recommended before any treatment is administered
  • Management (first-line standard of care):17
    • Early-stage disease:
      • Surgery is the treatment of choice in limited disease, with disease histology and stage guiding the choice of technique: endoscopic submucosal dissection, radical and transthoracic oesophagectomy, endoscopic therapy, endoscopic resection or endoscopic en bloc resection
      • For patients unable or unwilling to undergo surgery, combined chemoradiotherapy is superior to radiotherapy alone
      • Metastatic disease:
    • Management focuses on palliative treatment, with options (e.g. brachytherapy, chemotherapy, BSC) governed by clinical situation

Uncommon tumours at a glance

GI NETs

GI NETS account for a very small proportion of newly diagnosed malignancies (approximately 0.5%), but 62–67% of NETs occur in the GI tract.18

GI NETs can arise from the pancreas or neuroendocrine cells distributed throughout the mucosa and submucosa of the GI tract. GI NETs comprise a heterogeneous group of tumours that can present with a variety of clinical symptoms.19 The risk factors are not well characterised, but multiple endocrine neoplasia type 1 syndrome is implicated, and genetic and familial associations have been observed.18

Neuroendocrine neoplasms are broadly divided into two groups on the basis of clinical behaviour, histology and proliferation rate:18

  • Well-differentiated (low to intermediate grade) NETs
  • Poorly differentiated (high grade) neuroendocrine carcinoma

Treatment and prognosis depends on the grade of differentiation and the stage of the tumour at the time of presentation;19 12–22% are metastatic at time of presentation.18  Treatment typically includes surgical resection in low-grade tumours and somatostatin analogues and/or interferon-α in patients with unresectable, symptomatic disease.18

GISTs

GISTs account for approximately 1% of all GI tumours, but they are the most common mesenchymal tumours of the GI tract.5 They are thought to grow from specialised interstitial cells of Cajal (ICCs) that function as pacemaker-like intermediates between the GI autonomic nervous system and smooth muscle cells, regulating GI motility and autonomic nerve function.5,20

GISTs may be either malignant or benign and can occur anywhere in or near the GI tract; they appear most often in the stomach (60%) or small intestine (30%). They are typically diagnosed in adults aged 40–70 years.5,20

Some people with GISTs may experience pain or swelling in the abdomen, nausea, vomiting, loss of appetite or weight loss. Anaemia, black and tarry stools and vomiting of blood can also occur in cases where GISTs cause GI bleeding.20 A family history of GISTs is generally associated with more symptomatic disease and multiple (rather than single, ‘sporadic’) tumours.

The formation of GISTs is most commonly associated with mutations in the tyrosine-protein kinase KIT gene (approximately 80% of cases) and the platelet-derived growth factor receptor alpha gene (PDFGRA; approximately 10% of cases).20

Treatment may involve surgery and/or use of tyrosine kinase inhibitors (TKIs), depending on the extent of disease and TKI sensitivity.5

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References

1

Ferlay J, et al. Int J Cancer 2015;136(5):E359–86.

2

Pourhoseingholi MA, et al. Gastro Hepat Bed to Bench 2015;8(1):19.

3

GI Cancer Alliance. GI Cancers. http://www.gicancersalliance.org/gi-cancers (Accessed: September 2019).

4

Hirabayashi K, et al. Front Oncol 2013;3:2.

5

National Cancer Institute. Gastrointestinal Stromal Tumors Treatment (PDQ®)–Health Professional Version. https://www.cancer.gov/types/soft-tissue-sarcoma/hp/gist-treatment-pdq (Accessed: September 2019).

6

International Agency for Research on Cancer (IARC). https://gco.iarc.fr/today/home (Accessed: September 2019).

7

Van Cutsem E, et al. Ann Oncol 2016;27:1386–422.

8

Labianca R, et al. Ann Oncol 2013;24(Suppl. 6):vi64–vi72.

9

Johnson CM, et al. Cancer Causes Control 2013;24(6):1207–22.

10

Glynne-Jones R, et al. Ann Oncol 2017;28(Suppl. 4):iv22–iv40.

11

Fearon ER. Annu Rev Pathol Mech Dis 2011;6:479–507.

12

Zarkavelis G, et al. Ann Gastroenterol 2017;30(6):613.

13

Smyth EC, et al. Ann Oncol 2016;27(Suppl. 5):v38–49.

14

Vogel A, et al. Ann Onol 2018;29(Suppl. 4): iv238–iv255.

15

Sun VC, Sarna L. Clin J Oncol Nurs 2008;12(5):759–66.

16

Harris C, et al. Ann Cardiothorac Surg 2017;6(2):190.

17

Lordick F, et al. Ann Oncol 2016;27(suppl_5):v50–7.

18

Oronsky B, et al. Neoplasia 2017;19:991–1002.

19

Yang Z, et al. Cell Physiol Biochem 2018;45:389–96.

20

U.S. National Library of Medicine. Genetics Home Reference: Gastrointestinal stromal tumor. https://ghr.nlm.nih.gov/condition/gastrointestinal-stromal-tumor#resources (Accessed: September 2019).

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Page last updated: September 2019