Neuroendocrine Tumors: Causes, Diagnosis, and Treatment

Neuroendocrine tumors (NETs) are rare, complex cancers that start in neuroendocrine cells. These are cells that can secrete hormones into the bloodstream because they have characteristics of both nerve cells and endocrine system cells that secrete hormones. Although they can occur anywhere in the body, these tumors are most commonly discovered in the lungs, the pancreas, the gastrointestinal tract, and occasionally even the thyroid, adrenal glands, or the ovaries.

Types of Neuroendocrine Tumors

NETs are divided on the basis of their site of origin and their functionality:

• Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)These arise in the pancreas or gastrointestinal tract and are further divided into two types:
  • Pancreatic NETs (pNETs): These occur in the pancreas and may produce hormones like insulin or gastrin.
  • Carcinoid tumors: Often located in the small intestine, stomach, and lungs, carcinoid tumors may secrete serotonin and cause a distinct set of symptoms known as carcinoid syndrome.
• Pulmonary NETs
  • These develop in the lungs and may cause symptoms such as coughing, wheezing, or pneumonia-like symptom.

• Other NETs
  • NETs can also develop in other rare locations, including the adrenal glands, thyroid, and more.

Symptoms of Neuroendocrine Cancer

The symptoms of neuroendocrine tumors vary on the site of the tumor, function of the tumor (hormone producing), and stage of the disease.

General Symptoms:

• Pain: Abdominal pain or chest pain occur due to the tumor pressing against other organs.
• Unexplained weight loss: Sudden and unexpected weight loss can be a sign of advanced NETs.
• Fatigue: General tiredness, weakness, or lethargy.

Functioning NET Symptoms:

NETs that produce hormones may often cause hormone-related syndromes:

• Carcinoid Syndrome

  • Caused by the overproduction of serotonin, symptoms include flushing of the skin, diarrhoea, abdominal cramps, wheezing, and heart palpitations.

• Hypoglycemia

  • If a pancreatic NET produces insulin, it may cause low blood sugar symptoms such as dizziness, sweating, and confusion.

Diagnosis of Neuroendocrine Cancer

NETs are hard to diagnose, as symptoms can mimic other common conditions. Diagnosis usually involves various methods such as:

• Blood and Urine Tests

  • Markers like Chromogranin A, 5-HIAA (a serotonin metabolite), and others can indicate the presence of a NET.

• Imaging Tests

  • CT scans or MRI: These imaging techniques help visualise the tumor and determine its size, location, and whether it has spread.

  • PET scans: PET scans using Gallium-68 or DOTATATE can provide detailed images of NETs.

• Biopsy: A sample from the tumor is extracted and examined under a microscope to confirm the diagnosis and determine the grade of the tumor.

Staging and Grading Neuroendocrine Tumors

The appropriate stage and grade of NETs must be identified with the help of specific tests to tailor the most suitable treatment plan for the patient.

• Staging: Stages are based on the tumor size, spread to lymph nodes, and metastasis to other organs (Stage I to IV).
• Grading: 
  • Low-grade (Grade 1) Slow-growing and less aggressive.
  • Intermediate-grade (Grade 2) Moderately growing with potential for more aggressive behaviour.
  • High-grade (Grade 3) Rapidly growing and more likely to spread.

Treatment Options for Neuroendocrine Tumors

Treatment for neuroendocrine cancer varies depending on the tumor's location, grade, stage, and whether it’s producing hormones.

Surgical Approaches:

Surgical Resection: If the tumor is localised and is not spreading, then surgery is the first option to remove the tumor.Liver-directed Therapies: If NETs have spread to the liver, surgical removal or procedures like radiofrequency ablation, embolization, or liver transplantation might be considered for the treatment.

Medications:

• Somatostatin Analogues (SSAs): Drugs like octreotide and lanreotide can control hormone related symptoms by inhibiting hormone production in functioning NETs.
• Targeted Therapies
  • Peptide Receptor Radionuclide Therapy (PRRT): PRRT uses a radioactive substance attached to a hormone-like drug that specifically targets NET cells.
  • Everolimus and Sunitinib: These targeted therapies block pathways that are involved in spreading and growing tumors.

Chemotherapy and Radiation:

Chemotherapy or radiation therapy may be used to limit the growth of high grade or advanced NETs. However, traditional chemotherapy often has little impact on slow-growing NETs.

Living with Neuroendocrine Cancer

Living with NETs involves managing both the disease and its symptoms, which can differ between patients.

• Symptom Management: Patients with carcinoid syndrome may need medications to control flushing, diarrhoea, and other symptoms.
• Mental and Emotional Well-being: A diagnosis of neuroendocrine cancer can be overwhelming. Seeking support from mental health professionals or cancer support groups can be beneficial.
• Diet and Lifestyle: Some patients get benefits from just adjusting their diets, especially those with carcinoid syndrome.

Research and Future Therapies

Neuroendocrine cancer research is evolving with new treatments and procedures for the treatment of the NETs:

• Immunotherapy: In its early stages, immunotherapy shows potential in treating certain types of NETs by harnessing the immune system to fight cancer cells.
• Clinical Trials: Clinical trials provide access to new drugs that are not yet generally accessible, and patients may profit from taking part.

Conclusion

Neuroendocrine cancer presents unique challenges due to its diverse appearance. It is impossible to overstate the importance of early identification and tailored treatment for this illness. PRRT, tailored treatment, and immunotherapy are examples of research advancements that enable effective disease management. In addition, managing emotions and changes in life is a vital component of living with NETs. Patients with neuroendocrine cancer can live happy lives if they receive the right kind of treatment and have a strong support system.