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Neuroendocrine tumours (NETs) are a complex figure within the realm of oncology, characterised by their diversity, mystery, and impact on patients. Nevertheless, medical specialists are working all over the world to better understand how NETs work.
A crucial aspect of understanding and managing NETs is the classification into functioning and non-functioning tumour types. Each classification poses distinct challenges and requires tailored approaches to diagnosis and treatment.
For more information and support, get in touch with NeuroEndocrine Cancer Australia’s NET cancer nurse line.
Classifying NETs as functional or non-functional can have a significant impact on a patient’s outlook and future treatment. Classification can usually be made by examining a range of clinical symptoms.
Functional NETs are characterised by their ability to produce hormones. This unique feature sets them apart from their non-functional counterparts. The hormones produced by functional NETs can lead to a variety of symptoms, often dependent on the type of hormone overproduced. For instance, serotonin-producing NETs may contribute to carcinoid syndrome, marked by facial flushing, diarrhoea, and wheezing.
Non-functional NETs do not produce excessive hormones that result in recognisable symptoms. Instead, their impact is often related to the size and location of the tumour. These tumours can grow without causing the classic hormonal imbalances seen in functional NETs, making them challenging to detect in the early stages.
The symptoms of functioning NETs are primarily attributed to the overproduction of hormones. Common symptoms include:
Carcinoid syndrome, a hallmark of some functioning NETs, can lead to a distinctive set of symptoms, including flushing, diarrhoea, and wheezing.
In contrast, non-functioning NETs may present with more subtle symptoms related to the physical presence of the tumour. Depending on the size and location of the tumour, patients may experience symptoms such as:
The challenge with non-functioning NETs lies in their ability to remain asymptomatic until they reach a more advanced stage. Early intervention and diagnosis are critical steps in creating the best outlook for these patients.
The diagnostic journey for NETs is intricate and can diverge significantly based on whether the tumour is functioning or non-functioning. The nature of symptoms often dictates the initial investigative steps undertaken by healthcare professionals.
Given the symptomatic nature of functioning NETs, the diagnostic process often begins with a focus on identifying the specific hormonal imbalances.
Specialised tests to measure hormone levels, such as serotonin and 5-HIAA for carcinoid syndrome, may be conducted.
Imaging techniques, such as Somatostatin Receptor Imaging (SRI) or gallium-68 DOTATATE PET/CT, can pinpoint the location and extent of functioning NETs.
The diagnosis of non-functioning NETs may follow a different trajectory, often initiated by symptoms related to the physical presence of the tumour.
Diagnostic imaging, including computed tomography (CT) scans and ultrasound, plays a pivotal role in visualising the tumour and determining its size and location.
Biomarkers like Chromogranin A may also be assessed, although their specificity to non-functioning NETs generally is limited.
There are a range of common diagnostic tests that your healthcare team can undertake to assess whether your tumour is functioning or non-functioning. Using additional confirmation is helpful to ensure that symptoms aren’t the only marker. Refer to Neuroendocrine Cancer Optimal Care Pathway – Quick Reference Guide for tests to perform.
CT scans are valuable tools in diagnosing both functioning and non-functioning NETs. They provide detailed images of the small intestine, aiding in the identification of tumours and assessment of the extent of the disease. For non-functioning NETs, CT scans can aid in visualising the physical characteristics of the tumour.
Ultrasound is employed to visualise structures within the affected organs through sound waves. It provides valuable information for diagnosing and directing treatment for both functioning and nonfunctioning NETs. Ultrasound is particularly effective in assessing the size and location of tumours.
Endoscopic procedures, including upper endoscopy or capsule endoscopy, offer a direct visual examination of the small intestine. This is especially relevant for functioning NETs where the focus is on identifying hormone-producing tumours. Capsule endoscopy provides a non-invasive way to examine the entire small bowel.
SRI, such as gallium-68 DOTATATE PET/CT, is a specialised imaging technique targeting somatostatin receptors on NET cells. It is particularly useful in identifying functioning NETs, where the overproduction of hormones is a key diagnostic criterion.
Chromogranin A (CgA) levels in the blood can be indicative of both functioning and non-functioning NETs, though it might lack specificity. For functioning NETs, measuring serotonin and 5-HIAA levels aids in the diagnosis of conditions like carcinoid syndrome.
Genetic testing can potentially identify mutations or abnormalities in specific genes associated with NETs. This information can provide insights into treatment options and prognoses for both functioning and non-functioning NETs.
A tissue biopsy, obtained during endoscopy or surgery, remains a crucial step in confirming the presence of NETs and determining their specific type and grade. Biopsies contribute to the overall diagnostic picture for both functioning and non-functioning NETs.
In cases where functioning NETs are localised, surgery often stands as the primary treatment modality. The goal is to remove the tumour and surrounding tissue, addressing the source of hormone overproduction. For example, in insulin-secreting tumours, partial pancreatectomy may be performed to remove the tumour while preserving pancreatic function.
Similarly, surgery is a cornerstone for localised non-functioning NETs. The focus is on removing the tumour, and alleviating symptoms related to its physical presence. The extent of surgery depends on factors such as tumour size, location, and involvement of nearby structures.
No treatment, active surveillance or watchful waiting, may be suitable for some NET patients especially if the NET is not causing symptoms or problems, there is little disease, the disease is stable, or the tumour is low grade (G1). In some circumstances, poor general health or complications secondary to treatments may also make further NET treatment inadvisable.
PRRT is a specialised treatment that leverages a radioactive substance attached to a somatostatin analogue. It is particularly effective for NETs that express somatostatin receptors, both functioning and non-functioning. By delivering radiation directly to NET cells while sparing healthy tissue, PRRT has shown promise in managing advanced cases and improving quality of life.
Somatostatin analogues, such as octreotide and lanreotide, play a crucial role in managing functioning NETs. By controlling hormone production, these drugs alleviate symptoms like diarrhoea and flushing associated with hormone overproduction.
While the primary focus is on symptom control for functioning NETs, SSAs may still be considered for non-functioning NETs if there is evidence of somatostatin receptor expression. However, their role in this context is not as central as in functioning cases.
In cases of poorly differentiated NETs, chemotherapy may be necessary. Chemotherapy drugs target rapidly dividing cells, aiming to slow down or stop the cancer’s progression. This approach is more common for aggressive, fast-growing tumours, regardless of their functional status.
Targeted therapies, such as sunitinib and everolimus, have shown efficacy in managing advanced NETs. They work by inhibiting specific pathways involved in NET cell growth. The choice of targeted therapy may vary based on the tumour’s characteristics, including its grade and stage, rather than its functional status.
If the tumour has metastasised to the liver, various liver-directed therapies may be considered. Transarterial chemoembolisation (TACE), hepatic artery embolisation (HAE), or selective internal radiation therapy (SIRT) can target liver metastases, improving outcomes for both functioning and non-functioning NETs.
Radiotherapy may be considered for NETs for symptom relief. It involves using targeted radiation to destroy or damage cancer cells. The role of radiotherapy for NETs is more frequently used when there are bone metastases.
Participation in clinical trials is an option for patients with both functioning and non-functioning NETs. These trials explore novel treatments, contributing to the ongoing evolution of NET management. Enrolling in a clinical trial provides access to cutting-edge therapies that may not be available through standard treatments.
Patients with functioning NETs may experience relief from symptoms such as diarrhoea, flushing, and abdominal pain through targeted interventions. The goal is not only to manage symptoms but also to control hormone production and potentially shrink the tumour.
For non-functioning NETs, the emphasis is often on alleviating symptoms related to the physical presence of the tumour, such as abdominal pain or bowel obstruction. Treatment aims to enhance quality of life by controlling the growth and spread of the tumour.
Managing daily life with functioning NETs involves a multifaceted approach. Patients may need to adapt to the management of hormone-related symptoms, such as dietary adjustments for diarrhoea or medications for flushing. Regular follow-ups are essential to monitor treatment efficacy and adjust interventions as needed.
Patients with non-functioning NETs may focus on managing symptoms related to the physical impact of the tumour. Nutritional support, pain management, and close monitoring of tumour growth become integral components of daily life. Regular communication with healthcare providers ensures timely adjustments to the treatment plan.
The journey with NETs is not a solitary one. Support groups offer a platform for individuals with both functioning and non-functioning NETs to share experiences, seek advice, and find solidarity in facing the unique challenges posed by these tumours.
Neuroendocrine Cancer Australia offers comprehensive resources to provide information and support for individuals affected by NETs. Our specialised NET cancer nurse line is available to talk to you about your condition, what to expect and support services available.
Australian Cancer Councils are national and state-based cancer non-profits that have a plethora of information related to living with cancer, practical and financial support.
The treatment landscape for NETs is diverse and dynamic. Tailoring interventions to the specific characteristics of functioning and nonfunctioning NETs can deliver optimal outcomes and enhance the quality of life for individuals navigating this complex journey.
Regular communication with healthcare providers, participation in support networks, and staying informed about available resources contribute to a holistic approach in managing the challenges posed by functional and nonfunctional NETs.
