Article

Role of PET Imaging and Nuclear Medicine in Treating Neuroendocrine Gastric Tumors

Objectives of medical imaging for cancer involve finding better ways to visualize tumors and using that information to determine the least invasive/most effective management tactics possible. Use of nuclear medicine in the treatment of neuroendocrine gastric tumors is playing an increasing role in that strategy.

Rare type of tumor with devastating consequences

Neuroendocrine cells respond to signals from the nervous system (hence the "neuro") by releasing hormones (where the "endocrine" part comes into play) into the blood. A NET or neuroendocrine tumor arises from an abnormality of these cells, and thus, the tumor itself can produce hormones. While a NET can develop in any area of the body, carcinoid NETS most often occur in the GI tract or lungs, and pancreatic NETS in the pancreas. There is great variation in this type of tumor. NETS may be benign or malignant (and capable of metastasizing); slow- or fast-growing. Symptoms vary depending on whether the tumor is functional (hormone-producing), or non-functional. Occurrence is not generally hereditary, but rather sporadic.1

Neuroendocrine cancer is rare, responsible for only about 0.5% of all cancers, with incidence peaking between the ages of 50 and 70. Most are diagnosed at an advanced stage.2

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Among NETS, occurrence3 is as follows:

  • 30% in the bronchial system (lungs)
  • 20% large intestine
  • 19% small intestine
  • 7% pancreas
  • 4% appendix

The primary site cannot be identified in about 15% of cases.3

While NETs were historically considered to be extremely rare, there has been an increase in incidence. According to Melissa Burkett, Global PET Applications Leader at GE Healthcare, “It is primarily believed to be due to improved methods of diagnosis and a greater awareness for people to go to the doctor earlier.”4

Burkett went on to say, "You wouldn't necessarily think of ‘neuro' as being in your belly. But someone could for a year be having indigestion that doesn't seem to go away. They go for endoscopy. Doctors perform a biopsy, and it comes back as a neuroendocrine tumor."4

While survival depends on many factors, including location and stage, a diagnosis of NET is grave. The Canadian Cancer Society cites 5-year observed survival rates as low as 14% (colon) to 25% for stomach and 27% for pancreas at the third or distant stage.5 

Conventional treatment path

Using pancreatic cancer as an example, a NET interferes with cells that make insulin. In the past, this patient was likely diagnosed with Type 2 diabetes, yet did not respond favorably to traditional insulin-controlling treatment. Not every patient is conscientious about diet and lifestyle changes, nor takes medication as prescribed. Recognizing that this is human nature, the physician may have attributed blood sugar level fluctuations to non-compliance, and thus continued conventional diabetes treatment. Misdiagnosis may have persisted for some time before an accurate diagnosis of pancreatic cancer was reached.

By this time, the condition might have reached stage four. At this point, the physician knew if it wasn’t aggressively treated the first time, there probably would not be a second chance to catch it before it spread throughout the body. That meant removing the entire host organ (where possible) as well as structures around it to improve the survival rate and reduce the risk of recurrence, followed up with radiation therapy and chemotherapy.  

Targeted treatment

Today, earlier confirmation of the disease and location of NETs can be accomplished by adding PET (positron emission tomography) imaging to conventional endoscopy and biopsy.4 In the preceding example, for instance, this is leading to protocols such as immediate testing for pancreatic cancer when a patient is newly diagnosed with uncontrolled diabetes.

Treatment may follow these general steps:

  • Diagnosis begins with endoscopy and CT (computed tomography) or MRI (magnetic resonance imaging).
  • Cyclotron production of necessary radiopharmaceuticals.
  • A PET scan with an injected radioactive tracer – 68 GA-Dotatoc or indium-111 – shows uptake into various tissues. The radioactive sugar binds to somatostatin receptors, which are denser in cancerous cells than healthy ones. This activity is clearly visible in the PET scan, lighting up NETs (with allowance for known uptake in organs such as the pituitary gland).4
  • Then, treatment consists of Lu 177 dotatate, a somatostatin analog which delivers radiation directly to tumors. The course of treatment is generally four 8-hour infusion sessions (hydration then slow titration) spaced about six weeks apart.4 

Benefits of the PET imaging/nuclear medicine approach 

  • A precision PET/CT scanner can detect a small tumor (5 to 7mm) in a patient up to 500 pounds.4
  • Reduced need for resection. Rather than a “when in doubt, take it all out” methodology, more unaffected tissue can be spared. In addition, the scan indicates advanced staging and metastasizing. Surgical removal of organs can then be avoided, as it would be of no benefit.
  • Treatment is customized. The specificity of radiopharmaceuticals targets the NET with minimal radioactive uptake in healthy tissues.
  • With the infusion method, kidneys are hydrated in advance of treatment, so tracers are flushed promptly. This reduces unpleasant chemo-type side effects.

More to come

The use of nuclear medicine in diagnosis and in treatment holds great promise for improved patient outcomes. Burkett4 indicated that this treatment concept has been used for decades for thyroid cancer. Initial research for neuroendocrine tumors was conducted in Europe for years before the technique came to the United States (Lu 177 dotatate therapy was approved by the FDA in January 20186). 

She said that similar treatment for prostate cancer has received FDA approval. It brings new hope for patients who have had a recurrence after a traditional course of chemo and radiation. Research is also underway for specific radiopharmaceuticals to target other types of pancreatic tumors and breast cancers.4

References:

  1. Neuroendocrine tumor. National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/13445/neuroendocrine-tumor August 27, 2019.
  2. Epidemiology of Neuroendocrine Tumors. Springer, Berlin, Heidelberg. https://link.springer.com/chapter/10.1007/978-3-662-45215-8_3#citeas August 27, 2019.
  3. Neuroendocrine Tumors: Introduction. Cancer.Net. https://www.cancer.net/cancer-types/neuroendocrine-tumors/introduction August 27, 2019.
  4. Interview with Melissa Burkett, Global PET Applications Leader. GE Healthcare. August 27, 2019.
  5. Neuroendocrine tumors. Canadian Cancer Society. https://www.cancer.ca/en/cancer-information/cancer-type/neuroendocrine/prognosis-and-survival/survival-statistics/?region=on August 27, 2019.
  6. FDA approves lutetium Lu 177 dotatate for treatment of GEP-NETS. U. S. Food and Drug Administration. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-dotatate-treatment-gep-nets August 27, 2019.