Peptide-Targeted Radiation Therapy Achieved Partial Response in Rare Neuroendocrine Tumor That First Appeared as a Thyroid Nodule | Research

The takeaway

A 41-year-old woman with metastatic neuroendocrine tumor initially misdiagnosed as thyroid cancer achieved a partial response to 177Lu-DOTATATE peptide receptor radionuclide therapy with no side effects.

Partial response, zero side effects
4 cycles of 177Lu-DOTATATE over 8 months produced a partial response with no reported toxicity in a patient with widespread metastatic disease

What the researchers found

A 41-year-old female underwent thyroidectomy for suspected medullary thyroid cancer, but pathology revealed a neuroendocrine tumor (NET) of unknown primary origin metastatic to the thyroid.

68Ga-DOTATATE PET/CT identified somatostatin receptor-expressing lesions in: liver, right cervical nodes, thoracic paravertebral soft tissue, precoccygeal soft tissue, and right acetabulum (bone).

Disease progressed on octreotide injections. The patient received 4 cycles of 177Lu-DOTATATE (Lutathera) PRRT over 8 months with:

- No side effects or toxicities reported

- Partial treatment response on early post-treatment scan at 6 weeks

Key diagnostic lesson: somatostatin receptor PET imaging both identifies the full extent of neuroendocrine disease and predicts response to PRRT, regardless of the organ of origin.

Why it matters

This case illustrates two important concepts: first, that neuroendocrine tumors can mimic other cancers (initially thought to be thyroid cancer), making correct diagnosis critical for proper treatment. Second, that peptide-based imaging (68Ga-DOTATATE PET) and therapy (177Lu-DOTATATE PRRT) form a powerful 'theranostic' pair — the same peptide used for diagnosis also delivers therapy. If a tumor lights up on the diagnostic scan, it's likely to respond to the therapeutic version.

How the study worked

This is a single-patient case report documenting the clinical course of a 41-year-old female with metastatic NET of unknown primary. Diagnosis involved thyroid biopsy, thyroidectomy, and 68Ga-DOTATATE PET/CT imaging. Treatment included octreotide injections (which failed) followed by 4 cycles of 177Lu-DOTATATE PRRT. Response was assessed by post-treatment imaging at 6 weeks.

What this study cannot tell us

This is a single case report — the lowest level of clinical evidence. The partial response at 6 weeks is early and long-term outcomes are unknown. NETs of unknown primary are heterogeneous, and this patient's response may not generalize. The claim of 'no side effects' over 8 months, while encouraging, differs from larger clinical trials showing that PRRT commonly causes some hematologic toxicity. No comparison to other treatment options was possible.

How to read the evidence

Single case report providing the lowest level of clinical evidence. While the diagnostic and therapeutic outcomes are favorable, no generalizable conclusions can be drawn. The case is most valuable as a teaching example of theranostic peptide medicine and the importance of accurate NET diagnosis.

When this study was published

Published in 2023, this case reflects the current standard of care for somatostatin receptor-positive neuroendocrine tumors, where 177Lu-DOTATATE PRRT has been FDA-approved since 2018.

The bigger picture

The theranostic approach — using the same molecule for both diagnosis and therapy — is one of the most exciting developments in nuclear medicine. DOTATATE-based theranostics (68Ga for imaging, 177Lu for therapy) have transformed neuroendocrine tumor management. This case extends the paradigm by showing that even when the primary tumor site is unknown, somatostatin receptor expression on PET imaging can guide treatment decisions and predict therapy response. Similar theranostic pairs are being developed for prostate cancer (PSMA-targeted) and other malignancies.

Questions still open

Will this patient's partial response deepen into a complete response, or is additional treatment needed?
Could earlier initiation of PRRT (before octreotide failure) have produced better outcomes in this case?
How often do neuroendocrine tumors first present as thyroid metastases, and how many are initially misdiagnosed?

Common questions

What is the theranostic approach used in this case?

Theranostics means using the same molecular target for both diagnosis and therapy. In this case, the DOTATATE peptide binds to somatostatin receptors on tumor cells. For diagnosis, it's labeled with gallium-68 (68Ga) for PET imaging — lighting up tumors wherever they are. For therapy, the same peptide is labeled with lutetium-177 (177Lu), which emits radiation that kills the tumor cells it binds to. If tumors show up brightly on the diagnostic scan, they're good candidates for the therapeutic version.

Why was this tumor initially thought to be thyroid cancer?

Neuroendocrine tumors metastasizing to the thyroid are extremely rare, so when a patient has growing thyroid nodules, doctors naturally suspect primary thyroid cancer first. The biopsy findings were suspicious for medullary thyroid cancer, which is itself a neuroendocrine tumor. Only after surgery and full pathological analysis was it determined that this was actually a NET from somewhere else that had spread to the thyroid — a diagnosis that completely changed the treatment approach.

Read the original research

Neuroendocrine metastasis to the thyroid from unknown primary and extrathyroidal disease response to peptide receptor radionuclide therapy.

Radiology case reports, 18(11), 3945-3948

View on PubMed ↗Publisher’s paper ↗

Citation

Khessib, Tasnim; Khessib, Samy; Berry, Gerald; Aparici, Mari. (2023). Neuroendocrine metastasis to the thyroid from unknown primary and extrathyroidal disease response to peptide receptor radionuclide therapy.. Radiology case reports, 18(11), 3945-3948. https://doi.org/10.1016/j.radcr.2023.07.044