Very good effect of rescue treatment with ¹⁷⁷Lu-DOTATATE in the patient with advanced metastatic atypical lung carcinoid

The incidence of typical and atypical pulmonary carcinoids (ACs) accounts for approximately 2% of all lung cancers, with ACs being much rarer [1]. In Poland, patients with advanced disease whose tumors express somatostatin receptors may be eligible for salvage therapy with lutetium 177 (¹⁷⁷Lu)-DOTATATE known as peptide receptor radionuclide therapy (PRRT) after all other therapeutic options have been exhausted. It is necessary to assess the expression of somatostatin receptors in neuroendocrine tumors before initiating targeted radionuclide therapy. For this purpose, patients undergo receptor scintigraphy with a gallium 68 (⁶⁸Ga)-DOTATATE positron emission tomography/computed tomography (PET/CT) or single-photon emission computed tomography (SPECT)/CT using technetium 99m (^99mTc)-tectrotide.

PRRT involves the intravenous administration of “hot” somatostatin analogs labeled with radioisotopes such as yttrium 90 [⁹⁰Y] or ¹⁷⁷Lu [2, 3]. The use of ¹⁷⁷Lu-DOTATATE in PRRT is associated with prolonged survival and the lowest incidence of adverse events [4]. The most commonly reported temporary adverse events include fatigue, nausea, vomiting, decreased appetite and signs of transient hematological toxicity [5].

A 72-year-old female patient with a history of neuroendocrine cancer since 2010, initially was treated surgically with a radical lobectomy of the right lower lobe and mediastinal lymphadenectomy.

Subsequently, due to liver metastasis, a hemihepatectomy was performed. The following year, due to recurrence in the right lung hilum and pleural metastasis, a complete right pneumonectomy was performed, followed by adjuvant chemotherapy.

In 2019, CT and 18F-fludeoxyglucose (¹⁸F-FDG) PET revealed new lesions in the postpneumectomy space (PPS) and liver, leading to treatment with the mTOR inhibitor everolimus, during which she developed pneumonia with acute respiratory failure, requiring hospitalization in the Intensive Care Unit, leading to the discontinuation of therapy. A Ga-68 DOTATATE PET/CT at the end of 2020 showed liver and mediastinal lesions with somatostatin receptor overexpression, indicating disease progression. The patient received chemotherapy with the capecitabine and temozolomide (CAPTEM) regimen, achieving disease stabilization for approximately two years. However, a ⁶⁸Ga-DOTATATE PET/CT in early 2023 showed tumor progression, and she was qualified for PRRT with ¹⁷⁷Lu-DOTATATE under emergency access, due to limited effectiveness of prior therapies. This type of therapy is not routinely used in patients with pulmonary ACs and is considered salvage therapy. Prior to initiating therapy, receptor scintigraphy with ^99mTc-tectrotide was performed in the patient to evaluate somatostatin receptor expression (Fig 1). Confirmation of receptor expression allows the patient to be qualified for the treatment.

Figure 1.

A1, A2. Receptor scintigraphy using technetium 99m (^99mTc)-tectrotide showing a lesion in the right postpneumectomy space (PPS). A1. Hybrid single-photon emission computed tomography/computed tomography (SPECT/CT) image axial view; A2. Metabolic SPECT axial view. B1, B2. Receptor scintigraphy using ⁹⁹mTc-tectrotide showing a lesion in the liver. B1. Hybrid SPECT/CT image axial view; B2. Metabolic SPECT axial view

The treatment involved four cycles — intravenous infusions of ¹⁷⁷Lu-DOTATATE, each with ~7.6 GBq activity, at 6–8 week intervals, alongside 2000 mL of Nephrotec for kidney protection. The patient experienced nausea and vomiting during infusions but remained stable overall, with persistent weakness between doses. After each infusion, whole-body scans (Fig. 2) and chest/abdomen SPECT/CT were performed, showing pathological lesions in the liver and the right PPS. The standardized uptake value (SUV) calculated for the pathological lesions after each cycle showed the lowest values at the end compared to the baseline scans, suggesting a good metabolic response.

Figure 2.

A, B. Whole-body scan after lutetium 177 (¹⁷⁷Lu) DOTATATE administration. A. Anteroposterior (AP); B. Posteroanterior (PA) performed on the 8^th day after the first cycle of peptide receptor radionuclide therapy (PRRT); CD. Whole-body scan after ¹⁷⁷Lu-administration: C — AP, D — PA performed on the 8^th day after the fourth cycle of PRRT. Arrows indicate the lesion in the apex of the right postpneumectomy space (PPS) (yellow) and the liver lesions (green and red)

A PET/CT with Ga-68 DOTATATE performed 7 months later showed no new lesions and partial regression of existing ones, with subsequent CT scans confirming disease regression and stabilization. The patient’s clinical condition significantly improved after the PRRT. Up until writing this article (February 2025) the patient had felt very well, reported a significant improvement in quality of life, and been satisfied with the treatment outcomes.

Conclusions

Aggressive neuroendocrine tumors of the lung, including atypical carcinoids, are characterized by a high metastatic rate and bad prognosis. The available medical literature reports good outcomes of therapy with ¹⁷⁷Lu-DOTATATE with few side effects [4, 6].

However, the number of patients with lung localization included in these studies is limited [7, 8]. The described case is an example of a successful use of radionuclide treatment in a patient with advanced AC.