Value of [68Ga]Ga-somatostatin receptor PET/CT in the grading of pulmonary neuroendocrine (carcinoid) tumours and the detection of disseminated disease: single-centre pathology-based analysis and review of the literature

Abstract

Background: Although most guidelines suggest performing a positron emission tomography/computed tomography (PET/CT) with somatostatin receptor (SSTR) ligands for staging of pulmonary carcinoid tumours (PC), only a limited number of studies have evaluated the role of this imaging tool in this specific patient population. The preoperative differentiation between typical carcinoid (TC) and atypical carcinoid (AC) and the extent of dissemination (N/M status) are crucial factors for treatment allocation and prognosis of these patients. Therefore, we performed a pathology-based retrospective analysis of the value of SSTR PET/CT in tumour grading and detection of nodal and metastatic involvement of PC and compared this with the previous literature and with [¹⁸F]FDG PET/CT in a subgroup of patients.

Methods: SSTR PET/CT scans performed between January 2007 and May 2020 in the context of PC were included. If available, [¹⁸F]FDG PET/CT images were also evaluated. The maximum standardized uptake (SUV_max) values of the primary tumour, of the pathologically examined hilar and mediastinal lymph node stations, as well as of the distant metastases, were recorded. Tumoural SUV_max values were related to the tumour type (TC versus AC) for both SSTR and [¹⁸F]FDG PET/CT in diagnosing and differentiating both tumour types. Nodal SUV_max values were compared to the pathological status (N⁺ versus N^-) to evaluate the diagnostic accuracy of SSTR PET/CT in detecting lymph node involvement. Finally, a mixed model analysis of all pathologically proven distant metastatic lesions was performed.

Results: A total of 86 SSTR PET/CT scans performed in 86 patients with PC were retrospectively analysed. [¹⁸F]FDG PET/CT was available in 46 patients. Analysis of the SUV_max values in the primary tumour showed significantly higher SSTR uptake in TC compared with AC (median SUV_max 18.4 vs 3.8; p = 0.003) and significantly higher [¹⁸F]FDG uptake in AC compared to TC (median SUV_max 5.4 vs 3.5; p = 0.038). Receiver operating characteristic (ROC) curve analysis resulted in an area under the curve (AUC) of 0.78 for the detection of TC on SSTR PET/CT and of 0.73 for the detection of AC on [¹⁸F]FDG PET/CT. A total of 267 pathologically evaluated hilar and mediastinal lymph node stations were analysed. ROC analysis of paired SSTR/[¹⁸F]FDG SUV_max values for the detection of metastasis of TC in 83 lymph node stations revealed an AUC of 0.91 for SSTR PET/CT and of 0.74 for [¹⁸F]FDG PET/CT (difference 0.17; 95% confidence interval - 0.03 to 0.38; p = 0.10). In a sub-cohort of 10 patients with 12 distant lesions that were pathologically examined due to a suspicious aspect on SSTR PET/CT, a positive predictive value (PPV) of 100% was observed.

Conclusion: Our findings confirm the higher SSTR ligand uptake in TC compared to AC and vice versa for [¹⁸F]FDG uptake. More importantly, we found a good diagnostic performance of SSTR PET/CT for the detection of hilar and mediastinal lymph node metastases of TC. Finally, a PPV of 100% for SSTR PET/CT was found in a small sub-cohort of patients with pathologically investigated distant metastatic lesions. Taken together, SSTR PET/CT has a very high diagnostic value in the TNM assessment of pulmonary carcinoids, particularly in TC, which underscores its position in European guidelines.

Keywords: Atypical carcinoid; Bronchial carcinoid; Neuroendocrine tumour; PET; Pulmonary carcinoid; Somatostatin receptor; Typical carcinoid; [18F]FDG; [68Ga]Ga-DOTATATE; [68Ga]Ga-DOTATOC.

Fig. 1

Box plots of the distribution of SUV_max values in function of tracer and tumour type, yielding a median SUV_max on SSTR PET/CT of 18.4 and 3.8 for 52 typical bronchial carcinoid tumours and 12 atypical bronchial carcinoid tumours, respectively, and a median SUV_max on [¹⁸F]FDG PET/CT of 3.5 and 5.4 for 28 typical bronchial carcinoid tumours and 9 atypical bronchial carcinoid tumours, respectively

Fig. 2

Scatter plot of the paired SUV_max values on SSTR PET/CT and [¹⁸F]FDG PET/CT scans for typical (TC) and atypical (AC) bronchial carcinoid tumours (n = 36), with dashed reference lines on the cut-off SUV_max values (5.1 for SSTR PET/CT and 4.5 for [¹⁸F]FDG PET/CT) based on the maximal Youden’s index derived from the ROC curves of the non-paired SUV_max values on SSTR and [¹⁸F]FDG PET/CT scans for TC and AC, respectively (see Additional file figures)

Fig. 3

ROC curve analysis of paired SUV_max values of hilar/mediastinal lymph node stations of typical bronchial carcinoid tumours (TC) on SSTR PET/CT (blue curve) and [¹⁸F]FDG PET/CT (green curve), yielding an area under the curve (AUC) of 0.91 and 0.74, respectively. The difference between the AUC values for SSTR and [¹⁸F]FDG was 0.17 (p = 0.10)

Fig. 4

21-year-old patient with a typical bronchial carcinoid (TC) who underwent a [⁶⁸Ga]Ga-DOTATOC PET/CT scan showing two foci of intense tracer uptake on the MIP image (A) corresponding to the primary hilar tumour (red arrow, B) and to an infracarinal nodal metastasis (blue arrow, C), as well as an [¹⁸F]FDG PET/CT scan showing only a limited tracer uptake in the tumour (red arrow, visible on the MIP image (A) and an axial fusion image (E)) and no increased tracer uptake in the infracarinal nodal metastasis (blue arrow, F). The SUV_max values on [⁶⁸Ga]Ga-DOTATOC PET/CT were 110 and 9.2 in the tumour and in the infracarinal lymph node, respectively, whereas those on [¹⁸F]FDG PET/CT were 4.7 and 2.3 in the tumour and the infracarinal lymph node, respectively

Fig. 5

MIP image of an [¹⁸F]FDG PET/CT scan (A) and a [⁶⁸Ga]Ga-DOTATATE PET/CT scan (D) performed during staging of a typical bronchial carcinoid tumour (TC) of a 62-year-old patient with a clear discrepancy between an intense [⁶⁸Ga]Ga-DOTATATE uptake (E) and no increased [¹⁸F]FDG uptake (B) in the primary tumour (red arrow) as well as in a subcarinal lymph node metastasis (blue arrow). The axial fusion images with CT in bone window of the [¹⁸F]FDG PET/CT (C) and the [⁶⁸Ga]Ga-DOTATATE PET/CT (F) also show this discrepancy with regard to the bone metastases. The bone metastasis in the left hemisacrum (yellow circle) has a SUV_max on [⁶⁸Ga]Ga-DOTATATE PET/CT of 39.6. A chest CT 53 days before the [⁶⁸Ga]Ga-DOTATATE PET/CT did not show any bone metastasis