Carcinoid crisis: The challenge is still there.

Carcinoid crisis (CC) has classically been considered the extreme end of the spectrum of carcinoid syndrome (CS). However, this presumption and other aspects of CC remain poorly understood. Consequently, current clinical guidelines are based on a low quality of evidence. There is no standard definition of CC and its incidence is unknown. Patients with florid CS and elevated serotonin (or its derivatives) which develop CC have been reported during decades. Nevertheless, the hypothesis that CC is due to the sudden massive release of serotonin or other vasoactive substances is unproven. Many triggers of CC (surgery, anaesthesia, peptide receptor radionuclide therapy, tumour biopsy or liver-directed treatments) have been proposed. However, data from studies are heterogeneous and even contradictory. Finally, the role of octreotide in the prevention of CC has been questioned. Herein, we report a clinical case and perform a critical review of the evidence available today on this topic.

Is long-term follow-up solely by imaging tests safe in non-operated pancreatic neuroendocrine tumors?

INTRODUCTION: the diagnosis of asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has increased significantly due to the widespread use of high-resolution imaging tests, which is why the most appropriate management at the time of diagnosis is the subject of debate, as is how to follow-up patients. AIMS: the objective of this study was to analyze the frequency of imaging and endoscopic studies performed during long-term follow-up. METHODS: a retrospective review was performed of a database collected between January 2008 and December 2020 of patients with an incidental diagnosis of small NF-PNETs; follow-up was closed in March 2023. The imaging tests performed at the time of diagnosis and long-term follow-up were recorded. Growing less than 1 mm per year has not been considered as a worrisome feature. Follow-up was performed through imaging tests, considering endoscopic cytology for lesions with a faster grow rate. RESULTS: fifty-eight patients were included; the median age was 69 years. The initial mean size of the lesions studied was 12.79 mm (5-27). Follow-up was carried out only with computed tomography (CT) or magnetic resonance imaging (MRI). The initial size did not influence the behavior of the lesion in a statistically significant manner. Twenty-eight tumors (45 %) increased in size, with a growth equal to or less than 4 mm in 24 cases. The mean follow-up time was 82.41 months (12-164). No patient developed metastasis or died from PNET progression. CONCLUSIONS: the follow-up of neuroendocrine tumors of small size can be performed safely with only imaging tests.

Is long-term follow-up solely by imaging tests safe in non-operated pancreatic neuroendocrine tumors?

Introduction: the diagnosis of asymptomatic sporadic nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) has increased significantly due to the widespread use of high-resolution imaging tests, which is why the most appropriate management at the time of diagnosis is the subject of debate, as is how to follow-up patients. Aims: the objective of this study was to analyze the frequency of imaging and endoscopic studies performed during long-term follow-up. Methods: a retrospective review was performed of a database collected between January 2008 and December 2020 of patients with an incidental diagnosis of small NF-PNETs; follow-up was closed in March 2023. The imaging tests performed at the time of diagnosis and long-term follow-up were recorded. Growing less than 1 mm per year has not been considered as a worrisome feature. Follow-up was performed through imaging tests, considering endoscopic cytology for lesions with a faster grow rate. Results: fifty-eight patients were included; the median age was 69 years. The initial mean size of the lesions studied was 12.79 mm (5-27). Follow-up was carried out only with computed tomography (CT) or magnetic resonance imaging (MRI). The initial size did not influence the behavior of the lesion in a statistically significant manner. Twenty-eight tumors (45 %) increased in size, with a growth equal to or less than 4 mm in 24 cases. The mean follow-up time was 82.41 months (12-164). No patient developed metastasis or died from PNET progression. Conclusions: the follow-up of neuroendocrine tumors of small size can be performed safely with only imaging tests. (AU)

Ectopic insulinoma: a systematic review.

Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [68Ga]Ga-DOTA-exedin-4 PET/CT (100%), 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [68Ga]Ga-DOTA-exedin-4 PET/CT and 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.

Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). RESULTS: The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7-not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8-28.1) in pancreatic, and 17.6 months (14.4-33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. CONCLUSION: This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.

N3 hilar sampling decision in the staging of mediastinal lung cancer.

There is insufficient evidence for the sampling of morphometabolically normal N3 hilar lymph nodes https://bit.ly/3gWcar7.

Tumor volume delineation: A pilot study comparing a digital positron-emission tomography prototype with an analog positron-emission tomography system.

We evaluated the potential differences of a digital positron-emission tomography (PET) prototype equipped with photon-counting detectors (D-PET, Philips Healthcare, Cleveland, Ohio, USA) in tumor volume delineation compared with the analog Gemini TF PET system (A-PET, Philips). Eleven oncologic patients first underwent clinical fluorodeoxyglucose (FDG) PET/computed tomography (CT) on A-PET. The D-PET ring was then inserted between the PET and CT scanner of A-PET and the patient was scanned for the second time. Two interpreters reviewed the two sets of PET/CT images for image quality and diagnostic confidence. FDG avid lesions were evaluated for volume measured at 35% and 50% of maximum standard uptake value (SUV) thresholds (35% SUV, 50% SUV), and for SUV gradient as a measure of lesion sharpness. Bland-Altman plots were used to assess the agreement between the two PET scans. Qualitative lesion conspicuity, sharpness, and diagnostic confidence were greater at D-PET than that of A-PET with favorable inter-rater agreements. Median lesion size of the 24 measured lesions was 1.6 cm. The lesion volume at D-PET was smaller at both 35% SUV and 50% SUV thresholds compared with that of A-PET, with a mean difference of - 3680.0 mm3 at 35% SUV and - 835.3 mm3 at 50% SUV. SUV gradient was greater at D-PET than at A-PET by 49.2% (95% confidence interval: 34.1%-60.8%). Given the smaller volume definition, coupled with improved conspicuity and sharpness, digital PET may be more robust and accurate in tumor rendering compared with analog PET not only for radiotherapy planning but also in prognostication and systemic treatment monitoring.

Diagnostic Accuracy of 18F-FDG PET/CT in Patients With Biochemical Evidence of Recurrent, Residual, or Metastatic Medullary Thyroid Carcinoma.

OBJECTIVE: Medullary thyroid carcinoma (MTC) is a rare malignancy. Location of residual, recurrent, or metastatic disease is crucial to treatment management and outcome. We aimed to evaluate the use of F-FDG PET/CT in localizing MTC foci in patients with biochemical relapse. METHODS: This is a retrospective cohort study. Review of 51 FDG PET/CT studies of 45 patients referred to restage MTC due to increased calcitonin (Ctn) and carcinoembryonic antigen (CEA) values at follow-up. FDG PET/CT diagnostic accuracy was determined through a patient-based analysis, using histology as criterion standard when available, or other imaging studies and clinical follow-up otherwise (mean, 4 years). RESULTS: There were 25 positive scans. Sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and positive likelihood ratio were 66.7%, 83.3%, 88.0%, 57.7%, 72.5%, and 4.0, respectively. Using a Ctn cutoff of 1000 pg/mL, sensitivity increased to 76.9%. There were significant differences of Ctn and CEA values between positive and negative FDG PET/CT (P < 0.05). Regarding true-positive studies, average SUVmax comparing locoregional and metastatic disease was at the limit of significance (P = 0.046). CONCLUSIONS: PET/CT can be useful to restage patients with biochemical relapse of MTC, with a better performance in higher Ctn levels. Its high positive predictive value (88%) may impact in the therapeutic management, although its low negative predictive value (57.7%) makes strict follow-up mandatory in examinations without pathologic findings.

Phantom, clinical, and texture indices evaluation and optimization of a penalized-likelihood image reconstruction method (Q.Clear) on a BGO PET/CT scanner.

INTRODUCTION: The aim of this study was to evaluate the behavior of a penalized-likelihood image reconstruction method (Q.Clear) under different count statistics and lesion-to-background ratios (LBR) on a BGO scanner, in order to obtain an optimum penalization factor (ß value) to study and optimize for different acquisition protocols and clinical goals. METHODS: Both phantom and patient images were evaluated. Data from an image quality phantom were acquired using different Lesion-to-Background ratios and acquisition times. Then, each series of the phantom was reconstructed using ß values between 50 and 500, at intervals of 50. Hot and cold contrasts were obtained, as well as background variability and contrast-to-noise ratio (CNR). Fifteen 18 F-FDG patients (five brain scans and 10 torso acquisitions) were acquired and reconstructed using the same ß values as in the phantom reconstructions. From each lesion in the torso acquisition, noise, contrast, and signal-to-noise ratio (SNR) were computed. Image quality was assessed by two different nuclear medicine physicians. Additionally, the behaviors of 12 different textural indices were studied over 20 different lesions. RESULTS: Q.Clear quantification and optimization in patient studies depends on the activity concentration as well as on the lesion size. In the studied range, an increase on ß is translated in a decrease in lesion contrast and noise. The net product is an overall increase in the SNR, presenting a tendency to a steady value similar to the CNR in phantom data. As the activity concentration or the sphere size increase the optimal ß increases, similar results are obtained from clinical data. From the subjective quality assessment, the optimal ß value for torso scans is in a range between 300 and 400, and from 100 to 200 for brain scans. For the recommended torso ß values, texture indices present coefficients of variation below 10%. CONCLUSIONS: Our phantom and patients demonstrate that improvement of CNR and SNR of Q.Clear algorithm which depends on the studied conditions and the penalization factor. Using the Q.Clear reconstruction algorithm in a BGO scanner, a ß value of 350 and 200 appears to be the optimal value for 18F-FDG oncology and brain PET/CT, respectively.

Performance Characteristics of the Whole-Body Discovery IQ PET/CT System.

The aim of this study was to assess the physical performance of a new PET/CT system, the Discovery IQ with 5-ring detector blocks. Methods: Performance was measured using the National Electrical Manufacturers Association NU2-2012 methodology. Image quality was extended by accounting for different acquisition parameters (lesion-to-background ratios [8:1, 4:1, and 2:1] and acquisition times) and reconstruction algorithms (VUE-point HD [VPHD], VPHD with point-spread-function modeling [VPHD-S], and Q.Clear). Tomographic reconstruction was also assessed using a Jaszczak phantom. Additionally, 30 patient lesions were analyzed to account for differences in lesion volume and SUV quantification between reconstruction algorithms. Results: Spatial resolution ranged from 4.2 mm at 1 cm to 8.5 mm at 20 cm. Sensitivity measured at the center and at 10 cm was 22.8 and 20.4 kps/kBq, respectively. The noise-equivalent counting rate peak was 124 kcps at 9.1 kBq/cm3 The scatter fraction was 36.2%. The accuracy of correction for count losses and randoms was 3.9%. In the image quality test, contrast recovery for VPHD, VPHD-S, and Q.Clear ranged from 18%, 18%, and 13%, respectively (hot contrast; 10-mm sphere diameter; ratio, 2:1), to 68%, 67%, and 81%, respectively (cold contrast; 37-mm sphere diameter; ratio, 8:1). Background variability ranged from 3.4%, 3.0%, and 2.1%, respectively (ratio, 2:1), to 5.5%, 4.8%, and 3.7%, respectively (ratio, 8:1). On Q.Clear reconstruction, the decrease in the penalty term (ß) increased the contrast recovery coefficients and background variability. With the Jaszczak phantom, image quality increased overall when a reconstruction algorithm modeling the point-spread function was used, and use of Q.Clear increased the signal-to-noise ratio. Lesions analyzed using VPHD-S and Q.Clear had an SUVmean of 6.5 ± 3 and 7 ± 3, respectively (P < 0.01), and an SUVmax of 11 ± 4.8 and 12 ± 4, respectively (P < 0.01). No significant difference in mean lesion volume was found between algorithms. Conclusion: Among the various Discovery bismuth germanium oxide-based PET/CT scanners, the IQ with 5-ring detector blocks has the highest overall performance, with improved sensitivity and counting rate performance. Q.Clear reconstruction improves the PET image quality, with higher recovery coefficients and lower background variability.

Image Quality and Diagnostic Performance of a Digital PET Prototype in Patients with Oncologic Diseases: Initial Experience and Comparison with Analog PET.

UNLABELLED: We report our initial clinical experience for image quality and diagnostic performance of a digital PET prototype scanner with time-of-flight (DigitalTF), compared with an analog PET scanner with time-of-flight (GeminiTF PET/CT). METHODS: Twenty-one oncologic patients, mean age 58 y, first underwent clinical (18)F-FDG PET/CT on the GeminiTF. The scanner table was then withdrawn while the patient remained on the table, and the DigitalTF was inserted between the GeminiTF PET and CT scanner. The patients were scanned for a second time using the same PET field of view with CT from the GeminiTF for attenuation correction. Two interpreters reviewed the 2 sets of PET/CT images for overall image quality, lesion conspicuity, and sharpness. They counted the number of suggestive (18)F-FDG-avid lesions and provided the TNM staging for the 5 patients referred for initial staging. Standardized uptake values (SUVs) and SUV gradients as a measure of lesion sharpness were obtained. RESULTS: The DigitalTF showed better image quality than the GeminiTF. In a side-by-side comparison using a 5-point scale, lesion conspicuity (4.3 ± 0.6), lesion sharpness (4.3 ± 0.6), and diagnostic confidence (3.4 ± 0.7) were better with DigitalTF than with GeminiTF (P < 0.01). In 52 representative lesions, the lesion maximum SUV was 36% higher with DigitalTF than with GeminiTF, lesion-to-blood-pool SUV ratio was 59% higher, and SUV gradient was 51% higher, with good correlation between the 2 scanners. Lesions less than 1.5 cm showed a greater increase in SUV from GeminiTF to DigitalTF than those lesions 1.5 cm or greater. In 5 of 21 patients, DigitalTF showed an additional 8 suggestive lesions that were not seen using GeminiTF. In the 15 restaging patients, the true-negative rate was 100% and true-positive rate was 78% for both scanners. In the 5 patients for initial staging, DigitalTF led to upstaging in 2 patients and showed the same staging in the other 3 patients, compared with GeminiTF. CONCLUSION: DigitalTF provides better image quality, diagnostic confidence, and accuracy than GeminiTF. DigitalTF may be the most beneficial in detecting small tumor lesions and disease staging.

The impact of orthopedic metal artifact reduction software on interreader variability when delineating areas of interest in the head and neck.

PURPOSE: Metal artifacts during computed tomography (CT) hinder the evaluation of diagnostic images and impair the delineation of tumor volume in treatment planning. Several solutions are available to minimize these artifacts. Our objective was to determine the impact of one of those tools on the interreader variability when measuring head and neck structures in the presence of metal artifacts. METHODS AND MATERIALS: Eleven patients were retrospectively selected from an institutional review board-approved study based on the presence of metallic artifacts in the head and neck region. CT raw data were postprocessed using a metal artifact reduction tool. A single matching CT slice from the filtered backprojection and postprocessed data sets was selected in the region of the metal artifact. Areas of selected anatomical structures were measured by independent readers, including an anatomical structure selected from a CT slice with no metal artifact in each patient as control. The intraclass correlation coefficient was calculated. RESULTS: Two extreme outliers were identified and the intraclass correlation coefficient was performed with and without them. The intraclass correlation on filtered backprojection, postprocessed, and control images was 0.903, 0.948, and 0.985 with outliers and 0.884, 0.971, and 0.989 without outliers, respectively, for all readers. On the other hand, the intraclass correlation on filtered backprojection, postprocessed, and control images for experienced readers was 0.904, 0.979, and 0.976 with outliers and 0.934, 0.975, and 0.990 without outliers, respectively. CONCLUSIONS: The interreader variability of areas measured in the presence of metal artifact was greatly decreased by the use of the metal artifact reduction tool and almost matched the variability observed in the absence of the metal artifact.

Positron Emission Tomography in Breast Cancer.

Gradually, FDG-PET/CT has been strengthening within the diagnostic algorithms of oncological diseases. In many of these, PET/CT has shown to be useful at different stages of the disease: diagnosis, staging or re-staging, treatment response assessment, and recurrence. Some of the advantages of this imaging modality versus CT, MRI, bone scan, mammography, or ultrasound, are based on its great diagnostic capacity since, according to the radiopharmaceutical used, it reflects metabolic changes that often occur before morphological changes and therefore allows us to stage at diagnosis. Moreover, another advantage of this technique is that it allows us to evaluate the whole body so it can be very useful for the detection of distant disease. With regard to breast cancer, FDG-PET/CT has proven to be important when recurrence is suspected or in the evaluation of treatment response. The technological advancement of PET equipment through the development of new detectors and equipment designed specifically for breast imaging, and the development of more specific radiopharmaceuticals for the study of the different biological processes of breast cancer, will allow progress not only in making the diagnosis of the disease at an early stage but also in enabling personalized therapy for patients with breast cancer.

Clinical oncologic applications of PET/MRI: a new horizon.

Positron emission tomography/magnetic resonance imaging (PET/MRI) leverages the high soft-tissue contrast and the functional sequences of MR with the molecular information of PET in one single, hybrid imaging technology. This technology, which was recently introduced into the clinical arena in a few medical centers worldwide, provides information about tumor biology and microenvironment. Studies on indirect PET/MRI (use of positron emission tomography/computed tomography (PET/CT) images software fused with MRI images) have already generated interesting preliminary data to pave the ground for potential applications of PET/MRI. These initial data convey that PET/MRI is promising in neuro-oncology and head & neck cancer applications as well as neoplasms in the abdomen and pelvis. The pediatric and young adult oncology population requiring frequent follow-up studies as well as pregnant woman might benefit from PET/MRI due to its lower ionizing radiation dose. The indication and planning of therapeutic interventions and specifically radiation therapy in individual patients could be and to a certain extent are already facilitated by performing PET/MRI. The objective of this article is to discuss potential clinical oncology indications of PET/MRI.