Assessment of clinical benefit of systemic treatments of rare diseases including gastroenteropancreatic neuroendocrine tumours (GEP-NET) is challenging. Recently several tools have been developed to ...grade the clinical benefit of cancer drugs. The European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). The American Society of Clinical Oncology (ASCO) has developed and revised the ASCO framework consisting of the Net Health Benefit (NHB) score juxtaposed against the costs of the treatment. In this review, we graded systemic treatments for GEP-NET patients with both frameworks.
The electronic databases (PubMed and EMBASE) were searched for papers reporting comparative trials, conducted in adult GEP-NET patients in the English language. Papers were assessed according to the ESMO-MCBS and the NHB part of the ASCO revised Framework (NHB-ASCO-F) by four independent assessors, and discrepancies were discussed.
The search yielded 32 trials of which 6 were eligible for grading with the ESMO-MCBS resulting in scores of 2 or 3. Eight trials were eligible for grading with the NHB-ASCO-F, resulting in scores between 37.6 and 57.4. Trials that were not primary assessable by the tools were analysed separately. Consensus between assessors was reached in 68% of trials with the ESMO-MCBS and in 23% of trials with the NHB-ASCO-F.
The currently used systemic treatments for GEP-NET patients had low scores according to the NHB-ASCO-F and none could be graded as meaningful clinical beneficial according to the ESMO-MCBS. Despite the low incidence, the heterogeneous patient population and relatively long natural course of NET, future studies on new treatment modalities should aim for high clinical benefit outcomes.
Background
Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The ...subset of patients at high risk of disease recurrence has not been clearly defined to date.
Objective
The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence.
Patients and Methods
This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) G1/G2 that underwent R0/R1 surgery (years 2000–2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan–Meier method and risk factor analysis was performed using the Cox regression model.
Results
Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (
p
< 0.01).
Conclusions
Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.
Background
Identifying the correct location of a parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) is crucial as it can guide surgical treatment. This study aimed to determine ...the diagnostic performance of
11
C-choline PET/CT in patients with pHPT as a next in-line scan after primary negative or discordant first-line imaging.
Methods
This was a retrospective single-center cohort study. All patients with pHPT that were scanned utilizing
11
C-choline PET/CT, after prior negative or discordant imaging, between 2015 and 2019 and who subsequently underwent parathyroid surgery were included. The results of the
11
C-choline PET/CT were evaluated lesion-based, with surgical exploration and histopathological examination as the gold standard.
Results
In total, 36 patients were included of which three patients were known to have Multiple Endocrine Neoplasia (MEN) syndrome. In these 36 patients, 40 lesions were identified on
11
C-choline PET/CT and 37 parathyroid lesions were surgically removed. In 34/36 (94%) patients a focused parathyroidectomy was performed, in one patient a cervical exploration due to an ectopically identified adenoma, and in one patient a bilateral exploration was performed because of a double adenoma. Overall, per-lesion sensitivity of
11
C-choline PET/CT was 97%, the positive predictive value was 95% and the accuracy was 94% for all parathyroid lesions.
Conclusions
In patients with pHPT and prior negative or discordant first-line imaging results, pathological parathyroid glands can be localized by
11
C-choline PET/CT with high sensitivity and accuracy.
Peptide receptor radionuclide therapy (PRRT) is an established treatment of metastatic neuroendocrine tumors grade 1–2 (G1–G2). However, its possible benefit in high-grade gastroenteropancreatic ...(GEP) neuroendocrine neoplasms (NEN G3) is largely unknown. We therefore aimed to assess the benefits and side effects of PRRT in patients with GEP NEN G3. We performed a retrospective cohort study at 12 centers to assess the efficacy and toxicity of PRRT in patients with GEP NEN G3. Outcomes were response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicity. We included 149 patients (primary tumor: pancreatic n = 89, gastrointestinal n = 34, unknown n = 26). PRRT was first-line (n = 30), second-line (n = 62) or later-line treatment (n = 57). Of 114 patients evaluated, 1% had complete response, 41% partial response, 38% stable disease and 20% progressive disease. Of 104 patients with documented progressive disease before PRRT, disease control rate was 69%. The total cohort had median PFS of 14 months and OS of 29 months. Ki-67 21–54% (n = 125) vs Ki-67 ≥55% (n = 23): PFS 16 vs 6 months (P < 0.001) and OS 31 vs 9 months (P < 0.001). Well (n = 60) vs poorly differentiated NEN (n = 62): PFS 19 vs 8 months (P < 0.001) and OS 44 vs 19 months (P < 0.001). Grade 3–4 hematological or renal toxicity occurred in 17% of patients. This large multicenter cohort of patients with GEP NEN G3 treated with PRRT demonstrates promising response rates, disease control rates, PFS and OS as well as toxicity in patients with mainly progressive disease. Based on these results, PRRT may be considered for patients with GEP NEN G3.
Purpose
Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after ...negative first-line imaging. In this study, we compare the diagnostic effectiveness of
11
Cmethionine PET/CT,
11
Ccholine PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan.
Methods
We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and
99m
Tc-sestamibi. All patients underwent
11
Cmethionine PET/CT,
11
Ccholine PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT.
Results
A total of 32 patients were included in the study. With blinded evaluation,
11
Ccholine PET/CT was positive in 28 patients (88%),
11
Cmethionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of
11
Ccholine PET/CT,
11
Cmethionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of
11
Ccholine PET/CT differed significantly from that of
11
Cmethionine PET/CT and 4D-CT (
p
= 0.031 and
p
< 0.0005, respectively).
Conclusion
In the setting of pHPT with negative first-line imaging,
11
Ccholine PET/CT is superior to
11
Cmethionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost–benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques.
Identifying the correct location of a parathyroid adenoma in patients with primary hyperparathyroidism (pHPT) is crucial as it can guide surgical treatment. This study aimed to determine the ...diagnostic performance of
C-choline PET/CT in patients with pHPT as a next in-line scan after primary negative or discordant first-line imaging.
This was a retrospective single-center cohort study. All patients with pHPT that were scanned utilizing
C-choline PET/CT, after prior negative or discordant imaging, between 2015 and 2019 and who subsequently underwent parathyroid surgery were included. The results of the
C-choline PET/CT were evaluated lesion-based, with surgical exploration and histopathological examination as the gold standard.
In total, 36 patients were included of which three patients were known to have Multiple Endocrine Neoplasia (MEN) syndrome. In these 36 patients, 40 lesions were identified on
C-choline PET/CT and 37 parathyroid lesions were surgically removed. In 34/36 (94%) patients a focused parathyroidectomy was performed, in one patient a cervical exploration due to an ectopically identified adenoma, and in one patient a bilateral exploration was performed because of a double adenoma. Overall, per-lesion sensitivity of
C-choline PET/CT was 97%, the positive predictive value was 95% and the accuracy was 94% for all parathyroid lesions.
In patients with pHPT and prior negative or discordant first-line imaging results, pathological parathyroid glands can be localized by
C-choline PET/CT with high sensitivity and accuracy.
Monoamine oxidase (mao) inhibitors are antidepressants with potentially severe side-effects. For this reason, the registration of this drug was suspended for some time when safer alternatives became ...available. However, mao inhibitors can be very effective in cases where depression has proved to be treatment resistant. Consequently, last year tranylcypromine was re-registered for use in the Netherlands. Since mao inhibitors have been used only sporadically in the Netherlands over the last few years, health professionals have only limited knowledge about the side-effects. On the basis of a recent case, we discuss the two most important side-effects of using mao inhibitors, namely hypertension and orthostatic hypotension. We discuss the possible causes and suggest ways on which these two side-effects can be prevented, or treated, should they arise.
A large area position sensitive X-ray detector for astrophysical observations
Nuclear instruments and methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment/Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/1988
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