Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: Agonist, Antagonist and Alternatives.

Peptide receptor radionuclide therapy (PRRT) today is a well-established treatment strategy for patients with neuroendocrine tumors (NET). First performed already more than 30 years ago, PRRT was incorporated only in recent years into the major oncology guidelines, based on its proven efficacy and safety in clinical trials. Following the phase 3 NETTER-1 trial, which led to the final registration of the radiopharmaceutical Luthatera® for G1/G2 NET patients in 2017, the long-term results of the phase 3 NETTER-2 trial may pave the way for a new treatment option also for advanced G2/G3 patients as first-line therapy. The growing knowledge about the synergistic effect of combined therapies could also allow alternative (re)treatment options for NET patients, in order to create a tailored treatment strategy. The evolving thera(g)nostic concept could be applied for the identification of patients who might benefit from different image-guided treatment strategies. In this scenario, the use of dual tracer PET/CT in NET patients, using both [18F]F-FDG/[68Ga]Ga-DOTA-somatostatin analog (SSA) for diagnosis and follow-up, is under discussion and could also result in a powerful prognostic tool. In addition, alternative strategies based on different metabolic pathways, radioisotopes, or combinations of different medical approaches could be applied. A number of different promising "doors" could thus open in the near future for the treatment of NET patients - and the "key" will be thera(g)nostic!

Predicting resection margin status of pancreatic neuroendocrine tumors on CT: performance of NCCN resectability criteria.

OBJECTIVE: To test the performance of the National Comprehensive Cancer Network (NCCN) CT resectability criteria for predicting the surgical margin status of pancreatic neuroendocrine tumor (PNET) and to identify factors associated with margin-positive resection. METHODS: Eighty patients with pre-operative CT and upfront surgery were retrospectively enrolled. Two radiologists assessed the CT resectability (resectable [R], borderline resectable [BR], unresectable [UR]) of the PNET according to NCCN criteria. Logistic regression was used to identify factors associated with resection margin status. κ statistics were used to evaluate interreader agreements. Kaplan-Meier method with log-rank test was used to estimate and compare recurrence-free survival (RFS). RESULTS: Forty-five patients (56.2%) received R0 resection and 35 (43.8%) received R1 or R2 resection. R0 resection rates were 63.6-64.2%, 20.0-33.3%, and 0% for R, BR, and UR diseases, respectively (all p ≤ 0.002), with a good interreader agreement (κ, 0.74). Tumor size (<2 cm, 2-4 cm, and >4 cm; odds ratio (OR), 9.042-18.110; all p ≤ 0.007) and NCCN BR/UR diseases (OR, 5.918; p = 0.032) were predictors for R1 or R2 resection. The R0 resection rate was 91.7% for R disease <2 cm and decreased for larger R disease. R0 resection and smaller tumor size in R disease improved RFS. CONCLUSION: NCCN resectability criteria can stratify patients with PNET into distinct groups of R0 resectability. Adding tumor size to R disease substantially improves the prediction of R0 resection, especially for PNETs <2 cm. ADVANCES IN KNOWLEDGE: Tumor size and radiologic resectability independently predicted margin status of PNETs.

EANM enabling guide: how to improve the accessibility of clinical dosimetry.

Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [131I]-NaI for benign thyroid disorders, [177Lu]-DOTATATE and 131I-mIBG for neuroendocrine tumours and [90Y]-microspheres for unresectable hepatic carcinoma.

3p-C-NETA: A versatile and effective chelator for development of Al18F-labeled and therapeutic radiopharmaceuticals.

Background: Radiolabeled somatostatin analogues (e.g. [68Ga]Ga-DOTATATE and [177Lu]Lu-DOTATATE) have been used to diagnose, monitor, and treat neuroendocrine tumour (NET) patients with great success. [18F]AlF-NOTA-octreotide, a promising 18F-labeled somatostatin analogue and potential alternative for 68Ga-DOTA-peptides, is under clinical evaluation. However, ideally, the same precursor (combination of chelator-linker-vector) can be used for production of both diagnostic and therapeutic radiopharmaceuticals with very similar (e.g. Al18F-method in combination with therapeutic radiometals 213Bi/177Lu) or identical (e.g. complementary Tb-radionuclides) pharmacokinetic properties, allowing for accurate personalised dosimetry estimation and radionuclide therapy of NET patients. In this study we evaluated 3p-C-NETA, as potential theranostic Al18F-chelator and present first results of radiosynthesis and preclinical evaluation of [18F]AlF-3p-C-NETA-TATE. Methods: 3p-C-NETA was synthesized and radiolabeled with diagnostic (68Ga, Al18F) or therapeutic (177Lu, 161Tb, 213Bi, 225Ac and 67Cu) radionuclides at different temperatures (25-95 °C). The in vitro stability of the corresponding radiocomplexes was determined in phosphate-buffered saline (PBS) and human serum. 3p-C-NETA-TATE was synthesized using standard solid/liquid-phase peptide synthesis. [18F]AlF-3p-C-NETA-TATE was synthesized in an automated AllinOne® synthesis module and the in vitro stability of [18F]AlF-3p-C-NETA-TATE was evaluated in formulation buffer, PBS and human serum. [18F]AlF-3p-C-NETA-TATE pharmacokinetics were evaluated using µPET/MRI in healthy rats, with [18F]AlF-NOTA-Octreotide as benchmark. Results: 3p-C-NETA quantitatively sequestered 177Lu, 213Bi and 67Cu at 25 °C while heating was required to bind Al18F, 68Ga, 161Tb and 225Ac efficiently. The [18F]AlF-, [177Lu]Lu- and [161Tb]Tb-3p-C-NETA-complex showed excellent in vitro stability in both PBS and human serum over the study period. In contrast, [67Cu]Cu- and [225Ac]Ac-, [68Ga]Ga-3p-C-NETA were stable in PBS, but not in human serum. [18F]AlF-3p-C-NETA-TATE was obtained in good radiochemical yield and radiochemical purity. [18F]AlF-3p-C-NETA-TATE displayed good in vitro stability for 4 h in all tested conditions. Finally, [18F]AlF-3p-C-NETA-TATE showed excellent pharmacokinetic properties comparable with the results obtained for [18F]AlF-NOTA-Octreotide. Conclusions: 3p-C-NETA is a versatile chelator that can be used for both diagnostic applications (Al18F) and targeted radionuclide therapy (213Bi, 177Lu, 161Tb). It has the potential to be the new theranostic chelator of choice for clinical applications in nuclear medicine.

Sequential Duo-Peptide Receptor Radionuclide Therapy With Indigenous 90Y-DOTATATE and 177Lu-DOTATATE in Large-Volume Neuroendocrine Tumors: Posttherapy Bremsstrahlung and PET/CT Imaging Following 90Y-DOTATATE Treatment.

The efficacy of Lu-DOTATATE in large neuroendocrine tumors (NETs) is reduced because of the lower energy (Eßmax 0.497 MeV) and shorter range of Lu. The pure ß-emitter Y with its longer ß range is more effective in larger tumors. This should be balanced with the greater risk of Y-DOTATATE-related nephrotoxicity. Sequential duo-peptide receptor radionuclide therapy may result in a better response with minimal adverse effects in large-volume heterogeneous NETs. A 56-year-old man with large rectal NET liver metastases, treated with Y-DOTATATE and Lu-DOTATATE and sequential duo-peptide receptor radionuclide therapy, presented with post-Y-DOTATATE bremsstrahlung and PET/CT in comparison with Ga-DOTATATE PET/CT and Lu-DOTATATE scans.

Long-term survival of a patient with an inoperable thymic neuroendocrine tumor stage IIIa under sole treatment with Viscum album extract: A CARE compliant clinical case report.

RATIONALE: Thymic neuroendocrine tumor (TNET) is very rare and characterized by a tendency to invade adjacent structures, frequent metastasis, resistance to therapy, and a poor prognosis. Viscum album extracts (VAE) have shown immunological, apoptogenic, and cytotoxic properties. PATIENT CONCERNS: A 54-year-old Peruvian man was suffering from constant fatigue, cough, dyspnea, and fever for a couple of months. DIAGNOSES: He was diagnosed with TNET (12.8 cm × 10 cm × 7 cm) stage IIIa, G1. Due to the size and extensive invasiveness (vena cava superior, also obstructing 85% of its lumen, pericardium, and pleura), the TNET was inoperable. INTERVENTIONS: We report the case of this patient who declined chemotherapy and was treated instead with sole subcutaneous VAE 3 times per week for 85 months. No other tumor-specific intervention was applied. OUTCOMES: Quality of life (QoL) improved substantially. The patient returned to work, and the tumor remained stable for 71 months. Thereafter, the tumor progressed, and the patient died 90 months after initial diagnosis. Besides self-limited local skin reactions around the application site, no side effects occurred. LESSONS: This is an exceptionally good course of disease of an inoperable, large, obstructing, and invasive TNET with a reduced baseline condition (Karnofsky index: 50-60) due to pronounced symptoms. Given the considerable reduction of symptoms and improved QoL following the onset of VAE therapy and other reports describing long disease stability and improvement of the QoL using VAE in different cancer types, we presume that the VAE treatment was supportive in this case. As TNETs are rare and few trials are available, future treatments of TNETs using VAE should be carefully documented and published to help determine whether further investigation of the use of VAE in TNET treatment is worthwhile.

68Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) changes management in a majority of patients with neuroendocrine tumors.

BACKGROUND: 68Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) has shown superior accuracy in detecting grade 1 and 2 neuroendocrine tumors over previous imaging modalities and was recently included in National Comprehensive Cancer Network guidelines. It remains unclear which patients benefit most from this imaging modality. We therefore reviewed our initial experience with 68Gallium-DOTATATE PET CT to evaluate its usefulness in diagnosing, staging, and surveilling neuroendocrine tumors. METHODS: Records of patients who underwent 68Gallium-DOTATATE PET CT from March to December 2017 were prospectively evaluated. The primary endpoint was whether 68Gallium-DOTATATE PET CT changes treatment in patients with neuroendocrine tumors. Descriptive statistics, Fisher exact tests, and nested logistic regressions were conducted. RESULTS: A total of 50 consecutive patients were included. Of these, 41 patients (82%) had a biopsy-proven neuroendocrine tumor at the time of imaging. The remaining 9 patients (18%) had symptoms or biochemistry suggestive of a neuroendocrine tumor with negative cross-sectional imaging. 68Gallium-DOTATATE PET CT changed management in 33 patients (66%). There were 24 patients with intermodality changes in management and 9 patients with intramodality changes in management. Patients with scans performed for staging had a higher likelihood of a change in management (P = .006). CONCLUSION: Performing 68Gallium-DOTATATE PET CT should be considered for staging and surveillance of neuroendocrine tumors because it is frequently associated with changes in management.

Neuroendocrine Tumor Diagnosis and Management: 68Ga-DOTATATE PET/CT.

OBJECTIVE: The purpose of this article is to provide a review of the use of 68Ga tetraazacyclododecanetetraacetic acid-DPhe1-Tyr3-octreotate (DOTATATE) PET/CT, a functional imaging modality for assessment of well-differentiated neuroendocrine tumors (NETs). It has become the preferred imaging modality for initial diagnosis, selection of patients for peptide receptor radionuclide therapy, and localization of unknown primary tumors. The National Comprehensive Cancer Network guideline has added 68Ga-DOTATATE PET/CT as an appropriate test in the management of NETs. CONCLUSION: In combination with FDG PET/CT, 68Ga-DOTATATE PET/CT can noninvasively assess tumor heterogeneity, especially in G2 and G3 NETs, for personalized management of patients.

Randomized Embolization Trial for NeuroEndocrine Tumor Metastases to the Liver (RETNET): study protocol for a randomized controlled trial.

BACKGROUND: Neuroendocrine tumors (NETs) are the second most common gastrointestinal malignancy after colon cancer. Up to 90% of patients with NETs develop liver metastases, which are a major determinant of symptoms and survival. Current guidelines recommend embolotherapy for progressive or symptomatic NET liver metastases, but the optimal technique among bland embolization, lipiodol chemoembolization, and drug-eluting bead chemoembolization remains unknown and controversial. METHODS/DESIGN: A prospective, open-label, multicenter randomized controlled trial will be conducted in patients with progressive or symptomatic unresectable NET liver metastases. Patients will be randomized to treatment with bland embolization, lipiodol chemoembolization, or drug-eluting microsphere chemoembolization, with 60 enrollees per arm. The primary endpoint will be hepatic progression-free survival (HPFS) following initial embolotherapy by RECIST criteria. The sample size is powered to detect an HR of 1.78 for HPFS following chemoembolization compared with bland embolization, which was estimated on the basis of existing retrospective studies. Secondary endpoints include overall progression-free survival, duration of symptom control, quality of life, rate of adverse events, and interval between embolotherapy cycles. Interim safety analyses will be performed at 10 and 30 patients per arm. DISCUSSION: The RETNET trial is a prospective, multicenter randomized controlled trial designed to determine the optimal embolotherapy technique for NET liver metastases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02724540 . Registered on March 31, 2016.

Outcomes after endoscopic ultrasound-guided ethanol-lipiodol ablation of small pancreatic neuroendocrine tumors.

BACKGROUND AND AIM: Little is known about the standard care of small (<2 cm in diameter) pancreatic neuroendocrine tumors (PNET). The aim of the present study was to determine the clinical outcomes of small PNET after endoscopic ultrasound (EUS)-guided ethanol-lipiodol ablation (EUS-ELA). METHODS: In this prospective cohort study, consecutive patients who underwent EUS-ELA for PNET were enrolled and were followed for ≥3 years. Treatment efficacy was the primary outcome measure. RESULTS: In total, 33 patients who had 40 pathologically confirmed PNET (<2 cm in diameter) were enrolled for final analysis. A total of 63 EUS-ELA sessions were successfully carried out (mean, 1.9 sessions per patient, 1.6 sessions per tumor), which included 40 initial sessions and 23 repeated sessions owing to incomplete ablation. Median actual volume of ethanol-lipiodol mixture injected per session was 1.1 mL (IQR 0.8-1.9 mL). Complete ablation was achieved in 24 of 40 tumors (60%) with one (18 tumors, 45%) or two (24 tumors, 60%) sessions of EUS-ELA. Lipiodol retention within tumor had better treatment outcomes (P = 0.004). Rate of procedure-related adverse events was 3.2%. No malignancy or lymph node metastasis was discovered during a median follow up of 42 months (IQR 39-46 months). CONCLUSIONS: We found that EUS-ELA was a safe and effective alternative option in the management of PNET <2.0 cm in diameter; 60% of patients achieved complete ablation. Lipiodol retention within tumor may be a useful early predictor of treatment effectiveness. Trial registered at ClinicalTrials.gov (NCT 01902238).

Duodenum and ventral pancreas preserving subtotal pancreatectomy for low-grade malignant neoplasms of the pancreas: An alternative procedure to total pancreatectomy for low-grade pancreatic neoplasms.

AIM: To describe the indications, technique and outcomes of the novel surgical procedure of duodenum and ventral pancreas preserving subtotal pancreatectomy (DVPPSP). METHODS: Data collected retrospectively from 43 patients who underwent DVPPSP and TP between 2009 and 2015 in our single centre were analysed. For enrolment, only patients with low-grade pancreatic neoplasms, such as pancreatic neuroendocrine tumors, intraductal papillary mucinous neoplasms (IPMNs), and solid pseudo-papillary tumors, were included. Ten DVPPSP (group 1) and 13 TP (group 2) patients were selected in this study. RESULTS: There were no significant differences in age, gender, comorbidities, preoperative symptoms, American Society of Anesthesiologists score or indications for surgery between the two groups. The most common indication was IPMN for DVPPSP and TP (60% vs 85%, P = 0.411). Compared with the TP group, the DVPPSP group had comparable postoperative morbidities (P = 0.405) and mortalities (both nil), but significantly shorter operative time (232 ± 19.6 min vs 335 ± 32.3 min, P < 0.001). DVPPSP preserved better long-term pancreatic function with less supplementary therapy (P < 0.001) and better quality of life (QoL) after surgery, including better scores in social (P = 0.042) and global health (P = 0.047) on functional scales and less appetite loss (P = 0.049) on the symptom scale. CONCLUSION: DVPPSP is a feasible and safe procedure that could be an alternative to TP for low-grade neoplasms arising from the body and tail region but across the neck region of the pancreas; DVPPSP had better metabolic function and QoL after surgery.

Role of contrast-enhanced ultrasound to define prognosis and predict response to biotherapy in pancreatic neuroendocrine tumors.

PURPOSE: The incidence of neuroendocrine tumors (NETs) is progressively increasing. Most cases arise from the digestive system, where ileum, rectum and pancreas represent the commonest site of origin. Liver metastases are frequently detected at diagnosis or during the follow-up. Contrast-enhanced ultrasound (CEUS) is used in patients with pancreatic NETs (P-NETs) and liver metastases from P-NET but its role has not been standardized. The aim of this retrospective study was to investigate CEUS in patients with P-NETs and liver metastases from P-NET both as prognostic factor and predictor of response to therapy with somatostatin analogues (SSAs). METHODS: CEUS was performed at the diagnosis of NET and 3, 6 and 12 months after the beginning of SSAs. CEUS pattern was compared with contrast-enhanced computed tomography (CT) pattern. RESULTS: There was a significant association between CEUS and CT pattern (X 2 = 79.0; p < 0.0001). A significant association was found between CEUS pattern and Ki-67 index (X 2 = 24.6; p < 0.0001). The hypervascular homogeneous CEUS typical pattern was associated with low tumor grading (G1 or G2) (X 2 = 24.0; p < 0.0001). CEUS pattern changed from hypervascular homogeneous in baseline to hypovascular/hypervascular inhomogeneous after SSA therapy, with a significant association between tumor response at CT scan and appearance of hypervascular inhomogeneous pattern at CEUS evaluation (6 months: X 2 = 57.0; p < 0.0001; 12 months: X 2 = 49.8; p < 0.0001). CONCLUSIONS: In patients with P-NET, CEUS pattern correlates with tumor grading, being homogeneous in G1-G2 but not in G3 tumors. After therapy with SSAs, CEUS is predictive of response to SSAs. These findings seem to support a role of CEUS as prognostic and predictive factor of response.

Successful percutaneous CT-guided microwave ablation of adrenal gland for ectopic Cushing syndrome.

Adrenocorticotropic hormone production by pancreatic neuroendocrine tumor (PNET) is rare and results in hyperstimulation of the adrenal gland to produce ectopic Cushing syndrome. Our case showcases the safety and effectiveness of percutaneous CT-guided microwave ablation of the adrenal gland in a 49-year-old female with PNET and hepatic metastases who presented with ectopic Cushing syndrome despite surgical resection of the primary pancreatic tumor and left adrenal gland. Prior to ablation, the right adrenal gland measured 4.3×1.6×2.0cm and the patient had malignant hypertension with elevated morning serum cortisol level (1976nmol/L). After microwave ablation of the right adrenal gland, the hypertension resolved and the cortisol level decreased dramatically (74nmol/L). As expected after successful treatment, the patient developed adrenal insufficiency and was placed on glucocorticoid and mineralocorticoid supplementation.

Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion.

Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014 .

Can complementary 68Ga-DOTATATE and 18F-FDG PET/CT establish the missing link between histopathology and therapeutic approach in gastroenteropancreatic neuroendocrine tumors?

UNLABELLED: Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are indolent neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. Tumor size, existence of metastasis, and histopathologic classification remain incapable in terms of treatment decision and prognosis estimation. This study aimed to compare (68)Ga-DOTATATE and (18)F-FDG PET/CT in GEPNETs and to investigate the relation between the complementary PET/CT results and histopathologic findings in the management of therapy, particularly in intermediate-grade patients. METHODS: The relation between complementary (68)Ga-DOTATATE and (18)F-FDG PET/CT results of 27 GEPNET patients (mean age, 56 y; age range, 33-79 y) and histopathologic findings was evaluated according to grade and localization using standardized maximum uptake values and Ki67 indices. Grade 2 (G2) patients were further evaluated in 2 groups as G2a (3%-9%) and G2b (10%-20%) according to Ki67 indices. RESULTS: The sensitivity of (68)Ga-DOTATATE and (18)F-FDG PET/CT was 95% and 37%, respectively, and the positive predictive values were 93.8% and 36.2%, respectively. The sensitivity in detecting liver metastasis, lymph nodes, bone metastasis, and primary lesion was 95%, 95%, 90%, and 93% for (68)Ga-DOTATATE and 40%, 28%, 28%, and 75% for (18)F-FDG, respectively. Statistically significant differences were found between grades 1-2, 2a-2b, and 1-2b with respect to (68)Ga-DOTATATE PET/CT as well as between 1-2a and 1-2b with respect to (18)F-FDG PET/CT. However, no statistical differences were found between 1 and 2a (P > 0.05) for (68)Ga-DOTATATE and 2a and 2b (P = 0.484) for (18)F-FDG. The impact of the combined (18)F-FDG and (68)Ga-DOTATATE PET/CT on the therapeutic decision was 59%. CONCLUSION: Combined (68)Ga-DOTATATE and (18)F-FDG PET/CT is helpful in the individual therapeutic approach of GEPNETs and can overcome the shortcomings of histopathologic grading especially in intermediate-grade GEPNETs.

Individualized dosimetry-based activity reduction of 9°Y-DOTATOC prevents severe and rapid kidney function deterioration from peptide receptor radionuclide therapy.

PURPOSE: Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney. METHODS: In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL). RESULTS: Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT. CONCLUSION: Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.

The value of preoperative imaging in small bowel neuroendocrine tumors.

BACKGROUND: Neuroendocrine tumors of the small bowel (SBNETs) are a rare but important subgroup of malignancies. Since 30 % of SBNETs present with metastatic disease, often with an occult primary, preoperative imaging is critical for determining who will benefit most from abdominal exploration. We set out to evaluate the usefulness of the two most commonly performed imaging modalities in predicting the extent of disease found at exploration in patients with SBNETs. METHODS: A retrospective chart review was performed on patients with SBNETs resected at 1 institution. Data from preoperative computed tomography (CT) scans were reviewed to determine whether the primary tumor, nodal, or liver metastases were seen, then compared with intraoperative findings. Results of preoperative somatostatin receptor scintigraphy (SRS) were similarly examined. RESULTS: A total of 62 patients with SBNETs were included. Of these patients, 42 of 62 (68 %) had distant metastases and 48 of 62 (77 %) had nodal metastases at exploration. A total of 56 patients had preoperative CT scans and 47 had SRS. Using CT, a primary tumor was localized to the small bowel in 27 of 56 (48 %) and nodal metastases seen in 33 of 56 (79 %) of cases. SRS found intra-abdominal uptake in 35 of 47 cases (74 %). CONCLUSIONS: CT and SRS are complementary in making the diagnosis of SBNET, with CT giving more precise anatomical detail, while SRS helps to confirm that lesions are NETs and is useful for identifying occult extrahepatic sites of metastatic disease. However, 10-15 % of SBNETs were not identified by either test preoperatively, and therefore surgical exploration still plays an important role in making the diagnosis in these patients.

Well-differentiated neuroendocrine tumor and osteoporosis: incidental findings?

The neuroendocrine tumors (NETs) have an increased incidence related to the age. Secondary osteoporosis might be found in patients with bone metastases and in those with NETs associated Cushing's disease or primary hyperparathyroidism. Primary osteoporosis might be found in postmenopausal women, but in case with non-metastatic NET as G1 NET it is difficult to establish the NET contribution to the bone loss. We present the case of a 53-year-old female accidentally diagnosed with G1 lung NET after surgery of the tumor. The immunohistochemistry pointed positive reaction for CHROMO, SYN and negative for CK7 and TTF1, and a Ki67 of 1-2% (well-differentiated neuroendocrine tumor). The central Dual X-Ray Absorptiometry (DXA) showed osteoporosis based on a T-score of -3. The patient had normal neuroendocrine markers and she was asymptomatic. She remained so for one year and the only therapy provided was weekly alendronate with adequate vitamin D and calcium supplements. Based on the pathological and immunohistochemistry profile, the low risk NET was diagnosed. We encourage the skeletal status assessment as central DXA in postmenopausal women with NETs, regardless clinical evidence of bone loss. The future will provide more epidemiological and pathogenic connections between the two dynamic fields of medicine as neuroendocrine tumors and osteoporosis.