Phase II study of everolimus and temozolomide as first-line treatment in metastatic high-grade gastroenteropancreatic neuroendocrine neoplasms.

BACKGROUND: The optimal treatment for metastatic high-grade gastroenteropancreatic (GEP) neuroendocrine neoplasms when Ki-67 ≤55% is unknown. A prospective multi-centre phase 2 study was performed to evaluate the efficacy and safety of everolimus and temozolomide as first-line treatment for these patients. METHODS: Patients received everolimus 10 mg daily continuously and temozolomide 150 mg/m2 for 7 days every 2 weeks. Endpoints included response, survival, safety and quality of life (QoL). Histopathological re-evaluation according to the 2019 WHO classification was performed. RESULTS: For 37 eligible patients, the primary endpoint with 65% disease control rate (DCR) at 6 months (m) was reached. The response rate was 30%, the median progression-free survival (PFS) 10.2 months and the median overall survival (OS) 26.4 months. Considering 26 NET G3 patients, 6 months DCR was 77% vs. 22% among nine NEC patients (p = 0.006). PFS was superior for NET G3 vs. NEC (12.6 months vs. 3.4 months, Log-rank-test: p = 0.133, Breslow-test: p < 0.001). OS was significantly better for NET G3 (31.4 months vs. 7.8 months, p = 0.003). Grade 3 and 4 toxicities were reported in 43% and 38%. QoL remained stable during treatment. CONCLUSION: Everolimus and temozolomide may be a treatment option for selected GEP-NET G3 patients including careful monitoring. Toxicity did not compromise QoL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NTC02248012).

A phase I prospective, non-randomized trial of autologous dendritic cell-based cryoimmunotherapy in patients with metastatic castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) is an immunologically cold disease with dismal outcomes. Cryoablation destroys cancer tissue, releases tumor-associated antigens and creates a pro-inflammatory microenvironment, while dendritic cells (DCs) activate immune responses through processing of antigens. Immunotherapy combinations could enhance the anti-tumor efficacy. This open-label, single-arm, single-center phase I trial determined the safety and tolerability of combining cryoablation and autologous immature DC, without and with checkpoint inhibitors. Immune responses and clinical outcomes were evaluated. Patients with mCRPC, confirmed metastases and intact prostate gland were included. The first participants underwent prostate cryoablation with intratumoral injection of autologous DCs in a 3 + 3 design. In the second part, patients received cryoablation, the highest acceptable DC dose, and checkpoint inhibition with either ipilimumab or pembrolizumab. Sequentially collected information on adverse events, quality of life, blood values and images were analyzed by standard descriptive statistics. Neither dose-limiting toxicities nor adverse events > grade 3 were observed in the 18 participants. Results indicate antitumor activity through altered T cell receptor repertoires, and 33% durable (> 46 weeks) clinical benefit with median 40.7 months overall survival. Post-treatment pain and fatigue were associated with circulating tumor cell (CTC) presence at inclusion, while CTC responses correlated with clinical outcomes. This trial demonstrates that cryoimmunotherapy in mCRPC is safe and well tolerated, also for the highest DC dose (2.0 × 108) combined with checkpoint inhibitors. Further studies focusing on the biologic indications of antitumor activity and immune system activation could be considered through a phase II trial focusing on treatment responses and immunologic biomarkers.

F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis.

BACKGROUND: Positron emission tomography (PET) with fluor-18-deoxy-glucose (FDG) is widely used for diagnosing recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC). PURPOSE: To assess the diagnostic accuracy of FDG-PET for DTC in patients after ablative therapy. MATERIAL AND METHODS: A systematic search was conducted in Medline/PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey looking for all English-language original articles on the performance of FDG-PET in series of at least 20 patients with DTC having undergone ablative therapy including total thyroidectomy. Diagnostic performance measures were pooled using Reitsma's bivariate model. RESULTS: Thirty-four publications between 1996 and 2014 met the inclusion criteria. Pooled sensitivity and specificity were 79.4% (95% confidence interval [CI], 73.9-84.1) and 79.4% (95% CI, 71.2-85.4), respectively, with an area under the curve of 0.858. CONCLUSION: F18-FDG-PET is a useful method for detecting recurrent DTC in patients having undergone ablative therapy.

Specific efficacy of peptide receptor radionuclide therapy with (177)Lu-octreotate in advanced neuroendocrine tumours of the small intestine.

PURPOSE: Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with (177)Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. METHODS: A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with (177)Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. RESULTS: The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2%). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1%), minor response in 19 (31.1%), stable disease in 29 (47.5%) and progressive disease in 5 (8.2%) patients. The disease control rate was 91.8%. Median progression-free survival (PFS) and overall survival (OS) was 33 [95% confidence interval (CI) 25-41] and 61 months (95% CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were functionality [hazard ratio (HR) 2.1, 95% CI 1.0-4.5, p = 0.05] and high plasma chromogranin A (CgA) levels > 600 ng/ml (HR 2.9, 95% CI 1.5-5.5, p < 0.001) at baseline. CONCLUSION: PRRT is well tolerated and very effective in advanced well-differentiated small intestinal (midgut) NET. A high disease control rate and long PFS can be achieved with this modality after failure of standard biotherapy with somatostatin analogues. Tumour functionality and high plasma CgA appear to be independent predictors of unfavourable patient outcome.

Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with (177)Lu-octreotate.

PURPOSE: Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine-allowing only approximate estimates of GFR-the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. METHODS: Nephrotoxicity was analysed using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with (177)Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by (99m)Tc-DTPA clearance versus serum creatinine. RESULTS: The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m(2) per year, relative yearly reduction -1.8 ± 18.9%). Fifteen patients (21%) experienced a mild (2-10 ml/min/m(2) per year) and 16 patients (22%) a significant (>10 ml/min/m(2) per year) decline of GFR following PRRT. However, 11 patients (15%) showed an increase of >10 ml/min/m(2) per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3%) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15% of the assessments and led to underestimation in 12% of patients. None of the investigated factors including cumulative administered activity contributed to the decline of renal function. CONCLUSION: Serious nephrotoxicity after PRRT with (177)Lu-octreotate is rare (1.3%). However, slight renal impairment (GFR loss >2 ml/min/m(2) per year) can frequently (43%) be detected by (99m)Tc-DTPA clearance assessments. Cumulative administered activity of (177)Lu-octreotate is not a major determinant of renal impairment in our study.

Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours.

PURPOSE: We assessed the outcome and toxicity of salvage therapy (repeat treatment) with (177)Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET). METHODS: We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0-83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p < 0.05. RESULTS: Radiographic responses consisted of complete response in 1 patient (3.0%), partial response in 6 patients (18.2%), minor response in 1 patient (3.0%), stable disease in 14 patients (42.4%), and progressive disease in 11 patients (33.3%). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95% CI 9-18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p = 0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2%). The cumulative administered activity was not associated with an increased incidence of haematotoxicity. CONCLUSION: PRRT with (177)Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET.

Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours.

PURPOSE: The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with (177)Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). METHODS: We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with (177)Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial (99m)Tc-DTPA clearance measurements. RESULTS: The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis. Variables linked to impaired OS, on the other hand, were a reduced performance status (Karnofsky score ≤ 70 %, p = 0.007), a high hepatic tumour burden (≥ 25 % liver volume, p = 0.017), and an elevated plasma level of neuron-specific enolase (NSE >15 ng/ml, p = 0.035). CONCLUSION: The outstanding response rates and survival outcomes suggest that PRRT is highly effective in advanced G1/2 pNET when compared to data of other treatment modalities. Independent predictors of survival are the tumour proliferation index, the patient's performance status, tumour burden and baseline plasma NSE level.

Rebooting nuclear medicine specialist education under the COVID-19 pandemic: From plenary lectures to active e-learning.

Despite major reforms of specialist training in the Nordic countries towards concrete learning outcomes and promoting active learning, most specialist courses continue to be based on lectures. We redesigned our mandatory 5-day course in clinical nuclear medicine (NM) that was last held in 2016 towards active learning. Thirty 1-h lectures were replaced with 10 thematic blocks of 3 h each. Each block was taught by a single teacher in a blend of short introductory lectures alternating with small groups of residents reading NM cases from our newly established national case library in diagnostic format. Due to COVID-19, the entire course in 2021 needed to be run on a videoconferencing system rather than in a computer laboratory as had been originally planned. At the end of the course, we conducted the same anonymized survey as in 2016. All 19 course participants responded. 74% fully agreed that the e-course format had been 'good'. One hundred per cent fully agreed that the practical exercises were 'useful' versus 50% in 2016 (p < 0.001). In their free text answers on the merits or downsides of e-learning, 12/12 respondents only mentioned advantages. Our newly established library of anonymized teaching cases within our national health network is an effective tool for organising courses based on active learning. Despite the change towards distance learning enforced by the pandemic, course participants reported the same high levels of satisfaction with active learning in small groups as in the earlier traditional lecture-based course format.

VEXAS Syndrome in a Patient with Myeloproliferative Neoplasia.

VEXAS syndrome stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused by a somatic mutation in the UBA1. There is an association between VEXAS and hematological conditions such as myelodysplastic syndrome (MDS), monoclonal gammopathies of uncertain conditions (MGUS), multiple myeloma (MM), and monoclonal B-cell lymphoproliferative conditions. There are not many descriptions of patients having VEXAS in combination with myeloproliferative neoplasm (MPN). With this article, we want to present a case history of a man in his sixties with a JAK2V617F mutated essential thrombocythemia (ET) developing VEXAS syndrome. The inflammatory symptoms occurred three and a half years after the ET diagnosis. He started to experience symptoms of autoinflammation and an overall worsening of his health, and blood work showed high inflammatory markers, leading to repeated hospitalizations. His major complaint was stiffness and pain, and high dosages of prednisolone were necessary to obtain pain relief. He subsequently developed anemia and significantly variable levels of thrombocytes, which previously were at a steady level. To evaluate his ET, we made a bone marrow smear demonstrating vacuolated myeloid and erythroid cells. Having VEXAS syndrome in mind, genetic testing identifying the UBA1 gene mutation was performed, thus confirming our suspicion. The work-up with myeloid panel on his bone marrow identified genetic mutation in the DNMT3 too. After developing VEXAS syndrome, he experienced thromboembolic events with both cerebral infarction and pulmonary embolism. Thromboembolic events are also common in JAK2 mutated patients, but in his case, they presented first after VEXAS had developed. Throughout the course of his condition, several attempts with prednisolone tapering and steroid sparing drugs were tried. He could not get pain relief unless the combination of medications included a relatively high dose of prednisolone. Currently, the patient uses prednisolone, anagrelide, and ruxolitinib, with partial remission and fewer hospitalizations and more stabilized hemoglobin and thrombocytes.

The significance of bremsstrahlung SPECT/CT after yttrium-90 radioembolization treatment in the prediction of extrahepatic side effects.

Purpose Unwanted deposition of 90Y microspheres in organs other than the liver during radioembolization of liver tumours may cause severe side effects such as duodenal ulcer. The aim of this study was to evaluate the significance of posttherapy bremsstrahlung (BS) SPECT/CT images of the liver in comparison to planar and SPECT images in the prediction of radioembolization-induced extrahepatic side effects.Methods A total of 188 radioembolization procedures were performed in 123 patients (50 women, 73 men) over a 2-year period. Planar, whole-body and BS SPECT/CT imaging were performed 24 h after treatment as a part of therapy work-up.Any focally increased extrahepatic accumulation was evaluated as suspicious. Clinical follow-up and gastroduodenoscopy served as reference standards. The studies were reviewed to evaluate whether BS SPECT/CT imaging was of benefit.Results In the light of anatomic data obtained from SPECT/CT, apparent extrahepatic BS in 43% of planar and in 52% of SPECT images proved to be in the liver and hence false positive.The results of planar scintigraphy could not be analysed further since 12 images were not assessable due to high scatter artefacts. On the basis of the gastrointestinal (GI)complications and the results of gastroduodenoscopy, true positive,true-negative, false-positive and false-negative results of BS SPECT and SPECT/CT imaging in the prediction of GI ulcers were determined. The sensitivity, specificity, positive and negative predictive values and the accuracy of SPECT and SPECT/CT in the prediction of GI ulcers were 13%, 88%, 8%,92% and 82%, and 87%, 100%, 100%, 99% and 99%,respectively.Conclusion Despite the low quality of BS images, BSSPECT/CT can be used as a reliable method to confirm the safe distribution of 90Y microspheres and in the prediction of GI side effects.

Basosquamous Basal Cell Carcinoma with Bone Marrow Metastasis.

Basal cell carcinoma (BCC) is the most common cancer in Caucasians. It is slow growing and rarely metastasizes. If left untreated over time, invasive growth can occur. We present a patient case with a primary BCC located in the right sub-mammary area, with extensive metastases to the skeleton and bone marrow. Histopathological examination of the tumour showed BCC with a diverse growth pattern. There were no signs of local metastases. Surgery was successfully performed. Three months post-surgery the patient developed normocytic anaemia and elevated inflammation markers. [18F]FDG PET/CT showed extensive FDG uptake in the entire skeleton and bone marrow. Biopsy confirmed the infiltration of BCC with similar histopathological features as the primary tumour. Prognosis of metastasized BCC is poor and, therefore, long-term follow-up of patients with risk factors is of importance.

Enhancing PSMA-PET/CT with intravenous contrast: Improved tracer clearance in the prostate bed.

AIMS: We observed hitherto unreported layering of radioactivity in the bladder on PET/CT in prostate cancer (PC) when combined with contrast-enhanced CT (CECT). This effect facilitates assessment of the prostate bed in PC. METHODS: Among 128 patients imaged with [18F]PSMA-1007, we selected all 8 studies without and 28 studies with CECT. 20 patients also underwent PET/MR. As controls, we chose 20 and 16 males studied with [18F]FDG for extrapelvic disease with and without CECT. Posterior anterior (PA) ratio was calculated as SUVpost/SUVant * 100 % based on maximal standard uptake values (SUV) in 20 mm spheres in the anterior and posterior bladder. Four nuclear physicians scored assessibility of the bladder base on a 3-point Likert scale (3 = optimal, 1 = poor). We acquired serial PET/CT over 4 hours of a flask with layering of 100 ml intravenous contrast agent and 100 ml physiological saline with 40 MBq of [18F]PSMA-1007, while a control flask was shaken at the start of the experiment. RESULTS: Layering of tracer was observed in all PET/CT studies with CE-CT, but not in studies without contrast. Median PA ratios were 44 % (interquartile range 33-62) for [18F]PSMA-1007 and 73 % (52-67) for [18F]FDG, respectively. Intravenous contrast improved assessibility scores in PET of the bladder base, but the effect only reached significance in the PET/MR data. In the in vitro data, radioactivity was retained in the aqueous supernatant over the entire experiment whereas there was no separation of phases in the control flask over time. CONCLUSION: When performing PET combined with CECT, sedimentation of contrast agent in the bladder leads to upward displacement of radioactivity, enhancing clarity of PET images in the posterior bladder and the prostate bed on both PET/CT and PET/MR.

The overriding role of surgery and tumor grade for long-term survival in patients with gastroenteropancreatic neuroendocrine neoplasms: A population-based cohort study.

BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous disease group. Factors that affect long-term survival remain uncertain. Complete population-representative cohorts with long-term follow-up are scarce. AIM: To evaluate factors of importance for the long-term survival. METHODS AND RESULTS: An Observational population-based study on consecutive GEP-NEN patients diagnosed from 2003 to 2013, managed according to national guidelines. Univariable and multivariable survival analyses were performed to evaluate overall survival (OS) and to identify independent prognostic factors. One hundred ninety eligible patients (males, 58.9%) (median age, 60.0 years; range, 10.0-94.2 years) were included. The small bowel, appendix, and pancreas were the most common tumor locations. The World Health Organization (WHO) tumor grade 1-3 distributions varied according to the primary location and disease stage. Primary surgery with curative intent was performed in 66% of the patients. The median OS of the study population was 183 months with 5- and 10-year OS rates of 66% and 57%, respectively. Only age, WHO tumor grade, and primary surgical treatment were independent prognostic factors for OS. CONCLUSION: The outcomes of GEP-NEN patients are related to several factors including age and primary surgical treatment. WHO tumor grading, based on the established criteria, should be routine in clinical practice. This may improve clinical decision-making and allow the comparison of outcomes among different centers.

Is prophylactic embolization of the hepatic falciform artery needed before radioembolization in patients with 99mTc-MAA accumulation in the anterior abdominal wall?

PURPOSE: While influx of chemoembolic agents into the hepatic falciform artery (HFA) from the hepatic artery can cause supraumbilical skin rash, epigastric pain and even skin necrosis, the significance of a patent HFA in patients undergoing radioembolization is not completely clear. Furthermore, the presence of tracer in the anterior abdominal wall seen in (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) images, which is generally performed prior to radioembolization, has been described as a sign of a patent HFA. The aim of this retrospective study was to evaluate the incidence and consequences of (99m)Tc-MAA accumulation in the anterior abdominal wall, indicating a patent HFA, in patients undergoing radioembolization of liver tumours. METHODS: A total of 224 diagnostic hepatic angiograms combined with (99m)Tc-MAA SPECT/CT were acquired in 192 patients with different types of cancer, of whom 142 were treated with a total of 214 radioembolization procedures. All patients received a whole-body scan, and planar and SPECT/CT scans of the abdomen. Only patients with extrahepatic (99m)Tc-MAA accumulation in the anterior abdominal wall were included in this study. Posttreatment bremsstrahlung SPECT/CT and follow-up results for at least 3 months served as reference standards. RESULTS: Tracer accumulation in the anterior abdominal wall was present in pretreatment (99m)Tc-MAA SPECT/CT images of 18 patients (9.3%). The HFA was found and embolized by radiologists before treatment in one patient. In the remaining patients radioembolization was performed without any modification in the treatment plan despite the previously mentioned extrahepatic accumulation. Only one patient experienced abdominal muscle pain above the navel, which started 24 h after treatment and lasted for 48 h without any skin changes. The remaining patients did not experience any relevant side effects during the follow-up period. CONCLUSION: Side effects after radioembolization in patients with tracer accumulation in the anterior abdominal wall on (99m)Tc-MAA scans indicating a patent HFA are neither common nor severe. Thus, there is no absolute need for prophylactic embolization of the HFA or modification of the treatment plan if the HFA is not detectable on angiography.

Kidney Failure and Abdominal Discomfort as Initial Signs of Extramedullary Acute Myelogenous Leukemia.

Although rare, acute myelogenous leukemia (AML) can include extramedullary manifestations, sometimes presenting as a solid tumor called a myeloid sarcoma. Myeloid sarcoma can be the cause of the initial presenting complaint before AML diagnosis, or may be detected as a sign of disease-relapse after treatment. Here, we report a case in which the initial presentation included abdominal discomfort and signs of kidney failure. Further investigation revealed signs of unilateral hydronephrosis. Due to a diagnostic delay, the patient was diagnosed with AML with extramedullary manifestation only after the development of full-blown leukemia. Biopsy of the compressive tumor confirmed an extramedullary myeloid sarcoma, and [18F]-FDG-PET/CT proved useful for patient diagnosis and follow-up. This case report illustrates the importance of thorough examination and diagnosis, as a serious underlying disease with a rare cause can debut with an unusual presentation.

E-learning for medical imaging specialists: introducing blended learning in a nuclear medicine specialist course.

BACKGROUND: While e-learning has become an important tool in teaching medical students, the training of specialists in medical imaging is still dominated by lecture-based courses. PURPOSE: To assess the potential of e-learning in specialist education in medical imaging. MATERIAL AND METHODS: An existing lecture-based five-day course in Clinical Nuclear Medicine (NM) was enhanced by e-learning resources and activities, including practical exercises. An anonymized survey was conducted after participants had completed and passed the multiple choice electronic course examination. RESULTS: Twelve out of 15 course participants (80%) responded. Overall satisfaction with the new course format was high, but 25% of the respondents wanted more interactive elements such as discussions and practical exercises. The importance of lecture handouts and supplementary online material such as selected original articles and professional guidelines was affirmed by all the respondents (92% fully, 8% partially), while 75% fully and 25% partially agreed that the lectures had been interesting and relevant. CONCLUSION: E-learning represents a hitherto unrealized potential in the education of medical specialists. It may expedite training of medical specialists while at the same time containing costs.

Bone metastases in GEP-NET: response and long-term outcome after PRRT from a follow-up analysis.

Bone metastases of gastroenteropancreatic neuroendocrine tumors (GEP NET) can be associated with pain and a poor prognosis. Peptide receptor radionuclide therapy (PRRT) has been shown to be effective against this tumor manifestation. This study represents an update of the therapeutic assessment of PRRT with (177)Lu-octreotate in GEP NET patients with bone metastases focusing on potential predictors for impaired outcome and overall survival.We retrospectively analyzed a consecutive subgroup of n=68 patients with bone metastases (BM) of GEP NET treated with (177)Lu-octreotate (4 intended cycles at 3 monthly intervals; mean activity per cycle, 8.1 GBq). Baseline characteristics, including age, performance status, tumor origin, tumor load, plasma chromogranin A (CgA), and neuron-specific enolase (NSE) were analyzed regarding the impact on tumor regression (modified M.D. Anderson criteria) and survival of the patients. Survival analyses were performed using Kaplan-Meier curves, log-rank test at a significance level of p <0.05, and Cox proportional hazards model for uni- and multivariate analyses. Median follow-up was 48 months. The observed response of BMs consisted of complete remission in 2 (2.9%), partial remission in 23 (33.8%), minor response in 8 (11.8%), stable disease in 26 (38.2%), and progressive disease in 8 (13.2%) patients. Median time-to-progression (TTP) of BMs and overall survival (OS) were 35 mo (95% CI: 25-45) and 51 mo (95% CI: 38-64), respectively. Patients with responding BMs survived significantly longer than other patients (median 56 mo vs. 39 mo, p=0.034). NSE >15 ng/ml (p=0.002) and Ki67 index >10% (p=0.008) were associated with shorter overall survival. BM of GEP NET are effectively controlled by PRRT with a long median progression-free survival of approx. 3 years. Non-regression of BM, high proliferation rate and increased plasma NSE at baseline are predictive of shorter survival. However, this study confirms that poor patient condition (Karnofsky-Index ≤70%) and multifocality of BM (>10 lesions) do not affect outcome efficacy, further encouraging the use of PRRT in advanced bone metastatic disease.

90Y Radioembolization after radiation exposure from peptide receptor radionuclide therapy.

UNLABELLED: Previous radiation therapy of the liver is a contraindication for performing (90)Y microsphere radioembolization, and its safety after internal radiation exposure through peptide receptor radionuclide therapy (PRRT) has not yet been investigated. METHODS: We retrospectively assessed a consecutive cohort of 23 neuroendocrine tumor (NET) patients with liver-dominant metastatic disease undergoing radioembolization with (90)Y microspheres as a salvage therapy after failed PRRT. Toxicity was recorded throughout follow-up and reported according to Common Terminology Criteria for Adverse Events (version 3). Radiologic (response evaluation criteria in solid tumors), biochemical, and symptomatic responses were investigated at 3 mo after treatment, and survival analyses were performed with the Kaplan-Meier method (log-rank test, P < 0.05). RESULTS: The median follow-up period after radioembolization was 38 mo (95% confidence interval, 18-58 mo). The mean previous cumulative activity of (177)Lu-DOTA-octreotate was 31.8 GBq. The mean cumulative treatment activity of (90)Y microspheres was 3.4 ± 2.1 GBq, administered to the whole liver in a single session (n = 8 patients), in a sequential lobar fashion (n = 10 patients), or to only 1 liver lobe (n = 5 patients). Only transient, mostly minor liver toxicity (no grade 4) was recorded. One patient (4.3%) developed a gastroduodenal ulcer (grade 2). The overall response rates for radiologic, biochemical, and symptomatic responses were 30.4%, 53.8%, and 80%, respectively. The median overall survival was 29 mo (95% confidence interval, 4-54 mo) from the first radioembolization session and 54 mo (95% confidence interval, 47-61 mo) from the first PRRT cycle. A tumor proliferation index Ki-67 greater than 5% predicted shorter survival (P = 0.007). CONCLUSION: Radioembolization is a safe and effective salvage treatment option in advanced NET patients with liver-dominant tumor burden who failed or reprogressed after PRRT. The lack of relevant liver toxicity despite high applied (90)Y activities and considerable previous cumulative activities of (177)Lu-octreotate is noteworthy and disputes internal radiation exposure by PRRT as a toxicity risk factor in subsequent radioembolization.

Significance of oral administration of sodium perchlorate in planning liver-directed radioembolization.

UNLABELLED: (99m)Tc-macroaggregated albumin ((99m)Tc-MAA) scanning precedes radioembolization of the liver to detect extrahepatic shunting to the lung or gastrointestinal tract. Despite strict preventive measures in the production of (99m)Tc-MAA and in scanning protocols, the images frequently show a gastric concentration of free (99m)Tc-pertechnetate, hindering accurate evaluation of the gastroduodenal region. Our aim was to evaluate whether oral administration of sodium perchlorate (NaClO(4)) before (99m)Tc-MAA scanning will improve its accuracy by blocking free (99m)Tc-pertechnetate gastric uptake. METHODS: In 144 patients, 171 diagnostic hepatic angiograms combined with a (99m)Tc-MAA scan were performed; 86 angiograms were performed after oral administration of NaClO(4), and 85 were performed without this premedication. Clinical follow-up, esophagogastroduodenoscopy, and angiography served as reference standards. RESULTS: (99m)Tc-MAA studies showed tracer uptake in the gastric region of 25 patients who did not receive NaClO(4). The uptake was interpreted as a free (99m)Tc-pertechnetate concentration in 21 studies and as a (99m)Tc-MAA accumulation in 4 studies. In 5 patients with a free (99m)Tc-pertechnetate concentration, aberrant vessels were detected in angiographic reexamination, and 3 patients developed gastrointestinal ulcer. In 7 studies, gastric findings viewed pretherapeutically as free (99m)Tc-pertechnetate were retrospectively classified as equivocal. Of the patients receiving NaClO(4), 2 showed gastric accumulation of (99m)Tc-MAA but no equivocal or free (99m)Tc-pertechnetate. Oral administration of NaClO(4) increased the negative predictive value and accuracy of the test concerning the detection of gastric perfusion from 68% and 69%, respectively, to 93% and 94%, respectively. CONCLUSION: Oral administration of NaClO(4) before the test angiogram with (99m)Tc-MAA resulted in effective avoidance of free (99m)Tc-pertechnetate concentration and, consequently, of equivocal findings in the gastroduodenal region. This technique increased test accuracy and reporter confidence, saved time in reviewing the angiograms, and can improve treatment planning and reduce therapeutic side effects.