(18)F-fluorodeoxyglucose uptake by positron emission tomography in patients with IPAH and CTEPH.

Pulmonary arterial hypertension (PAH) is driven by pathologies associated with increased metabolism such as pulmonary revascularization, vasoconstriction and smooth muscle cell proliferation in pulmonary artery wall. 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) is an imaging technique sensitive to glucose metabolism and might be considered as a non-invasive method for diagnosis due to significant role of inflammation in idiopathic pulmonary artery hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study aimed to investigate the role of PET/CT imaging of patients with IPAH and CTEPH as an alternative diagnosis method. Demographic characteristics, FDG uptake in lungs, pulmonary artery and right ventricle (RV) of 17 patients (10 IPAH, 7 CTEPH), and 30 controls were evaluated. PET scanning, 6-min walk test, pro-BNP level, right heart catheterization of patients were performed both at the onsert and after 6-month PAH specific treatment. IPAH and CTEPH patients had significantly higher left lung FDG (p = 0.006), right lung FDG (p = 0.004), right atrial (RA) FDG (p < 0.001) and RV FDG (p < 0.001) uptakes than controls. Positive correlation was detected between the RV FDG uptake and the mean pulmonary artery pressure (mPAP) (r = 0.7, p = 0.012) and between the RA FDG uptake and the right atrial pressure (RAP) (r = 0.5, p = 0.02). Increased RV FDG and RA FDG uptakes predicts the presence of pulmonary hypertension and correlates with mPAP and RAP, respectively, which are important indicators in the prognosis of PAH. Further studies are required whether FDG PET imaging can be used to diagnose or predict the prognosis of pulmonary hypertension.

An anthropomorphic body phantom for the determination of calibration factor in radionuclide treatment dosimetry.

The aim of this study is to create an inhomogeneous human-like phantom, whose attenuation and scattering effects are similar to the human body, as an alternative to the homogeneous phantoms traditionally used in calibration factor (CF) determination. The phantom was designed to include the thorax, abdomen and upper pelvis regions sized to represent a 75-kg male with a body mass index of 25. Measurements using Lu-177 with 50- and 100-mL lesion volumes were performed using inhomogeneous anthropomorphic body phantom (ABP) and homogeneous NEMA PET body phantom. There was a difference of 5.7% of Calibration Factor including attenuation and scatter effect between ABP and NEMA PET body phantom. Because it better reflects the attenuation and scatter effect, it is recommended to use a human-like inhomogeneous phantom for determination of CF instead of a homogeneous phantom.

A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study.

PURPOSE: To investigate the relationships between tumor absorbed dose (TAD) or normal tissue absorbed dose (NTAD) and clinical outcomes in hepatocellular carcinoma (HCC) treated with yttrium-90 glass microspheres. METHODS: TARGET was a retrospective investigation in 13 centers across eight countries. Key inclusion criteria: liver-dominant HCC with or without portal vein thrombosis, < 10 tumors per lobe (at least one ≥ 3 cm), Child-Pugh stage A/B7, BCLC stages A-C, and no prior intra-arterial treatment. Multi-compartment pre-treatment dosimetry was performed retrospectively. Primary endpoint was the relationship between ≥ grade 3 hyperbilirubinemia (such that > 15% of patients experienced an event) without disease progression and NTAD. Secondary endpoints included relationships between (1) objective response (OR) and TAD, (2) overall survival (OS) and TAD, and (3) alpha fetoprotein (AFP) and TAD. RESULTS: No relationship was found between NTAD and ≥ grade 3 hyperbilirubinemia, which occurred in 4.8% of the 209 patients. The mRECIST OR rate over all lesions was 61.7%; for the target (largest) lesion, 70.8%. Responders and non-responders had geometric mean total perfused TADs of 225.5 Gy and 188.3 Gy (p = 0.048). Probability of OR was higher with increasing TAD (p = 0.044). Higher TAD was associated with longer OS (HR per 100 Gy increase = 0.83, 95% CI: 0.71-0.95; p = 0.009). Increased TAD was associated with higher probability of AFP response (p = 0.046 for baseline AFP ≥ 200 ng/mL). CONCLUSION: Real-world data confirmed a significant association between TAD and OR, TAD and OS, and TAD and AFP response. No association was found between ≥ grade 3 hyperbilirubinemia and NTAD. TRIAL REGISTRATION NUMBER: NCT03295006.

An Analysis for Therapeutic Doses of Patients with Neuroendocrine Tumor Treated with Lutetium 177 (177Lu)-DOTATATE.

Background: The aim of this study is to clarify the critical organs that limit treatment scheme and also evaluate the validity of currently used critical organ threshold values in neuroendocrine tumor (NET) patients, receiving peptide receptor radionuclide therapy (PRRT) with Lutetium 177 (177Lu)-DOTATATE. Materials and Methods: Thirty-six NET patients (ages 16-73 years) who received 177Lu-DOTATATE treatment were evaluated retrospectively in this study. Dosimetric calculations were made using medical internal radionuclide dose method. For calculation of organ doses, Internal Dose Assessment at Organ Level/Exponential Modelling 1.1 software program was used. Follow-up data were used to determine the organ failure. Results: A total of 141 cycles and mean of 3.91 (±1.33) cycles were applied to the patients. A mean of 691 mCi (±257 mCi) 177Lu-DOTATATE infusion in total and a dose between 70 and 200 mCi per treatment was applied to patients. Seven of 36 patients reached 23 Gy renal dose limit. In these patients, although kidney doses were between 23 and 29 Gy, there was no diminution in renal functions during follow-up. Two of 36 patients reached total bone marrow dose of 2 Gy limit. Bone marrow suppression did not develop in these patients. Conclusion: The critical organs that seem to affect the treatment scheme in PRRT with 177Lu-DOTATATE are kidney and bone marrow. Although there are established threshold levels, derived from radiotherapy experience, more studies are needed to clarify these dose limits in systemic radionuclide therapies such as PRRT.

The position of transarterial chemoembolization with drug-eluting beads and yttrium-90 transarterial radioembolization in patients with hepatocellular carcinoma: Consensus statements from a Delphi-method expert panel in Turkey.

PURPOSE: Clinical studies conducted in different geographic regions using different methods to compare transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) have demonstrated discordant results. Meta-analyses in this field indicate comparable overall survival (OS) with TACE and TARE, while reporting a longer time to progression and a higher downstaging effect with TARE treatment. In terms of isolated procedure costs, treatment with TARE is 2 to 3 times more, and in some countries even more, expensive than TACE. However, relevant literature indicates that TARE is more advantageous compared to TACE regarding the need for repeat procedures, costs of complication management, total hospital stay and quality of life. Heterogeneity of hepatocellular carcinoma (HCC) patients as well as the shortcomings of clinical classifications, randomized clinical trials and cost-effectiveness studies make it difficult to choose between treatment alternatives in this field. As in other countries, these challenges lead to differences in treatment choice across different centers in Turkey. METHODS: The present expert panel used two round modified Delphi method to investigate the resources and clinical parameters referenced while selecting patients for drug-eluting beads (DEB)-TACE and TARE treatment modalities in Turkish clinical practice. The cost-effectiveness parameters and comparisons of these treatments have also been evaluated at a prediction level. RESULTS: The panelists stated that they most commonly use the BCLC staging system for the management of HCC patients in Turkey. However, they did not find any of the staging systems or treatment guidelines sufficient enough for their clinical practice in terms of covering the down-staging intent of treatments. Since living donor transplant preference is higher in Turkey than the rest of the Western countries, down-staging treatments are thought to be more prioritized in Turkey than that in other Western countries. The panelists reached a consensus that TARE may provide improved OS and reduce the number of repeat procedures compared to DEB-TACE in intermediate-stage patients with a single tumor spanning a diameter above 5 cm who experience recurrence after previous treatment with TACE and most TACE-naïve patient groups in intermediate stage. CONCLUSION: Based on the consensus on OS and the number of procedures, the panelists assumed that TARE would be more cost-effective than DEB-TACE in most groups of TACE-naïve patients in intermediate stage and in those with a single tumor spanning a diameter above 5 cm. It was also stated that the predicted cost-effectiveness advantage of TARE could be more pronounced in patients with a tumor diameter greater than 7 cm.

Safety of Fibroblast Activation Protein-Targeted Radionuclide Therapy by a Low-Dose Dosimetric Approach Using 177Lu-FAPI04.

OBJECTIVES: This study is set out to estimate the radiation-absorbed doses to normal organs and tumor tissue using low-dose 177Lu-FAPI04 dosimetry to determine the safety and theranostic potential of fibroblast activation protein-targeted radionuclide therapy. PATIENTS AND METHODS: Four patients with metastatic advanced-stage cancer were administered low-dose 177Lu-FAPI04 for dosimetry measurements. Data acquisition for dosimetry of normal organs and tumors was performed by whole-body and 3D SPECT/CT imaging at 4, 24, 48, and 96 hours after administering 177Lu-FAPI04. Blood samples were drawn at 5, 15, 30, 60, 60, 120, and 180 minutes, and at 24, 48, and 96 hours for bone marrow dosimetry calculations. RESULTS: Mean absorbed doses per megabecquerel were 0.25 ± 0.16 mGy (range, 0.11-0.47 mGy), 0.11 ± 0.08 mGy (range, 0.06-0.22 mGy), and 0.04 ± 0.002 mGy (range, 0.04-0.046 mGy) for kidneys, liver, and bone marrow, respectively. The respective maximum estimated amount of radioactivity to reach radiation-absorbed dose limits were 120.9 ± 68.6 GBq, 47.5 ± 2.8 GBq, 397.8 ± 217.1 GBq, and 52.4 ± 15.3 GBq for kidneys, bone marrow, liver, and total body. The mean absorbed dose per megabecquerel was 0.62 ± 0.55 mGy for bone metastases, 0.38 ± 0.22 mGy for metastatic lymph nodes, 0.33 ± 0.21 mGy for liver metastases, and 0.37 ± 0.29 for metastatic soft tissue. The maximum absorbed dose in a tumor lesion was 1.67 mGy/MBq for bone, 0.6 mGy/MBq for lymph node, 0.62 mGy/MBq for liver, and 1 mGy/MBq for soft tissue. CONCLUSIONS: The mean absorbed dose to organs at risk with 177Lu-FAPI04 is reasonably low, allowing for low tumor-absorbed dose rates by administering a higher dose. Further research on optimizing therapeutic efficacy and using alternative radioisotopes is necessary, along with an individualized dosimetric approach.

Y90 selective internal radiation therapy and peptide receptor radionuclide therapy for the treatment of metastatic neuroendocrine tumors: combination or not?

BACKGROUND: Peptide receptor radionuclide therapy and selective internal radiation therapy are effective radionuclide therapy modalities for unresectable metastatic neuroendocrine tumor patients that cannot be controlled with somatostatin analogs. The present study is intended to evaluate the therapeutic efficacy and toxicity of the combined therapy of selective internal radiation therapy and peptide receptor radionuclide therapy and stand-alone selective internal radiation therapy in patients with neuroendocrine tumor, a liver-dominant disease. METHODS: This cohort consists of 27 patients with metastatic neuroendocrine tumor and liver-dominant disease. They were grouped as the patients who were treated with selective internal radiation therapy for unresectable liver metastasis (n = 15) and the patients who received a combination of selective internal radiation therapy and peptide receptor radionuclide therapy (n = 12) for hepatic and extrahepatic metastasis. Treatment efficacy and treatment-associated toxicity were retrospectively assessed in both groups. RESULTS: The objective treatment response and stable disease were found in 13 patients (86.6%) in the selective internal radiation therapy group and eight patients (66.6%) in the selective internal radiation therapy + peptide receptor radionuclide therapy group. The median overall survival rate was found to be 34.9 months, in the selective internal radiation therapy group and 67.5 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.217). The median progression-free survival data was not reached, and the mean values of progression-free survival were 53.1 ± 9.9 months in the selective internal radiation therapy group, and 27.2 ± 5.9 months in the selective internal radiation therapy + peptide receptor radionuclide therapy group (P = 0.561). Temporary lymphopenia was the most common side effect. Grade 1-2 hepatotoxicity was observed to be 6.6% in the selective internal radiation therapy group, while it was not observed in selective internal radiation therapy + peptide receptor radionuclide therapy group. CONCLUSIONS: In the neuroendocrine tumors with liver-dominant metastatic disease, personalized selective internal radiation therapy and peptide receptor radionuclide therapy and their combinations result in increased survival rates. Selective internal radiation therapy alone could be an effective treatment in patients with liver-limited and -dominant disease.

Prognostic factors of radiosynovectomy in haemophilia patients with inhibitors: Survival analysis in a 19-year period.

INTRODUCTION: People with haemophilia (PwH) with inhibitors have an increased risk of bleeding and early development of progressive arthropathy. Radiosynovectomy (RS) has been effective in dramatically reducing the frequency of haemarthroses. In the present study, the mid- and long-term results of the efficacy of RS in PwHs with inhibitors and prognostic factors that influence success and failure of RS were presented. MATERIAL AND METHOD: Radiosynovectomy was performed in 51 joints of 22 PwHs with inhibitors diagnosed with chronic haemophilic synovitis between January 2000 and December 2018. Two patients were lost to follow-up and four joints were excluded. Number of bleeding episodes within the pre- and post-treatment 6 months were documented. Treatment failure was defined as need for repeat RS injection. RESULTS: Results of 47 RS were analysed. The mean bleeding frequency of the joints was 11.2 ± 6.2 (median 9) within the last 6 months in the pre-treatment evaluation. After the treatment, the mean bleeding frequency of the joints decreased to 1.2 ± 2.8 (median 0) for first 6 months (P < .0001). The cumulative survival rate at 12 months was 87% and 78% at 36 months. The receiver operating characteristic (ROC) curve analysis revealed that cut-off points of 12 bleeding episodes within the last 6 months (sensitivity, 71.4; specificity, 81.8 P = .0022) and an inhibitor titre of 63.4 BU (sensitivity, 57.1; specificity, 75.8; P = .31) were threshold levels for a predisposition for failure. CONCLUSION: Radiosynovectomy is an effective and safe intervention in PwHs with inhibitors. Bleeding frequency is a prognostic marker for the success of RS treatment. Patients who have more than 12 bleeding episodes within the last 6 months before the RS treatment have a higher rate of failure.

Evidence of Prostate-Specific Membrane Antigen Expression in Hepatocellular Carcinoma Using 68Ga-PSMA PET/CT.

Prostate specific membrane antigen (PSMA) expression has been demonstrated in tumor neovasculature of many solid tumors, including hepatocellular carcinoma (HCC). The purpose of this study is to evaluate PSMA expression in patients with HCC. MATERIALS AND METHODS: Nineteen HCC patients who underwent F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) as part of restaging procedure also underwent Ga-PSMA PET. F-FDG PET and Ga-PSMA findings were compared visually as well as quantitatively using maximized standardized uptake values (SUVmax). RESULTS: FDG was positive in 15 patients while 16 patients demonstrated PSMA expression. The only extrahepatic finding was one metastatic lymph node detected by both tracers. Mean SUVmax of liver lesions on FDG PET/CT was 8.3 ± 2.3 and mean tumor to background ratio was 2.3 ± 1.5. Respective values for Ga-PSMA PET/CT were 17.4 ± 9 and 3.3 ± 2.2. On visual and quantitative evaluation uptake was higher with PSMA in nine patients and higher with FDG in four patients. PSMA and FDG activity were similar in three patients. One of the FDG positive patients was PSMA negative whereas two patients were PSMA positive but FDG negative. Heterogeneous uptake pattern was observed in three patients. Comparison of mean SUVmax and T/B values between PET studies revealed no statistically significant difference (P > 0.1). The mean survival was 25 months (range: 18-32 months) and SUVmax of PSMA (P = 0.05) and FDG (P = 0.012) showed medium strength of correlation with overall survival. CONCLUSION: PSMA expression in advanced HCC can be demonstrated by Ga-PSMA PET but is not superior to FDG PET however it could be useful for identifying patients with limited therapeutic options.

Relationships between serum PSA levels, Gleason scores and results of 68Ga-PSMAPET/CT in patients with recurrent prostate cancer.

AIM: To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga68-PSMA PET/CT in patients with recurrent PCa. METHODS: A total of 109 consecutive patients (median age 71 years; range 48-89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented. RESULTS: In 91(83.4%) patients at least one lesion characteristic for PCa was detected by68Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2-640) ng/ml.There was a significant difference between 68Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative 68Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases [oligometastasis, (n = 20); multimetastasis, (n = 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative 68Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911-0.993). CONCLUSIONS: 68Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and 68Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive 68Ga-PSMA PET/CT results.

An Incidental Solitary Plasmacytoma of Bone Mimicking Neuroendocrine Tumor Metastasis on 68Ga-DOTATATE Positron Emission Tomography/Computed Tomography.

A 54-year-old woman with suspicion of neuroendocrine tumor (NET) was referred for 68Ga-DOTATATE positron emission tomography/computed tomography (CT) imaging due to clinical findings. A well-defined osteolytic lesion on the corpus of the third lumbar vertebra was evident on CT images with mild uptake of 68Ga-DOTATATE, which led to suspicion of NET metastasis. Histopathologic examination revealed solitary plasmacytoma of the bone. The patient received local external radiotherapy for plasmacytoma. This case indicatesthat other diseases expressing somatostatin receptors may be inaccurately reported as tumor recurrence and highlights the importance of meticulous evaluation of positive findings.

Do 18F-FDG PET/CT findings have a relationship with histopathological and immunohistochemical factors of breast cancer in men?

PURPOSE: We aimed to investigate the relationship between histopathological and immunohistochemical features of male breast cancer (MBC) and comprehensive fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) parameters. METHODS: Fifteen male patients with newly diagnosed breast cancer who underwent F-FDG PET/CT were included in the study. Maximum and average standardized uptake value (SUVmax and SUVavg), metabolic total volume, and total lesion glycolysis (TLG) were compared with the histopathological and immunohistochemical findings of patients. In addition, metabolic tumor-node-metastases (TNM) staging was performed following the determination of metastatic axillary lymph nodes and tumor size by F-FDG PET/CT and verified by histopathological evaluation. RESULTS: There were no significant differences between all groups classified on the basis of histopathological and immunohistochemical parameters for SUVmax, SUVavg, TLG, and metabolic total volume. The only difference was found in patients with distant metastases and stage IV. SUVmax, SUVavg, and TLG were higher in patients with distant metastases compared with patients without distant metastases (P: 0.005, 0.011, and 0.042, respectively). Strong correlations were found between metabolic TNM staging and histopathological TNM staging (for T stage; r: 0.590, P: 0.021, N stage; r: 0.694, P: 0.002, TNM stage; r: 0.835, P: 0.002). In addition, no differences were found with any metabolic F-FDG PET/CT parameters in survival. CONCLUSION: Although no correlation was found between metabolic parameters and groups categorized on the basis of histopathological or immunohistochemical features, F-FDG PET/CT is a reliable imaging modality to determine tumor size, axillary lymph node involvement, and metabolic TNM staging of MBC. In addition, none of those metabolic F-FDG PET/CT parameters predicted survival in MBC.

Outcomes of first-line long-acting octreotide treatment in non-functional, advanced gastroenteropancreatic neuroendocrine tumors.

PURPOSE: Benefits of somatostatin analogues have been mostly studied in mixed samples of patients including both functional and non-functional neuroendocrine tumors. This study aimed to examine the response of patients with non-functional metastatic or inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that received first-line treatment with the somatostatin analogue octreotide LAR. METHODS: The medical records of 23 patients with locally inoperable or metastatic non-functional neuroendocrine tumors who received octreotide LAR (long acting release) treatment were retrospectively reviewed for clinical data and disease course. All patients had received first-line octreotide LAR 30 mg for 4 weeks. Progression free survival (PFS) and overall survival (OS) were the primary and secondary endpoints, respectively. RESULTS: All patients were followed for a median of 47 months. Mean PFS and OS were 25.0 ± 3.4 months (95% CI: 18.4-31.5) and 71.3 ± 9.5 months (95% CI: 52.7-89.9), respectively, with an estimated 5-year OS of 58%. Patients with ≤ 25% of hepatic tumor load had better PFS when compared to patients with >25% hepatic tumor load (32.2 ± 6.2 vs 19.4 ± 2.7 months, p=0.043). During treatment, the following adverse events developed: skin reaction (N=1, 4.3%), cholestasis (N=1, 4.3%), grade 1 diarrhea (N=1, 4.3%), and newly onset diabetes (N=3; 13.0%). CONCLUSION: Octreotide LAR seems to be an effective treatment option with acceptable tolerability for patients with well-differentiated non-functional GEP-NETs. Survival benefits warrant further testing in future large-scale prospective trials.

Selective Spleen Scintigraphy in the Evaluation of Accessory Spleen/Splenosis in Splenectomized/Nonsplenectomized Patients and the Contribution of SPECT Imaging.

OBJECTIVE: We aimed to evaluate the results of selective spleen scintigraphy (SSS) and contribution of SPECT imaging to planar imaging in splenectomized and nonsplenectomized patients. METHODS: We retrospectively examined 112 SSSs of 96 patients. The patients were divided into two groups as splenectomized group (SP) and non-splenectomized group (NSP). The findings were evaluated by comparing the results of surgery,computerized tomography (CT), ultrasonography (USG) and magnetic resonance imaging (MRI). In addition, whether or not differences existed between the results of SPECT and planar imaging was determined. RESULTS: Of 66 scintigraphies performed in the NSP group, 3 (5%) had positive, 3 (5%) had suspicious and 60 (90%) had negative results. In the NSP group, 28 patients underwent surgery and 12 accessory spleens were removed. Only 3 of these tissues were detected by scintigraphy. Of 46 patients in the SP group, 26 (57%) had positive findings whereas 20 (43%) had negative scintigraphies. Twelve accessory spleens/splenosis were removed surgically in 10 patients with a positive SSS in the SP group. There were no false positive results in both groups of patients who underwent surgery. There was no significant difference between the results of SSS, USG and CT. Of 39 patients to whom SPECT were performed, 10 had positive results both with planar and SPECT imaging. On the other hand, 26 patients, 3 of whom had suspected findings in SPECT images, demonstrated negative results when evaluated with both imaging methods. Remaining 3 were considered suspicious by only SPECT images for the hilar area. CONCLUSION: SSS has high specificity in the detection of accessory spleens/splenosis. The sensitivity of SSS is low in the NSP group,but higher in the SP group. There is no contribution of SPECT imaging to planar imaging.

Favorable survival time provided with radioembolization in hepatocellular carcinoma patients with and without portal vein thrombosis.

PURPOSE: Although some algorithms are defined for the treatment of advanced hepatocellular carcinoma (HCC), the expected survival cannot be prolonged as it is intended. Treatment options for this group of patients are limited. Radioembolization with yttrium-90 (Y-90) microspheres is a new treatment modality, which has also been used in advanced HCC patients. In this study, the authors aimed to assess the efficiency of radioembolization with Y-90 microspheres and evaluate prognostic factors that influence the survival in HCC patients. PATIENTS AND METHODS: The authors retrospectively evaluated data of 29 HCC patients who had radioembolization with Y-90 resin or glass microspheres between May 2009 and January 2014. Patient survival was evaluated by using the Kaplan-Meier method. Subgroup comparisons in terms of age, sex, prior treatment status before radioembolization, tumor burden, time between HCC diagnosis and radioembolization, alpha fetoprotein (AFP) level before radioembolization, presence of portal vein thrombosis (PVT), hepatopulmonary shunt ratio, extrahepatic disease burden, multifocality, bilaterality, Eastern Cooperative Oncology Group (ECOG), Child-Pugh, and Barcelona Clinic Liver Cancer (BCLC) status were performed to evaluate prognostic factors that affected survival. RESULTS: There were 29 HCC patients (mean age: 59.9±12 years) in the patient group. Grade ≤1 and 2 ECOG performance status was present in 19 and 10 patients, respectively. Twenty-six patients were classified as Child A and 3 patients as Child B. According to the BCLC staging system, 18 patients were in stage B and 11 patients were in stage C. PVT was diagnosed in 12 patients. The median follow-up was 15 months. The median overall survival was 17±2.5 months. BCLC disease stage was a significant prognostic variable associated with survival, but other parameters, even the presence of PVT, were found to be not significantly affecting survival. CONCLUSION: Radioembolization provides favorable survival time in advanced HCC patients. Even patients who are not eligible for transarterial chemoembolization due to PVT can have radioembolization without a decrease in the median survival time.

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.

The value of somatostatin receptor imaging with In-111 Octreotide and/or Ga-68 DOTATATE in localizing Ectopic ACTH producing tumors.

OBJECTIVE: We aimed to evaluate the value of somatostatin receptor imaging (SRI) with In-111 octreotide and Ga-68 DOTATATE in localizing ectopic ACTH producing tumors. METHODS: Nineteen patients who had In-111 octreotide somatostatin receptor scintigraphy (SRS) and/or Ga-68 DOTATATE PET-CT to localize ectopic ACTH producing tumors between the years 2000 and 2012 were included retrospectively in our study. The results of SRI were compared with clinical onset, radiological findings and surgical data of the patients. RESULTS: Sixteen In-111 octreotide SRS and five Ga-68 DOTATATE PET-CT were performed in 19 patients. In eight out of 19 patients, ectopic ACTH secretion site could be detected. In five patients, SRS showed pathologic uptake. In four of these patients, surgery revealed pulmonary carcinoid tumors and in one patient pancreatic neuroendocrine tumor. In one patient, Ga-68 DOTATATE PET-CT revealed pathologic uptake in lung nodule which came out to be pulmonary carcinoid tumor. In another patient who had resection of metastases of atypical carcinoid tumor prior to scans, new metastatic foci were detected both with SRS and Ga-68 DOTATATE PET-CT imaging. In one patient, although SRS was negative, CT which was performed three years later showed a lung nodule diagnosed as pulmonary carcinoid tumor. In 11 patients, ectopic ACTH secretion site could not be detected. In 10 of those patients, scintigraphic and radiological imaging did not show any lesions and in one patient, Ga-68 DOTATATE PET-CT was false positive. CONCLUSION: SRI has a complementary role with radiological imaging in localizing ectopic ACTH secretion sites. PET-CT imaging with Ga-68 peptide conjugates is a promising new modality for this indication. CONFLICT OF INTEREST: None declared.

Initial outcome after selective intraarterial radionuclide therapy with yttrium-90 microspheres as salvage therapy for unresectable metastatic liver disease.

PURPOSE: The aim of the study was to retrospectively evaluate the potential benefit on survival outcomes of selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 microspheres as a salvage therapy in liver metastasis of different tumors. MATERIAL AND METHODS: Sixty-one patients who had unresectable liver metastases from colorectal carcinoma (n=23), neuroendocrine tumor (NET; n=12), cholangiocarcinoma (n=9), and others (n=17) received yttrium-90 microspheres. All patients were treated in a salvage setting with an 11-month mean follow-up. Early metabolic treatment response was evaluated by 18F-Fluorodeoxyglucose positron emission tomography (FDG PET-CT) in the sixth week after treatment. RESULTS: Of the 61 patients, 32 were alive at the end of the study; median overall survival (OS) was 17.0 ± 2.5 months (95% confidence interval: 11.9-22.0). A subset analysis of colorectal and noncolorectal groups demonstrated median OS rates of 14.0 ± 5.8 and 17.0 ± 4.8 months, respectively (p=0.543). The mean OS for patients with NET and cholangiocarcinoma was 29.0 ± 3.1 months and 17.7 ± 3.2 months, respectively (p=0.010). According to the early metabolic treatment response, the mean OS of responder and nonresponder groups was 32.0 ± 5.6 months and 11.4 ± 2.1 months, respectively (p=0.054). Eastern Cooperative Oncology Group performance status <1 (p=0.018) and chemotherapy-naive patients (p=0.008) showed significant correlation with survival. CONCLUSION: SIRT is an effective treatment option for patients with metastatic liver disease in a salvage setting with acceptable toxicity.

Role of red blood cell scintigraphy for determining the localization of gastrointestinal bleeding.

BACKGROUND: We aimed to evaluate the role of Tc-99m labeled red blood cell (RBC) scintigraphy for determination of localization of gastrointestinal system (GIS) bleeding. METHODS: Fifty-seven cases (27 females, 30 males; mean age 43.9±24; range 1 to 91 years) who referred to our clinic between 1995-2010 were evaluated for determination of localization of GIS bleeding with RBC scintigraphy. Prior to scintigraphy, gastroscopy in 51, colonoscopy in 45, and angiography in 9 patients were performed. RESULTS: RBC scintigraphies were positive and negative in 31 and 26 patients, respectively. Positive scintigraphic findings were obtained within the 1st hour of dynamic imaging in 19 patients, within the 1st-4th hour static images in 7, and within the 4th-24th hour images in 5 patients. Fourteen patients underwent surgical exploration. In 13 patients, the surgery confirmed the diagnosis by RBC scintigraphy (accuracy: 92.8%). Of 43 patients without surgical exploration, 12 had anemia due to iron deficiency and their scintigraphic evaluation were negative. Four patients died and in 27 patients, GIS bleeding ceased spontaneously or with conservative measures. CONCLUSION: Scintigraphy should be the primary tool for accurate diagnosis of patients with active GIS bleeding. Positive dynamic images obtained within the first hour of imaging may be more accurate for demonstrating bleeding localization and a good predictor of requirement of surgical exploration.