Update of PSMA Theranostics in Prostate Cancer: Current Applications and Future Trends.

There is now an increasing trend for targeting cancers to go beyond early diagnosis and actually improve Progression-Free Survival and Overall Survival. Identifying patients who might benefit from a particular targeted treatment is the main focus for Precision Medicine. Radiolabeled ligands can be used as predictive biomarkers which can confirm target expression by cancers using positron emission tomography (PET). The same ligand can subsequently be labeled with a therapeutic radionuclide for targeted radionuclide therapy. This combined approach is termed "Theranostics". The prostate-specific membrane antigen (PSMA) has emerged as an attractive diagnostic and therapeutic target for small molecule ligands in prostate cancer. It can be labeled with either positron emitters for PET-based imaging or beta and alpha emitters for targeted radionuclide therapy. This review article summarizes the important concepts for Precision Medicine contributing to improved diagnosis and targeted therapy of patients with prostate cancer and we identify some key learning points and areas for further research.

Role of Combined 68Ga DOTA-Peptides and 18F FDG PET/CT in the Evaluation of Gastroenteropancreatic Neuroendocrine Neoplasms.

This review article summarizes the role of combined 68Ga DOTA-peptides and 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the evaluation of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Patients with GEP-NENs can initially present themselves to a gastroenterologist or endocrinologist rather than cancer specialist; hence, it is vital for a wider group of clinicians to be familiar with the range of tests available for the evaluation of these patients. The role of PET scanning by using 68Ga DOTA-peptides has a high sensitivity in the diagnosis of GEP-NENs and to guide patient selection for treatment with somatostatin analogues (SSA) and/or peptide receptor radionuclide therapy (PRRT). The loss of somatostatin receptor (SSTR) expression was found to be associated with an increased glucose metabolism in cells. However, the routine use of SSTR targeted radiotracers in combination with 18F-FDG to evaluate glucose utilization in GEP-NENs is still debatable. In our opinion, in patients with NENs, 18F-FDG PET should be performed in the case of a negative or slightly positive 68Ga DOTA-peptides PET scan for assessing the dedifferentiation status, to guide correct therapeutic strategy and to evaluate the prognosis. The approach of combined receptor and metabolic imaging can improve diagnostic accuracy, especially considering the heterogeneity of these lesions. Therefore, 68Ga DOTA-peptides and 18F-FDG PET should be considered complementary in patients with GEP-NENs.

In-hospital mortality of hepatorenal syndrome in the United States: Nationwide inpatient sample.

BACKGROUND: Hepatorenal syndrome (HRS) is a life-threatening condition among patients with advanced liver disease. Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited. AIM: To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States. METHODS: We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014 (weighted sample of 23973 admissions). The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality. We estimated odds ratios from multi-level mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality. RESULTS: Overall hospital mortality was 32%. Hospital mortality decreased from 44% in 2005 to 24% in 2014 (P < 0.001), while there was an increase in the rate of liver transplantation (P = 0.02), renal replacement therapy (P < 0.001), length of hospital stay (P < 0.001), and hospitalization cost (P < 0.001). On multivariable analysis, older age, alcohol use, coagulopathy, neurological disorder, and need for mechanical ventilation predicted higher hospital mortality, whereas liver transplantation, transjugular intrahepatic portosystemic shunt, and abdominal paracentesis were associated with lower hospital mortality. CONCLUSION: Although there was an increase in resource utilizations, hospital mortality among patients admitted for HRS significantly improved. Several predictors for hospital mortality were identified.

Outcomes following I-131 treatment with cumulative dose exceeding or equal to 600 mCi in differentiated thyroid carcinoma patients.

To evaluate treatment outcomes following radioactive iodine (RAI) treatment with a cumulative dose of ≥≥600 mCi in differentiated thyroid carcinoma (DTC) patients, a retrospective review of medical records was done in 176 DTC patients with a cumulative dose of ≥600 mCi from January 1993 to December 2013. All patients were followed up for at least 2 years after receiving 600 mCi of I-131 treatment. Remission criteria were no clinical and imaging evidence of disease and low serum thyroglobulin levels during thyroid-stimulating hormone suppression of <0.2 ng/ml or of <1 ng/ml after stimulation in the absence of interfering antibodies. A total of 176 patients were included in the study: 137 - papillary thyroid cancer, 29 - follicular thyroid cancer, 9 - mixed papillary and follicular thyroid cancer, and 1 - Hurthle cell carcinoma. Most of the patients (118, 67%) had locoregional metastasis, whereas 48 patients (27%) had distant metastases at presentation. The median cumulative dose was 900 mCi (range: 600-2200 mCi). The mean follow-up period was 82.84 ± 42.41 months. Only 16 patients (9.1%) met remission criteria at the end of treatment. The rest of patients (160, 90.9%) were not remitted: stable disease in 94 (53.4%), at least 1 metastasis without I-131 uptake in 34 (19.3%), progressive disease in 21 (11.9%), and death during the whole follow-up period in 11 (6.3%). Two patients (1.1%) developed second primary malignancy. Eighteen cases were suspected of bone marrow suppression (14 cases [7.9%] had anemia and 5 cases [2.8%] had neutropenia). Seven patients (3.9%) developed permanent salivary gland dysfunction. Although the complications after receiving RAI treatment with a cumulative dose of ≥≥600 mCi were low and not severe, the patients with remission were in <10%. Our study suggests that the decision to administer further treatments should be made on an individual basis because beneficial effects may be controversial.

Rate of kidney function decline and factors predicting progression of kidney disease in type 2 diabetes mellitus patients with reduced kidney function: A nationwide retrospective cohort study.

Currently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD are limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline estimated glomerular filtration rate (eGFRs) between 15 and 59 mL/min/1.73 m2 . This study was composed of a nationwide retrospective cohort of adult T2DM patients from 831 public hospitals in Thailand during the year 2015. T2DM patients with CKD stages 3 and 4 were followed up, until development of CKD stage 5, requirement of chronic dialysis, loss to follow-up, death, or 31 May 2018, whichever came first. Cox proportional hazard regression was utilized for analysis. A total of 8464 participants were included; 30.4% were male. The mean age was 69 ± 10 years. The mean eGFR was 45 ± 11 mL/min/1.73 m2 . The incidence of CKD stage 5 or the need for chronic dialysis was 16.4 per 1000 person-years. The annual rate of eGFR decline during a mean follow-up of 29 months was -2.3 mL/min/1.73 m2 ; 14.4% had a rapid decline in eGFR. The risk factors associated with progression to CKD stage 5 or the need for chronic dialysis were diabetes duration, systolic blood pressure, serum uric acid, albuminuria, and baseline eGFR. Conversely, older age and the use of renin-angiotensin aldosterone system blockade were associated with decreased risks for rapid CKD progression and incidence CKD stage 5 or dialysis. This study identifies multiple predictive risk factors that support a multifaceted approach to prevent progression of advanced CKD.

Correlation between Standardized Uptake Value of 68Ga-DOTA-NOC Positron Emission Tomography/Computed Tomography and Pathological Classification of Neuroendocrine Tumors.

The aim of our study was to correlate tumor uptake of 68Ga-DOTA-NOC positron emission tomography/computed tomography (PET/CT) with the pathological grade of neuroendocrine tumors (NETs). 68Ga-DOTA-NOC PET/CT examinations in 41 patients with histopathologically proven NETs were included in the study. Maximum standardized uptake value (SUVmax) and averaged SUV SUVmean of "main tumor lesions" were calculated for quantitative analyses after background subtraction. Uptake on main tumor lesions was compared and correlated with the tumor histological grade based on Ki-67 index and pathological differentiation. Classification was performed into three grades according to Ki-67 levels; low grade: Ki-67 <2, intermediate grade: Ki-67 3-20, and high grade: Ki-67 >20. Pathological differentiation was graded into well- and poorly differentiated groups. The values were compared and evaluated for correlation and agreement between the two parameters was performed. Our study revealed negatively fair agreement between SUVmax of tumor and Ki-67 index (r = -0.241) and negatively poor agreement between SUVmean of tumor and Ki-67 index (r = -0.094). SUVmax of low-grade, intermediate-grade, and high-grade Ki-67 index is 26.18 ± 14.56, 30.71 ± 24.44, and 6.60 ± 4.59, respectively. Meanwhile, SUVmean of low-grade, intermediate-grade, and high-grade Ki-67 is 8.92 ± 7.15, 9.09 ± 5.18, and 3.00 ± 1.38, respectively. As expected, there was statistically significant decreased SUVmax and SUVmean in high-grade tumors (poorly differentiated NETs) as compared with low- and intermediate-grade tumors (well-differentiated NETs). SUV of 68Ga-DOTA-NOC PET/CT is not correlated with histological grade of NETs. However, there was statistically significant decreased tumor uptake of 68Ga-DOTA-NOC in poorly differentiated NETs as compared with the well-differentiated group. As a result of this pilot study, we confirm that the lower tumor uptake of 68Ga-DOTA-NOC may be associated with aggressive behavior and may, therefore, result in poor prognosis.

Systematic Review on the Accuracy of Positron Emission Tomography/Computed Tomography and Positron Emission Tomography/Magnetic Resonance Imaging in the Management of Ovarian Cancer: Is Functional Information Really Needed?

Ovarian cancer (OC) often presents at an advanced stage with frequent relapses despite optimal treatment; thus, accurate staging and restaging are required for improving treatment outcomes and prognostication. Conventionally, staging of OC is performed using contrast-enhanced computed tomography (CT). Nevertheless, recent advances in the field of hybrid imaging have made positron emission tomography/CT (PET/CT) and PET/magnetic resonance imaging (PET/MRI) as emerging potential noninvasive imaging tools for improved management of OC. Several studies have championed the role of PET/CT for the detection of recurrence and prognostication of OC. We provide a systematic review and meta-analysis of the latest publications regarding the role of molecular imaging in the management of OC. We retrieved 57 original research articles with one article having overlap in both diagnosis and staging; 10 articles (734 patients) regarding the role of PET/CT in diagnosis of OC; 12 articles (604 patients) regarding staging of OC; 22 studies (1429 patients) for detection of recurrence; and 13 articles for prognostication and assessment of treatment response. We calculated pooled sensitivity and specificity of PET/CT performance in various aspects of imaging of OC. We also discussed the emerging role of PET/MRI in the management of OC. We aim to give the readers and objective overview on the role of molecular imaging in the management of OC.

Comparison of renal uptake of 68Ga-DOTANOC PET/CT and estimated glomerular filtration rate before and after peptide receptor radionuclide therapy in patients with metastatic neuroendocrine tumours.

BACKGROUND: Ga-DOTA-conjugated peptide PET/CT is used widely for diagnosis and treatment planning in patients with neuroendocrine tumours. As nephrotoxicity is a major limiting factor during peptide receptor radionuclide therapy (PRRT), it is important to evaluate renal function before, during and after treatment. The aim of our study is to compare renal uptake of Ga-DOTANOC and estimated glomerular filtration rate (eGFR) before and after PRRT and to identify any surrogate indicators of renal toxicity. MATERIALS AND METHODS: We included 64 Ga-DOTANOC PET/CT examinations in 32 patients with metastatic neuroendocrine tumours who underwent Y-DOTATATE therapy between May 2013 and April 2016. An amino acid infusion was used routinely for renal protection. Renal uptake was quantified as mean standardized uptake value (SUVmean) of both kidneys after background subtraction. eGFR was calculated using standard software. The values were compared and evaluation of correlation and agreement between the two parameters was performed. RESULTS: Our study showed fair agreement between SUVmean of the kidneys on Ga-DOTANOC PET/CT and eGFR (r=0.33) before PRRT and poor agreement between SUVmean of the kidneys and eGFR (r=0.16) after PRRT. As expected, there was a statistically significant difference in eGFR before and after PRRT (mean difference=4.41±9.24 ml/min/1.73 m, P=0.01). On comparison of renal uptake before and after PRRT, the post-PRRT scans showed a statistically significant increase in uptake (SUVmean=-1.25±3.17, P=0.03). CONCLUSION: Renal quantitative analysis on Ga-DOTANOC PET/CT before and after PRRT showed no significant correlation with the eGFR. However, there was a statistically significant increase in the renal uptake of Ga-DOTANOC, with a higher uptake after PRRT. As a result of this pilot study, we suggest that the higher renal uptake in the post-PRRT scans could be an indicator of early renal dysfunction and could have implications for further cycles of PRRT. Further longitudinal studies and further evaluation of such data across multiple centres are suggested.

Severe hyponatremia: a comorbidity with I131 therapy in a patient with papillary thyroid cancer.

Hyponatremia is the most common electrolyte disorder in hospitalized patients, especially in elderly patients, in which morbidity varies widely in severity. A 64-year-old Thai woman with papillary thyroid cancer who developed hypothyroid state after thyroid hormone withdrawal for preparation of 1-131 treatment, had severe hyponatremia within the day of 1-131 administration. It is possible that the combination of old age, hypothyroidism, severe nausea and vomiting, and inappropriate secretion of antidiuretic hormone (SIADH) may all have precipitated the severe hyponatremia in the presented case.