Factors Influencing Outcome Post-Radium-223 Dichloride in Castrate Resistant Prostate Cancer: A Review of Some Real-World Challenges.

Aim Radium-223 has been the first-approved targeted Alpha therapy agent. We retrospectively assessed different factors influencing the overall survival (OS) and patient management. Setting and Design Thirty-two metastatic castration-resistant prostate cancer (mCRPC) patients' hematological parameters, number of cycles, performance status, and toxicities were evaluated for OS. Radium 223 dichloride (Radium-223) was administered every 4 weeks for a maximum of six cycles. Primary and secondary end points were OS, progression free survival (PFS), therapy toxicities, change in performance status, biochemical response, and skeletal-related events (SREs). Materials and Methods Patients' median age was 77 years (range: 57-90 years) and median follow-up was 399 days (range: 5-1,761 days). A total of 163 cycles were administered in 32 patients, with 4 or less cycles in 8 patients (25%) and 5 or more cycles in 24 patients (75%). Among eight patients with 4 or less cycles, three patients died, of which two patients died due to neutropenic sepsis. Statistical Analysis Mann-Whitney test was used to compare the cycle groups; Spearman's correlation coefficient was used to see the relation of different variables with OS. Log rank test was used for group comparison while Kaplan-Meier survivorship was used for OS. Results Statistical correlation was seen between the number of cycles ( p =0.037) and hemoglobin ( p =0.028). Kaplan-Meier OS ( p =0.038) was correlated with the number of cycles (≤ 4 cycles and ≥ 5 cycles). OS was 173 days in patients with one to four cycles, 226 days in five cycles, and 493 days in six cycles. Myelosuppression leading to stopping of full six cycles was seen in 7 of 32 patients (22%) and significantly correlated to inferior OS ( p =0.048). Conclusion Higher number of Radium-223 cycles was seen to be associated with better OS. Prior myelosuppression was associated with poor OS. Patients with better hematological profile were more likely to complete the maximum number of the cycles with a better OS.

Indeterminate skeletal and lymph node lesion on 18F PSMA 1007 PET/CT scanning: lessons from a review at 12 months with PSMA-RADS.

AIMS OF THE STUDY: The study utilizes the prostate-specific membrane antigen-reporting and data system (PSMA-RADS) version 1.0 in a real-world patient scenario in the evaluation of equivocal lesions using the PSMA-RADS categorization for patient management and communication in multidisciplinary team (MDT) meetings. METHODS: A retrospective analysis of 203 patients who had 18F PSMA PET/CT for either restaging or staging over 12 months was undertaken. The scans were evaluated for local disease, lymph node involvement and distant metastases. The scan findings were classified as suspicious for metastases, and equivocal and benign lesions. Experience with PSMA ligand imaging was considered while classifying the lesions, equivocal lesions were assessed with PSMA-RADS and followed up with complementary imaging and/or clinical follow-up assessment or MDT for further patient management. RESULTS: A total of 91 of 203 patients had equivocal lesions. Follow-up assessment was performed in 47 of 91 patients with imaging ( n = 36) or MDT discussion ( n = 11).On follow-up imaging ( n = 36), equivocal lesion was seen in skeletal lesions ( n = 24), pelvic lymph nodes ( n = 6), both skeletal and pelvic nodes ( n = 4), hilar and mediastinal lymph nodes ( n = 1) and spleen ( n = 1). The patients were reclassified as benign, metastatic with few lesion remained equivocal. Overall follow-up assessment impacted clinical management in 47% patients. CONCLUSION: 18F PSMA PET/CT may show equivocal lesions; many of them in the skeleton, a small proportion of which are ultimately proven metastatic. In contrast, a higher proportion of the equivocal nodes in the pelvis end up being metastatic on follow-up. A structured reporting with PSMA-RADS grading helps in the proper classification of lesions and standardization of reports.

Tubercular Spondylitis: A Rare Complication of BCGosis Masquerading as Metastasis on 18F-PSMA-1007 PET/CT.

ABSTRACT: BCGosis is a rare complication of intravesical BCG immunotherapy as adjuvant therapy for urinary bladder cancer manifesting in the form of disseminated tuberculosis or organ-specific tuberculosis, rarely involving the vertebra. PSMA is overexpressed in prostate cancer but also expressed in a variety of benign and malignant conditions. We present a patient with incidental detection of abnormal uptake in a vertebral lesion during assessment of prostate cancer with 18F-PSMA PET/CT, subsequently proven to be vertebral osteitis, likely due to BCG immunotherapy. The case highlights the role of interdisciplinary patient assessment to confirm nature of abnormal foci on 18F-PSMA PET/CT.

Incidental detection of Os acromiale mimicking a fracture on 18F-Fluoride PET-CT.

Os acromiale represents an unfused accessory centre of ossification of the acromion of scapula. It may cause shoulder impingement, rotator cuff tear or degenerative acromio-clavicular joint disease. A 38-year-old male with history of degenerative disc disease presented with persistent backache. MRI of the lumbar spine had earlier showed left paracentral disc protrusion of L5/S1 vertebrae impinging the left S1 nerve root for which the patient underwent fluoroscopic guided nerve root block. Due to persistent bilateral sciatica and worsening leg pain a decompression surgery was planned. A bone scan was requested to exclude other causes of pain prior to surgery for which the patient underwent 18F- Fluoride PET-CT examination. We report a case of incidental detection of Os acromiale mimicking fracture. As the management strategy for both is quite different this case highlights the importance of correct recognition of this identity for appropriate management.

Renal Manifestation of Birt-Hogg-Dubé Syndrome Depicted by 18F-fludeoxyglucose Positron Emission Tomography/Computed Tomography in a Patient with Hurtle Cell Thyroid Malignancy.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant genetic disorder characterized by small papular skin lesions (fibrofolliculomas) causing susceptibility to kidney cancer, renal and pulmonary cysts, spontaneous pneumothoraces, and several noncutaneous tumors. We report a case of a 67-year-old woman, with a previous history of right hemithyroidectomy for adenomatous lesion. She presented with a swelling in the right thyroid bed that on subsequent biopsy revealed features of metastatic carcinoma. 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed for the detection of primary malignancy showed increased high-grade metabolic activity in the right supraclavicular soft tissue mass extending into the superior mediastinum. Moreover, on low-dose CT, there have been bilateral renal interpolar cortical lesions with mild metabolic activity. Given the fact that the right neck mass was highly unlikely to represent renal metastases in the absence of widespread metastatic disease, surgical excision of the right neck mass was performed. The histology of the mass was in keeping with hurtle cell thyroid carcinoma. In regard to renal lesions, bilateral partial nephrectomy was performed, which was consistent with chromophobe renal cell carcinoma, raising the suspicion of BHD that was confirmed by the subsequent genetic evaluation. It is well established that 18F-FDG PET/CT study is not an optimal modality for evaluation of renal lesions. However, careful assessment of the CT features in conjunction with the associated metabolic activity of the 18F-FDG PET component increases the diagnostic accuracy of PET/CT.

Skeletal Metastases and Benign Mimics on NaF PET/CT: A Pictorial Review.

OBJECTIVE: The aim of this article is to present examples in which sodium fluoride labelled with 18F (NaF) bone PET/CT would be a useful adjunct to guide complex clinical decisions about the staging, restaging, and treatment approach for patients with skeletal metastases and benign causes of NaF activity that can be mistaken for bone metastases. We present a pictorial review of selected cases of this cohort of patients. CONCLUSION: NaF PET/CT hybrid fusion imaging is extremely useful in identifying potential causes of pain in patients with malignancies that have an affinity for skeletal metastases. This technique can help detect bone metastases, in problem solving, and to direct appropriate management.

68Ga-DOTANOC Focal Pulmonary Activity With No Corresponding CT Abnormality.

A 28-year-old woman with medullary thyroid cancer treated with total thyroidectomy and bilateral central and right lateral neck nodal resection postoperatively had increasing calcitonin and carcinoembryonic antigen values. A Ga-DOTANOC PET/CT study performed showed tracer-avid disease in the neck, mediastinal, and hilar lymph nodes. However, there were 3 tracer-avid foci in the lungs bilaterally, suggestive of lung metastases but with no corresponding abnormalities on low-dose CT. A negative contrast-enhanced CT of the lungs along with clinical and radiological follow-up confirmed that the lung activity was artifactual, demonstrating the possibility of Ga-DOTANOC-avid iatrogenic pulmonary microembolism.

Higher extracellular fluid volume in women is concealed by scaling to body surface area.

OBJECTIVE: The objective was to assess body surface area (BSA) for scaling extracellular fluid volume (ECV) in comparison with estimated lean body mass (LBM) and total body water (TBW) across a range of body mass indices (BMI). METHODS: This was a multi-centre study from 15 centres that submitted raw data from routine measurement of GFR in potential kidney transplant donors. There were 819 men and 1059 women in total. ECV was calculated from slope-intercept and slope-only measurements of GFR. ECV was scaled using two methods: Firstly, division of ECV by the scaling variable (ratio method), and secondly the regression method of Turner and Reilly. Subjects were placed into five BMI groups: < 20, 20-24.9, 25-29.9, 30-34.9, and 35 + kg/m(2). LBM and TBW were estimated from previously published, gender-specific prediction equations. RESULTS: Ratio and regression scaling gave almost identical results. ECV scaled to BSA by either method was higher in men in all BMI groups but ECV scaled to LBM and TBW was higher in women. There was, however, little difference between men and women in respect to ECV per unit weight in any BMI group, even though women have 10% more adipose tissue. The relations between TBW and BSA and between LBM and BSA, but not between LBM and TBW, were different between men and women. CONCLUSION: Lean tissue in women contains more extracellular water than in men, a difference that is obscured by scaling to BSA. The likely problem with BSA is its insensitivity to body composition.

The reliability of glomerular filtration rate measured from plasma clearance: a multi-centre study of 1,878 healthy potential renal transplant donors.

PURPOSE: The objective of the study was to undertake a clinical audit of departmental performance in the measurement of glomerular filtration rate (GFR) using the coefficient of variation (CV) of extracellular fluid volume (ECFV) as the benchmark. ECFV is held within narrow limits in healthy subjects, narrower than GFR, and should therefore have a low CV. METHODS: Fifteen departments participated in this retrospective study of healthy renal transplant donors. Data were analysed separately for men (n ranged from 28 to 115 per centre; total = 819) and women (n = 28-146; 1,059). All centres used the slope-intercept method with blood sample numbers ranging from two to five. Subjects did not fast prior to GFR measurement. GFR was scaled to body surface area (BSA) and corrected for the single compartment assumption. GFR scaled to ECFV was calculated as the terminal slope rate constant and corrected for the single compartment assumption. ECFV/BSA was calculated as the ratio of GFR/BSA to GFR/ECFV. RESULTS: The departmental CVs of ECFV/BSA and GFR/BSA ranged from 8.3 to 25.8% and 12.8 to 21.9%, respectively, in men, and from 9.6 to 21.1% and 14.8 to 23.7%, respectively, in women. Both CVs correlated strongly between men and women from the same centre, suggesting department-specific systematic errors. GFR/BSA was higher in men in 14 of 15 centres, whereas GFR/ECFV was higher in women in 14 of 15 centres. Both correlated strongly between men and women, suggesting regional variation in GFR. CONCLUSION: The CV of ECFV/BSA in normal subjects is a useful indicator of the technical robustness with which GFR is measured and, in this study, indicated a wide variation in departmental performance.

Extracellular fluid volume and glomerular filtration rate in 1878 healthy potential renal transplant donors: effects of age, gender, obesity and scaling.

UNLABELLED: Aim. The aim of this study was to investigate the influence of age, gender, obesity and scaling on glomerular filtration rate (GFR) and extracellular fluid volume (ECV) in healthy subjects. METHODS: This is a retrospective multi-centre study of 1878 healthy prospective kidney transplant donors (819 men) from 15 centres. Age and body mass index (BMI) were not significantly different between men and women. Slope-intercept GFR was measured (using Cr-51-EDTA in 14 centres; Tc-99m-DTPA in one) and scaled to body surface area (BSA) and lean body mass (LBM), both estimated from height and weight. GFR was also expressed as the slope rate constant, with one-compartment correction (GFR/ECV). ECV was measured as the ratio, GFR to GFR/ECV. RESULTS: ECV was age independent but GFR declined with age, at a significantly faster rate in women than men. GFR/BSA was higher in men but GFR/ECV and GFR/LBM were higher in women. Young women (<30 years) had higher GFR than young men but the reverse was recorded in the elderly (>65 years). There was no difference in GFR between obese (BMI>30 kg/m2) and non-obese men. Obese women, however, had lower GFR than non-obese women and negative correlations were observed between GFR and both BMI and %fat. The decline in GFR with age was no faster in obese versus non-obese subjects. ECV/BSA was higher in men but ECV/LBM was higher in women. ECV/weight was almost gender independent, suggesting that fat-free mass in women contains more extracellular water. BSA is therefore a misleading scaling variable. CONCLUSION: There are several significant differences in GFR and ECV between healthy men and women.

Clinical significance of scintigraphic rapid gastric emptying.

OBJECTIVES: To analyse our results of gastric-emptying scintigraphy in relation to presenting symptoms, and examine in detail the clinical significance of rapid gastric emptying (RGE). MATERIALS AND METHODS: Results of 642 consecutive patients who underwent a solid gastric-emptying scintigraphy in our department over an 11-year period were retrospectively reviewed with particular emphasis to the presenting symptoms and the clinical profile of patients, especially of those who showed an accelerated pattern of emptying. RESULTS: Seventy (11%) patients were clinically suspected to have a RGE and 572 (89%) patients had presumed gastroparesis. Gastric emptying was found to be normal in 290 (45%), rapid in 182 (28%) and delayed in 170 (27%) patients. Normal, rapid and delayed gastric emptying were seen, respectively, in 17 (24%), 48 (69%) and five (7%) patients with the clinical suspicion of dumping and 273 (48%), 134 (23%) and 165 (29%) patients with suspected gastroparesis. The positive predictive value of clinical suspicion for RGE was 62%, whereas the positive predictive value of delayed gastric emptying was 29%. Of the 182 patients with RGE, 144 (79%) were found to have no obvious explanation for this result; reactive hypoglycaemia was present in a quarter of these patients, but diarrhoea was seen only in 3%. CONCLUSION: Upper gastrointestinal symptoms have a poor clinical specificity to the actual rate of gastric emptying on scintigraphy. Diarrhoea as a symptom does not appear to be associated frequently with RGE, but our results confirm its relationship with hypoglycaemia. The majority of patients with a rapid emptying on gastric-emptying scintigraphy have no identifiable cause for an accelerated motility. Scintigraphic gastric-emptying studies provide a reliable and noninvasive method of investigation in patients where conventional investigations have failed to establish the cause of upper gastrointestinal dysfunction.

Primary hepatic (extranodal) lymphoma: utility of [(18)F]fluorodeoxyglucose-PET/CT.

Primary hepatic lymphoma is extremely rare. Although the utility of fluorodeoxyglucose (FDG)-positron emission tomography (PET) for imaging extranodal lymphoma has been reported, there is very little literature describing its use in primary hepatic lymphoma. This case report demonstrates the effect of FDG-PET/computed tomography (CT) in a case of unifocal primary hepatic lymphoma and its usefulness in the assessment of treatment response.

What is the significance of solitary bony abnormalities on bone scintigrams of children with malignancy?

This investigation was undertaken to evaluate the significance of solitary bony abnormalities on bone scintigrams of children with known or suspected malignancy. A total of 215 bone scans were performed in 183 children in order to look for possible metastasis over a 10-year period. Forty-nine scans (22.8%) were found to have single lesions, of which 18 were due to uptake at the primary site and were excluded from further consideration. Of the remaining 31 lesions, 13 (41.9%) were confirmed as metastases, 17 lesions were proved to be benign, and 1 indeterminate. Solitary hot spots in children with known or suspected malignancy are common and therefore have to be taken seriously due to their higher malignant potential.

Utility of 111In-labelled leucocyte scintigraphy in patients with fever of unknown origin in an era of changing disease spectrum and investigational techniques.

BACKGROUND: (111)In-labelled leucocyte, imaging is often used to investigate patients with fever of unknown origin (FUO). Its diagnostic performance, however, has been variable and a broad range of sensitivities and specificities have been reported. The purpose of this investigation was to evaluate the usefulness of (111)In-labelled leucocytes scintigraphy in the detection of a cause of FUO in the light of a changing spectrum of diseases causing it and advances in investigational techniques. MATERIALS AND METHODS: Sixty-one patients with a clinical diagnosis of FUO underwent whole-body (111)In-troponolate-labelled leucocyte scintigraphy in our department over a 2-year period between February 2004 and February 2006. Of these, 54 patients were retrospectively reviewed to identify a cause of FUO. Other parameters such as C-reactive protein (CRP), leucocyte count and radiological findings were also evaluated. RESULTS: Leucocyte scintigraphy was found to be true positive in 12 patients, true negative in 24 patients, false positive in 10 patients and false negative in eight patients. The overall sensitivity of scintigraphy was 60%, specificity 71%, positive predictive value 55%, and negative predictive value 75%. There was no difference in the scintigraphic sensitivity between patients with spontaneous FUO and those with post-operative FUO although the latter showed a higher specificity and PPV. CRP and leucocyte count did not differ significantly between patients with true positive and true negative scintigrams. Overall, 83% of patients with abnormal radiological examinations had positive findings on scintigraphy and 87% of patients with negative findings on radiology had normal scintigraphy. CONCLUSION: Despite changes in disease spectrum and advances in investigational techniques, our results suggest that (111)In-leucocyte scintigraphy is still a useful technique in establishing the cause of FUO. A higher PPV of this test in post-operative situations makes it especially applicable in this category of patients. Equally, the higher NPV in patients with spontaneous FUO virtually excludes infection/inflammation. Finally, a higher pre-test probability based on the radiological tests seems to be important in the optimal use of leucocyte imaging.

Clinical and scintigraphic evaluation of insufficiency fractures in the elderly.

BACKGROUND: We have undertaken a retrospective review of 1017 Tc-methylene diphosphonate (Tc-MDP) skeletal scintigrams performed in patients over 70 years of age in order to identify those with insufficiency fractures. METHOD: Patients with the diagnosis of insufficiency fracture then underwent clinical follow-up of 2 years for mortality, which was compared to the national aged-matched population. RESULTS: One hundred and ninety-four patients were found to have scintigraphic evidence of fractures categorized as insufficiency fractures. Typical H-shaped sacral fractures were present in only 17 (4%) patients. Multiple sites of fracture were observed in 114 patients; the commonest being in the vertebrae. Radiological corroboration was available in 161 patients (83%) and bone scintigraphic findings were concordant with at least one of plain radiograph, computed tomography or magnetic resonance imaging in 107 (55%) patients. Of the 48 patients with insufficiency fracture who had undergone measurement for bone mineral density (BMD), 38 were found to have osteoporosis/osteopenia. Eighty-six patients died during the follow-up period, which was markedly higher than expected in the age-matched population. There was no definite relationship between the mortality in insufficiency fracture and BMD or the number of fractures. CONCLUSIONS: Our findings demonstrate that insufficiency fractures are common in the elderly and generally occur at multiple sites. The typical H-shaped fractures are rare and their absence should not lead to any mistaken diagnosis. The patients with insufficiency fractures appear to have poor survival but this does not appear to have any significant relationship with either BMD or the number of fractures. Finally, insufficiency fracture is an important diagnosis to make because survival may be improved if specific management is used.