Elba C. Etchebehere

Prognostic Factors in Patients Treated with 223Ra: The Role of Skeletal Tumor Burden on Baseline 18F-Fluoride PET/CT in Predicting Overall Survival

The purpose of this study was to evaluate outcome after 223Ra dichloride therapy (223Ra) and to determine whether skeletal tumor burden on whole-body 18F-fluoride PET/CT can be used as a predictive biomarker of survival in patients treated with 223Ra. Methods: Forty-two patients with hormone-refractory prostate cancer underwent 223Ra and a baseline fluoride PET/CT scan. Fluoride PET/CT parameters were generated, including maximum standardized uptake value (SUVmax) of the hottest lesion (hSUVmax), average SUV of disease (Mean10), and skeletal tumor burden indices of total fluoride skeletal metastatic lesion uptake (TLF10) and total volume of fluoride avid bone metastases (FTV10). Overall survival (OS) was the primary endpoint. Secondary endpoints were progression-free survival and skeletal-related event (SRE). Results: Skeletal tumor burden indices (TLF10 and FTV10) derived from fluoride PET/CT at baseline were highly correlated and significant independent predictors of OS (P = 0.0212; hazard ratio = 5.990; 95% confidence interval = 1.306–27.475). A TLF10 cutoff value of 8,000 discriminated survivors from nonsurvivors after 223Ra (with TLF10 values < 8,000, the median OS was not estimated, whereas with TLF10 > 8,000, the median OS was 6.67 mo). Visual analysis, Mean10, and hSUVmax were not predictors of OS or progression-free survival. Mean10 was found to be a significant univariate predictor of the odds of having an SRE (P = 0.0445; odds ratio = 1.30; 95% confidence interval = 1.006–1.681), with a Mean10 greater than 19 increasing the risk of SRE. Conclusion: Skeletal tumor burden on baseline fluoride PET/CT is a predictive biomarker of OS and the risk of an SRE in patients treated with 223Ra.

Determination of Skeletal Tumor Burden on 18F-Fluoride PET/CT

The purpose of this study was to define a method to assess skeletal tumor burden with 18F-labeled sodium fluoride PET/CT (18F-fluoride PET/CT) and evaluate the reproducibility of these measurements. Methods: Ninety-eight consecutive patients (90 men; mean age ± SD, 65.7 ± 14.2 y) underwent 158 18F-fluoride PET/CT scans for evaluation of skeletal metastatic disease. In order to determine the mean normal bone SUV, initially a 1-cm spheric volume of interest (VOI) was placed over 5 bone sites: T12, L5, sacrum, right iliac bone, and right femur. For each patient, the mean SUVmax for all sites was generated. Afterward, a threshold value of normal bone uptake was established. Subsequently, skeletal tumor burden was determined by generating volumetric data using a whole-body segmentation method. Any SUVmax below the normal threshold was excluded from analysis, as were VOIs not related to metastatic disease. Statistics for the remaining VOIs were then generated and defined as the skeletal metastatic tumor burden by 2 parameters: total lesion fluoride uptake above an SUVmax of 10 (TLF10) and fluoride tumor volume above an SUVmax of 10 (FTV10). TLF10 and FTV10 reproducibility was determined using 2 independent and experienced PET/CT interpreters analyzing a subset of 13 18F-fluoride PET/CT scans. Results: Mean (±SD) normal bone SUVmax was 6.62 ± 1.55 for T12, 6.11 ± 1.73 for L5, 4.59 ± 1.74 for sacrum, 5.39 ± 1.72 for right iliac bone, and 3.90 ± 1.57 for right femur. The mean normal SUVmax for all 543 sites was 5.32 ± 0.99. On the basis of these values, an SUVmax threshold of 10 was chosen to exclude normal bone from the volumetric calculations. Semiautomated measurements of TLF10 and FTV10 exhibited high interobserver reproducibility, within ±0.77% and ±3.62% of the interinterpreter average for TLF10 and FTV10, respectively. Conclusion: Determination of skeletal tumor burden with 18F-fluoride PET/CT is feasible and highly reproducible. Using an SUVmax threshold of 10 excludes nearly all normal bone activity from volumetric calculations.

Factors affecting 223Ra therapy: clinical experience after 532 cycles from a single institution

PurposeThe aim of this study was to identify baseline features that predict outcome in 223Ra therapy.MethodsWe retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with 223Ra. End points were overall survival (OS), progression-free survival (PFS), bone event-free survival (BeFS), and bone marrow failure (BMF). The following parameters were evaluated prior to the first 223Ra cycle: serum levels of hemoglobin (Hb), prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam radiation therapy (EBRT). During/after 223Ra we evaluated: the total number of radium cycles (RaTot), the PSA doubling time (PSADT), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide.ResultsA significant reduction of ALP (pu2009<u20090.001) and pain score (pu2009=u20090.041) occurred throughout the 223 Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR)u2009=u20093.79; pu2009<u20090.001] and decrease in PSADT (HRu2009=u20098.22; pu2009<u20090.001). RaTot, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (pu2009≤u20090.008), PFS (pu2009≤u20090.003), and BeFS (pu2009≤u20090.020). RaTot, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (pu2009≤u20090.001) as well as Hb (pu2009<u20090.001) and EBRT (pu2009=u20090.009). On multivariable analysis, only RaTot and abiraterone remained significantly associated with OS (pu2009<u20090.001; pu2009=u20090.033, respectively), PFS (pu2009<u20090.001; pu2009=u20090.041, respectively), and BeFS (pu2009<u20090.001; pu2009=u20090.019, respectively). Additionally, RaTot (pu2009=u20090.027) and EBRT (pu2009=u20090.013) remained significantly associated with BMF.ConclusionConcomitant use of abiraterone and 223Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF.

Assessing the role of 18F-FDG PET and 18F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis

PurposeTwelve years ago a meta-analysis evaluated the diagnostic performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of 18F-FDG PET/CT and determine if there is added value when compared to PET.MethodsA systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of 18F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included.ResultsOur meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60xa0%) malignant tumors and 306 benign lesions. The 18F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95xa0% highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively).Conclusion18F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.

Skeletal tumor burden on baseline 18F-fluoride PET/CT predicts bone marrow failure after 223Ra therapy

Purpose Determine if skeletal tumor burden on 18F-fluoride PET/CT (fluoride PET/CT) predicts the risk of bone marrow failure (BMF) after 223Ra dichloride therapy (223Ra). Methods Forty-one metastatic prostate cancer patients (43-89 years old; mean, 71 ± 9 years.) underwent fluoride PET/CT prior to 223Ra. Bone marrow failure was the primary end point and was defined as (1) development of hematologic toxicity (World Health Organization grade 3 or 4) associated with no recovery after 6 weeks or (2) death due to BMF after the last 223Ra dose. Bone marrow failure was correlated to fluoride PET/CT skeletal tumor burden (TLF10 [total lesion on fluoride PET/CT with SUVmax of 10 or greater]), use of chemotherapy, serum hemoglobin concentration, serum ALP, and serum prostate-specific antigen. Results The number of 223Ra cycles ranged from 2 to 6 (mean, 5). Of the 41 patients, 16 developed BMF (G3 = 12; G4 = 4). A significantly increased risk of developing BMF was observed in patients with TLF10 of 12,000 or greater (hazard ratio [HR], 11.09; P < 0.0001), hemoglobin of less than 10 g/dL (HR, 7.35; P = 0.0002), and AP > 146 UI/L (HR, 4.52; P = 0.0100). Neither concomitant (HR, 0.91; P = 0.88) nor subsequent use of chemotherapy (HR, 0.14; P = 0.84) increased the risk of BMF, nor was prostate-specific antigen greater than 10 &mgr;g/L (HR, 0.90; P = 0.86). Moreover, in a multivariable analysis, TLF10 was the only independent predictor of BMF (HR, 6.66; P = 0.0237). Conclusions 223Ra was beneficial and reduced the risk of death even in patients with a high skeletal tumor burden. Fluoride PET/CT is able to determine which patients will benefit from 223Ra and which will develop BMF.

18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients.

INTRODUCTIONnThe purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS).nnnMATERIALS AND METHODSnThirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12 ± 2 days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUV max) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS.nnnRESULTSnAmong the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% confidence interval (CI): 19.9-NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p = 0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG (p = 0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p = 0.01 and 0.03, respectively).nnnCONCLUSIONnNone of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS.

Gallium-68 in Medical Imaging

Over the past several years, Positron Emission Tomography (PET) imaging agents labeled with ;68Gallium (68Ga) have undergone a significant increase in clinical utilization. 68Ga is conveniently produced from a germanium-68/gallium-68 (68Ge/68Ga) generator. Because of the compact size and ease of use of the generator, 68Ga labeled compounds may be more cost-effective than PET radioisotopes that are cyclotron-produced. The convenient half-life of 68Ga (T1/2=68 min) provides sufficient radioactivity for various PET imaging applications, while delivering acceptable radiation doses to patients. This chapter summarizes the emerging clinical utilization of 68Ga-based radiotracers in medical imaging.

Whole-body 99mtc-octreotide Scintigraphy With Spect/ct to Detect Occult Tumor Inducing Paraneoplastic Osteomalacia

A 32-year-old woman presented with progressive myalgia, bone pain, fatigue, insufficiency hip fractures, high urine phosphate, and low serum phosphate and vitamin D levels. These findings were suggestive of oncogenic osteomalacia. A whole-body Tc-octreotide scintigraphy with SPECT/CT showed uptake on a sclerotic intramedullary lesion in the left medial tibia plateau. MRI depicted a solid lesion. The lesion was surgically removed; the patient became asymptomatic, and follow-up laboratory results normalized. Histopathologic examination revealed a vascular hemangiopericytoma-like tumor, positive for somatostatin receptor (SSR-2). Whole-body Tc-octreotide scintigraphy with SPECT/CT may detect occult oncogenic osteomalacia tumors.

The role of 18F-FDG PET/CT in diagnosis and staging of musculoskeletal soft tissue sarcomas

Adequate resection of soft tissue tumors reduces the risk of local recurrence and improves survival. Lymphatic dissemination of these tumors may occur and is related to worst prognosis. Proper staging thus improves patient management. Therefore, 18F-FDG PET/CT has increasingly been incorporated in the management of patients with soft tissue sarcomas, from grading, prognostic evaluation, diagnosis, staging and subsequent patient management. Formerly, soft tissue malignancies, after diagnosis, were staged with only chest radiographs and chest CT. Initial studies using solely dedicated PET scanners revealed a low sensitivity to detect metastases, especially in the detection of lung nodules. However, with the advent of 18F-FDG PET/CT hybrid imaging, there is growing evidence of the added benefit in performing this whole-body imaging modality in the work-up of these patients. In this review, we will discuss the incremental value of 18F-FDG PET/CT in the diagnosis and staging of soft tissue sarcomas, the patterns of uptake according to the different histological types as well as alert the nuclear medicine physician of the false-positive and false-negative situations.

Prognostic factors in patients treated with radium-223: the role of skeletal tumor burden on baseline 18F-fluoride-PET/CT in predicting overall survival

The purpose of this study was to evaluate outcome after 223Ra dichloride therapy (223Ra) and to determine whether skeletal tumor burden on whole-body 18F-fluoride PET/CT can be used as a predictive biomarker of survival in patients treated with 223Ra. Methods: Forty-two patients with hormone-refractory prostate cancer underwent 223Ra and a baseline fluoride PET/CT scan. Fluoride PET/CT parameters were generated, including maximum standardized uptake value (SUVmax) of the hottest lesion (hSUVmax), average SUV of disease (Mean10), and skeletal tumor burden indices of total fluoride skeletal metastatic lesion uptake (TLF10) and total volume of fluoride avid bone metastases (FTV10). Overall survival (OS) was the primary endpoint. Secondary endpoints were progression-free survival and skeletal-related event (SRE). Results: Skeletal tumor burden indices (TLF10 and FTV10) derived from fluoride PET/CT at baseline were highly correlated and significant independent predictors of OS (P = 0.0212; hazard ratio = 5.990; 95% confidence interval = 1.306–27.475). A TLF10 cutoff value of 8,000 discriminated survivors from nonsurvivors after 223Ra (with TLF10 values < 8,000, the median OS was not estimated, whereas with TLF10 > 8,000, the median OS was 6.67 mo). Visual analysis, Mean10, and hSUVmax were not predictors of OS or progression-free survival. Mean10 was found to be a significant univariate predictor of the odds of having an SRE (P = 0.0445; odds ratio = 1.30; 95% confidence interval = 1.006–1.681), with a Mean10 greater than 19 increasing the risk of SRE. Conclusion: Skeletal tumor burden on baseline fluoride PET/CT is a predictive biomarker of OS and the risk of an SRE in patients treated with 223Ra.