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 µg/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.

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

PURPOSE: The aim of this study was to identify baseline features that predict outcome in (223)Ra therapy. METHODS: We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with (223)Ra. 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 (223)Ra 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 (223)Ra we evaluated: the total number of radium cycles (RaTot), the PSA doubling time (PSADT), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide. RESULTS: A significant reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the (223) Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSADT (HR = 8.22; p < 0.001). RaTot, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (p ≤ 0.008), PFS (p ≤ 0.003), and BeFS (p ≤ 0.020). RaTot, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (p ≤ 0.001) as well as Hb (p < 0.001) and EBRT (p = 0.009). On multivariable analysis, only RaTot and abiraterone remained significantly associated with OS (p < 0.001; p = 0.033, respectively), PFS (p < 0.001; p = 0.041, respectively), and BeFS (p < 0.001; p = 0.019, respectively). Additionally, RaTot (p = 0.027) and EBRT (p = 0.013) remained significantly associated with BMF. CONCLUSION: Concomitant use of abiraterone and (223)Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF.

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

UNLABELLED: 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.

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

UNLABELLED: The purpose of this study was to evaluate outcome after (223)Ra dichloride therapy ((223)Ra) and to determine whether skeletal tumor burden on whole-body (18)F-fluoride PET/CT can be used as a predictive biomarker of survival in patients treated with (223)Ra. METHODS: Forty-two patients with hormone-refractory prostate cancer underwent (223)Ra 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 (223)Ra (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 (223)Ra.

Is imaging the extremities with PEM feasible? A novel application for a high-resolution positron emission scanner.

INTRODUCTION: Positron emission mammography (PEM) has better spatial resolution than positron emission tomography/computed tomography (PET/CT), or PET/CT. We evaluated the feasibility of extremity imaging with PEM using PET as a standard. METHODS/MATERIALS: Fourteen patients underwent sequential PET/CT and PEM. RESULTS/DISCUSSION: PEM visualized with equal or improved resolution all of the lesions identified on PET/CT. It often provided additional information such improved uptake localization and also visualized activity in an adjacent structures that was not seen on PET/CT or magnetic resonance imaging. We believe PEM can image the extremities in diseases like melanoma, arthritis and osteomyelitis and patients with metallic hardware.

Correlation of PUV and SUV in the extremities while using PEM as a high-resolution positron emission scanner.

OBJECTIVE: Owing to its unique configuration of two adjustable plate detectors positron emission mammography, or PEM, could theoretically also function as a high-resolution positron emission scanner for the extremities or neck. PEM quantitates its activity via a "PEM uptake value," or PUV, and although its relationship to the standardized uptake value, or SUV, has been demonstrated in the breasts, to our knowledge there are no studies validating PUV in other sites such as the extremities. MATERIALS AND METHODS: This was a retrospective chart review of two separate protocols of a total of 15 patients. The patients all had hypermetabolic lesions in the extremities or neck on imaging with PET/CT and were sent after their PET/CT to PEM for further imaging. Owing to the sequential nature of these examinations no additional radiotracer was administered. RESULTS: Spearman's rank order correlation was calculated between the PUVmax obtained from PEM images, and the SUVmax for all. Spearman's rank order correlation for all sites was 0.42, which is not significantly different from 0 (p = 0.13). When neck lesions were excluded from the group, there was a strong and statistically significant correlation between PUVmax and SUVmax, with Spearman's rank correlation of 0.73, and significantly different from 0 (p = 0.0068). DISCUSSION: The correlation of PUV and SUV in the extremities indicates the potential use of PEM as a semiquantitative, high-resolution positron emission scanner and warrants further investigation, especially in the realms of disease processes that often present in the extremities, such as melanoma, osteomyelitis, and arthritis, as well as playing a role in the imaging of patients with metallic hardware post-limb salvage surgery.

Implementation of automated tube current modulation in PET/CT: prospective selection of a noise index and retrospective patient analysis to ensure image quality.

UNLABELLED: Automated tube current modulation (ATCM) has been shown to be a useful tool for reducing CT dose. However, its implementation can be complicated, because the correlation between noise index (NI) settings and noise production can change as parameters are manipulated. The goal was to create a methodology to prospectively select ATCM parameters and retrospectively ensure consistent image quality. METHODS: An anthropomorphic phantom was scanned at various NIs to determine a baseline NI versus image noise. The noise was measured in SDs of the CT number reported in Hounsfield units. A physician then reviewed 45 studies performed with the same fixed-tube-current protocol to obtain a preferred noise level. The noise level was compared with our phantom baseline scans to find a suitable NI value. This value was implemented in clinical operation. Then, the next 50 patient examinations were retrospectively reviewed to ensure that image quality was maintained to our physician's cutoff noise levels. Radiation dose reductions through tube current reduction were measured for all CT slices of each patient study. RESULTS: In the phantom study, tube current modulation was observed at an NI of 15. The preferred noise level established in the physician's review correlated with an NI of 20. In our postimplementation analysis, we found that our noise level was 10.75 SDs in Hounsfield units. CT dose reductions of up to 52% were seen. CONCLUSION: We were able to prospectively select an NI for ATCM CT by correlating phantom scans to a physician's preferred noise level while maintaining consistent image quality.

Positron emission tomography-computed tomography protocols for radiation therapy planning and therapy response assessment.

This article covers positron emission tomography-computed tomography (PET-CT) scan protocols for radiation therapy planning purposes and therapy response assessment. For radiation therapy planning PET-CT scans, protocols used will depend on the intended use of the PET-CT images in the radiation therapy planning. In general scans are performed on a flat radiation therapy pallet with the patient in the treatment position or closely approximating the treatment position. PET-CT protocols used in radiation therapy planning are typically otherwise very similar to diagnostic protocols. An important component in PET-CT imaging performed for therapy monitoring and assessment is consistency in patient preparation, image acquisition, and imaging processing of the baseline scan and subsequent therapy assessment scans.

Effect of colony-stimulating factor and conventional- or high-dose chemotherapy on FDG uptake in bone marrow.

PURPOSE: Granulocyte or granulocyte-macrophage colony stimulating factor (CSF), usually used in conjunction with chemotherapy, may interfere with the( 18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) reading. The purpose of this study is to evaluate the effects of CSF, conventional-or high-dose chemotherapy on bone marrow FDG uptake. METHODS: Two hundred and forty-one FDG PET scans obtained in 163 patients with lymphoma and no pathologically and radiologically proven bone marrow involvement were analyzed. The standardized uptake value (SUV) of each patient's spine was measured. RESULTS: Among patients with no recent history of CSF use, the average SUV in 36 patients with no history of chemotherapy was 1.60+/-0.34, that in 49 patients with a history of conventional-dose chemotherapy was 1.37+/-0.32, and that in 12 patients with a history of high-dose chemotherapy was 1.26+/-0.25 (P=0.008 and 0.002, respectively by Mann-Whitney U test). In 80 patients treated with conventional-dose chemotherapy and CSF, the average SUV after discontinuation of CSF was as follows: 0-7 days, 2.37+/-1.19; 8-14 days: 2.04+/-0.67; 15-21 days: 1.87+/-0.52; 22-30 days: 1.59+/-0.18; 31-90 days: 1.54+/-0.36. In 45 patients treated with high-dose chemotherapy and CSF, no significant increase in bone marrow uptake was seen in most of them. CONCLUSION: Bone marrow FDG uptake may be increased by CSF treatment and may be decreased by chemotherapy. In patients treated with conventional-dose chemotherapy and CSF, increased marrow uptake will return to the pretreatment value approximately 1 month after discontinuation of CSF.

The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors.

UNLABELLED: Gastrointestinal stromal tumors (GISTs) are gaining the interest of researchers because of impressive metabolic response to the targeted molecular therapeutic drug imatinib mesylate. Initial reports suggest an impressive role for (18)F-FDG PET in follow-up of therapy for these tumors. However, the role of (18)F-FDG PET versus that of CT has not been established. Therefore, we compared the roles of (18)F-FDG PET and CT in staging and evaluation of early response to imatinib mesylate therapy in recurrent or metastatic GIST. METHODS: The study included 54 patients who underwent (18)F-FDG PET and CT scans within 3 wk before initiation of imatinib mesylate therapy. Forty-nine of these patients underwent repeat scans 2 mo after therapy. The numbers of sites or organs containing lesions on (18)F-FDG PET and CT scans were compared. Corresponding lesions on (18)F-FDG PET and CT scans or those confirmed to be malignant in appearance by other imaging modalities or on follow-up were considered true positives. Lesions seen on (18)F-FDG PET or CT scans but not seen or confirmed to be of benign appearance with other imaging modalities or on follow-up were considered false positives. Measurements of the maximum standard uptake value (SUV) on (18)F-FDG PET scans and tumor size on CT scans were used for quantitative evaluation of early tumor response to therapy. RESULTS: A total of 122 and 114 sites and/or organs were involved on pretherapy (18)F-FDG PET and CT scans, respectively. The sensitivity and positive predictive values (PPVs) for CT were 93% and 100%; whereas these values for (18)F-FDG PET were 86% and 98%. However, the differences between these values for CT and (18)F-FDG PET were not statistically significant (P = 0.27 for sensitivity and 0.25 for PPV). This suggests comparable performance of (18)F-FDG PET and CT in staging GISTs. Repeat scans at 2 mo after therapy showed agreement between (18)F-FDG PET and CT scans in 71.4% of patients (57.1% having a good response to therapy and 14.3% lacking a response). Discrepant results between (18)F-FDG PET and CT were recorded for 28.6% of the patients. (18)F-FDG PET predicted response to therapy earlier than did CT in 22.5% of patients during a longer follow-up interval (4-16 mo), whereas CT predicted lack of response to therapy earlier than (18)F-FDG PET in 4.1%. One patient did not undergo long-term follow-up. These findings suggest that (18)F-FDG PET is superior to CT in predicting early response to therapy in recurrent or metastatic GIST patients. CONCLUSION: The performances of (18)F-FDG PET and CT are comparable in staging GISTs before initiation of imatinib mesylate therapy. However, (18)F-FDG PET is superior to CT in predicting early response to therapy. Thus, (18)F-FDG PET is a better guide for imatinib mesylate therapy.