Yttrium-90 Infusion: Incidence and Outcome of Delivery System Occlusions during 885 Deliveries.

PURPOSE: To evaluate the incidence, cause, and management of delivery system occlusions during yttrium-90 (90Y) microsphere infusions and to identify techniques to prevent occlusions. MATERIALS AND METHODS: A retrospective review was conducted of 885 consecutive radioembolization deliveries during 820 procedures (some with multiple deliveries) in 503 patients (mean age, 65 y; 293 male) performed between June 2001 and July 2013 at a single academic tertiary care hospital. Occlusions were reported prospectively, and procedural details were reviewed. Statistical analysis assessed associations between catheter occlusions and patient and procedural characteristics. RESULTS: Of 885 90Y microsphere deliveries, 11 resulted in occlusion (1.2%). Five occlusions were associated with contained leakage of radioactive material, and one was associated with a spill. Treatment was completed in the same day in 10 patients; repeat catheterization was required in five patients. One patient returned 1 week later to complete treatment. Occlusions were more frequent with deliveries of resin (11/492; 2.2%) versus glass (0/393; 0%) microspheres (P = .002). Occlusions were more likely to occur within the proximal portion of the delivery apparatus (P = .002). There was no significant relationship with any patient characteristics, and there was no improvement with operator experience. The most common cause of occlusion was resin microsphere delivery device failure. CONCLUSIONS: (90)Y microsphere delivery device occlusion is uncommon but does occur with resin microspheres. Understanding causes and how to troubleshoot can limit the incidence and detrimental effects.

Unresectable chemorefractory liver metastases: radioembolization with 90Y microspheres--safety, efficacy, and survival.

PURPOSE: To prospectively evaluate the safety, efficacy, and survival of patients with chemorefractory liver metastases who have been treated with yttrium 90 ((90)Y) glass microspheres. MATERIALS AND METHODS: Institutional review boards from two institutions approved the HIPAA-compliant study; all patients provided informed consent. One hundred thirty-seven patients underwent 225 administrations of (90)Y microspheres by using intraarterial infusion. Primary sites (origins) included colon, breast, neuroendocrine, pancreas, lung, cholangiocarcinoma, melanoma, renal, esophageal, ovary, adenocarcinoma of unknown primary, lymphoma, gastric, duodenal, bladder, angiosarcoma, squamous cell carcinoma, thyroid, adrenal, and parotid. Patients underwent evaluation of baseline and follow-up liver function and tumor markers and computed tomographic or magnetic resonance imaging. Patients were observed for survival from first treatment. Median survival (in days) and corresponding 95% confidence intervals were computed by using the Kaplan-Meier method. The log-rank statistic was used for statistical significance testing of survival distributions between various subgroups of patients. RESULTS: There were 66 men and 71 women. All patients were treated on an outpatient basis. Median age was 61 years. The mean number of treatments was 1.6. The median activity and dose infused were 1.83 GBq and 112.8 Gy, respectively. Clinical toxicities included fatigue (56%), vague abdominal pain (26%), and nausea (23%). At follow-up imaging, according to World Health Organization criteria, there was a 42.8% response rate (2.1% complete response, 40.7% partial response). There was a biologic tumor response (any decrease in tumor size) of 87%. Overall median survival was 300 days. One-year survival was 47.8%, and 2-year survival was 30.9%. Median survival was 457 days for patients with colorectal tumors, 776 days for those with neuroendocrine tumors, and 207 days for those with noncolorectal, nonneuroendocrine tumors. CONCLUSION: (90)Y hepatic treatments are well tolerated with acceptable toxicities; tumor response and median survival are promising.

Clinical implications of defining the gross tumor volume with combination of CT and 18FDG-positron emission tomography in non-small-cell lung cancer.

PURPOSE: To compare the planning target volume (PTV) definitions for computed tomography (CT) vs. positron emission tomography (PET) in non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A total of 21 patients with NSCLC underwent three-dimensional conformal radiotherapy planning. All underwent a staging F-18 fluorodeoxyglucose-position emission tomography (18FDG-PET) scan and underwent treatment simulation using CT plus a separate planning 18FDG-PET scan. Three sets of target volumes were defined: Set 1, CT volumes (CT tumor + staging PET nodal disease); Set 2, PET volumes (planning PET tumor {gross tumor volume (GTV) = [(0.3069 x mean standardized uptake value) + 0.5853])}; Set 3, composite CT-PET volumes (fused CT-PET tumor). Sets 1 and 2 were compared using a matching index. Three-dimensional conformal radiotherapy plans were created using the Set 1 (CT) volumes; and coverage of the Set 3 (composite) volumes was evaluated. Separate three-dimensional conformal radiotherapy plans were designed for the Set 3 volumes. RESULTS: For the primary tumor GTV, the Set 1 (CT) volume was larger than the Set 2 (PET) volume in 48%, smaller in 33%, and equal in 19%. The mean matching index was 0.65 (35% CT-PET mismatch). Although quantitatively similar, the volumes differed qualitatively. The Set 3 (composite) volume was larger than either CT or PET alone in 62%, smaller in 24%, and equal in 14%. The dose-volume histogram parameters did not differ among the plans for Set 1 (CT) vs. Set 3 (composite) volumes. Small portions of the Set 3 PTV were significantly underdosed in 40% of cases using the CT-only plan. CONCLUSION: Computed tomography and PET are complementary and should be obtained in the treatment position and fused to define the GTV for NSCLC. Although the quantitative absolute target volume is sometimes similar, the qualitative target locations can be substantially different, leading to underdosage of the target when planning is done using CT alone without PET fusion.

Thyroid-stimulating hormone-stimulated fused positron emission tomography/computed tomography in the evaluation of recurrence in 131I-negative papillary thyroid carcinoma.

UNLABELLED: Fluorine-18 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) detects recurrence of papillary thyroid carcinoma (PTC) in thyroidectomized patients with elevated thyroglobulin (Tg) levels and negative (131)I-whole-body scans. This paper describes the utility of thyroid-stimulating hormone (TSH)-stimulated fused FDG-PET/computed tomography (CT) scanning on our first 15 patients of this population. METHODS: Patients were prepared for PET/CT imaging with thyroid hormone withdrawal (n = 7) or recombinant human TSH (n = 8). All other imaging before the PET/CT did not demonstrate evidence of recurrence. RESULTS: PET/CT scans revealed active foci in 9 patients, 4 prepared with hypothyroidism, and 5 with exogenous TSH. Positive results were demonstrated even in those with relatively low stimulated-TSH Tg values (13 and 14 microg/L). Six patients with positive PET/CT scans were treated surgically, yielding malignant tissue for 5 of those patients. CONCLUSION: PET/CT scans performed under TSH stimulation are an effective method of detecting of recurrence of PTC and direct surgical interventions, even in those with persistently elevated but relatively low Tg levels.

Optimizing 18F-FDG Uptake Time Before Imaging Improves the Accuracy of PET/CT in Liver Lesions.

UNLABELLED: (18)F-FDG PET/CT has emerged as one of the fastest-growing imaging modalities. A shorter protocol results in a lower target-to-background ratio, which can increase the challenge of identifying mildly (18)F-FDG-avid lesions and differentiating inflammatory or physiologic activity from malignant activity. The purpose of this study was to determine the delay between radiotracer injection and imaging that optimizes target-to-background ratio while maintaining counts high enough to ensure scan sensitivity. METHODS: The study included 140 patients (66 male and 74 female; age range, 42-95 y) with suspected hepatic lesions as seen on an (18)F-FDG PET scan. SUV was determined as region-of-interest activity/(dose/total body weight). RESULTS: The mean injected dose was 610 ± 66.6 MBq (16.5 ±1.8 mCi), with a mean glucose level of 107 ± 26.6 mg/dL (standardized to 90 mg/dL). The uptake time before imaging ranged from 61 to 158 min, with a mean of 108.8 ± 24.8 min. The P values for the correlation of SUV to time were 0.004, 0.003, and 0.0001 for malignant lesions, benign lesions, and background hepatic tissue, respectively. CONCLUSION: An approximately 90-min time window from (18)F-FDG injection to PET imaging would significantly improve target-to-background ratio and, thus, quantitation and visual interpretation. This benefit outweighs the minimal loss in patient throughput.

Defining a radiotherapy target with positron emission tomography.

PURPOSE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is now considered the most accurate clinical staging study for non-small-cell lung cancer (NSCLC) and is also important in the staging of multiple other malignancies. Gross tumor volume (GTV) definition for radiotherapy, however, is typically based entirely on computed tomographic data. We performed a series of phantom studies to determine an accurate and uniformly applicable method for defining a GTV with FDG-PET. METHODS AND MATERIALS: A model-based method was tested by a phantom study to determine a threshold, or unique cutoff of standardized uptake value based on body weight (standardized uptake value [SUV]) for FDG-PET based GTV definition. The degree to which mean target SUV, background FDG concentration, and target volume influenced that GTV definition were evaluated. A phantom was constructed consisting of a 9.0-L cylindrical tank. Glass spheres with volumes ranging from 12.2 to 291.0 cc were suspended within the tank, with a minimum separation of 4 cm between the edges of the spheres. The sphere volumes were selected based on the range of NSCLC patient tumor volumes seen in our clinic. The tank and spheres were filled with a variety of known concentrations of FDG in several experiments and then scanned using a General Electric Advance PET scanner. In the initial experiment, six spheres with identical volumes were filled with varying concentrations of FDG (mean SUV = 1.85 approximately 9.68) and suspended within a background bath of FDG at a similar concentration to that used in clinical practice (0.144 muCi/mL). The second experiment was identical to the first, but was performed at 0.144 and 0.036 muCi/mL background concentrations to determine the effect of background FDG concentration on sphere definition. In the third experiment, six spheres with volumes of 12.2 to 291.0 cc were filled with equal concentrations of FDG and suspended in a standard background FDG concentration of 0.144 muCi/mL. Sphere images in each experiment were auto-contoured (simulating a GTV) using the threshold SUV that yielded a volume matching that of the known sphere volume. A regressive function was constructed to represent the relationship between the threshold SUV and the mean target SUV. This function was then applied to define the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined by a fixed image intensity threshold proposed by other investigators. RESULTS: There was a strong linear relationship between the threshold SUV and the mean target SUV. The linear regressive function derived was: threshold SUV = 0.307 x (mean target SUV) + 0.588. The background concentration and target volume indirectly affect the threshold SUV by way of their influence on the mean target SUV. We applied the linear regressive function, as well as a fixed image intensity threshold (42% of maximum intensity) to the sphere phantoms and 15 patients with NSCLC. The results indicated that a much smaller deviation occurred when the threshold SUV regressive function was utilized to estimate the phantom volume as compared to the fixed image intensity threshold. The average absolute difference between the two methods was 21% with respect to the true phantom volume. The deviation became even more pronounced when applied to true patient GTV volumes, with a mean difference between the two methods of 67%. This was largely due to a greater degree of heterogeneity in the SUV of tumors over phantoms. CONCLUSIONS: An FDG-PET-based GTV can be systematically defined using a threshold SUV according to the regressive function described above. The threshold SUV for defining the target is strongly dependent on the mean target SUV of the target, and can be uniquely determined through the proposed iteration process.

High predictive value of F-18 FDG PET patterns of the spine for metastases or benign lesions with good agreement between readers.

Two nuclear medicine physicians retrospectively evaluated fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) spine abnormalities in patients with cancer with the purpose of identifying straightforward criteria for benign versus malignant spine abnormalities. Four hundred seventy-five consecutive patients with colon, breast, and lung cancer were evaluated with FDG. Thirty-two patients (32) had spine abnormalities, 30 of 32 patients had adequate follow up for a final diagnosis, and 29 of 30 patients' studies were available to both PET readers for this retrospective review. The readers categorized the FDG PET abnormalities as benign, metastatic, or equivocal using a straightforward set of criteria. A final diagnosis was made using magnetic resonance imaging (MRI), computed tomography (CT), plain films, bone scans, previous studies, and clinical follow up. A single spinal focus of increased FDG activity had a relatively high probability of being a spinal metastasis (71%); and the more foci, the higher the probability. Segmental decreased activity of the spine after radiation therapy indicated benignity. The only discrepancies were with 3 abnormalities, each called metastasis by 1 reader and equivocal by the other, with a final diagnosis of metastasis in each case. Equivocal patterns required CT or MR correlation, because these could be either malignant or benign. However, abnormal patterns fulfilling either the benign or metastatic criteria described here resulted in the correct diagnoses of benign spinal changes or spinal metastases, respectively, in 100% of cases with low interobserver variation. No study was interpreted as benign by 1 reader and metastasis by the other. The 2 nuclear medicine readers agreed in their interpretations in 90% of cases.

Complementary role of 18F-FDG PET and 123I-ioflupane SPECT in the diagnosis of Lewy body disease.

We present a case demonstrating how correlative imaging with (123)I-ioflupane SPECT and (18)F-FDG PET can be used to help make the diagnosis of Lewy body disease more specific.

Time sensitivity-corrected retention index: an enhanced metabolic index from 18F-FDG PET to differentiate between benign and malignant pulmonary nodules.

The aim of the study was to evaluate pulmonary nodules (PNs) by incorporating time sensitivity (S) factor in the retention index (RI) and compare with the traditional fixed interval method. After obtaining approval from the Human Investigations Committee, 97 PNs from 81 patients (age=70±11) referred for dual-time fluorine-18 fluorodeoxyglucose PET (16.1±1.9 mCi) with definite pathological diagnosis or 1-year computed tomography follow-up were retrospectively studied. S=d{ln[SUV]]/d{ln[T]} was obtained by logarithmic regression using scan times, T (0, 1, 2), and standard uptake value (SUV) (0, 1, 2). This time-corrected RI, RIs=[(T2/T1)-1]×100%, was compared with traditional fixed time interval RI, RIx=[(SUV2/SUV1)-1]×100%, by means of receiver operating characteristic curve analysis. The mean±SD of T1 and T2 (72.3±14.0 and 134.9±17.6 min, respectively) skewed markedly from the intended time of PET scans (skewness=2.076 and 1.356, respectively). There were 27 benign tumors, 37 cases of non-small-cell lung cancer, 15 other types of cancer, and 18 stable lesions by 1-year computed tomography follow-up. There were significant differences between the nonmalignant group (NM, n=45) and the cancer group (CA, n=52) in time sensitivity (0.186±0.161 vs. 0.483±0.180, P<0.0005) and RIs (12.7±12.5 vs. 37.4±17.5%, P<0.0005). The RIx showed wider variation than RIs, although the difference between NM and CA was also significant (18.0±28.8 vs. 37.8±32.0%, P=0.002). The RIs and RIx were only weakly correlated (r=0.257, P=0.011). Receiver operating characteristic curve analysis performed for the CA or NM groups revealed a significant improvement in the diagnostic accuracy for malignancy by RIs (area under the curve=0.880±0.035, P<0.0005) compared with RIx (area under the curve=0.694±0.054, P=0.001). Incorporating the time sensitivity factor improves the diagnostic performance of RI for malignant PNs by using additional biologic information from the variation in fluorine-18 fluorodeoxyglucose uptake times and rates.

Metabolic activity measured by F-18 FDG PET in natural killer-cell lymphoma compared to aggressive B- and T-cell lymphomas.

PURPOSE: We aim to compare the metabolic activity by F-18 fluorodeoxyglucose (FDG) uptake across the various histologic subtypes of non-Hodgkin lymphoma (NHL) in a single center, with particular interest in the natural killer (NK)-cell lymphoma subtype for which literature is scarce because of the rarity of these lymphomas in Western populations. MATERIALS AND METHODS: We retrospectively evaluated the FDG-avidity of pretreatment positron emission tomography-computed tomography scans of 117 consecutive NHL patients by measuring the lesion with the highest maximum standardized uptake value (SUV(max)) in each patient. Mean SUV(max) of 4 major groups of NHL; aggressive B-cell (n = 63), indolent B-cell (n = 31), NK-cell (n = 14) and aggressive T-cell lymphoma (n = 9), was compared using one-way analysis of variance. P value <0.05 was considered statistically significant. RESULTS: SUV(max) (mean +/- standard deviation) of NK-cell lymphoma (9.2 +/- 4.5) was significantly lower than aggressive B-cell lymphoma (14.1 +/- 6.4) (P = 0.013), similar to aggressive T-cell lymphoma (7.6 +/- 3.9) and significantly higher than that of indolent B-cell lymphoma (5.3 +/- 3.1) (P = 0.039). CONCLUSION: The metabolic phenotype, characterized by FDG uptake of the various NHL subtypes is described. Although NK-cell lymphomas demonstrate high metabolic activity, SUV(max) is significantly lower than its aggressive B-cell counterparts. This may reflect the large amount of coagulative necrosis and inflammatory component of the tumor, and the relatively slower tumor growth rate compared with aggressive B-cell lymphomas.

Correlating metabolic and anatomic responses of primary lung cancers to radiotherapy by combined F-18 FDG PET-CT imaging.

BACKGROUND: To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy. METHODS: 36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy. RESULTS: There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 +/- 32.7% vs 47.1 +/- 26.1% respectively, p = 0.03) CONCLUSION: Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.

Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival.

PURPOSE: To present safety and efficacy results obtained in treatment of a cohort of patients with unresectable hepatocellular carcinoma (HCC) with use of 90Y microspheres (TheraSphere). PATIENTS AND METHODS: Forty-three consecutive patients with HCC were treated with 90Y microspheres over a 4-year period. Patients were treated by liver segment or lobe on one or more occasions based on tumor distribution, liver function, and vascular flow dynamics. Patients were followed for adverse events, objective tumor response, and survival. Patients were stratified into three risk groups according to method of treatment and risk stratification (group 0, segmental; group 1, lobar low-risk; group 2, lobar high-risk) and Okuda and Child-Pugh scoring systems. RESULTS: Based on follow-up data from 43 treated patients, 20 patients (47%) had an objective tumor response based on percent reduction in tumor size and 34 patients (79%) had a tumor response when percent reduction and/or tumor necrosis were used as a composite measure of tumor response. There was no statistical difference among the three risk groups with respect to tumor response. Survival times from date of diagnosis were different among the risk groups (P < .0001). Median survival times were 46.5 months, 16.9 months, and 11.1 months for groups 0, 1, and 2, respectively. Median survival times of 24.4 months and 12.5 months by Okuda scores of I and II, respectively, were achieved (mean, 25.8 months vs 13.1). Patients had median survival times of 20.5 months and 13.8 months according to Child class A and class B/C disease, respectively (mean, 22.7 months vs 13.6 months). Patients classified as having diffuse disease exhibited decreased survival and reduced tumor response. There were no life-threatening adverse events related to treatment. CONCLUSIONS: Use of 90Y microspheres (TheraSpheres) provides a safe and effective method of treatment for a broad spectrum of patients presenting with unresectable HCC. Further investigation is warranted.

90Y microsphere (TheraSphere) treatment for unresectable colorectal cancer metastases of the liver: response to treatment at targeted doses of 135-150 Gy as measured by [18F]fluorodeoxyglucose positron emission tomography and computed tomographic imaging.

PURPOSE: The purpose of this phase II study was to determine the safety and efficacy of TheraSphere treatment (90Y microspheres) in patients with liver-dominant colorectal metastases in whom standard therapies had failed or were judged to be inappropriate. MATERIALS AND METHODS: Twenty-seven patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 135-150 Gy. Safety and toxicity were assessed according to the National Cancer Institute's Common Toxicity Criteria, version 3.0. Response was assessed with use of computed tomography (CT) and was correlated with response on [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Survival from first treatment was estimated with use of the Kaplan-Meier method. RESULTS: Tumor response measured by FDG PET imaging exceeded that measured by CT imaging for the first (88% vs 35%) and second (73% vs 36%) treated lobes. Tumor replacement of 25% or less (vs >25%) was associated with a statistically significant increase in median survival (339 days vs 162 days; P = .002). Treatment-related toxicities included mild fatigue (n = 13; 48%), nausea (n = 4; 15%), and vague abdominal pain (n = 5; 19%). There was one case of radiation-induced gastritis from inadvertent deposition of microspheres to the gastrointestinal tract (n = 1; 4%). Three patients (11%) experienced ascites/pleural effusion after treatment with TheraSphere as a consequence of liver failure in advanced-stage metastatic disease. With the exception of these three patients whose sequelae were not considered to be related to treatment, all observed toxicities were transient and resolved without medical intervention. CONCLUSION: TheraSphere administration appears to provide stabilization of liver disease with minimal toxicity in patients in whom standard systemic chemotherapy regimens have failed.

Angiographic considerations in patients undergoing liver-directed therapy.

The rapid evolution and increasing complexity of liver-directed therapies has forced the medical community to further advance its understanding of hepatic arterial anatomy. The anatomy of the mesenteric system, and particularly the hepatic arterial bed, has been demonstrated to have a high degree of variation. This is important when considering presurgical planning, catheterization, and transarterial hepatic therapies. Although anatomic variants have been well described, the characterization and understanding of regional hepatic perfusion is also required to optimize endovascular therapy and intervention. Although this is true for patients undergoing bland embolization or chemoembolization, drug delivery, and hepatic infusional pump therapy, it is particularly true for intraarterial brachytherapy. The purpose of this review is to provide historical perspective in angiographic aspects of liver-directed therapy, as well as a discussion of normal vascular anatomy, commonly encountered variants, and factors involved in changes to regional perfusion in the presence of liver tumors. Methods of optimizing the safety and efficacy of liver-directed therapies with use of percutaneous techniques will be discussed. This review is based on the experience gained in treating more than 500 patients with transarterial liver-directed therapies. Although the principles described in this article apply to all liver-directed therapies such as chemoembolization and administration of drug-coated microspheres, they apply particularly to intraarterial brachytherapy.