Effect of Positron Emission Tomography Imaging in Women With Locally Advanced Cervical Cancer: A Randomized Clinical Trial.

Importance: In women with locally advanced cancer of the cervix (LACC), staging defines disease extent and guides therapy. Currently, undetected disease outside the radiation field can result in undertreatment or, if disease is disseminated, overtreatment. Objective: To determine whether adding fludeoxyglucose F 18 positron emission tomography-computed tomography (PET-CT) to conventional staging with CT of the abdomen and pelvis affects therapy received in women with LACC. Design, Setting, and Participants: A randomized clinical trial was conducted. Women with newly diagnosed histologically confirmed International Federation of Gynecology and Obstetrics stage IB to IVA carcinoma of the cervix who were candidates for chemotherapy and radiation therapy (CRT) were allocated 2:1 to PET-CT plus CT of the abdomen and pelvis or CT alone. Enrollment occurred between April 2010 and June 2014 at 6 regional cancer centers in Ontario, Canada. The PET-CT scanners were at 6 associated academic institutions. The median follow-up at the time of the analysis was 3 years. The analysis was conducted on March 30, 2017. Interventions: Patients received either PET-CT plus CT of the abdomen and pelvis or CT of the abdomen and pelvis. Main Outcomes and Measures: Treatment delivered, defined as standard pelvic CRT vs more extensive CRT, ie, extended field radiotherapy or therapy with palliative intent. Results: One hundred seventy-one patients were allocated to PET-CT (n = 113) or CT (n = 58). The trial stopped early before the planned target of 288 was reached because of low recruitment. Mean (SD) age was 48.1 (11.2) years in the PET-CT group vs 48.9 (12.7) years in the CT group. In the 112 patients who received PET-CT, 68 (60.7%) received standard pelvic CRT, 38 (33.9%) more extensive CRT, and 6 (5.4%) palliative treatment. The corresponding data for the 56 patients who received CT alone were 42 (75.0%), 11 (19.6%), and 3 (5.4%). Overall, 44 patients (39.3%) in the PET-CT group received more extensive CRT or palliative treatment compared with 14 patients (25.0%) in the CT group (odds ratio, 2.05; 95% CI, 0.96-4.37; P = .06). Twenty-four patients in the PET-CT group (21.4%) received extended field radiotherapy to para-aortic nodes and 14 (12.5%) to common iliac nodes compared with 8 (14.3%) and 3 (5.4%), respectively, in the CT group (odds ratio, 1.64; 95% CI, 0.68-3.92; P = .27). Conclusions and Relevance: There was a trend for more extensive CRT with PET-CT, but the difference was not significant because the trial was underpowered. This trial provides information on the utility of PET-CT for staging in LACC. Trial Registration: ClinicalTrials.gov Identifier: NCT00895349.

Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. METHODS: 82Rb or 13N-ammonia (1,100-3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-to-myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. RESULTS: Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence counting rates, and 2%-10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. CONCLUSION: Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit.

Long-Term Follow-Up of Outcomes With F-18-Fluorodeoxyglucose Positron Emission Tomography Imaging-Assisted Management of Patients With Severe Left Ventricular Dysfunction Secondary to Coronary Disease.

BACKGROUND: Whether viability imaging can impact long-term patient outcomes is uncertain. The PARR-2 study (Positron Emission Tomography and Recovery Following Revascularization) showed a nonsignificant trend toward improved outcomes at 1 year using an F-18-fluorodeoxyglucose positron emission tomography (PET)-assisted strategy in patients with suspected ischemic cardiomyopathy. When patients adhered to F-18-fluorodeoxyglucose PET recommendations, outcome benefit was observed. Long-term outcomes of viability imaging-assisted management have not previously been evaluated in a randomized controlled trial. METHODS AND RESULTS: PARR-2 randomized patients with severe left ventricular dysfunction and suspected CAD being considered for revascularization or transplantation to standard care (n= 195) versus PET-assisted management (n=197) at sites participating in long-term follow-up. The predefined primary outcome was time to composite event (cardiac death, myocardial infarction, or cardiac hospitalization). After 5 years, 105 (53%) patients in the PET arm and 111 (57%) in the standard care arm experienced the composite event (hazard ratio for time to composite event =0.82 [95% confidence interval 0.62-1.07]; P=0.15). When only patients who adhered to PET recommendations were included, the hazard ratio for the time to primary outcome was 0.73 (95% confidence interval 0.54-0.99; P=0.042). CONCLUSIONS: After a 5-year follow-up in patients with left ventricular dysfunction and suspected CAD, overall, PET-assisted management did not significantly reduce cardiac events compared with standard care. However, significant benefits were observed when there was adherence to PET recommendations. PET viability imaging may be best applied when there is likely to be adherence to imaging-based recommendations. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00385242.

Positron Emission Tomography-Computed Tomography (PET-CT) Versus No PET-CT in the Management of Potentially Resectable Colorectal Cancer Liver Metastases: Cost Implications of a Randomized Controlled Trial.

PURPOSE: To evaluate whether positron emission tomography (PET) combined with computed tomography (PET-CT) is cost saving, or cost neutral, compared with conventional imaging in management of patients with resectable colorectal cancer liver metastases. METHODS: Cost evaluation of a randomized trial that compared the effect of PET-CT on surgical management of patients with resectable colorectal cancer liver metastases. Health care use data ≤ 1 year after random assignment was obtained from administrative databases. Cost analysis was undertaken from the perspective of a third-party payer (ie, Ministry of Health). Mean costs with 95% credible intervals (CrI) were estimated by using a Bayesian approach. RESULTS: The estimated mean cost per patient in the 263 patients who underwent PET-CT was $45,454 CAD (range, $1,340 to $181,420) and in the 134 control patients, $40,859 CAD (range, $279 to $293,558), with a net difference of $4,327 CAD (95% CrI, -$2,207 to $10,614). The primary cost driver was hospitalization for liver surgery (difference of $2,997 CAD for PET-CT; 95% CrI, -$2,144 to $8,010), which was mainly a result of a longer length of hospital stay for the PET-CT arm (median, 7 v 6 days; P = .03) and a higher postoperative complication rate (20% v 10%; P = .01). Baseline characteristics were similar between groups, including the number of liver segments involved with cancer, number of segments resected, and type of liver resection performed. No difference in survival was detected between arms. CONCLUSION: PET-CT was associated with limited clinical benefit and a nonsignificant increased cost. Universal funding of PET-CT in the management of patients with resectable colorectal cancer liver metastases does not seem justified.

Imaging Biomarkers in Immunotherapy.

Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer.

Effectiveness of Quality Improvement Interventions at Reducing Inappropriate Cardiac Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND: Between 5% and 25% of cardiac imaging tests are performed for inappropriate indications. Studies have examined the impact of appropriate use criteria-based quality improvement initiatives on inappropriate testing, but they have not been systematically evaluated. METHODS AND RESULTS: We performed a systematic review of studies evaluating quality improvement initiatives aimed at reducing inappropriate cardiac imaging. The primary outcome was the proportion of inappropriate tests based on appropriate use criteria. Studies were analyzed using a random effects meta-analysis model, and heterogeneity was examined using subgroup analyses. We identified 6 observational studies and 1 randomized control trial. Most interventions (n=6) had a formal education component, and 5 included a mechanism for physician audit and feedback. Although these interventions were associated with lower odds of inappropriate testing (odds ratio, 0.44 [95% confidence interval, 0.32-0.61]; P<0.001), significant heterogeneity was observed (I(2)=70%), which was best explained by the utilization of physician audit and feedback. Interventions that employed physician audit and feedback were associated with significantly lower odds of inappropriate testing (odds ratio, 0.36 [95% confidence interval, 0.31-0.41]; P<0.001; I(2)=0%), whereas those that did not had no effect (odds ratio, 0.89 [95% confidence interval, 0.61-1.29]; P=0.51; I(2)=0%; P value for difference <0.001). All studies had potential sources of bias that could have affected the observed estimates. CONCLUSIONS: Interventions using physician audit and feedback are associated with lower odds of inappropriate cardiac testing. Further research is needed to evaluate a greater diversity of intervention types, with improved study designs.

Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans.

The biological effects of exposure to radioactive fluorodeoxyglucose ((18)F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo (18)F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of (18)F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of (18)F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual's radiation response. In summary, the results of this study indicate(18)F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures.

Effect of PET before liver resection on surgical management for colorectal adenocarcinoma metastases: a randomized clinical trial.

IMPORTANCE: Patients with colorectal cancer with liver metastases undergo hepatic resection with curative intent. Positron emission tomography combined with computed tomography (PET-CT) could help avoid noncurative surgery by identifying patients with occult metastases. OBJECTIVES: To determine the effect of preoperative PET-CT vs no PET-CT (control) on the surgical management of patients with resectable metastases and to investigate the effect of PET-CT on survival and the association between the standardized uptake value (ratio of tissue radioactivity to injected radioactivity adjusted by weight) and survival. DESIGN, SETTING, AND PARTICIPANTS: A randomized trial of patients older than 18 years with colorectal cancer treated by surgery, with resectable metastases based on CT scans of the chest, abdomen, and pelvis within the previous 30 days, and with a clear colonoscopy within the previous 18 months was conducted between 2005 and 2013, involving 21 surgeons at 9 hospitals in Ontario, Canada, with PET-CT scanners at 5 academic institutions. INTERVENTIONS: Patients were randomized using a 2 to 1 ratio to PET-CT or control. MAIN OUTCOMES AND MEASURES: The primary outcome was a change in surgical management defined as canceled hepatic surgery, more extensive hepatic surgery, or additional organ surgery based on the PET-CT. Survival was a secondary outcome. RESULTS: Of the 263 patients who underwent PET-CT, 21 had a change in surgical management (8.0%; 95% CI, 5.0%-11.9%). Specifically, 7 patients (2.7%) did not undergo laparotomy, 4 (1.5%) had more extensive hepatic surgery, 9 (3.4%) had additional organ surgery (8 of whom had hepatic resection), and the abdominal cavity was opened in 1 patient but hepatic surgery was not performed and the cavity was closed. Liver resection was performed in 91% of patients in the PET-CT group and 92% of the control group. After a median follow-up of 36 months, the estimated mortality rate was 11.13 (95% CI, 8.95-13.68) events/1000 person-months for the PET-CT group and 12.71 (95% CI, 9.40-16.80) events/1000 person-months for the control group. Survival did not differ between the 2 groups (hazard ratio, 0.86 [95% CI, 0.60-1.21]; P = .38). The standardized uptake value was associated with survival (hazard ratio, 1.11 [90% CI, 1.07-1.15] per unit increase; P < .001). The C statistic for the model including the standardized uptake value was 0.62 (95% CI, 0.56-0.68) and without it was 0.50 (95% CI, 0.44-0.56). The difference in C statistics is 0.12 (95% CI, 0.04-0.21). The low C statistic suggests that the standard uptake value is not a strong predictor of overall survival. CONCLUSIONS AND RELEVANCE: Among patients with potentially resectable hepatic metastases of colorectal adenocarcinoma, the use of PET-CT compared with CT alone did not result in frequent change in surgical management. These findings raise questions about the value of PET-CT scans in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265356.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

UNLABELLED: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. METHODS: Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences greater than 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. RESULTS: Qualifying scores of SSS = 2, SDS = 2, were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). CONCLUSION: (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.

Clinical utility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in the staging of patients with potentially resectable esophageal cancer.

INTRODUCTION: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may play an important role in staging patients with potentially resectable esophageal cancer but its impact on clinical management remains unclear. METHODS: In a multicenter prospective cohort study of patients with potentially resectable esophageal cancer, we compared stage of disease based on PET/CT with the stage based on conventional staging performed before PET/CT (American Joint Committee on Cancer, 6th edition). The primary outcome was the proportion of patients with a clinically important change in stage, based on PET/CT findings. We used health administrative databases to track health services use and mortality after the index PET/CT scan. RESULTS: Four hundred ninety-one patients who received a PET/CT scan for staging of potentially resectable esophageal cancer were included in the study cohort. PET/CT led to clinically important changes in stage for a total of 188 patients (24.0%): 107 patients (21.8%) were upstaged and 11 patients (2.2%) were downstaged. Results of PET/CT were associated with differences in actual management. At the 6-month follow-up, use of surgery was greater in patients with M0 disease (54.4%) compared with those with M1a (25.0%; p < 0.001) or M1b (7.3%; p < 0.001) disease based on PET/CT. The overall cohort had a median survival of 603 days, and higher stage of disease on PET/CT (i.e., M stage) was associated with shorter survival (p < 0.001). CONCLUSIONS: PET/CT identifies disease not otherwise detected on conventional staging and results in clinically important changes in stage for an appreciable number of patients with potentially resectable esophageal cancer and can make important contributions to the management of these patients.

Prospective study of 2-[¹8F]fluorodeoxyglucose positron emission tomography in the assessment of regional nodal spread of disease in patients with breast cancer: an Ontario clinical oncology group study.

PURPOSE: 2-[(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is potentially useful in assessing lymph nodes and detecting distant metastases in women with primary breast cancer. PATIENTS AND METHODS: Women diagnosed with operable breast cancer within 3 months underwent FDG-PET at one of five Ontario study centers followed by axillary lymph node assessment (ALNA) consisting of sentinel lymph node biopsy (SLNB) alone if sentinel lymph nodes (SLNs) were negative, SLNB with axillary lymph node dissection (ALND) if SLNB or PET was positive, or ALND alone if SLNs were not identified. RESULTS: Between January 2005 and March 2007, 325 analyzable women entered this study. Sentinel nodes were found for 312 (96%) of 325 women and were positive for tumor in 90 (29%) of 312. ALND was positive in seven additional women. Using ALNA as the gold standard, sensitivity for PET was 23.7% (95% CI, 15.9% to 33.6%), specificity was 99.6% (95% CI, 97.2% to 99.9%), positive predictive value was 95.8% (95% CI, 76.9% to 99.8%), negative predictive value was 75.4% (95% CI, 70.1% to 80.1%), and prevalence was 29.8% (95% CI, 25.0% to 35.2%). Using logistic regression, tumor size was predictive for prevalence of tumor in the axilla and for PET sensitivity. PET scan was suspicious for distant metastases in 13 patients; three (0.9%) were confirmed as metastatic disease and 10 (3.0%) were false positive. CONCLUSION: FDG-PET is not sufficiently sensitive to detect positive axillary lymph nodes, nor is it sufficiently specific to appropriately identify distant metastases. However, the very high positive predictive value (96%) suggests that PET when positive is indicative of disease in axillary nodes, which may influence surgical care.

The use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and metaanalysis including the Ontario experience.

UNLABELLED: Cardiac sarcoidosis is a potentially fatal complication of sarcoidosis. The 1993 guidelines of the Ministry of Health, Labour, and Welfare (MHLW) of Japan have been used as the diagnostic gold standard and for comparison with imaging modalities. (18)F-FDG PET is not currently included in the guidelines. However, studies have shown promising data using (18)F-FDG PET. We conducted a systematic review of studies that evaluated the accuracy of (18)F-FDG PET for the diagnosis of cardiac sarcoidosis compared with MHLW guidelines. Data from a prospective Ontario provincial registry are also reported and included in the metaanalysis. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies that satisfied predetermined criteria. Quality evaluation using the Quality Assessment for Diagnostic Accuracy Studies was performed by 2 independent masked observers. Data were extracted and analyzed to measure study-specific and pooled accuracy for (18)F-FDG PET compared with the MHLW as the reference. RESULTS: A total of 519 titles was identified; 7 studies, including the Ontario registry, were selected for inclusion. Metaanalysis of these 7 studies was conducted, with a total of 164 patients, most of whom had been diagnosed with systemic sarcoidosis. The prevalence of cardiac sarcoidosis was 50% in the whole population. Pooled estimates for (18)F-FDG PET yielded 89% sensitivity (95% confidence interval [CI], 79%-96%), 78% specificity (95% CI, 68%-86%), a 4.1 positive likelihood ratio (95% CI, 1.7-10), and a 0.19 negative likelihood ratio (95% CI, 0.1-0.4). The overall diagnostic odds ratio was 25.6 (95% CI, 7.3-89.5), and the area under the summary receiver operator characteristic curve was 93% ± 3.5. The Ontario study yielded sensitivity and specificity of 79% and 70%, respectively. CONCLUSION: The high diagnostic accuracy determined for (18)F-FDG PET in this metaanalysis suggests potential value for diagnosis of cardiac sarcoidosis compared with the MHLW guidelines. These results may affect patient care by providing supportive evidence for more effective use of (18)F-FDG PET in the diagnosis of cardiac sarcoidosis. Large-scale multicenter studies are required to further evaluate this role.

Does FDG PET-assisted management of patients with left ventricular dysfunction improve quality of life? A substudy of the PARR-2 trial.

BACKGROUND: Patients with left ventricular dysfunction whose management is directed by F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging may have a quality of life (QOL) benefit over standard care. METHODS: Among 430 patients randomized in the PET and Recovery Following Revascularization (PARR)-2 trial to FDG PET-assisted management vs standard, QOL scores were obtained using the European Quality of Life-5 Dimensions (EQ-5D) in 427 patients at baseline (FDG PET n = 216; standard n = 211) and 355 patients at 12-month follow-up (FDG PET n = 184; standard n = 171). EQ-5D scores between FDG PET and standard arms were compared using mixed model repeated measures (MMRM). Subgroup analysis compared EQ-5D scores between patients in FDG PET who adhered to PET recommendations (Adherence) vs standard using MMRM. Interaction of revascularization with management was assessed using a general linear model. RESULTS: A trend toward higher EQ-5D scores in FDG PET was observed (P = 0.056). Subgroup analysis showed a significant difference favouring adherence (P = 0.04). Higher QOL at 6 months for FDG PET (P = 0.02) and Adherence (P = 0.02) were observed. For revascularization, an interaction with management (FDG PET vs standard) for QOL was observed (6 months: P = 0.01; 12 months: P = 0.1); Adherence (6 months: P = 0.01; 12 months: P = 0.1). CONCLUSIONS: FDG PET-directed management improves QOL, at least in the short-term and with adherence to recommendations. This may relate to revascularization, and may indicate better treatment selection using FDG PET.

PET/CT using ¹8F-FDOPA provides improved staging of carcinoid tumor patients in a Canadian setting.

AIM: In Canada, staging of carcinoid tumors is largely based on computed tomography (CT) imaging sometimes complemented with somatostatin receptor scintigraphy (SRS). This study assessed the diagnostic accuracy of 6-[¹8F]fluoro-3,4-dihydroxyphenylalanine (¹8F-FDOPA) PET/CT in neuroendocrine tumors. METHODS: We prospectively included 27 patients with either suspected carcinoid (n=6, with all prior tests negative) or with an established diagnosis of intestinal carcinoid tumor (n=21) from two Canadian treatment centers. Findings of ¹8F-FDOPA PET/CT were compared with SRS, CT, and combined SRS/CT using a composite reference standard comprising all available imaging, biochemistry, surgery, and follow-up data. Sensitivity was calculated per patient, per body region, and per lesion. The contribution to patient management was estimated from the feedback of attending physicians. RESULTS: In documented carcinoid patients, ¹8F-FDOPA PET/CT identified disease in 20 of 21 patients (patient-based sensitivity 95%). In 56 positive regions, ¹8F-FDOPA PET/CT detected 53, CT detected 34, SRS detected 34, and CT+SRS detected 39 regions, leading to region-based sensitivities of 95, 61, 62, and 71%, respectively. Lesion-based sensitivities were 96, 69, 50, and 72%, respectively. In the six patients with suspected disease only, one CT scan was positive, but ¹8F-FDOPA PET/CT was negative for all. ¹8F-FDOPA PET contributed to patient management in 12/21 patients (57%). CONCLUSION: ¹8F-FDOPA PET/CT proved to be an excellent modality for staging of carcinoid tumor patients, with superior performance compared with currently applied methods in Canada. In patients with suspected disease with negative prior imaging investigations, ¹8F-FDOPA was not helpful.

Positron emission tomography-computed tomography compared with invasive mediastinal staging in non-small cell lung cancer: results of mediastinal staging in the early lung positron emission tomography trial.

INTRODUCTION: Patients with non-small cell lung cancer (NSCLC) require careful preoperative staging to define resectability for potential cure. Fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is widely used to stage NSCLC. If the mediastinum is positive on PET-CT examination, some practitioners conclude that the patient is inoperable and refer the patient for nonsurgical treatment. METHODS: In this analysis of a previously reported trial comparing PET-CT with conventional imaging in the diagnostic work-up of patients with clinical stage I, II, or IIIA NSCLC, we determined the accuracy of PET-CT in mediastinal staging compared with invasive mediastinal staging either by mediastinoscopy alone or by mediastinoscopy combined with thoracotomy. RESULTS: All 149 patients had mediastinal nodal staging at mediastinoscopy alone (14), thoracotomy alone (64), or both (71). The sensitivity of PET-CT was 70% (95% confidence interval [CI], 48-85%), and specificity was 94% (95% CI, 88-97%). Of 22 patients with a PET-CT interpreted as positive for mediastinal nodes, 8 did not have tumor. The positive predictive value and negative predictive value were 64% (95% CI, 43-80%) and 95% (95% CI, 90-98%), respectively. Based on PET-CT alone, eight patients would have been denied potentially curative surgery if the mediastinal abnormalities detected by PET-CT had not been evaluated with an invasive mediastinal procedure. CONCLUSIONS: PET-CT assessment of the mediastinum is associated with a clinically relevant false-positive rate. Our study confirms the need for pathologic confirmation of mediastinal lymph node abnormalities detected by PET-CT.

Radiation doses originating from diagnostic procedures during the treatment and follow-up of children and adolescents with malignant lymphoma.

Children with malignant lymphoma undergo many diagnostic procedures that involve exposure to ionising radiation. In addition, many, but by no means all, undergo further exposure to ionising radiation during radiotherapy. While therapeutic radiation exposures are prescribed, the extent of radiation exposure arising from diagnostic procedures utilised in such children is largely unknown. We completed an audit of the radiation doses arising from diagnostic imaging procedures performed in a cohort of children with malignant lymphoma. The cumulative effective radiation dose associated with radiographic and radioisotopic procedures was derived for 81 children and adolescents with malignant lymphoma during their diagnosis, treatment and follow-up. Thirty-eight of the 42 patients (90%) with Hodgkin lymphoma were alive at study termination, with follow-up periods ranging from 1.9 to 11.7 years (median 5.3). Thirty-three of the 39 patients (85%) with non-Hodgkin lymphoma were alive at study termination with follow-up periods ranging from 2.4 to 12.3 years (median 7.5). The median effective dose was 518 mSv for patients with Hodgkin lymphoma and 309 mSv for those with non-Hodgkin lymphoma. The maximum effective dose was 1.7 Sv. The principal contributors to the effective dose were computed tomography (CT) and nuclear medicine imaging procedures using (67)Ga. Protocols for the management of children and adolescents with malignant lymphoma should be reviewed in order to reduce the radiation detriment without loss of essential diagnostic information.

Combined vertebral fracture assessment and bone mineral density measurement: a patient-friendly new tool with an important impact on the Canadian Risk Fracture Classification.

PURPOSE: Vertebral fractures often go unnoticed, while they constitute a significant risk factor for new fractures, independent of the bone density. Vertebral Fracture Assessment (VFA) is a new feature on DXA bone densitometry equipment. Our purpose was to determine the added value of VFA and its impact on the Canadian fracture risk classification using data from a Dutch academic cohort. METHODS: All 958 consecutive patients (64% female, mean age 53 [20-94], mean weight 75 kg [32-150]) who underwent BMD measurement at the University Medical Center Groningen, The Netherlands also underwent VFA in the same session. RESULTS: The prevalence of vertebral fractures was 26%. In 68% of these patients this fracture was unknown. The severity was "mild" (20%-25% height loss) in 43%, "moderate" (25%-35%) in 44% and "severe" (>35% height loss) in 13%. Even after excluding mild fractures, the prevalence of vertebral fractures was 17%. In the 28% with normal BMD the vertebral fracture prevalence was still 18%, in the 43% with osteopenia 23%, and in the 29% with osteoporosis 36%. The Canadian risk classification was "low fracture risk" in 68%, "moderate" in 19%, and "high" in 13%. Adding VFA altered the classification in 20% of the patients, to become 54%, 27%, and 19%, respectively. CONCLUSIONS: VFA added to BMD is a patient friendly diagnostic tool with a high diagnostic yield, as it detected unknown vertebral fractures and altered diagnostic classification in approximately 1 out of every 5 patients. These results suggest that BMD plus VFA may become the new standard in osteoporosis testing.

Is a fixed value for the least significant change appropriate?

The least significant change (LSC) represents the smallest difference between successive measurements of bone mineral density (BMD) that can be considered to be a real change and not attributable to chance. The LSC is derived from same-day in vivo BMD precision measurements. Our first objective was to determine if the LSC differs between technologists. Our second objective was to determine if patient body size influenced the LSC. Each of 8 technologists measured same-day precision in groups of 30 patients for the lumbar spine and the total trochanter and neck regions of the proximal femur. At the spine, precision ranged from 0.008 to 0.011g/cm(2) and did not differ between technologists. Precision for the total region of the left proximal femur ranged from 0.006 to 0.016g/cm(2) and did differ between technologists. For the trochanter and neck regions, precision ranged from 0.008 to 0.013g/cm(2) for the former and from 0.010 to 0.020g/cm(2) for the latter, again, with inter-technologist differences. The LSC for the lumbar spine increased linearly from 0.022 to 0.031g/cm(2) when body mass index (BMI) increased from 19.5 to 31.3kg/m(2). In contrast, there was no discernable impact of BMI on the LSC for any of the proximal femur regions. The LSC at the spine is determined by the patient, whereas the LSC at the femur is determined by the technologist. Use of a single value for the LSC will lead to misinterpretations of the significance of BMD changes at both the spine and the proximal femur.

Evidence-based approach to the introduction of positron emission tomography in ontario, Canada.

PURPOSE: The uptake of new health care technologies is usually driven by industry promotion, physician interest, patient demand, and institutional ability to acquire the technology. The introduction of positron emission tomography (PET) scanning in the province of Ontario, Canada, followed a different path. METHODS: The Ontario provincial government, through its Ministry of Health and Long-Term Care, commissioned a systematic review of the literature. When this found only weak evidence that PET has a positive impact on clinical outcomes, the Ministry introduced a provincial PET evaluation program to close the evidence gap. RESULTS: This article describes the challenges encountered establishing the PET evaluation program. These included the design and conduct of the initial clinical trials, the establishment of a PET cancer registry, standardizing how PET scans were performed and reported, and gaining acceptance by health professionals for the evaluative program. CONCLUSION: The proliferation of health technologies is a key driver of increasing health care costs. The Ontario approach to the introduction of PET is a model worth consideration by health systems seeking to ensure that they receive value for money based on a strong evidentiary base when introducing new health technologies.