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.

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.

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.

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.

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.

Positron emission tomography in staging early lung cancer: a randomized trial.

BACKGROUND: Among patients with early-stage non-small cell lung cancer (NSCLC), preoperative imaging tests are important in defining surgical candidates. OBJECTIVE: To assess whether whole-body positron emission tomography and computed tomography (PET-CT) plus cranial imaging correctly upstages cancer in more patients with NSCLC than does conventional staging plus cranial imaging. DESIGN: Randomized clinical trial with recruitment from June 2004 to August 2007. The centralized, computer-generated, variable block size randomization scheme was stratified by treatment center and cancer stage. Participants, health care providers, and outcome assessors were not blinded to imaging modality assignment. SETTING: 8 hospitals and 5 PET-CT centers in academic institutions. PATIENTS: Eligible patients were older than 18 years; had histologic or cytologic proof of stage I, II, or IIIA NSCLC on the basis of chest radiography and thoracic CT; and had a tumor considered to be resectable. INTERVENTION: PET-CT or conventional staging (abdominal CT and bone scan). All patients also had cranial imaging using CT or magnetic resonance imaging. MEASUREMENTS: The primary outcome was correct upstaging, thereby avoiding stage-inappropriate surgery. Secondary outcomes were incorrect upstaging and incorrect understaging. RESULTS: 170 patients were assigned to PET-CT and 167 to conventional staging. Eight patients (3 who had PET-CT and 5 who had conventional staging) did not have planned surgery. Disease was correctly upstaged in 23 of 167 PET-CT recipients and 11 of 162 conventional staging recipients (13.8% vs. 6.8%; difference, 7.0 percentage points [95% CI, 0.3 to 13.7 percentage points]), thereby sparing these patients from surgery. Disease was incorrectly upstaged in 8 PET-CT recipients and 1 conventional staging recipient (4.8% vs. 0.6%; difference, 4.2 percentage points [CI, 0.5 to 8.6 percentage points]), and it was incorrectly understaged in 25 and 48 patients, respectively (14.9% vs. 29.6%; difference, 14.7 percentage points [CI, 5.7 to 23.4 percentage points]). At 3 years, 52 patients who had PET-CT and 57 patients who had conventional staging had died. LIMITATION: The relatively small sample and the fact that some patients did not have planned surgery limited the ability to determine precise differences in clinical outcomes that were attributable to testing strategies. CONCLUSION: Preoperative staging with PET-CT and cranial imaging identifies more patients with mediastinal and extrathoracic disease than conventional staging, thereby sparing more patients from stage-inappropriate surgery, but the strategy also incorrectly upstaged disease in more patients.

6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects and emerging clinical applications.

In recent years, 6-l-18F-fluorodihydroxyphenylalanine (18F-DOPA) PET has emerged as a new diagnostic tool for the imaging of neuroendocrine tumors. This application is based on the unique property of neuroendocrine tumors to produce and secrete various substances, a process that requires the uptake of metabolic precursors, which leads to the uptake of 18F-DOPA. This nonsystematic review first describes basic aspects of 18F-DOPA imaging, including radiosynthesis, factors involved in tracer uptake, and various aspects of metabolism and imaging. Subsequently, this review provides an overview of current clinical applications in neuroendocrine tumors, including carcinoid tumors, pancreatic islet cell tumors, pheochromocytoma, paraganglioma, medullary thyroid cancer, hyperinsulinism, and various other clinical entities. The application of PET/CT in carcinoid tumors has unsurpassed sensitivity. In medullary thyroid cancer, pheochromocytoma, and hyperinsulinism, results are also excellent and contribute significantly to clinical management. In the remaining conditions, the initial experience with 18F-DOPA PET indicates that it seems to be less valuable, but further study is required.

Is there a role for positron emission tomography in breast cancer staging?

Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) is a radiotracer imaging method that is used in the care of patients with cancer. We conducted a nonsystematic review of the literature regarding the applicability of this technique in patients with breast cancer, encompassing the impact of FDG-PET on surgical management, including axillary node staging and sentinel lymph node biopsy; the use of FDG-PET in the evaluation of the primary tumor; the role of FDG-PET in the evaluation of distant metastases both at diagnosis and in the investigation of suspected recurrence; and the ability of FDG-PET to predict treatment response. FDG-PET is not sufficiently sensitive to replace histologic surgical staging of the axilla. Although FDG avidity of the primary tumor has been shown to be an unfavorable indicator, there is insufficient information to recommend its routine use for this indication. FDG-PET is more sensitive than conventional imaging in the detection of metastatic or recurrent disease, but the impact of increased sensitivity on patient care and outcome has not been demonstrated. The data regarding prediction of treatment response are insufficient to reach any conclusion. There are a number of prospective, adequately powered clinical trials currently in progress that should provide more definitive answers regarding the role, if any, of this technique in the management of patients with breast cancer.

Radiation exposure for 'caregivers' during high-dose outpatient radioiodine therapy.

On 27 occasions, radiation doses were measured for a family member designated as the 'caregiver' for a patient receiving high-dose radioiodine outpatient therapy for differentiated thyroid carcinoma. For 25 of the administrations, patients received 3.7 GBq of (131)I. Radiation doses for the designated caregivers were monitored on an hourly basis for 1 week using electronic personal dosemeters. The average penetrating dose was 98 +/- 64 microSv. The maximum penetrating dose was 283 microSv. Measured dose rate profiles showed that, on average, one-third of the caregiver dose was received during the journey home from hospital. The mean dose rate profile showed rapid clearance of (131)I with three distinct phases. The corresponding clearance half-times were <1 h, 21 h and approximately 8 d. These components were associated, respectively, with the drive home, the clearance of radioiodine from an athyreotic patient and small quantities of (131)I contaminating the home.